Acute Myelogenous Leukemia and Febrile Neutropenia

Aggressive chemotherapy has a deleterious effect on all components of the defense system of the human body. The resulting neutropenia as well as injury to the pulmonary and gastrointestinal mucosa allow pathogenic micro-organisms easy access to the body. The symptoms of an incipient infection are usually subtle and limited to unexplained fever due to the absence of granulocytes. This is the reason why prompt administration of antimicrobial agents while waiting for the results of the blood cultures, the so-called empirical approach, became an undisputed standard of care. Gram-negative pathogens remain the principal concern because their virulence accounts for serious morbidity and a high early mortality rate. Three basic intravenous antibiotic regimens have evolved: initial therapy with a single antipseudomonal β-lactam, the so-called monotherapy; a combination of two drugs: a β-lactam with an aminoglycoside, a second β-lactam or a quinolone; and, thirdly, a glycopeptide in addition to β-lactam monotherapy or combination. As there is no single consistently superior empirical regimen, one should consider the local antibiotic susceptibility of bacterial isolates in the selection of the initial antibiotic regimen. Not all febrile neutropenic patients carry the same risk as those with fever only generally respond rapidly, whereas those with a clinically or microbiologically documented infection show a much slower reaction and less favorable response rate. Once an empirical antibiotic therapy has been started, the patient must be monitored continuously for nonresponse, emergence of secondary infections, adverse effects, and the development of drug-resistant organisms. The averageduration of fever in serious infections in eventually successfully treated neutropenic patients is 4–5 days. Adaptations of an antibiotic regimen in a patient who is clearly not responding is relatively straightforward when a micro-organism has been isolated; the results of the cultures, supplemented by susceptibility testing, will assist in selecting the proper antibiotics. The management of febrile patients with pulmonary infiltrates is complex. Bronchoscopy and a high resolution computer-assisted tomographic scan represent the cornerstones of all diagnostic procedures, supplemented by serological tests for relevant viral pathogens and for aspergillosis. Fungi have been found to be responsible for two thirds of all superinfections that may surface during broad-spectrum antibiotic treatment of neutropenic patients. Antibiotic treatment is usually continued for a minimum of 7 days or until culture results indicate that the causative organism has been eradicated and the patient is free of major signs and symptoms. If a persistently neutropenic patient has no complaints and displays no evidence of infection, early watchful cessation of antibiotic therapy or a change to the oral regimen should be considered.