Cefoxitin testing in S. aureus

I was recently reviewing antibiotics on a patient and came across this microbiology result:

Source: Sputum

Results: Few presumptive Staph aureus; organism does not grow for identification and susceptibility testing by automated method.

Susceptibilities by Kirby-Bauer Method

               

Drug	Result	Interpretation
Cefoxitin	17 mm	R
Erythromycin	3 mcg/mL	I
Clindamycin	0.25 mcg/mL	S
Penicillin	32 mcg/mL	S
Linezolid	4 mcg/mL	S
Trimethoprim/Sulfamethoxazole	32 mcg/mL	R
Vancomycin	1.5 mcg/mL	S

I remembered some tidbits from a microbiology rotation about cefoxitin testing in S. aureus and thought this might be a good ID pearl for our pharmacy residents.  We teach our residents to look at the susceptibility interpretation for oxacillin to determine if the S. aureus is methicillin-susceptible or resistant (which makes a huge difference in selecting antimicrobials); but what do we do if there isn’t an oxacillin interpretation?

There are some cases where the automated machine can’t get a good read on the MIC of oxacillin for S. aureus; the microbiology lab will set up a culture on a plate with a cefoxitin disk as a surrogate marker to determine oxacillin susceptibility, which has a high sensitivity and specificity.¹ Currently, the CLSI guidelines recommend a zone of inhibition ≤ 21 mm to detect resistance to cefoxitin.²  Therefore, one would just need to look at the reading for the cefoxitin – if it’s susceptible, then it should be MSSA and if it’s resistant, MRSA.  (Interestingly enough, the lab had reported the above culture as “susceptible” and from this review, was corrected to “resistant”.)

You might ask: Why don’t we use oxacillin instead? Apparently, it seems the zone of inhibition created by oxacillin is hard to read (can be fuzzy) and can lead to misinterpretations, whereas the zone of inhibition from cefoxitin is much more clear (I couldn’t find a good image of this).  Additionally, oxacillin should be read under transmitted light for the best interpretation.³ There are a few studies that compare sensitivity and specificity of cefoxitin to oxacillin for detection of mecA; however, most of these were performed with the previous CLSI standard (cefoxitin zone diameter ≤ 19 for resistance) and new recommendations has increased the sensitivity and specificities of the test.  Lastly, cefoxitin is also a better inducer of the mecA gene (the gene responsible for the production of PBP2a, which is an altered PBP than beta-lactams have a low affinity to) than oxacillin; however, this means that cefoxitin detects only mecA-mediated oxacillin resistance, but fortunately, that’s the primary mechanism of resistance for S. aureus in the United States.

1.       Fernandes CJ, et al. Cefoxitin resistance as a surrogate marker for the detection of methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother. 2005;55:506-10.

2.       CLSI. Performance standards for antimicrobial susceptibility testing; Twenty-first informational supplement. CLSI document M100-S21. Wayne, PA: Clinical and Laboratory Standards Institute; 2011.

3.       Broekema NM, et al. Comparison of cefoxitin and oxacillin disk diffusion methods for detection of mecA-mediated resistance in Staphylococcus aureus in a large-scale study. J Clinical Microbiol. 2009;47:217-9.