Rising Incidence of Beta-Lactam Resistance among Pneumococci in Kuwait: Failure of Cefotaxime Therapy in Pneumococcal Meningitis

Abstract

Objective: Pneumococcal resistance to antimicrobial agents has become a global problem. This study was done to evaluate the resistance of Streptococcus pneumoniae (pneumococci) to penicillin G in Kuwait, and to assess the efficacy of other β-lactam agents (cefotaxime or ceftriaxone) in the management of invasive pneumococcal infections. Methods: Surveillance studies were done in a general teaching hospital in Kuwait for penicillin G resistance (intermediate or high level resistance) of pneumococci isolated from clinical specimens by agar diffusion method using oxacillin (1 µg) disc. In cases of pneumococcal meningitis, minimum inhibitory concentrations (MICs) of penicillin and cefotaxime were determined by agar dilution method, to differentiate intermediate resistance and high level resistance. Results: An increase in the incidence of penicillin G-resistant pneumococci from 20.6% (94 out of 457 isolates) for the period 1985–1988 to 28.5% (40 out of 140 isolates) during 1992–1994 and 38.3% (43 out of 112 isolates) during 1995/96 was observed. During the period 1992–1994, 40–45% (7 out of 16 isolates) blood culture isolates of pneumococci were intermediate or highly resistant to penicillin. Therapy with cefotaxime or ceftriaxone produced a positive outcome in 6 of the 7 patients. However, failure of cefotaxime therapy to achieve a cure was noted in 1 patient who had systemic lupus erythematosus and intermediate resistant (penicillin MIC 0.5 mg/l; cefotaxime MIC 1 mg/l) pneumococcal septicaemia complicated with meningitis. A cure was however achieved with the addition of chloramphenicol to the regimen. Conclusion: Resistance of pneumococci to penicillin G and other β-lactam agents is increasing in Kuwait. Penicillin-resistant pneumococcal bacteraemia in an immunosuppressed setting, if managed with cefotaxime or ceftriaxone, should be given high doses (cefotaxime 12 g/day or ceftriaxone 4 g/day) from the beginning. Cases of pneumococcal meningitis with cefotaxime-intermediate resistant strains (MIC 0.5–1 mg/l) on monotherapy consisting of cefotaxime or ceftriaxone should be viewed with caution. Chloramphenicol or vancomycin with rifampicin should be added to the regimen if therapeutic failure is suspected.