Three-Year Multicenter Surveillance of Pneumococcal Meningitis in Children: Clinical Characteristics, and Outcome Related to Penicillin Susceptibility and Dexamethasone Use

Abstract

Objectives. To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. Design and Patients. Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. Outcome. Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. Results. Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 μg/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (≥8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. Conclusions. Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. Only a well-designed, prospective, randomized, placebo-controlled study, conducted in centers where optimal supportive care can be provided, will determine the potential benefit, if any, of dexamethasone in patients with pneumococcal meningitis.