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Are coagulase-negative Staphylococcus (CoNS)
spp. important?
Although the clinical significance of CoNS isolated in
culture can be difficult to determine, members of this species have been associated with
increasing numbers of hospital-acquired infections. The increased use of invasive devices,
such as catheters, and the expanding number of patients with impaired host defenses have
contributed to the occurrence of infections due to CoNS.
What is the value of identifying CoNS to species level?
Although there are about 20 CoNS species, they often are
considered to be a single group. Some species are more resistant to commonly used
antimicrobial agents than others. Identification to species level can aid in the
recognition of outbreaks and in tracking resistance trends.
Which CoNS species are more frequently multidrug resistant?
S. epidermidis is the most common CoNS isolated in
clinical laboratories. Usually, S. epidermidis, S. haemolyticus, and S. hominis
are more likely to be multiply resistant to antimicrobial agents than are other CoNS
species. However, resistance patterns of CoNS may differ between hospitals and wards.
Why is oxacillin resistance in CoNS important?
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Limited treatment options. Oxacillin-resistant CoNS isolates are resistant to all b
-lactam agents, including penicillins, cephalosporins, and carbapenems. In addition,
oxacillin-resistant CoNS isolates are often resistant to other commonly used antimicrobial
agents, so vancomycin is frequently the drug of choice for treatment of clinically
significant infections.
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Oxacillin-resistant strains are transmissible. An outbreak of oxacillin-resistant
CoNS can occur when one strain is transmitted among patients.
Is it difficult to detect oxacillin resistance in CoNS?
Accurate detection of oxacillin resistance can be
difficult. Colony sizes of CoNS are often smaller than those of S. aureus, making
growth more difficult to read. In addition, like S. aureus, two subpopulations (one
susceptible and the other resistant) may coexist within a culture (1). All cells in a
culture may carry the genetic information for resistance but only a small number can
express the resistance in vitro. This phenomenon is termed heteroresistance and occurs in
staphylococci resistant to penicillinase-stable penicillins, such as oxacillin.
Heteroresistance is a problem for clinical laboratory personnel
because cells expressing resistance may grow more slowly than the susceptible population.
This is why NCCLS recommends incubating isolates being tested against oxacillin at 35° C
for a full 24 hours before reading (2).
What are the breakpoints for testing the
susceptibility of CoNS to oxacillin and why are the oxacillin breakpoints for CoNS
different from the breakpoints for S. aureus?
The 1999 National Committee for Clinical Laboratory Standards
(NCCLS) breakpoints for CoNS are different from those for S. aureus (2).
MICs |
Oxacillin Susceptible |
Oxacillin Intermediate |
Oxacillin Resistant |
CoNS |
< 0.25 µg/ml
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no intermediate MIC |
> 0.5 µg/ml
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S. aureus |
< 2 µg/ml
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no intermediate MIC |
> 4 µg/ml
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Zone sizes |
Oxacillin Susceptible |
Oxacillin Intermediate |
Oxacillin Resistant |
CoNS |
> 18 mm
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no intermediate zone |
< 17 mm
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S. aureus |
> 13 mm
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11-12mm |
< 10 mm
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When studies were performed
to evaluate oxacillin breakpoints for CoNS, the current breakpoints for
S. aureus failed to detect many CoNS that contained the mecA
gene. In general, the new breakpoints for CoNS correlate better with mecA
production for CoNS. Staphylococcal resistance to oxacillin/methicillin
occurs when an isolate carries an altered penicillin-binding protein,
PBP2a, which is encoded by the mecA gene. The alteration
of the penicillin-binding protein does not allow the drug to bind well
to the bacterial cell, causing resistance to -lactam
antimicrobial agents.
Why do the 1999 NCCLS guidelines not recommend testing CoNS
using the oxacillin screen plate when previously published guidelines indicated the test
could be used?
A recent study was performed that systematically evaluated
the detection of oxacillin resistance in CoNS (3). Because many resistant strains were not
detected in this study, the NCCLS decided that the oxacillin screen test should no longer
be recommended. This view was supported by anecdotal reports with the same findings.
Why is oxacillin tested instead of methicillin?
Oxacillin is more resistant to degradation in storage and
is more likely to detect most heteroresistant strains. Methicillin is not commercially
available in the United States, and NCCLS does not provide breakpoints for methicillin or
nafcillin for CoNS testing (2).
- Kloos, W.E. and T. L. Bannerman. 1999. Staphylococcus and Micrococcus,
p. 276. In P.R. Murray, E.J. Baron, M.A. Pfaller, F.C. Tenover, R.H. Yolken [ed.],
Manual of Clinical Microbiology, 7th ed. ASM Press, Washington, D.C.
- National Committee for Clinical Laboratory Standards. 1999. Performance standards
for antimicrobial susceptibility testing. NCCLS approved standard M100-S9. National
Committee for Clinical Laboratory Standards, Wayne, PA.
- Tenover, F.C., R.N. Jones, J.M. Swenson, B. Zimmer, S. McAllister, J. H.
Jorgensen, and the NCCLS Staphylococcus Working Group. 1999. Methods for improved
detection of oxacillin resistance in coagulase-negative staphylococci: results of a
multicenter study. Journal of Clinical Microbiology 37(12):4051-4058.
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