ORIGINAL ARTICLE
Predictive role of culture-based MIC testing vs. genotyping for carbapenem-resistant Enterobacterales in a non-universal screening, highly resourced setting
 
 
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Department of Microbiology, College of Medicine, King Fahad University Hospital, Imam Abdulrahman Bin Faisal University, Dammam, SAUDI ARABIA
 
 
Online publication date: 2023-04-12
 
 
Publication date: 2023-07-01
 
 
Electron J Gen Med 2023;20(4):em495
 
KEYWORDS
ABSTRACT
A lack of evidence of accuracy for various testing modalities for carbapenem-resistant Enterobacterales (CRE) reduces the efficiency of screening and delays the isolation of carriers. This study examined the performance of phenotypic detection of CRE in comparison to molecular testing. A cross-sectional study was conducted in an academic medical institution in Saudi Arabia on CRE-screened patients during a 36-month period (April 1, 2019, through March 31, 2022). Cases were followed up for their susceptibility status by the phenotypic gradient method and genotypes. Of 3,116 samples tested, 359 carbapenemase genes were detected in 297 strains (9.5%) belonging to 292 patients. Oxacilliniase-48 (OXA-48) was the most frequently detected genotype (n=190, 64%), followed by a combined New Delhi metallo-B-lactamase (NDM)/OXA-48 genotype (n=77, 25.9%). Variable missed isolation days were encountered for various genotypes (0-18.5 days), with an excellent clinical utility index obtained for screening the OXA-48 genotype phenotypically. The data provided some insights into the predictive role and shortcomings of the e-test alone in CRE screening. While it provided a reasonable approach in a CRE population dominated by OXA-48 genotypes, it was more likely to miss the NDM-incurred carbapenemase. Thus, local epidemiology in an institution must be considered when designing a local screening protocol in addition to consideration of cost and turnaround time.
 
REFERENCES (55)
1.
Jean SS, Harnod D, Hsueh PR. Global threat of carbapenem-resistant gram-negative bacteria. Front Cell Infect Microbiol. 2022;12:823684. https://doi.org/10.3389/fcimb.... PMid:35372099 PMCid:PMC8965008.
 
2.
Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin Infect Dis. 2007;45(9): 1179-81. https://doi.org/10.1086/522287 PMid:17918079.
 
3.
Castillo-Polo JA, Hernández-García M, Morosini MI, et al. Outbreak by KPC-62-producing ST307 klebsiella pneumoniae isolates resistant to ceftazidime/avibactam and cefiderocol in a university hospital in Madrid, Spain. J Antimicrob Chemother. 2023;dkad086. https://doi.org/10.1093/jac/dk... PMid:36964710.
 
4.
Centers for Disease Control and Prevention (CDC). Guidance for control of infections with carbapenem-resistant or carbapenemase-producing enterobacteria-ceae in acute care facilities. MMWR Morb Mortal Wkly Rep. 2009;58(10):256-60.
 
5.
Navon-Venezia S, Chmelnitsky I, Leavitt A, Schwaber MJ, Schwartz D, Carmeli Y. Plasmid-mediated imipenem-hydrolyzing enzyme KPC-2 among multiple carbapenem-resistant Escherichia coli clones in Israel. Antimicrob Agents Chemother. 2006;50(9):3098-101. https://doi.org/10.1128/AAC.00... PMid:16940107 PMCid:PMC1563531.
 
6.
Bratu S, Brooks S, Burney S, et al. Detection and spread of Escherichia coli possessing the plasmid-borne carbapenemase KPC-2 in Brooklyn, New York. Clin Infect Dis. 2007;44(7):972-5. https://doi.org/10.1086/512370 PMid:17342651.
 
7.
Hossain A, Ferraro MJ, Pino RM, et al. Plasmid-mediated carbapenem-hydrolyzing enzyme KPC-2 in an enterobacter sp. Antimicrob Agents Chemother. 2004;48(11):4438-40. https://doi.org/10.1128/AAC.48... PMid:15504876 PMCid:PMC525415.
 
8.
Gijón D, Curiao T, Baquero F, Coque TM, Cantón R. Fecal carriage of carbapenemase-producing enterobacteria-ceae: A hidden reservoir in hospitalized and nonhospitalized patients. J Clin Microbiol. 2012;50(5):1558-63. https://doi.org/10.1128/JCM.00... PMid:22403422 PMCid:PMC3347124.
 
9.
Holma T, Torvikoski J, Friberg N, et al. Rapid molecular detection of pathogenic microorganisms and antimicrobial resistance markers in blood cultures: Evaluation and utility of the next-generation FilmArray Blood Culture Identification 2 panel. Eur J Clin Microbiol Infect Dis. 2022; 41(3):363-71. https://doi.org/10.1007/s10096... PMid:34350523 PMCid:PMC8831274.
 
10.
Bratu S, Landman D, Haag R, et al. Rapid spread of carbapenem-resistant klebsiella pneumoniae in New York City: A new threat to our antibiotic armamentarium. Arch Intern Med. 2005;165(12):1430-5. https://doi.org/10.1001/archin... PMid:15983294.
 
11.
Hirakata Y, Izumikawa K, Yamaguchi T, et al. Rapid detection and evaluation of clinical characteristics of emerging multiple-drug-resistant gram-negative rods carrying the metallo-beta-lactamase gene blaIMP. Antimicrob Agents Chemother. 1998;42(8):2006-11. https://doi.org/10.1128/AAC.42... PMid:9687398 PMCid:PMC105724.
 
12.
Landman D, Salvani JK, Bratu S, Quale J. Evaluation of techniques for detection of carbapenem-resistant klebsiella pneumoniae in stool surveillance cultures. J Clin Microbiol. 2005;43(11):5639-41. https://doi.org/10.1128/JCM.43... PMid:16272497 PMCid:PMC1287836.
 
13.
Saliba R, Aho-Glélé LS, Karam-Sarkis D, Zahar JR. Evaluation of polymerase chain reaction assays for direct screening of carbapenemase-producing enterobacteria-ceae from rectal swabs: A diagnostic meta-analysis. J Hosp Infect. 2020;104(3):381-9. https://doi.org/10.1016/j.jhin... PMid:31790743.
 
14.
Viau R, Frank KM, Jacobs MR, et al. Intestinal carriage of carbapenemase-producing organisms: Current status of surveillance methods. Clin Microbiol Rev. 2016;29(1):1-27. https://doi.org/10.1128/CMR.00... PMid:26511484 PMCid:PMC4771221.
 
15.
Huang TD, Bogaerts P, Ghilani E, et al. Multicentre evaluation of the check-direct CPE® assay for direct screening of carbapenemase-producing enterobacteria-ceae from rectal swabs. J Antimicrob Chemother. 2015;70(6):1669-73. https://doi.org/10.1093/jac/dk... PMid:25637518.
 
16.
Cuzon G, Naas T, Bogaerts P, Glupczynski Y, Nordmann P. Evaluation of a DNA microarray for the rapid detection of extended-spectrum β-lactamases (TEM, SHV and CTX-M), plasmid-mediated cephalosporinases (CMY-2-like, DHA, FOX, ACC-1, ACT/MIR and CMY-1-like/MOX) and carbapenemases (KPC, OXA-48, VIM, IMP and NDM). J Antimicrob Chemother. 2012;67(8):1865-9. https://doi.org/10.1093/jac/dk... PMid:22604450.
 
17.
Dodémont M, De Mendonça R, Nonhoff C, Roisin S, Denis O. Performance of the verigene gram-negative blood culture assay for rapid detection of bacteria and resistance determinants. J Clin Microbiol. 2014;52(8):3085-7. https://doi.org/10.1128/JCM.01... PMid:24899026 PMCid:PMC4136123.
 
18.
Okoche D, Asiimwe BB, Katabazi FA, Kato L, Najjuka CF. Prevalence and characterization of carbapenem-resistant enterobacteriaceae isolated from Mulago National Referral Hospital, Uganda. PLoS One. 2015;10(8):e0135745. https://doi.org/10.1371/journa... PMid:26284519 PMCid:PMC4540283.
 
19.
Otter JA, Dyakova E, Bisnauthsing KN, et al. Universal hospital admission screening for carbapenemase-producing organisms in a low-prevalence setting. J Antimicrob Chemother. 2016;71(12):3556-61. https://doi.org/10.1093/jac/dk... PMid:27516471 PMCid:PMC5890656.
 
20.
World Health Organization. Guidelines for the prevention and control of carbapenem-resistant enterobacteriaceae, acinetobacter baumannii, and pseudomonas aeruginosa in health care facilities. Available at: https://apps.who.int/iris/hand... (Accessed: 18 July 2022).
 
21.
Banach DB, Bearman G, Barnden M, et al. Duration of contact precautions for acute-care settings. Infect Control Hosp Epidemiol. 2018;39(2):127-44. https://doi.org/10.1017/ice.20... PMid:29321078.
 
22.
Ho KW, Ng WT, Ip M, You JH. Active surveillance of carbapenem-resistant enterobacteriaceae in intensive care units: Is it cost-effective in a nonendemic region? Am J Infect Control. 2016;44(4):394-9. https://doi.org/10.1016/j.ajic... PMid:26698671.
 
23.
Vella V, Moore LS, Robotham JV, et al. Isolation demand from carbapenemase-producing enterobacteriaceae screening strategies based on a West London Hospital network. J Hosp Infect. 2016;94(2):118-24. https://doi.org/10.1016/j.jhin... PMid:27209055.
 
24.
Kim DK, Kim HS, Pinto N, et al. Xpert Carba-R assay for the detection of carbapenemase-producing organisms in intensive care unit patients of a Korean Tertiary Care Hospital. Ann Lab Med. 2016;36(2):162-5. https://doi.org/10.3343/alm.20... PMid:26709264 PMCid:PMC4713850.
 
25.
Moore NM, Cantón R, Carretto E, et al. Rapid identification of five classes of carbapenem resistance genes directly from rectal swabs by use of the Xpert Carba-R assay. J Clin Microbiol. 2017;55(7):2268-75. https://doi.org/10.1128/JCM.00... PMid:28515213 PMCid:PMC5483930.
 
26.
Tato M, Ruiz-Garbajosa P, Traczewski M, et al. Multisite evaluation of cepheid Xpert Carba-R assay for detection of carbapenemase-producing organisms in rectal swabs. J Clin Microbiol. 2016;54(7):1814-9. https://doi.org/10.1128/JCM.00... PMid:27122379 PMCid:PMC4922077.
 
27.
CLSI supplement M100. Wayne, PA: Clinical and Laboratory Standards Institute; 2022.
 
28.
Mitchell A. Sensitivity × PPV is a recognized test called the clinical utility index (CUI+). Eur J Epidemiol. 2011;26(3):251-2. https://doi.org/10.1007/s10654... PMid:21442261.
 
29.
Al Fadhli AH, Jamal WY, Rotimi VO. Prevalence of carbapenem-resistant enterobacteriaceae and emergence of high rectal colonization rates of blaOXA-181-positive isolates in patients admitted to two major hospital intensive care units in Kuwait. PLoS One. 2020;15(11): e0241971. https://doi.org/10.1371/journa... PMid:33201906 PMCid:PMC7671514.
 
30.
National Center for Emerging and Zoonotic Infectious Diseases (U.S.): Division of Healthcare Quality Promotion. CDC guidance for control of carbapenem-resistant enterobacteriaceae (CRE): 2015 update-CRE toolkit Corporate. Available at: https://stacks.cdc.gov/view/cd... (Accessed: 18July 2022).
 
31.
Lerner A, Adler A, Abu-Hanna J, Cohen Percia S, Kazma Matalon M, Carmeli Y. Spread of KPC-producing carbapenem-resistant enterobacteriaceae: The importance of super-spreaders and rectal KPC concentration. Clin Microbiol Infect. 2015;21(5):470.e1-7. https://doi.org/10.1016/j.cmi.... PMid:25684452.
 
32.
Abdalhamid B, Elhadi N, Alabdulqader N, Alsamman K, Aljindan R. Rates of gastrointestinal tract colonization of carbapenem-resistant enterobacteriaceae and pseudomonas aeruginosa in hospitals in Saudi Arabia. New Microbes New Infect. 2016;10:77-83. https://doi.org/10.1016/j.nmni... PMid:26933499 PMCid:PMC4765740.
 
33.
Musuuza JS, Watson L, Parmasad V, Putman-Buehler N, Christensen L, Safdar N. Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis. PLoS One. 2021;16(5):e0251170. https://doi.org/10.1371/journa... PMid:33956882 PMCid:PMC8101968.
 
34.
Alnimr AM, Alshahrani MS, Alwarthan S, et al. Bacterial and fungal coinfection in critically Ill COVID-19 cases and predictive role of procalcitonin during the first wave at an academic health center. J Epidemiol Glob Health. 2022;12(2):188-95. https://doi.org/10.1007/s44197... PMid:35397070 PMCid:PMC8994096.
 
35.
Falcone M, Suardi LR, Tiseo G, et al. Superinfections caused by carbapenem-resistant enterobacterales in hospitalized patients with COVID-19: A multicentre observational study from Italy (CREVID study). JAC Antimicrob Resist. 2022;4(3):dlac064. https://doi.org/10.1093/jacamr... PMid:35719203 PMCid:PMC9201238.
 
36.
Russotto A, Rolfini E, Paladini G, Gastaldo C, Vicentini C, Zotti CM. Hand hygiene and antimicrobial resistance in the COVID-19 era: An observational study. Antibiotics (Basel). 2023;12(3):583. https://doi.org/10.3390/antibi... PMid:36978450 PMCid:PMC10045068.
 
37.
Miftode IL, Leca D, Miftode RS, et al. The clash of the titans: COVID-19, carbapenem-resistant enterobacterales, and first MCR-1-mediated colistin resistance in humans in Romania. Antibiotics (Basel). 2023;12(2):324. https://doi.org/10.3390/antibi... PMid:36830235 PMCid:PMC9952164.
 
38.
Hawkey PM, Warren RE, Livermore DM, et al. Treatment of infections caused by multidrug-resistant gram-negative bacteria: Report of the British Society for Antimicrobial Chemotherapy/Healthcare Infection Society/British Infection Association Joint Working Party. J Antimicrob Chemother. 2018;73(suppl_3):iii2-78. https://doi.org/10.1093/jac/dk... PMid:29514274.
 
39.
Al Musawi S, Ur Rahman J, Aljaroodi SA, et al. mCIM test as a reliable assay for the detection of CRE in the Gulf Region. J Med Microbiol. 2021;70(7). https://doi.org/10.1099/jmm.0.... PMid:34232118.
 
40.
Al-Tawfiq JA, Rabaan AA, Saunar JV, Bazzi AM. Genotypes and prevalence of carbapenemase-producing enterobacteriaceae and pseudomonas aeruginosa in a hospital in Saudi Arabia. Trans R Soc Trop Med Hyg. 2022;116(1):50-3. https://doi.org/10.1093/trstmh... PMid:33765684.
 
41.
Alraddadi BM, Heaphy ELG, Aljishi Y, et al. Molecular epidemiology and outcome of carbapenem-resistant enterobacterales in Saudi Arabia. BMC Infect Dis. 2022;22(1):542. https://doi.org/10.1186/s12879... PMid:35698046 PMCid:PMC9190113.
 
42.
Woodworth KR, Walters MS, Weiner LM, et al. Vital signs: Containment of novel multidrug-resistant organisms and resistance mechanisms-United States, 2006-2017. MMWR Morb Mortal Wkly Rep. 2018;67(13):396-401. https://doi.org/10.15585/mmwr.... PMid:29621209 PMCid:PMC5889247.
 
43.
Castanheira M, Kimbrough JH, DeVries S, Mendes RE, Sader HS. Trends of β-lactamase occurrence among escherichia coli and klebsiella pneumoniae in United States hospitals during a 5-year period and activity of antimicrobial agents against isolates stratified by β-lactamase type. Open Forum Infect Dis. 2023;10(2):ofad038. https://doi.org/10.1093/ofid/o... PMid:36776778 PMCid:PMC9907474.
 
44.
Shortridge D, Kantro V, Castanheira M. Meropenem-vaborbactam activity against U.S. multidrug-resistant enterobacterales strains, including carbapenem-resistant isolates. Microbiol Spectr. 2023;11(1):e0450722. https://doi.org/10.1128/spectr... PMid:36622238 PMCid:PMC9927278.
 
45.
Pudpong K, Pattharachayakul S, Santimaleeworagun W, et al. Association between types of carbapenemase and clinical outcomes of infection due to carbapenem resistance enterobacterales. Infect Drug Resist. 2022;15:3025-37. https://doi.org/10.2147/IDR.S3... PMid:35720254 PMCid:PMC9205317.
 
46.
Hoyos-Mallecot Y, Ouzani S, Dortet L, Fortineau N, Naas T. Performance of the Xpert® Carba-R v2 in the daily workflow of a hygiene unit in a country with a low prevalence of carbapenemase-producing enterobacteriaceae. Int J Antimicrob Agents. 2017;49(6):774-7. https://doi.org/10.1016/j.ijan... PMid:28411078.
 
47.
Lau AF, Fahle GA, Kemp MA, Jassem AN, Dekker JP, Frank KM. Clinical performance of check-direct CPE, a multiplex PCR for direct detection of bla(KPC), bla(NDM) and/or bla(VIM), and bla(OXA)-48 from perirectal swabs. J Clin Microbiol. 2015;53(12):3729-37. https://doi.org/10.1128/JCM.01... PMid:26338860 PMCid:PMC4652088.
 
48.
Walsh TR, Toleman MA, Poirel L, Nordmann P. Metallo-beta-lactamases: The quiet before the storm? Clin Microbiol Rev. 2005;18(2):306-25. https://doi.org/10.1128/CMR.18... PMid:15831827 PMCid:PMC1082798.
 
49.
Kochar S, Sheard T, Sharma R, et al. Success of an infection control program to reduce the spread of carbapenem-resistant klebsiella pneumoniae. Infect Control Hosp Epidemiol. 2009;30(5):447-52. https://doi.org/10.1086/596734 PMid:19301985.
 
50.
Hayden MK, Lin MY, Lolans K, et al. Prevention of colonization and infection by klebsiella pneumoniae carbapenemase-producing enterobacteriaceae in long-term acute-care hospitals. Clin Infect Dis. 2015;60(8):1153-61. https://doi.org/10.1093/cid/ci... PMid:25537877 PMCid:PMC8381216.
 
51.
Ben-David D, Maor Y, Keller N, et al. Potential role of active surveillance in the control of a hospital-wide outbreak of carbapenem-resistant klebsiella pneumoniae infection. Infect Control Hosp Epidemiol. 2010;31(6):620-6. https://doi.org/10.1086/652528 PMid:20370465.
 
52.
Falcone M, Tiseo G, Galfo V, et al. Bloodstream infections in patients with rectal colonization by klebsiella pneumoniae producing different type of carbapenemases: A prospective, cohort study (CHIMERA study). Clin Microbiol Infect. 2022;28(2):298.e1-7. https://doi.org/10.1016/j.cmi.... PMid:34197935.
 
53.
Schwaber MJ, Lev B, Israeli A, et al. Containment of a country-wide outbreak of carbapenem-resistant klebsiella pneumoniae in Israeli hospitals via a nationally implemented intervention. Clin Infect Dis. 2011;52(7):848-55. https://doi.org/10.1093/cid/ci... PMid:21317398.
 
54.
Alotaibi F. Carbapenem-resistant enterobacteriaceae: An update narrative review from Saudi Arabia. J Infect Public Health. 2019;12(4):435-71. https://doi.org/10.1016/j.jiph... PMid:31060974.
 
55.
Queenan AM, Bush K. Carbapenemases: The versatile beta-lactamases. Clin Microbiol Rev. 2007;20(3):440-58. https://doi.org/10.1128/CMR.00... PMid:17630334 PMCid:PMC1932750.
 
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