Bactericidal activities of ceftizoxime and cefotaxime against Streptococcus pneumoniae.

Patel et al. (4) compared the serum bactericidal titers (SBTs) and the time serum drug concentrations remained above the MICs (T . MIC) of ceftizoxime and cefotaxime against three intermediately penicillin-resistant Streptococcus pneumoniae isolates. MICs were # 1.0 mg/ml, SBTs were . 1:2, and T . MIC exceeded 50% of dosage intervals. They concluded that ceftizoxime’s longer T . MIC compensates for its lower microbiologic activity, that both agents should produce comparable clinical outcomes in the treatment of infections caused by intermediately penicillin-resistant S. pneumoniae, and that the two agents can be viewed as being therapeutically similar. While we do not dispute the accuracy of the data, some conclusions are not justified based on the information presented. Furthermore, Patel et al. (4) do not address other clinical and laboratory implications regarding the choice of a cephalosporin for hospital formularies. Even though T . MIC is important for predicting bactericidal activities and clinical success of cephalosporins, achievable concentrations in serum are also quite relevant when MICs approach or exceed such concentrations. Maximum concentrations of cefotaxime and ceftizoxime after a 1-g dose were 53.9 6 11.2 and 56 6 9.1 mg/ml, respectively, in Patel et al.’s study (4). In our study of 66 penicillin-resistant or intermediately resistant S. pneumoniae isolates (6), the ceftizoxime MICs were $ 64 mg/ml for 5 isolates. Haas et al. (1) reported ceftizoxime MICs of $ 256 mg/ml for some intermediately penicillin-resistant S. pneumoniae isolates versus a maximum cefotaxime MIC of 4 mg/ml. These findings, and those of others (2), indicate that the microbiologic activity of ceftizoxime can be 32-fold less than that of cefotaxime. It is unrealistic to expect uniformly favorable outcomes for infections treated with a drug when MICs exceed peak concentration (T . MIC 5 0). Stratton et al. (5) concluded that an infection with an S. pneumoniae isolate for which the cefotaxime or ceftizoxime MIC was 0.5 to 1.0 mg/ml should respond to treatment with either agent. However, like Patel et al. (4), they provided data for organisms with minimal resistance and made no claims regarding organisms which required higher MICs. To our knowledge, no clinical trials using ceftizoxime against microbiologically documented invasive S. pneumoniae infections have been performed since the widespread dissemination of beta-lactam resistance of the past few years. Among 121 S. pneumoniae isolates tested at the University of Alabama Hospital in 1997, 71 (55%) were susceptible, 36 (30%) were intermediately resistant, and 22 (17%) were resistant to penicillin. These numbers reflect an ever-increasing shift towards higher MICs of penicillin and other beta-lactams which is being experienced elsewhere. It is impossible to predict on a clinical basis which infections will be due to a resistant organism or what the cephalosporin MICs will be for intermediately penicillin-resistant or resistant isolates. This clinical uncertainty coupled with the fact that in many instances there may be no organisms isolated to test for susceptibility dictate that empiric treatment cover all possibilities. Patel et al. (4) stated that S. pneumonia has intermediate to high-level resistance to cefotaxime, ceftriaxone, and ceftizoxime as delineated by MIC breakpoints in a National Committee for Clinical Laboratory Standards (NCCLS) document (3). Although the NCCLS provides interpretive breakpoints for cefotaxime and ceftriaxone, none are published for ceftizoxime and this agent is not recommended for in vitro susceptibility testing against S. pneumoniae. This omission can be problematic for laboratories asked to provide susceptibility data for ceftizoxime. Although many laboratories use the Etest (AB Biodisk, Solna, Sweden) to determine the MICs of penicillin and cefotaxime or ceftriaxone, ceftizoxime is not available in appropriate concentrations for use against S. pneumoniae. For the reasons stated above, we have not considered ceftizoxime for formulary inclusion with therapeutic equivalency to cefotaxime or ceftriaxone.