Genomic characterization of two distinct Klebsiella pneumoniae strains in a fatal case of relapsed acute myelogenous leukemia: a case report

Background: 

Patients with acute myelogenous leukemia (AML) are at high risk for infections due to prolonged neutropenia and immunosuppression. The emergence of multidrug-resistant Gram-negative pathogens, particularly carbapenem-resistant Klebsiella pneumoniae (CRKP), presents a critical therapeutic challenge in this vulnerable population. 

Case presentation: 

We describe a fatal case of a 67-year-old male with relapsed AML who developed cavitary pneumonia and bacteremia. Microbiological investigation identified K. pneumoniae with differing resistance phenotypes from blood and bronchoalveolar lavage samples. Despite escalation to combination therapy with ceftazidime-avibactam and aztreonam, the patient succumbed to the infection. 

Genomic findings: 

Whole-genome sequencing revealed co-infection with two genetically distinct K. pneumoniae strains with sequence types (ST) of ST147 and ST967. The ST147 isolates (AG1 and AG3) harbored bla_OXA−181, extensive plasmid replicons, and a high burden of virulence and resistance genes, consistent with a high-risk multidrug-resistant clone. In contrast, the ST967 isolate (AG2) carried a limited resistome without carbapenemase genes and clustered phylogenetically with strains from Qatar, suggesting transregional dissemination. Notably, ST967 has not been previously reported in the UAE. 

Conclusion: 

This case highlights the importance of genome-based diagnostics in identifying mixed-strain infections and uncovering resistance mechanisms that may not be apparent in routine phenotypic assays. The presence of the high-risk clone ST147 and the emerging ST967 lineage in a single host highlights the complexity of managing infections in immunocompromised patients and the urgent need for real-time genomic surveillance to guide antimicrobial stewardship and infection control.