Failure of Cefotaxime and Meropenem to Eradicate Meningitis Caused by an Intermediately Susceptible Streptococcus pneumoniae Strain

Abstract

During the last decade the epidemiology of bacterial meningitis has changed dramatically. Since the introduction of Haemophilus influenzae type b vaccination for young children, Neisseria meningitidis and Streptococcus pneumoniae have emerged as the major causes of bacterial meningitis both in adults and infants [1]. Worldwide, Streptococcus pneumoniae strains with decreased susceptibility to penicillin and third-generation cephalosporins are emerging as a matter of concern. In 1998 Kaplan and Mason [2] reviewed 16 cases of treatment failure with third-generation cephalosporins in episodes of meningitis caused by cephalosporin-resistant (13 cases) or intermediately susceptible (3 cases) Streptococcus pneumoniae strains. Since that time at least three additional cases have been published [3,4,5]. We report here a case of antibiotic failure that occurred in a patient with Streptococcus pneumoniae meningitis treated with cefotaxime and meropenem. This is the first report of antibiotic failure in the treatment of meningitis in Belgium, and, to the best of our knowledge, the fifth report of treatment failure with thirdgeneration cephalosporins in a strain with only lowlevel resistance.In November 2000 a 7-month-old girl was admitted to a regional hospital with high fever, meningeal irritation and convulsions. The girl had been well until 3 days before admission, when she developed an upper airway infection. One day prior to admission she had received cefuroxime axetil. Treatment with cefotaxime 250 mg/kg divided over six doses, lorazepam and phenobarbital was started directly after admission. Due to intractable seizures and altered consciousness, the patient was transferred to a tertiary care hospital after a few hours. Diazepam and dexamethasone (0.25 mg/kg for 4 days) were added to the treatment regimen.Cerebrospinal fluid (CSF) at admission contained a protein concentration of 1,614 mg/l and a leukocyte count of 6,260 cells/µl. CSF and blood cultures yielded a Streptococcus pneumoniae, capsular type 14 strain. From day 2 until day 5 after admission, the patient's general condition improved, but the meningeal irritation was slow to disappear. The girl was transferred back to the regional hospital on day 5. She continued to have a fever (39-40°C) without other clinical symptoms. Given the possibility of drug-induced fever, and in view of the reduced susceptibility of the strain to cefotaxime, the treatment was switched to meropenem (110 mg/kg/d) on day 6. On day 8 the patient's level of consciousness deteriorated. Therefore, a second lumbar puncture was performed. The CSF demonstrated a protein concentration of 1,255 mg/l and a leukocyte count of 2,750 cells/µl. Gram staining of the CSF showed rare, gram-positive cocci in chains, and culture grew Streptococcus pneumoniae, capsular type 14. Vancomycin (40 mg/kg/d) was added to the treatment regimen. The fever and meningeal irritation resolved quickly. On day 16 a third lumbar puncture was performed, and culture of the CSF was sterile. The girl was discharged on day 22...

Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

“…However, there have been only a few studies on the therapeutic efficacy of meropenem or a meropenem-based regimen in the treatment of penicillin-resistant pneumococcal meningitis (16-19). We have herein evaluated the therapeutic efficacy of meropenem monotherapy and the combination of meropenem plus vancomycin for meningitis using a rabbit model of meningitis caused by penicillin-resistant S. pneumoniae (PRSP).…”