title: A randomized trial of high-dose ciprofloxacin versus azlocillin and netilmicin in the empirical therapy of febrile neutropenic patients.
abstract: A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of azlocillin 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(seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia.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 azlocillin/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% azlocillin/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 azlocillin/netilmicin treated patients respectively, with skin rash (five ciprofloxacin and four azlocillin/netilmicin), nephrotoxicity (two azlocillin/netilmicin), abnormal liver function tests (two azlocillin/netilmicin), ototoxicity (one azlocillin/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 azlocillin/netilmicin, and has the advantages of twice daily administration, iv and oral presentations, no cross allergy in beta-lactam-hypersensitive patients, and no nephro- or oto-toxicity.
authors.affiliation: Department of Clinical Haematology, Manchester Royal Infirmary, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Johnson
authors.forename: J A
authors.initials: JA
authors.lastname: Liu Yin
authors.forename: J A
authors.initials: JA
authors.lastname: Tooth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001390:Azlocillin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009428:Netilmicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009503:Neutropenia / Q000150:complications*
chemical_list: D009428:Netilmicin; D002939:Ciprofloxacin; D001390:Azlocillin