Emerging role of cephalosporins in bacterial meningitis

Since 1974, ampicillin and chloramphenicol have been standard therapeutic agents for initial treatment of bacterial meningitis occurring after the newborn period. Emerging problems necessitate a reappraisal and a search for alternatives to those drugs. The problems include the following: (1) Some strains of pneumococci (between 3 and 16 percent) are relatively resistant, with minimal inhibitory concentrations between 0.1 and 1.0 microgram/ml) to penicillin G and ampicillin. Such strains are not eradicated from the cerebrospinal fluid by the usual dosages of penicillin G or ampicillin. (2) Some strains of Hemophilus influenzae type B are resistant to ampicillin and chloramphenicol by virtue of beta-lactamase and acetyltransferase production. Such strains are currently rare in the United States, but it has been predicted that they might account for as many as one quarter of the isolates within a few years. (In Barcelona, Spain, their prevalence is 18 percent.) (3) Patients with meningitis often receive phenobarbital or phenytoin. Those drugs, and others metabolized by the liver, can significantly affect the pharmacology of chloramphenicol and result in either subtherapeutic or toxic concentrations of chloramphenicol in some patients. (4) For a variety of reasons, neither ampicillin plus gentamicin nor ampicillin plus chloramphenicol is an ideal combination for infants between one and four months of age when etiologic agents include coliform bacilli and group B streptococci, as well as Hemophilus, pneumococci, and meningococci. First-generation cephalosporins were unsuitable for the treatment of meningitis because of their low concentrations in the cerebrospinal fluid in relation to the bactericidal concentrations required for the common pathogens. Several of the newer cephalosporins achieve therapeutic concentrations in the cerebrospinal fluid and, in the case of three cephalosporin derivatives (cefuroxime, cefotaxime, and moxalactam), large, controlled clinical trials have demonstrated activity comparable to that of standard therapy. Limited experience suggests that several other cephalosporins (e.g., ceftizoxime, ceftazidime) will be shown to be effective when more experience is gained. Furthermore, the use of these drugs, with the exception of moxalactam, which has insufficient activity against gram-positive cocci, obviates the four problems just cited.