Skip to main content
Top
Published in: Antimicrobial Resistance & Infection Control 1/2019

Open Access 01-12-2019 | Escherichia Coli | Research

Using the best available data to estimate the cost of antimicrobial resistance: a systematic review

Authors: Teresa M. Wozniak, Louise Barnsbee, Xing J. Lee, Rosana E. Pacella

Published in: Antimicrobial Resistance & Infection Control | Issue 1/2019

Login to get access

Abstract

Background

Valuation of the economic cost of antimicrobial resistance (AMR) is important for decision making and should be estimated accurately. Highly variable or erroneous estimates may alarm policy makers and hospital administrators to act, but they also create confusion as to what the most reliable estimates are and how these should be assessed. This study aimed to assess the quality of methods used in studies that quantify the costs of AMR and to determine the best available evidence of the incremental cost of these infections.

Methods

In this systematic review, we searched PubMed, Embase, Cinahl, Cochrane databases and grey literature sources published between January 2012 and October 2016. Articles reporting the additional burden of Enterococcus spp., Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) resistant versus susceptible infections were sourced. The included studies were broadly classified as reporting oncosts from the healthcare/hospital/hospital charges perspective or societal perspective. Risk of bias was assessed based on three methodological components: (1) adjustment for length of stay prior to infection onset and consideration of time-dependent bias, (2) adjustment for comorbidities or severity of disease, and (3) adjustment for inappropriate antibiotic therapy.

Results

Of 1094 identified studies, we identified 12 peer-reviewed articles and two reports that quantified the economic burden of clinically important resistant infections. Two studies used multi-state modelling to account for the timing of infection minimising the risk of time dependent bias and these were considered to generate the best available cost estimates. Studies report an additional CHF 9473 per extended-spectrum beta-lactamases -resistant Enterobacteriaceae bloodstream infections (BSI); additional €3200 per third-generation cephalosporin resistant Enterobacteriaceae BSI; and additional €1600 per methicillin-resistant S. aureus (MRSA) BSI. The remaining studies either partially adjusted or did not consider the timing of infection in their analysis.

Conclusions

Implementation of AMR policy and decision-making should be guided only by reliable, unbiased estimates of effect size. Generating these estimates requires a thorough understanding of important biases and their impact on measured outcomes. This will ensure that researchers, clinicians, and other key decision makers concerned with increasing public health threat of AMR are accurately guided by the best available evidence.
Appendix
Available only for authorised users
Literature
3.
go back to reference Cosgrove SE, Carmeli Y. The impact of antimicrobial resistance on health and economic outcomes. Clin Infect Dis. 2003;36(11):1433–7.CrossRef Cosgrove SE, Carmeli Y. The impact of antimicrobial resistance on health and economic outcomes. Clin Infect Dis. 2003;36(11):1433–7.CrossRef
5.
go back to reference Wozniak TM. Letter to the editor in response to estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control. 2018;7(1):91.CrossRef Wozniak TM. Letter to the editor in response to estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control. 2018;7(1):91.CrossRef
6.
go back to reference Smith R, Coast J. The economic burden of antimicrobial resistance: Why it is more serious than current studies suggest. London: London School of Hygiene & Tropical Medicine; 2012. Smith R, Coast J. The economic burden of antimicrobial resistance: Why it is more serious than current studies suggest. London: London School of Hygiene & Tropical Medicine; 2012.
7.
go back to reference Smith RD, Yago M, Millar M, Coast J. Assessing the macroeconomic impact of a healthcare problem: the application of computable general equilibrium analysis to antimicrobial resistance. J Health Econ. 2005;24(6):1055–75. Smith RD, Yago M, Millar M, Coast J. Assessing the macroeconomic impact of a healthcare problem: the application of computable general equilibrium analysis to antimicrobial resistance. J Health Econ. 2005;24(6):1055–75.
8.
go back to reference Cohen B, Larson EL, Stone PW, Neidell M, Glied SA. Factors associated with variation in estimates of the cost of resistant infections. Med Care. 2010;48(9):767–75.CrossRef Cohen B, Larson EL, Stone PW, Neidell M, Glied SA. Factors associated with variation in estimates of the cost of resistant infections. Med Care. 2010;48(9):767–75.CrossRef
9.
go back to reference Blot S, Depuydt P, Vandewoude K, De Bacquer D. Measuring the impact of multidrug resistance in nosocomial infection. Curr Opin Infect Dis. 2007;20(4):391–6.CrossRef Blot S, Depuydt P, Vandewoude K, De Bacquer D. Measuring the impact of multidrug resistance in nosocomial infection. Curr Opin Infect Dis. 2007;20(4):391–6.CrossRef
10.
go back to reference Gandra S, Barter DM, Laxminarayan R. Economic burden of antibiotic resistance: how much do we really know? Clin Microbiol Infect. 2014;20(10):973–80.CrossRef Gandra S, Barter DM, Laxminarayan R. Economic burden of antibiotic resistance: how much do we really know? Clin Microbiol Infect. 2014;20(10):973–80.CrossRef
11.
go back to reference de Kraker ME, Stewardson AJ, Harbarth S. Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Med. 2016;13(11):e1002184.CrossRef de Kraker ME, Stewardson AJ, Harbarth S. Will 10 million people die a year due to antimicrobial resistance by 2050? PLoS Med. 2016;13(11):e1002184.CrossRef
12.
go back to reference Smith R, Coast J. The true cost of antimicrobial resistance. BMJ. 2013;346:f1493.CrossRef Smith R, Coast J. The true cost of antimicrobial resistance. BMJ. 2013;346:f1493.CrossRef
13.
go back to reference Smith RD, Yago M, Millar M, Coast J. A macroeconomic approach to evaluating policies to contain antimicrobial resistance: a case study of methicillin-resistant Staphylococcus aureus (MRSA). Appl Health Econ Health Policy. 2006;5(1):55–65.CrossRef Smith RD, Yago M, Millar M, Coast J. A macroeconomic approach to evaluating policies to contain antimicrobial resistance: a case study of methicillin-resistant Staphylococcus aureus (MRSA). Appl Health Econ Health Policy. 2006;5(1):55–65.CrossRef
14.
go back to reference Graves N, Harbarth S, Beyersmann J, Barnett A, Halton K, Cooper B. Estimating the cost of health care-associated infections: mind your p’s and q’s. Clin Infect Dis. 2010;50(7):1017–21.CrossRef Graves N, Harbarth S, Beyersmann J, Barnett A, Halton K, Cooper B. Estimating the cost of health care-associated infections: mind your p’s and q’s. Clin Infect Dis. 2010;50(7):1017–21.CrossRef
15.
go back to reference Barnett AG, Beyersmann J, Allignol A, Rosenthal VD, Graves N, Wolkewitz M. The time-dependent bias and its effect on extra length of stay due to nosocomial infection. Value Health. 2011;14(2):381–6.CrossRef Barnett AG, Beyersmann J, Allignol A, Rosenthal VD, Graves N, Wolkewitz M. The time-dependent bias and its effect on extra length of stay due to nosocomial infection. Value Health. 2011;14(2):381–6.CrossRef
16.
go back to reference Naylor NR, Atun R, Zhu N, Kulasabanathan K, Silva S, Chatterjee A, et al. Estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control. 2018;7(1):58.CrossRef Naylor NR, Atun R, Zhu N, Kulasabanathan K, Silva S, Chatterjee A, et al. Estimating the burden of antimicrobial resistance: a systematic literature review. Antimicrob Resist Infect Control. 2018;7(1):58.CrossRef
17.
go back to reference Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.CrossRef Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.CrossRef
18.
go back to reference Spoorenberg V, Hulscher ME, Akkermans RP, Prins JM, Geerlings SE. Appropriate antibiotic use for patients with urinary tract infections reduces length of hospital stay. Clin Infect Dis. 2014;58(2):164–9.CrossRef Spoorenberg V, Hulscher ME, Akkermans RP, Prins JM, Geerlings SE. Appropriate antibiotic use for patients with urinary tract infections reduces length of hospital stay. Clin Infect Dis. 2014;58(2):164–9.CrossRef
20.
go back to reference Thampi N, Showler A, Burry L, Bai AD, Steinberg M, Ricciuto DR, et al. Multicenter study of health care cost of patients admitted to hospital with Staphylococcus aureus bacteremia: impact of length of stay and intensity of care. Am J Infect Control. 2015;43(7):739–44.CrossRef Thampi N, Showler A, Burry L, Bai AD, Steinberg M, Ricciuto DR, et al. Multicenter study of health care cost of patients admitted to hospital with Staphylococcus aureus bacteremia: impact of length of stay and intensity of care. Am J Infect Control. 2015;43(7):739–44.CrossRef
23.
go back to reference MacVane SH, Tuttle LO, Nicolau DP. Impact of extended-spectrum beta-lactamase-producing organisms on clinical and economic outcomes in patients with urinary tract infection. J Hosp Med. 2014;9(4):232–8.CrossRef MacVane SH, Tuttle LO, Nicolau DP. Impact of extended-spectrum beta-lactamase-producing organisms on clinical and economic outcomes in patients with urinary tract infection. J Hosp Med. 2014;9(4):232–8.CrossRef
24.
go back to reference Stewardson AJ, Allignol A, Beyersmann J, Graves N, Schumacher M, Meyer R, et al. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study. Euro Surveill. 2016;21(33). https://doi.org/10.2807/1560-7917.ES.2016.21.33.30319. Stewardson AJ, Allignol A, Beyersmann J, Graves N, Schumacher M, Meyer R, et al. The health and economic burden of bloodstream infections caused by antimicrobial-susceptible and non-susceptible Enterobacteriaceae and Staphylococcus aureus in European hospitals, 2010 and 2011: a multicentre retrospective cohort study. Euro Surveill. 2016;21(33). https://​doi.​org/​10.​2807/​1560-7917.​ES.​2016.​21.​33.​30319.
25.
go back to reference Stewardson A, Fankhauser C, De Angelis G, Rohner P, Safran E, Schrenzel J, et al. Burden of bloodstream infection caused by extended-spectrum beta-lactamase-producing enterobacteriaceae determined using multistate modeling at a Swiss University hospital and a nationwide predictive model. Infect Control Hosp Epidemiol. 2013;34(2):133–43.CrossRef Stewardson A, Fankhauser C, De Angelis G, Rohner P, Safran E, Schrenzel J, et al. Burden of bloodstream infection caused by extended-spectrum beta-lactamase-producing enterobacteriaceae determined using multistate modeling at a Swiss University hospital and a nationwide predictive model. Infect Control Hosp Epidemiol. 2013;34(2):133–43.CrossRef
26.
go back to reference Neidell MJ, Cohen B, Furuya Y, Hill J, Jeon CY, Glied S, et al. Costs of healthcare- and community-associated infections with antimicrobial-resistant versus antimicrobial-susceptible organisms. Clin Infect Dis. 2012;55(6):807–15.CrossRef Neidell MJ, Cohen B, Furuya Y, Hill J, Jeon CY, Glied S, et al. Costs of healthcare- and community-associated infections with antimicrobial-resistant versus antimicrobial-susceptible organisms. Clin Infect Dis. 2012;55(6):807–15.CrossRef
27.
go back to reference Morales E, Cots F, Sala M, Comas M, Belvis F, Riu M, et al. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. BMC Health Serv Res. 2012;12:122.CrossRef Morales E, Cots F, Sala M, Comas M, Belvis F, Riu M, et al. Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition. BMC Health Serv Res. 2012;12:122.CrossRef
28.
go back to reference Maslikowska JA, Walker SA, Elligsen M, Mittmann N, Palmay L, Daneman N, et al. Impact of infection with extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella species on outcome and hospitalization costs. J Hosp Infect. 2016;92(1):33–41.CrossRef Maslikowska JA, Walker SA, Elligsen M, Mittmann N, Palmay L, Daneman N, et al. Impact of infection with extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella species on outcome and hospitalization costs. J Hosp Infect. 2016;92(1):33–41.CrossRef
29.
go back to reference Leistner R, Bloch A, Sakellariou C, Gastmeier P, Schwab F. Costs and length of stay associated with extended-spectrum beta-lactamase production in cases of Escherichia coli bloodstream infection. J Glob Antimicrob Resist. 2014;2(2):107–9.CrossRef Leistner R, Bloch A, Sakellariou C, Gastmeier P, Schwab F. Costs and length of stay associated with extended-spectrum beta-lactamase production in cases of Escherichia coli bloodstream infection. J Glob Antimicrob Resist. 2014;2(2):107–9.CrossRef
30.
go back to reference Esteve-Palau E, Solande G, Sanchez F, Sorli L, Montero M, Guerri R, et al. Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: a matched cohort study. J Infect. 2015;71(6):667–74.CrossRef Esteve-Palau E, Solande G, Sanchez F, Sorli L, Montero M, Guerri R, et al. Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: a matched cohort study. J Infect. 2015;71(6):667–74.CrossRef
31.
go back to reference Cheah AL, Spelman T, Liew D, Peel T, Howden BP, Spelman D, et al. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect. 2013;19(4):E181–9.CrossRef Cheah AL, Spelman T, Liew D, Peel T, Howden BP, Spelman D, et al. Enterococcal bacteraemia: factors influencing mortality, length of stay and costs of hospitalization. Clin Microbiol Infect. 2013;19(4):E181–9.CrossRef
32.
go back to reference Chandy SJ, Naik GS, Balaji V, Jeyaseelan V, Thomas K, Lundborg CS. High cost burden and health consequences of antibiotic resistance: the price to pay. J Infect Dev Ctries. 2014;8(9):1096–102.CrossRef Chandy SJ, Naik GS, Balaji V, Jeyaseelan V, Thomas K, Lundborg CS. High cost burden and health consequences of antibiotic resistance: the price to pay. J Infect Dev Ctries. 2014;8(9):1096–102.CrossRef
33.
go back to reference Campbell RS, Emons MF, Mardekian J, Girgenti D, Gaffney M, Yu H. Adverse clinical outcomes and resource utilization associated with methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections after elective surgery. Surg Infect. 2015;16(5):543–52.CrossRef Campbell RS, Emons MF, Mardekian J, Girgenti D, Gaffney M, Yu H. Adverse clinical outcomes and resource utilization associated with methicillin-resistant and methicillin-sensitive Staphylococcus aureus infections after elective surgery. Surg Infect. 2015;16(5):543–52.CrossRef
34.
go back to reference Davison HC, Woolhouse MEJ, Low JC. What is antibiotic resistance and how can we measure it? Trends Microbiol. 2000;8(12):554–9.CrossRef Davison HC, Woolhouse MEJ, Low JC. What is antibiotic resistance and how can we measure it? Trends Microbiol. 2000;8(12):554–9.CrossRef
35.
go back to reference Rottier WC, Ammerlaan HS, Bonten MJ. Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis. J Antimicrob Chemother. 2012;67(6):1311–20.CrossRef Rottier WC, Ammerlaan HS, Bonten MJ. Effects of confounders and intermediates on the association of bacteraemia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae and patient outcome: a meta-analysis. J Antimicrob Chemother. 2012;67(6):1311–20.CrossRef
36.
go back to reference Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54(11):4851–63.CrossRef Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E, Leibovici L. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother. 2010;54(11):4851–63.CrossRef
37.
go back to reference Thom KA, Shardell MD, Osih RB, Schweizer ML, Furuno JP, Perencevich EN, et al. Controlling for severity of illness in outcome studies involving infectious diseases: impact of measurement at different time points. Infect Control Hosp Epidemiol. 2008;29(11):1048–53.CrossRef Thom KA, Shardell MD, Osih RB, Schweizer ML, Furuno JP, Perencevich EN, et al. Controlling for severity of illness in outcome studies involving infectious diseases: impact of measurement at different time points. Infect Control Hosp Epidemiol. 2008;29(11):1048–53.CrossRef
38.
go back to reference Wolkewitz M, Vonberg RP, Grundmann H, Beyersmann J, Gastmeier P, Barwolff S, et al. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care. 2008;12(2):R44.CrossRef Wolkewitz M, Vonberg RP, Grundmann H, Beyersmann J, Gastmeier P, Barwolff S, et al. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Crit Care. 2008;12(2):R44.CrossRef
39.
go back to reference Page K, Barnett AG, Graves N. What is a hospital bed day worth? A contingent valuation study of hospital chief executive officers. BMC Health Serv Res. 2017;17(1):137.CrossRef Page K, Barnett AG, Graves N. What is a hospital bed day worth? A contingent valuation study of hospital chief executive officers. BMC Health Serv Res. 2017;17(1):137.CrossRef
40.
go back to reference Stewardson AJ, Harbarth S, Graves N, on behalf of the TIMBER Study Group. Valuation of hospital bed-days released by infection control programs: a comparison of methods. Infect Control Hosp Epidemiol. 2014;35(10):1294–7. Stewardson AJ, Harbarth S, Graves N, on behalf of the TIMBER Study Group. Valuation of hospital bed-days released by infection control programs: a comparison of methods. Infect Control Hosp Epidemiol. 2014;35(10):1294–7.
41.
go back to reference Temkin E, Fallach N, Almagor J, Gladstone BP, Tacconelli E, Carmeli Y. Estimating the number of infections caused by antibiotic-resistant Escherichia coli and Klebsiella pneumoniae in 2014: a modelling study. Lancet Glob Health. 2018;6(9):e969–e79. Temkin E, Fallach N, Almagor J, Gladstone BP, Tacconelli E, Carmeli Y. Estimating the number of infections caused by antibiotic-resistant Escherichia coli and Klebsiella pneumoniae in 2014: a modelling study. Lancet Glob Health. 2018;6(9):e969–e79.
42.
go back to reference Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated health economic evaluation reporting standards (CHEERS)--explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value Health. 2013;16(2):231–50. Husereau D, Drummond M, Petrou S, Carswell C, Moher D, Greenberg D, et al. Consolidated health economic evaluation reporting standards (CHEERS)--explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force. Value Health. 2013;16(2):231–50.
Metadata
Title
Using the best available data to estimate the cost of antimicrobial resistance: a systematic review
Authors
Teresa M. Wozniak
Louise Barnsbee
Xing J. Lee
Rosana E. Pacella
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Antimicrobial Resistance & Infection Control / Issue 1/2019
Electronic ISSN: 2047-2994
DOI
https://doi.org/10.1186/s13756-019-0472-z

Other articles of this Issue 1/2019

Antimicrobial Resistance & Infection Control 1/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine