title: Eradication of endotracheal tube biofilm by nebulised gentamicin.
abstract: OBJECTIVE
  To compare the efficacy of gentamicin, nebulised via the endotracheal tube (ET), with that of parenteral cefotaxime or parenteral cefuroxime in preventing the formation of ET biofilm.
  
  
  METHODS
  General intensive care units in two university teaching hospitals.
  
  
  METHODS
  The microbiology of ET biofilm from 36 ICU patients eligible to receive antibiotic prophylaxis was examined. Peak and trough tracheal concentrations of gentamicin, cefotaxime or cefuroxime were measured in each patient group, on the 2nd day of intubation.
  
  
  METHODS
  Twelve patients received gentamicin (80 mg) nebulised in 4 ml normal saline every 8 h, 12 cefotaxime (1 g, 12 hourly) and 12 cefuroxime (750 mg, 8 hourly). Prophylaxis was continued for the duration of intubation.
  
  
  RESULTS
  Samples of tracheal secretions were taken on the 2nd day of ventilation for determination of antibiotic concentrations. Following extubation, ETs were examined for the presence of biofilm. Pathogens considered to be common aetiological agents for VAP included Staphylococcus aureus, enterococci, Enterobacteriaceae and pseudomonads. While microbial biofilm was found on all ETs from the cephalosporin group, microbial biofilm of these micro-organisms was found on 7 of the 12 ET tubes from patients receiving cefotaxime [ S. aureus (4), pseudomonads (1), Enterobacteriaceae (1), enterococcus (1)] and 8 of the 12 ET tubes from patients receiving cefuroxime [Enterobacteriaceae (6), P. aeruginosa (1) and enterococcus (1)]. While microbial biofilm was observed on five ETs from patients receiving nebulised gentamicin, none of these were from pathogens for ventilator-associated pneumonia (VAP). Tracheal concentrations of both cephalosporins were lower than those needed to inhibit the growth of pathogens recovered from ET tube biofilm. The median (and range) concentrations for cefotaxime were 0.90 (<0.23-1.31) mg/l and 0.28 (<0.23-0.58) mg/l for 2 h post-dose and trough samples, respectively. Two hours post-dose concentrations of cefuroxime (median and range) were 0.40 (0.34-0.83) mg/l, with trough concentrations of 0.35 (<0.22-0.47) mg/l. Tracheal concentrations (median and range) of gentamicin measured 1 h post-nebulisation were 790 (352-->1250) mg/l and then, before the next dose, were 436 (250-1000) mg/l.
  
  
  CONCLUSIONS
  Nebulised gentamicin attained high concentrations in the ET lumen and was more effective in preventing the formation of biofilm than either parenterally administered cephalosporin and therefore may be effective in preventing this complication of mechanical ventilation.
authors.affiliation: School of Pharmacy, The Queen's University of Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: C G
authors.initials: CG
authors.lastname: Adair
authors.forename: S P
authors.initials: SP
authors.lastname: Gorman
authors.forename: L M
authors.initials: LM
authors.lastname: Byers
authors.forename: D S
authors.initials: DS
authors.lastname: Jones
authors.forename: B
authors.initials: B
authors.lastname: Feron
authors.forename: M
authors.initials: M
authors.lastname: Crowe
authors.forename: H C
authors.initials: HC
authors.lastname: Webb
authors.forename: G J
authors.initials: GJ
authors.lastname: McCarthy
authors.forename: K R
authors.initials: KR
authors.lastname: Milligan
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019072:Antibiotic Prophylaxis; D018441:Biofilms / Q000187:drug effects*; D002439:Cefotaxime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002444:Cefuroxime / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003428:Cross Infection / Q000517:prevention & control; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007263:Infusions, Parenteral; D007442:Intubation, Intratracheal / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000517:prevention & control; D018709:Statistics, Nonparametric
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005839:Gentamicins; D002439:Cefotaxime; D002444:Cefuroxime