Citation Information :
Rajendran S, Tarigopula A, D SK, Nambi PS, Ramasubramanian V. Xpert Carba-R Assay on Flagged Blood Culture Samples: Clinical Utility in Intensive Care Unit Patients with Bacteremia Caused by Enterobacteriaceae. Indian J Crit Care Med 2023; 27 (9):655-662.
Introduction and background: Rapid molecular diagnostics to predict carbapenem resistance well before the availability of routine drug sensitivity testing (DST) can serve as an antimicrobial stewardship tool in the context of high rates of Carbapenem-resistant Enterobacteriaceae (CRE).
Materials and methods: A retrospective observational study of patients more than 18 years of age on whom Xpert Carba-R (FDA approved for rectal swab specimen) was done on gram-negative bacteria (GNB) flagged blood culture samples, in an Indian intensive care unit between January 2015 and November 2018. We analyzed the performance of Xpert Carba-R in comparison with routine DST.
Results: A total of 164 GNBs were isolated from 160 patients. Klebsiella pneumoniae and Escherichia coli were the predominant isolates. Carba-R was positive in 35.36% of samples and 45.34% were carbapenem-resistant (CR) on routine DST. The distribution of the CR gene was: Oxacillinase (OXA) (50%), NDM (32.7%) followed by OXA and NDM co-expression (15.51%). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of Carba-R were 90.74, 93.15, 13.25, 0.10, 83.58 and 96.31% for Enterobacteriaceae. The median time to obtain the Carba-R report was 30 hours 34 minutes vs 74 hours and 20 minutes for routine DST. Based on the Carba-R report, 9.72% of patients had escalation and 27.08% had de-escalation of antibiotics.
Conclusion: Xpert Carba-R serves as a rapid diagnostic tool for predicting carbapenem resistance in intensive care unit patients with bacteremia caused by Enterobacteriaceae.
Global antimicrobial resistance surveillance system (GLASS) report: Early implementation 2017–2018. Geneva: World Health Organization; 2018. Available at: https://www.who.int/publications/i/item/9789241515061.
Patel G, Bonomo RA. “Stormy waters ahead”: Global emergence of carbapenemases. Front Microbiol 2013;4:1–17. DOI: 10.3389/fmicb.2013.00048.
Zak-Doron Y, Dishon Benattar Y, Pfeffer I, Daikos G, Skiada A, Antoniadou A, et al. The association between empirical antibiotic treatment and mortality in severe infections caused by carbapenem-resistant gram-negative bacteria: A prospective study. Clin Infect Dis 2018;67(12):1815–1823. DOI: 10.1093/cid/ciy371.
Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: Results from a guideline-based performance improvement program. Crit Care Med 2014;42(8):1749–1755. DOI: 10.1097/CCM.0000000000000330.
Matthaiou DK, Michalopoulos A, Rafailidis PI, Karageorgopoulos DE, Papaioannou V, Ntani G, et al. Risk factors associated with the isolation of colistin-resistant Gram-negative bacteria: A matched case-control study. Crit Care Med 2008;36(3):807–811. DOI: 10.1097/CCM.0B013E3181652FAE.
De Waele JJ, Dhaese S. Antibiotic stewardship in sepsis management: Toward a balanced use of antibiotics for the severely ill patient. Expert Rev Anti Infect Ther 2019;17(2):89–97. DOI: 10.1080/14787210.2019.1568239.
Jauréguy F, Mansour H, Bigot J, Walewski V, Billard-Pomares T, Rahajamanana L, et al. Use of the XpertCarbaR assay for direct detection of carbapenemase genes from blood cultures and urine samples. J Hosp Infect 2018;98(3):245–246. DOI: 10.1016/j.jhin.2017.09.026.
Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious diseases society of America guidance on the treatment of extended-spectrum β-lactamase producing enterobacterales (Esbl-E), carbapenem-resistant enterobacterales (CRE), and pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis 2021;72(7):1109–1116. DOI: 10.1093/cid/ciab295.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial disc susceptibility testing; approved standard. 12th edition. CLSI document M02-A12.35(1). Wayne (PA); 2015.
Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing; twenty fifth informational supplement. Wayne (PA): Clinical and Laboratory Standards Institute. CLSI document; 2015. pp. M100–S25.
The European Committee on Antimicrobial Susceptibility Testing. Routine internal quality control as recommended by EUCAST. 2017., Version 7.0. Available from: http://www.eucast.org/.
Veeraraghavan B, Jesudason MR, Prakasah JA, Anandan S, Sahni RD, Pragasam AK, et al. Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report. Indian J Med Microbiol 2018;36(1):32–36. DOI: 10.4103/ijmm.IJMM_17_415.
AMR surveillance network Indian Council of Medical Research 2017. Annual report Antimicrobial Resistance Surveillance Network January 2017–December 2017. Retrieved from: https://icmr.nic.in/sites/default/files/reports/annual_report_amr_jan2017-18.pdf.
Tamma PD, Goodman KE, Harris AD, Tekle T, Roberts A, Taiwo A, et al. Comparing the outcomes of patients with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae bacteremia. Clin Infect Dis 2016;64(3):257–264. DOI: 10.1093/cid/ciw741.
Banerjee R, Humphries R. Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae. Virulence 2016;8(4):427–439. DOI: 10.1080/21505594.2016.1185577.
Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, et al. Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clini Infect Dis 2016;62(10):e51–e77. DOI: 10.1093/cid/ciw118.
Veeraraghavan B, Shankar C, Karunasree S, Kumari S, Ravi R, Ralph R. Carbapenem resistant Klebsiellapneumoniae isolated from bloodstream infection: Indian experience. Patho Glob Health 2017;111(5):240–246. DOI: 10.1080/20477724.2017.1340128.
Duin DV, Doi Y. The global epidemiology of carbapenemase-producing Enterobacteriaceae. Virulence 2017;8(4):460–469. DOI: 10.1080/21505594.2016.1222343.
Lutgring JD, Limbago BM. The problem of carbapenemase producing- carbapenem-resistant-Enterobacteriaceae detection. J Clin Microbiol 2016;54(3):529–534. DOI: 10.1128/JCM.02771-15.
Castanheira M, Farrell SE, Krause KM, Jones RN, Sader HS. Contemporary diversity of β-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent β-lactamase groups. Antimicrob Agents Chemother 2014;58(2):833–838. DOI: 10.1128/AAC.01896-13.
Mohanty S, Gajanand M, Gaind R. Identification of carbapenemase-mediated resistance among Enterobacteriaceae bloodstream isolates: A molecular study from India. Indian J Med Microbiol 2017:35(3);421–425. DOI: 10.4103/ijmm.IJMM_16_386.
Anandan S, Damodaran S, Gopi R, Bakthavatchalam YD, Veeraraghavan B. Rapid screening for carbapenem resistant organisms: Current results and future approaches. J Clin Diagn Res 2015;9(9):DM01–3. DOI: 10.7860/JCDR/2015/14246.6530.
Sharma A, Bakthavatchalam YD, Gopi R, Anandan S, Verghese VP, Veeraraghavan B. Mechanisms of carbapenem resistance in K. pneumoniae and E. Coli from bloodstream infections in India. J Infect Dis Ther 2016;4:293. DOI: 10.4172/2332-0877.1000293.
Dortet L, Fusaro M, Naas T. Improvement of the Xpert Carba-R kit for the detection of carbapenemase-producing Enterobacteriaceae. Antimicrob Agents Chemother 2016;60(6):3832–3837. DOI: 10.1128/AAC.00517-16.
Nagvekar V, Shah A, Unadkat VP, Chavan A, Kohli R, Hodgar S, et al. Clinical outcome of patients on Ceftazidime – Avibactam and combination therapy in carbapenem-resistant enterobacteriaceae. Indian J Crit Care Med 2021;25(7):780–784. DOI: 10.5005/jp-journals-10071-23863.
Traczewski MM, Carretto E, Canton R, Moore NM; Carba-R Study Team. Multicenter evaluation of the Xpert Carba-R assay for detection of carbapenemase genes in gram-negative isolates. J Clin Microbiol 2018;56(8):e00272–e002718. DOI: 10.1128/JCM.00272-18.
Bonomo R, Szabo D. Mechanisms of multidrug resistance in acinetobacter species and pseudomonas aeruginosa. Clinical Infectious Diseases 2006;43(Suppl 2):S49–S56. DOI: 10.1086/504477.
Wangchinda W, Pati N, Maknakhon N, Seenama C, Tiengrim S, Thamlikitkul V. Collateral damage of using colistin in hospitalized patients on emergence of colistin-resistant Escherichia coli and Klebsiella pneumoniae colonization and infection. Antimicrob Resist Infect Control 2018;7(1):84. DOI: 10.1186/s13756-018-0375-4.
Prayag PS, Patwardhan SA, Panchakshari S, Sambasivam R, Dhupad S, Soman RN, et al. Ceftazidime-avibactam with or without Aztreonam vs Polymyxin-based combination therapy for carbapenem-resistant Enterobacteriaceae: A retrospective analysis. Indian J Crit Care Med 2023;27(6):444–450. DOI: 10.5005/jp-journals-10071-24481.