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dkw076 PDF
dkw076 PDF
doi:10.1093/jac/dkw076
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Independent States countries, to provide detailed and compara- susceptibility to amoxicillin alone), cefixime, cefuroxime, cefaclor, cefpro-
tive information on resistance trends among strains from docu- zil, clarithromycin, azithromycin, erythromycin, ciprofloxacin, trimetho-
mented CA-RTIs caused by S. pneumoniae, H. influenzae and prim/sulfamethoxazole, tetracycline, chloramphenicol and clindamycin.
S. pyogenes.13 – 16 S. pyogenes strains were tested against penicillin, amoxicillin, cefaclor, cef-
ixime, erythromycin, azithromycin, clarithromycin, clindamycin, tetracyc-
line and chloramphenicol. Finally, susceptibility of H. influenzae was
Materials and methods assessed against ampicillin, amoxicillin/clavulanic acid, cefaclor, cefixime,
cefprozil, cefuroxime, clarithromycin, azithromycin, ciprofloxacin, levofloxa-
Collaborating centres cin, trimethoprim/sulfamethoxazole, tetracycline and chloramphenicol.
Isolates were collected from two sites in Pakistan: Aga Khan University For the 2014 –15 isolates, susceptibility testing was carried out using a
more limited range of antibiotics. S. pneumoniae susceptibility was tested
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Table 1. MIC breakpoints (mg/L) used for S. pneumoniae and H. influenzae isolates
CLSI breakpointsa
Antimicrobial S R S I R S I R
such as amoxicillin, were also recommended for treatment of PISP 91.2% of S. pneumoniae isolates were found to be susceptible.
or penicillin-resistant S. pneumoniae infections. S. pneumoniae strains showing reduced susceptibility to penicil-
These changes are documented in Table 1 and show that lin were more likely to show increased resistance to macrolides
S. pneumoniae with penicillin MICs ≤2.0 mg/L are regarded as sus- and other antimicrobial agents, particularly older agents such as
ceptible, whereas previously some of these isolates would have first-generation cephalosporins (cefaclor), tetracycline or tri-
been regarded as having intermediate susceptibility. Clinical stud- methoprim/sulfamethoxazole (Table 3). Almost all PISP strains
ies showed that, provided penicillin was used in adequate dosage, were resistant to trimethoprim/sulfamethoxazole, .70% were
the new susceptibility category could be used as a breakpoint for resistant to tetracycline and 50% were resistant to macrolides
non-meningeal isolates. (erythromycin and clarithromycin). This contrasted with the
macrolide resistance rate in penicillin-susceptible S. pneumoniae
strains, which was only 10% – 15%. In the Lahore 2014 – 15
Antibiotic resistance in S. pneumoniae study, the erythromycin susceptibility of all S. pneumoniae isolates
Overall, non-susceptibility to penicillin among S. pneumoniae was 70%.
strains rose steeply, from 10% in 2002 to 34.1% in 2009. The Clindamycin resistance plus macrolide resistance is a use-
prevalence of penicillin-non-susceptible S. pneumoniae was 10% ful proxy for detection of the erm(B) resistance marker. 24
during 2002 – 03, 18.3% during 2004 – 06 and 34.1% during In the 2007 – 09 study period, clindamycin resistance was
2007– 09. During 2014 –15, only 10 S. pneumoniae isolates were 22.6% among PISP strains and this was coupled with a concomi-
collected, of which two were non-susceptible to penicillin. Of the tant high incidence of macrolide resistance (50%) (Table 3). This
31 isolates that were penicillin non-susceptible in the 2007 – 09 finding suggests that a number of these isolates are more likely
survey, all had MICs of 4 mg/L, making them intermediate to have macrolide resistance attributable to the erm(B) resist-
(Table 2). No isolates of S. pneumoniae obtained during the ance marker rather than the efflux mechanism of macrolide
study were highly resistant to penicillin (MICs ≥8.0 mg/L), resistance. In the 2007 – 09 study period, of the S. pneumoniae
although 1.1% of strains in the 2004 – 06 survey were penicillin isolates, 93.4% were susceptible to chloramphenicol (Table 2).
resistant using the lower CLSI breakpoint in use at that time.
Macrolide resistance rose from 13% to 29.7% (depending on
the macrolide being tested) over the study period (Figure 1 and Antibiotic resistance in H. influenzae
Table 2, respectively). By contrast, susceptibility to amoxicillin/ H. influenzae isolates studied in Pakistan during the 2002 –03 win-
clavulanic acid (or amoxicillin alone) between 2002 and 2015 ter season (n ¼ 93) were fully susceptible (100%) to amoxicillin/
has remained between 99.4% and 100% among S. pneumoniae clavulanic acid, cefuroxime, cefprozil, cefaclor, cefixime, clarithro-
isolates. Ciprofloxacin was tested only during 2007 – 09, when mycin and azithromycin (Table 4). Furthermore, 3.2% of isolates
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Table 2. Susceptibility (%) of S. pneumoniae in Pakistan to antimicrobials using CLSI or PK/PD breakpoints
Penicillin 90.0 10.0 NA 81.7 18.3 (1.1) NA 65.9 34.1 (0) NA 80.0 20.0
AMC, amoxicillin/clavulanic acid; SXT, trimethoprim/sulfamethoxazole; S, susceptible; I, intermediate; R, resistant; NA, not applicable; —, no data
available.
a
Data for strains from Pakistan summarized by Shibl et al.13
b
Data from Pakistan summarized by Sievers et al. 15
c
Pakistan current SOAR study data.
d
PK/PD breakpoint used.
e
Revised breakpoints for Etestw used.
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SOAR: Pakistan 2002 – 15 JAC
Table 3. Susceptibility (%) of penicillin-susceptible S. pneumoniae (PSSP) The SOAR studies have been conducted using the Etestw
and penicillin-intermediate S. pneumoniae (PISP) strains from CA-RTIs in because reliable MIC results can be obtained relatively easily
Pakistan in SOAR during 2007 –09 and subsequently the results can be analysed with reference to
different breakpoint criteria. In these studies, analyses have
PSSP (n¼60), penicillin PISP (n¼31), penicillin been performed using breakpoints defined by CLSI and also
MIC ≤2.0 mg/La MIC ≥4 mg/La newer breakpoints defined by PK/PD criteria, which take account
of both susceptibility and attainable antibiotic concentrations in
Antimicrobial S (PK/PD) S (CLSI) R (CLSI) S (PK/PD) S (CLSI) R (CLSI) the blood. Interpretation of the data has also been made with
the revised breakpoints issued in 2009. Use of these new break-
Penicillin NA 100 0 NA 0 0 points means that direct comparison between time periods is
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10 days of oral penicillin V. The high level of macrolide resistance 6 Bravo LC, Asian Strategic Alliance for Pneumococcal Disease Prevention
means that this class of antibiotic may not be an appropriate (ASAP) Working Group. Overview of the disease burden of invasive
treatment for GAS in Pakistan. Shorter treatments (4 – 5 days) pneumococcal disease in Asia. Vaccine 2009; 27: 7282– 9.
with amoxicillin/clavulanic acid (or amoxicillin) or cefuroxime axe- 7 Rizvi SF, Khan MA, Kundi A et al. Status of rheumatic heart disease in
til have been shown to be as effective, or superior to, standard rural Pakistan. Heart 2004; 90: 394–9.
penicillin treatment and may aid compliance.27 8 Zafar A, Hussain Z, Lomama E et al. Antibiotic susceptibility of pathogens
In conclusion, when choosing antibiotic therapy for CA-RTIs, local isolated from patients with community-acquired respiratory tract in-
antibiotic susceptibility/resistance data are essential to support fections in Pakistan—the active study. J Ayub Med Coll Abbottabad
informed therapy choices. The SOAR studies over the period from 2008; 20: 7 –9.
2002 to 2009, along with the further study in 2014–15, have con- 9 Pallares R, Fenoll A, Linares J et al. The epidemiology of antibiotic resist-
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21 Clinical and Laboratory Standards Institute. Performance Standards 25 Wang H, Chen M, Xu Y et al. Antimicrobial susceptibility of bacterial
for Antimicrobial Susceptibility Testing: Twenty Fourth Informational pathogens associated with community-acquired respiratory tract infec-
Supplement M100-S24. Wayne, PA, USA, 2014. tions in Asia: report from the Community-Acquired Respiratory Tract
22 Clinical and Laboratory Standards Institute. Performance Standards for Infection Pathogen Surveillance (CARTIPS) study, 2009 – 2010. Int J
Antimicrobial Disk Susceptibility Tests—Tenth Edition: Approved Standard Antimicrob Agents 2011; 38: 376–83.
M2-A10. CLSI, Wayne, PA, USA, 2009. 26 Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of
23 Jacobs MR. Optimisation of antimicrobial therapy using pharmacoki- community-acquired pneumonia in the era of pneumococcal resistance.
netic and pharmacodynamic parameters. Clin Microbiol Infect 2001; 7: Arch Int Med 2000; 160: 1399–408.
589–96. 27 Adam D, Scholz H, Helmerking M. Comparison of short-course (5 day)
24 Shibl AM. Patterns of macrolide resistance determinants among cefuroxime axetil with a standard 10 day oral penicillin V regimen in the
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