Cost-effectiveness of IMI/CIL/REL for the treatment of carbapenem non-susceptible Gram-negative bacterial infections


  • Martina Paoletti Centre for Economics and International Studies – Economic Evaluation and Health Technology Assessment, Faculty of Economics, University of Rome “Tor Vergata”, Rome - Italy
  • Andrea Marcellusi Centre for Economics and International Studies – Economic Evaluation and Health Technology Assessment, Faculty of Economics, University of Rome “Tor Vergata”, Rome - Italy
  • Joe Yang Merck & Co., Inc., Rahway, NJ - USA
  • Francesco Saverio Mennini Centre for Economics and International Studies – Economic Evaluation and Health Technology Assessment, Faculty of Economics, University of Rome “Tor Vergata”, Rome - Italy and Institute for Leadership and Management in Health, Kingston University London, Kingston Hill, Kingston upon Thames KT2 7LB, London - UK



Cost-effectiveness, Economic evaluation, Gram-negative bacterial infection


Objective: The objective of this analysis was to evaluate the cost-effectiveness of imipenem/cilastatin/relebactam compared to colistin-imipenem in the treatment of hospitalized patients with Gram-negative bacterial infections caused by imipenem-resistant pathogens. The perspective was both that of the National Health Service (NHS) and the social one.

Methodology: A mixed model was developed to simulate a cohort of patients capable of highlighting the impacts of the disease on the quality of life and the absorption of economic resources of the patients in analysis. Modelled patients were those with hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infection (cIAI) or complicated urinal tract infection (cUTI) caused by carbapenem-resistant Gram-negative (GN) pathogens. The model begins with a short-term decision tree describing possible treatment routes and outcomes for patients during the hospitalization period. Patients who are healed in the decision tree enter the long-term Markov model, designed to capture the follow-up costs and health-related quality of life (HRQL) of patients healed over their lifetime.

Results: The analysis, conducted on a hypothetical cohort of 1,000 patients, highlights how the use of imipenem/cilastatin/relebactam is advantageous both in terms of diagnosis and treatment in the short term and in terms of cost-effectiveness. In fact, it is dominant compared to colistin-imipenem both in the NHS and in the social perspective since, compared to an average saving of € 2,800.15 and € 3,174.63 respectively, it would generate an increase of 4.76 years of life and of 4.12 QALYs per patient.


Download data is not yet available.


Cassini A, Högberg LD, Plachouras D, et al; Burden of AMR Collaborative Group. Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis. Lancet Infect Dis. 2019;19(1):56-66. PMID:30409683 DOI:

Fondazione House of Ambrosetti. Rapporto Meridiano Sanità 2017. Online: (Accessed August 2022).

Antibacterial agents in clinical development - An analysis of the antibacterial clinical development pipeline. Online (Accessed August 2022)

Istituto Superiore di Sanità. Antibiotico-resistenza. Aspetti epidemiologici in Italia. Online (Accessed August 2022)

Circolare Min. Sal. del 3/12/2019. Rapid Risk Assessment dell’ECDC: enterobatteri resistenti ai carbapenemi (CRE) 26 settembre 2019. Ten threats to global health in 2019. Online (Accessed August 2022)

Girometti N, Lewis RE, Giannella M, et al. Klebsiella pneumoniae bloodstream infection: epidemiology and impact of inappropriate empirical therapy. Medicine (Baltimore). 2014;93(17):298-309. PMID:25398065 DOI:

De Angelis G, D’Inzeo T, Fiori B et al. Burden of Antibiotic Resistant Gram Negative Bacterial Infections: evidence and Limits. J Med Microbiol Diagn. 2014;3:1. Online (Accessed August 2022)

Motsch J, Murta de Oliveira C, Stus V, et al. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections. Clin Infect Dis. 2020;70(9):1799-1808. PMID:31400759 DOI:

CHEERS 2022 Checklist. Online (Accessed August 2022)

Fattore G; AIES. Proposta di Linee-Guida per la valutazione economica degli interventi sanitari. PharmacoEcon Ital Res Artic. 2009;11(2):83-93. DOI:

Mennini FS, Paoletti M, Bini C, Marcellusi A, Falcone M, Andreoni M. Cost-utility analysis of ceftolozane/tazobactam vs meropenem in patients with hospital-acquired pneumonia (HABP) or ventilator-associated pneumonia (VABP). Glob Reg Health Technol Assess. 2022;9(1):45-57. PMID:36628307 DOI:

Suetens C, Latour K, Kärki T, et al; Healthcare-Associated Infections Prevalence Study Group. Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two European point prevalence surveys, 2016 to 2017. Euro Surveill. 2018;23(46):1800516. PMID:30458912 DOI:

Sievert DM, Ricks P, Edwards JR, et al; National Healthcare Safety Network (NHSN) Team and Participating NHSN Facilities. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34(1):1-14. PMID:23221186 DOI:

Zarb P, Coignard B, Griskeviciene J, et al; National Contact Points for the ECDC pilot point prevalence survey; Hospital Contact Points for the ECDC pilot point prevalence survey. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. Euro Surveill. 2012;17(46):20316. PMID:23171822 DOI:

European Centre for Disease Prevention and Control. Point prevalence survey of healthcare associated infections and antimicrobial use in European acute care hospitals. 2013; Online (Accessed August 2022)

ECDC. Antimicrobial resistance surveillance in Europe 2012. List of microorganism - pneumoniae. Online (Accessed August 2022)

Malacarne P, Langer M, Nascimben E, et al; Italian Group for the Evaluation of Interventions in Intensive Care Medicine. Building a continuous multicenter infection surveillance system in the intensive care unit: findings from the initial data set of 9,493 patients from 71 Italian intensive care units. Crit Care Med. 2008;36(4):1105-1113. PMID:18379234 DOI:

Sartelli M, Catena F, Ansaloni L, et al. Complicated intra-abdominal infections in Europe: a comprehensive review of the CIAO study. World J Emerg Surg. 2012;7(1):36. PMID:23190741 DOI:

Archivio Farmadati. Online

Lucioni, C., et al., I costi della sepsi in Italia. Farmeconomia e percorsi terapeutici, 2001. 2(3). DOI:

Ministero dell’Economia e delle Finanze. Libro verde sulla spesa pubblica. Online (Accessed August 2022)

Tariffario nazionale. Remunerazione delle prestazioni di assistenza specialistica ambulatoriale. 2013. Online (Accessed August 2022)

Simon MS, Sfeir MM, Calfee DP, Satlin MJ. Cost-effectiveness of ceftazidime-avibactam for treatment of carbapenem-resistant Enterobacteriaceae bacteremia and pneumonia. Antimicrob Agents Chemother. 2019;63(12):e00897-e19. DOI:

Tariffario nazionale. Remunerazione delle prestazioni di assistenza ospedaliera. 2013. Online (Accessed August 2022)

Alexander EL, Loutit J, Tumbarello M, et al. Carbapenem-Resistant EnterobacteriaceaeInfections: Results From a Retrospective Series and Implications for the Design of Prospective Clinical Trials. Open Forum Infect Dis. 2017;4(2):ofx063. DOI:

ISTAT. Tasso di occupazione. 2018. Online (Accessed August 2022)

Whittington MD, Atherly AJ, Curtis DJ, Lindrooth RC, Bradley CJ, Campbell JD. Recommendations for Methicillin-Resistant Staphylococcus aureus Prevention in Adult ICUs: A Cost-Effectiveness Analysis. Crit Care Med. 2017;45(8):1304-1310. PMID:28471887 DOI:

Lee BY, Wiringa AE, Bailey RR, et al. The economic effect of screening orthopedic surgery patients preoperatively for methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2010;31(11):1130-1138. PMID:20923285 DOI:

Ara R, Brazier JE. Using health state utility values from the general population to approximate baselines in decision analytic models when condition-specific data are not available. Value Health. 2011;14(4):539-545. PMID:21669378 DOI:

ISTAT. Tavole di mortalità. Online (Accessed August 2022)

Righi E, Peri AM, Harris PN, et al. Global prevalence of carbapenem resistance in neutropenic patients and association with mortality and carbapenem use: systematic review and meta-analysis. J Antimicrob Chemother. 2017 Mar 1;72(3):668-677. PMID:27999023 DOI:

ISTAT. Indice dei prezzi al consumo per famiglie, operai ed impiegati. Online

Gold MR, Franks P, McCoy KI, Fryback DG. Toward consistency in cost-utility analyses: using national measures to create condition-specific values. Med Care. 1998;36(6):778-792. PMID:9630120 DOI:

Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111. PMID:27418577 DOI:

Jim O’Neill. Wellcome Trust and UK Government. Tackling Drug-Resistant Infections Globally: final report and recommendations. The Review on Antimicrobial Resistance. May 2016; Online (Accessed August 2022)

Additional Files



How to Cite

Paoletti, M., Marcellusi, A., Yang, J., & Mennini, F. S. (2023). Cost-effectiveness of IMI/CIL/REL for the treatment of carbapenem non-susceptible Gram-negative bacterial infections. Global and Regional Health Technology Assessment, 10(1), 18–28.



Original Research Articles


Received 2022-08-30
Accepted 2023-02-26
Published 2023-04-11


Most read articles by the same author(s)

1 2 > >>