Cephalosporinase

Cephalosporinase is a term used for beta-lactamase enzymes that predominantly hydrolyze cephalosporins, reducing their antibacterial activity. In many contexts, cephalosporinase refers to AmpC beta-lactamases, a subgroup of Ambler class C enzymes found in various Gram-negative bacteria. These enzymes confer resistance to many cephalosporins and cephamycins and are not reliably inhibited by early beta-lactamase inhibitors such as clavulanic acid.

Biochemical properties and inhibitors: Cephalosporinases are serine beta-lactamases that cleave the beta-lactam ring. Their substrate spectrum includes many cephalosporins and cephamycins (such as cefoxitin). They are typically poorly inhibited by traditional inhibitors, though newer inhibitors like avibactam and relebactam can suppress AmpC activity in combination therapies. Aztreonam may remain active against some AmpC producers, but resistance can occur with certain enzymes or additional resistance mechanisms.

Genetics and expression: AmpC enzymes can be chromosomally encoded and inducible in organisms such as Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Morganella morganii. Plasmid-encoded AmpCs (for example CMY, DHA families) are spread among Enterobacterales and other Gram-negative species and may be constitutively expressed or inducible, contributing to rapid acquisition of resistance.

Clinical significance and detection: Cephalosporinases are a major mechanism of beta-lactam resistance in hospital-associated infections. They reduce susceptibility to many penicillins and cephalosporins, and sometimes to aztreonam, complicating therapy. Laboratory detection relies on resistance patterns (such as cephalosporin resistance with cefoxitin resistance) and specific phenotypic or molecular tests to identify AmpC production.

Treatment considerations: Carbapenems are generally effective against many AmpC producers, while some fourth-generation cephalosporins retain activity under lower expression. Inhibitor combinations such as ceftazidime-avibactam offer activity against many AmpC enzymes. Management often includes susceptibility-guided therapy and de-escalation when possible.