MONOTHERAPY WITH MEROPENEM VERSUS COMBINATION THERAPY WITH CEFTAZIDIME PLUS AMIKACIN AS EMPIRIC THERAPY FOR FEVER IN GRANULOCYTOPENIC PATIENTS WITH CANCER

Combinations of beta-lactams plus aminoglycosides have been standard t herapy for suspected infections in granulocytopenic cancer patients, e specially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended -spectrum cephalosporins or carbapenems, the need to combine beta-lact ams with aminoglycosides became more controversial. The objective of t his prospective randomized multicenter study was to compare the effica cy, safety, and tolerance of meropenem monotherapy with those of the c ombination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patien ts, 958 were assessable in the intent-to-treat analysis for response t o antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutro penia were 16 and 17 days, respectively. A successful outcome was repo rted in 270 of 483 (56%) patients treated with monotherapy compared wi th 245 of 475 (52%) patients treated with the combination group (P = 0 .20). The success rates in the monotherapy group and the combination g roup were similar by type of infection (single gram-negative bacteremi a, single gram-positive bacteremia, clinically documented infection, a nd possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not di ffer between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patie nts treated with the monotherapy compared with 13 patients treated wit h the combination). A total of 1,027 patients were evaluable for adver se events; the proportion of those who developed adverse effects was s imilar between the two groups (29% in both groups), and only 19 (4%) p atients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protoco l antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persis tently granulocytopenic cancer patients, and both regimens were well t olerated.