A RANDOMIZED TRIAL OF HIGH-DOSE CIPROFLOXACIN VERSUS AZLOCILLIN AND NETILMICIN IN THE EMPIRICAL THERAPY OF FEBRILE NEUTROPENIC PATIENTS

A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of aziocillin and netilmicin in the empirical treatment of febrile episodes in neutropenic patients was performed. One hundred and forty-six patient episodes were randomized, but ten (seven ciprofloxacin and three aziocilhin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia. Of the remaining 133 episodes, infections resolved without modification of therapy in 25/66(38%) versus 28/67(42%) of ciprofloxacin and azlocillin/netilmicin treated groups respectively (P=0·72). Considering all randomized episodes, therapy was modified in 46/73(63%) episodes with ciprofloxacin and 39/70(56%) with aziocillin/netilmicin (P=0·40). Of 73 patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on therapy after a median of three days of intravenous therapy. Infections were microbiologically documented in 31/73 (42%;) ciprofloxacin and 32/70 (46%) azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes resolved without modification of therapy respectively (P=0·28). Gram-positive organisms accounted for 78% of all organisms cultured with 36% coagulase-negative staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29 (90%) evaluable patient episodes treated with ciprofloxacin and azlocillin/netilmicin respectively (P=0·27). Superinfections were seen in 14% of episodes in both groups, and subsequent infections in 12% ciprofloxacin and 14% aziocillin/netilmicin treated patients. Two patients (one ciprofloxacin and one azlocillin/netilmicin) died within 48 h of randomization, and a further 13 patients (four ciprofloxacin and nine azlocillin/netilmicin) died before resolution of neutropenia. Adverse events were recorded in 9% and 15% of ciprofloxacin and azlocilhin/netilmicin treated patients respectively, with skin rash (five ciprofloxacin and four azlocillin/netilmicin), nephrotoxicity (two azlocillin/netilmicin), abnormal liver function tests (two azlocillin/netihnicin), ototoxicity (one azlocilhin/netilmicin) and nausea (one ciprofloxacin) being the major events recorded. It was concluded that monotherapy with ciprofloxacin at this dosage is a safe alternative to combination therapy with azjocillin/netilmicin, and has the advantages of twice daily administration, iv and oral presentations, no cross allergy in β-lactam-hypersensitive patients, and no nephro or oto-toxicity. © 1992 The British Society for Antimicrobial Chemotherapy.