Results of a two-center, before and after study of piperacillin–tazobactam versus ampicillin and gentamicin as empiric therapy for suspected sepsis at birth in neonates ⩽1500 g

Abstract

We changed from ampicillin and gentamicin (AG) to piperacillin-tazobactam (PT) for routine treatment of suspected early-onset sepsis. The rationale for this change included ototoxic and renal toxic effects of gentamicin, resistance to gentamicin in late-onset infections and emergence of ampicillin resistant Escherichia coli. A before and after study was designed before the start of PT administration to monitor whether PT was associated with altered outcomes within the 501 to 1500 g birth weight (Very Low Birth Weight) population. Both unmatched and matched comparisons of AG (2007 to 2009) and PT (2010 to 2011) exposed infants are reported. Cohorts were evaluated for initial effectiveness for congenital infections, subsequent morbidities and mortality. Data from 714 patients were collected (499 AG and 215 PT in the unmatched and 301 AG and 183 PT in the matched cohorts). No significant differences in demographics or initial Apgar scores were noted in the unmatched or matched comparisons. There were significant differences in many of the outcomes of interest in both the matched and unmatched comparisons including less necrotizing enterocolitis (NEC) and less diaper rash with PT versus AG. The only adverse finding with PT was a small, but statistically significant elevation in alkaline phosphatase. Use of PT as the initial empiric antibiotic for very low birth weight infants was not associated with adverse microbiological outcomes. There was no increase in major morbidities. Although outcomes were superior in ≤ 1500 g infants treated with PT when compared with AG, the study design does not allow us to conclude that others will see a reduction in NEC or diaper rash if they implement this alternative.