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

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

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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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only $21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AMPICILLIN DOSING IN PREMATURE INFANTS FOR EARLY-ONSET SEPSIS: EXPOSURE-DRIVEN EFFICACY, SAFETY, AND STEWARDSHIP Article 24 February 2022 SHORT-COURSE EMPIRIC ANTIBIOTIC THERAPY FOR POSSIBLE EARLY-ONSET SEPSIS IN THE NICU Article 22 February 2023 EARLY ANTIBIOTIC EXPOSURE IN VERY-LOW BIRTH WEIGHT INFANTS AND INFECTION RISK AT 3–7 DAYS AFTER BIRTH Article 25 July 2023 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. Article  Google Scholar  * 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. Article  Google Scholar  * Puopolo KM, Eichenwald EC . No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18 years. _Pediatrics_ 2010; 125: e1031–e1038. Article  Google Scholar  * Marget W, Seeliger HP . Listeria monocytogenes infections–therapeutic possibilities and problems. _Infection_ 1988; 16: S175–S177. Article  Google Scholar  * Hof H . An update on the medical management of listeriosis. _Expert Opin Pharmacother_ 2004; 5: 1727–1735. Article  CAS  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  Google Scholar  * 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. Article  CAS  Google Scholar  * Boles RG, Friedlich P . Should patients be screened for 12S rRNA mutations before treatment with aminoglycosides? _Mitochondrion_ 2010; 10: 391–392. Article  CAS  Google Scholar  * Giapros VI, Cholevas VI, Andronikou SK . Acute effects of gentamicin on urinary electrolyte excretion in neonates. _Pediatr Nephrol_ 2004; 19: 322–325. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pediatrics, Tulane University School of Medicine Pediatrics: Neonatology, New Orleans, LA, USA E Chong, J Reynolds, L Forur & P Gordon * Department of Pediatrics, Wesley Medical Center, Wichita KS, USA J Shaw & P Delmore * Department of Pediatrics, Kansas University of School of Medicine-Wichita, Wichita KS, USA H Uner * Wichita Medical Research and Education Foundation, Wichita, KS, USA B T Bloom Authors * E Chong View author publications You can also search for this author inPubMed Google Scholar * J Reynolds View author publications You can also search for this author inPubMed Google Scholar * J Shaw View author publications You can also search for this author inPubMed Google Scholar * L Forur View author publications You can also search for this author inPubMed Google Scholar * P Delmore View author publications You can also search for this author inPubMed Google Scholar * H Uner View author publications You can also search for this author inPubMed Google Scholar * B T Bloom View author publications You can also search for this author inPubMed Google Scholar * P Gordon View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to P Gordon. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Journal of Perinatology website SUPPLEMENTARY INFORMATION SUPPLEMENTARY APPENDIX (DOC 81 KB) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 16 October 2012 * Revised: 03 November 2012 * Accepted: 07 November 2012 * Published: 17 January 2013 * Issue Date: July 2013 * DOI: https://doi.org/10.1038/jp.2012.169 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * necrotizing enterocolitis * ampicillin * gentamicin * piperacillin–tazobactam * diaper rash

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. Access through your institution Buy or subscribe This is a preview of


subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $259.00 per year only


$21.58 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout


ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AMPICILLIN DOSING IN


PREMATURE INFANTS FOR EARLY-ONSET SEPSIS: EXPOSURE-DRIVEN EFFICACY, SAFETY, AND STEWARDSHIP Article 24 February 2022 SHORT-COURSE EMPIRIC ANTIBIOTIC THERAPY FOR POSSIBLE EARLY-ONSET SEPSIS


IN THE NICU Article 22 February 2023 EARLY ANTIBIOTIC EXPOSURE IN VERY-LOW BIRTH WEIGHT INFANTS AND INFECTION RISK AT 3–7 DAYS AFTER BIRTH Article 25 July 2023 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. Article 


Google Scholar  * 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. Article  Google Scholar  * Puopolo KM, Eichenwald EC . No change in the incidence of ampicillin-resistant, neonatal, early-onset sepsis over 18


years. _Pediatrics_ 2010; 125: e1031–e1038. Article  Google Scholar  * Marget W, Seeliger HP . Listeria monocytogenes infections–therapeutic possibilities and problems. _Infection_ 1988; 16:


S175–S177. Article  Google Scholar  * Hof H . An update on the medical management of listeriosis. _Expert Opin Pharmacother_ 2004; 5: 1727–1735. Article  CAS  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS 


Google Scholar  * 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.


Article  Google Scholar  * 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. Article  CAS  Google Scholar  * Boles RG, Friedlich P . Should patients be screened for 12S rRNA mutations before treatment with


aminoglycosides? _Mitochondrion_ 2010; 10: 391–392. Article  CAS  Google Scholar  * Giapros VI, Cholevas VI, Andronikou SK . Acute effects of gentamicin on urinary electrolyte excretion in


neonates. _Pediatr Nephrol_ 2004; 19: 322–325. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  Google Scholar  * 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. Article  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Pediatrics, Tulane


University School of Medicine Pediatrics: Neonatology, New Orleans, LA, USA E Chong, J Reynolds, L Forur & P Gordon * Department of Pediatrics, Wesley Medical Center, Wichita KS, USA J


Shaw & P Delmore * Department of Pediatrics, Kansas University of School of Medicine-Wichita, Wichita KS, USA H Uner * Wichita Medical Research and Education Foundation, Wichita, KS, USA


B T Bloom Authors * E Chong View author publications You can also search for this author inPubMed Google Scholar * J Reynolds View author publications You can also search for this author


inPubMed Google Scholar * J Shaw View author publications You can also search for this author inPubMed Google Scholar * L Forur View author publications You can also search for this author


inPubMed Google Scholar * P Delmore View author publications You can also search for this author inPubMed Google Scholar * H Uner View author publications You can also search for this author


inPubMed Google Scholar * B T Bloom View author publications You can also search for this author inPubMed Google Scholar * P Gordon View author publications You can also search for this


author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to P Gordon. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION


Supplementary Information accompanies the paper on the Journal of Perinatology website SUPPLEMENTARY INFORMATION SUPPLEMENTARY APPENDIX (DOC 81 KB) RIGHTS AND PERMISSIONS Reprints and


permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 16


October 2012 * Revised: 03 November 2012 * Accepted: 07 November 2012 * Published: 17 January 2013 * Issue Date: July 2013 * DOI: https://doi.org/10.1038/jp.2012.169 SHARE THIS ARTICLE


Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided


by the Springer Nature SharedIt content-sharing initiative KEYWORDS * necrotizing enterocolitis * ampicillin * gentamicin * piperacillin–tazobactam * diaper rash