Document Type : Research Articles
Authors
1
Department of Pharmacology and Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor, Malaysia.
2
Faculty of Pharmacy, Al Rafidain University, 10001, Baghdad, Iraq.
3
School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Subang Jaya, Selangor, Malaysia.
4
Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Universiti Teknologi MARA, 42300 Bandar Puncak Alam, Selangor, Malaysia.
5
Medical Oncology Department, Oncology Teaching Hospital Baghdad, Baghdad, Iraq.
6
Department of Haematology, Medical City Complex, Haematology and Transplant Centre, Baghdad, Iraq.
7
Medical Oncology Department, Alamal National Hospital for Cancer Treatment, Baghdad, Iraq.
Abstract
Background: Multidrug-resistant (MDR) Klebsiella pneumoniae is an important cause of bloodstream infection (BSI) in cancer patients, particularly those with haematological malignancies, where delayed or inappropriate therapy is associated with high mortality. Genomic data on resistance mechanisms in oncology settings in Iraq remain limited. This study aimed to characterise, using whole-genome sequencing, the antibiotic resistance determinants of MDR K. pneumoniae bloodstream isolates from cancer patients and to explore their potential implications for empirical treatment strategies in this high-risk population. Methods: This genomic substudy was nested within a prospective multi-centre cohort of cancer patients with bloodstream infection at oncology hospitals in Baghdad. Adult patients with haematological malignancies and solid tumours with monomicrobial MDR K. pneumoniae infection were included. Identification and antimicrobial susceptibility testing were performed using the VITEK 2 system and interpreted according to Clinical and Laboratory Standards Institute standards. MDR was defined as non-susceptibility to at least three antibiotic classes. Whole-genome sequencing was performed using an Illumina platform. Resistance genes were identified using curated databases and grouped into β-lactamase/carbapenemase, non-β-lactam, and efflux/regulatory categories. Clinical data (age, sex, and malignancy type) were extracted from medical records. Results: Thirty-five MDR K. pneumoniae bloodstream isolates were analysed, with most infections occurring in patients with haematological malignancies (30/35, 85.7%). Detected resistance genes included CTX-M-type extended-spectrum β-lactamases (including CTX-M-15), SHV and TEM enzymes, and OXA-48-like carbapenemases (OXA-48 and OXA-232). Non-β-lactam resistance determinants (aadA, EreA, Mph(A), Mrx, sul1, sulI) and efflux-related genes were also identified. Conclusions: MDR K. pneumoniae bloodstream infections in this cohort were predominantly observed in patients with haematological malignancies. Whole-genome sequencing identified multiple resistance determinants. These findings provide genomic insights that may help explain resistance patterns in this setting and support the need for strengthened infection prevention and locally tailored antimicrobial stewardship strategies.
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