Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial.
OBJECTIVE
We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically.


METHODS
Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day.


RESULTS
Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species.


CONCLUSIONS
We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.
Pico
J L
JL
Service d'Hématologie, Institut Gustave Roussy, Villejuif, France.
Marie
J P
JP
Chiche
D
D
Guiguet
M
M
Andremont
A
A
Lapierre
V
V
Richet
H
H
Tancrede
C
C
Lagrange
P
P
Hayat
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy; D002442:Ceftazidime / Q000008:administration & dosage; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D005334:Fever / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000209:etiology*; D014640:Vancomycin / Q000627:therapeutic use*
D014640:Vancomycin; D000583:Amikacin; D002442:Ceftazidime