A comparison of ampicillin-cefotaxime and ampicillin-chloramphenicol in childhood bacterial meningitis: an experience in 55 patients

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Abstract
Ampicillin-cefotaxime was tested as initial therapy of presumptive bacterial meningitis in 55 children ≥ 2 months of age at our hospital. During the first year of this ongoing trial, 11 patients, 10 whose CSF yielded ampicillin-resistant Haemophilus influenzae type b (MIC > 16 mg/l, β -lactamase+) and one, indole-negative proteus (MIC 4 mg/l), were begun on ampicillin-cefotaxime and then continued on cefotaxime alone. All did well clinically except one who convulsed briefly but recovered without sequelae. The cefotaxime MICs/MBCs of the β -lactamase-positive H. influenzae isolates (≤ 0.007 to 0.03/ ≤ 0.007 to 0.12) and the proteus isolate (0.03/0.12) were significantly lower than chloramphenicol MICs/MBCs (0.25 to 1..0/0.5 to 1.0 and 8/> 16). We followed 44 other children with meningitis due to ampicillin-sensitive organisms who were treated with ampicillin or penicillin after 1 or 2 days of ampicillin-cefotaxime. Aetiological agents included ampicillin-sensitive H. influenzae (25), pneumococci (9), meningococci (8), Strept. MG (1) and Listeria monocytogenes (1). 40/44 recovered uneventfully. There were 4 neurological complications: the streptococcal meningitis sustained a brain abscess and the three others were motor incoordination (sensitive haemophilus), hearing loss and subdural effusion (2 pneumococci). There were no deaths. 18/48 children managed initially with ampicillin-chloramphenicol during the same 12-month period one year earlier had significant neurological complications and/or sequelae and there was one death; aetiological agents included sensitive H. influenzae (30), pneumococci (9), ampicillin-resistant haemophilus (5), meningococci (3) and pneumococci plus strept. MG (1). The two groups were comparable except for the number of resistant haemophilus and meningococcal strains and underlying disease more frequent in the ampicillin-cefotaxime group. A significant reduction of neurological morbidity (5/55 or 9.1 % vs. 18/48 or 37.5%: P < 0.001) was therefore associated with the ampicillin-cefotaxime schedule in the initial treatment of proven bacterial meningitis. A prolonged hospitalization (> 15 days) was less frequent ( P < 0.01) in the ampicillin-cefotaxime group (3/55 or 5.5% vs. 13/48 or 27.1 %). The results of the trial to date are considered to be very promising.

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