Comparative Kill andGrowth RatesDetermined withCefdinir and Cefaclor andwithStreptococcus pneumoniae and1-Lactamase- Producing Haemophilus influenzae

strains ofHaemophilus influenzae. Thesefrequently encountered pathogens ofcommunity-acquired respiratory tract infections areusually susceptible tobothdrugs. TheMICranges forcefdinir andcefaclor were, respectively, 0.03 to0.06 and0.25 to0.5,ug/ml forS.pneumoniae and0.25 and4to8,ug/mi forH.influenzae. Thecolony counts (CFUpermilliliter) measured after 6hofexposure toarange ofantibiotic concentrations inbroth wereplotted against thecolony countofthecontrol culture overthesameperiod, of time. Higher kill rates versus bacterial growth rates werenoted forS.pneumoniae forbothdrugs (positive balance). Conversely, lower kill rates versus growth rates werenoted forH.influenzae forbothdrugs (negative balance). Inconclusion, thebactericidal activities ofbothdrugs against S.pneumoniae andH.influenzae were similar whenexpressed bytherelationship between thegrowth rate andthekill rateat6h,butcefdinir was moreactive atlower concentrations. Theevaluation ofthebactericidal activities ofantibiotics against different bacterial species remains anunresolved problem inclinical microbiology. Thereisconsiderable controversy about thefrequency ofantibiotic tolerance (17) indifferent species ofbacteria. Technical factors, suchas antibiotic carryover, adherence totest tubewalls, medium composition, andpH,etc., areknowntoinfluence bactericidal activities (3,4,6,7,10,11,18,19). Theorganisms being tested should beinthelogarithmic phase ofgrowth, since mostantibiotics actmorerapidly ongrowing bacteria. On theother hand, therapid autolysis ofStreptococcus pneumoniae andthepossible degradation ofantibiotics during thefirst 24hinfluence theconventional measurement oftheMBC.Classically, theMBCisdefined astheminimum concentration ofdrugrequired tokill 99.9%oftheinoculum. Usually, only onemeasurement oftheMBC isperformed, after 24h. Cefdinir isaneworalbeta-lactam thatisstable against ,-lactamase (14) andthat should beuseful forthetreatment ofupperandlowerrespiratory tract infections. We compared thebactericidal activity ofcefdinir withthatofcefaclor, oneofthemostcommonly usedoralcephalosporins inthese clinical settings. Thetest modelusedinourlaboratoryexamined kill rates inrelationship togrowth rates for strains ofS.pneumoniae andHaemophilus influenzae after 6 h.Thismethodreduced theinfluence oftherapid autolysis ofS.pneumoniae onbactericidal activity measurements, the possible degradation ofthetest antibiotics invitro, andthe potential forstrain-dependent growth rates. (This workwaspresented inpart atthe17thInternational Congress ofChemotherapy, Berlin, Germany, 23to28June 1991.)