In vitro activities and targets of three cephem antibiotics against Haemophilus influenzae

Abstract

The antimicrobial activities of cefixime, cefpodoxime, and ceftibuten were determined with 18 ampicillinsusceptible (Amp'), 13 ampicillin-resistant P-lactamase-producing (AmprBLP), and 7 ampiciln-resistant non-j-lactamase-producing (AmprNBLP) strains of Haemophilus influenzae. An effect of inoculum density on apparent MIC, the bactericidal activity of these agents, and the targets of the three cephems were determined. The MICs of cefixime, cefpodoxime, and ceftibuten for 90% of the Amps and Amp%BLP isolates were 0.04, 0.08, and 0.08 ,ug/ml, respectively. In contrast, the MICs for 90% of the Amp'NBLP strains were 0.96, 1.92, and 7.68 ,ug/ml. No significant inoculum effect was observed for any group of strains comparing inocula of 103 and 105 CFU, whereas only the AmprNBLP isolates showed a marked effect at an inoculum of 106 CFU. Although bactericidal levels were achieved for the Amp' and AmnprBLP strains, tolerance to cefixime and ceftibuten was observed. The bactericidal activity for the AmprNBLP strains was limited, with cefixime showing the highest activity of the three cephems. Penicillin-binding proteins 2, 4, and 5 revealed high affinity, with 50% inhibitory concentration levels below the MIC for all three cephems, suggesting that these are important targets of these agents in H. influenzae. We conclude that the cephems are highly active in vitro against Amps and AmprBLP strains of H. influenzae, but less so against AmprNBLP isolates.

Problems with current recommendations for susceptibility testing of Haemophilus influenzae

“…Recently, we used HTM to compare the in vitro susceptibility of H. influenzae to three cephem antibiotics (6). In that study, we observed that the ampicillin MICs with HTM were lower for AmprNBLP strains compared with our previous data obtained with the same isolates in our laboratory when we used supplemented brain heart infusion medium (sBHI; Difco Laboratories, Detroit, Mich.); those data prompted this investigation.…”

In vitro Activity of a New Broad-Spectrum, Beta-Lactamase-Stable Oral Cephalosporin, Cefixime, in Comparison with Other Drugs, against <i>Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis </i>and <i>Streptococcus pneumoniae</i>

“…Our cefixime MICqq value of 0.12 pg/ml for Haemophilus strains are consistent with those reported by Powell and Williams [12] in AMPs and AMPr BLP strains and with the data pub lished by other authors (8,13].…”

Susceptibilities of beta-lactamase-producing and -nonproducing ampicillin-resistant strains of Haemophilus influenzae to ceftibuten, cefaclor, cefuroxime, cefixime, cefotaxime, and amoxicillin-clavulanic acid

“…Such ampicillin-resistant, 3-lactamasenonproducing (Ampr NBLP) strains probably represent <1% of all H. influenzae isolates recovered in the United States (4, 9, 18), but they are becoming more prevalent in the United Kingdom (19). Ampr NBLP strains are thought to have altered penicillin-binding proteins with decreased affinities for ampicillin and other ,-lactams (13,14,18 (2,3,8,16,17). Interpretive criteria for microdilution tests and disk diffusion tests were those described in the current National Committee for Clinical Laboratory Standards documents (16,17).…”