CTX-M, TEM, and SHV Genes in Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp Isolated from Hematologic Cancer Patients with Bacteremia in Uganda

Margaret Lubwama; David P Kateete; George Katende; Edgar Kigozi; Jackson Orem; Warren Phipps; Freddie Bwanga

doi:10.2147/IDR.S442646

CTX-M, TEM, and SHV Genes in Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp Isolated from Hematologic Cancer Patients with Bacteremia in Uganda

Infect Drug Resist. 2024 Feb 16:17:641-653. doi: 10.2147/IDR.S442646. eCollection 2024.

Authors

Margaret Lubwama¹, David P Kateete², George Katende¹, Edgar Kigozi², Jackson Orem³, Warren Phipps^{4

5}, Freddie Bwanga²

Affiliations

¹ Department of Medical Microbiology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
² Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.
³ Uganda Cancer Institute, Kampala, Uganda.
⁴ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
⁵ Allergy and Infectious Diseases Division, Department of Medicine, University of Washington, Seattle, WA, USA.

Abstract

Purpose: We determined the phenotypic resistance to third-generation cephalosporins, phenotypic extended spectrum beta-lactamase (ESBL) prevalence, and genotypic prevalence of ESBL-encoding genes bla_CTX-M, bla_TEM, and bla_SHV in Enterobacteriaceae isolated from hematologic cancer patients with febrile neutropenia and bacteremia at the Uganda Cancer Institute (UCI).

Patients and methods: Blood cultures from hematologic cancer patients with febrile neutropenia were processed in BACTEC 9120. E. coli, K. pneumoniae, and Enterobacter spp. isolates were identified using conventional biochemical methods. Antimicrobial susceptibility tests, phenotypic ESBL characterization, and genotypic characterization of the ESBL-encoding genes bla_CTX-M, bla_TEM, and bla_SHV were determined for pure isolates of E. coli, K. pneumoniae, and Enterobacter spp.

Results: Two hundred and two patients were included in the study. Median age of patients was 19 years (IQR: 10-30 years). Majority (N=119, 59%) were male patients. Sixty (30%) of the participants had at least one febrile episode due to Enterobacteriaceae. Eighty-three organisms were isolated with E. coli being predominant (45, 54%). Seventy-nine (95%) Enterobacteriaceae were multidrug resistant. The ESBL phenotype was detected in 54/73 (74%) of Enterobacteriaceae that were resistant to third-generation cephalosporins. A higher proportion of Enterobacteriaceae with ESBL-positive phenotype were resistant to piperacillin-tazobactam (p=0.024), gentamicin (p=0.000), ciprofloxacin (p=0.000), and cotrimoxazole (p=0.000) compared to Enterobacteriaceae, which were sensitive to third-generation cephalosporins. The organisms were more susceptible to carbapenems and chloramphenicol than resistant. ESBL-encoding genes (bla_CTX-M, bla_TEM, and bla_SHV) were detected in 55 (75%) of the 73 Enterobacteriaceae that were resistant to third-generation cephalosporins. Bla_CTX-M, was the most common ESBL-encoding gene identified with 50 (91%).

Conclusion: ESBL-producing Enterobacteriaceae are a predominant cause of bacteremia in hematologic cancer patients at UCI. The most common ESBL-encoding gene identified in the ESBL-PE was bla_CTX-M. Resistance to imipenem and meropenem was low.

Keywords: CTX-M; Uganda; antimicrobial resistance; cancer; enterobacteriaceae; extended spectrum beta-lactamases.

Grants and funding

This research was funded by D43 TW009759 NCI Training Grant; UCI-AfDB Training Scholarship (ADM 342/411/01); and Alliance for Global Health and Science Small Grants award, Center for Emerging & Neglected Diseases, University of California, Berkeley.