Transmission Routes of Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae in a Neonatology Ward in Madagascar

Mélanie Bonneault UMR1181 Biostatistique, Biomathématique, Pharmaco-épidémiologie et Maladies Infectieuses (B2PHI), Institut Pasteur, Université de Versailles–Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Inserm Paris, France;

Search for other papers by Mélanie Bonneault in
Current site
Google Scholar
PubMed
Close
,
Volasoa Herilalaina Andrianoelina Institut Pasteur Madagascar, Antananarivo, Madagascar;

Search for other papers by Volasoa Herilalaina Andrianoelina in
Current site
Google Scholar
PubMed
Close
,
Perlinot Herindrainy Institut Pasteur Madagascar, Antananarivo, Madagascar;

Search for other papers by Perlinot Herindrainy in
Current site
Google Scholar
PubMed
Close
,
Mamitina Alain Noah Rabenandrasana Institut Pasteur Madagascar, Antananarivo, Madagascar;

Search for other papers by Mamitina Alain Noah Rabenandrasana in
Current site
Google Scholar
PubMed
Close
,
Benoit Garin Institut Pasteur Madagascar, Antananarivo, Madagascar;

Search for other papers by Benoit Garin in
Current site
Google Scholar
PubMed
Close
,
Sebastien Breurec Institut Pasteur de la Guadeloupe, Centre Hospitalier Universitaire de Pointe-à-Pitre/les Abymes, Pointe-à-Pitre, France, Guadeloupe, Faculté de Médecine, Pointe-à-Pitre, Guadeloupe;

Search for other papers by Sebastien Breurec in
Current site
Google Scholar
PubMed
Close
,
Elisabeth Delarocque-Astagneau UMR1181 Biostatistique, Biomathématique, Pharmaco-épidémiologie et Maladies Infectieuses (B2PHI), Institut Pasteur, Université de Versailles–Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Inserm Paris, France;

Search for other papers by Elisabeth Delarocque-Astagneau in
Current site
Google Scholar
PubMed
Close
,
Didier Guillemot UMR1181 Biostatistique, Biomathématique, Pharmaco-épidémiologie et Maladies Infectieuses (B2PHI), Institut Pasteur, Université de Versailles–Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Inserm Paris, France;

Search for other papers by Didier Guillemot in
Current site
Google Scholar
PubMed
Close
,
Zafitsara Zo Andrianirina Service de Pédiatrie et Néonatologie, Centre Hospitalier de Soavinandriana, Antananarivo, Madagascar

Search for other papers by Zafitsara Zo Andrianirina in
Current site
Google Scholar
PubMed
Close
,
Jean-Marc Collard Institut Pasteur Madagascar, Antananarivo, Madagascar;

Search for other papers by Jean-Marc Collard in
Current site
Google Scholar
PubMed
Close
,
Bich-Tram Huynh UMR1181 Biostatistique, Biomathématique, Pharmaco-épidémiologie et Maladies Infectieuses (B2PHI), Institut Pasteur, Université de Versailles–Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Inserm Paris, France;

Search for other papers by Bich-Tram Huynh in
Current site
Google Scholar
PubMed
Close
, and
Lulla Opatowski UMR1181 Biostatistique, Biomathématique, Pharmaco-épidémiologie et Maladies Infectieuses (B2PHI), Institut Pasteur, Université de Versailles–Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Inserm Paris, France;

Search for other papers by Lulla Opatowski in
Current site
Google Scholar
PubMed
Close
Restricted access

The diffusion of extended-spectrum beta-lactamase (E-ESBL)–producing Enterobacteriaceae is a major concern worldwide, especially in low-income countries, where they may lead to therapeutic failures. In hospitals, where colonization is the highest, E-ESBL transmission is poorly understood, limiting the possibility of establishing effective control measures. We assessed E-ESBL–acquisition routes in a neonatalogy ward in Madagascar. Individuals from a neonatology ward were longitudinally followed-up (August 2014–March 2015). Newborns’ family members’ and health-care workers (HCWs) were stool-sampled and tested for E-ESBL colonization weekly. Several hypothetical acquisition routes of newborns—e.g. direct contact with family members and HCWs and indirect contact with other newborns through environmental contamination, colonization pressure, or transient hand carriage—were examined and compared using mathematical modeling and Bayesian inference. In our results, high E-ESBL acquisition rates were found, reaching > 70% for newborns, > 55% for family members, and > 75% for HCWs. Modeling analyses indicated transmission sources for newborn colonization to be species dependent. Health-care workers’ route were selected for Klebsiella pneumoniae and Escherichia coli, with respective estimated transmission strengths of 0.05 (0.008; 0.14) and 0.008 (0.001; 0.021) ind−1 day−1. Indirect transmissions associated with ward prevalence, e.g. through hand carriage or environment, were selected for Enterobacter cloacae, E. coli, and K. pneumoniae (range 0.27–0.41 ind−1 day−1). Importantly, family members were not identified as transmission source. To conclude, E-ESBL acquisition sources are strongly species dependent. Escherichia coli and E. cloacae involve more indirect contamination, whereas K. pneumoniae also spreads through contact with colonized HCWs. These findings should help improve control measures to reduce in-hospital transmission.

    • Supplemental Materials (PDF 2488 KB)

Author Notes

Address correspondence to Lulla Opatowski, UMR 1181 Biostatistics, Biomathematics, Pharmacoepidemiology and Infectious Diseases (B2PHI), Institut Pasteur, Université de Versailles–Saint-Quentin-en-Yvelines, 25-28 rue du docteur Roux, Paris 75015, France. E-mail: lulla.opatowski@pasteur.fr

 These authors contributed equally to this work.

Financial support: This work was supported by the program “Actions Concertées Inter-Pasteuriennes” (ACIP) (grant no. A-22-2013). This work was also supported directly by internal resources of the French National Institute for Health and Medical Research (Inserm), the Institut Pasteur, the University of Versailles–Saint-Quentin-en-Yvelines (UVSQ) and the French Government’s “Investissement d’Avenir” program, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID).

Authors’ addresses: Mélanie Bonneault, Elisabeth Delarocque-Astagneau, Didier Guillemot, Bich-Tram Huynh, and Lulla Opatowski, UMR1181 Biostatistique, Biomathématique, Pharmaco-épidémiologie et Maladies Infectieuses (B2PHI), Institut Pasteur, Inserm, Université de Versailles–Saint-Quentin-en-Yvelines (UVSQ), Paris, France, E-mails: melanie.bonneault@pasteur.fr, elisabeth.delarocque-astagne@pasteur.fr, didier.guillemot@pasteur.fr, bich-tram.huynh@pasteur.fr, and lulla.opatowski@pasteur.fr. Volasoa Herilalaina Andrianoelina, Perlinot Herindrainy, Mamitina Alain Noah Rabenandrasana, Benoit Garin, and Jean-Marc Collard, Institut Pasteur Madagascar, Antananarivo, Madagascar, E-mails: volasoa@pasteur.mg, perlinot@pasteur.mg, rnoah@pasteur.mg, benoitgarin@gmail.com, and jmcollard@pasteur.mg. Sebastien Breurec, Faculté de médecine, Institut Pasteur de la Guadeloupe, Pointe-à-Pitre, Guadeloupe, E-mail: sbreurec@gmail.com. Zafitsara Zo Andrianirina, Service de Pédiatrie et Néonatologie, Centre Hospitalier de Soavinandriana, Antananarivo, Madagascar, E-mail: zozand03@yahoo.fr.

  • 1.

    Lubell Y, Ashley EA, Turner C, Turner P, White NJ, 2011. Susceptibility of community-acquired pathogens to antibiotics in Africa and Asia in neonates–an alarmingly short review. Trop Med Int Health 16: 145151.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Rajaratnam JK, Marcus JR, Flaxman AD, Wang H, Levin-Rector A, Dwyer L, Costa M, Lopez AD, Murray CJ, 2010. Neonatal, postneonatal, childhood, and under-5 mortality for 187 countries, 1970–2010: a systematic analysis of progress towards Millennium Development Goal 4. Lancet 375: 19882008.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    O'Neill JIM, 2014. Antimicrobial resistance: tackling a crisis for the health and wealth of nations. Rev Antimicrob Resist 20: 116.

  • 4.

    Huynh B-T, Padget M, Garin B, Herindrainy P, Kermorvant-Duchemin E, Watier L, Guillemot D, Delarocque-Astagneau E, 2015. Burden of bacterial resistance among neonatal infections in low income countries: how convincing is the epidemiological evidence? BMC Infect Dis 15: 127.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    WHO, 2015. Global Action Plan on Antimicrobial Resistance.

  • 6.

    Cipolla D, Giuffrè M, Mammina C, Corsello G, 2011. Prevention of nosocomial infections and surveillance of emerging resistances in NICU. J Matern Fetal Neonatal Med 24 (Suppl 1): 2326.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    de Kraker ME, Stewardson AJ, Harbarth S, 2016. Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Med 13: 16.

  • 8.

    Coen P, 2012. Models of hospital acquired infection. Infection Control–Update, Section 2, 3964. IntechOpen. Available at: http://www.intechopen.com/books/infection-control-updates.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    van Kleef E, Robotham JV, Jit M, Deeny SR, Edmunds WJ, 2013. Modelling the transmission of healthcare associated infections: a systematic review. BMC Infect Dis 13: 294.

  • 10.

    Cooper BS, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Medley GF, Duckworth GJ, Lai R, Ebrahim S, 2005. Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling. Int J Technol Assess in Health Care 21: 146.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Saito R, Koyano S, Nagai R, Okamura N, Moriya K, Koike K, 2010. Evaluation of a chromogenic agar medium for the detection of extended spectrum β-lactamase-producing Enterobacteriaceae. Lett Appl Microbiol 51: 704706.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Members of the SFM Antibiogram Committee, 2003. Comité de l’antibiogramme de la société Française de microbiologie report 2003. Int J Antimicrob Agents 21: 364391.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Grohs P et al. 2014. Assessment of five screening strategies for optimal detection of carriers of third-generation cephalosporin-resistant Enterobacteriaceae in intensive care units using daily sampling. Clin Microbiol Infect 20: O879O886.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Cooper BS, Medley GF, Bradley SJ, Scott GM, 2008. An augmented data method for the analysis of nosocomial infection data. Am J Epidemiol 168: 548557.

  • 15.

    Spiegelhalter DJ, Best NG, Carlin BP, van der Linde A, 2002. Bayesian measures of model complexity and fit. J R Statist Soc B 64: 583639.

  • 16.

    Rakotonirina HC, Garin B, Randrianirina F, Richard V, Talarmin A, Arlet G, 2013. Molecular characterization of multidrug-resistant extended-spectrum β-lactamase-producing Enterobacteriaceae isolated in Antananarivo, Madagascar. BMC Microbiol 13: 85.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Randrianirina F, Soares JL, Carod JF, Ratsima E, Thonnier V, Combe P, Grosjean P, Talarmin A, 2007. Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in Antananarivo, Madagascar. J Antimicrob Chemother 59: 309312.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Randrianirina F et al. 2010. Antimicrobial resistance in pathogens causing nosocomial infections in surgery and intensive care wards in Antananarivo, Madagascar. J Infect Dev Ctries 4: 074082.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Randrianirina F, Vedy S, Rakotovao D, Ramarokoto CE, Ratsitohaina H, Carod JF, Ratsima E, Morillon M, Talarmin A, 2009. Role of contaminated aspiration tubes in nosocomial outbreak of Klebsiella pneumoniae producing SHV-2 and CTX-M-15 extended-spectrum beta-lactamases. J Hosp Infect 72: 2329.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Woerther P-L et al. 2011. Massive increase, spread, and exchange of extended spectrum β-lactamase-encoding genes among intestinal Enterobacteriaceae in hospitalized children with severe acute malnutrition in Niger. Clin Infect Dis 53: 677685.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Woodford N, Turton JF, Livermore DM, 2011. Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev 35: 736755.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Clermont O et al. 2009. Rapid detection of the O25b-ST131 clone of Escherichia coli encompassing the CTX-M-15-producing strains. J Antimicrob Chemother 64: 274277.

  • 23.

    Haverkate MR, Platteel TN, Fluit AC, Cohen Stuart JW, Leverstein-van Hall MA, Thijsen SFT, Scharringa J, Kloosterman RC, Bonten MJM, Bootsma MCJ, 2016. Quantifying within-household transmission of extended-spectrum β-lactamase-producing bacteria. Clin Microbiol Infect 23: 46.e146.e7.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Bootsma MCJ, Bonten MJM, Nijssen S, Fluit AC, Diekmann O, 2007. An algorithm to estimate the importance of bacterial acquisition routes in hospital settings. Am J Epidemiol 166: 841851.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Domenech de Cellès M, Zahar J-R, Abadie V, Guillemot D, 2013. Limits of patient isolation measures to control extended-spectrum beta-lactamase-producing Enterobacteriaceae: model-based analysis of clinical data in a pediatric ward. BMC Infect Dis 13: 187.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Harris AD, Kotetishvili M, Shurland S, Johnson JA, Morris JG, Nemoy LL, Johnson JK, 2007. How important is patient-to-patient transmission in extended-spectrum β-lactamase Escherichia coli acquisition. Am J Infect Control 35: 97101.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Fankhauser C, Zingg W, Francois P, Dharan S, Schrenzel J, Pittet D, Harbarth S, 2009. Surveillance of extended-spectrum-beta-lactamase-producing Enterobacteriaceae in a Swiss tertiary care hospital. Swiss Med Wkly 139: 747751.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Hilty M et al. 2012. Transmission dynamics of extended-spectrum β-lactamase–producing Enterobacteriaceae in the tertiary care hospital and the household setting. Clin Infect Dis 55: 967975.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Chereau F, Herindrainy P, Garin B, Huynh B-T, Randrianirina F, Padget M, Piola P, Guillemot D, Delarocque-Astagneau E, 2015. Colonization of extended-spectrum-β-lactamase- and NDM-1-producing Enterobacteriaceae among pregnant women in the community in a low-income country: a potential reservoir for transmission of multiresistant Enterobacteriaceae to neonates. Antimicrob Agents Chemother 59: 36523655.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Gurieva T, Dautzenberg MJD, Gniadkowski M, Derde LPG, Bonten MJM, Bootsma MCJ, 2018. The transmissibility of antibiotic-resistant Enterobacteriaceae in intensive care units. Clin Infect Dis 66: 489493.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Smit PW, Stoesser N, Pol S, van Kleef E, Oonsivilai M, Tan P, Neou L, Turner C, Turner P, Cooper BS, 2018. Transmission dynamics of hyper-endemic multi-drug resistant Klebsiella pneumoniae in a southeast Asian neonatal unit: a longitudinal study with whole genome sequencing. Front Microbiol 9: 1197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Harris AD, Perencevich EN, Johnson JK, Paterson DL, Morris JG, Strauss SM, Johnson JA, 2007. Patient-to-patient transmission is important in extended-spectrum -lactamase-producing Klebsiella pneumoniae acquisition. Clin Infect Dis 45: 13471350.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Paterson DL, Singh N, Rihs JD, Squier C, Rihs BL, Muder RR, 2001. Control of an outbreak of infection due to extended‐spectrum β‐lactamase–producing Escherichia coli in a liver transplantation unit. Clin Infect Dis 33: 126128.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Abdel AR, Hafez S, Abdelhakam S, Ali-Eldin Z, Esmat I, Elsayed M, Aboul-Fotouh A, 2010. Antimicrobial resistant bacteria among health care workers in intensive care units at Ain Shams University Hospitals. J Egypt Soc Parasitol 40: 7183. Available at: https://europepmc.org/abstract/med/20503587. Accessed January 3, 2019.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Demir S, Soysal A, Bakir M, Kaufmann ME, Yagci A, 2008. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in paediatric wards: a nested case-control study. J Paediatr Child Health 44: 548553.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Thurlow CJ, Prabaker K, Lin MY, Weinstein RA, Hayden MK; Centers for Disease Control and Prevention Epicenters Program, 2013. Anatomic sites of patient colonization and evironmental contamination with Klebsiella pneumoniae carbapenemase–producing Enterobacteriaceae at long-term acute care hospitals. Infect Control Hosp Epidemiol 34: 5661.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Mueller NT, Bakacs E, Combellick J, Grigoryan Z, Maria G, 2015. HHS public access. Trends Mol Med 21: 109117.

  • 38.

    Herindrainy P et al. 2018. Acquisition of extended spectrum beta-lactamase-producing Enterobacteriaceae in neonates: a community based cohort in Madagascar. PLoS One 13: e0193325.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Turner P, Pol S, Soeng S, Sar P, Neou L, Chea P, Day NP, Cooper BS, Turner C, 2016. High prevalence of antimicrobial-resistant gram-negative colonization in hospitalized Cambodian infants. Pediatr Infect Dis J 35: 856861.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Kramer A, Schwebke I, Kampf G, 2006. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis 6: 130.

  • 41.

    Bhutta ZA, Khan I, Salat S, Raza F, Ara H, 2004. Reducing length of stay in hospital for very low birthweight infants by involving mothers in a stepdown unit: an experience from Karachi (Pakistan). BMJ 329: 11511155.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 318 300 59
Full Text Views 756 33 3
PDF Downloads 317 32 3
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save