Association Between Types of Carbapenemase and Clinical Outcomes of Infection Due to Carbapenem Resistance Enterobacterales

Korawan Pudpong; Sutthiporn Pattharachayakul; Wichai Santimaleeworagun; Ozioma F Nwabor; Varaporn Laohaprertthisan; Thanaporn Hortiwakul; Boonsri Charernmak; Sarunyou Chusri

doi:10.2147/IDR.S363588

Association Between Types of Carbapenemase and Clinical Outcomes of Infection Due to Carbapenem Resistance Enterobacterales

Infect Drug Resist. 2022 Jun 13:15:3025-3037. doi: 10.2147/IDR.S363588. eCollection 2022.

Authors

Korawan Pudpong^{1

2}, Sutthiporn Pattharachayakul³, Wichai Santimaleeworagun^{4

5}, Ozioma F Nwabor⁶, Varaporn Laohaprertthisan⁷, Thanaporn Hortiwakul⁶, Boonsri Charernmak⁶, Sarunyou Chusri⁶

Affiliations

¹ Department of Pharmacy, College of Pharmacotherapy Thailand, Nontaburi, 11000, Thailand.
² Pharmaceutical Care Unit, Department of Pharmacy, Sunpasitthiprasong Hospital, Ubon Ratchathani, 34000, Thailand.
³ Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand.
⁴ Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom, 73000, Thailand.
⁵ Department of Pharmacy, Pharmaceutical Initiative for Resistant Bacteria and Infectious Disease Working Group (PIRBIG), Nakorn Pathom, 73000, Thailand.
⁶ Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, 90110, Songkhla, Thailand.
⁷ Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, 90110, Thailand.

Abstract

Purpose: Compared with non-carbapenemase producing carbapenem-resistant Enterobacterales (non-CP-CRE), carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) are associated with considerable mortality. However, given that the patients are treated with various therapeutic options, it remains unclear whether differences in types of carbapenemase genes yield different mortality rates. Therefore, this study aims to identify carbapenemase genes and identify whether clinical outcomes differ according to the prevalence of genotype and phenotype of carbapenemase among Enterobacterales clinical isolated.

Patients and methods: A retrospective cohort study was performed to determine whether types of carbapenemase genes have an impact on clinical outcomes. Carbapenem-resistant clinical isolates were collected at a tertiary care university hospital in Songkhla, Thailand, between June 2018 and February 2020. Demographic and microbiological data such as antimicrobial susceptibility, carbapenemase genes, and overall mortality were evaluated.

Results: A total of 121 Enterobacterales clinical isolated were evaluated. The bla _NDM-1 gene was detected in 44% of the isolates, followed by bla _OXA-48 (28%) and bla _NDM-1/OXA-48 (28%). NDM-1- or NDM-1/OXA-48- producing isolates were more likely to require meropenem MICs of ≥16 mg/L, while OXA-48-producing isolates were more likely to require meropenem MICs of <16 mg/L. The patients with NDM-1 or NDM-1/OXA-48 had a higher 14 days mortality rate than those with OXA-48 after treating with carbapenem-containing regimens (P-value 0.001) or colistin-containing regimens (P-value < 0.001).

Conclusion: Our findings suggest that the mortality for CP-CRE infection in patients with NDM-1 or NDM-1/OXA-48 was higher than the mortality in those with OXA-48, which It seems that the type of carbapenemase gene may affect meropenem MIC levels. Hence, in treatment decisions involving the use of either carbapenem-containing regiment or colistin-containing regiment in patients with CP-CRE infection, especially those in the NDM-1 and NDM-1/OXA-48 groups, the patient symptoms should be closely monitored.

Keywords: NDM-1; NDM-1/OXA-48; OXA-48; carbapenem resistance Enterobacterales; carbapenemase.

Grants and funding

This work was supported by the Faculty of Medicine, Prince of Songkla University, Faculty of Pharmaceutical Sciences, Prince of Songkla University, and Docter Kasem Pangsrivongse Foundation. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.