Abstract

Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum β-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients.

Highlights

  • Clinical manifestations of acute leukemia (AL) result either from the proliferation of leukemic cells or from bone marrow failure that leads to a decrease in normal cells; AL patients usually present with pancytopenia, including neutropenia

  • We address important issues regarding carbapenem-resistant Enterobacteriaceae (CRE) infections in AL patients

  • We performed a nonsystematic review of carbapenem-resistant Enterobacteriaceae, with implications for treating acute leukemias, a subgroup of hematological malignancies

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Summary

Introduction

Clinical manifestations of acute leukemia (AL) result either from the proliferation of leukemic cells or from bone marrow failure that leads to a decrease in normal cells; AL patients usually present with pancytopenia, including neutropenia. Identification of sepsis and microbiological diagnostics including cultures from blood and possible foci of infection, followed by prompt administration of intravenous antibiotics covering the most likely pathogens, remain the cornerstone in the initial management of sepsis. Increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE), often in combination with resistance to non-β-lactam antibiotics, considerably complicates both empirical and targeted treatment of infections in AL patients [2,3,4,5]. Lack of randomized clinical trials (RCTs) leaves the optimal treatment algorithm for CRE infections largely unknown. We address important issues regarding CRE infections in AL patients. A limited number of studies focused on CRE infections in AL patients. Risk factors, clinical implications, microbiological aspects, and diagnostics in AL patients with CRE infections.

Methods
Acute Leukemia and Infection Risks
The Epidemiology of CRE Globally
The Epidemiology of CRE in HM Patients
CRE: Clinical Aspects
Detection of CRE and Characterizing of Carbapenemases
Management of CRE Infections in Adult Acute Leukemia Patients
Findings
10. Future Challenges and Perspective
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