Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer. A trial of oral penicillin V or placebo combined with pefloxacin. International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer.

OBJECTIVE

To determine the effect of oral penicillin V combined with a fluoroquinolone (pefloxacin) on the occurrence of fever and streptococcal and other gram-positive coccal bacteremic infections in granulocytopenic patients with cancer.

DESIGN

Prospective randomized double-blinded placebo-controlled prophylactic trial.

SETTING

Inpatient setting in multiple cooperating cancer centers.

SUBJECTS

Convenience sample with a total of 551 granulocytopenic patients, 95% of whom had leukemia or underwent bone marrow transplantation.

INTERVENTIONS

Penicillin V (500 mg twice a day) vs placebo given in combination with oral pefloxacin (400 mg twice a day).

MAIN OUTCOME MEASURES

Occurrence of fever and/or infection.

RESULTS

Fever or infection (without fever) developed in 190 (71%) of 268 evaluable patients in the penicillin arm compared with 213 (80%) of 268 evaluable patients in the placebo arm (P = .03; 95% confidence interval [CI] for the difference, -16% to -1%). Bacteremia occurred in 58 (22%) of 268 placebo-treated patients and in 38 (14%) of 268 penicillin-treated patients (P = .03; 95% CI for the difference, -14% to -1%), primarily due to a reduction in streptococcal bacteremic episodes that occurred in 14 penicillin-treated patients (5%) and in 27 placebo-treated patients (10%) (P = .05; 95% CI for the difference, -9% to -0.3%). Gram-negative rod bacteremias occurred in only two patients (1%) and in five patients (2%), respectively. Logistic regression analysis also supported the treatment effect on the development of bacteremia.

CONCLUSIONS

These results demonstrate that the addition of penicillin V to fluoroquinolone prophylaxis in granulocytopenic patients with cancer effectively reduces febrile episodes and the incidence of bacteremia, especially that due to streptococcal species.