S12 | www.pidj.com The Pediatric Infectious Disease Journal •  Volume 32, Number 9, Supplement, September 2013 SUPPLEMENT Background: Because access to care is limited in settings with high mortal- ity, exclusive reliance on the current recommendation of 7–10 days of par- enteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections. Methods: We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural sur- veillance site in Bangladesh. The reference regimen of intramuscular pro- caine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicil- lin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant’s home. The primary out- come is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013. Discussion: The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large num- ber of injections. The proposed research that includes fewer doses of paren- teral antibiotics if shown efficacious will address this concern. Key Words: safety, efficacy, simplified antibiotic regimens, young infants, clinical severe infection (Pediatr Infect Dis J 2013;32:S12–S18) A n estimated 3.0 million annual neonatal deaths occur glob- ally; 99% of these deaths occur in developing countries. 1–4 In many settings, neonatal and infant mortality now make up the vast majority of under-5 child deaths. For example, in Bangladesh, 57% of under-5 deaths occur within the first 28 days after birth and another 23% take place in the postneonatal period. 5 Approximately 10–20% of newborns develop life-threatening infections 6 and one- third to one-half of all neonatal deaths are due to infection, 1,7–9 including sepsis, pneumonia, tetanus, meningitis and diarrhea. Timely and appropriate treatment can avert most of these deaths. 6,10 The World Health Organization (WHO) recommends that all cases of clinical severe infection in neonates and young infants (0–59 days old) be treated in hospitals with a 7- to 10-day course of injectable antibiotics—penicillin or ampicillin and gentamicin. In low-resource settings, however, reliance on a strategy of hos- pitalization of young infants with clinical severe infections has a number of inherent disadvantages. Parents/caregivers often con- sider care-seeking outside the home to be unacceptable in the early postpartum period, or they may not be able to travel to a health facility; upon reaching the facility, infants may receive inadequate treatment because of barriers due to cost, under-staffing or lack of available beds and supplies. 11–15 Hospitalization increases the risk of exposure to multidrug-resistant nosocomial pathogens that are increasingly difficult to treat 16,17 and raises the cost of health care. 18 Strategies for community-based management of severe infections in young infants have been developed and evaluated in several research settings. 8,19,20 A cluster-randomized controlled trial of a package of maternal and neonatal interventions, which included assessment and management of newborns by village- based community health workers, was conducted by our group in Sylhet district, Bangladesh. Neonates with signs of severe infec- tion were referred to a qualified provider or treated in the home with intramuscular procaine penicillin and gentamicin (Treatment regimen included a total of 10 days of gentamicin and procaine penicillin. Dosage of gentamicin was adjusted based on neonate’s weight as follows: 10 mg every other day if <2.0 kg, 10 mg/day if 2.0–2.5 kg and 13.5 mg/day if >2.5 kg. Dosage for penicillin was Copyright © 2013 by USAID. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. ISSN: 0891-3668/13/3209-0S12 DOI: 10.1097/INF.0b013e31829ff790 Safety and Eficacy of Simpliied Antibiotic Regimens for  Outpatient Treatment of Serious Infection in Neonates and  Young Infants 0–59 Days of Age in Bangladesh Design of a Randomized Controlled Trial Abdullah H. Baqui, DrPH,* Samir Kumar Saha, PhD,† A. S. M. Nawshad Uddin Ahmed, FCPS,† Mohammad Shahidullah, FCPS,‡ Iftekhar Quasem, MPH,† Daniel E. Roth, PhD,§ Emma K. Williams, MHS,* Dipak Mitra, PhD,* A. K. M. Shamsuzzaman, DCH,¶ Wazir Ahmed, DCH,‖ Luke C. Mullany, PhD,* Simon Cousens, PhD,** Stephen Wall, MD,†† Neal Brandes, MHS,‡‡ and Robert E. Black, MD* Accepted for publication June 5, 2013. From the *Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; †Child Health Research Founda- tion/Dhaka Shishu Hospital; ‡Bangabandhu Sheikh Mujib Medical Uni- versity, Dhaka, Bangladesh; §Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada; ¶Shishu Sasthya Foundation, Dhaka; ‖Chittagong Ma O Shishu Hospital, Chittagong, Bangla- desh; **Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom; ††Saving Newborn Lives, Save the Children Federation, Inc; and ‡‡United States Agency for International Development, Washington DC. The trial registration number was ClinicalTrials.gov NCT00844337. The views and opinions expressed in this article are those of the author(s) and not necessarily the views and opinions of the United States Agency for Inter- national Development. This research was funded by the United States Agency for International Develop- ment, through a cooperative agreement (GHS-A-00-09-00004-00) with the Johns Hopkins Bloomberg School of Public Health and by the Saving New- born Lives program of Save the Children Federation, Inc, through a grant from the Bill and Melinda Gates Foundation. The authors have no other fund- ing or conflicts of interest to disclose. Address for correspondence: Abdullah H. Baqui, DrPH, Department Of Interna- tional Health, International Center for Maternal and Newborn Health, Johns Hopkins Bloomberg School of Public Health, Room E-8138, 615 N Wolfe St, Baltimore, MD 21205. E-mail: abaqui@jhsph.edu.