Susceptibility of Haemophilus influenzae to chloramphenicol and eight beta-lactam antibiotics

Abstract

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates ofHaemophilus influenzae, 25 of which produced fl-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for f-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for ,8-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicoL ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10' or 106 colony-forming units per ml).The inoculum size had no appreciable effect on the rate of killing of fi-lactamasenegative strains. The rates at which ,B-lactamase-producing strains were killed by chloramphenicoL cefotaxime, and moxalactam were not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 106 colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the ,-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of ,-lactamase-producing H. influenzae.

Cefuroxime treatment of bacterial meningitis in infants and children

“…Treatment failures of HIB meningitis with cefamandole (150 to 200 mg/kg per day) have been reported (1,16) and are believed to be due to the instability of cefamandole to the Haemophilus beta-lactamase (1,16,18). McCracken and coworkers (11) showed that cefuroxime was relatively ineffective in experimental meningitis compared with chloramphenicol, cefoperazone, ceftriaxone, or moxalactam.…”

Haemophilus influenzae: antibiotic susceptibility.

“…For example, cefamandole appears to be relatively active against beta-lactamase-producing strains of H. influenzae when the inoculum size used in testing is 104 CFU/ml (110). When the inoculum size is increased to 106 CFU/ml, most strains test as resistant (9,106,107). Early clinical trials with cefamandole yielded treatment failures when beta-lactamase-producing strains were isolated (5).…”

Haemophilus influenzae: antibiotic susceptibility

“…For example, cefamandole appears to be relatively active against beta-lactamase-producing strains of H. influenzae when the inoculum size used in testing is 104 CFU/ml (110). When the inoculum size is increased to 106 CFU/ml, most strains test as resistant (9,106,107). Early clinical trials with cefamandole yielded treatment failures when beta-lactamase-producing strains were isolated (5).…”