title: A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate.
abstract: OBJECTIVE
  The primary purpose of the clinical trial was to assess the safety and efficacy of once-a-day compared with three-times-a-day gentamicin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations.
  
  
  METHODS
  A total of 249 hospitalized patients with suspected or proven serious infections were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC, or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dosage for patients with estimated creatinine clearance values of > or =80 mL/min was 5.1 mg/kg. With lower creatinine clearance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Evaluability required documentation of achievement of protocol-defined peak serum gentamicin levels.
  
  
  RESULTS
  Of the total 175 evaluable patients, there were no significant differences found between treatment regimens with respect to clinical or microbiologic efficacy. Bedside audiometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinine values from baseline values, no differences in renal toxicity between the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of renal function, preservation of renal function was better in the gentamicin once-a-day patients as opposed to the gentamicin three-times-a-day patients, P <0.01.
  
  
  CONCLUSIONS
  Gentamicin once a day plus TC, gentamicin three times a day plus TC, and TC alone had similar effects in seriously ill hospitalized patients. The incidence of nephrotoxicity was similar in the three treatment groups. Using a nonvalidated post-hoc analysis, renal function was better preserved in gentamicin once-a-day + TC and TC-only patients as opposed to gentamicin three-times-a-day + TC.
authors.affiliation: Earle A. Chiles Research Institute, Providence Medical Center and Oregon Health Sciences University, Portland, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: Gilbert
authors.forename: B L
authors.initials: BL
authors.lastname: Lee
authors.forename: R J
authors.initials: RJ
authors.lastname: Dworkin
authors.forename: J L
authors.initials: JL
authors.lastname: Leggett
authors.forename: H F
authors.initials: HF
authors.lastname: Chambers
authors.forename: G
authors.initials: G
authors.lastname: Modin
authors.forename: M G
authors.initials: MG
authors.lastname: Täuber
authors.forename: M A
authors.initials: MA
authors.lastname: Sande
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy; D019818:Clavulanic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003051:Cochlea / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010406:Penicillins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013982:Ticarcillin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010406:Penicillins; D019818:Clavulanic Acid; D003404:Creatinine; D013982:Ticarcillin