Quinolone-based antibacterial chemoprophylaxis in neutropenic patients: effect of augmented gram-positive activity on infectious morbidity. National Cancer Institute of Canada Clinical Trials Group.
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.


METHODS
Open, randomized, controlled, multicenter clinical trial.


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


METHODS
111 eligible and evaluable patients hospitalized for severe neutropenia (neutrophil count < 0.5 x 10(9)/L lasting at least 14 days) who were receiving cytotoxic therapy for acute leukemia or bone marrow autografting.


METHODS
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.


METHODS
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.
Bow
E J
EJ
Health Sciences Centre, Winnipeg, Manitoba, Canada.
Mandell
L A
LA
Louie
T J
TJ
Feld
R
R
Palmer
M
M
Zee
B
B
Pater
J
J
D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016470:Bacteremia / Q000382:microbiology / Q000517:prevention & control*; D015169:Colony Count, Microbial; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D009643:Norfloxacin / Q000627:therapeutic use; D015242:Ofloxacin / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013203:Staphylococcal Infections / Q000517:prevention & control; D013290:Streptococcal Infections / Q000517:prevention & control; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D015242:Ofloxacin; D009643:Norfloxacin; D012293:Rifampin