Abstract
Objective:
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.
Method:
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.
Results:
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.
Conclusions:
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.
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References
Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med 2002; 347: 240–247.
Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG . Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics 2008; 121: 689–696.
Puopolo KM, Eichenwald EC . No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18 years. Pediatrics 2010; 125: e1031–e1038.
Marget W, Seeliger HP . Listeria monocytogenes infections–therapeutic possibilities and problems. Infection 1988; 16: S175–S177.
Hof H . An update on the medical management of listeriosis. Expert Opin Pharmacother 2004; 5: 1727–1735.
Cotten CM, Taylor S, Stoll B, Goldberg RN, Hansen NI, Sanchez PJ et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 2009; 123: 58–66.
Alexander VN, Northrup V, Bizzarro MJ . Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing enterocolitis. J Pediatr 2011; 159: 392–397.
Weintraub AS, Ferrara L, Deluca L, Moshier E, Green RS, Oakman E et al. Antenatal antibiotic exposure in preterm infants with necrotizing enterocolitis. J Perinatol 2012; 32: 705–709.
Sheffield MJ, Lambert DK, Baer VL, Henry E, Butler A, Snow GL et al. Effect of ampicillin on bleeding time in very low birth-weight neonates during the first week after birth. J Perinatol 2011; 31: 477–480.
Sheffield MJ, Lambert DK, Henry E, Christensen RD . Effect of ampicillin on the bleeding time of neonatal intensive care unit patients. J Perinatol 2009; 30: 527–530.
Ealy M, Lynch KA, Meyer NC, Smith RJ . The prevalence of mitochondrial mutations associated with aminoglycoside-induced sensorineural hearing loss in an NICU population. Laryngoscope 2011; 121: 1184–1186.
Boles RG, Friedlich P . Should patients be screened for 12S rRNA mutations before treatment with aminoglycosides? Mitochondrion 2010; 10: 391–392.
Giapros VI, Cholevas VI, Andronikou SK . Acute effects of gentamicin on urinary electrolyte excretion in neonates. Pediatr Nephrol 2004; 19: 322–325.
Chiruvolu A, Engle WD, Sendelbach D, Manning MD, Jackson GL . Serum calcium values in term and late-preterm neonates receiving gentamicin. Pediatr Nephrol 2008; 23: 569–574.
Tugay S, Bircan Z, Caglayan C, Arisoy AE, Gokalp AS 2006 Acute effects of gentamicin on glomerular and tubular functions in preterm neonates. Pediatr Nephrol 21: 1389–1392.
Reese J, Veldman A, Shah L, Vucovich M, Cotton RB . Inadvertent relaxation of the ductus arteriosus by pharmacologic agents that are commonly used in the neonatal period. Semin Perinatol 2010; 34: 222–230.
Mtitimila EI, Cooke RW 2004 Antibiotic regimens for suspected early neonatal sepsis. Cochrane Database Syst Rev CD004495.
Clark RH, Bloom BT, Spitzer AR, Gerstmann DR . Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death. Pediatrics 2006; 117: 67–74.
Kuck NA, Jacobus NV, Petersen PJ, Weiss WJ, Testa RT . Comparative in vitro and in vivo activities of piperacillin combined with the beta-lactamase inhibitors tazobactam, clavulanic acid, and sulbactam. Antimicrob Agents Chemother 1989; 33: 1964–1969.
Daley D, Mulgrave L, Munro R, Neville S, Smith H, Dimech W . An evaluation of the in vitro activity of piperacillin/tazobactam. Pathology 1996; 28: 167–172.
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Chong, E., Reynolds, J., Shaw, J. et al. 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. J Perinatol 33, 529–532 (2013). https://doi.org/10.1038/jp.2012.169
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DOI: https://doi.org/10.1038/jp.2012.169
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