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.


METHODS
Prospective randomized double-blinded placebo-controlled prophylactic trial.


METHODS
Inpatient setting in multiple cooperating cancer centers.


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


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


METHODS
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.
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000150:complications*; D016470:Bacteremia / Q000209:etiology / Q000517:prevention & control*; D016026:Bone Marrow Transplantation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000209:etiology / Q000517:prevention & control*; D016908:Gram-Positive Bacterial Infections / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009369:Neoplasms / Q000150:complications* / Q000628:therapy; D015366:Pefloxacin / Q000008:administration & dosage / Q000627:therapeutic use; D010404:Penicillin V / Q000008:administration & dosage / Q000627:therapeutic use; D012044:Regression Analysis; D013290:Streptococcal Infections / Q000209:etiology / Q000517:prevention & control*
D015366:Pefloxacin; D010404:Penicillin V