Abstract
Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Conclusion Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.
Similar content being viewed by others
References
American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn (1997) Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. Pediatrics 99(3):489–496
Benitz WE, Gould JB, Druzin ML (1999) Preventing early-onset group B streptococcal sepsis: strategy development using decision analysis. Pediatrics 103(6):e76
Benitz WE, Gould JB, Druzin ML (1999) Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review. Pediatrics 103(6):e77
Benitz WE, Han MY, Madan A, Ramachandra P (1998) Serial serum C-reactive protein levels in the diagnosis of neonatal infection. Pediatrics 102(4):e41
Berardi A, Lugli L, Baronciani D, Creti R, Rossi K, Ciccia M, Gambini L, Mariani S, Papa I, Serra L, Tridapalli E, Ferrari F, GBS Prevention Working Group of Emilia-Romagna (2007) Group B streptococcal infections in a northern region of Italy. Pediatrics 120(3):e487–493
Bizzarro MJ, Raskind C, Baltimore RS, Gallagher PG (2005) Seventy-five years of neonatal sepsis at Yale: 1928–2003. Pediatrics 116(3):595–602
Bizzarro MJ, Dembry LM, Baltimore RS, Gallagher PG (2008) Changing patterns in neonatal Escherichia coli sepsis and ampicillin resistance in the era of intrapartum antibiotic prophylaxis. Pediatrics 121(4):689–696
Blond MH, Gold F, Pierre F, Quentin R, Aujard Y (2001) [Neonatal bacterial infection by maternal–fetal contamination: for a change in approach? 1. Detection of Streptococcus agalactiae infection: methods and evaluation of results]. J Gynecol Obstet. Biol Reprod 30(6):521–531
Blond MH, Gold F, Pierre F, Quentin R, Aujard Y (2001) [Neonatal bacterial infection by maternal–fetal contamination: for a change in approach? 2. Uncertainties and proposals]. J Gynecol Obstet. Biol Reprod 30(6):533–551
Byington CL, Rittichier KK, Bassett KE, Castillo H, Glasgow TS, Daly J, Pavia AT (2003) Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens. Pediatrics 111(5):964–968
Centers for Disease Control and Prevention (2005) Early-onset and late-onset neonatal group b streptococcal disease—United States, 1996–2004. Morb Mortal Wkly Rep Recomm Rep 54(47):1205–1208
Centers for Disease Control and Prevention (2008) Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Group B Streptococcus, 2007. http://www.cdc.gov/abcs/reports-findings/survreports/gbs07.pdf
De Man P, Verhoeven BA, Verbrugh HA, Vos MC, Van den Anker JN (2000) An antibiotic policy to prevent emergence of resistant bacilli. Lancet 355(9208):973–978
Fluegge K, Siedler A, Heinrich B, Schulte-Moenting J, Moennig MJ, Bartels DB, Dammann O, von Kries R, Berner R, German Pediatric Surveillance Unit Study Group (2006) Incidence and clinical presentation of invasive neonatal group B streptococcal infections in Germany. Pediatrics 117(6):e1139–1145
Franz AR, Steinbach G, Kron M, Pohlandt F (1999) Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Pediatrics 104(3):447–453
Glasgow TS, Young PC, Wallin J, Kwok C, Stoddard G, Firth S, Samore M, Byington CL (2005) Association of intrapartum antibiotic exposure and late-onset serious bacterial infections in infants. Pediatrics 116(3):696–702
Guerti K, Devos H, Leven MM, Mahieu LM (2011) Time to positivity of neonatal blood cultures: fast and furious? J Med Microbiol 60:446–53
Guilbert J, Levy C, Cohen R, Delacourt C, Renolleau S, Flamant C (2010) Late and ultra late onset Streptococcus B meningitis: clinical and bacteriological data over 6 years in France. Acta Paediatr 99:47–51
Haute Autorité de Santé 2001. Prévention anténatale du risque infectieux néonatal précoce. Recommandations pour la pratique clinique. DOI: http://www.has-sante.fr/portail/upload/docs/application/pdf/Antenatal_prevention.pdf
Heath PT, Balfour G, Weisner AM, Efstratiou A, Lamagni TL, Tighe H, O’Connell LA, Cafferkey M, Verlander NQ, Nicoll A, McCartney AC, PHLS Group B Streptococcus Working Group (2004) Group B streptococcal disease in UK and Irish infants younger than 90 days. Lancet 363:292–294
Jourdan-Da-Silva N, Antona D, Six C, Georges S, Goulet V, Judin P (2008) Infections néonatales à streptocoque B en France: données d’incidence de 1997 à 2006 et pratiques de prévention en maternité. Bull Epidemiol Hebd 4:14–15
Kuhn P, Dheu C, Bolender C, Chognot D, Keller L, Demil H, Donato L, Langer B, Messer J, Astruc D (2010) Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics. Paediatr Perinat Epidemiol 24(5):479–487
Labenne M, Michaut F, Gouyon B, Ferdynus C, Gouyon JB (2007) A population-based observational study of restrictive guidelines for antibiotic therapy in early-onset neonatal infections. Pediatr Infect Dis J 26(7):593–599
Langhendries JP, Denoel A, Rousseaux D (2000) Antibiotic therapy in pregnancy: importance of rational use. Arch Pediatr 7(Suppl 2):292–294
Laugel V, Kuhn P, Beladdale J, Donato L, Escande B, Astruc D (2003) Effects of antenatal antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis. A retrospective study over five years. Biol Neonate 84(1):24–30
Lin FY, Azimi PH, Weisman LE, Philips JB, Regan J, Clark P, Rhoads GG, Clemens J, Troendle J, Pratt E, Brenner RA, Gill V (2000) Antibiotic susceptibility profiles for group B streptococci isolated from neonates, 1995–1998. Clin Infect Dis 31(1):76–79
Schrag SJ, Phil D, Zywicki S, Farley MM, Reingold AL, Harisson LH, Lefkowitz LB, Hadler JL, Danila R, Cieslak PR, Schuchat A (2000) Group B streptococcal disease in the era of intrapartum antibiotic prophylaxis. N Engl J Med 342(1):15–20
Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK (2002) Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants. N Engl J Med 347(4):240–247
Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, Oh W, Bauer CR, Korones SB, Shankaran S, Laptook AR, Stevenson DK, Papile LA, Poole WK (2002) Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 110(2):285–291
Terrone DA, Rinehart BK, Einstein MH, Britt LB, Martin JN Jr, Perry KG (1999) Neonatal sepsis and death caused by resistant Escherichia coli: possible consequences of extended maternal ampicillin administration. Am J Obstet Gynecol 180(6):1345–1348
Towers CV, Carr MH, Padilla G, Asrat T (1998) Potential consequences of widespread antepartal use of ampicillin. Am J Obstet Gynecol 179(4):879–883
Trijbels-Smeulders M, De Jonge GA, Pasker-de Jong PC, Gerards LJ, Adriaanse AH, Van Lingen RA, Kollée LA (2007) Epidemiology of neonatal group B streptococcal disease in the Netherlands before and after introduction of guidelines for prevention. Arch Dis Child Fetal Neonatal Ed 92(4):F271–276
Acknowledgements
The following investigators also participated in this trial. All investigators are members of the Eastern Neonatology Study Group and/or the regional perinatal network, “Naître en Alsace”: Centre Hospitalier de Haguenau—André Geraudel, Centre Hospitalier de Colmar—Michel Kretz, Centre Hospitalier de Mulhouse—Marc Benoît, Centre Hospitalier de Saverne—Houria Demil, Clinique Adassa Strasbourg—Ziad Mansour, Clinique Sainte Anne Strasbourg—Mohamed Jernite, Centre Hospitalier de Wissembourg—Izzat Mikaïl, and Centre Médico-Chirurgical et Obstétrical de Schiltigheim—Michèle Weil. The authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Didier, C., Streicher, MP., Chognot, D. et al. Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics. Eur J Pediatr 171, 681–687 (2012). https://doi.org/10.1007/s00431-011-1639-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-011-1639-7