Antibiotic Susceptibility

Pediatr. Rev. 2009;30;499-501

DOI: 10.1542/pir.30-12-499

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located on the World Wide Web at:
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In Brief
Antibiotic Susceptibility
Blaise Congeni, MD
Akron Children’s Hospital
Akron, Ohio
Author Disclosure
Dr Congeni has disclosed that he is a
member of the Speaker’s Bureau for
GlaxoSmithKline’s Vaccine Division.
Dr Adam has disclosed no financial
relationships relevant to this In Brief.
This commentary does contain a
discussion of an unapproved/
investigative use of a commercial
product/device.
Predicting Efficacy of Antiinfectives
with Pharmacodynamics and Monte
Carlo Simulation. Bradley JS, Dudley
MN, Drusano GL. Pediatr Infect Dis J.
2003;22:982–992
Haemophilus influenzae Infections.
American Academy of Pediatrics. In:
Pickering LK, Baker CJ, Kimberlin DW,
Long SS, eds. Red Book: 2009 Report
of the Committee on Infectious Dis-
eases. 28th ed. Elk Grove Village, Ill:
American Academy of Pediatrics;
2009:314 –320
Pneumococcal Infections. American
Academy of Pediatrics. In: Pickering
LK, Baker CJ, Kimberlin DW, Long SS,
eds. Red Book: 2009 Report of the
Committee on Infectious Diseases.
28th ed. Elk Grove Village, Ill: Ameri-
can Academy of Pediatrics; 2009:
524 –535
Staphylococcal Infections. American
Academy of Pediatrics. In: Pickering LK,
Baker CJ, Kimberlin DW, Long SS, eds.
Red Book: 2009 Report of the Com-
mittee on Infectious Diseases. 28th ed.
Elk Grove Village, Ill: American Acad-
emy of Pediatrics; 2009:601– 615
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Group A Streptococcal Infections.
American Academy of Pediatrics. In:
Pickering LK, Baker CJ, Kimberlin DW,
Long SS, eds. Red Book: 2009 Report
of the Committee on Infectious Dis-
eases. 28th ed. Elk Grove Village, Ill:
American Academy of Pediatrics;
2009:616 – 628
Understanding the role of clinical mi-
crobiology is critical for the physician
treating children presumed to have in-
fections. Appropriate cultures with
properly interpreted sensitivity testing
allow the physician to choose an effec-
tive antibiotic.
Obtaining cultures that provide the
most useful information depends on the
likelihood that the organism recovered
is, in fact, the offending pathogen.
Cultures from normally sterile sites
such as blood, urine, cerebrospinal fluid,
pleural fluid, or synovial fluid are most
likely to yield the offending organism,
as are cultures taken before antibiotics
are begun. Finally, the specimen should
be obtained from the proper site, fol-
lowing proper preparation of the site,
with proper handling of the specimen.
Yield of the culture also may be in-
creased by optimum collection, such as
increasing the volume of blood col-
lected for blood culture.
Once the pathogen is identified,
sensitivity testing may help in deciding
appropriate drug and dosing. In addi-
tion to knowing that a pathogen is
resistant to a particular drug, the phy-
sician must understand the likely
mechanism of resistance. For example,
if a penicillin-resistant strain of Strep-
tococcus pneumoniae is identified, pro-
viding a drug that has beta-lactamase
stability is of no benefit, but increasing
in brief
the dose of amoxicillin may prove ef-
fective.
A better understanding of sensitivity
testing can be gained by examining the
specific management principles for sev-
eral of the most common infectious
syndromes seen in pediatric patients,
including respiratory tract infections,
skin and skin structure infections, in-
fections with gram-negative organisms,
and central nervous system infections.
Respiratory tract infections are most
common and include pharyngitis, pneu-
monia, acute otitis media, and sinusitis.
Streptococcus pyogenes is the major
pathogen responsible for bacterial
pharyngitis. Recovery of Staphylococ-
cus aureus, S pneumoniae, or Hae-
mophilus influenzae from the throat
represents normal flora, and treatment
directed against these organisms is not
necessary. Moreover, S pyogenes is so
predictably susceptible to penicillin and
ampicillin that susceptibility testing for
a throat isolate generally is not per-
formed. Approximately 10% of group
A streptococci are resistant to macro-
lides, a consideration, for example, in
the patient who has an immediate and
severe allergy to penicillins. Recently,
more of these macrolide-resistant
strains also have been demonstrating
inducible resistance to clindamycin.
In contrast, S pneumoniae and non-
typeable H influenzae account for most
of the other bacterial respiratory syn-
dromes, with Moraxella catarrhalis oc-
casionally responsible for acute otitis
media and sinusitis. The clinical, micro-
biological, and treatment issues are
entirely different for patients who have
these infections compared with pa-
tients who have streptococcal pharyn-
gitis. Cultures from sterile sites, the
only ones of reliable significance, rarely
Pediatrics in Review Vol.30 No.12 December 2009 499
in brief
are available for pneumonia (pleural
fluid) or otitis media (middle ear fluid).
Blood cultures, although predictive, are
not often positive. Throat and nose
cultures correlate poorly with results
from sterile sites for these infections.
S pneumoniae, H influenzae, and
M catarrhalis frequently demonstrate
resistance to beta-lactam antibiotics
such as penicillin and ampicillin, but
by different mechanisms. For S pneu-
moniae, an alteration of the organism’s
penicillin-binding proteins (PBPs) re-
sults in decreased affinity for the anti-
biotic. Screening for drug-resistant
S pneumoniae (DRSP) begins with the
application of a 1-mcg oxacillin disk.
Organisms showing a clear zone of less
than 20 mm are potentially nonsuscep-
tible and require quantitative testing to
establish their level of resistance, ex-
pressed as the minimal inhibitory con-
centration (MIC). Approximately 15%
of clinical isolates of S pneumoniae
are not susceptible to penicillin, and
approximately 50% of these isolates
are highly resistant, having MICs of
2 mcg/mL or greater.
Penicillin-nonsusceptible strains
also are more likely to be resistant to
non-beta-lactam antibiotics, including
trimethoprim-sulfamethoxazole, mac-
rolides, and clindamycin. Resistance to
vancomycin has not yet been reported
in the United States. Despite in vitro
pneumococcal resistance to beta-
lactam agents, sufficient drug concen-
trations often can be achieved for non-
meningitic infections, such as otitis
media, with high-dose therapy.
For several decades, a substantial
proportion of H influenzae isolates,
both nontypeable and type b, and vir-
tually all M catarrhalis strains have
been resistant to ampicillin and amoxi-
cillin. In contrast to DRSP resistance,
the resistance of these organisms is
mediated by beta-lactamase produc-
tion, which opens the beta-lactam ring
and renders it inactive. Therefore, for
infections that may involve these or-
500 Pediatrics in Review Vol.30 No.12 December 2009
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ganisms, the preferred therapy has be-
come beta-lactamase-stable drugs:
second- and third-generation cephalo-
sporins and combinations that include
a beta-lactamase inhibitor (amoxicillin-
clavulanate, ampicillin-sulbactam).
S aureus and S pyogenes are the
pathogens usually responsible for skin
and skin structure infections and for
musculoskeletal infections. The emer-
gence of methicillin-resistant S aureus
(MRSA) as a major pathogen makes
obtaining appropriate cultures impera-
tive. Methicillin resistance is mediated
by an alteration of PBPs, similar to the
mechanism of resistance of S pneu-
moniae. Therefore, when treating MRSA,
beta-lactam microbials are not appropri-
ate. For life-threatening infections, van-
comycin or linezolid often are used. For
nonlife-threatening infections, clindamy-
cin, trimethoprim-sulfamethoxazole, and
doxycycline in patients older than 7 years
are all considerations, even though pre-
scribing these agents for MRSA infections
constitutes off-label use.
Given all of the options for treating
MRSA, obtaining cultures for suscepti-
bility testing is critical. Susceptibility
testing for clindamycin deserves special
mention because resistance can be ei-
ther constitutive or inducible. A D test
is employed to identify apparently sen-
sitive strains that might have resistance
induced in the course of treatment. The
mechanism of induced resistance is
linked to the erm gene of erythromycin
resistance, and in the presence of an
erythromycin disc, the clear zone
around the clindamycin disc takes on
the appearance of a “D.”
Even when S aureus strains are sen-
sitive to methicillin (MSSA), they are
predictably resistant to penicillin and
ampicillin because of beta-lactamase
production. Therefore, when MSSA is
the offending pathogen, beta-
lactamase-stable drugs are most ap-
propriate: antistaphylococcal penicillins
(nafcillin, oxacillin) or first-generation
cephalosporins.
Gram-negative organisms often are
implicated in genitourinary and in some
gastrointestinal infections as well as in
systemic infections in compromised
hosts. With such a diverse group of
pathogens, establishing treatment prin-
ciples is difficult, and sensitivity testing
becomes crucial to guiding therapy. The
following general principles may be
helpful:
1. For life-threatening infections
such as neonatal sepsis or presumed
sepsis in a compromised patient, broad-
spectrum therapy that includes both a
beta-lactam antibiotic and an amino-
glycoside provides coverage for gram-
negative rods such as Escherichia coli.
2. If Pseudomonas is a likely patho-
gen, an extended-spectrum penicillin
(piperacillin or ticarcillin) or a cephalo-
sporin active against Pseudomonas
(ceftazidime) should be used as the
beta-lactam agent.
3. Combination therapy may be
continued even after identification of
the pathogen for a synergistic effect if
Pseudomonas is the recovered patho-
gen. For patients who have simple uri-
nary tract infections with Pseudomo-
nas, a single agent may be used.
4. Escherichia coli and other enteric
gram-negative rods may produce a va-
riety of beta-lactamases and cephalo-
sporinases, including extended-
spectrum beta-lactamases, which lead
to multidrug resistance. Use of a car-
bapenem (meropenem) or an aminogly-
coside then is indicated.
5. Neisseria gonorrhoeae also may
demonstrate resistance to penicillin or
ampicillin by way of beta-lactamase
production, identical to the situation
that occurs with H influenzae. Again,
beta-lactamase-stable antibiotics are
the appropriate treatment choice.
Widespread vaccination against
H influenzae has made bacterial men-
ingitis less common, with S pneu-
moniae and N meningitidis as the likely
pathogens beyond the neonatal period.
Patients who are presumed to have
 in brief

meningitis from S pneumoniae are
started initially on vancomycin in addi-
tion to ceftriaxone or cefotaxime, in the
event that the organism is resistant to
the cephalosporin. In vitro susceptibility
testing guides therapy from that point
onward.
Comment: Since our last In Brief on
antibiotic susceptibility testing in 2004
(Pediatr Rev. 2004;25:110 –111), resis-
tant S pneumoniae have continued to
proliferate, and we have seen the epi-
demic emergence of MRSA. Around the
world, resistance to vancomycin now
has been reported both in pneumococ-
cus and Staphylococcus, as well as in
Enterococcus. I can only repeat what I
wrote those few years ago: “If you
believe in evolution and natural selec-
tion, can you doubt that the more we
expose pathogenic bacteria to antibiot-
ics, the greater will their repertoire of
resistance become? We are, in fact,
facing a worldwide epidemic of multi-
ply resistant organisms that once were
easily treated, and much of the fault is
our own. Bad enough how often we use
antibiotics to treat viral infections, but
as new broad-spectrum antibiotics be-
come available, we are quick to jump,
as advertising would have us do, on
their bandwagons. The price we pay for
the ride is high in more ways than one.
Susceptibility testing offers an alterna-
tive: the opportunity to avoid broader
spectrum (and more expensive) antibi-
otics when a more narrowly active (and
cheaper) drug will do.”
Henry M. Adam, MD
Editor, In Brief

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 Antibiotic Susceptibility
Pediatr. Rev. 2009;30;499-501
DOI: 10.1542/pir.30-12-499

Updated Information including high-resolution figures, can be found at:

& Services http://pedsinreview.aappublications.org/cgi/content/full/30/12/49
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