Quinolone-Based Antibacterial Chemoprophylaxis in Neutropenic Patients: Effect of Augmented Gram-Positive Activity on Infectious Morbidity

Abstract

Objective: To determine whether augmented quinolone-based antibacterial prophylaxis in neutropenic patients with cancer reduces infections caused by gram-positive cocci and preserves the protective effect against aerobic gram-negative bacilli.

Design: Open, randomized, controlled, multicenter clinical trial.

Setting: Centers participating in the National Cancer Institute of Canada Clinical Trials Group.

Patients: 111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count less than 0.5 × 10⁹/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting.

Intervention: One of three oral antibacterial prophylactic regimens (norfloxacin, 400 mg every 12 hours; ofloxacin, 400 mg every 12 hours; or ofloxacin, 400 mg, plus rifampin, 300 mg every 12 hours) beginning with cytotoxic therapy.

Measurements: Incidence and cause of suspected or proven infection.

Results: Microbiologically documented overall infection rates for norfloxacin, ofloxacin, and ofloxacin plus rifampin were 47%, 24%, and 9%, respectively (P < 0.001). Corresponding rates were 24%, 13%, and 3%, respectively for staphylococcal bacteremia (P = 0.03) and, 21%, 3%, and 3%, respectively for streptococcal bacteremia (P < 0.01). The pattern of bacteremia suggested that rifampin played a role in suppressing staphylococcal infection. Both ofloxacin alone and ofloxacin plus rifampin had a clinically significant antistreptococcal effect. Aerobic gram-negative rods were cleared from rectal surveillance cultures in all patients after a median of 5.5 days and caused infection in only one patient (0.9%). The reductions in the number of microbiologically documented infections among ofloxacin recipients and ofloxacin plus rifampin recipients were offset by concomitant increases in the number of unexplained fevers (24% of norfloxacin recipients, 53% of ofloxacin recipients, and 49% of ofloxacin plus rifampin recipients; P = 0.02). No statistically significant difference was found among the treatment arms with respect to the overall incidence of febrile neutropenic episodes as defined for this trial (79% for the norfloxacin group, 82% for the ofloxacin group, and 77% for the ofloxacin plus rifampin group).

Conclusions: Quinolone-based antibacterial chemoprophylaxis protected patients from aerobic gram-negative bacillary infections. Augmentation of the gram-positive activity reduced the incidence of gram-positive infections but did not influence the overall incidence of febrile neutropenic episodes.

*For additional investigators, see the Appendix.