Community-based Treatment of Serious Bacterial Infections in Newborns and Young Infants: A Randomized Controlled Trial Assessing Three Antibiotic Regimens

Zaidi AKM et al. – When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin–gentamicin was superior to trimethoprim–sulfamethoxazole (TMP–SMX)–gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.

Methods

• Eligible infants were randomly assigned to 7 days of: (1) procaine penicillin [50,000 units/kg once daily (OD) by intramuscular injection (IM)] and gentamicin (5 mg/kg OD IM) reference arm, (2) ceftriaxone (50 mg/kg OD IM), or (3) oral trimethoprim-sulfamethoxazole (TMP-SMX) at 10 mg/kg/day divided twice daily and gentamicin IM OD.
• Primary outcome was treatment failure, defined as death, deterioration in clinical condition during therapy or no improvement after 2 days.

Results

• Possible serious bacterial infection was diagnosed in 704 infants, among 5766 screened.
• Among 434 (61.6%) randomized to clinic-based therapy, there were 13 of 145 failures with penicillin-gentamicin, 22 of 145 with ceftriaxone and 26 of 143 with TMP-SMX-gentamicin.
• Treatment failure was significantly higher with TMP-SMX-gentamicin compared with penicillin-gentamicin [relative risk 2.03, 95% confidence interval: 1.09 – 3.79] by intention-to-treat analysis.
• Differences were not significant in the ceftriaxone versus penicillin-gentamicin comparison [relative risk 1.69, 95% confidence interval 0.89–3.23).
• By 14 days, there were 2 deaths in the penicillin-gentamicin group, 3 in the ceftriaxone group and 11 in the TMP-SMX-gentamicin group [relative risk 5.58, 95% confidence interval: 1.26–24.72 (group 3 versus 1)].

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