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Prior antibiotic use and acquisition of multidrug-resistant organisms in hospitalized children: A systematic review

Published online by Cambridge University Press:  30 July 2019

Meghan T. Murray*
Affiliation:
School of Nursing, Columbia University Medical Center, New York, New York
Melissa P. Beauchemin
Affiliation:
School of Nursing, Columbia University Medical Center, New York, New York
Natalie Neu
Affiliation:
Department of Pediatrics, Columbia University Medical Center, New York, New York
Elaine L. Larson
Affiliation:
School of Nursing, Columbia University Medical Center, New York, New York
*
Author for correspondence: Meghan T. Murray, Email: [email protected]

Abstract

Objective:

Multidrug-resistant organisms (MDROs) cause ~5%–10% of infections in hospitalized children, leading to an increased risk of death, prolonged hospitalization, and additional costs. Antibiotic exposure is considered a driving factor of MDRO acquisition; however, consensus regarding the impact of antibiotic factors, especially in children, is lacking. We conducted a systematic review to examine the relationship between antibiotic use and subsequent healthcare-associated infection or colonization with an MDRO in children.

Design:

Systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline.

Methods:

We searched PubMed and Embase for all English, peer-reviewed original research studies published before September 2018. Included studies evaluated hospitalized children, antibiotic use as an exposure, and bacterial MDRO as an outcome.

Results:

Of the 535 studies initially identified, 29 met the inclusion criteria. Overall, a positive association was identified in most studies evaluating a specific antibiotic exposure (17 of 21, 81%), duration of antibiotics (9 of 12, 75%), and number of antibiotics received (2 of 3, 67%). Those studies that evaluated any antibiotic exposure had mixed results (5 of 10, 50%). Study sites, populations, and definitions of antibiotic use and MDROs varied widely.

Conclusions:

Published studies evaluating this relationship are limited and are of mixed quality. Limitations include observation bias in recall of antibiotic exposure, variations in case definitions, and lack of evaluation of antibiotic dosing and appropriateness. Additional studies exploring the impact of antibiotic use and MDRO acquisition may be needed to develop effective antibiotic stewardship programs for hospitalized children.

Type
Original Article
Copyright
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. 

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References

Hidron, AI, Edwards, JR, Patel, J, et al. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006–2007. Infect Control Hosp Epidemiol 2008;29:9961011.CrossRefGoogle Scholar
Magiorakos, AP, Srinivasan, A, Carey, RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012;18:268281.CrossRefGoogle ScholarPubMed
Cosgrove, SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis 2006;42 suppl 2:S82S89.CrossRefGoogle Scholar
Logan, LK, Gandra, S, Mandal, S, et al. Multidrug- and carbapenem-resistant Pseudomonas aeruginosa in children, United States, 1999–2012. J Pediatr Infect Dis Soc 2017;6:352359.Google ScholarPubMed
Logan, LK, Renschler, JP, Gandra, S, et al. Carbapenem-resistant Enterobacteriaceae in children, United States, 1999–2012. Emerg Infect Dis 2015;21:20142021.CrossRefGoogle ScholarPubMed
Meropol, SB, Haupt, AA, Debanne, SM. Incidence and outcomes of infections caused by multidrug-resistant Enterobacteriaceae in children, 2007–2015. J Pediatric Infect Dis Soc 2018;7:3645.CrossRefGoogle Scholar
Adams, DJ, Eberly, MD, Goudie, A, Nylund, CM. Rising vancomycin-resistant Enterococcus infections in hospitalized children in the United States. Hosp Pediatr 2016;6:404411.CrossRefGoogle ScholarPubMed
Hamdy, RF, Hsu, AJ, Stockmann, C, et al. Epidemiology of methicillin-resistant Staphylococcus aureus bacteremia in children. Pediatrics 2017;139(6). pii: e20170183. doi: 10.1542/peds.2017-0183.CrossRefGoogle Scholar
Folgori, L, Bernaschi, P, Piga, S, et al. Healthcare-associated infections in pediatric and neonatal intensive care units: impact of underlying risk factors and antimicrobial resistance on 30-day case fatality in Italy and Brazil. Infect Control Hosp Epidemiol 2016;37:13021309.CrossRefGoogle ScholarPubMed
Milstone, AM, Song, X, Coffin, S, Elward, A, Society for Healthcare Epidemiology of America Pediatric Special Interest Group. Identification and eradication of methicillin-resistant Staphylococcus aureus colonization in the neonatal intensive care unit: results of a national survey. Infect Control Hosp Epidemiol 2010;31:766768.CrossRefGoogle ScholarPubMed
Murray, CJ, Vos, T, Lozano, R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:21972223.CrossRefGoogle ScholarPubMed
Gerber, JS, Newland, JG, Coffin, SE, et al. Variability in antibiotic use at children’s hospitals. Pediatrics 2010;126:10671073.CrossRefGoogle ScholarPubMed
Anderson, DJ, Jenkins, TC, Evans, SR, et al. The role of stewardship in addressing antibacterial resistance: Stewardship and Infection Control Committee of the Antibacterial Resistance Leadership Group. Clin Infect Dis 2017;64 suppl 1:S36S40.CrossRefGoogle Scholar
Araujo da Silva, AR, Albernaz de Almeida Dias, DC, Marques, AF, et al. Role of antimicrobial stewardship programmes in children: a systematic review. J Hosp Infect 2018;99:117123.CrossRefGoogle ScholarPubMed
McDonald, LC. Trends in antimicrobial resistance in health care-associated pathogens and effect on treatment. Clin Infect Dis 2006;42 suppl 2:S65S71.CrossRefGoogle Scholar
Foster, CB, Sabella, C. Health care–associated infections in children. JAMA 2011;305:14801481.CrossRefGoogle ScholarPubMed
Moher, D, Liberati, A, Tetzlaff, J, Altman, DG, Group, P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 2009;62:10061012.CrossRefGoogle ScholarPubMed
Wells, GA SB, O’Connell, D, Peterson, J, Welch, V, Losos, M, Tugwell, P. The Newcastle-Ottawa Scale (NOS) for assessing the quality if nonrandomized studies in meta-analyses. http://wwwohri.ca/programs/clinical_epidemiology/oxford.htm. Accessed December 29, 2017.Google Scholar
Chiu, S, Huang, YC, Lien, RI, Chou, YH, Lin, TY. Clinical features of nosocomial infections by extended-spectrum beta-lactamase-producing Enterobacteriaceae in neonatal intensive care units. Acta Paediatr 2005;94:16441649.CrossRefGoogle ScholarPubMed
Ozsurekci, Y, Aykac, K, Cengiz, AB, et al. Bloodstream infections in children caused by carbapenem-resistant versus carbapenem-susceptible gram-negative microorganisms: risk factors and outcome. Diagnos Microbiol Infect Dis 2017;87:359364.CrossRefGoogle ScholarPubMed
Pessoa-Silva, CL, Meurer Moreira, B, Camara Almeida, V, et al. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit: risk factors for infection and colonization. J Hosp Infect 2003;53:198206.CrossRefGoogle Scholar
Renk, H, Stoll, L, Neunhoeffer, F, et al. Suspicion of respiratory tract infection with multidrug-resistant Enterobacteriaceae: epidemiology and risk factors from a paediatric intensive care unit. BMC Infect Dis 2017;17:163.CrossRefGoogle ScholarPubMed
Kim, YK, Pai, H, Lee, HJ, et al. Bloodstream infections by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in children: epidemiology and clinical outcome. Antimicrob Agents Chemother 2002;46:14811491.CrossRefGoogle ScholarPubMed
Rao, YB, Ren, ZX, Zhong, JJ, et al. Risk factors for imipenem-resistant Pseudomonas aeruginosa in neonatal intensive care units in south China. J Hosp Infect 2018;98:305308.CrossRefGoogle ScholarPubMed
Deeks, SL, Palacio, R, Ruvinsky, R, et al. Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae. The Streptococcus pneumoniae Working Group. Pediatrics 1999;103:409413.CrossRefGoogle ScholarPubMed
Arhoune, B, Oumokhtar, B, Hmami, F, et al. Rectal carriage of extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae among hospitalised neonates in a neonatal intensive care unit in Fez, Morocco. J Glob Antimicrob Resist 2017;8:9096.CrossRefGoogle Scholar
Ariffin, H, Navaratnam, P, Mohamed, M, et al. Ceftazidime-resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia. Int J Infect Dis 2000;4:2125.CrossRefGoogle ScholarPubMed
Crivaro, V, Bagattini, M, Salza, MF, et al. Risk factors for extended-spectrum beta-lactamase-producing Serratia marcescens and Klebsiella pneumoniae acquisition in a neonatal intensive care unit. J Hosp Infect 2007;67:135141.CrossRefGoogle Scholar
Sultan, AM, Seliem, WA. Identifying risk factors for healthcare-associated infections caused by carbapenem-resistant Acinetobacter baumannii in a neonatal intensive care unit. Sultan Qaboos Univ Med J 2018;18:e75e80.CrossRefGoogle Scholar
Costa Pde, O, Atta, EH, Silva, AR. Infection with multidrug-resistant gram-negative bacteria in a pediatric oncology intensive care unit: risk factors and outcomes. J Pediatr 2015;91:435441.CrossRefGoogle Scholar
Haas, EJ, Zaoutis, TE, Prasad, P, Li, M, Coffin, SE. Risk factors and outcomes for vancomycin-resistant Enterococcus bloodstream infection in children. Infect Control Hosp Epidemiol 2010. doi: 10.1086/655464.CrossRefGoogle Scholar
Thatrimontrichai, A, Techato, C, Dissaneevate, S, et al. Risk factors and outcomes of carbapenem-resistant Acinetobacter baumannii ventilator-associated pneumonia in the neonate: a case-case-control study. J Infect Chemother 2016;22:444449.CrossRefGoogle ScholarPubMed
Allen, UD, MacDonald, N, Fuite, L, Chan, F, Stephens, D. Risk factors for resistance to “first-line” antimicrobials among urinary tract isolates of Escherichia coli in children. CMAJ 1999;160:14361440.Google ScholarPubMed
Asensio, A, Oliver, A, Gonzalez-Diego, P, et al. Outbreak of a multiresistant Klebsiella pneumoniae strain in an intensive care unit: antibiotic use as risk factor for colonization and infection. Clin Infect Dis 2000;30:5560.CrossRefGoogle Scholar
Chiotos, K, Tamma, PD, Flett, KB, et al. Multicenter study of the risk factors for colonization or infection with carbapenem-resistant Enterobacteriaceae in children. Antimicrob Agents Chemother 2017;61(12):e01440-17.CrossRefGoogle ScholarPubMed
Dirajlal-Fargo, S, DeBiasi, R, Campos, J, Song, X. Carbapenem-resistant Enterobacteriaceae in pediatric patients: epidemiology and risk factors. Infect Control Hosp Epidemiol 2014;35:447449.CrossRefGoogle ScholarPubMed
Gaynes, RP, Simpson, D, Reeves, SA, et al. A nursery outbreak of multiple-aminoglycoside-resistant Escherichia coli . Infect Control 1984;5:519524.CrossRefGoogle ScholarPubMed
Gupta, A, Della-Latta, P, Todd, B, et al. Outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit linked to artificial nails. Infect Control Hosp Epidemiol 2004;25:210215.CrossRefGoogle Scholar
Karaaslan, A, Soysal, A, Altinkanat Gelmez, G, Kepenekli Kadayifci, E, Soyletir, G, Bakir, M. Molecular characterization and risk factors for carbapenem-resistant gram-negative bacilli colonization in children: emergence of NDM-producing Acinetobacter baumannii in a newborn intensive care unit in Turkey. J Hosp Infect 2016;92:6772.CrossRefGoogle Scholar
Katragkou, A, Kotsiou, M, Antachopoulos, C, et al. Acquisition of imipenem-resistant Acinetobacter baumannii in a pediatric intensive care unit: a case-control study. Intensive Care Med 2006;32:13841391.CrossRefGoogle Scholar
Logan, LK, Meltzer, LA, McAuley, JB, et al. Extended-spectrum beta-lactamase-producing Enterobacteriaceae infections in children: a two-center case-case-control study of risk factors and outcomes in Chicago, Illinois. J Pediatric Infect Dis Soc 2014;3:312319.CrossRefGoogle ScholarPubMed
Nieminen, O, Korppi, M, Helminen, M. Healthcare costs doubled when children had urinary tract infections caused by extended-spectrum beta-lactamase-producing bacteria. Acta Paediatr 2017;106:327333.CrossRefGoogle ScholarPubMed
Nolan, SM, Gerber, JS, Zaoutis, T, et al. Outbreak of vancomycin-resistant Enterococcus colonization among pediatric oncology patients. Infect Control Hosp Epidemiol 2009;30:338345.CrossRefGoogle ScholarPubMed
Nourse, C, Murphy, H, Byrne, C, et al. Control of a nosocomial outbreak of vancomycin resistant Enterococcus faecium in a paediatric oncology unit: risk factors for colonisation. Eur J Pediatr 1998;157:2027.CrossRefGoogle Scholar
Rubin, LG, Tucci, V, Cercenado, E, Eliopoulos, G, Isenberg, HD. Vancomycin-resistant Enterococcus faecium in hospitalized children. Infect Control Hosp Epidemiol 1992;13:700705.CrossRefGoogle ScholarPubMed
Zaoutis, TE, Goyal, M, Chu, JH, et al. Risk factors for and outcomes of bloodstream infection caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella species in children. Pediatrics 2005;115:942949.CrossRefGoogle ScholarPubMed
Huang, Y, Zhuang, S, Du, M. Risk factors of nosocomial infection with extended-spectrum beta-lactamase-producing bacteria in a neonatal intensive care unit in China. Infection 2007;35:339345.CrossRefGoogle Scholar
Paterson, DL, Rice, LB. Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive? Clin Infect Dis 2003;36:10061012.CrossRefGoogle ScholarPubMed
Baggs, J, Fridkin, SK, Pollack, LA, Srinivasan, A, Jernigan, JA. Estimating national trends in inpatient antibiotic use among US hospitals from 2006 to 2012. JAMA Intern Med 2016;176:16391648.CrossRefGoogle ScholarPubMed
Ruhe, JJ, Hasbun, R. Streptococcus pneumoniae bacteremia: duration of previous antibiotic use and association with penicillin resistance. Clin Infect Dis 2003;36:11321138.CrossRefGoogle ScholarPubMed
Miliani, K, L’Heriteau, F, Lacave, L, Carbonne, A, Astagneau, P, Antimicrobial Surveillance Network Study Group. Imipenem and ciprofloxacin consumption as factors associated with high incidence rates of resistant Pseudomonas aeruginosa in hospitals in northern France. J Hosp Infect 2011;77:343347.CrossRefGoogle Scholar
Tamma, PD, Avdic, E, Li, DX, Dzintars, K, Cosgrove, SE. Association of adverse events with antibiotic use in hospitalized patients. JAMA Intern Med 2017;177:13081315.CrossRefGoogle ScholarPubMed
Ingram, PR, Seet, JM, Budgeon, CA, Murray, R. Point-prevalence study of inappropriate antibiotic use at a tertiary Australian hospital. Intern Med J 2012;42:719721.CrossRefGoogle Scholar
Camins, BC, King, MD, Wells, JB, et al. Impact of an antimicrobial utilization program on antimicrobial use at a large teaching hospital: a randomized controlled trial. Infect Control Hosp Epidemiol 2009;30:931938.CrossRefGoogle Scholar
Tamma, PD, Avdic, E, Keenan, JF, et al. What is the more effective antibiotic stewardship intervention: preprescription authorization or postprescription review with feedback? Clin Infect Dis 2017;64:537543.Google ScholarPubMed
Talbot, GH, Jezek, A, Murray, BE, et al. The Infectious Diseases Society of America’s 10 x ‘20 initiative (10 new systemic antibacterial agents US Food and Drug Administration approved by 2020): Is 20 x ‘20 a possibility? Clin Infect Dis 2019;69:111.CrossRefGoogle ScholarPubMed
Neuman, H, Forsythe, P, Uzan, A, Avni, O, Koren, O. Antibiotics in early life: dysbiosis and the damage done. FEMS Microbiol Rev 2018;42:489499.Google Scholar
Langdon, A, Crook, N, Dantas, G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med 2016;8:39.CrossRefGoogle ScholarPubMed
Wang, J, Foxman, B, Mody, L, Snitkin, ES. Network of microbial and antibiotic interactions drive colonization and infection with multidrug-resistant organisms. Proc Natl Acad Sci U S A 2017;114:1046710472.CrossRefGoogle ScholarPubMed
Chai, G, Governale, L, McMahon, AW, Trinidad, JP, Staffa, J, Murphy, D. Trends of outpatient prescription drug utilization in US children, 2002–2010. Pediatrics 2012;130:2331.CrossRefGoogle Scholar
Roberts, JA, Kruger, P, Paterson, DL, Lipman, J. Antibiotic resistance—what’s dosing got to do with it? Crit Care Med 2008;36:24332440.CrossRefGoogle Scholar
Di Pentima, MC, Chan, S, Hossain, J. Benefits of a pediatric antimicrobial stewardship program at a children’s hospital. Pediatrics 2011;128:10621070.CrossRefGoogle ScholarPubMed
Principi, N, Esposito, S. Antimicrobial stewardship in paediatrics. BMC Infect Dis 2016;16:424.CrossRefGoogle ScholarPubMed
Milstone, AM, Bryant, KA, Huskins, WC, Zerr, DM. The past, present, and future of healthcare-associated infection prevention in pediatrics: multidrug-resistant organisms. Infect Control Hosp Epidemiol 2010;31 suppl 1:S18S21.CrossRefGoogle Scholar
Ramphal, R, Ambrose, PG. Extended-spectrum β-lactamases and clinical outcomes: current data. Clin Infect Dis 2006;42 suppl 4:S164S172.CrossRefGoogle Scholar
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