title: Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa.
abstract: OBJECTIVE
  Emergence of multidrug-resistant strains in intensive care units has renewed interest in colistin, which often remains the only available antimicrobial agent active against resistant Pseudomonas aeruginosa. The aim of this study is to compare lung tissue deposition and antibacterial efficiency between nebulized and intravenous administration of colistin in piglets with pneumonia caused by P. aeruginosa.
  
  
  METHODS
  In ventilated piglets, colistimethate was administered 24 h following bronchial inoculation of Pseudomonas aeruginosa (minimum inhibitory concentration of colistin = 2 microg ml(-1)) either by nebulization (8 mg kg(-1) every 12 h, n = 6) or by intravenous infusion (3.2 mg kg(-1) every 8 h, n = 6). All piglets were killed 49 h after inoculation. Colistin peak lung tissue concentrations and lung bacterial burden were assessed on multiple post mortem subpleural lung specimens.
  
  
  RESULTS
  Median colistin peak lung concentration following nebulization was 2.8 microg g(-1) (25-75% interquartile range = 0.8-13.7 microg g(-1)). Colistin was undetected in lung tissue following intravenous infusion. In the aerosol group, peak lung tissue concentrations were significantly greater in lung segments with mild pneumonia (median = 10.0 microg g(-1), 25-75% interquartile range = 1.8-16.1 microg g(-1)) than in lung segments with severe pneumonia (median = 1.2 microg g(-1), 25-75% interquartile range = 0.5-3.3 microg g(-1)) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts <10(2) cfu g(-1) following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts <10(2) cfu g(-1) 49 h following bronchial inoculation.
  
  
  CONCLUSIONS
  Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.
authors.affiliation: Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care Medicine, La Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, UPMC Univ Paris 06, Paris, France.
authors.forename: Qin
authors.initials: Q
authors.lastname: Lu
authors.forename: Cassio
authors.initials: C
authors.lastname: Girardi
authors.forename: Mao
authors.initials: M
authors.lastname: Zhang
authors.forename: Belaïd
authors.initials: B
authors.lastname: Bouhemad
authors.forename: Kamel
authors.initials: K
authors.lastname: Louchahi
authors.forename: Olivier
authors.initials: O
authors.lastname: Petitjean
authors.forename: Frédéric
authors.initials: F
authors.lastname: Wallet
authors.forename: Marie-Helene
authors.initials: MH
authors.lastname: Becquemin
authors.forename: Gilles
authors.initials: G
authors.lastname: Le Naour
authors.forename: Charles-Hugo
authors.initials: CH
authors.lastname: Marquette
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Rouby
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003091:Colistin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D007275:Injections, Intravenous; D009330:Nebulizers and Vaporizers; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
references.citation: Thorax. 1987 Jan;42(1):1-10
references.pmid: 3303423
references.citation: JAMA. 1995 Aug 23-30;274(8):639-44
references.pmid: 7637145
references.citation: Clin Infect Dis. 2003 May 1;36(9):1111-8
references.pmid: 12715304
references.citation: Arch Intern Med. 1966 Oct;118(4):326-34
references.pmid: 5925230
references.citation: J Antimicrob Chemother. 2003 Dec;52(6):987-92
references.pmid: 14585859
references.citation: Clin Microbiol Infect. 2006 Dec;12(12):1227-30
references.pmid: 17121631
references.citation: Clin Infect Dis. 2005 Sep 1;41(5):754-7
references.pmid: 16080101
references.citation: Am J Respir Crit Care Med. 2002 Jan 15;165(2):171-5
references.pmid: 11790649
references.citation: Clin Ther. 2008 Jan;30(1):143-51
references.pmid: 18343250
references.citation: Circ Res. 1984 Aug;55(2):155-67
references.pmid: 6430590
references.citation: J Antimicrob Chemother. 2006 Feb;57(2):306-11
references.pmid: 16396919
references.citation: Intensive Care Med. 2005 Aug;31(8):1058-65
references.pmid: 15983759
references.citation: Ther Drug Monit. 2000 Oct;22(5):589-93
references.pmid: 11034265
references.citation: Intensive Care Med. 2008 Sep;34(9):1718-23
references.pmid: 18542922
references.citation: J Antimicrob Chemother. 2008 Dec;62(6):1311-8
references.pmid: 18922815
references.citation: Chest. 1996 Apr;109(4):1019-29
references.pmid: 8635325
references.citation: Respir Med. 2008 Mar;102(3):407-12
references.pmid: 18060758
references.citation: Anesthesiology. 2005 May;102(5):995-1000
references.pmid: 15851887
references.citation: Intensive Care Med. 2007 Jul;33(7):1162-1167
references.pmid: 17530220
references.citation: Antimicrob Agents Chemother. 2009 Aug;53(8):3430-6
references.pmid: 19433570
references.citation: N Engl J Med. 1962 Apr 12;266:759-62
references.pmid: 14008070
references.citation: J Antimicrob Chemother. 2001 Jul;48 Suppl 1:17-28
references.pmid: 11420334
references.citation: Lancet Infect Dis. 2006 Sep;6(9):589-601
references.pmid: 16931410
references.citation: Clin Microbiol Infect. 2007 Jun;13(6):560-78
references.pmid: 17266725
references.citation: Anesthesiology. 2002 Jul;97(1):199-206
references.pmid: 12131123
references.citation: Crit Care. 2007;11(1):R14
references.pmid: 17274806
references.citation: J Antimicrob Chemother. 2009 Mar;63(3):534-42
references.pmid: 19147523
references.citation: Chest. 1999 Jan;115(1):200-9
references.pmid: 9925085
references.citation: Am J Respir Crit Care Med. 2002 Nov 15;166(10):1375-81
references.pmid: 12406838
references.citation: Intensive Care Med. 2009 Oct;35(10):1792-800
references.pmid: 19652947
references.citation: Antimicrob Agents Chemother. 2003 Mar;47(3):905-9
references.pmid: 12604520
references.citation: Clin Infect Dis. 2005 May 1;40(9):1333-41
references.pmid: 15825037
references.citation: Antimicrob Agents Chemother. 1991 Oct;35(10):1953-9
references.pmid: 1759813
references.citation: Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):912-6
references.pmid: 9517611
references.citation: Anesthesiology. 1996 Apr;84(4):757-9
references.pmid: 8638828
references.citation: Respir Med. 2009 May;103(5):707-13
references.pmid: 19118994
references.citation: Ann Pharmacother. 1999 Sep;33(9):960-7
references.pmid: 10492501
references.citation: Crit Care. 2005 Feb;9(1):R53-9
references.pmid: 15693967