Cefotaxime breakpoint for Streptococcus pneumoniae

Cefotaxime Breakpoint for Streptococcus pneumoniae I read with interest the recent article "Increased rate of isolation of penicillin-resistant Streptococcus pneumoniae in a children's hospital and in vitro susceptibilities to antibiot- ics of potential therpaeutic use" by Mason et al. (5).In their article, the authors complain of the lack of adequate antibi- otic susceptibility interpretation criteria for and clinical experience in treating systemic infections caused by S. pneumoniae with antibiotics, other than penicillin, and of the lack of data that correlate clinical outcome with MICs of antibiotics.In their study, the authors applied the interpretative criteria of the National Committee for Clinical Labo- ratory Standards (NCCLS) for Haemophilus influenzae to S. pneumoniae and found that all isolates were susceptible to cefotaxime at an MIC of .2Fg/ml, including those isolates highly resistant to penicillin, with the breakpoint being 2 j,g/ml for cefotaxime.Here, I report a failure in the treat- ment with cefotaxime of meningitis caused by S. pneumo- niae with intermediate resistance to penicillin.I will report just the microbiological results and antibiotic therapy, be- cause the case study will be published elsewhere (1).Briefly, an 18-month-old girl was admitted to the hospital with meningeal syndrome that had been previously treated with oral cephradine because of otitis media.Cerebrospinal fluid (CSF) smear showed gram-positive cocci, and the patient was treated empirically with penicillin (500,000 units/kg of body weight per day) and cefotaxime (200 mg/kg/day) intra- venously.After 72 h, fever persisted and no clinical im- provement was observed.Laboratory results reported S. pneumoniae serotype 23, with MICs for penicillin, cefotax- ime, and imipenem at 1, 0.5, and 0.03 ,g/ml, respectively.Treatment was then changed to 300 mg of cefotaxime per kg per day (8); nevertheless, 48 h later, fever still persisted and S. pneumoniae was again isolated from CSF with the same susceptibility results.The treatment was changed to intra- venous imipenem-cilastatin (100 mg/kg/day), and after 72 h of this new treatment, a favorable clinical response was recorded and the CSF proved sterile.Therapy was contin- ued for 14 days, and clinical healing and normal CSF were achieved.No sequelae were recorded.Considering the cefotaxime concentrations achieved in CSF, about 4 ,g/ml in the acute phase of purulent meningitis (7), the minimal concentrations (0.5 to 1 p,g/ml) in the CSF of children with bacterial meningitis reported by Ellmen et al.(3), and the clinical outcome of the case described above, it seems that a breakpoint for cefotaxime of 2 ,g/ml is too high, although until now, the published cases of S. pneumoniae resistant to cefotaxime isolated from CSF reported MICs of >2 ,ug/ml (2, 4, 6).If in the report of Mason et al. (5) the breakpoint of cefotaxime were lowered by only 1 step dilution, non-cefotaxime-susceptible S. pneumoniae strains would be found in both groups of pneumonocci, the inter- mediate group and the group highly resistant to penicillin.From here, I encourage the NCCLS to elaborate on the interpretative susceptibility criteria for S. pneumoniae, be- cause the increasing number of penicillin-resistant cases of S. pneumoniae reported makes it necessary to look for alternative antibiotics, and specific criteria are needed.