Bacteremia in hematologic cancer patients with febrile neutropenia in Uganda

Abstract

Background There were 19.3 million new cancer cases and 10 million cancer deaths which occurred in 2020. Compared to high-income countries cancer is a growing public health problem in sub-Saharan Africa, where mortality rates are significantly higher than in high-income countries. While several factors contribute to cancer outcomes in sub-Saharan Africa, infectious complications of cancer are likely an important contributor to high mortality. Bacteremia is a life-threatening complication in patients with cancer, particularly in the setting of febrile neutropenia. Moreover, infections are complicated by the current trend of antimicrobial resistance. This in turn complicates antimicrobial therapy, especially in SSA where access to antibiotics is challenging. Methods In the first sub-study, in a cross-sectional study between March 2014 to November 2014, the predominant bacterial species causing bacteremia among febrile cancer patients, and their antibacterial resistance profiles at the Uganda Cancer Institute were determined. In the second sub-study, in a prospective cohort study between November 2017 to March 2020, the etiology, risk factors and outcomes associated with bacteremia in patients with hematologic malignancies and febrile neutropenia were determined. In the third sub-study, in a cross-sectional between Nov 2017 and December 2021, the phenotypic and genotypic characteristics of bacteria isolated from blood of febrile neutropenic patients with hematologic malignancies were determined.

Results The study found 14.1% positive blood cultures were obtained from febrile cancer patients. Positive cultures were predominant in patients with hematologic malignancies and neutropenia. Multidrug resistant Gram-negative bacteria were the main causes of bacteremia in febrile cancer patients at the Uganda Cancer Institute. The study found a bacteremia rate of 33% among patients with hematologic malignancies and febrile neutropenia. Patients with younger age, severe neutropenia, hypotension, mucositis, and receiving chemotherapy were more likely to have bacteremia. 78% of bacteria isolated were Gram negative. E. coli was predominant. 86% of bacteremia episodes were caused by multidrug resistant bacteria. 30-day overall survival for participants with bacteremia was significantly lower than that of patients with no bacteremia. MDR bacteremia was associated with increased risk of death. The study found that 95% of Enterobacteriaceae were MDR and 74% of Enterobacteriaceae that were resistant to third generation cephalosporins had the ESBL phenotype. ESBL-encoding genes (blaCTX-M, blaTEM and blaSHV) were detected in 75% of the Enterobacteriaceae that were resistant to third generation cephalosporins. BlaCTX-M, was the most common ESBL-encoding gene identified. All Enterococcus faecium isolated were MDR and belonged to the clonal complex 17 (CC17) ST80. Phylogeny revealed relatedness among the isolates with spread between patients in the same ward and different wards. The study also identified rare bacteria isolated from patients with hematologic malignancies and febrile neutropenia. These included Rhodococcus equi, Cupriavidus pauculus, Leclercia adecarboxylata, Empedobacter brevis, Streptococcus oralis, and Weissella confusa.

Conclusion Bacteremia was frequent in hematologic cancer patients with febrile neutropenia and was associated with poor survival. Multidrug resistant Gram-negative bacteria consistently defined the causes of bacteremia in hematologic cancer patients with febrile neutropenia and was associated with mortality. CTX-M ESBL-producing Enterobacteriaceae and multidrug resistant E. faecium CC17 ST80, were the main cause of bacteremia and increase mortality in febrile neutropenic hematologic cancer patients at the UCI, accounting for the treatment of bacteremia using inappropriate antimicrobial therapy.