The scourge of carbapenem resistant Enterobacteriaceae: how to fight back

Samveda S. Samel; Suruchi S. Mandrekar; Prashant N. Walse; Syed Haroon Iqubal; Raja Y. Bafna; Mrityunjay K. Singh; Paresh P. Alwani; Bharatkumar D. Dholu

doi:10.18203/2349-3933.ijam20241630

Authors

Samveda S. Samel Department of Medical Affairs, GUFIC Biosciences Ltd, Mumbai, Maharashtra, India
Suruchi S. Mandrekar Department of Internal Medicine, Manipal Hospital, Pune, Maharashtra, India
Prashant N. Walse Department of Medicine and Critical Care, Asian Citicare Super Speciality Hospital, Aurangabad, Maharashtra, India
Syed Haroon Iqubal Department of General Medicine, Khushlok Hospital, Bareilly, Uttar Pradesh, India
Raja Y. Bafna Department of General Medicine, Akshat Health Care, Balaghat, Madhya Pradesh, India
Mrityunjay K. Singh Department of Internal Medicine, Jay Prabha Medanta Super Specialty Hospital, Patna, Bihar, India
Paresh P. Alwani Department of Internal Medicine, Ashoka Medicover Hospital, Nashik, Maharashtra, India
Bharatkumar D. Dholu Department of General Medicine, KEM Hospital, Sardar Moodliar Road, Pune Maharashtra, India

DOI:

https://doi.org/10.18203/2349-3933.ijam20241630

Keywords:

Ceftazidime-avibactam, Gram-negative bacteria, Enterobacteriaceae infections, Carbapenemases, Drug resistance, Carbapenem-resistant

Abstract

The Enterobacteriaceae species cause both community acquired and health care associated infections like bloodstream infections, ventilator-associated pneumonia, intra-abdominal infections and urinary tract infections. Carbapenem-resistant Enterobacteriaceae (CRE) have been included in the list of global priority pathogens (GPP) declared by WHO in 2017. These infections pose a serious threat due to the associated significant morbidity and mortality. The mechanisms of antimicrobial resistance in these organisms are numerous; however, β-lactamase genes carried on mobile genetic elements are a key mechanism for the rapid spread of these antibiotic-resistant strains on a global scale. The carbapenem resistance (CR) in Enterobacteriaceae has been recognized for the past two decades, but the carbapenemase-producing Enterobacteriaceae (CPE) has been a more recent issue and is spreading at an alarming pace worldwide. In this article, we conducted a systematic literature search of the PubMed, Embase, Web of Science and Cochrane Library databases to identify relevant studies that reported the epidemiology and the outcomes for hospitalised patients with confirmed infections due to CRE and carbapenem-susceptible Enterobacteriaceae (CSE) published between 1 January 2010 and 30 August 2023.The results emphasize that patients with CRE infection still face a greater risk of mortality and need an urgent need for newer antibiotics and appropriate treatment regimens to reduce the risk of morbidity and mortality.

Metrics

Metrics Loading ...

References

Jean SS, Harnod D, Hsueh PR. Global threat of carbapenem-resistant Gram-negative bacteria. Front Cellular Infect Microbiol. 2022;12: 823684.

Laxminarayan R, Heymann DL. Challenges of drug resistance in the developing world. BMJ. 2012;344(apr032):e1567.

Morata L, Cobos-Trigueros N, Martínez JA, Soriano Á, Almela M, Marco F, et al. Influence of multidrug resistance and appropriate empirical therapy on the 30-day mortality rate of Pseudomonas aeruginosa bacteraemia. Antimicrob Agents Chemother. 2012;56(9):4833-7.

Aguilera-Alonso D, Escosa-García L, Saavedra-Lozano J, Cercenado E, Baquero-Artigao F. Carbapenem-resistant Gram-negative bacterial infections in children. Antimicrob Agents Chemother. 2020;64:e02183-19.

Marston HD, Dixon DM, Knisely JM, Palmore TN, Fauci AS. Antimicrobial resistance. JAMA. 2016;316:1193-204.

Vivo A, Fitzpatrick MA, Suda KJ, Jones MM, Perencevich EN, Rubin MA, et al. Epidemiology and outcomes associated with carbapenem-resistant Acinetobacter baumannii and carbapenem-resistant Pseudomonas aeruginosa: a retrospective cohort study. BMC Infect Dis. 2022;22:1.

Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: The impact and evolution of a global menace. J Infect Dis. 2017;215(1):S28-36.

Aldali HJ, Khan A, Alshehri AA, Aldali JA, Meo SA, Hindi A, et al. Hospital-acquired infections caused by carbapenem-resistant Enterobacteriaceae: An observational study. Microorganisms. 2023;11(6):1595.

Hovan MR, Narayanan N, Cedarbaum V, Bhowmick T, Kirn TJ. Comparing mortality in patients with carbapenemase-producing carbapenem resistant Enterobacterales and non-carbapenemase-producing carbapenem resistant Enterobacterales bacteraemia. Diagn Microbiol Infect Dis. 2021;101(4):115505.

Falagas ME, Tansarli GS, Karageorgopoulos DE, Vardakas KZ. Deaths attributable to carbapenem-resistant Enterobacteriaceae infections. Emerg Infect Dis. 2014;20(7):1170-5.

Zarkotou O, Pournaras S, Tselioti P, Dragoumanos V, Pitiriga V, Ranellou K, et al. A. Predictors of mortality in patients with bloodstream infections caused by KPC-producing Klebsiella pneumoniae and impact of appropriate antimicrobial treatment. Clin. Microbiol. Infect. 2011;17:1798-803.

CRE Technical Information j CRE j HAI j CDC. 2019. Available at: https://www.cdc.gov/hai/organisms/cre/technical-info.html. Accessed on 12 April, 2024.

Centers for Disease Control and Prevention (CDC). Detection of Enterobacteriaceae isolates carrying metallo-beta-lactamase -United States, 2010. MMWR Morb Mortal Wkly Rep. 2010;59(24):750

Bhardwaj R, Robinson ML, Balasubramanian U, Kulkarni V, Kagal A, Raichur P, et al. Drug resistant Enterobacteriaceae colonization is associated with healthcare utilization and antimicrobial use among inpatients in Pune, India. BMC Infect Dis. 2018;18:504.

Mohan B, Prasad A, Kaur H, Hallux V, Gautam N, Taneja N. Fecal carriage of carbapenem-resistant Enterobacteriaceae and risk factor analysis in hospitalised patients: A single centre study from India. Indian J Med Microbiol. 2017;35:555e62.

Bakthavatchalam YD, Routray A, Mane A, Kamat S, Gupta A, Bari AK, et al. In vitro activity of Ceftazidime–Avibactam and its comparators against Carbapenem resistant Enterobacterales collected across India: results from ATLAS surveillance 2018 to 2019. Diagnostic Microbiology and Infectious Disease. 2022;103(1):115652.

Zhou R, Fang X, Zhang J. Impact of carbapenem resistance on mortality in patients infected with Enterobacteriaceae: a systematic review and meta-analysis. BMJ Open. 2021;11:e054971.

McConville TH, Sullivan SB, Gomez Simmonds A, Whittier S, Uhlemann A-C. Carbapenem-resistant Enterobacteriaceae colonization (CRE) and subsequent risk of infection and 90-day mortality in critically ill patients, an observational study. PLoS One. 2017;12(10):e0186195.

Sharma K, Tak V, Nag VL, Bhatia PK, Kothari N. An observational study on carbapenem-resistant Enterobacterales (CRE) colonisation and subsequent risk of infection in an adult intensive care unit (ICU) at a tertiary care hospital in India. Infect Prev Pract. 2023;5(4):100312.

Yamamoto N, Asada R, Kawahara R, Hagiya H, Akeda Y, Shanmugakani RK, et al. Prevalence of, and risk factors for carriage of carbapenem-resistant Enterobacteriaceae among hospitalized patients in Japan. J Hosp Infect 2017;97(3):212e7.

Nordmann P, Naas T, Poirel L Global Spread of Carbapenemase-producing Enterobacteriaceae. Emerging Infectious Diseases. 2011;17(10):1791-8.

Duina D, Doib Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence. 2017;8(4):460-9.

Pawar SK, Mohite ST, Shinde RV, Patil SR, Karande GS. Carbapenem-resistant Enterobacteriaceae: Prevalence and bacteriological profile in a tertiary teaching hospital from rural western India. Indian J Microbiol Res. 2018;5(3):342-7.

Chatterjee B, Khanduri N, Kakati B, Kotwal A. Universal Presence of blaNDM-1 Gene in Carbapenem-Resistant Gram-Negative Bacilli in an Indian Hospital in 2015. J Clin Diagn Res. 2017;11(9):DL01-2.

Lorenzoni VV. Silva D, Rampelotto RF, Brats PC, Villa B, Hörner R. Evaluation of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Rio Grande do Sul, Brazil. Rev Soc Bras Med Trop. 2017;50:5.

Kang JS, Yi J, Ko MK, Lee SO, Lee JE, Kim KH. Prevalence and Risk Factors of Carbapenem-resistant Enterobacteriaceae Acquisition in an Emergency Intensive Care Unit in a Tertiary Hospital in Korea: A Case-Control Study. J Korean Med Sci. 2019;34(18):e140.

Logan LK, Renschler JP, Gandra S, Weinstein RA, Laxminarayan R, Centers for Disease Control and Prevention Epicenters Program. Carbapenem-resistant Enterobacteriaceae in children, United States,1999-2012. Emerg Infect Dis. 2015;21:2014-21.

Logan LK, Gandra S, Mandal S, Klein EY, Levinson J, Weinstein RA, et al. Prevention Epicenters Program, U.S. Centers for Disease Control and Prevention. 2016. Multidrug- and carbapenem resistant Pseudomonas aeruginosa in children, United States, 1999-2012. J Pediatric Infect Dis Soc. 2016;6:352-9.

Logan LK, Gandra S, Trett A, Weinstein RA, Laxminarayan R. Acinetobacter baumannii resistance trends in children in the United States, 1999-2012. J Pediatric Infect Dis Soc. 2019;8:136-42.

Bielicki JA, Lundin R, Sharland M, ARPEC Project. Antibiotic resistance prevalence in routine bloodstream isolates from children’s hospitals varies substantially from adult surveillance data in Europe. Pediatr Infect Dis J. 2015;34:734-41.

Kouni S, Tsolia M, Roilides E, Dimitriou G, Tsiodras S, Skoutelis A, et al. PHIG Investigators. Establishing nationally representative central line associated bloodstream infection surveillance data for paediatric patients in Greece. J Hosp Infect. 2019;101:53-9.

Investigators of the Delhi Neonatal Infection Study (DeNIS) Collaboration. Characterisation and antimicrobial resistance of sepsis pathogens in neonates born in tertiary care centres in Delhi, India: a cohort study. Lancet Glob Health. 2016;4:e752-60.

Alp E, Perçin D, Colakog˘ lu S, Durmaz S, Kürkcü CA, Ekinciog˘ lu P, et al. Molecular characterization of carbapenem-resistant Klebsiella pneumoniae in a tertiary university hospital in Turkey. J Hosp Infect. 2013;84:178-80.

Nabarro LEB, Shankar C, Pragasam AK, Mathew G, Jeyaseelan V, Veeraraghavan B, et al. Clinical and bacterial risk factors for mortality in children with carbapenem-resistant Enterobacteriaceae bloodstream infections in India. Pediatr Infect Dis J. 2017;36:e161-6.

Chiotos K, Han JH, Tamma PD. Carbapenem-resistant Enterobacteriaceae infections in children. Curr Infect Dis Rep. 2016;18:2.

Armin S, Fallah F, Karimi A, Karbasiyan F, Alebouyeh M, Rafiei Tabatabaei S, et al. Antibiotic susceptibility patterns for carbapenem-resistant Enterobacteriaceae. Int J Microbiol. 2023;2023:1-5.

Zhang S, Zhang X, Wu Q, Zheng X, Dong G, Fang R, et al. Clinical, microbiological, and molecular epidemiological characteristics of Klebsiella pneumoniae-induced pyogenic liver abscess in south-eastern China. Antimicrob Resist Infect Control. 2019;8(1):166.

Ansari AS. Therapeutic Options for the Treatment of Carbapenem-resistant Enterobacteriaceae Infections: Hope in the Times of Hype and Despair. Indian J Crit Care Med. 2021;25(7):752-3.

Papp-Wallace KM. The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections. Expert Opinion Pharmacotherapy. 2019;20(17):2169-84.

Yang P, Li Y, Wang X, Chen N, Lu X. Efficacy and safety of ceftazidime-avibactam versus polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infection: a systematic review and meta-analysis. BMJ Open. 2023;13(5): e070491.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.