Expert Review of Anti-infective Therapy

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The epidemiology of carbapenemases in Latin

America and the Caribbean

Kevin Escandón-Vargas, Sergio Reyes, Sergio Gutiérrez & María Virginia

Villegas

To cite this article: Kevin Escandón-Vargas, Sergio Reyes, Sergio Gutiérrez & María Virginia
Villegas (2017) The epidemiology of carbapenemases in Latin America and the Caribbean, Expert
Review of Anti-infective Therapy, 15:3, 277-297, DOI: 10.1080/14787210.2017.1268918

To link to this article: https://doi.org/10.1080/14787210.2017.1268918

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EXPERT REVIEW OF ANTI-INFECTIVE THERAPY, 2017
VOL. 15, NO. 3, 277–297
http://dx.doi.org/10.1080/14787210.2017.1268918

REVIEW

The epidemiology of carbapenemases in Latin America and the Caribbean

a
Kevin Escandón-Vargas , Sergio Reyesa, Sergio Gutiérreza and María Virginia Villegasa,b
a
Bacterial Resistance and Hospital Epidemiology Unit, International Center for Medical Research and Training (CIDEIM), Cali, Colombia; bMolecular
Genetics and Antimicrobial Resistance Unit, International Center for Microbial Genomics, Universidad El Bosque, Bogotá, Colombia

ABSTRACT ARTICLE HISTORY

Introduction: Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. infections are major causes of Received 26 September 2016
morbidity and mortality, especially due to the emergence and spread of β-lactamases. Carbapenemases, Accepted 2 December 2016
which are β-lactamases with the capacity to hydrolyze or inactivate carbapenems, have become a serious KEYWORDS
concern as they have the largest hydrolytic spectrum and therefore limit the utility of most β-lactam Carbapenemases;
antibiotics. β-lactamases; carbapenems;
Areas covered: Here, we present an update of the current status of carbapenemases in Latin America Enterobacteriaceae;
and the Caribbean. Pseudomonas aeruginosa;
Expert commentary: The increased frequency of reports on carbapenemases in Latin America and the Acinetobacter baumannii;
Caribbean shows that they have successfully spread and have even become endemic in some countries. antimicrobial resistance;
Countries such as Brazil, Colombia, Argentina, and Mexico account for the majority of these reports. Latin America
Early suspicion and detection along with implementation of antimicrobial stewardship programs in all
healthcare settings are crucial for the control and prevention of carbapenemase-producing bacteria.

1. Introduction might be underestimated as their detection is difficult to per-

Gram-negative bacteria, namely Enterobacteriaceae and non-
fermenters such as Pseudomonas spp. and Acinetobacter spp.,
are pathogens responsible for numerous infections and out-
breaks in clinical settings, representing a major cause of mor-
bidity and mortality. Such bacteria frequently display
resistance to β-lactams and other antibiotics (e.g. quinolones
and aminoglycosides) and therefore pose a public health
threat and a therapeutic challenge. β-lactamase production
is regarded as the most important mechanism of resistance
to β-lactams in gram-negative bacteria. Carbapenemases,
which are β-lactamases with the capacity to hydrolyze or
inactivate carbapenems, have become a serious concern as
they have the largest hydrolytic spectrum and therefore limit
the utility of most β-lactam antibiotics.
Based on Ambler’s molecular classification, carbapene-
mases are divided into the class A serine-β-lactamases, class
B metallo-β-lactamases, and class D serine-β-lactamases [1].
Whereas the serine-β-lactamases require a serine moiety at
their active site, metallo-β-lactamases require divalent metal
cations, usually zinc, for enzyme activity. Although the first
carbapenemases described were chromosomally encoded and
species specific, worldwide dissemination of plasmid-
mediated carbapenemases has occurred, leading to interspe-
cies spread through horizontal gene transfer.
Carbapenemases represent a serious problem among infec-
tious diseases and microbiology professionals, and Latin
America and the Caribbean are not immune to this problem.
Numerous and novel carbapenemase variants of different
classes are continuously being identified [2]. However, they
form in most clinical microbiology laboratories. Additionally,
not all carbapenemase producers exhibit a carbapenem resis-
tance phenotype that raises suspicion warranting molecular
confirmation [3].
Despite the fact that infections due to carbapenem-resis-
tant bacteria are associated with higher mortality rates, pro-
longed hospital stays, and increased healthcare costs [3,4], few
studies have been performed to evaluate the clinical impact of
carbapenem resistance in Latin America. Recently, a Latin
American study of patients with bloodstream infections due
to Enterobacteriaceae determined that carbapenemase-produ-
cing Enterobacteriaceae infection (53/255 episodes, 21%) is an
independent mortality predictor (adjusted odds ratio 4; 95%
confidence interval 1.7–9.5; p = 0.002) [5]. Higher costs were
also found associated with carbapenemase-producing
Enterobacteriaceae infections in this cohort [6]. These findings
underscore the importance of performing campaigns for pre-
venting the spread of carbapenemase producers in healthcare
facilities in Latin America.
Due to the changing epidemiology of the carbapenemases
and their associated clinical implications, we present a review
on their current epidemiology in Latin America and the
Caribbean. Studies describing the presence of carbapene-
mases in patient isolates were included by carefully reviewing
abstracts and manuscripts identified using PubMed, SciELO,
LILACS, and Google Scholar databases. Also, other kind of
reports (abstracts from the Interscience Conference on
Antimicrobial Agents and Chemotherapy [ICAAC], reports
from National Institutes of Health, etc.) were considered only

CONTACT Kevin Escandón-Vargas kevin.escandonvargas@gmail.com; María Virginia Villegas mariavirginia.villegas@gmail.com

© 2016 Informa UK Limited, trading as Taylor & Francis Group
Table 1. Carbapenemases reported in Latin America and the Caribbean.
Class/Family Enzyme variant Bacteria Country References
278

Class A
NMC-A NMC-A E. cloacae Argentina, Colombia [11,12]
KPC KPC-2 K. pneumoniae, K. oxytoca, C. freundii, Enterobacter spp., E. coli, S. Argentina, Brazil, Chile, Colombia, Cuba, Ecuador, Mexico, Puerto [17,18,21,23,25–54,56–61,66,69–71,73–
marcescens, P. mirabilis, S. enterica, Kluyvera georgiana Rico, Uruguay, Venezuela 76,81,82,84,139,190,242,243]
KPC-2 P. aeruginosa, P. putida Argentina, Brazil, Chile, Colombia, Puerto Rico, Trinidad and Tobago [18,54,85,87–93,175,176]
KPC-2 Acinetobacter spp.a Puerto Rico [94]
KPC-3 K. pneumoniae Argentina, Brazil, Colombia, Mexico, Panama [19,22,24,27,28,54,67,68,78]
KPC-3 Acinetobacter spp.a Puerto Rico [94]
KPC-4 Acinetobacter spp.a Puerto Rico [94]
KPC-5 P. aeruginosa Puerto Rico [85,86]
KPC-8 K. pneumoniae Puerto Rico [61]
KPC-10 Acinetobacter spp.a Puerto Rico [94]
KPC-24 K. pneumoniae Chile [76]
KPC (unknown Enterobacter spp., E. coli, K. pneumoniae, K. oxytoca, C. freundii, S. Brazil, Chile, Panama, Paraguay, Perub, Puerto Rico, Venezuela [55,62–65,72,75,77,79,83,187,225–227]
K. ESCANDÓN-VARGAS ET AL.

variant) marcescens, S. enterica

KPC (unknown A. baumannii Puerto Rico [62]
variant)
GES GES-2 P. aeruginosa Argentina [104]
GES-5 P. aeruginosa Brazil, Mexico [90,105–107,110]
GES-5 K. pneumoniae Brazil [108,109]
GES-16 S. marcescens Brazil [101]
GES-20 K. pneumoniae, E. coli, P. aeruginosa Mexico [103,111]
BKC BKC-1 K. pneumoniae Brazil [112,113]
Class B
IMP IMP-1 K. pneumoniae, E. cloacae, P. rettgeri Brazil [121,133,135,136]
IMP-1 P. aeruginosa, P. fluorescens, P. putida Brazil, Mexico [106,107,122–130,132,140]
IMP-1 A. baumannii Brazil, Mexico [132,134,146]
IMP-1 A. junii Argentina [149]
IMP-1 Acinetobacter spp.a Argentina, Brazil [130–133,148]
IMP-6 A. baumannii Brazil [120]
IMP-8 E. cloacae, K. oxytoca, C. freundii Argentina [153,154]
IMP-10 S. marcescens Brazil [139]
IMP-10 A. baumannii Brazil [138]
IMP-13 P. aeruginosa Argentina [150–152]
IMP-15 P. aeruginosa Mexico [111,143–145]
IMP-16 P. aeruginosa Argentina, Brazil [123,128–130,137,140,152]
IMP-18 K. oxytoca Mexico [147]
IMP-18 P. aeruginosa Brazil, Costa Rica, Mexico, Puerto Rico [85,133,140–142,155–157]
IMP-36 P. aeruginosa Mexico [111]
IMP-49 P. aeruginosa Brazil [140]
IMP (unknown P. aeruginosa Peru, Venezuela [158,159]
variant)
IMP (unknown P. rettgeri Colombia [160]
variant)
VIM VIM-1 A. baumannii Mexico [193]
VIM-2 P. aeruginosa, P. fluorescens, P. putida, P. fulva Argentina, Brazil, Chile, Colombia, Costa Rica, Mexico, Uruguay, [26,54,90,110,111,122,130,133,140,144,155,165–
Venezuela 172,174–177,180–184]
VIM-2 K. pneumoniae, Enterobacter spp., K. oxytoca, P. rettgeri Argentina, Mexico, Venezuela [153,185–188]
VIM-2 Brevundimonas diminuta Argentina [192]
VIM-4 A. baumannii Mexico [146]
VIM-8 P. aeruginosa Colombia [173]
VIM-11 P. aeruginosa Argentina, Mexico [110,178–180]
VIM-16 S. marcescens Argentina [191]
VIM-23 E. cloacae, K. oxytoca, C. freundii, E. aerogenes Mexico [140,147]
VIM-24 K. pneumoniae Colombia [189,190]
VIM (unknown P. aeruginosa Perub -
variant)
(Continued )
Table1. (Continued).
Class/Family Enzyme variant Bacteria Country References
NDM NDM-1 K. pneumoniae, P. rettgeri, E. coli, M. morganii, S. fonticola, E. Argentina, Brazil, Chile, Colombia, Costa Rica, Guadeloupe, [75,140,223–230,233–243,246,248,250–252]
cloacae, E. hormaechei, C. freundii, P. mirabilis Guatemala, Jamaica, Mexico, Nicaragua, Perub, Uruguay,
Venezuela
NDM-1 P. aeruginosa Colombia [226,227]
NDM-1 A. baumannii Brazil, Colombia, Honduras, Nicaragua, Paraguay [225–229,232,244,248]
NDM-1 A. faecalis Colombia [226]
NDM-1 A. haemolyticus Colombia [226]
NDM-1 A. junii Argentina [247]
NDM-1 A. nosocomialis Colombia [228]
NDM-1 A. pittii Brazil, Paraguay [231,245]
NDM-1 A. soli Cuba [249]
SPM SPM-1 P. aeruginosa Brazil [90,106,107,122–
127,129,130,171,172,196,197,202–220]
Class Dc
OXA-23 subgroup OXA-23 A. baumannii Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guadeloupe, [134,226,251,261–276,278–290,292,295–297]
Mexico, Paraguay, Uruguay, Venezuela
OXA-23 A. nosocomialis Brazil, Colombia [272,277,291]
OXA-23 A. pittii Brazil [277]
OXA-23 Acinetobacter spp.a Brazil, Cuba, Jamaica, Venezuela [148,249,276,293]
OXA-239 A. baumannii Mexico [294,295]
OXA-469 A. baumannii Mexico [295]
OXA-40/24 OXA-40 A. baumannii Mexico [146,147,295]
subgroup
OXA-40-like A. baumannii Chile, Cuba, Jamaica [249,292,293]
OXA-40-like Acinetobacter spp.a Argentina, Brazil, Mexico [147,300]
OXA-72 A. baumannii Brazil, Colombia, Ecuador, Mexico [193,265,275,282,287,295,296,301–303,305]
OXA-72 A. pittii Colombia [304]
OXA-58 subgroup OXA-58 A. baumannii Argentina, Bolivia, Brazil, Chile, Mexico, Venezuela [265,268,279–
281,283,292,294,295,301,308,309,316]
OXA-58 A. junii Argentina [149]
OXA-58 A. seifertii Brazil [315]
OXA-58 A. pittii Colombia [291]
OXA-58 Acinetobacter spp.a Argentina, Chile, Cuba, Jamaica, Puerto Rico [94,147,249,293,300,307]
OXA-48 subgroup OXA-48 K. pneumoniae Argentina [318]
OXA-48 K. oxytoca Colombia [319]
OXA-163 K. pneumoniae, E. cloacae Argentina [54,147,318,320,321]
OXA-247 K. pneumoniae Argentina [321]
OXA-370 Enterobacter spp., K. pneumoniae Brazil [322,323]
OXA-143 OXA-143 A. baumannii Brazil [134,265,266,273,276,324]
subgroup
OXA-231 A. baumannii Brazil [325,326]
OXA-253 A. baumannii Brazil, Honduras [326,327]
OXA-235 OXA-235 A. baumannii Mexico [310]
subgroup
a
Acinetobacter species not determined.
b
Personal communication.
c
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY

OXA-51 enzymes are intrinsic to A. baumannii. OXA-51 variants reported in Latin America and the Caribbean are OXA-51, -65, -66, -69, -77, -78, -83, -89, -94, -95, -99, -100, -132. blaOXA-51 -like has been detected in A.
nosocomialis and A. pittii in southern Brazil.
279
280 K. ESCANDÓN-VARGAS ET AL.
in the absence of formal journal reports. Latin America and the
Caribbean is the group of countries and dependencies com-
prising Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica,
Ecuador, El Salvador, French Guiana, Guatemala, Honduras,
Mexico, Nicaragua, Panama, Paraguay, Perú, Uruguay,
Venezuela, the Greater Antilles (Cuba, Dominican Republic,
Haiti, Jamaica, and Puerto Rico), and the Lesser Antilles
(Guadeloupe, Trinidad and Tobago, others).
2. Class A carbapenemases
Class A carbapenemases have predominantly been reported in
several members of the Enterobacteriaceae family, which are
causative agents of severe infections and outbreaks. Their hydro-
lytic mechanism confers resistance to many β-lactam antibiotics
including carbapenems. They can be located on the bacterial
chromosome or in mobile genetic elements allowing their trans-
fer and spread between gram-negative bacteria [2]. Nine main
types of class A carbapenemases are currently known: Serratia
marcescens enzyme (SME), imipenem-hydrolyzing β-lactamase
(IMI), non-metallo-carbapenemase of class A (NMC-A), Klebsiella
pneumoniae carbapenemase (KPC), Guiana extended-spectrum
β-lactamase (GES), Serratia fonticola carbapenemase (SFC),
Brazilian Klebsiella carbapenemase (BKC), Bicêtre carbapenemase
(BIC), and French imipenemase (FRI). Within this class of enzymes,
only NMC-A, KPC, GES, and BKC families have been reported in
Latin America and the Caribbean (Figure 1).
2.1. Non-metallo-carbapenemase of class A
NMC-A β-lactamase confers resistant to penicillins, narrow-
spectrum cephalosporins, cefoxitin, and aztreonam. NMC-A
was first identified as a novel chromosomally encoded carba-
penemase in 1990 from a clinical isolate of Enterobacter cloa-
cae in Paris, France [7,8]. This isolate was imipenem resistant
but cefotaxime susceptible. This rare enzyme was later found
in Seattle and New York City in the USA [9,10]. In Latin
Figure 1. Class A carbapenemases distribution in Latin America and the
Caribbean.
America, NMC-A was the first class A carbapenemase found
and was described in an E. cloacae isolate collected during
2000 in Buenos Aires, Argentina [11]. Later in 2009, NMC-A
was found in an E. cloacae isolate from Barranquilla,
Colombia [12].
2.2. Klebsiella pneumoniae carbapenemase
KPC enzymes are the most prevalent class A carbapenemases
worldwide. They efficiently hydrolyze penicillins, cephalospor-
ins, monobactams, and carbapenems, and are partially inhib-
ited by β-lactamase inhibitors such as clavulanic acid and
tazobactam. In the last two decades, these carbapenemases
have become an emerging threat given their resistance profile
and the wide capacity of dissemination across multiple con-
tinents. They are mostly plasmid encoded but chromosomal
locations have also been reported. Mobile genetic elements,
such as the plasmid-borne transposon Tn4401, have played a
role in the acquisition and spread of successful blaKPC-carrying
clones including the sequence type (ST) 258 clone [13].
Up to date, 23 valid KPC variants (KPC-2 to −24) (http://
www.lahey.org/studies) have been identified differing by one
to three amino acid substitutions [14]. KPC-1 (sequence later
recognized to be identical to KPC-2) was first identified in 1996
in a carbapenem-resistant Klebsiella pneumoniae strain col-
lected from North Carolina, USA during the ICARE (Intensive
Care Antimicrobial Resistance Epidemiology) surveillance
study [15]. Subsequently, as a result of clonal expansion and
horizontal gene transfer, blaKPC genes have disseminated in
multiple regions of the world and have been recognized
throughout diverse gram-negative species, but remain most
prominent in K. pneumoniae [16]. Currently, KPCs have been
identified mainly in Enterobacteriaceae with KPC-2 and KPC-3
being the most widespread KPC variants worldwide.
The first Latin American report of a KPC took place in
Medellín, Colombia in 2005. The presence of KPC-2 was
described in two clinical isolates of K. pneumoniae collected
from unrelated healthcare facilities [17]. In 2006, an imipenem-
resistant Citrobacter freundii isolate from one of these medical
centers was found to harbor blaKPC-2 [18] and later in 2008, a
KPC-3-producing K. pneumoniae strain was identified in an
Israeli patient who had traveled to Medellin, Colombia for a
liver transplantation [19]. The clone was indistinguishable from
a KPC-3-producing clone previously described in multiple out-
breaks in Israel [20]. Investigation of this Colombian isolate led
to the demonstration of the first carbapenemase outbreak in
Latin America consisting of at least 36 KPC-3-producing K.
pneumoniae isolates collected throughout 2008 [19]. The
active dissemination of both KPC-2 and KPC-3 has been
demonstrated in several Enterobacteriaceae members from
Colombia [21–28], reaching rates of KPC production of 13–
86% among carbapenem-non-susceptible isolates. Colombian
KPC-producing K. pneumoniae isolates have been found
mostly associated with ST258 and ST512 [27,28].
KPC enzymes have also been present in Brazil since at
least 2005 but they were not detected at that time. The first
KPC (KPC-2) in this country was retrospectively identified in
K. pneumoniae isolates collected from hospitals in São Paulo
and Florianópolis [29,30], and since then, wide dispersion of

the blaKPC gene has occurred throughout the country and
many other cases have been reported including KPC-2
detected in K. pneumoniae, Enterobacter spp., Escherichia
coli, Serratia marcescens, and K. oxytoca clinical isolates
[31–45]. Recently, the first Latin American Enterobacter ger-
goviae harboring blaKPC-2 has been reported in Brazil [46].
Molecular epidemiology studies have revealed the predomi-
nant dissemination of the clonal complex (CC) 11/258 (ST11,
ST258, ST437, and ST340) among KPC-2-producing K. pneu-
moniae isolates collected from multiple Brazilian hospitals
from 2006 to 2010 [47–52]. Likewise, great clonal diversity
has been reported for KPC-2-producing non-K. pneumoniae
Enterobacteriaceae in Brazil [53]. KPC-3 variant has occasion-
ally been reported in Brazil [54]. Although K. pneumoniae is
the predominant KPC producer in most of the country,
Enterobacter spp. have been found as the main KPC produ-
cers in southern Brazil [33,55]. Recently, the first Latin
American report of KPC-2-producing Proteus mirabilis has
been made in Recife, Brazil [56].
In Argentina, the first detection of KPC (KPC-2) occurred in
2006 in a patient coinfected with K. pneumoniae and C. freundii in
Buenos Aires [57]. Subsequently, 77 KPC-2 producers, mostly K.
pneumoniae but including strains of E. cloacae, C. freundii, E. coli
and S. marcescens, were collected from 30 hospitals across the
country during 2008–2010 [58]. Several studies demonstrated
the major occurrence of clonal dissemination of K. pneumoniae
ST258 harboring the blaKPC-2 gene [50,58–60], but KPC-3-produ-
cing K. pneumoniae isolates have also been reported [54]. In
Puerto Rico, the first hospital outbreak caused by KPC-positive
K. pneumoniae occurred in 2008, in which KPC-2 and -8 variants
were identified [61]. KPC-producing E. coli was later found in this
country in 2009 [62]. In Venezuela, KPC-producing K. pneumoniae
and E. cloacae were first described between 2009 and 2010 [63];
currently KPC-2 is the KPC variant which has been predominantly
identified in K. pneumoniae in this country [54]. Other KPC-pro-
ducing Enterobacteriaceae, including Enterobacter spp., E. coli, K.
oxytoca, and C. freundii, have also been identified in Venezuela
[64–66]. In Mexico, the first outbreaks of KPC-3 and KPC-2-produ-
cing K. pneumoniae were identified in 2010 and between 2012
and 2013, respectively [67–69]; all isolates of these Mexican out-
breaks belonged to the pandemic clone ST258, which is part of
the CC292. In Ecuador, the first case report of a KPC-2-producing
K. pneumoniae was identified in 2010 [70], and since that time,
dissemination of different KPC-2 clones has been reported [71].
Likewise, in 2011, KPC was first detected in Chile in a K. pneumo-
niae isolated from a patient who had traveled from Italy [72], in
Uruguay in two patients infected with KPC-2-producing K. pneu-
moniae (ST258) [73], and in Cuba in three K. pneumoniae clinical
isolates harboring blaKPC-2 (ST1271, CC29) [74]. Subsequently,
several other cases of KPC-2-producing Enterobacteriaceae
[75,76] and a novel KPC-24-producing K. pneumoniae [76] have
been reported in Chile; most of these strains belonged to CC258
[76]. KPC-producing K. pneumoniae isolates have been detected
in Panama since at least 2011 [77]; KPC-3 seems to be the
predominant variant identified thus far [78]. Thereafter, the first
KPC-producing K. pneumoniae clinical isolate was identified in
Peru in 2013 [79], and other cases of KPC-producing K. pneumo-
niae and E. cloacae have since identified (Edgar Gonzales-
Escalante, personal communication).
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 281
Although dissemination of KPC has already been reported in
virtually all Enterobacteriaceae species, KPC-producing
Salmonella enterica isolates remain infrequent. Since the first
KPC-producing S. enterica serovar Cubana described in 1998 in
Maryland, USA [80], KPC-2 has been described in Latin America
in a S. enterica serovar Typhimurium isolate in Colombia [81], in
a S. enterica serovar Schwarzengrund isolate in Argentina [82],
and in a S. enterica serovar Javiana in Paraguay [83]. Likewise,
reports of multidrug-resistant Kluyvera spp. isolates also remain
extremely rare. KPC-2-producing K. georgiana was reported in a
tracheal aspirate from a Brazilian patient in 2011 [84].
On the other hand, the identification of KPC (KPC-2) in P.
aeruginosa was reported for the first time globally in Colombia
in 2007 [18]. Soon afterwards, KPC-2 and KPC-5 were reported
in P. aeruginosa isolates from several hospitals in Puerto Rico
[85,86]. Emergence of KPC-2 in P. aeruginosa was reported in
Trinidad and Tobago in 2009 in a patient with no history of
travel abroad [87]. In Brazil, KPC-2 was detected in a P. putida
bloodstream isolate from a child in 2008 [88], and subse-
quently in P. aeruginosa clinical isolates from two unrelated
hospitals [89,90]. In Argentina, KPC-2-positive P. aeruginosa
isolates have been found since 2006 and have been associated
to the import and local clonal expansion of the international
multidrug-resistant clone ST654 (CC244) [91–93]. Interestingly,
Chile has also identified KPC-2-producing P. aeruginosa iso-
lates during 2012–2014 [54].
With regard to A. baumannii-calcoaceticus complex isolates,
KPC-2, -3, -4, and -10 were for the first time described in
hospital isolates collected from Puerto Rico in 2009 [62,94].
To the best of our knowledge, no other countries in the world
have since reported KPC enzymes in Acinetobacter spp. iso-
lates, but the existence of KPC-producing Enterobacteriaceae
and P. aeruginosa highlights the possibility of further dissemi-
nation of KPC in Acinetobacter spp. elsewhere in the world.
2.3. Guiana extended-spectrum β-lactamase
The GES family has 31 enzyme variants (ftp://ftp.ncbi.nlm.nih.
gov/pathogen/betalactamases/Allele.tab) encoded by genes
that mostly occur in the form of cassettes carried by class 1
integrons in both chromosomes (mostly in P. aeruginosa) and
plasmids (Enterobacteriaceae, P. aeruginosa, and A. baumannii).
GES-type β-lactamases have been found in several gram-nega-
tive bacterial species since the first description of the ceftazi-
dime-hydrolyzing enzyme GES-1 in 1998 in a K. pneumoniae
isolate from a French Guiana patient [95]. All GES variants are
capable to hydrolyze broad-spectrum cephalosporins, but only
some of them (GES-2, -4, -5, -6, -11, -14, -15, -16, -18, -20, -21,
and -24) have been reported to possess activity toward carba-
penems as a result of specific amino acid substitutions inside
the active site [96–103]. In Latin America, few GES-type carba-
penemases have been reported. GES-2 was identified in P.
aeruginosa in Argentina in 2004 [104]. In Brazil, GES-5 has
been reported in clinical isolates of P. aeruginosa [90,105–
107] and K. pneumoniae [108,109]. In Mexico, GES-5 was
reported coexpressed with the metallo-β-lactamases VIM-2
and VIM-11 in several P. aeruginosa isolates recovered during
2004 [110]. Of note, the novel GES-16 variant was for first time
identified in two clinical isolates of S. marcescens from Brazil in
282 K. ESCANDÓN-VARGAS ET AL.
2011 [101]. Finally, the GES-20 carbapenemase has been
reported in clinical isolates of K. pneumoniae, E. coli, and P.
aeruginosa collected during 2004–2011 in Mexico [103,111].
2.4. Brazilian Klebsiella carbapenemase
Recently, a novel plasmidic class A serine carbapenemase,
named BKC-1, was reported in three clinical isolates of K.
pneumoniae (ST1781) collected in 2008 from different patients
hospitalized in São Paulo, Brazil [112]. BKC-1 hydrolyzes peni-
cillins, cephalosporins, monobactams, and carbapenems but
spares cephamycins. Further screening for BKC among
Brazilian clinical isolates of Klebsiella spp. allowed identifying
two other BKC-1-producing K. pneumoniae strains (ST 1781
and its single-locus variant ST442) [113]. To date, all BKC-1
producers described belong to CC442 and harbor BKC-1 gene
on a small nonconjugative plasmid.
3. Class B carbapenemases
Class B carbapenemases are also known as metallo-β-lactamases
due to the presence of a metal ion, usually zinc (Zn2+), in their
active site. Consequently, they are inhibited by metal-chelating
agents such as ethylenediaminetetraacetic acid (EDTA). Metallo-
β-lactamases are resistant to all commercially available β-lacta-
mase inhibitors and preserve susceptibility to monobactams (e.g.
aztreonam) in the absence of simultaneous expression of other
resistance mechanisms [2]. Metallo-β-lactamases are classified
into three subclasses (B1, B2, and B3) according to sequence
alignments and zinc coordination [114]. Subclass B1 needs two
zinc ions coordinated for enzyme activity and has a broad spec-
trum of action including carbapenems. This subclass includes the
largest number of clinically relevant members as imipenemase
(IMP), Verona integron-encoded metallo-β-lactamase (VIM), New
Delhi metallo-β-lactamase (NDM), São Paulo metallo-β-lacta-
mase (SPM), German imipenemase (GIM), Seoul imipenemase
(SIM), Kyorin health science metallo-β-lactamase (KHM),
Australian imipenemase (AIM), Dutch imipenemase (DIM), and
Florence imipenemase (FIM), and the chromosomally encoded
BcII (Bacillus cereus), CcrA (Bacteroides fragilis), Bla2 (Bacillus
anthracis), IND (Chryseobacterium indologenes), BlaB
(Elizabethkingia meningoseptica), CGB-1 (Chryseobacterium
gleum), TUS-1 (Myroides odoratus), MUS-1 (Myroides odoratimi-
mus), JOHN-1 (Flavobacterium johnsoniae), EBR-1 (Empedobacter
brevis), SFB-1 (Shewanella frigidimarina) and SLB (Shewanella
livingstonensis). Subclass B2 binds one zinc ion in their active
site and are inhibited when a second zinc ligand is bound. These
metallo-β-lactamases are chromosomally encoded and have a
preferential hydrolytic profile for carbapenems. This subclass
includes CphA (Aeromonas hydrophila), ImiS and AsbM1
(Aeromonas veronii), SFH-1 (S. fonticola). Enzymes of subclass B3
are binuclear zinc-dependent, as subclass B1, but possesses pre-
ferential hydrolysis of cephalosporins. The subclass B3 includes
chromosomally-encoded enzymes which are L1
(Stenotrophomonas maltophilia), Mbl1b (Caulobacter crescentus),
CAU-1 (Caulobacter vibrioides), THIN-B (Janthinobacterium livi-
dum), FEZ-1 (Legionella gormanii), GOB (E. meningoseptica), BJP-
Figure 2. Class B carbapenemases distribution in Latin America and the
Caribbean.
1 (Bradyrhizobium japonicum), SMB-1 (S. marcescens), and Tripoli
metallo-β-lactamase (TMB).
Among the metallo-β-lactamases, VIMs and NDMs are the
most prevalent in the world [2]. The acquired metallo-β-lacta-
mase families reported in Latin America and the Caribbean to
date are IMP, VIM, NDM, and SPM (Figure 2).
3.1. Imipenemase
IMP-type metallo-β-lactamases were the first acquired carba-
penemases to be identified in the world. The first report of this
enzyme (IMP-1) was in 1988 from an imipenem-resistant P.
aeruginosa isolate in Japan [115], which was followed by IMP-
1-producing S. marcescens isolates collected in the same coun-
try [116–118]. So far, 58 IMP variants have been assigned
(ftp://ftp.ncbi.nlm.nih.gov/pathogen/betalactamases/Allele.
tab), and IMP-type carbapenemase producers have spread
throughout Asia and the world [2]. IMP hydrolyses a broad
range of β-lactams, including penicillins, cephalosporins, and
carbapenems, but spares aztreonam. The blaIMP gene is com-
monly found as a gene cassette within class 1 integrons which
can mobilize by transposition or plasmid conjugation [119].
IMP was not identified in Latin America until 2003, when
IMP-6 and IMP-1 were isolated in A. baumannii [120] and K.
pneumoniae [121] isolates, respectively, in Brazil. Thereafter,
IMP-1 was reported in several other clinical isolates of P.
aeruginosa [106,107,122–129], Acinetobacter spp. [130–134],
P. fluorescens [130], K. pneumoniae [135,136], E. cloacae [133],
and P. putida [132] throughout the country. The first Latin
American report of a metallo-β-lactamase in a Providencia
rettgeri isolate was an IMP-1 identified in 2005 in Brazil [135].
There are also Brazilian reports of IMP-16 in P. aeruginosa
[123,128–130,137], IMP-10 in A. baumannii [138], IMP-18 in P.
aeruginosa [133], IMP-10 in S. marcescens coproducing KPC-2
[139], and IMP-49 in P. aeruginosa [140].
In Mexico, IMP-18 [140–142], IMP-15 [111,143–145], IMP-36
[111], and recently IMP-1 [140] have been identified in P.

aeruginosa clinical isolates. Interestingly, IMP-1 has been found
in A. baumannii isolates [146] and IMP-18 has been described
in a K. oxytoca isolate [147]. In Argentina, IMP-1 was first
reported in three Acinetobacter spp. isolates in 2005 [148]
and then in two A. junii isolates identified in 2005–2006
[149]. This was followed by several reports of IMP-13 [150–
152] and IMP-16 [140,152] in P. aeruginosa isolates. Among
Enterobacteriaceae, E. cloacae, K. oxytoca and C. freundii har-
boring blaIMP-8 have been reported in this country [153,154]. In
Costa Rica, IMP-18 was first reported among several P. aerugi-
nosa isolates collected during 2004–2005 in a tertiary-level
hospital [155]. In Puerto Rico, IMP-18 has been identified in
several P. aeruginosa isolates collected from different hospitals
since 2006 [85,156,157]. A P. aeruginosa isolate simultaneously
producing IMP-18 and KPC-2 was reported in 2012 [157].
Additionally, IMP-type carbapenemases have been recently
described in P. aeruginosa isolates from Peru [158] and
Venezuela [159]. In Colombia, only one clinical isolate identi-
fied as P. rettgeri has been found to carry blaIMP [160].
Overall, studies comprising carbapenem-resistant P. aerugi-
nosa isolates in Latin America and the Caribbean have
reported rates of IMP production of 1–16%.
3.2. Verona integron-encoded metallo-β-lactamase
At the time of this review, 51 VIM variants (ftp://ftp.ncbi.nlm.
nih.gov/pathogen/betalactamases/Allele.tab) have been
described around the world but VIM-2 has actually spread
and become the most commonly metallo-β-lactamase world-
wide [2]. Like IMPs, VIMs exhibit a very broad hydrolytic profile
and are encoded by genetic determinants harbored in cas-
settes by generally class 1 integrons [161]. The first VIM-type
carbapenemase (VIM-1) was identified in isolates of P. aerugi-
nosa from Verona, Italy in 1997 [162,163], followed by VIM-2 in
a P. aeruginosa strain isolated in France in 1996 but reported
in 2000 [164].
In Latin America, VIM-2 was identified for first time in 2002 in
Chile and Venezuela in isolates of P. fluorescens and P. aeruginosa,
respectively [130,165]. Several VIM-2-producing P. aeruginosa
clinical isolates have since been reported in these countries
[54,140,166–170]. VIM-2 has also been reported in P. aeruginosa
isolates in Brazil since 2005 [90,122,133,140,171,172]. In
Colombia, VIM-8 was initially described in 2004 in an outbreak
of multidrug-resistant P. aeruginosa in one hospital [173], fol-
lowed by the report of VIM-2 in P. aeruginosa isolates in several
cities across the country since 2006 [26,140,174,175]. Recently, it
has been found the ST111 as the predominant lineage of carba-
penem-resistant P. aeruginosa strains carrying the blaVIM-2 gene
[176,177]. In Argentina, the first VIM-type enzyme identified was
VIM-11 in 2002 in P. aeruginosa isolates [178–180], followed by
VIM-2 described in several P. aeruginosa [180] and P. putida
[181,182] isolates. The first case of human infection caused by
P. fulva in the world was reported in 2010 in Argentina; this
isolate carried the blaVIM-2 gene cassette [183]. In Mexico, there
are reports of P. aeruginosa producing VIM-2 [110,111,140,144]
and VIM-11 [110]. Likewise, VIM-2-producing P. aeruginosa iso-
lates have been reported in Uruguay (2011, 184] and Peru (2013)
(Edgar Gonzales-Escalante, personal communication). A recent
study in Costa Rica reported simultaneous expression of VIM-2
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 283
and IMP-18 in several P. aeruginosa isolates collected during
2004–2005 [155].
In contrast to Europe, few reports of VIM exist in
Enterobacteriaceae in Latin America and the Caribbean. In
Venezuela, VIM-2 was first reported in 2008 among isolates
of K. pneumoniae [185] and recently in Enterobacter spp.
[186,187]. Since 2009 in Mexico, VIM-2 has been reported in
a few isolates of E. cloacae and K. oxytoca [188] and VIM-23 has
been described in E. cloacae, K. oxytoca, C. freundii, and E.
aerogenes [140,147]. In addition, VIM-24 has been reported in
a couple of K. pneumoniae isolates from Colombia [189,190]. In
Argentina, a P. rettgeri isolate expressing VIM-2 [153] and
seven S. marcescens expressing VIM-16 [191] were reported
in 2011 and 2013, respectively.
Interestingly, other non-fermenters different that of
Pseudomonas spp. carrying the blaVIM gene have been
reported in Latin America and the Caribbean. VIM-2-producing
Brevundimonas diminuta was once reported in 2012 in an
immunocompromised patient from Argentina [192]. A. bau-
mannii clinical isolates producing VIM-1 [193] or VIM-4 [146]
have been reported in Mexico.
Additionally, coproduction of VIM-2 and KPC-2 in P. aerugi-
nosa was reported for the first time in the world in Colombia
in 2012 [175,176], followed by the copresence of the same
enzyme variants in P. aeruginosa from Chile [54] and E. cloacae
from Venezuela [187]. Also, coproduction of VIM-24 and KPC-2
has been found in K. pneumoniae in Colombia [190]. The
coexpression of VIM-2 and VIM-11 with GES-5 was reported
in 2012 in Mexico [110]. Overall, in Latin America and the
Caribbean, rates of VIM-producing organisms are 2–19%
among carbapenem-resistant P. aeruginosa isolates.
3.3. São Paulo metallo-β-lactamase
SPM comprises a family of mobile metallo-β-lactamases in
which only one allelic variant (SPM-1) has been described
[194]. It confers broad-spectrum resistance to β-lactams
except for aztreonam which is not a good substrate. SPM
production has been mostly found in P. aeruginosa so far but
clinical isolates of A. baumannii harboring blaSPM-1 have been
described [195]. The blaSPM-1 gene is either plasmid encoded
[195–197] or chromosomal [198], but has not been found as
part of a gene cassette nor in the vicinity of a class 1 integron
[199]. It has been rather associated with insertion sequence
common region (ISCR) elements such as the ISCR4 variant
which can be responsible for mobilization and expression of
blaSPM-1 via a mechanism named rolling-circle transposition
[197,199]. Recently, blaSPM-1 has been located within integra-
tive and conjugative elements such as the transposon Tn4371
[200,201].
SPM-1 was originally described in a P. aeruginosa clinical strain
isolated in 2001 in São Paulo, Brazil [196]. Since then, SPM-1 has
been described in virtually all regions of this country and has
been linked to the high-level carbapenem resistance observed in
multiple P. aeruginosa hospital outbreaks with high mortality
[106,107,122–125,127,129,130,171,172,197,202–216]. Rates of
SPM-positive P. aeruginosa in these studies vary from 5% to as
high as 95% of all carbapenem-resistant isolates. Dissemination
284 K. ESCANDÓN-VARGAS ET AL.
of the SPM-1-producing P. aeruginosa clone SP/ST277 has been
extensively documented throughout Brazil [126,202,217–219]. It
should be noted that SPM-1 has been reported in P. aeruginosa
ST235 in this country as well (http://pubmlst.org/paeruginosa/)
[126]. Overall, SPM-1 is a β-lactamase with great epidemiological
importance in Brazil since it is by far the most prevalent type of
metallo-β-lactamase and display a colistin-only-sensitive pheno-
type in most isolates [202,217,219,220]. Additionally, nine P.
aeruginosa isolates coharboring blaSPM-1 and blaKPC-2, and a P.
aeruginosa isolate coharboring blaSPM-1, blaKPC-2, and blaVIM-2
have been reported in Brazil [90].
There were no reports of SPM outside Brazil in the world until
2007 when one strain of SPM-1-producing P. aeruginosa was
isolated from a patient hospitalized in Switzerland [198]. This
was followed by the report of six clinical isolates of A. baumannii
harboring blaSPM-1 collected between 2009 and 2010 in Iran
[195]. Last, in 2013, a SPM-1-producing P. aeruginosa isolate
was cultured from an impatient in the UK for the first time
[201]. Both P. aeruginosa strains collected in Switzerland and
the UK were isolated from patients previously admitted to
Brazilian hospitals for medical assistance and were genetically
related to the P. aeruginosa clone SP/ST277 which is endemic in
Brazil.
It is unclear why the epidemiology of SPM-1 has been mostly
restricted to Brazil in contrast to the worldwide dissemination
observed for the other acquired metallo-β-lactamases IMP, VIM,
and NDM [220]. The different types of mobile genetic elements
involved in the horizontal transfer of SPM could be related to this
phenomenon [194]. Nevertheless, the risk of SPM dissemination
is imminent. Andrade et al. have highlighted the opportunity for
SPM to spread globally after international gatherings, including
the 2016 Olympic Games recently held in Rio de Janeiro [220].
Further, there exists the possibility that blaSPM-1 spreads beyond
non-fermenting gram-negative aerobes to a broader range of
bacteria.
Intriguingly, isolates belonging to the P. aeruginosa clone
ST277 have been submitted to the MLST database from
Austria, Australia, Central African Republic, China, and Spain
(http://pubmlst.org/paeruginosa/), showing the potential of
SPM-1 to become widespread globally. However, there are
no data regarding the presence of blaSPM-1 in those isolates
nor known epidemiological links of patients from those coun-
tries with Brazil. Until now, the acquisition of SPM-1 in P.
aeruginosa ST277 seems to be a feature limited to Brazil with
a few exceptions of international spread.
3.4. New Delhi metallo-β-lactamase
Currently, the NDM family members number up to 16 variants
(http://www.lahey.org/studies). The first international descrip-
tion of NDM took place in 2008 in E. coli and K. pneumoniae
isolates from a Swedish patient who had previously been hospi-
talized in New Delhi, India [221]. Since then, NDM-type enzymes
have spread worldwide and are present largely in
Enterobacteriaceae, but also in non-fermenting gram-negative
bacteria and Vibrionaceae. NDM efficiently hydrolyzes all β-lac-
tams except monobactams such as aztreonam. The blaNDM-1
gene is often carried by different plasmids and, more rarely,
becomes chromosomally integrated [222]. blaNDM is associated
with different types of insertion sequences [194].
The first NDM-1 report in Latin America came from
Guatemala in two isolates of K. pneumoniae collected in
2011 [223], followed by Colombia in which a nosocomial
outbreak of NDM-1-producing K. pneumoniae occurred in a
neonatal unit during 2011–2012 [224]. Since then, diverse
NDM-1-producing Enterobacteriaceae isolates have been
increasingly reported in Colombia including K. pneumoniae,
P. rettgeri, E. coli, M. morganii, and S. fonticola [225–228].
Few isolates of Acinetobacter species (A. baumannii, A. hae-
molyticus, A. faecalis, A. nosocomialis) [225–228], and P. aer-
uginosa [226,227] have been found to harbor NDM-1 in
Colombia. Recently, the complete genome sequences of
four different NDM-1 gram-negative producers were pub-
lished [228]. In Uruguay, NDM-1 was initially identified in P.
rettgeri isolates in 2012 [229], but there exists a report of this
metallo-β-lactamase in a M. morganii isolate [230]. In
Paraguay, A. baumannii [229] and A. pittii isolates [231]
were found to carry blaNDM-1 in 2012. Also, in the same
year, one NDM-1-producing A. baumannii isolate was
reported in Honduras [232]. Since 2013, NDM-1 has been
reported in clinical isolates of P. rettgeri, K. pneumoniae, E.
coli, and E. cloacae in Mexico [233–235], and in P. rettgeri, E.
cloacae, E. hormaechei, M. morganii, E. coli, K. pneumoniae, C.
freundii, A. baumannii, and A. pittii in different regions of
Brazil [236–245]. In 2014, NDM-1 was reported in a K. pneu-
moniae isolate in Chile [75], followed by Argentina in which
NDM-1 has been identified in three genetically related iso-
lates of P. rettgeri [246] and one A. junii isolate [247]. A Pan
American Health Organization epidemiological update in
2014 has also given account of the presence of NDM-1 in
K. pneumoniae, E. cloacae, E. coli and A. baumannii in
Nicaragua and in E. coli in Costa Rica [248]. More recently,
NDM-1 has been reported in a strain of A. soli from Cuba
[249], in two K. pneumoniae isolates from Jamaica [250] and
Guadeloupe, French West Indies [251], and in two K. pneu-
moniae and E. coli isolates from Venezuela [140,252]; the E.
coli isolated in the latter country was also found to harbor
the mcr-1 gene [252]. Finally, NDM-producing P. mirabilis, P.
rettgeri, E. coli, and K. pneumoniae have been detected in
Peru (Edgar Gonzales-Escalante, personal communication).
The coexpression of other carbapenem resistance determi-
nants has been described in a few isolates producing NDM,
including KPC in K. pneumoniae from Colombia [225–227],
KPC-2 in Enterobacter spp. from Brazil [242,243], and OXA-23
in A. baumannii from Colombia [226].
4. Class D carbapenemases
Class D β-lactamases (oxacillinases) are an ever-expanding
group of enzymes that includes over 500 members/variants
with a wide variety of amino acid sequences and hydrolyzing
profiles [253,254] (ftp://ftp.ncbi.nlm.nih.gov/pathogen/betalac
tamases/Allele.tab). These enzymes confer resistance to
amino- and carboxypenicillins and the majority are neither
inhibited by β-lactamase inhibitors nor EDTA. Only some sub-
groups of oxacillinases, called carbapenem-hydrolyzing class D
β-lactamases (CHDLs), display carbapenemase activity. To

Figure 3. Class D carbapenemases distribution in Latin America and the Caribbean.
date, at least twelve major phylogenetic subgroups or gene
clusters of CHDLs have been acknowledged [254] and the
number of new variants has increased alarmingly during the
last years. Although CHDLs are not as efficient hydrolyzing
carbapenems in vitro as other carbapenemases, their presence
is a significant cause of carbapenem resistance in
Acinetobacter species and Enterobacteriaceae worldwide
[114]. Overall, the hydrolytic profile of these enzymes spare
the extended-spectrum cephalosporins. Whereas the mem-
bers belonging to OXA-51 subgroup are chromosomally
located and intrinsic to A. baumannii, the other subgroups
comprise acquired CHDLs that can be either chromosomally
or plasmid encoded [254]. Mobile elements (i.e. plasmids) have
in part contributed to the dissemination of CHDL genes invol-
ving diverse STs [254,255]. Mobilization and enhanced expres-
sion of most blaOXA genes is often associated with insertion
sequences (e.g. ISAba1) that provide additional promoter
sequences leading to carbapenem resistance or decreased
susceptibility [256].
Apart from the OXA-51-related family typically present in A.
baumannii, six subgroups of acquired CHDLs have been iden-
tified in Latin America and the Caribbean, namely OXA-23-like,
OXA-40/24-like, OXA-58-like, OXA-48-like, OXA-143-like, and
OXA-235-like enzymes (Figure 3).
4.1. OXA-23 subgroup
OXA-23, formerly referred to as ARI-1 (for Acinetobacter resistant to
imipenem), was first reported in 1993 in a multidrug-resistant A.
baumannii strain which had been isolated in 1985 from a patient in
Edinburgh, Scotland [257,258]. Later, it was demonstrated that
OXA-23 was plasmid mediated [259]. Members belonging to the
OXA-23-like family have been described in both chromosomes and
plasmids, and have spread worldwide with a very high prevalence
[254,255]. OXA-23-like enzymes are the most prevalent acquired
CHDLs and have been isolated mainly from Acinetobacter spp. and
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 285
rarely from Enterobacteriaceae (P. mirabilis and K. pneumoniae)
[254,260].
In 1999, an outbreak of carbapenem-resistant A. baumannii
producing OXA-23 occurred for the first time in Latin America in
two hospitals in Curitiba, Brazil, in which five of the eight patients
infected with this strain died [261]. Thereafter, Carvalho et al.
reported that 96 of 110 (87%) imipenem-resistant A. baumannii
isolates from 8 hospitals in Rio de Janeiro carried the blaOXA-23
gene [262]. Since then, several other publications have reported
the presence and wide dissemination of OXA-23 in A. baumannii
throughout Brazil [134,263–276]. The blaOXA-23 gene have also
been reported in this country in non-baumannii Acinetobacter
species [272,276,277], including A. nosocomialis and A. pittii.
Interestingly, Carvalho et al. provided evidence that imipenem-
susceptible A. baumannii isolates may harbor blaOXA-23 gene and,
consequently, silently spread this resistance determinant in the
hospital environment [278]. In Buenos Aires, Argentina, the mole-
cular characterization of 41 epidemiologically unrelated A. bau-
mannii isolates ended in the identification of 26 of them carrying
the blaOXA-23 gene, which were collected between 2001 and 2006
[279]. Other authors have also reported OXA-23-producing A.
baumannii isolates in Argentina [280–282], collected even in
1995 [281]. In Venezuela, Fritsche et al. reported the first OXA-
23-producing Acinetobacter spp. strain isolated in 2002 [148].
Thereafter, Cuaical Ramos et al. identified the presence of OXA-
23 in 56/60 (93%) A. baumannii isolates with diminished suscept-
ibility to carbapenems collected during 2008 [283]. In Colombia,
Villegas et al. published a study of 65 OXA-23 producing A. bau-
mannii isolates which were collected during 2005 from a surveil-
lance project conducted in seven tertiary care hospitals from six
cities [284]. This work was the first description of OXA-23 nation-
wide dissemination in Latin America in which the prevalence of
carbapenem resistance was related mostly to clonal spread of
OXA-23 producers. Since then, OXA-23 has been predominantly
found among carbapenem-resistant A. baumannii isolates (75–
100%) collected in the country [285–291] and seldom in A. noso-
comialis [291]. In Chile, OXA-23 has been reported in Acinetobacter
baumannii isolates collected since 2007 [282,292]. In Jamaica, 2/82
Acinetobacter spp. collected during 2009–2011 were reported to
harbor blaOXA-23 [293]. In Mexico, there are recent reports from
multicenter studies which provide evidence of the presence of
OXA-23 and its novel variants OXA-239 and OXA-469 in A. bau-
mannii isolates recovered in 2006–2013 [294,295]. Between 2010
and 2012, the first National Surveillance Program of Acinetobacter
spp. in Cuba revealed a high prevalence of blaOXA-23 (130/220,
59%) among meropenem-non-susceptible A. baumannii-calcoace-
ticus complex isolates [249]. Most recently, the presence of OXA-23
has been reported in a few A. baumannii isolates from Ecuador
[282,296], Bolivia [282,297], Guadeloupe (French West Indies)
[251], Paraguay [282], and Uruguay [282].
In terms of molecular epidemiology, a distinct genetic diver-
sity has been described for OXA-23-like-producing carbapenem-
resistant A. baumannii isolates collected in Argentina [281], Brazil
[267,272–275], Colombia [289,290], Mexico [294,295], and Bolivia
[297], being CC79P/CC113B, CC636B, CC15P/CC104B,, and CC110B
the main clones involved in the spread of blaOXA-23 in the region.
In Latin America, MLST allelic profiles have rarely been related to
CC92B [295,298] which is one of the worldwide predominant
OXA-23 A. baumannii clones.
286 K. ESCANDÓN-VARGAS ET AL.

4.2. OXA-40/24 subgroup blaOXA-65 [280,310], blaOXA-66 [267,271,280,287], blaOXA-69

[267,280,286,287,311], blaOXA-77 [280], blaOXA-78 [280], blaOXA-83
The first OXA-24, later renamed OXA-40, was first identified
[193], blaOXA-89 [280], blaOXA-94 [228], blaOXA-95 [267,287], blaOXA-
from an outbreak caused by A. baumannii in 1997 in Madrid,
99 [287], blaOXA-100 [138], and blaOXA-132 [267]. blaOXA-66, blaOXA-64,
Spain [299]. OXA-40/24 subgroup is less disseminated than
blaOXA-65, and blaOXA-69 seem to be the most widespread blaOXA-51-
OXA-23 subgroup but there are increasing reports of these
like alleles. Further, blaOXA-51-like has been detected in a few isolates
enzymes in distant locations such as Asia and the Americas
of A. nosocomialis and A. pittii in southern Brazil [277].
[254]. A relevant OXA-40/24-like variant, OXA-72, is a point
Some years ago, there was controversy regarding the role
mutant of OXA-40 which was first reported in an A. baumannii
of OXA-51-like β-lactamases on A. baumannii carbapenem
isolate from Thailand in 2004 (GenBank accession no.
resistance due to their weak carbapenemase activity and the
AY739646) and then in some Asian and European countries.
identification of these enzymes in both carbapenem-resistant
In Latin America, OXA-40/24-like carbapenemases were
and -susceptible strains [254,280]. Currently, there is no doubt
initially reported in two Acinetobacter spp. isolates collected
that these enzymes play a role in resistance or decreased
in 2007 from Mexico and Brazil [300]. Since then, in Mexico,
susceptibility largely associated with the insertion sequence
the variants OXA-40 [146,147,295] and OXA-72 [193,295,301]
ISAba1 or ISAba9, which when located upstream of the blaOXA-
have been reported in A. baumannii isolates. Two of these
51 gene may promote its expression conferring resistance to
studies, which comprised a large number of A. baumannii
carbapenems [254,256,312]. Concern remains regarding the
isolates collected during 2004–2012, found that 26–50%
possibility that all A. baumannii isolates become intrinsically
harbored the blaOXA-72 gene [193,301]. In Brazil, OXA-72 is
resistant to the carbapenems as blaOXA-51-type genes repre-
the only variant found in A. baumannii isolates to date
sent a direct reservoir of β-lactamase-mediated carbapenem
[265,275,302,303]. Vasconcelos et al. reported the interhos-
resistance [254,280].
pital dissemination of A. baumannii carrying blaOXA-72 in
Further, because the kinetic properties of few OXA-51-like
Brazil for the first time in Latin America and the Caribbean
enzymes have been detailed [306,313], characterization stu-
[275]. In Colombia, Montealegre and colleagues identified in
dies of other variants are needed to determine whether all
2010 the first case of OXA-72 in an isolate of A. pittii from a
OXA-51 variants confer carbapenem resistance.
70-year-old woman [304]. After that report made in 2012,
Saavedra et al. described the first Colombian OXA-72-produ-
cing A. baumannii strain cultured from the peritoneal fluid; 4.4. OXA-58 subgroup
the strain was collected in 2006, four years earlier than the
OXA-58-like enzymes belonging to this subgroup are globally
OXA-72-producing A. pittii [287,305]. Few isolates of A. bau-
distributed with a very high prevalence in southern European
mannii carrying blaOXA-40/24-like have been reported in
Mediterranean countries [254]. The founding member, OXA-
Argentina [147] and Chile [292]. Recently, Jamaica [293],
58, was first detected in Toulouse, France in 2003 [314], but
and Cuba [249] have also reported blaOXA-40/24-like in
other works have identified the earliest known OXA-58 produ-
15–16% of carbapenem-non-susceptible A. baumannii iso-
cers in the world. Cayô et al. have recently reported two OXA-
lates. Ecuador is the latest Latin American country in report-
58-producing A. seifertii isolates collected in São Paulo, Brazil
ing OXA-72 from a nosocomial outbreak due to A.
in 1993 and 1997 [315], and Coelho et al. found the same
baumannii at two medical centers in Guayaquil, finding
carbapenemase in six A. baumannii/calcoaceticus complex iso-
blaOXA-72 in 86% of 35 isolates tested [282,296].
lates collected in Buenos Aires, Argentina in 1995 [307].
Overall, several studies have continued to report this glob-
ally scattered OXA variant in Latin America and the Caribbean.
4.3. OXA-51 subgroup
In Argentina, OXA-58 has been detected in A. baumannii [279–
The blaOXA-51-type genes are naturally harbored on the chro- 281] and A. junii [149], showing a polyclonal pattern. In
mosome of A. baumannii and are therefore ubiquitous in this Venezuela, researchers identified in a molecular epidemiology
species [254,280]. OXA-51 subgroup includes the greatest study two OXA-58-producing A. baumannii isolates collected
number of allelic variants (at least 95) [254]. The huge allelic in Mérida during 1998–1999 [316]. Another study conducted
diversity of these chromosomally encoded β-lactamases sug- in six hospitals in Caracas confirmed the presence of this
gests that A. baumannii has been under dramatic selective carbapenemase in four A. baumannii isolates [283]. In Brazil,
pressure driven by antibiotic use [254]. two reports have described a couple of A. baumannii isolates
The founding member of this subgroup, OXA-51, was identi- collected in 2004 and 2005 carrying blaOXA-58 [265,268].
fied for first time in six A. baumannii isolates from Buenos Aires, Alarmingly, OXA-58 has been identified since 2006 in a num-
Argentina collected between 1993 and 1994 [306]. However, ber of other countries including Mexico [294,295,301], Chile
Merkier and Centrón studied 194 A. baumannii isolates collected [147,292,300], Bolivia [308,309], Puerto Rico [94], Jamaica [293],
from 1982 to 2005 and determined the presence of blaOXA-51-type and Cuba [249]. In Colombia, the blaOXA-58 gene was detected
genes in all of them [280]. Several studies conducted in different for the first time in one A. pittii isolate [291].
nations from Latin America and the Caribbean have looked for
blaOXA-51-like, finding its presence in virtually all A. baumannii iso-
4.5. OXA-48 subgroup
lates [94,134,138,193,249,263,265,267,269–276,278,280,283,284,
286–290,292–296,301,307–309]. Sequencing of these genes has In contrast to the clear predominance of the other OXA-type
revealed the presence of blaOXA-51 [280], blaOXA-64 [232,286,297], carbapenemases in Acinetobacter spp. strains, OXA-48-like

enzymes prevail in K. pneumoniae and other Enterobacteriaceae
members [254]. However, OXA-48-like has been reported in A.
baumannii as well. OXA-48 was first discovered in a clinical K.
pneumoniae isolate recovered in Istanbul, Turkey in 2001 [317],
and now has spread to Middle East, North Africa, Europe, and
most recently the USA and Japan [254]. OXA-48-like enzymes
represent one of the most threatening carbapenemases in the
last decade [254].
In Latin America and the Caribbean, the OXA-48-related
CHDLs (variants OXA-48, OXA-163, OXA-247, and OXA-370)
have been detected in Enterobacteriaceae species in
Argentina, Brazil, and Colombia. OXA-48 has been reported
in few publications, being identified in a K. pneumoniae
isolate from Argentina [318] and in a K. oxytoca from
Colombia [319]. In 2008, OXA-163, an OXA-48 variant differ-
ing by a single amino acid substitution and a 4-amino-acid
deletion, was discovered in Buenos Aires, Argentina in a K.
pneumoniae and an E. cloacae isolates as part of a multidrug
resistance survey [320]. OXA-163 is the first CHDL able to
hydrolyze extended-spectrum cephalosporins but has a
weaker carbapenemase activity when compared with OXA-
48. Other studies have reported OXA-163 in few isolates of
K. pneumoniae in Argentina [54,147,318,321]. Interestingly,
Gomez et al. reported in Buenos Aires the intrapatient
emergence of the novel carbapenemase gene blaOXA-247 in
a K. pneumoniae strain from a patient previously infected
with a genetically related K. pneumoniae harboring blaOXA-
163 [321]. OXA-247 showed susceptibility to carbapenems
and expanded-spectrum cephalosporins similar to OXA-48.
On the other hand, a novel variant called OXA-370 was
originally described in an E. hormaechei isolate in Porto
Alegre, Brazil [322]. This variant differs from OXA-48 by a
unique amino acid substitution and represents the first
report an OXA-48-like enzyme in Brazil. Recently, in Rio de
Janeiro, the blaOXA-370 gene has been detected in 24
Enterobacteriaceae isolates, namely 22 K. pneumoniae, 1 E.
cloacae, and 1 E. aerogenes [323].
4.6. OXA-143 subgroup
OXA-143 is the representative variant of a recently discov-
ered subgroup of CHDLs. OXA-143 was first identified in 2004
in an A. baumannii isolate from Brazil that was resistant to
carbapenems but susceptible to extended-spectrum cepha-
losporins [324]. Further studies have shown the dissemina-
tion of OXA-143 among A. baumannii isolates in different
Brazilian regions [134,265,266,273,276]. It seems that the
prevalence of OXA-143 (8–76%) varies geographically
depending on the circulating clones and the specific regions
and hospitals [266].
OXA-231 is a novel variant described in two A. baumannii
isolates collected in Brazil in 2007 and 2008 [325,326]. Most
recently, two studies evidenced the first detection of OXA-253,
an OXA-143 variant, in an A. baumannii isolates collected in
Honduras [326] and Brazil [327]. The identification of these
variants along with the report of an OXA-255-producing A.
pittii from Indiana, USA suggests that OXA-143-type β-lacta-
mases are spreading in the Americas [326].
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 287
4.7. OXA-235 subgroup
This OXA subgroup includes the OXA-235 carbapenemase
which was found on the chromosome and plasmid of an A.
baumannii isolate recovered in Mexico in 2007 [310]. Other
nine blaOXA-235-like-harboring A. baumannii isolates were also
obtained from the USA. As expected for most CHDLs, OXA-235
hydrolyzes penicillins and carbapenems but spares extended-
spectrum cephalosporins.
5. Conclusion
Carbapenemases have become a public health problem of
global dimensions since they threaten the efficacy of most
β-lactams including the carbapenems. In Latin America and
the Caribbean, carbapenemases belonging to the three
Ambler molecular classes have been identified. Of note,
mobile genetic elements such as plasmids and integrons
play a role facilitating the dissemination of several types of
carbapenemase-encoding genes. Predominantly, KPC-type
enzymes have been described in Enterobacteriaceae,
metallo-β-lactamases in P. aeruginosa, and OXA-type
enzymes in A. baumannii. The increased frequency of reports
on carbapenemases in Latin America and the Caribbean
suggests they have successfully spread and become ende-
mic in some countries. A low threshold for suspicion and
early detection of carbapenemase-producing clinical isolates
are of paramount importance for appropriate treatment and
implementation of infection control measures. Rational use
of antibiotics, accurate and rapid diagnostic techniques, and
strict adherence to hygiene measures are needed to prevent
and control the acquisition and spread of carbapenemase-
encoding genes; however, multidisciplinary action and poli-
tical engagement are crucial in order to tackle antimicrobial
resistance.
6. Expert commentary
Carbapenems were for many years the most potent and
broad-spectrum β-lactam antibiotics, traditionally reserved
for the treatment of serious gram-negative bacterial infections.
For this reason, the dissemination of carbapenemase-produ-
cing Enterobacteriaceae, P. aeruginosa, and A. baumannii repre-
sents an alarming public health threat of global dimensions.
Despite radical efforts in infection control and improvements
in rapid molecular diagnostics, carbapenem-resistant gram-
negative bacteria remain a formidable threat as few antimi-
crobial agents are reliably active and the landscape for novel
agents becoming commercially available in upcoming years is
uncertain. The emergence of carbapenemases among diverse
gram-negative bacteria has not spared Latin America and the
Caribbean. Countries such as Brazil, Colombia, Argentina, and
Mexico account for the majority of these reports.
Carbapenemase detection requires a high index of suspicion
and can be resource intensive. Diagnostic microbiology
laboratories with sophisticated assays in addition to surveil-
lance programs run by research centers are essential to iden-
tifying these challenging resistance mechanisms. This may
explain the underreporting or even absence of reporting in
288 K. ESCANDÓN-VARGAS ET AL.
several countries in Latin America and the Caribbean. A joint
effort is required from hospitals, governments and scientific
organizations in order to curb the overwhelming challenge of
antibiotic resistance. Early suspicion and detection along with
implementation of antimicrobial stewardship programs in all
healthcare settings are crucial for the control and prevention
of carbapenemase-producing bacteria. Efforts to improve
national and international surveillance systems as well as edu-
cational awareness among healthcare professionals should
also be prioritized.
7. Five-year view
In five years from now, there will be recognition of novel
carbapenemases and even greater dissemination of the exist-
ing ones. Likewise, coexpression of other resistance mechan-
isms (e.g. mcr-1 gene) will be increasingly reported in gram-
negative pathogens. Overall, healthcare-associated infections
caused by carbapenemase-producing bacteria will reach an
unprecedented impact in terms of morbidity and mortality,
length of hospital stay, and healthcare costs.
In Latin America and the Caribbean, a ‘bundle’ approach for
the containment of these organisms will be deployed. This will
be accomplished through integrated strategies, including
accurate, affordable, and readily accessible diagnostics, reli-
ably effective new antimicrobials, active surveillance, success-
ful antimicrobial stewardship programs, and augmented
infection control practices. Research funding and support for
the description of resistance mechanisms, validation of current
infection control practices, and antimicrobial development will
be prioritized by the government. Institutions that practice
infection control, support state-of-the-art microbiology labora-
tories, and fund stewardship programs will receive recognition
and incentives for their foresight. Collaborative and joint
efforts will lead to an enhanced understanding and awareness
of the epidemiology of carbapenemases, and the contribution
of antimicrobial use and the environment in the propagation
of these enzymes.
On the other hand, antibiotic alternatives would be cur-
rently in development or in clinical trials for the treatment of
multidrug-resistant, extensively drug-resistant, and pandrug-
resistant bacteria infections. Recognition and incentives for all
of the above is imperative in the ongoing struggle against
antimicrobial resistance and to prevent antimicrobials from
essentially becoming obsolete.
Key issues
● Enterobacteriaceae, Pseudomonas spp., and Acinetobacter
spp. are responsible for numerous infections in clinical set-
tings and represent a major cause of morbidity and mortal-
ity in part due to their resistance to β-lactams and
frequently to other antibiotics such as quinolones and
aminoglycosides.
● β-lactamase production is the most important mechanism
of resistance to β-lactams in gram-negative bacteria. Within
β-lactamases, carbapenemases have the greatest hydrolytic
spectrum affecting most β-lactams, including the carbape-
nems, and are continuously being identified worldwide.
● Based on Ambler’s molecular description, carbapenemases
are classified into class A serine-β-lactamases, class B
metallo-β-lactamases, and class D serine-β-lactamases.
Carbapenemases are chromosomally-encoded and/or plas-
mid-mediated, are found in different gram-negative bacter-
ial species, and have different hydrolytic profiles.
● Numerous and novel carbapenemases belonging to three
molecular classes have been described in Latin America and
the Caribbean. The increased frequency of reports on car-
bapenemases in the region suggests they have successfully
spread and even become endemic in some countries.
● Not metalloenzyme carbapenemase A (NMC-A), K. pneumo-
niae carbapenemase (KPC), Guiana extended-spectrum β-
lactamase (GES), and Brazilian Klebsiella carbapenemase
(BKC) are the class A carbapenemases described thus far
in Latin America and the Caribbean.
● Imipenemase (IMP), Verona integron-encoded metallo-β-lac-
tamase (VIM), New Delhi metallo-β-lactamase (NDM), and São
Paulo metallo-β-lactamase (SPM) are the acquired class B
carbapenemases described thus far in Latin America and the
Caribbean.
● The OXA-23, −40/24, −51, −58, −48, −143, and −235 sub-
groups are the class D carbapenemases described to date in
Latin America and the Caribbean.
● Overall, KPC-type enzymes have been described in
Enterobacteriaceae, metallo-β-lactamases in P. aeruginosa,
and OXA-type enzymes in A. baumannii.
Funding
This paper was not funded.
Declaration of interest
MV Villegas has received research grants and/or consultant fees from
Merck Sharp & Dohme (MSD), Merck Colombia, Pfizer, and AstraZeneca.
The authors have no other relevant affiliations or financial involvement
with any organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the manuscript
apart from those disclosed.
ORCID
Kevin Escandón-Vargas http://orcid.org/0000-0002-7173-7486
References
Papers of special note have been highlighted as either of interest (•) or of
considerable interest (••) to readers.
1. Bush K, Jacoby GA. Updated functional classification of β-lacta-
mases. Antimicrob Agents Chemother. 2010;54(3):969–976.
2. Patel G, Bonomo RA. “Stormy waters ahead”: global emergence of
carbapenemases. Front Microbiol. 2013;4:48.
•• Excellent revision of general aspects of carbapanemases in the
world.
3. Tzouvelekis LS, Markogiannakis A, Psichogiou M, et al.
Carbapenemases in klebsiella pneumoniae and other enterobacter-
iaceae: an evolving crisis of global dimensions. Clin Microbiol Rev.
2012;25(4):682–707.
4. Falagas ME, Tansarli GS, Karageorgopoulos DE, et al. Deaths attri-
butable to carbapenem-resistant enterobacteriaceae infections.
Emerg Infect Dis. 2014;20(7):1170–1175.

5. Villegas MV, Pallares CJ, Escandón-Vargas K, et al. Characterization
and clinical impact of bloodstream infection caused by carbapene-
mase-producing enterobacteriaceae in seven Latin American coun-
tries. Plos One. 2016;11(4):e0154092.
•• Latin American cohort study of patients with bloodstream infec-
tions due to carbapenemase-producing Enterobacteriaceae
(CPE) and non-CPE.
6. Hernández-Gómez C, Motoa G, Pallares C, et al. Economic impact of
carbapenemase-producing Enterobacteriaceae causing blood-
stream infections in Latin America. Open Forum Infect Dis. 2015;2
(Suppl 1):S447.
7. Nordmann P, Mariotte S, Naas T, et al. Biochemical properties of a
carbapenem-hydrolyzing β-lactamase from enterobacter cloacae
and cloning of the gene into escherichia coli. Antimicrob Agents
Chemother. 1993;37(5):939–946.
• First report of NMC-A in the world, identified in an E. cloacae
isolate from France.
8. Naas T, Nordmann P. Analysis of a carbapenem-hydrolyzing class A
β-lactamase from enterobacter cloacae and of its LysR-type regu-
latory protein. Proc Natl Acad Sci U S A. 1994;91(16):7693–7697.
9. Pottumarthy S, Moland ES, Juretschko S, et al. NmcA carbapenem-
hydrolyzing enzyme in enterobacter cloacae in North America.
Emerg Infect Dis. 2003;9(8):999–1002.
10. Deshpande LM, Jones RN, Fritsche TR, et al. Occurrence and char-
acterization of carbapenemase-producing enterobacteriaceae:
report from the SENTRY antimicrobial surveillance program (2000-
2004). Microb Drug Resist. 2006;12(4):223–230.
11. Radice M, Power P, Gutkind G, et al. First class A carbapenemase
isolated from enterobacteriaceae in Argentina. Antimicrob Agents
Chemother. 2004;48(3):1068–1069.
• First report of NMC-A in Latin America, identified in an E.
cloacae isolate from Argentina.
12. Blanco VM, Rojas LJ, De La Cadena E, et al. First report of a nonmetallo-
carbapenemase class A carbapenemase in an enterobacter cloacae
isolate from Colombia. Antimicrob Agents Chemother. 2013;57(7):3457.
13. Cuzon G, Naas T, Truong H, et al. Worldwide diversity of klebsiella
pneumoniae that produces β-lactamase blaKPC-2 gene. Emerg
Infect Dis. 2010;16(9):1349–1356.
14. Yu W-L, Lee M-F, Tang H-J, et al. Emergence of KPC new variants
(KPC-16 and KPC-17) and ongoing outbreak in southern Taiwan.
Clin Microbiol Infect. 2015;21(4):347.e5-8.
15. Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydro-
lyzing β-lactamase, KPC-1, from a carbapenem-resistant strain of
klebsiella pneumoniae. Antimicrob Agents Chemother. 2001;45
(4):1151–1161.
• First report of KPC in the world, identified in a K. pneumoniae
isolate from North Carolina, USA.
16. Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of
the global expansion of klebsiella pneumoniae carbapenemases.
Lancet Infect Dis. 2013;13(9):785–796.
17. Villegas MV, Lolans K, Correa A, et al. First detection of the plasmid-
mediated class A carbapenemase KPC-2 in clinical isolates of kleb-
siella pneumoniae from South America. Antimicrob Agents
Chemother. 2006;50(8):2880–2882.
• First report of KPC in Latin America, identified in a K. pneumo-
niae isolates from Colombia.
18. Villegas MV, Lolans K, Correa A, et al. First identification of pseudomo-
nas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing
β-lactamase. Antimicrob Agents Chemother. 2007;51(4):1553–1555.
19. Lopez JA, Correa A, Navon- Venezia S, et al. Intercontinental spread
from Israel to Colombia of a KPC-3- producing klebsiella pneumo-
niae strain. Clin Microbiol Infect. 2011;17(1):52–56.
20. Navon-Venezia S, Leavitt A, Schwaber MJ, et al. First report on a
hyperepidemic clone of KPC-3-producing klebsiella pneumoniae
in Israel genetically related to a strain causing outbreaks in the
United States. Antimicrob Agents Chemother. 2009;53(2):818–
820.
21. Cuzon G, Naas T, Correa A, et al. Dissemination of the KPC-2
carbapenemase in non-klebsiella pneumoniae enterobacterial iso-
lates from Colombia. Int J Antimicrob Agents. 2013;42(1):59–62.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 289
22. Cuervo SI, Sánchez R, Gómez-Rincón JC, et al. Behavior of carba-
penemase-producing klebsiella pneumoniae cases in cancer
patients at a third level hospital in Bogotá, D.C. Biomedica.
2014;34(Suppl 1):170–180.
23. Martinez P, Sanchez L, Mattar S. Carbapenemase KPC-2 in ESBL-
producing enterobacteriaceae from two clinics from Villavicencio,
Colombia. Braz J Infect Dis. 2014;18(1):100–101.
24. Rodríguez EC, Saavedra SY, Leal AL, et al. The spread of KPC-3
klebsiella pneumoniae in hospitals in Bogotá over a three-year
period (2008-2010). Biomedica. 2014;34(Suppl 1):224–231.
25. Pacheco R, Osorio L, Correa AM, et al. Prevalence of gram-negative
bacteria harboring bla KPC gene in Colombian hospitals.
Biomedica. 2014;34(Suppl 1):81–90.
26. Vanegas JM, Parra OL, Jiménez JN. Molecular epidemiology of
carbapenem resistant gram-negative bacilli from infected pediatric
population in tertiary-care hospitals in Medellín, Colombia: an
increasing problem. BMC Infect Dis. 2016;16(1):463.
27. Mojica MF, Correa A, Vargas DA, et al. Molecular correlates of the
spread of KPC-producing enterobacteriaceae in Colombia. Int J
Antimicrob Agents. 2012;40(3):277–279.
28. Ocampo AM, Chen L, Cienfuegos AV, et al. A two-year surveillance
in five Colombian tertiary care hospitals reveals high frequency of
non-CG258 clones of carbapenem-resistant klebsiella pneumoniae
with distinct clinical characteristics. Antimicrob Agents Chemother.
2016;60(1):332–342.
29. Pavez M, Mamizuka EM, Lincopan N. Early dissemination of KPC-2-
producing klebsiella pneumoniae strains in Brazil. Antimicrob
Agents Chemother. 2009;53(6):2702.
30. Zavascki AP, Zoccoli CM, Machado ABMP, et al. KPC-2-producing
klebsiella pneumoniae in Brazil: a widespread threat in waiting? Int
J Infect Dis. 2010;14(6):e539–40.
31. Monteiro J, Santos AF, Asensi MD, et al. First report of KPC-2-
producing klebsiella pneumoniae strains in Brazil. Antimicrob
Agents Chemother. 2009;53(1):333–334.
32. Peirano G, Seki LM, Val Passos VL, et al. Carbapenem-hydrolysing β-
lactamase KPC-2 in klebsiella pneumoniae isolated in Rio de
Janeiro, Brazil. J Antimicrob Chemother. 2009;63(2):265–268.
33. Zavascki AP, Machado ABMP, De Oliveira KRP, et al. KPC-2-produ-
cing enterobacter cloacae in two cities from Southern Brazil. Int J
Antimicrob Agents. 2009;34(3):286–288.
34. D’Alincourt Carvalho-Assef AP, Leão RS, Da Silva RV, et al.
Escherichia coli producing KPC-2 carbapenemase: first report in
Brazil. Diagn Microbiol Infect Dis. 2010;68(3):337–338.
35. Del Peloso PF, Barros MFL, De Santos FA D. Serratia marcescens
KPC sepsis. J Bras Patol Med Lab. 2010;46(5):365–367.
36. Leão RS, Carvalho-Assef APDA, Correal JCD, et al. KPC-2 producing
klebsiella pneumoniae and escherichia coli co-infection in a cathe-
ter-related infection. Clin Microbiol Infect. 2011;17(3):380–382.
37. Bergamasco MD, Barroso Barbosa M, De Oliveira Garcia D, et al.
Infection with klebsiella pneumoniae carbapenemase (KPC)-produ-
cing K. pneumoniae in solid organ transplantation. Traspl Infect
Dis. 2012;14(2):198–205.
38. Almeida ACS, Cavalcanti FLS, Martins WMB, et al. First description
of KPC-2-producing klebsiella oxytoca in Brazil. Antimicrob Agents
Chemother. 2013;57(8):4077–4078.
39. Da Costa Guimarães AC, Almeida ACS, Nicoletti AG, et al. Clonal
spread of carbapenem-resistant serratia marcescens isolates shar-
ing an IncK plasmid containing blaKPC-2. Int J Antimicrob Agents.
2013;42(4):369–370.
40. Ribeiro VB, Andrade LN, Linhares AR, et al. Molecular characteriza-
tion of klebsiella pneumoniae carbapenemase-producing isolates
in southern Brazil. J Med Microbiol. 2013;62(Pt 11):1721–1727.
41. Freire MP, Pierrotti LC, Filho HHC, et al. Infection with klebsiella
pneumoniae carbapenemase (KPC)-producing klebsiella pneumoniae
in cancer patients. Eur J Clin Microbiol Infect Dis. 2015;34(2):277–286.
42. Arend LN, Pilonetto M, Siebra C, et al. Phenotypic and molecular
characterization of 942 carbapenem-resistant enterobacteriaceae
(CRE) in southern Brazil. J Infect Chemother. 2015;21(4):316–318.
43. Arend LN, Toledo P, Pilonetto M, et al. Molecular epidemiology of
klebsiella pneumoniae carbapenemase-producing
290 K. ESCANDÓN-VARGAS ET AL.
enterobacteriaceae in different facilities in Southern Brazil. Am J
Infect Control. 2015;43(2):137–140.
44. Tuon FF, Scharf C, Rocha JL, et al. KPC-producing enterobacter
aerogenes infection. Braz J Infect Dis. 2015;19(3):324–327.
45. Biberg CA, Rodrigues ACS, Do Carmo SF, et al. KPC-2-producing
klebsiella pneumoniae in a hospital in the midwest region of Brazil.
Braz J Microbiol. 2015;46(2):501–504.
46. Almeida ACS, De Castro KKA, Fehlberg LCC, et al. Carbapenem-
resistant enterobacter gergoviae harbouring blaKPC-2 in Brazil. Int
J Antimicrob Agents. 2014;44(4):369–370.
47. Seki LM, Pereira PS, De Souza M Da PAH, et al. Molecular epide-
miology of KPC-2- producing klebsiella pneumoniae isolates in
Brazil: the predominance of sequence type 437. Diagn Microbiol
Infect Dis. 2011;70(2):274–277.
48. Andrade LN, Curiao T, Ferreira JC, et al. Dissemination of blaKPC-2
by the spread of klebsiella pneumoniae clonal complex 258 clones
(ST258, ST11, ST437) and plasmids (IncFII, IncN, IncL/M) among
enterobacteriaceae species in Brazil. Antimicrob Agents
Chemother. 2011;55(7):3579–3583.
49. Pereira PS, De Araujo CFM, Seki LM, et al. Update of the molecular
epidemiology of KPC-2-producing klebsiella pneumoniae in Brazil:
spread of clonal complex 11 (ST11, ST437 and ST340). J Antimicrob
Chemother. 2013;68(2):312–316.
50. Castanheira M, Costello AJ, Deshpande LM, et al. Expansion of
clonal complex 258 KPC-2-producing klebsiella pneumoniae in
Latin American hospitals: report of the SENTRY antimicrobial sur-
veillance program. Antimicrob Agents Chemother. 2012;56
(3):1668–1669.
51. Fehlberg LCC, Carvalho AMC, Campana EH, et al. Emergence of
klebsiella pneumoniae-producing KPC-2 carbapenemase in Paraíba,
Northeastern Brazil. Braz J Infect Dis. 2012;16(6):577–580.
52. Nicoletti AG, Fehlberg LCC, Picão RC, et al. Clonal complex 258, the
most frequently found multilocus sequence type complex in KPC-
2-producing klebsiella pneumoniae isolated in Brazilian hospitals.
Antimicrob Agents Chemother. 2012;56(8):4563–4564.
53. Tavares CP, Pereira PS, Marques EDA, et al. Molecular epidemiology
of KPC-2-producing enterobacteriaceae (non-Klebsiella pneumo-
niae) isolated from Brazil. Diagn Microbiol Infect Dis. 2015;82
(4):326–330.
54. Kazmierczak KM, Biedenbach DJ, Hackel M, et al. Global dissemina-
tion of blaKPC into bacterial species beyond klebsiella pneumoniae
and in vitro susceptibility to ceftazidime-avibactam and aztreonam-
avibactam. Antimicrob Agents Chemother. 2016;60(8):4490–4500.
55. Jaskulski MR, Medeiros BC, Borges JV, et al. Assessment of
extended-spectrum β-lactamase, KPC carbapenemase and porin
resistance mechanisms in clinical samples of klebsiella pneumoniae
and enterobacter spp. Int J Antimicrob Agents. 2013;42(1):76–79.
56. Cabral AB, Maciel MAV, Barros JF, et al. Detection of bla KPC-2 in
proteus mirabilis in Brazil. Rev Soc Bras Med Trop. 2015;48(1):94–95.
57. Pasteran FG, Otaegui L, Guerriero L, et al. Klebsiella pneumoniae
carbapenemase-2, Buenos Aires, Argentina. Emerg Infect Dis.
2008;14(7):1178–1180.
58. Gomez SA, Pasteran FG, Faccone D, et al. Clonal dissemination of
klebsiella pneumoniae ST258 harbouring KPC-2 in Argentina. Clin
Microbiol Infect. 2011;17(10):1520–1524.
59. Cejas D, Fernandez Canigia L, Nastro M, et al. Hyperendemic clone
of KPC producing klebsiella pneumoniae ST 258 in Buenos Aires
hospitals. Infect Genet Evol. 2012;12(3):499–501.
60. Córdova E, Lespada MI, Gómez N, et al. Clinical and epidemiologi-
cal study of an outbreak of KPC-producing klebsiella pneumoniae
infection in Buenos Aires, Argentina. Enferm Infecc Microbiol Clin.
2012;30(7):376–379.
61. Gregory CJ, Llata E, Stine N, et al. Outbreak of carbapenem-resistant
klebsiella pneumoniae in Puerto Rico associated with a novel carbape-
nemase variant. Infect Control Hosp Epidemiol. 2010;31(5):476–484.
62. Robledo IE, Aquino EE, Vázquez GJ. Detection of the KPC gene in
escherichia coli, klebsiella pneumoniae, pseudomonas aeruginosa,
and acinetobacter baumannii during a PCR-based nosocomial sur-
veillance study in Puerto Rico. Antimicrob Agents Chemother.
2011;55(6):2968–2970.
63. Marcano D, De Jesús A, Hernández L, et al. Frequency of enzymes
associated with reduced sensitivity to beta-lactam antibiotics in
enterobacteria isolates, Caracas, Venezuela. Rev Panam Salud
Publica. 2011;30(6):529–534.
64. Luque J, Bohórquez P, Marcano D, et al. Spread of carbapenemase-
producing enterobacteriaceae type KPC in Venezuela. Bol Venez
Infectol. 2012;23(1):13–19.
65. Pena MC, Vierma H, Farina E, et al. First detection of escherichia coli
KPC carbapenemase in Venezuela. 51st ICAAC. Chicago, USA: ASM;
2011. p. Abstract C1–1219.
66. Labrador I, Araque M. First description of KPC-2-producing kleb-
siella oxytoca isolated from a pediatric patient with nosocomial
pneumonia in Venezuela. Case Rep Infect Dis. 2014;434987:2014.
67. Rodríguez-Zulueta P, Silva-Sánchez J, Barrios H, et al. First outbreak
of KPC-3-producing klebsiella pneumoniae (ST258) clinical isolates
in a Mexican medical center. Antimicrob Agents Chemother.
2013;57(8):4086–4088.
68. Garza-Ramos U, Moreno-Dominguez S, Hernández-Castro R, et al.
Identification and characterization of imipenem-resistant klebsiella
pneumoniae and susceptible klebsiella variicola isolates obtained
from the same patient. Microb Drug Resist. 2016;22(3):179–184.
69. Garza-Ramos U, Barrios H, Reyna-Flores F, et al. Characteristics of
KPC-2-producing klebsiella pneumoniae (ST258) clinical isolates
from outbreaks in 2 Mexican medical centers. Diagn Microbiol
Infect Dis. 2014;79(4):483–485.
70. Iñiguez D, Zurita J, Alcocer I, et al. Klebsiella pneumoniae carbape-
nemase type 2-producing bacteria: first case report in Ecuador. Rev
Fac Cien Med. 2012;37:39–42.
71. Zurita J, Alcocer I, Ortega-Paredes D, et al. Carbapenem-hydrolys-
ing β-lactamase KPC-2 in klebsiella pneumoniae isolated in ecua-
dorian hospitals. J Glob Antimicrob Resist. 2013;1(4):229–230.
72. Cifuentes M, García P, San Martín P, et al. First isolation of KPC in
Chile: from Italy to a public hospital in Santiago. Rev Chil Infectol.
2012;29(2):224–228.
73. Marquez C, Ingold A, Echeverría N, et al. Emergence of KPC-produ-
cing klebsiella pneumoniae in Uruguay: infection control and mole-
cular characterization. New Microbes New Infect. 2014;2(3):58–63.
74. Quiñones D, Hart M, Espinosa F, et al. Emergence of klebsiella
pneumoniae clinical isolates producing KPC-2 carbapenemase in
Cuba. New Microbes New Infect. 2014;2(4):123–126.
75. Instituto de Salud Pública de Chile. [Surveillance of antimicrobial
resistance in bacteria that can cause healthcare-associated infec-
tions]. Bol Inst Salud Pública Chile. 2015;5(4):1–25.
76. Barría-Loaiza C, Pincheira A, Quezada M, et al. Molecular typing and
genetic environment of the blaKPC gene in Chilean isolates of
klebsiella pneumoniae. J Glob Antimicrob Resist. 2016;4:28–34.
77. Zúñiga J, Cruz G, Pérez C, et al. The combined-disk boronic acid
test as an accurate strategy for the detection of KPC carbapene-
mase in Central America. J Infect Dev Ctries. 2016;10(3):298–303.
78. Jones RN, Guzman-Blanco M, Gales AC, et al. Susceptibility rates in
Latin American nations: report from a regional resistance surveil-
lance program (2011). Braz J Infect Dis. 2013;17(6):672–681.
79. Velásquez J, Hernández R, Pamo O, et al. Carbapenem-resistant
klebsiella pneumoniae: first case of KPC type carbapenemase in
Peru. Rev Soc Peru Med Interna. 2013;26(4):192–196.
80. Miriagou V, Tzouvelekis LS, Rossiter S, et al. Imipenem resistance in
a salmonella clinical strain due to plasmid-mediated class A carba-
penemase KPC-2. Antimicrob Agents Chemother. 2003;47(4):1297–
1300.
81. Rodríguez E, Bautista A, Barrero L. First report of a salmonella
enterica serovar typhimurium isolate with carbapenemase
(KPC-2) in Colombia. Antimicrob Agents Chemother. 2014;58
(2):1263–1264.
82. Jure MA, Duprilot M, Musa HE, et al. Emergence of KPC-2-produ-
cing salmonella enterica serotype schwarzengrund in Argentina.
Antimicrob Agents Chemother. 2014;58(10):6335–6336.
83. Melgarejo TN, Álvarez M, Irala J, et al. Primer aislamiento de
Salmonella productora de KPC en Paraguay. 10° Congreso
Paraguayo de Infectología. Asunción, Paraguay: Sociedad
Paraguaya de Infectología; 2015.

84. Ribeiro VB, Zavascki AP, Nodari CS, et al. Detection of blaKPC-2 in a
carbapenem-resistant kluyvera georgiana. J Antimicrob
Chemother. 2012;67(11):2776–2777.
85. Wolter DJ, Khalaf N, Robledo IE, et al. Surveillance of carbapenem-
resistant pseudomonas aeruginosa isolates from Puerto Rican med-
ical center hospitals: dissemination of KPC and IMP-18 β-lacta-
mases. Antimicrob Agents Chemother. 2009;53(4):1660–1664.
86. Wolter DJ, Kurpiel PM, Woodford N, et al. Phenotypic and enzy-
matic comparative analysis of the novel KPC variant KPC-5 and its
evolutionary variants, KPC-2 and KPC-4. Antimicrob Agents
Chemother. 2009;53(2):557–562.
87. Akpaka PE, Swanston WH, Ihemere HN, et al. Emergence of KPC-
producing pseudomonas aeruginosa in trinidad and tobago. J Clin
Microbiol. 2009;47(8):2670–2671.
88. Almeida ACS, Vilela MA, Cavalcanti FLS, et al. First description of
KPC-2-producing pseudomonas putida in Brazil. Antimicrob Agents
Chemother. 2012;56(4):2205–2206.
89. Jácome PRL De A, Alves LR, Cabral AB, et al. First report of KPC-
producing pseudomonas aeruginosa in Brazil. Antimicrob Agents
Chemother. 2012;56(9):4990.
90. Rizek C, Fu L, Dos Santos LC, et al. Characterization of carbapenem-
resistant Pseudomonas aeruginosa clinical isolates, carrying multi-
ple genes coding for this antibiotic resistance. Ann Clin Microbiol
Antimicrob. 2014;13(1):43.
91. Pasteran F, Faccone D, Gomez S, et al. Detection of an international
multiresistant clone belonging to sequence type 654 involved in
the dissemination of KPC-producing pseudomonas aeruginosa in
Argentina. J Antimicrob Chemother. 2012;67(5):1291–1293.
92. Santella G, Cittadini R, Papalia M, et al. First clonal spread of KPC-
producing pseudomonas aeruginosa in Buenos Aires, Argentina.
Infect Genet Evol. 2012;12(8):2003–2005.
93. García Ramírez D, Nicola F, Zarate S, et al. Emergence of pseudo-
monas aeruginosa with KPC-type carbapenemase in a teaching
hospital: an 8-year study. J Med Microbiol. 2013;62(Pt 10):1565–
1570.
94. Robledo IE, Aquino EE, Santé MI, et al. Detection of KPC in acine-
tobacter spp. in Puerto Rico. Antimicrob Agents Chemother.
2010;54(3):1354–1357.
95. Poirel L, Le Thomas I, Naas T, et al. Biochemical sequence analyses
of GES-1, a novel class A extended-spectrum β-lactamase, and the
class 1 integron In52 from klebsiella pneumoniae. Antimicrob
Agents Chemother. 2000;44(3):622–632.
96. Poirel L, Weldhagen GF, Naas T, et al. GES-2, a class A β-lactamase
from pseudomonas aeruginosa with increased hydrolysis of imipe-
nem. Antimicrob Agents Chemother. 2001;45(9):2598–2603.
97. Wachino J, Doi Y, Yamane K, et al. Molecular characterization of a
cephamycin-hydrolyzing and inhibitor-resistant class A β-lacta-
mase, GES-4, possessing a single G170S substitution in the Ω-
loop. Antimicrob Agents Chemother. 2004;48(8):2905–2910.
98. Vourli S, Giakkoupi P, Miriagou V, et al. Novel GES/IBC extended-
spectrum β-lactamase variants with carbapenemase activity in clin-
ical enterobacteria. FEMS Microbiol Lett. 2004;234(2):209–213.
99. Moubareck C, Brémont S, Conroy M-C, et al. GES-11, a novel
integron-associated GES variant in acinetobacter baumannii.
Antimicrob Agents Chemother. 2009;53(8):3579–3581.
100. Bonnin RA, Nordmann P, Potron A, et al. GES-type extended-spec-
trum β-lactamase in acinetobacter baumannii. Antimicrob Agents
Chemother. 2011;55(1):349–354.
101. Barbosa PP. Genetic and biochemical characterization of GES-16, a
novel GES-type β-lactamase with carbapenemase activity in
Serratia marcescens [master’s thesis]. São Paulo, Brazil:
Universidade Federal de São Paulo; 2011.
102. Bebrone C, Bogaerts P, Delbrück H, et al. GES-18, a new carbape-
nem-hydrolyzing GES-type β-lactamase from pseudomonas aerugi-
nosa that contains Ile80 and Ser170 residues. Antimicrob Agents
Chemother. 2013;57(1):396–401.
103. Barrios H, Garza-Ramos U, Ochoa-Sanchez LE, et al. A plasmid-
encoded class 1 integron contains GES-type extended-spectrum
β-lactamases in enterobacteriaceae clinical isolates in Mexico.
Antimicrob Agents Chemother. 2012;56(7):4032–4034.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 291
104. Pasteran F, Faccone D, Campos K, et al. Dissemination of GES
extended-spectrum β-lactamase-producing Pseudomonas aerugi-
nosa (PA) in Argentina. 44th ICAAC, Washington, DC, USA:
American Society for Microbiology p. Abstract C2–1327. 2004.
105. Da Fonseca EL, Vieira VV, Cipriano R, et al. Emergence of blaGES-
5 in clinical colistin-only-sensitive (COS) pseudomonas aerugi-
nosa strain in Brazil. J Antimicrob Chemother. 2007;59(3):576–
577.
106. Picão RC, Poirel L, Gales AC, et al. Diversity of β-lactamases pro-
duced by ceftazidime-resistant pseudomonas aeruginosa isolates
causing bloodstream infections in Brazil. Antimicrob Agents
Chemother. 2009;53(9):3908–3913.
107. Polotto M, Casella T, De Lucca Oliveira MG, et al. Detection of P.
aeruginosa harboring blaCTX-M-2, blaGES-1 and blaGES-5, blaIMP-1
and blaSPM-1 causing infections in Brazilian tertiary-care hospital.
BMC Infect Dis. 2012;12:176.
108. Picão RC, Santos AF, Nicoletti AG, et al. Detection of GES-5-produ-
cing klebsiella pneumoniae in Brazil. J Antimicrob Chemother.
2010;65(4):796–797.
109. Ribeiro VB, Falci DR, Rozales FP, et al. Carbapenem-resistant GES-5-
producing klebsiella pneumoniae in southern Brazil. Braz J Infect
Dis. 2014;18(2):231–232.
110. Castillo-Vera J, Ribas-Aparicio RM, Nicolau CJ, et al. Unusual diver-
sity of acquired β-lactamases in multidrug-resistant pseudomonas
aeruginosa isolates in a Mexican hospital. Microb Drug Resist.
2012;18(5):471–478.
111. Garza-Ramos U, Barrios H, Reyna-Flores F, et al. Widespread of
ESBL- and carbapenemase GES-type genes on carbapenem-resis-
tant pseudomonas aeruginosa clinical isolates: a multicenter study
in Mexican hospitals. Diagn Microbiol Infect Dis. 2015;81(2):135–
137.
112. Nicoletti AG, Marcondes MFM, Martins WMBS, et al.
Characterization of BKC-1 class A carbapenemase from klebsiella
pneumoniae clinical isolates in Brazil. Antimicrob Agents
Chemother. 2015;59(9):5159–5164.
• First report of BKC in the world, identified in K. pneumoniae
isolates from Brazil.
113. Martins WMBS, Nicoletti AG, Santos SR, et al. Frequency of BKC-1-
producing klebsiella species isolates. Antimicrob Agents
Chemother. 2016;60(8):5044–5046.
114. Queenan AM, Carbapenemases: BK. the versatile β-lactamases. Clin
Microbiol Rev. 2007;20(3):440–458.
•• Comprehensive review of carbapenemases, their classification
and mechanisms.
115. Watanabe M, Iyobe S, Inoue M, et al. Transferable imipenem resis-
tance in pseudomonas aeruginosa. Antimicrob Agents Chemother.
1991;35(1):147–151.
116. Osano E, Arakawa Y, Wacharotayankun R, et al. Molecular charac-
terization of an enterobacterial metallo β-lactamase found in a
clinical isolate of Serratia marcescens that shows imipenem resis-
tance. Antimicrob Agents Chemother. 1994;38(1):71–78.
117. Ito H, Arakawa Y, Ohsuka S, et al. Plasmid-mediated dissemination
of the metallo-β-lactamase gene blaIMP among clinically isolated
strains of Serratia marcescens. Antimicrob Agents Chemother.
1995;39(4):824–829.
118. Arakawa Y, Murakami M, Suzuki K, et al. A novel integron-like
element carrying the metallo-β-lactamase gene blaIMP.
Antimicrob Agents Chemother. 1995;39(7):1612–1615.
119. Zhao W-H, Hu Z-Q. IMP-type metallo-β-lactamases in gram-nega-
tive bacilli: distribution, phylogeny, and association with integrons.
Crit Rev Microbiol. 2011;37(3):214–226.
120. Gales AC, Tognim MCB, Reis AO, et al. Emergence of an IMP-like
metallo-enzyme in an acinetobacter baumannii clinical strain from
a Brazilian teaching hospital. Diagn Microbiol Infect Dis. 2003;45
(1):77–79.
121. Lincopan N, McCulloch JA, Reinert C, et al. First isolation of metallo-
β-lactamase-producing multiresistant klebsiella pneumoniae from
a patient in Brazil. J Clin Microbiol. 2005;43(1):516–519.
122. Sader HS, Reis AO, Silbert S, et al. IMPs, VIMs and SPMs: the
diversity of metallo-β-lactamases produced by carbapenem-
292 K. ESCANDÓN-VARGAS ET AL.
resistant Pseudomonas aeruginosa in a Brazilian hospital. Clin
Microbiol Infect. 2005;11(1):73–76.
123. Marra AR, Pereira CAP, Gales AC, et al. Bloodstream infections with
metallo-β-lactamase-producing pseudomonas aeruginosa: epide-
miology, microbiology, and clinical outcomes. Antimicrob Agents
Chemother. 2006;50(1):388–390.
124. Martins AF, Zavascki AP, Gaspareto PB, et al. Dissemination of
pseudomonas aeruginosa producing SPM-1-like and IMP-1-like
metallo-β-lactamases in hospitals from southern Brazil. Infection.
2007;35(6):457–460.
125. Gaspareto PB, Martins AF, Zavascki AP, et al. Occurrence of blaSPM-
1 and blaIMP-1 genes of metallo-β-lactamases in clinical isolates of
pseudomonas aeruginosa from three universitary hospitals in the
city of Porto Alegre, Brazil. Braz J Microbiol. 2007;38:108–109.
126. Silva FM, Carmo MS, Silbert S, et al. SPM-1-producing pseudomo-
nas aeruginosa: analysis of the ancestor relationship using multi-
locus sequence typing, pulsed-field gel electrophoresis, and
automated ribotyping. Microb Drug Resist. 2011;17(2):215–220.
127. Camargo CH, Bruder-Nascimento A, Mondelli AL, et al. Detection of
SPM and IMP metallo-β-lactamases in clinical specimens of pseu-
domonas aeruginosa from a Brazilian public tertiary hospital. Braz J
Infect Dis. 2011;15(5):478–481.
128. Fehlberg LCC, Xavier DE, Peraro PP, et al. Beta-lactam resistance
mechanisms in pseudomonas aeruginosa strains causing blood-
stream infections: comparative results between Brazilian and
American isolates. Microb Drug Resist. 2012;18(4):402–407.
129. Lucena A, Dalla Costa LM, Nogueira KS, et al. Nosocomial infections
with metallo-beta-lactamase-producing pseudomonas aeruginosa:
molecular epidemiology, risk factors, clinical features and out-
comes. J Hosp Infect. 2014;87(4):234–240.
130. Sader HS, Castanheira M, Mendes RE, et al. Dissemination and
diversity of metallo-β-lactamases in Latin America: report from
the SENTRY antimicrobial surveillance program. Int J Antimicrob
Agents. 2005;25(1):57–61.
131. Tognim MCB, Gales AC, Penteado AP, et al. Dissemination of IMP-1
metallo-β-lactamase-producing acinetobacter species in a Brazilian
teaching hospital. Infect Control Hosp Epidemiol. 2006;27(7):742–
747.
132. Mendes RE, Castanheira M, Toleman MA, et al. Characterization of
an integron carrying blaIMP-1 and a new aminoglycoside resis-
tance gene, aac(6ʹ)-31, and its dissemination among genetically
unrelated clinical isolates in a Brazilian hospital. Antimicrob
Agents Chemother. 2007;51(7):2611–2614.
133. Picão RC, Andrade SS, Nicoletti AG, et al. Metallo-β-lactamase
detection: comparative evaluation of double-disk synergy versus
combined disk tests for IMP-, GIM-, SIM-, SPM-, or VIM-producing
isolates. J Clin Microbiol. 2028–37;46(6):2008.
134. Mostachio AK, Levin AS, Rizek C, et al. High prevalence of OXA-143
and alteration of outer membrane proteins in carbapenem-resis-
tant acinetobacter spp. isolates in Brazil. Int J Antimicrob Agents.
2012;39(5):396–401.
135. Lincopan N, Leis R, Vianello MA, et al. Enterobacteria producing
extended-spectrum β-lactamases and IMP-1 metallo-β-lactamases
isolated from Brazilian hospitals. J Med Microbiol. 2006;55(Pt
11):1611–1613.
136. Penteado AP, Castanheira M, Pignatari ACC, et al. Dissemination of
blaIMP-1-carrying integron In86 among klebsiella pneumoniae iso-
lates harboring a new trimethoprim resistance gene dfr23. Diagn
Microbiol Infect Dis. 2009;63(1):87–91.
137. Mendes RE, Toleman MA, Ribeiro J, et al. Integron carrying a novel
metallo-β-lactamase gene, blaIMP-16, and a fused form of amino-
glycoside-resistant gene aac(6ʹ)-30/aac(6ʹ)-Ib’: report from the
SENTRY antimicrobial surveillance program. Antimicrob Agents
Chemother. 2004;48(12):4693–4702.
138. Cayô R, Rodrigues-Costa F, Matos AP, et al. Identification of a new
integron harboring blaIMP-10 in carbapenem-resistant acinetobac-
ter baumannii clinical isolates. Antimicrob Agents Chemother.
2015;59(6):3687–3689.
139. Silva KE, Cayô R, Carvalhaes CG, et al. Coproduction of KPC-2 and
IMP-10 in carbapenem-resistant Serratia marcescens isolates from
an outbreak in a Brazilian teaching hospital. J Clin Microbiol.
2015;53(7):2324–2328.
140. Kazmierczak KM, Rabine S, Hackel M, et al. Multiyear, multinational
survey of the incidence and global distribution of metallo-β-lacta-
mase-producing enterobacteriaceae and pseudomonas aeruginosa.
Antimicrob Agents Chemother. 2016;60(2):1067–1078.
141. Garza-Ramos U, Tinoco P, Silva-Sanchez J, et al. Metallo-β-lacta-
mase IMP-18 is located in a class 1 integron (In96) in a clinical
isolate of pseudomonas aeruginosa from Mexico. Int J Antimicrob
Agents. 2008;31(1):78–80.
142. Sánchez-Martinez G, Garza-Ramos UJ, Reyna-Flores FL, et al. In169,
a new class 1 integron that encoded blaIMP-18 in a multidrug-
resistant pseudomonas aeruginosa isolate from Mexico. Arch Med
Res. 2010;41(4):235–239.
143. Garza-Ramos U, Morfin-Otero R, Sader HS, et al. Metallo-β-lacta-
mase gene blaIMP-15 in a class 1 integron, In95, from pseudomo-
nas aeruginosa clinical isolates from a hospital in Mexico.
Antimicrob Agents Chemother. 2008;52(8):2943–2946.
144. Quinones-Falconi F, Galicia-Velasco M, Marchiaro P, et al.
Emergence of pseudomonas aeruginosa strains producing
metallo-β-lactamases of the IMP-15 and VIM-2 types in Mexico.
Clin Microbiol Infect. 2010;16(2):126–131.
145. Garza-Ramos JU, Sanchez-Martinez G, Barajas JM, et al. Variability of
the blaIMP-15-containing integrons, highly related to In95, on an
endemic clone of pseudomonas aeruginosa in Mexico. Microb
Drug Resist. 2010;16(3):191–195.
146. González-Chávez MI, Morfin-Otero R, Jarillo-Quijada C, et al. First
report of blaVIM-4, blaIMP-1 and blaOXA-24-producing
Acinetobacter baumannii clones isolated from nosocomial infections
in Mexico. 51st ICAAC. Chicago, USA: American Society for
Microbiology. 2011. p. Abstract C2–648.
147. Gales AC, Castanheira M, Jones RN, et al. Antimicrobial resistance
among gram-negative bacilli isolated from Latin America: results
from SENTRY antimicrobial surveillance program (Latin America,
2008-2010). Diagn Microbiol Infect Dis. 2012;73(4):354–360.
148. Fritsche TR, Sader HS, Toleman MA, et al. Emerging metallo-β-
lactamase-mediated resistances: a summary report from the world-
wide SENTRY antimicrobial surveillance program. Clin Infect Dis.
2005;41(Suppl 4):S276–8.
149. Fiorilli G, Faccone D, Lopardo H, et al. Emergence of metallo-β-
lactamases in acinetobacter spp clinical isolates from Argentina.
Rev Esp Quimioter. 2010;23(2):100–102.
150. Cejas D, Almuzara M, Santella G, et al. Phenotypic and genotypic
characterization of imipenem-resistant pseudomonas aeruginosa
isolated in a Buenos Aires hospital. Rev Argent Microbiol. 2008;40
(4):238–245.
151. Santella G, Cuirolo A, Almuzara M, et al. Full resistance and
decreased susceptibility to carbapenems in IMP-13-producing
pseudomonas aeruginosa isolates from an outbreak. Antimicrob
Agents Chemother. 2010;54(3):1381–1382.
152. Santella G, Pollini S, Docquier J-D, et al. Intercontinental dissemina-
tion of IMP-13-producing pseudomonas aeruginosa belonging in
sequence type 621. J Clin Microbiol. 2010;48(11):4342–4343.
153. Gomez S, Rapoport M, Togneri A, et al. Emergence of metallo-β-
lactamases in enterobacteriaceae from Argentina. Diagn Microbiol
Infect Dis. 2011;69(1):94–97.
154. Togneri AM, Gómez SA, Podestá LB, et al. Dissemination of blaIMP-
8 among enterobacteriaceae isolates from a Buenos Aires hospital.
Rev Argent Microbiol. 2013;45(2):104–109.
155. Toval F, Guzmán-Marte A, Madriz V, et al. Predominance of carba-
penem-resistant pseudomonas aeruginosa isolates carrying blaIMP
and blaVIM metallo-β-lactamases in a major hospital in Costa Rica.
J Med Microbiol. 2015;64(Pt 1):37–43.
156. Martínez T, Vazquez GJ, Aquino EE, et al. Two novel class I integron
arrays containing IMP-18 metallo-β-lactamase gene in
Pseudomonas aeruginosa clinical isolates from puerto rico.
Antimicrob Agents Chemother. 2012;56(4):2119–2121.
157. Martínez T, Vázquez GJ, Aquino EE, et al. First report of a pseudo-
monas aeruginosa clinical isolate co-harbouring KPC-2 and IMP-18
carbapenemases. Int J Antimicrob Agents. 2012;39(6):542–543.

158. Gonzales-Escalante E, Vicente-Taboada W, Champi-Merino R, et al.
Metallo-β-lactamases in clinical isolates of pseudomonas aerugi-
nosa in Lima, Peru. Rev Peru Med Exp Salud Publica. 2013;30
(2):241–245.
159. Perozo Mena AJ, Castellano González MJ, Chávez Kathyuska T, et al.
Assessment of phenotypic methods for metallobetalactamase
detection in clinical isolates of pseudomonas aeruginosa.
Kasmera. 2013;41(2):115–126.
160. Instituto Nacional de Salud. Caracterización fenotípica y genotípica
de perfiles de resistencia antimicrobiana de aislamientos bacteria-
nos recuperados en infecciones asociadas a la atención en salud
(IAAS) septiembre 2012 - junio 2014. Colombia. Bogota DC,
Colombia:Instituto Nacional de Salud. 2014.
161. Zhao W, Hu Z. Epidemiology and genetics of VIM-type metallo-β-
lactamases in gram-negative bacilli. Future Microbiol. 2011;6
(3):317–333.
162. Lauretti L, Riccio ML, Mazzariol A, et al. Cloning and characteriza-
tion of blaVIM, a new integron-borne metallo-β-lactamase gene
from a pseudomonas aeruginosa clinical isolate. Antimicrob
Agents Chemother. 1999;43(7):1584–1590.
163. Cornaglia G, Mazzariol A, Lauretti L, et al. Hospital outbreak of
carbapenem-resistant pseudomonas aeruginosa producing VIM-1,
a novel transferable metallo-β-lactamase. Clin Infect Dis. 2000;31
(5):1119–1125.
164. Poirel L, Naas T, Nicolas D, et al. Characterization of VIM-2, a carba-
penem-hydrolyzing metallo-β-lactamase and its plasmid- and inte-
gron-borne gene from a pseudomonas aeruginosa clinical isolate in
France. Antimicrob Agents Chemother. 2000;44(4):891–897.
165. Mendes RE, Castanheira M, Garcia P, et al. First isolation of blaVIM-2
in Latin America: report from the SENTRY antimicrobial surveillance
program. Antimicrob Agents Chemother. 2004;48(4):1433–1434.
166. Pérez IA, García CP, Poggi MH, et al. Presence of metallo β-lacta-
mases in imipenem-resistant pseudomonas aeruginosa. Rev Med
Chile. 2008;136:423–432.
167. Sánchez GDI, Marcano ZD, Spadola CE, et al. VIM-type metalloen-
zymes detected in clinical isolates of pseudomonas aeruginosa in
four venezuelan hospitals. Rev Del Inst Nac Hig Rafael Rangel.
2008;39(2):17–22.
168. Guevara A, De Waard J, Araque M. blaVIM-2 gene detection in
metallo-β-lactamase-producing pseudomonas aeruginosa strains
isolated in an intensive care unit in Ciudad Bolívar, Venezuela.
Rev Chil Infectol. 2009;26(4):336–341.
169. Guevara A, Sierra RCI, De Waard J. Molecular characterization of
carbapenem-resistant pseudomonas aeruginosa from four hospi-
tals of Venezuela. Rev Chil Infectol. 2012;29(6):614–621.
170. Guevara A, Sahai JM, Tedesco-Maiullari R. Clonal persistence of
pseudomonas aeruginosa producing metallo-β-lactamases in a
hospital in Ciudad Bolivar, Venezuela. Rev Soc Venez Microbiol.
2015;35:77–82.
171. Franco MRG, Caiaffa-Filho HH, Burattini MN, et al. Metallo-β-lacta-
mases among imipenem-resistant pseudomonas aeruginosa in a
Brazilian university hospital. Clinics. 2010;65(9):825–829.
172. Paez J, Levin AS, Fu L, et al. Clusters of infection due to metallo-β-
lactamase-producing pseudomonas aeruginosa in stem cell trans-
plant and haematology units. J Hosp Infect. 2011;77(1):76–77.
173. Crespo MP, Woodford N, Sinclair A, et al. Outbreak of carbapenem-
resistant pseudomonas aeruginosa producing VIM-8, a novel
metallo-β-lactamase, in a tertiary care center in Cali, Colombia. J
Clin Microbiol. 2004;42(11):5094–5101.
174. Villegas MV, Lolans K, Del Rosario Olivera M, et al. First detection of
metallo-β-lactamase VIM-2 in pseudomonas aeruginosa isolates from
Colombia. Antimicrob Agents Chemother. 2006;50(1):226–229.
175. Correa A, Montealegre MC, Mojica MF, et al. First report of a
pseudomonas aeruginosa isolate coharboring KPC and VIM carba-
penemases. Antimicrob Agents Chemother. 2012;56(10):5422–
5423.
176. Vanegas JM, Cienfuegos AV, Ocampo AM, et al. Similar frequencies
of pseudomonas aeruginosa isolates producing KPC and VIM car-
bapenemases in diverse genetic clones at tertiary-care hospitals in
Medellín, Colombia. J Clin Microbiol. 2014;52(11):3978–3986.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 293
177. Correa A, Del Campo R, Perenguez M, et al. Dissemination of high-
risk clones of extensively drug-resistant pseudomonas aeruginosa
in colombia. Antimicrob Agents Chemother. 2015;59(4):2421–2425.
178. Pasteran F, Faccone D, Petroni A, et al. Novel variant (blaVIM-11) of
the metallo-β-lactamase blaVIM family in a GES-1 extended-spec-
trum-β-lactamase-producing pseudomonas aeruginosa clinical iso-
late in Argentina. Antimicrob Agents Chemother. 2005;49(1):474–
475.
179. Marchiaro P, Tomatis PE, Mussi MA, et al. Biochemical characteriza-
tion of metallo-β-lactamase VIM-11 from a pseudomonas aerugi-
nosa clinical strain. Antimicrob Agents Chemother. 2008;52
(6):2250–2252.
180. Pagniez G, Radice M, Cuirolo A, et al. Prevalence of metallo-β-
lactamase in carbapenem resistant pseudomonas aeruginosa at a
university hospital of Buenos Aires city. Rev Argent Microbiol.
2006;38(1):33–37.
181. Almuzara M, Radice M, De Gárate N, et al. VIM-2-producing pseu-
domonas putida, Buenos Aires. Emerg Infect Dis. 2007;13(4):668–
669.
182. Marchiaro P, Viale AM, Ballerini V, et al. First report of a Tn402-like
class 1 integron carrying blaVIM-2 in pseudomonas putida from
Argentina. J Infect Dev Ctries. 2010;4(6):412–416.
183. Almuzara MN, Vazquez M, Tanaka N, et al. First case of human infec-
tion due to pseudomonas fulva, an environmental bacterium isolated
from cerebrospinal fluid. J Clin Microbiol. 2010;48(2):660–664.
184. Ingold AJ, Castro M, Nabón A, et al. metallo-ß-lactamase gene
detection in a class 1 integron associated to blaCTX-M-2 in a
pseudomonas aeruginosa clinical isolate in Uruguay: first commu-
nication. Rev Argent Microbiol. 2011;43(3):198–202.
185. Marcano D, Pasterán F, Rapoport M, et al. First isolation of a VIM-
producing klebsiella pneumoniae from a seven-year-old child in
Venezuela. J Infect Dev Ctries. 2008;2(3):241–244.
186. Martínez D, Rodulfo HE, Rodríguez L, et al. First report of metallo-β-
lactamases producing enterobacter spp. strains from Venezuela.
Rev Inst Med Trop Sao Paulo. 2014;56(1):67–69.
187. Martínez D, Marcano D, Rodulfo H, et al. KPC and VIM producing
enterobacter cloacae strain from a hospital in northeastern
Venezuela. Invest Clin. 2015;56(2):182–187.
188. Morfin-Otero R, Rodriguez-Noriega E, Deshpande LM, et al.
Dissemination of a blaVIM-2-carrying integron among enterobac-
teriaceae species in Mexico: report from the SENTRY antimicrobial
surveillance program. Microb Drug Resist. 2009;15(1):33–35.
189. Montealegre MC, Correa A, Briceño DF, et al. Novel VIM metallo-β-
lactamase variant, VIM-24, from a klebsiella pneumoniae isolate
from Colombia. Antimicrob Agents Chemother. 2011;55(5):2428–
2430.
190. Rojas LJ, Mojica MF, Blanco VM, et al. Emergence of klebsiella
pneumoniae coharboring KPC and VIM carbapenemases in
Colombia. Antimicrob Agents Chemother. 2013;57(2):1101–1102.
191. Nastro M, Monge R, Zintgraff J, et al. First nosocomial outbreak of
VIM-16-producing serratia marcescens in Argentina. Clin Microbiol
Infect. 2013;19(7):617–619.
192. Almuzara MN, Barberis CM, Rodríguez CH, et al. First report of an
extensively drug-resistant VIM-2 metallo-β-lactamase-producing
brevundimonas diminuta clinical isolate. J Clin Microbiol. 2012;50
(8):2830–2832.
193. Alcántar-Curiel MD, García-Torres LF, González-Chávez MI, et al.
Molecular mechanisms associated with nosocomial carbapenem-
resistant acinetobacter baumannii in Mexico. Arch Med Res.
2014;45(7):553–560.
194. Cornaglia G, Giamarellou H, Rossolini GM. Metallo-β-lactamases: a
last frontier for β-lactams? Lancet Infect Dis. 2011;11(5):381–393.
195. Shahcheraghi F, Abbasalipour M, Feizabadi MM, et al. Isolation and
genetic characterization of metallo-β-lactamase and carbapena-
mase producing strains of acinetobacter baumannii from patients
at Tehran hospitals. Iran J Microbiol. 2011;3(2):68–74.
196. Toleman MA, Simm AM, Murphy TA, et al. Molecular characteriza-
tion of SPM-1, a novel metallo-β-lactamase isolated in Latin
America: report from the SENTRY antimicrobial surveillance pro-
gramme. J Antimicrob Chemother. 2002;50(5):673–679.
294 K. ESCANDÓN-VARGAS ET AL.
• First report of SPM in the world, identified in a P. aeruginosa
isolate from Brazil.
197. Poirel L, Magalhaes M, Lopes M, et al. Molecular analysis of metallo-
β-lactamase gene blaSPM-1-surrounding sequences from dissemi-
nated pseudomonas aeruginosa isolates in Recife, Brazil.
Antimicrob Agents Chemother. 2004;48(4):1406–1409.
198. Salabi AE, Toleman MA, Weeks J, et al. First report of the metallo-β-
lactamase SPM-1 in Europe. Antimicrob Agents Chemother.
2010;54(1):582.
199. Toleman MA, Bennett PM, Walsh TR. ISCR elements: novel gene-
capturing systems of the 21st century? Microbiol Mol Biol Rev.
2006;70(2):296–316.
200. Fonseca EL, Marin MA, Encinas F, et al. Full characterization of the
integrative and conjugative element carrying the metallo-β-lacta-
mase blaSPM-1 and bicyclomycin bcr1 resistance genes found in
the pandemic pseudomonas aeruginosa clone SP/ST277. J
Antimicrob Chemother. 2015;70(9):2547–2550.
201. Hopkins KL, Meunier D, Findlay J, et al. SPM-1 metallo-β-lactamase-
producing pseudomonas aeruginosa ST277 in the UK. J Med
Microbiol. 2016;65(7):696–697.
202. Gales AC, Menezes LC, Silbert S, et al. Dissemination in distinct
Brazilian regions of an epidemic carbapenem-resistant pseudomo-
nas aeruginosa producing SPM metallo-β-lactamase. J Antimicrob
Chemother. 2003;52(4):699–702.
203. Zavascki AP, Gaspareto PB, Martins AF, et al. Outbreak of carbape-
nem-resistant pseudomonas aeruginosa producing SPM-1 metallo-
β-lactamase in a teaching hospital in southern Brazil. J Antimicrob
Chemother. 2005;56(6):1148–1151.
204. Magalhaes V, Lins AK, Magalhaes M. Metallo-β-lactamase produ-
cing pseudomonas aeruginosa strains isolated in hospitals in
Recife, PE, Brazil. Braz J Microbiol. 2005;36:123–125.
205. Viana Vieira V, Lourenço Da Fonseca E, Paulo VAC. Metallo-β-lacta-
mases produced by carbapenem-resistant pseudomonas aerugi-
nosa in Brazil. Clin Microbiol Infect. 2005;11(11):937.
206. Carvalho APD, Albano RM, De Oliveira DN, et al. Characterization of
an epidemic carbapenem-resistant pseudomonas aeruginosa pro-
ducing SPM-1 metallo-β-lactamase in a hospital located in Rio de
Janeiro, Brazil. Microb Drug Resist. 2006;12(2):103–108.
207. Pellegrino FLPC, Casali N, Dos Santos KRN, et al. Pseudomonas
aeruginosa epidemic strain carrying blaSPM metallo-beta-lacta-
mase detected in Rio de Janeiro, Brazil. J Chemother. 2006;18
(2):151–156.
208. Zavascki AP, Goldani LZ, Gonçalves ALS, et al. High prevalence of
metallo-β-lactamase-mediated resistance challenging antimicrobial
therapy against pseudomonas aeruginosa in a Brazilian teaching
hospital. Epidemiol Infect. 2007;135(2):343–345.
209. Cipriano R, Vieira VV, Fonseca EL, et al. Coexistence of epidemic
colistin-only-sensitive clones of pseudomonas aeruginosa, includ-
ing the blaSPM clone, spread in hospitals in a Brazilian Amazon
City. Microb Drug Resist. 2007;13(2):142–146.
210. Pellegrino FLPC, Casali N, Nouér SA, et al. A carbapenem-suscep-
tible pseudomonas aeruginosa strain carrying the blaSPM gene.
Diagn Microbiol Infect Dis. 2008;61(2):214–216.
211. Wirth FW, Picoli SU, Cantarelli VV, et al. Metallo-β-lactamase-produ-
cing pseudomonas aeruginosa in two hospitals from southern
Brazil. Braz J Infect Dis. 2009;13(3):170–172.
212. Gonçalves DCPS, Lima ABM, Leão LSNDO, et al. Detection of
metallo-beta-lactamase in pseudomonas aeruginosa isolated from
hospitalized patients in Goiânia, State of Goiás. Rev Soc Bras Med
Trop. 2009;42(4):411–414.
213. Jácome PRLDA, Alves LR, Cabral AB, et al. Phenotypic and molecu-
lar characterization of antimicrobial resistance and virulence factors
in pseudomonas aeruginosa clinical isolates from Recife, State of
Pernambuco, Brazil. Rev Soc Bras Med Trop. 2012;45(6):707–712.
214. De Oliveira RA, Gales AC, Da Silva RC, et al. Description and
molecular characterization of metallo-β-lactamase SPM-1 in pseu-
domonas aeruginosa clinical strains from Goiânia, Brazil. Perspect
Médicas. 2014;25(1):11–19.
215. Barros EMLR, Morais VMS, Castro KCB, et al. First detection of
metallo-β-lactamases in nosocomial isolates of pseudomonas
aeruginosa in Alagoas, Brazil. J Bras Patol Med Lab. 2015;51(5):291–
295.
216. Costa LMDA, Fleming MEDCK, Paula GRD, et al. Production of
metallo-β-lactamase among pseudomonas aeruginosa strains iso-
lated in the State of Sergipe, Brazil. Rev Soc Bras Med Trop. 2015;48
(2):212–215.
217. Fonseca ELD, Freitas FDS, Vicente ACP. The colistin-only-sensitive
Brazilian pseudomonas aeruginosa clone SP (sequence type 277)
is spread worldwide. Antimicrob Agents Chemother. 2010;54
(6):2743.
218. Woodford N, Turton JF, Livermore DM. Multiresistant gram-nega-
tive bacteria: the role of high-risk clones in the dissemination of
antibiotic resistance. FEMS Microbiol Rev. 2011;35(5):736–755.
219. Rossi F. The challenges of antimicrobial resistance in Brazil. Clin
Infect Dis. 2011;52(9):1138–1143.
220. Andrade LN, Woodford N, Darini ALC. International gatherings and
potential for global dissemination of São Paulo metallo-β-lacta-
mase (SPM) from Brazil. Int J Antimicrob Agents. 2014;43(2):196–
197.
221. Yong D, Toleman MA, Giske CG, et al. Characterization of a new
metallo-β-lactamase gene, blaNDM-1, and a novel erythromycin
esterase gene carried on a unique genetic structure in klebsiella
pneumoniae sequence type 14 from India. Antimicrob Agents
Chemother. 2009;53(12):5046–5054.
• First report of NDM in the world, identified in E. coli and K.
pneumoniae isolates from a Swedish patient who had pre-
viously been hospitalized in India.
222. Nordmann P, Poirel L, Walsh TR, et al. The emerging NDM carba-
penemases. Trends Microbiol. 2011;19(12):588–595.
223. Pasteran F, Albornoz E, Faccone D, et al. Emergence of NDM-1-
producing klebsiella pneumoniae in Guatemala. J Antimicrob
Chemother. 2012;67(7):1795–1797.
• First report of NDM in Latin America, identified in K. pneumo-
niae isolates from Guatemala.
224. Escobar Pérez JA, Olarte Escobar NM, Castro-Cardozo B, et al.
Outbreak of NDM-1-producing klebsiella pneumoniae in a neonatal
unit in Colombia. Antimicrob Agents Chemother. 2013;57(4):1957–
1960.
225. Ovalle MV, Duarte C, Saavedra SY, et al. Circulación de carbapene-
masas tipo New Delhi metalo-β-lactamasa (NDM), Colombia, 2011 a
2013. Inf Quinc Epidemiol Nac. 2013;18(11):122–132.
226. Instituto Nacional de Salud. Circulación de carbapenemasas tipo
Nueva Delhi metalo-β-lactamasa (NDM) en Colombia 2012-2014.
Colombia: Instituto Nacional de Salud. 2014.
227. Saavedra-Rojas S-Y, Duarte-Valderrama C, González-de-Arias M-N,
et al. Emergence of providencia rettgeri NDM-1 in two depart-
ments of Colombia, 2012-2013. Enferm Infecc Microbiol Clin.
2013. DOI:10.1016/j.eimc.2015.05.011
228. Rojas LJ, Wright MS, De La Cadena E, et al. Initial assessment of the
molecular epidemiology of blaNDM-1 in Colombia. Antimicrob
Agents Chemother. 2016;60(7):4346–4350.
229. Pan American Health Organization (PAHO). Epidemiological alert:
nosocomial transmission of NDM-type multiresistant bacteria.
Washington, DC: Pan American Health Organization (PAHO). 2012
Dec 19.
230. Seija V, Medina Presentado JC, Bado I, et al. Sepsis caused by New
Delhi metallo-β-lactamase (blaNDM-1) and qnrD-producing
Morganella morganii, treated successfully with fosfomycin and
meropenem: case report and literature review. Int J Infect Dis.
2015;30:20–26.
231. Pasteran F, Mora MM, Albornoz E, et al. Emergence of genetically
unrelated NDM-1-producing acinetobacter pittii strains in
Paraguay. J Antimicrob Chemother. 2014;69(9):2575–2578.
232. Waterman PE, McGann P, Snesrud E, et al. Bacterial peritonitis due
to acinetobacter baumannii sequence type 25 with plasmid-borne
New Delhi metallo-β-lactamase in Honduras. Antimicrob Agents
Chemother. 2013;57(9):4584–4586.
233. Barrios H, Garza-Ramos U, Reyna-Flores F, et al. Isolation of carba-
penem-resistant NDM-1-positive providencia rettgeri in Mexico. J
Antimicrob Chemother. 2013;68(8):1934–1936.

234. Barrios H, Silva-Sanchez J, Reyna-Flores F, et al. Detection of a
NDM-1-producing klebsiella pneumoniae (ST22) clinical isolate
at a pediatric hospital in Mexico. Pediatr Infect Dis J. 2014;33
(3):335.
235. Torres-González P, Bobadilla-Del Valle M, Tovar-Calderón E, et al.
Outbreak caused by enterobacteriaceae harboring NDM-1 metallo-
β-lactamase carried in an IncFII plasmid in a tertiary care hospital in
Mexico city. Antimicrob Agents Chemother. 2015;59(11):7080–
7083.
236. Carvalho-Assef APD, Pereira PS, Albano RM, et al. Isolation of NDM-
producing providencia rettgeri in Brazil. J Antimicrob Chemother.
2013;68(12):2956–2957.
237. Carvalho-Assef APD, Pereira PS, Albano RM, et al. Detection of
NDM-1-, CTX-M-15-, and qnrB4-producing enterobacter hormae-
chei isolates in Brazil. Antimicrob Agents Chemother. 2014;58
(4):2475–2476.
238. Rozales FP, Ribeiro VB, Magagnin CM, et al. Emergence of NDM-1-
producing enterobacteriaceae in Porto Alegre, Brazil. Int J Infect
Dis. 2014;25:79–81.
239. Carneiro M, Gonçalves RA, De Souza JG, et al. New carbapenases in
Brazil. Expert Rev Anti Infect Ther. 2014;12(2):155–156.
240. Carmo Junior NVD, Filho HF, Gomes E Costa DA, et al. First report of
a NDM-producing providencia rettgeri strain in the state of São
Paulo. Braz J Infect Dis. 2015;19(6):675–676.
241. Andrade LN, Darini ALC. Response to detection of New Delhi
metallo-β-lactamase-producing bacteria, Brazil. Emerg Infect Dis.
2015;21(6):1069–1071.
242. Quiles MG, Rocchetti TT, Fehlberg LC, et al. Unusual association of
NDM-1 with KPC-2 and armA among Brazilian enterobacteriaceae
isolates. Braz J Med Biol Res. 2015;48(2):174–177.
243. Pereira PS, Borghi M, Albano RM, et al. Coproduction of NDM-1 and
KPC-2 in enterobacter hormaechei from Brazil. Microb Drug Resist.
2015;21(2):234–236.
244. Pillonetto M, Arend L, Vespero EC, et al. First report of NDM-1-
producing acinetobacter baumannii sequence type 25 in Brazil.
Antimicrob Agents Chemother. 2014;58(12):7592–7594.
245. Pagano M, Poirel L, Martins AF, et al. Emergence of NDM-1-produ-
cing acinetobacter pittii in Brazil. Int J Antimicrob Agents. 2015;45
(4):444–445.
246. Pasteran F, Meo A, Gomez S, et al. Emergence of genetically related
NDM-1-producing providencia rettgeri strains in Argentina. J Glob
Antimicrob Resist. 2014;2(4):344–345.
247. Montaña S, Cittadini R, Del Castillo M, et al. Presence of New Delhi
metallo-β-lactamase gene (NDM-1) in a clinical isolate of acineto-
bacter junii in Argentina. New Microbes New Infect. 2016;11:43–44.
248. Pan American Health Organization (PAHO) /World Health
Organization (WHO). Epidemiological update. Carbapenemases of
type New Delhi metallo-β-lactamase (NDM). Washington, DC: Pan
American Health Organization (PAHO). 2014 Mar 7.
249. Quiñones D, Carvajal I, Perez Y, et al. High prevalence of blaOXA-23
in acinetobacter spp. and detection of blaNDM-1 in A. soli in Cuba:
report from national surveillance program (2010-2012). New
Microbes New Infect. 2015;7:52–56.
250. Thoms-Rodriguez C-A, Mazzulli T, Christian N, et al. New Delhi
metallo-β-lactamase in Jamaica. J Infect Dev Ctries. 2016;10
(2):183–187.
251. Bastian S, Nordmann P, Creton E, et al. First case of NDM-1 produ-
cing klebsiella pneumoniae in Caribbean islands. Int J Infect Dis.
2015;34:53–54.
252. Delgado-Blas JF, Ovejero CM, Abadia-Patiño L, et al. Coexistence of
mcr-1 and blaNDM-1 in escherichia coli from Venezuela.
Antimicrob Agents Chemother. 2016;60(10):6356–6358.
253. Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of
class D β-lactamases. Antimicrob Agents Chemother. 2010;54(1):24–38.
254. Evans BA, Amyes SGB. OXA β-lactamases. Clin Microbiol Rev.
2014;27(2):241–263.
•• Excellent revision of OXA β-lactamases.
255. Mugnier PD, Poirel L, Naas T, et al. Worldwide dissemination of the
blaOXA-23 carbapenemase gene of acinetobacter baumannii.
Emerg Infect Dis. 2010;16(1):35–40.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 295
256. Turton JF, Ward ME, Woodford N, et al. The role of ISAba1 in
expression of OXA carbapenemase genes in acinetobacter bau-
mannii. FEMS Microbiol Lett. 2006;258(1):72–77.
257. Paton R, Miles RS, Hood J, et al. ARI 1: β-lactamase-mediated
imipenem resistance in acinetobacter baumannii. Int J Antimicrob
Agents. 1993;2(2):81–87.
• First report of an OXA-type carbapenemase in the world, OXA-
23 (formerly ARI-1), identified in an A. baumannii isolate from
Scotland.
258. Donald HM, Scaife W, Amyes SG, et al. Sequence analysis of ARI-1, a
novel OXA β-lactamase, responsible for imipenem resistance in
acinetobacter baumannii 6B92. Antimicrob Agents Chemother.
2000;44(1):196–199.
259. Scaife W, Young HK, Paton RH, et al. Transferable imipenem-resis-
tance in acinetobacter species from a clinical source. J Antimicrob
Chemother. 1995;36(3):585–586.
260. Bonnet R, Marchandin H, Chanal C, et al. Chromosome-encoded
class D β-lactamase OXA-23 in proteus mirabilis. Antimicrob Agents
Chemother. 2002;46(6):2004–2006.
261. Dalla-Costa LM, Coelho JM, Souza HAPHM, et al. Outbreak of
carbapenem-resistant acinetobacter baumannii producing the
OXA-23 enzyme in Curitiba, Brazil. J Clin Microbiol. 2003;41
(7):3403–3406.
• First report of OXA-23 in Latin America, from an A. baumannii
outbreak in Brazil.
262. Carvalho KR, Carvalho-Assef APD, Peirano G, et al. Dissemination of
multidrug-resistant acinetobacter baumannii genotypes carrying
blaOXA-23 collected from hospitals in Rio de Janeiro, Brazil. Int J
Antimicrob Agents. 2009;34(1):25–28.
263. Martins AF, Kuchenbecker R, Sukiennik T, et al. Carbapenem-resis-
tant acinetobacter baumannii producing the OXA-23 enzyme: dis-
semination in Southern Brazil. Infection. 2009;37(5):474–476.
264. Schimith Bier KE, Luiz SO, Scheffer MC, et al. Temporal evolution of
carbapenem-resistant acinetobacter baumannii in Curitiba, south-
ern Brazil. Am J Infect Control. 2010;38(4):308–314.
265. Antonio CS, Neves PR, Medeiros M, et al. High prevalence of
carbapenem-resistant acinetobacter baumannii carrying the
blaOXA-143 gene in Brazilian hospitals. Antimicrob Agents
Chemother. 2011;55(3):1322–1323.
266. Werneck JS, Picão RC, Girardello R, et al. Low prevalence of blaOXA-
143 in private hospitals in Brazil. Antimicrob Agents Chemother.
2011;55(9):4494–4495.
267. Grosso F, Carvalho KR, Quinteira S, et al. OXA-23-producing acine-
tobacter baumannii: a new hotspot of diversity in Rio de Janeiro? J
Antimicrob Chemother. 2011;66(1):62–65.
268. Figueiredo DQD, Santos KRND, Pereira EM, et al. First report of the
blaOXA-58 gene in a clinical isolate of acinetobacter baumannii in
Rio de Janeiro, Brazil. Mem Inst Oswaldo Cruz. 2011;106(3):368–370.
269. Corrêa LL, Botelho LAB, Barbosa LC, et al. Detection of blaOXA-23
in acinetobacter spp. isolated from patients of a university hospital.
Braz J Infect Dis. 2012;16(6):521–526.
270. Martins AF, Kuchenbecker RS, Pilger KO, et al. High endemic levels
of multidrug-resistant acinetobacter baumannii among hospitals in
southern Brazil. Am J Infect Control. 2012;40(2):108–112.
271. Fonseca EL, Scheidegger E, Freitas FS, et al. Carbapenem-resistant
acinetobacter baumannii from Brazil: role of carO alleles expression
and blaOXA-23 gene. BMC Microbiol. 2013;13(1):245.
272. Martins N, Martins IS, De Freitas WV, et al. Imported and intensive
care unit-born acinetobacter baumannii clonal complexes: one-
year prospective cohort study in intensive care patients. Microb
Drug Resist. 2013;19(3):216–223.
273. Clímaco EC, Oliveira ML, De, Pitondo-Silva A, et al. Clonal com-
plexes 104, 109 and 113 playing a major role in the dissemination
of OXA-carbapenemase-producing acinetobacter baumannii in
Southeast Brazil. Infect Genet Evol. 2013;19:127–133.
274. Chagas TPG, Carvalho KR, De Oliveira Santos IC, et al.
Characterization of carbapenem-resistant acinetobacter baumannii
in Brazil (2008-2011): countrywide spread of OXA-23-producing
clones (CC15 and CC79). Diagn Microbiol Infect Dis. 2014;79
(4):468–472.
296 K. ESCANDÓN-VARGAS ET AL.
275. Vasconcelos ATR, Barth AL, Zavascki AP, et al. The changing epide-
miology of acinetobacter spp. producing OXA carbapenemases
causing bloodstream infections in Brazil: a BrasNet report. Diagn
Microbiol Infect Dis. 2015;83(4):382–385.
276. Dias VC, Diniz CG, Peter ACDO, et al. Epidemiological characteristics
and antimicrobial susceptibility among carbapenem-resistant non-
fermenting bacteria in Brazil. J Infect Dev Ctries. 2016;10(6):544–553.
277. Teixeira AB, Martins AF, Barin J, et al. First report of carbapenem-
resistant acinetobacter nosocomialis isolates harboring ISAba1-
blaOXA-23 genes in Latin America. J Clin Microbiol. 2013;51
(8):2739–2741.
278. Carvalho KR, Carvalho-Assef APD, Santos LGD. Occurrence of
blaOXA-23 gene in imipenem-susceptible acinetobacter bauman-
nii. Mem Inst Oswaldo Cruz. 2011;106(4):505–506.
279. Merkier AK, Catalano M, Ramírez MS, et al. Polyclonal spread of
blaOXA-23 and blaOXA-58 in acinetobacter baumannii isolates
from Argentina. J Infect Dev Ctries. 2008;2(3):235–240.
280. Merkier AK, Centrón D. blaOXA-51-type β-lactamase genes are
ubiquitous and vary within a strain in acinetobacter baumannii.
Int J Antimicrob Agents. 2006;28(2):110–113.
281. Stietz MS, Ramírez MS, Vilacoba E, et al. Acinetobacter baumannii
extensively drug resistant lineages in Buenos Aires hospitals differ
from the international clones I-III. Infect Genet Evol. 2013;14
(1):294–301.
282. Rodriguez CH, Balderrama Yarhui N, Nastro M, et al. Molecular epide-
miology of carbapenem-resistant acinetobacter baumannii in South
America. J Med Microbiol. 2016. DOI:10.1099/jmm.0.000328
283. Cuaical Ramos NM, Delgado Borrero YA, Anzola Anzola YM, et al.
Detection of OXA type carbapenemases in acinetobacter bauman-
nii from different hospital centers in Caracas, Venezuela. Rev Soc
Ven Microbiol. 2012;32(2):95–100.
284. Villegas MV, Kattan JN, Correa A, et al. Dissemination of acineto-
bacter baumannii clones with OXA-23 carbapenemase in
Colombian hospitals. Antimicrob Agents Chemother. 2007;51
(6):2001–2004.
285. Pinzon JO, Mantilla JR, Valenzuela EM, et al. Molecular characteriza-
tion of acinetobacter baumannii isolations from a burns unit in a
third level attention hospital in Bogotá. Infectio. 2006;10(2):71–78.
286. Saavedra SY, Nuñez JC, Pulido IY, et al. Characterisation of carba-
penem-resistant acinetobacter calcoaceticus-A. baumannii com-
plex isolates in a third-level hospital in Bogotá, Colombia. Int J
Antimicrob Agents. 2008;31(4):389–391.
287. Saavedra-Trujillo CH, Arias-León G, Gualtero-Trujillo SM, et al. Risk
factors for colonisation or infection by Acinetobacter baumannii
resistant to carbapenems in adult patients hospitalised in intensive
care units in Bogota, Colombia. Infectio. 2016;20(4):238–249.
288. Martínez P, Mattar S. Imipenem-resistant acinetobacter baumannii
carrying the ISAba1-blaOXA-23,51 and ISAba1-blaADC-7 genes in
Monteria, Colombia. Braz J Microbiol. 2012;43(4):1274–1280.
289. Vanegas JM, Higuita LF, Vargas CA, et al. Carbapenem-resistant
acinetobacter baumannii causing osteomyelitis and infections of
skin and soft tissues in hospitals of Medellín, Colombia. Biomedica.
2015;35(4):522–530.
290. Correa A, Del Campo R, Escandón-Vargas K, et al. Distinct genetic
diversity of carbapenem-resistant Acinetobacter baumannii from
Colombian hospitals. Microb Drug Resist. 2016.
291. Reguero MT, Medina OE, Hernández MA, et al. Antibiotic resistance
patterns of acinetobacter calcoaceticus-A. baumannii complex spe-
cies from Colombian hospitals. Enferm Infecc Microbiol Clin.
2013;31(3):142–146.
292. Opazo A, Bello H, Dominguez M, et al. First report of blaOXA-23 in
acinetobacter baumannii isolates from Chilean hospitals. J Glob
Antimicrob Resist. 2015;3(1):54–55.
293. Thoms-Rodriguez C-A, Nicholson A, Christian N, et al. The detection
of the NDM-1 and other carbapenemase genes in multidrug resis-
tant gram negative bacilli (MDRGNB) in a Jamaican hospital. Int J
Infect Dis. 2012;16(2):e434–e435.
294. Tamayo-Legorreta EM, Garza-Ramos U, Barrios-Camacho H, et al.
Identification of OXA-23 carbapenemases: novel variant OXA-239 in
acinetobacter baumannii ST758 clinical isolates in Mexico. New
Microbes New Infect. 2014;2(6):173–174.
295. Gonzalez-Villoria AM, Tamayo-Legorreta E, Garza-Ramos U, et al. A
multicenter study in Mexico finds acinetobacter baumannii clinical
isolates belonging to clonal complexes 636B (113B) and 92B har-
boring OXA-72, OXA-239, and OXA-469. Antimicrob Agents
Chemother. 2016;60(4):2587–2588.
296. Nuñez Quezada T, Rodríguez CH, Castro Cañarte G, et al. Outbreak
of blaOXA-72-producing acinetobacter baumannii in South
America. J Chemother. 2016. DOI:10.1080/1120009X.2016.1158936
297. Sennati S, Villagran AL, Bartoloni A, et al. OXA-23-producing ST25
acinetobacter baumannii: first report in Bolivia. J Glob Antimicrob
Resist. 2016;4:70–71.
298. Karah N, Sundsfjord A, Towner K, et al. Insights into the global
molecular epidemiology of carbapenem non-susceptible clones of
acinetobacter baumannii. Drug Resist Updat. 2012;15(4):237–247.
299. Bou G, Oliver A, Martínez-Beltrán J. OXA-24, a novel class D β-
lactamase with carbapenemase activity in an acinetobacter bau-
mannii clinical strain. Antimicrob Agents Chemother. 2000;44
(6):1556–1561.
300. Mendes RE, Castanheira M, Deshpande LM, et al. Rapid emergence
and spread of Acinetobacter spp. producing carbapenem-hydrolyzing
oxacillinases: report from the SENTRY program. 48th ICAAC/46th
IDSA. Washington, DC, USA: American Society for Microbiology
(ASM) and Infectious Diseases Society of America (IDSA). 2008. p.
Abstract C2–3857.
301. Bocanegra-Ibarias P, Peña-López C, Camacho-Ortiz A, et al. Genetic
characterisation of drug resistance and clonal dynamics of acine-
tobacter baumannii in a hospital setting in Mexico. Int J Antimicrob
Agents. 2015;45(3):309–313.
302. Werneck JS, Picão RC, Carvalhaes CG, et al. OXA-72-producing
acinetobacter baumannii in Brazil: a case report. J Antimicrob
Chemother. 2011;66(2):452–454.
303. De Sá Cavalcanti FL, Almeida ACS, Vilela MA, et al. Emergence of
extensively drug-resistant OXA-72-producing acinetobacter bau-
mannii in Recife, Brazil: risk of clonal dissemination? Diagn
Microbiol Infect Dis. 2013;77(3):250–251.
304. Montealegre MC, Maya JJ, Correa A, et al. First identification of
OXA-72 carbapenemase from acinetobacter pittii in Colombia.
Antimicrob Agents Chemother. 2012;56(7):3996–3998.
305. Saavedra SY, Cayô R, Gales AC, et al. Early dissemination of OXA-72-
producing acinetobacter baumannii strain in Colombia: a case
report. Braz J Infect Dis. 2014;18(6):678–680.
306. Brown S, Young HK, Amyes SGB. Characterisation of OXA-51, a
novel class D carbapenemase found in genetically unrelated clin-
ical strains of acinetobacter baumannii from Argentina. Clin
Microbiol Infect. 2005;11(1):15–23.
• First report of OXA-51 in the world, identified in A. baumannii
isolates from Argentina.
307. Coelho J, Woodford N, Afzal-Shah M, et al. Occurrence of OXA-58-
like carbapenemases in acinetobacter spp. collected over 10 years
in three continents. Antimicrob Agents Chemother. 2006;50
(2):756–758.
308. Fernández Colón E, Bustamante García Z, Zamora Balderrama J,
et al. Determining carbapenemases and its relationship to genetic
structures in clinical isolates of acinetobacter baumannii at hospi-
tals in the city of Cochabamba. Biofarbo. 2009;17(1):30–38.
309. Sevillano E, Fernández E, Bustamante Z, et al. Emergence and
clonal dissemination of carbapenem-hydrolysing OXA-58-produ-
cing acinetobacter baumannii isolates in Bolivia. J Med Microbiol.
2012;61(Pt 1):80–84.
310. Higgins PG, Pérez-Llarena FJ, Zander E, et al. OXA-235, a novel class D
β-lactamase involved in resistance to carbapenems in acinetobacter
baumannii. Antimicrob Agents Chemother. 2013;57(5):2121–2126.
311. Hamouda A, Evans BA, Towner KJ, et al. Characterization of epide-
miologically unrelated acinetobacter baumannii isolates from four
continents by use of multilocus sequence typing, pulsed-field gel
electrophoresis, and sequence-based typing of blaOXA-51-like
genes. J Clin Microbiol. 2010;48(7):2476–2483.

312. Figueiredo S, Poirel L, Papa A, et al. Overexpression of the naturally
occurring blaOXA-51 gene in acinetobacter baumannii mediated
by novel insertion sequence ISAba9. Antimicrob Agents
Chemother. 2009;53(9):4045–4047.
313. Héritier C, Poirel L, Fournier P-E, et al. Characterization of the
naturally occurring oxacillinase of acinetobacter baumannii.
Antimicrob Agents Chemother. 2005;49(10):4174–4179.
314. Poirel L, Marqué S, Héritier C, et al. OXA-58, a novel class D β-
lactamase involved in resistance to carbapenems in acinetobac-
ter baumannii. Antimicrob Agents Chemother. 2005;49(1):202–
208.
315. Cayô R, Rodrigues-Costa F, Pereira Matos A, et al. Old clinical
isolates of acinetobacter seifertii in Brazil producing OXA-58.
Antimicrob Agents Chemother. 2016;60(4):2589–2591.
316. Salazar De Vegas EZ, Nieves B, Ruiz M, et al. Molecular epidemiol-
ogy and characterization of resistance mechanisms to various anti-
microbial agents in acinetobacter baumannii isolated in Mérida,
Venezuela. Med Sci Monit. 2007;13(4):BR89–94.
317. Poirel L, Héritier C, Tolün V, et al. Emergence of oxacillinase-
mediated resistance to imipenem in klebsiella pneumoniae.
Antimicrob Agents Chemother. 2004;48(1):15–22.
318. Lascols C, Peirano G, Hackel M, et al. Surveillance and molecular
epidemiology of klebsiella pneumoniae isolates that produce car-
bapenemases: first report of OXA-48-like enzymes in North
America. Antimicrob Agents Chemother. 2013;57(1):130–136.
319. Vanegas JM, Ospina WP, Higuita-Gutiérrez LF, et al. First reported
case of an OXA-48-producing isolate from a Colombian patient. J
Glob Antimicrob Resist. 2016;6:67–68.
EXPERT REVIEW OF ANTI-INFECTIVE THERAPY 297
320. Poirel L, Castanheira M, Carrër A, et al. OXA-163, an OXA-48-related
class D β-lactamase with extended activity toward expanded-spec-
trum cephalosporins. Antimicrob Agents Chemother. 2011;55
(6):2546–2551.
321. Gomez S, Pasteran F, Faccone D, et al. Intrapatient emergence of
OXA-247: a novel carbapenemase found in a patient previously
infected with OXA-163-producing klebsiella pneumoniae. Clin
Microbiol Infect. 2013;19(5):E233–5.
322. Sampaio JLM, Ribeiro VB, Campos JC, et al. Detection of OXA-
370, an OXA-48-related class D β-lactamase, in enterobacter
hormaechei from Brazil. Antimicrob Agents Chemother. 2014;58
(6):3566–3567.
323. Pereira PS, Borghi M, De Araújo CFM, et al. Clonal dissemination of
OXA-370-producing klebsiella pneumoniae in Rio de Janeiro, Brazil.
Antimicrob Agents Chemother. 2015;59(8):4453–4456.
324. Higgins PG, Poirel L, Lehmann M, et al. OXA-143, a novel carbape-
nem-hydrolyzing class D β-lactamase in acinetobacter baumannii.
Antimicrob Agents Chemother. 2009;53(12):5035–5038.
325. Gionco B, Pelayo JS, Venancio EJ, et al. Detection of OXA-231, a
new variant of blaOXA-143, in acinetobacter baumannii from Brazil:
a case report. J Antimicrob Chemother. 2012;67(10):2531–2532.
326. Zander E, Bonnin RA, Seifert H, et al. Characterization of blaOXA-
143 variants in acinetobacter baumannii and acinetobacter pittii.
Antimicrob Agents Chemother. 2014;58(5):2704–2708.
327. Girlich D, Damaceno QS, Oliveira AC, et al. OXA-253, a variant of the
carbapenem-hydrolyzing class D β-lactamase OXA-143 in
Acinetobacter baumannii. Antimicrob Agents Chemother. 2014;58
(5):2976–2976.