Examination of gram-negative bacilli from meningitis patients who failed or relapsed on moxalactam therapy

One Salmonella and four Escherichia coli isolates from patients with bacterial meningitis who had responded slowly, relapsed, or failed to respond to monotherapy with moxalactam were examined. For purposes of comparison, an E. coli isolate from one patient who had responded promptly to therapy was also studied. On testing, moxalactam had higher MICs and MBCs (two to four times) than cefotaxime or ceftriaxone for all isolates; the rates of killing of the isolates were dependent on the antibiotic concentrations used. At comparable multiples of the MIC, these isolates were generally killed more slowly by moxalactam than by cefotaxime or ceftriaxone. In addition, a reduction of 3 in the logarithm of the number of CFU per milliliter could be attained at far lower concentrations with cefotaxime or ceftriaxone than with moxalactam. The degree of concentration-related killing of bacteria produced by the beta-lactams appeared to correlate with the clinical responses of the patients. Furthermore, real differences appeared to exist among the third-generation cephalosporins, which were not evident by the MIC and MBC points alone but were evident in the concentration-related killing curves: Determination of a reduction of 3 in the logarithm of the number of CFU per milliliter after a 6-h incubation is suggested as the criterion for the screening of antibiotics for the therapy for gram-negative bacillary meningitis.