extended-spectrum beta-lactamase

**Definition & mechanism:** ESBLs are beta-lactamases (Ambler class A, e.g., TEM, SHV, and especially CTX-M types) that hydrolyze the beta-lactam ring of penicillins, 1st–4th generation cephalosporins (including ceftriaxone, ceftazidime, cefepime), and monobactams (aztreonam). They are NOT active against cephamycins (cefoxitin, cefotetan) or carbapenems. They are inhibited in vitro by clavulanic acid, sulbactam, and tazobactam (the basis of the confirmatory lab test: zone enlargement with clavulanate).

**Genetics/epidemiology:** Genes are usually on plasmids, which allows horizontal transfer (conjugation) between bacteria and often co-carry resistance to fluoroquinolones, aminoglycosides, and TMP-SMX (multidrug resistance). Most common in E. coli (CTX-M, a major cause of community-onset UTIs) and Klebsiella pneumoniae. Risk factors: recent hospitalization, long-term care residence, prior antibiotic use (especially cephalosporins/fluoroquinolones), indwelling catheters, recent travel to endemic regions.

**Clinical significance:** UTIs, intra-abdominal infections, bacteremia, hospital-acquired pneumonia. Treatment failure and higher mortality occur if ceftriaxone or other third-generation cephalosporins are used empirically. Suspect on a board question when an E. coli or Klebsiella infection fails to respond to ceftriaxone.

**Treatment:** - Carbapenems (meropenem, imipenem, ertapenem) are the drug of choice for serious infections (bacteremia, sepsis); the MERINO trial showed piperacillin-tazobactam was inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia. - Uncomplicated cystitis: nitrofurantoin, fosfomycin, or TMP-SMX if susceptible. - Cefepime and piperacillin-tazobactam are generally avoided for serious infections despite in vitro susceptibility.

**Related concepts (high-yield comparisons):** - AmpC beta-lactamases (chromosomal or plasmid; Enterobacter, Citrobacter, Serratia): resistant to cephamycins and NOT inhibited by clavulanate; cefepime is often used. - Carbapenemases (KPC, NDM, OXA-48, VIM): hydrolyze carbapenems (CRE); treat with ceftazidime-avibactam, meropenem-vaborbactam, etc. - Narrow-spectrum penicillinases (e.g., S. aureus) are cleaved by penicillin/ampicillin but respond to beta-lactamase inhibitors or anti-staphylococcal penicillins. - Resistance via altered PBPs (MRSA PBP2a, mecA) is a separate mechanism.

**Infection control:** Contact precautions are often used in hospitals; antibiotic stewardship (limit cephalosporin and fluoroquinolone use) helps reduce spread.