title: Renal impairment after high-dose flucloxacillin and single-dose gentamicin prophylaxis in patients undergoing elective hip and knee replacement.
abstract: BACKGROUND
  Following advice from the Scottish Antimicrobial Prescribing Group, we switched our antibiotic prophylaxis for elective hip and knee replacement surgery from cefuroxime to flucloxacillin with single-dose gentamicin in order to reduce the incidence of Clostridium difficile associated diarrhoea (CDAD). A clinical impression that more patients subsequently developed acute kidney injury (AKI) led us to examine this possibility in more detail.
  
  
  METHODS
  We examined the incidence of AKI in 198 consecutive patients undergoing elective hip or knee surgery. These patients were given the following prophylactic antibiotics: cefuroxime (n = 48); then high-dose (HD) flucloxacillin (5-8 g) with single-dose gentamicin (n = 52); then low-dose (LD) flucloxacillin (3-4 g) with single-dose gentamicin (n = 46) and finally cefuroxime again (n = 52).
  
  
  RESULTS
  Patients receiving HD flucloxacillin required more vasopressors during surgery (P = 0.02); otherwise, there were no statistically significant differences in pre- and peri-operative characteristics between the four groups. The proportion of patients with any form of AKI by RIFLE criteria was first cefuroxime (8%), HD flucloxacillin with gentamicin (52%), LD flucloxacillin with gentamicin (22%) and second cefuroxime (14%; P < 0.0001). Odds ratios for AKI derived from a multivariate logistic regression model, adjusted also for sex and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, with the first cefuroxime group as a reference category were: HD flucloxacillin with gentamicin 14.53 (4.25-49.71); LD flucloxacillin with gentamicin 2.96 (0.81-10.81) and second cefuroxime 2.01 (0.52-7.73). Three patients required temporary haemodialysis. Biopsies in two of these showed acute tubulo-interstitial nephritis. All three patients belonged to the HD flucloxacillin with gentamicin group. None of the patients developed CDAD.
  
  
  CONCLUSIONS
  We have shown an association between the prophylactic antibiotic regimen and subsequent development of AKI following primary hip and knee arthroplasty that appeared to be due to the use of HD flucloxacillin with single-dose gentamicin. We found no evidence to suggest that this association was confounded by any of the co-variates we measured.
authors.affiliation: Department of Orthopaedics, Dumfries and Galloway RoyalInfirmary, Dumfries, UK.
authors.forename: Sudhakar Rao
authors.initials: SR
authors.lastname: Challagundla
authors.forename: David
authors.initials: D
authors.lastname: Knox
authors.forename: Amanda
authors.initials: A
authors.lastname: Hawkins
authors.forename: David
authors.initials: D
authors.lastname: Hamilton
authors.forename: Robert
authors.initials: R
authors.lastname: W V Flynn
authors.forename: Sue
authors.initials: S
authors.lastname: Robertson
authors.forename: Chris
authors.initials: C
authors.lastname: Isles
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D019072:Antibiotic Prophylaxis / Q000009:adverse effects*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005436:Floxacillin / Q000008:administration & dosage / Q000009:adverse effects*; D005500:Follow-Up Studies; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D013530:Surgical Wound Infection / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D005436:Floxacillin