Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species

Cefditoren, a third generation orally administered aminothiazolyl cephalosp orin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important B- lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1435 recently isolated strains of streptococci (312 Streptococcus p neumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococc i), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 st rains). Streptococcus pneumoniae and viridans group streptococci had penici llin nonsusceptible rates of 37.8 and 35.8, respectively. cefditoren (MIC90 in mu g/ml% susceptible) activity against all tested H. influenzae (0.03/1 00) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and signif icantly greater than cefaclor. Cefditoren (MIC90, 0.5 mu g/ml) was 4- to 12 8- fold more active than comparison beta-lactams against the pneumoococci a nd was the most potent beta-lactam (including penicillin) versus beta-haemo lytic streptococci, Cefditoren pharmacokinetics demonstrate a T-1/2 of 1.5- 2h and C-max values of 2.8 and 4.6 mu g/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 mu g/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of less than or equal to 1 mu g/ml or less than or equal to 2 mu g/ml was prop osed with zone dimeter correlates of greater than or equal to 18 and greate r than or equal to 15 mm (5-mu g disk) for all cited fastidious species tes ted. Categorical agreement between MIC and disk tests was 95.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. i nfluenzae intermethod comparison results using the same interpretive criter ia were in complete agreement, but exhibited a low r = 0.39. Cefditoren cle arly possesses the most potent activity among currently studied oral cephal osporins or penicillin against commonly isolated bacterial pathogens causin g bronchitis, pneumonia, sinusitis, or pharyngitis and was active against n early all penicilllin-resisitant streptococci at less than or equal to 0.5 mu g/ml. Expanded clinical investigations seem warranted. (C) Elsevier Scie nce Inc. All rights reserved.