title: Prospective, randomized, controlled study comparing two dosing regimens of gentamicin/oral ciprofloxacin switch therapy for acute pyelonephritis.
abstract: Aminoglycosides are drugs of choice for severe gram-negative urinary tract sepsis. Recent evidence suggests that they are just as efficacious, but less nephrotoxic and ototoxic, if given as a single daily dose rather than in divided doses. We considered that a single, large dose of an aminoglycoside followed by oral therapy with a different antibiotic might be equally effective and possibly less toxic. This randomized, controlled study compared a single large i.v. dose (10 mg/kg) of gentamicin (S) with a standard multiple dose regimen (M) of gentamicin (2.5 mg/kg i.v. stat and then computer generated divided doses aiming for peak and trough concentrations of 8 and 1.5 mg/l respectively) for the treatment of patients with suspected acute pyelonephritis requiring hospitalization for parenteral antibiotic treatment. All patients were switched to oral ciprofloxacin either four hours after the S dose or when clinically appropriate in the M regimen. For all patients the total duration of treatment was five days. Fifty-three patients (48 women; mean age 32 yr) were enrolled. Clinical and bacteriological efficacy could be assessed in 41 patients. Thirteen of 16 in the S arm and 24 of 25 in the M arm were clinically cured and the other four clinically improved. Fifteen of 16 in the S arm and 23 of 25 in the M arm were cured bacteriologically (sterile urine 7-10 days after treatment). In 41 patients high tone audiometry was carried out before or very soon after the start of treatment, and again at the end of treatment. Ototoxicity (> or = 10 dB loss in > or = 2 frequencies in both ears) was observed in 3 of 18 in the S group (17%) and 7 of 23 in the M group (30%) (NS). Other side-effects and toxicity were mild and not different between groups. Substantial cost savings occurred in the S group. In summary, a large single dose of gentamicin was comparable in efficacy and toxicity to a standard regimen, but cheaper and more convenient to use.
authors.affiliation: Department of Nephrology, Christchurch Hospital, New Zealand.
authors.forename: R R
authors.initials: RR
authors.lastname: Bailey
authors.forename: E J
authors.initials: EJ
authors.lastname: Begg
authors.forename: A H
authors.initials: AH
authors.lastname: Smith
authors.forename: R A
authors.initials: RA
authors.lastname: Robson
authors.forename: K L
authors.initials: KL
authors.lastname: Lynn
authors.forename: S T
authors.initials: ST
authors.lastname: Chambers
authors.forename: M L
authors.initials: ML
authors.lastname: Barclay
authors.forename: J
authors.initials: J
authors.lastname: Hornibrook
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011446:Prospective Studies; D011704:Pyelonephritis / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D005839:Gentamicins; D002939:Ciprofloxacin