Antibiotics are empirically used for the treatment of neonatal sepsis. Ampicillin and gentamicin regimen is generally the first choice. In view of rising antibiotic resistance and occurrence of Staphylococcus aureaus as a common pathogen in India in both early- and late-onset sepsis,  co-amoxyclav and amikacin may be a better choice. In this study we will compare the  efficacy and safety of ampicillin and gentamicin versus co-amoxyclav and amikacin as an initial empirical therapy in the treatment of neonatal sepsis. Neonatal sepsis will be suspected on the basis of  modified criteria given by European Medicines Agency, 2010. Sepsis work-up will consist of total WBC count, absolute neutrophil count, I/T ratio, platelet count, CRP, Procalcitonin and blood culture. CRP will be repeated 12-24 hours later in an unwell baby if initial result is less than 10 mg/dl. Lumbar puncture will be done in all cases of suspected sepsis.  In critically sick newborns lumbar puncture will be delayed by 24-48 hours.Other relevant investigations such as chest xray, arterial blood gases, renal and liver profile, cranial sonography and echocardiography will be done as per need.

Primary outcome variable is treatment failure which is defined as need to change initial antibiotic regimen within 72 hours of enrollment or earlier if clinician considers it necessary in view of deteriorating clinical condition of the baby, or not cured by 7 days after enrollment. Antibiotics will be changed under the following circumstances (one or more): 1. failure to improve or worsening clinical status, 2. new or worsening infiltrates on chest xray, 3. CRP increases by  more than 10 mg/dl  in an unwell newborn, 4. isolation of bacteria resistant to initial antibiotic regimen in an unwell newborn.

In the event of treatment failure as defined above, antibiotics will be changed as per blood/cerebrospinal fluid culture culture report, or empirically keeping in mind the sensitivity pattern of prevalent organisms in the unit.  Ampicillin and gentamicin will be replaced empirically with  piperacillin-tazobactam and amikacin.  Likewise, co-amoxyclav  will be replaced empirically with piperacillin-tazobactam while amikacin will be continued as such, or modified as per culture report.  In case of meningitis cefotaxime will be added empirically to the existing regimen.  Sepsis screen and blood culture will be repeated in the event of treatment failure and before change of antibiotics. Duration of antibiotics will be 7 days in culture-negative sepsis, 10 days in culture-positive sepsis and pneumonia and 21 days in meningitis. Antibiotics will be administered intravenously.

Newborns will be closely monitored for clinical improvement/deterioration, adverse effects of therapy and daily progress using a predesigned proforma. Newborns will be followed up at one week and one month of age  for general well being and any other problem.