Comparative kill and growth rates determined with cefdinir and cefaclor and with Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae

Abstract

The relationship between the growth rate and the kill rate was used to evaluate and to compare the in vitro bactericidal activities of cefdinir, a new oral cephalosporin, and cefaclor against Streptococcus pneumoniae and ,-lactamase-producing strains of Haemophilus influenzae. These frequently encountered pathogens of community-acquired respiratory tract infections are usually susceptible to both drugs. The MIC ranges for cefdinir and cefaclor were, respectively, 0.03 to 0.06 and 0.25 to 0.5 ,ug/ml for S. pneumoniae and 0.25 and 4 to 8 ,ug/mi for H. influenzae. The colony counts (CFU per milliliter) measured after 6 h of exposure to a range of antibiotic concentrations in broth were plotted against the colony count of the control culture over the same period, of time. Higher kill rates versus bacterial growth rates were noted for S. pneumoniae for both drugs (positive balance). Conversely, lower kill rates versus growth rates were noted for H. influenzae for both drugs (negative balance). In conclusion, the bactericidal activities of both drugs against S. pneumoniae and H. influenzae were similar when expressed by the relationship between the growth rate and the kill rate at 6 h, but cefdinir was more active at lower concentrations.The evaluation of the bactericidal activities of antibiotics against different bacterial species remains an unresolved problem in clinical microbiology. There is considerable controversy about the frequency of antibiotic tolerance (17) in different species of bacteria. Technical factors, such as antibiotic carryover, adherence to test tube walls, medium composition, and pH, etc., are known to influence bactericidal activities (3,4,6,7,10,11,18,19). The organisms being tested should be in the logarithmic phase of growth, since most antibiotics act more rapidly on growing bacteria. On the other hand, the rapid autolysis of Streptococcus pneumoniae and the possible degradation of antibiotics during the first 24 h influence the conventional measurement of the MBC. Classically, the MBC is defined as the minimum concentration of drug required to kill 99.9% of the inoculum. Usually, only one measurement of the MBC is performed, after 24 h.Cefdinir is a new oral beta-lactam that is stable against ,-lactamase (14) and that should be useful for the treatment of upper and lower respiratory tract infections. We compared the bactericidal activity of cefdinir with that of cefaclor, one of the most commonly used oral cephalosporins in these clinical settings. The test model used in our laboratory examined kill rates in relationship to growth rates for strains of S. pneumoniae and Haemophilus influenzae after 6 h. This method reduced the influence of the rapid autolysis of S. pneumoniae on bactericidal activity measurements, the possible degradation of the test antibiotics in vitro, and the potential for strain-dependent growth rates.( Fresh media were prepared on the day of use. Antimicrobial susceptibility testing. The susceptibilities of the five isolates of each of the two bacterial species were ...

Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodology

“…Yourassowsky and coworkers (27,28) have reported rapid killing rates for cefdinir and cefaclor against penicillin-susceptible pneumococci. Jacobs et al (15) have reported a paradoxical increase in viability count for four of eight strains tested with ciprofloxacin and with temafloxacin for two of eight strains tested.…”