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

Zaidi, Anita K. M. MB BS, SM*; Tikmani, Shiyam Sundar MB BS*; Warraich, Haider J. MB BS*; Darmstadt, Gary L. MD; Bhutta, Zulfiqar A. MB BS, PhD*; Sultana, Shazia MB BS, MSc*; Thaver, Durrane MB BS, MPH*

The Pediatric Infectious Disease Journal: July 2012 - Volume 31 - Issue 7 - p 667–672
doi: 10.1097/INF.0b013e318256f86c
Original Studies

Background: Sepsis in the neonatal period is a major cause of child mortality in low-income countries. Hospitalization and parenteral penicillin/ampicillin and gentamicin therapy are recommended for management. Many families, however, are unable to access hospital care, and most home-delivered newborns who develop sepsis die without receiving antibiotic therapy. Appropriate community-based therapy in such situations is undefined. We compared failure rates of 3 clinic-based antibiotic regimens in 0- to 59-day-old infants with possible serious bacterial infection whose families refused hospitalization in Karachi communities with high neonatal mortality rates >45/1000 live births.

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)].

Conclusion: When hospitalization of sick infants is unfeasible, outpatient therapy with injectable antibiotics is an effective option. Procaine penicillin-gentamicin was superior to TMP-SMX-gentamicin. Ceftriaxone is a more expensive option, and may be less effective, although this requires further research.

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From the *Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan; and International Center for Advancing Neonatal Health, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.

Accepted for publication March 1, 2012.

This work was published after the death of Dr. Thaver.

This study was funded by the Saving Newborn Lives Initiative, a program of the Bill and Melinda Gates Foundation at Save the Children, USA. Drs. Shiyam Sunder Tikmani and Shazia Sultana received training support by a grant from the Fogarty International Center, National Institutes of Health, USA (grant numbers: ID43 TW0075 85). The authors have no conflicts of interest to disclose.

Address for correspondence: Anita K. M. Zaidi, MB BS, SM, FAAP, Professor and Chair, Department of Pediatrics and Child Health, Aga Khan University, Stadium Road, PO Box 3500, Karachi 74800, Pakistan. E-mail:

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© 2012 Lippincott Williams & Wilkins, Inc.