Reduced Requirement for Antibiotic Therapy Targeting Gram-Negative Organisms in Febrile, Neutropenic Patients with Cancer Who Are Receiving Antibacterial Chemoprophylaxis with Oral Quinolones

Abstract

An open, nonrandomized, phase 2 study of 53 adult patients who had 60 neutropenic episodes was conducted to determine if quinolone antibacterial prophylaxis could reduce the need during febrile episodes for parenteral therapy directed at gram-negative organisms. Suspected infections among recipients of quinolones were treated empirically with vancomycin and ceftazidime; therapy with the latter was discontinued after 24-48 hours in the absence of infection due to gram-negative organisms. In five neutropenic episodes, patients had no fever or infection. An aerobic gram-negative bacillus was isolated during only 1 (1.8%) of 55 febrile episodes. Febrile episodes occurred at a median of day 15 of cytotoxic therapy. Vancomycin monotherapy was successful in 22 (50%) of 44 evaluable cases. Modification of the vancomycin regimen by the addition of metronidazole or rifampin increased the response rate to 40 (91%) of 44. Response occurred after a median of 4.5 days. Parenteral empirical therapy with amphotericin B was required in only 3 (7%) of 44 cases. The study strategy safely permitted a reduction in the amount and duration of antibiotic therapy directed against gram-negative organisms in febrile neutropenic patients.

Clinical Infections and Bloodstream Isolates Associated with Fever in Patients Undergoing Chemotherapy for Acute Myeloid Leukemia

“…Inadequate activity of ciprofloxacin against these microorganisms has likely contributed to their increased pathogenicity. The few gram-negative bacteremias occurred only in patients who were not receiving ciprofloxacin prophylaxis at the time of bacteremia, confirming the important role antibiotic prophylaxis plays in preventing gram-negative septicemia and in changing the spectrum of microorganisms that cause bloodstream infection in this group of patients, as previously described [19][20][21][22][23].…”

Neutropenic infections in 100 patients with non-Hodgkin’s lymphoma or Hodgkin’s disease treated with high-dose BEAM chemotherapy and peripheral blood progenitor cell transplant: out-patient treatment is a viable option

“…10,11 The absence of neutropenic gram-negative infections, despite a relatively high incidence of febrile neutropenia is consistent with the findings of other studies in which prophylactic quinolone antibiotics have been used. [12][13][14][15] Although the etiology of fever in many of these patients remains obscure, we believe that the low incidence of gram-negative infections may be especially important in patients treated in the outpatient setting, where there may be a longer period of time between signs and symptoms of an infection and the administration of (additional) antibiotic treatment. Nevertheless, given the concerns over the emergence of quinolone-resistant bacteria, and the absence of data supporting a reduction in mortality in patients given prophylactic antibiotics, this point will have to be tested in randomized trials.…”

Management of the febrile neutropenic cancer patient: lessons from 40 years of study

“…Cytotoxic therapy‐induced intestinal epithelial damage is an important component in the pathogenesis of first and subsequent fevers in neutropenic patients [33]. Microorganisms colonising damaged mucosal surface may then undergo translocation and subsequent tissue invasion [9].…”