title: The impact of mechanical ventilation on the moxifloxacin treatment of experimental pneumonia caused by Streptococcus pneumoniae.
abstract: OBJECTIVE
  Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and is responsible for early-onset ventilator-associated pneumonia as well. In intensive care units, community-acquired pneumonia is still associated with a mortality rate of up to 30%, especially when mechanical ventilation is required. Our objective was to study to what extent MV could influence the efficacy of moxifloxacin in a rabbit model of pneumonia.
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  University hospital laboratory.
  
  
  METHODS
  Male New Zealand White rabbits (n = 75).
  
  
  METHODS
  S. pneumoniae (16089 strain; minimal inhibitory concentration for moxifloxacin = 0.125 mg/L) was instilled intrabronchially. Four hours later, a human-like moxifloxacin treatment was initiated in spontaneously breathing (SB) and mechanically ventilated (MV) animals. Untreated rabbits were used as controls. Survivors were killed 48 hrs later. Pneumonia was assessed and moxifloxacin pharmacokinetics were analyzed.
  
  
  RESULTS
  Moxifloxacin treatment was associated with an improvement in survival in the SB animals (13 of 13 [100%] vs. eight of 37 [21.6%] controls). The survival rate was less influenced by treatment in MV rabbits (seven of 15 [46.1%] vs. one of eight [12.5%] controls). The lung bacterial burden was greater in MV compared with SB rabbits (5.1 +/- 2.4 vs. 1.6 +/- 1.4 log10 colony-forming units/g, respectively). Nearly all the untreated animals presented bacteremia as reflected by a positive spleen culture. No bacteremia was found in SB animals treated with moxifloxacin. In contrast, three of 13 (23.1%) moxifloxacin-treated and MV animals had positive spleen cultures. The apparent volume of distribution of moxifloxacin was lower in MV compared with SB rabbits.
  
  
  CONCLUSIONS
  In our model of moxifloxacin-treated S. pneumoniae pneumonia, mechanical ventilation was associated with a higher mortality rate and seemed to promote bacterial growth as well as systemic spread of the infection. In addition, the volume of distribution of moxifloxacin was reduced in the presence of mechanical ventilation. Although the roles of factors such as anesthesia, paralysis, and endotracheal tube insertion could not be established, these results suggest that mechanical ventilation may impair host lung defense, rendering antibiotic therapy less effective.
authors.affiliation: Laboratoire des Maladies Infectieuses, Dijon University Hospital, Dijon, France.
authors.forename: Pierre Emmanuel
authors.initials: PE
authors.lastname: Charles
authors.forename: Manuel
authors.initials: M
authors.lastname: Etienne
authors.forename: Delphine
authors.initials: D
authors.lastname: Croisier
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.forename: Catherine
authors.initials: C
authors.lastname: Lequeu
authors.forename: Jerome
authors.initials: J
authors.lastname: Pugin
authors.forename: Henri
authors.initials: H
authors.lastname: Portier
authors.forename: Pascal
authors.initials: P
authors.lastname: Chavanet
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001372:Aza Compounds / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017714:Community-Acquired Infections / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D024841:Fluoroquinolones; D006207:Half-Life; D008297:Male; D000077266:Moxifloxacin; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D012121:Respiration, Artificial / Q000009:adverse effects*
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin