1 Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
2 VID Specialized University, Faculty of Health, Bergen, Norway.
3 Department of Cardiology, Haukeland University Hospital, Bergen, Norway.
4 Department of Anesthesiology and Intensive care, Haukeland University Hospital, Bergen, Norway.
5 Department of Medicine, Haukeland University Hospital, Bergen, Norway.
6 Department of Clinical Science, University of Bergen, Bergen, Norway.
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leukemias are a group of aggressive malignant diseases associated with
a high degree of morbidity and mortality. An important cause of both
the latter is infectious complications. Patients with acute leukemia
are highly susceptible to diseases due to factors related to the
disease itself, factors attributed to treatment, and specific
individual risk factors in each patient. Patients with
chemotherapy-induced neutropenia are at particularly high risk, and
microbiological agents include viral, bacterial, and fungal agents. The
etiology is often unknown in infectious complications, although
adequate patient evaluation and sampling have diagnostic, prognostic
and treatment-related consequences. Bacterial infections include a wide
range of potential microbes, both Gram-negative and Gram-positive
species, while fungal infections include both mold and yeast. A
recurring problem is increasing resistance to antimicrobial agents, and
in particular, this applies to extended-spectrum beta-lactamase
resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae
(CPE). International guidelines for the treatment of sepsis in leukemia
patients include the use of broad-spectrum Pseudomonas-acting
antibiotics. However, one should implant the knowledge of local
microbiological epidemiology and resistance conditions in treatment
decisions. In this review, we discuss infectious diseases in acute
leukemia with a major focus on febrile neutropenia and sepsis, and we
problematize the diagnostic, prognostic, and therapeutic aspects of
infectious complications in this patient group. Meticulously and
thorough clinical and radiological examination combined with adequate
microbiology samples are cornerstones of the examination. Diagnostic
and prognostic evaluation includes patient review according to the
multinational association for supportive care in cancer (MASCC) and
sequential organ failure assessment (SOFA) scoring system.
Antimicrobial treatments for important etiological agents are
presented. The main challenge for reducing the spread of resistant
microbes is to avoid unnecessary antibiotic treatment, but without
giving to narrow treatment to the febrile neutropenic patient that
reduce the prognosis.
Pathophysiology and Risk Factors
|Figure 1. Risk factors for infections in patients with leukemia. The figure summarizes risk factors for infection in leukemia patients, which broadly could be divided into disease specific factors, patient related factors, and treatment related factors.|
Febrile Neutropenia and Sepsis
Clinical Presentation and Diagnosis
|Figure 2. Risk factors for infections in patients with leukemia. The figure illustrates an algorithm for the management of FN in leukemia patients, including prognostic, diagnostic and treatment decision work up. Abbreviations: ANC, absolute neutrophil count; C, Celcius; FiO2, Fraction of inspired Oxygen; GCS, Glasgow coma scale; L, liter; MAP, Mean Arterial Pressure; MASCC, Multinational Association for Supportive Care in Cancer; PaO2, Partial pressure of Oxygen; Pip/tazo, piperacillin/tazobactam; qSOFA, quick Sepsis Related Organ Failure Assessment; SOFA, Sequential Organ Failure Assessment.|
|Table 1. Most common bacteria causing infection in acute leukemia patients. The most frequent Gram-positives and Gram-negatives, causing infections in acute leukemia patients are summarized in the Table. The table presents the most important microbes, their main source for entrance and the possible antimicrobial drugs of choice.|
Treatment of Bacterial Infections
|Table 2. Main antibiotics for infection treatment. The table the most relevant antibiotics when treating infections in leukemic patients. The table presents the most used drugs, their antimicrobial specter, and the main advantages and disadvantages in clinical practice.|
|Table 3. Treatment strategies for empiric antibiotic treatment in acute leukemia patients. The table shows the main escalation and de-escalation therapy in acute leukemia patients, the different patient groups suitable for the different strategies and recommended empiric therapy.|
|Table 4. Treatment options for special problematic microbes. The table shows treatment recommendations for microbes associated with special treatment challenges in patients with acute leukemias. The table is based on European (ECIL) and American (IDSA) recommendations, and references to relevant studies are given in the table. First line treatments are listed first, while second line alternatives are given in parentheses.|
Invasive Fungal Infections
|Table 5. Major invasive fungal infections in patients with acute leukemia. The table presents the most important fungus, divided in molds, yeasts and mucormycosis, and their main subclasses causing infection in acute leukemia patients.|
Treatment of Fungal Infections
|Table 6. Main antifungal treatment options. The table demonstrates the main treatment classes of antifungal therapy; azoles, echinocandins, and amphotericin. The most important drugs in each class, their main antifungal specter and main advantages and disadvantages are presented from left to right.|
|Table 7. Treatment options for particular problematic fungus. The table shows treatment recommendation for fungus associated with special treatment challenges in patients with acute leukemias. The table is based on European (ECIL) and American (IDSA) recommendations, and references to relevant studies are given in the table. First line treatments are listed first, while second line alternatives are given in parentheses.|
Prophylaxis of Bloodstream Infection and Fever During Neutropenia
Other Causes of Persistent Fever and Their Management