ESBL Labeling in Klebsiella with Cefoxitin Sensitivity
If Klebsiella shows cefoxitin sensitivity, the organism is likely producing an ESBL enzyme alone (without co-production of AmpC beta-lactamase), and should be labeled as ESBL-positive based on standard confirmatory testing with cephalosporin resistance patterns, not on cefoxitin results. 1
Understanding the Resistance Pattern
The key to interpreting this scenario lies in understanding that ESBL-producing Klebsiella has a specific resistance profile:
ESBL-producing bacteria are resistant to all penicillins, all cephalosporins (including third and fourth generation), and aztreonam, but remain susceptible to carbapenems and cephamycins like cefoxitin. 1
Cefoxitin is a cephamycin (second-generation cephalosporin) that is inherently resistant to hydrolysis by ESBL enzymes, which explains why ESBL-producing organisms can show cefoxitin sensitivity. 2, 3
The Critical Distinction: ESBL vs. ESBL + AmpC
Cefoxitin sensitivity actually helps differentiate between two resistance mechanisms:
Pure ESBL producers remain susceptible to cefoxitin because ESBL enzymes cannot hydrolyze cephamycins effectively. 1
When ESBL producers also express AmpC beta-lactamases, they gain additional resistance to cephamycins (including cefoxitin), but carbapenems remain effective. 1
Approximately 5-10% of oxyimino-lactam-resistant K. pneumoniae produce a plasmid-mediated AmpC-type enzyme rather than (or in addition to) an ESBL, and these strains may show cefoxitin resistance. 4
Laboratory Confirmation
The definitive ESBL designation should be based on:
ESBL-producing bacteria demonstrate resistance to extended-spectrum cephalosporins (ceftriaxone, cefotaxime, ceftazidime, cefepime) but are inhibited by clavulanic acid in confirmatory testing. 1
The Clinical and Laboratory Standards Institute (CLSI) states that routine ESBL testing is no longer necessary before reporting results when using newer interpretive criteria for cephalosporins, but ESBL testing remains valuable for epidemiological and infection control purposes. 1, 5
MIC determination and double-disk synergy testing (DDST) are common laboratory methods for ESBL detection. 5, 6
Clinical Implications
Cefoxitin sensitivity in an ESBL-producing Klebsiella does NOT mean the organism should be treated with cefoxitin for serious infections:
Carbapenems remain the treatment of choice for serious infections caused by ESBL-producing organisms. 1, 7
Cefoxitin may be considered as definitive therapy for select ESBL-producing Klebsiella bacteremia in ICU settings, with 30-day clinical success rates comparable to carbapenems (57% vs 53%), though antibiotic changes were more frequent with cefoxitin (17% vs 0%). 2
For uncomplicated urinary tract infections due to ESBL-producing Enterobacteriaceae, cefoxitin represents an alternative to carbapenems with demonstrated clinical efficacy. 8
Common Pitfall to Avoid
Do not assume cefoxitin susceptibility excludes ESBL production—it actually suggests pure ESBL without AmpC co-production. The organism should still be labeled as ESBL-positive based on resistance to extended-spectrum cephalosporins and confirmatory testing. 1, 3