Review| Volume 135, P106-118, May 2023

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Evaluation of antimicrobial consumption in the neonatal population undergoing antimicrobial stewardship programmes: a systematic review

  • D.M.D. Lima
    Universidade Federal de Minas Gerais, Faculdade de Medicina, Belo Horizonte, MG, Brazil
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  • R.V. Rezende
    Hospital da Polícia Militar de Belo Horizonte, MG, Brazil
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  • L.M.O. Diniz
    Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Pediatria, Belo Horizonte, MG, Brazil
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  • L.M. Anchieta
    Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Pediatria, Belo Horizonte, MG, Brazil

    Universidade Federal de Minas Gerais, Hospital Das Clínicas, Unidade Neonatal, Belo Horizonte, MG, Brazil
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  • R.M. de Castro Romanelli
    Corresponding author. Address: 190 Professor Alfredo Balena Drive, Belo Horizonte, Minas Gerais, 30130-100, Brazil. Tel.: +55 31 34099772.
    Universidade Federal de Minas Gerais, Faculdade de Medicina, Departamento de Pediatria, Belo Horizonte, MG, Brazil

    Universidade Federal de Minas Gerais, Hospital Das Clínicas, Comissão de Controle e Infecção Hospitalar, Belo Horizonte, MG, Brazil
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Published:March 21, 2023DOI:



      Indiscriminate use of antimicrobials in neonatal sepsis treatment contributes to consumption misuse, and the optimization of prescription programmes is encouraged as a way of reducing this inappropriate use.


      To evaluate the impact of intervention programmes for adequate antimicrobial use (antimicrobial stewardship programmes) in consumption measurements of such drugs in neonatology.


      The search for articles was performed in electronic databases and by manual search for citations in publications initially identified. Electronic databases searched were BVS (Virtual Health Library), Cochrane Library, Embase, MEDLINE/PubMed, SciELO, Scopus, and Web of Science. There was no date or period limit for inclusion of articles. The PICO question was defined as populations of neonates admitted to neonatal intensive care units undergoing an intervention programme to optimize antimicrobial therapy in relation to neonates not exposed to the programme and the outcome obtained in antimicrobials consumption.


      The initial search in databases resulted in 1223 articles. Articles were screened and 16 original studies related to subject were selected, which conducted a quantitative approach to antimicrobials consumption for the population of interest. Most articles used days of therapy (DOT) as the main measure of antimicrobial consumption and have had a high-quality rating by Newcastle–Ottawa Scale. All studies were carried out in local hospitals at a single centre and most were in high-income countries.


      Of all studies identified by the search, few evaluated antimicrobial consumption in neonatology. New studies are needed, and DOT was shown to be the most adequate metric to measure consumption.


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        • Araújo B.T.
        • Pereira D.C.R.
        Políticas para controle de infecções relacionadas à assistência à saúde (IRAS) no Brasil, 2017.
        Comunicação em Ciências da Saúde. 2017; 28: 333-342
        • Padoveze M.C.
        • Fortaleza C.M.C.B.
        Healthcare-associated infections: challenges to public health in Brazil.
        Rev Saúde Pública. 2014; 48: 995-1001
        • Silva A.C.
        • Anchieta L.M.
        • Rosado V.
        • Ferreira J.
        • Clemente W.T.
        • Coelho J.S.
        • et al.
        Antimicrobial use for treatment of healthcare-associated infections and bacterial resistance in a reference neonatal unit.
        J Pediatria. 2021; 97: 329-334
        • Srivastava S.
        • Shetty N.
        Healthcare-associated infections in neonatal units: lessons from contrasting worlds.
        J Hosp Infect. 2007; 65: 292-306
        • Sistema de Informação de Mortalidade Brazil
        Dados nacionais disponibilizados no Sistema de Informação de Mortalidade (SIM).
        2022 (Available at:)
        • Zea-Vera A.
        • Ochoa T.J.
        Challenges in the diagnosis and management of neonatal sepsis.
        J Trop Pediatr. 2015; 61: 1-13
        • Yusef D.
        • Shalakhti T.
        • Awad S.
        • Algharaibeh H.
        • Khasawneh W.
        Clinical characteristics, and epidemiology of sepsis in the neonatal intensive care unit in the era of multidrug resistant organisms: a retrospective review.
        Pediatr Neonatol. 2018; 59: 35-41
        • Patel S.J.
        • Saiman L.
        Principles and strategies of antimicrobial stewardship in the neonatal intensive care unit.
        Semin Perinatol. 2012; 36: 431-436
        • Cantey J.B.
        • Patel S.J.
        Antimicrobial stewardship in the NICU.
        Infect Dis Clin North Am. 2014; 28: 247-261
        • Chiu C.H.
        • Michelow I.C.
        • Cronin J.
        • Ringer S.A.
        • Ferris T.G.
        • Puopolo K.M.
        Effectiveness of a guideline to reduce vancomycin use in the neonatal intensive care unit.
        Pediatr Infect Dis J. 2011; 30: 273-278
        • Ramasethu J.
        • Kawakita T.
        Antibiotic stewardship in perinatal and neonatal care.
        Semin Fetal Neonatal Med. 2017; 22: 278-283
        • Tsai M.H.
        • Chu S.M.
        • Hsu J.F.
        • Lien R.
        • Huang H.R.
        • Chiang M.C.
        • et al.
        Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU.
        Pediatrics. 2014; 133: e322-e329
        • de Man P.
        • Verhoeven B.A.
        • Verbrugh H.A.
        • Vos M.C.
        • van der Anker J.N.
        An antibiotic policy to prevent emergence of resistant bacilli.
        Lancet. 2000; 355: 973-978
        • Cotten C.M.
        • McDonald S.
        • Stoll B.
        • Goldberg R.N.
        • Poole K.
        • Benjamin Jr., D.K.
        • National Institute for Child Health and Human Development Neonatal Research Network
        The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants.
        Pediatrics. 2006; 118: 717-722
        • Cotten C.M.
        • Taylor S.
        • Stoll B.
        • Goldberg R.N.
        • Hansen N.I.
        • Sánchez P.J.
        • et al.
        NICHD Neonatal Research Network. 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
        • Kuppala V.S.
        • Meinzen-Derr J.
        • Morrow A.L.
        • Schibler K.R.
        Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants.
        J Pediatr. 2011; 159: 720-725
        • Saiman L.
        • Ludington E.
        • Dawson J.D.
        • Patterson J.E.
        • Rangel-Frausto S.
        • Wiblin R.T.
        • et al.
        National Epidemiology of Mycoses Study Group. Risk factors for Candida species colonization of neonatal intensive care unit patients.
        Pediatr Infect Dis J. 2001; 20: 1119-1124
        • Alexander V.N.
        • Northrup V.
        • Bizzarro M.J.
        Antibiotic exposure in the newborn intensive care unit and the risk of necrotizing entero-colitis.
        J Pediatr. 2011; 159: 392-397
        • Lee J.H.
        • Hornik C.P.
        • Benjamin Jr., D.K.
        • Herring A.H.
        • Clark R.H.
        • Cohen-Wolkowiez M.
        • et al.
        Risk factors for invasive candidiasis in infants >1500 g birth weight.
        Pediatr Infect Dis J. 2013; 32: 222-226
        • Willis Z.
        • Maurice A.S.
        Strategies to improve antibiotic use in the neonatal ICU.
        Curr Opin Pediatr. 2019; 31: 127-134
        • Ting J.Y.
        • Roberts A.
        • Tilley P.
        • Robinson J.L.
        • Dunn M.S.
        • Paquette V.
        • et al.
        Development of a national neonatal intensive care unit-specific antimicrobial stewardship programme in Canada: protocol for a cohort study.
        BMJ Open. 2020; 10e043403
        • Page M.J.
        • McKenzie J.E.
        • Bossuyt P.M.
        • Boutron I.
        • Hoffmann T.C.
        • Mulrow C.D.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • Von E.
        • Rollin A.
        Ottawa Hospital Research Institute. The Newcastle–Ottawa quality assessment scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses.
        (Available at:) ([last accessed April 2023])
        • Flannery D.D.
        • Mukhopadhyay S.
        • Jensen E.A.
        • Gerber J.S.
        • Passarella M.R.
        • Dysart K.
        • et al.
        Influence of patient characteristics on antibiotic use rates among preterm infants.
        J Pediatr Infect Dis Soc. 2021; 10: 97-103
        • Gustavsson L.
        • Lindquist S.
        • Elfvin A.
        • Hentz E.
        • Studahl M.
        Reduced antibiotic use in extremely preterm infants with an antimicrobial stewardship intervention.
        BMJ Paediatr Open. 2020 7; 4e000872
        • Cantey J.B.
        • Wozniak P.S.
        • Pruszynski J.E.
        • Sanchez P.J.
        Reducing unnecessary antibiotic use in the neonatal intensive care unit (SCOUT): a prospective interrupted time-series study.
        Lancet Infect Dis. 2016; 16: 1178-1184
        • Berardi A.
        • Zinani I.
        • Rossi C.
        • Spaggiari E.
        • D’Amico V.
        • Toni G.
        • et al.
        Antibiotic use in very low birth weight neonates after an antimicrobial stewardship program.
        Antibiotics (Basel). 2021; 10: 411
        • Astorga M.C.
        • Piscitello K.J.
        • Menda N.
        • Ebert A.M.
        • Ebert S.C.
        • Porte M.A.
        • et al.
        Antibiotic stewardship in the neonatal intensive care unit: effects of an automatic 48-hour antibiotic stop order on antibiotic use.
        J Pediatr Infect Dis Soc. 2019; 8 (310–16)
        • Nzegwu N.I.
        • Rychalsky M.R.
        • Nallu L.A.
        • Song X.
        • Deng Y.
        • Natusch A.M.
        • et al.
        Implementation of an antimicrobial stewardship program in a neonatal intensive care unit.
        Infect Control Hosp Epidemiol. 2017; 38: 1137-1143
        • Lahart A.C.
        • McPherson C.C.
        • Gerber J.S.
        • Warner B.B.
        • Lee B.R.
        • Newland J.G.
        Application of an antibiotic spectrum index in the neonatal intensive care unit.
        Infect Control Hosp Epidemiol. 2019; 40: 1181-1183
        • Thampi N.
        • Shah P.S.
        • Nelson S.
        • Agarwal A.
        • Steinberg M.
        • Diambomba Y.
        • et al.
        Prospective audit and feedback on antibiotic use in neonatal intensive care: a retrospective cohort study.
        BMC Pediatrics. 2019; 19: 105
        • McCarthy K.N.
        • Hawke A.
        • Dempsey E.M.
        Antimicrobial stewardship in the neonatal unit reduces antibiotic exposure.
        Acta Paediatr. 2018; 107: 1716-1721
        • Begnaud Jr., C.M.
        • Lemoine J.
        • Broussard L.
        • Rholdon R.
        • Doshi H.
        A quality improvement project to reduce antibiotic utilization and ancillary laboratory tests in the appraisal of early-onset sepsis in the NICU.
        J Pediatr Nurs. 2021; 60: 215-222
        • Manjabosco A.C.
        • Michelin L.
        • Gallacci C.B.
        • Berezin E.N.
        Antimicrobial use in a neonatal intensive care unit during a 4-year period.
        J Clin Neonatol. 2021; 10: 108-112
        • Wang B.
        • Li G.
        • Jin F.
        • Weng J.
        • Peng Y.
        • Dong S.
        • et al.
        Effect of weekly antibiotic round on antibiotic use in the neonatal intensive care unit as antibiotic stewardship strategy.
        Front Pediatr. 2020; 8604244
        • Chimhini G.
        • Chimhuya S.
        • Madzudzo L.
        • Heys M.
        • Crehan C.
        • Robertson V.
        • et al.
        Auditing use of antibiotics in Zimbabwean neonates.
        Infect Prev Pract. 2020 Feb 19; 2100046
        • Kommalur A.
        • Baddadka V.
        • Devadas S.
        • Kariyappa M.
        • Dakshayani B.
        • Krishnapura Lakshminarayana S.
        • et al.
        Decreasing antibiotic over-use by implementation of an antibiotic stewardship programme in preterm neonates in resource limited settings – a quality improvement initiative.
        Paediatr Int Child Health. 2021; 41: 103-111
        • Makri V.
        • Davies G.
        • Cannell S.
        • Willson K.
        • Winterson L.
        • Webb J.
        • et al.
        Managing antibiotics wisely: a quality improvement programme in a tertiary neonatal unit in the UK.
        BMJ Open Qual. 2018; 7e000285
        • Lu C.
        • Liu Q.
        • Yuan H.
        • Wang L.
        Implementation of the smart use of antibiotics program to reduce unnecessary antibiotic use in a neonatal ICU: a prospective interrupted time-series study in a developing country.
        Crit Care Med. 2019; 47 (–e7): e1
        • Malviya M.N.
        • Murthi S.
        • Selim A.A.
        • Malik F.
        • Jayraj D.
        • Mendoza J.
        • et al.
        A neonatologist-driven antimicrobial stewardship program in a neonatal tertiary care center in Oman.
        Am J Perinatol. 2022 Oct 19;
      1. World Health Organization. DDD indicators. In: Essential medicines and health products: ATC/DDD toolkit. Geneva: WHO; n.d. Available at: [last accessed July 2022].

        • Ibrahim O.M.
        • Polk R.E.
        Antimicrobial use metrics and benchmarking to improve stewardship outcomes: methodology, opportunities, and challenge.
        Infect Dis Clin N Am. 2014; 28: 195-214
        • Barlam T.F.
        • Cosgrove S.E.
        • Abbo L.M.
        • MacDougall C.
        • Schuetz A.N.
        • Septimus E.J.
        • et al.
        Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.
        Clin Infect Dis. 2016; 62: e51-e77
        • Wen S.C.H.
        • Ezure Y.
        • Rolley L.
        • Spurling G.
        • Lau C.L.
        • Riaz S.
        • et al.
        Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: a systematic review and meta-analysis.
        PLoS Med. 2021; 18e1003787
      2. Center for Disease Control and Prevention (CDC) USA. Antimicrobial Use and Resistance (AUR) Module. Available at: [last accessed March 2022].

        • Gerber J.S.
        • Hersh A.L.
        • Kronman M.P.
        • Newland J.G.
        • Ross R.K.
        • Metjian T.A.
        Development and application of an antibiotic spectrum index for benchmarking antibiotic selection patterns across hospitals.
        Infect Control Hosp Epidemiol. 2017; 38: 993-997
        • Bebella L.
        • Muiru A.N.
        Antibiotic use and emerging resistance – how can resource limited countries turn the tide?.
        Glob Heart. 2014; 9: 347-358
        • Le Doare K.
        • Bielicki J.
        • Heath P.T.
        • Sharland M.
        Systematic review of antibiotic resistance rates among Gram-negative bacteria in children with sepsis in resource-limited countries.
        J Pediatr Infect Dis Soc. 2015; 4: 11-20
        • Zingg W.
        • Pfister R.
        • Posfay-Barbe K.M.
        • Huttner B.
        • Touveneau S.
        • Pittet D.
        Secular trends in antibiotic use among neonates: 2001–2008.
        Pediatr Infect Dis J. 2011; 30: 365-370
        • Flannery D.D.
        • Horbar J.D.
        Metrics of neonatal antibiotic use.
        Semin Perinatol. 2020; 44151329
        • Araujo da Silva A.R.
        • Marques A.
        • Di Biase C.
        • Faitanin M.
        • Murni I.
        • Dramowski A.
        • et al.
        Effectiveness of antimicrobial stewardship programmes in neonatology: a systematic review.
        Arch Dis Child. 2020; 105: 563-568
        • Couto B.R.G.M.
        • Ladeira A.P.
        • AMECI (Associação mineira de epidemiologia e controle de infecções)
        Epidemiologia, Prevenção e Controle de Infecções relacionadas à Assistência à Saúde. Cap 5 Estatística e informática aplicada ao controle de infecções relacionadas à assistência a saúde.
        2013: 51-70
        • Sofouli G.A.
        • Kanellopoulou A.
        • Vervenioti A.
        • Dimitriou G.
        • Gkentzi D.
        Predictive scores for late-onset neonatal sepsis as an early diagnostic and antimicrobial stewardship tool: what have we done so far?.
        Antibiotics. 2022; 11: 928
        • Kuzniewicz M.W.
        • Puopolo K.M.
        • Fischer A.
        • Walsh E.M.
        • Li S.
        • Newman T.B.
        • et al.
        A quantitative, risk-based approach to the management of neonatal early-onset sepsis.
        JAMA Pediatr. 2017; 171: 365-371
        • Helmbrecht A.R.
        • Marfurt S.
        • Chaaban H.
        Systematic review of the effectiveness of the neonatal early-onset sepsis calculator.
        J Perinat Neonatal Nurs. 2019; 33: 82-88
        • Benincasa B.C.
        • Silveira R.C.
        • Schlatter R.P.
        • Balbinotto Neto G.
        • Procianoy R.S.
        Multivariate risk and clinical signs evaluations for early-onset sepsis on late preterm and term newborns and their economic impact.
        Eur J Pediatr. 2020; 179: 1859-1865
        • Benitz W.E.
        • Achten N.B.
        Technical assessment of the neonatal early-onset sepsis risk calculator.
        Lancet Infect Dis. 2021; 21: e134-e140