Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa.
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.
Lu
Qin
Q
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.
Girardi
Cassio
C
Zhang
Mao
M
Bouhemad
Belaïd
B
Louchahi
Kamel
K
Petitjean
Olivier
O
Wallet
Frédéric
F
Becquemin
Marie-Helene
MH
Le Naour
Gilles
G
Marquette
Charles-Hugo
CH
Rouby
Jean-Jacques
JJ
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
D000900:Anti-Bacterial Agents; D003091:Colistin
Thorax. 1987 Jan;42(1):1-10
3303423
JAMA. 1995 Aug 23-30;274(8):639-44
7637145
Clin Infect Dis. 2003 May 1;36(9):1111-8
12715304
Arch Intern Med. 1966 Oct;118(4):326-34
5925230
J Antimicrob Chemother. 2003 Dec;52(6):987-92
14585859
Clin Microbiol Infect. 2006 Dec;12(12):1227-30
17121631
Clin Infect Dis. 2005 Sep 1;41(5):754-7
16080101
Am J Respir Crit Care Med. 2002 Jan 15;165(2):171-5
11790649
Clin Ther. 2008 Jan;30(1):143-51
18343250
Circ Res. 1984 Aug;55(2):155-67
6430590
J Antimicrob Chemother. 2006 Feb;57(2):306-11
16396919
Intensive Care Med. 2005 Aug;31(8):1058-65
15983759
Ther Drug Monit. 2000 Oct;22(5):589-93
11034265
Intensive Care Med. 2008 Sep;34(9):1718-23
18542922
J Antimicrob Chemother. 2008 Dec;62(6):1311-8
18922815
Chest. 1996 Apr;109(4):1019-29
8635325
Respir Med. 2008 Mar;102(3):407-12
18060758
Anesthesiology. 2005 May;102(5):995-1000
15851887
Intensive Care Med. 2007 Jul;33(7):1162-1167
17530220
Antimicrob Agents Chemother. 2009 Aug;53(8):3430-6
19433570
N Engl J Med. 1962 Apr 12;266:759-62
14008070
J Antimicrob Chemother. 2001 Jul;48 Suppl 1:17-28
11420334
Lancet Infect Dis. 2006 Sep;6(9):589-601
16931410
Clin Microbiol Infect. 2007 Jun;13(6):560-78
17266725
Anesthesiology. 2002 Jul;97(1):199-206
12131123
Crit Care. 2007;11(1):R14
17274806
J Antimicrob Chemother. 2009 Mar;63(3):534-42
19147523
Chest. 1999 Jan;115(1):200-9
9925085
Am J Respir Crit Care Med. 2002 Nov 15;166(10):1375-81
12406838
Intensive Care Med. 2009 Oct;35(10):1792-800
19652947
Antimicrob Agents Chemother. 2003 Mar;47(3):905-9
12604520
Clin Infect Dis. 2005 May 1;40(9):1333-41
15825037
Antimicrob Agents Chemother. 1991 Oct;35(10):1953-9
1759813
Am J Respir Crit Care Med. 1998 Mar;157(3 Pt 1):912-6
9517611
Anesthesiology. 1996 Apr;84(4):757-9
8638828
Respir Med. 2009 May;103(5):707-13
19118994
Ann Pharmacother. 1999 Sep;33(9):960-7
10492501
Crit Care. 2005 Feb;9(1):R53-9
15693967