Prevention of gram-positive and Candida albicans infections using teicoplanin and fluconazole: a randomized study in neutropenic children

Abstract

We have shown that the combination of teicoplanin (T) and ceftriaxone (C) given once daily as first-line empirical antimicrobial therapy is very effective (85%) and safe in febrile neutropenic children (ICAAC, 1988). Like others (ICAAC, 1989) we have stressed the new life-threatening problems with Streptococcus mitis and Strep. sanguis. Considering the regular sensitivity of Gram-positive organisms to T, it is possible that the introduction of the glycopeptide at the onset of aplasia may be helpful. The high incidence of fungal infection or superinfection supports the routine use of an effective antifungal agent when fever is still present or relapse occurs. Our study was designed to assess the prevention of (1) staphylococcal and streptococcal infections using T when the central catheter is being placed, and (2) candida infection by the simultaneous use of a new anti-mycotic agent fluconazole (F) administered once-daily. Patients were randomized into two arms of the study. Arm A received T 6 mg/kg/d and F 3 mg/kg/d starting when the catheter was put in place. If fever occurred, C 50 mg/kg/d and amikacin (A) 15 mg/kg/d were added and T increased to 10 mg/kg/d. If a febrile relapse occurred, amphotericin B was added. In arm B the combination of the three agents T 10 mg/kg/d, C 50 mg/kg/d and A 15 mg/kg/d was started only if there was fever. Amphotericin B was used in febrile relapses. Forty-six patients were eligible (23 in each arm; no statistically significant differences between the two groups). The mean age of the patients was 8 years and mean duration of aplasia 23 and 24 d. Results were as follows: arm A the duration of T + F alone was 10 d, 22 patients had a febrile episode with 1 Gram-positive, 11 Gram-negative and one candida strain isolated in eight patients. C + A were effective in 72% of these patients. There were no deaths. In arm B, fever occurred in all patients during the first 6 d, with eight Gram-positive and six Gram-negative organisms isolated in nine patients. C + T + A were successful in 83% of patients. A bacterial superinfection was documented in four patients, candida superinfection in seven patients and one patient died from Candida parakrusei septicaemia. When the total amount of C and A used in both arms was compared, there was a reduction in 20% of the two agents in arm A, but T was equivalent in both arms. Treatment was well tolerated in both arms.(ABSTRACT TRUNCATED AT 400 WORDS)