Cefoxitin Activity Against Multiply Antibiotic-Resistant Klebsiella pneumoniae In Vitro

Abstract
Due to the emergence of cephalothin- and gentamicin-resistant Klebsiella pneumoniae at this institution, we investigated the in vitro activity of two new cephalosporin compounds—cefoxitin and cefamandole. Whereas both drugs were active against cephalothin- and gentamicin-susceptible isolates of Klebsiella , only cefoxitin exhibited significant activity against cephalothin- and gentamicin-resistant isolates. Seventeen of 20 (85%) of the cephalothin- and gentamicin-resistant isolates were inhibited by ≤12.5 μg of cefoxitin per ml. The minimum bactericidal concentration in broth of representative isolates equaled the agar dilution minimum inhibitory concentration. Kirby-Bauer disk susceptibility testing correlated well with the agar dilution minimum inhibitory concentration. Cephalothin and cefamandole resistance of isolates could be correlated with antibiotic degradation by β-lactamase. Cephalothin and cefamandole evoked only a transient decrease in viable bacterial cell count with rapid inactivation of antibiotics, and full regrowth of the organisms. Cefoxitin, on the other hand, was quite effective in vitro against multiply resistant Klebsiella . No β-lactamase degradation of cefoxitin was detected. Growth curves with antibiotics indicated rapid killing of cephalothin- and gentamicin-resistant isolates by cefoxitin.