Intensive Care Medicine

, Volume 36, Issue 7, pp 1147–1155

Nebulized and intravenous colistin in experimental pneumonia caused by Pseudomonas aeruginosa

  • Qin Lu
  • Cassio Girardi
  • Mao Zhang
  • Belaïd Bouhemad
  • Kamel Louchahi
  • Olivier Petitjean
  • Frédéric Wallet
  • Marie-Helene Becquemin
  • Gilles Le Naour
  • Charles-Hugo Marquette
  • Jean-Jacques Rouby
Original

DOI: 10.1007/s00134-010-1879-4

Cite this article as:
Lu, Q., Girardi, C., Zhang, M. et al. Intensive Care Med (2010) 36: 1147. doi:10.1007/s00134-010-1879-4

Abstract

Purpose

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 μg 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 μg g−1 (25–75% interquartile range = 0.8–13.7 μg 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 μg g−1, 25–75% interquartile range = 1.8–16.1 μg g−1) than in lung segments with severe pneumonia (median = 1.2 μg g−1, 25–75% interquartile range = 0.5–3.3 μg g−1) (p < 0.01). After 24 h of treatment, 67% of pulmonary segments had bacterial counts <102 cfu g−1 following nebulization and 28% following intravenous administration (p < 0.001). In control animals, 12% of lung segments had bacterial counts <102 cfu g−1 49 h following bronchial inoculation.

Conclusion

Nebulized colistin provides rapid and efficient bacterial killing in ventilated piglets with inoculation pneumonia caused by Pseudomonas aeruginosa.

Keywords

AntibioticColistinNebulizationPneumoniaPseudomonas aeruginosaMechanical ventilation

Supplementary material

134_2010_1879_MOESM1_ESM.doc (68 kb)
Supplementary material 1 (DOC 68 kb)

Copyright information

© Copyright jointly held by Springer and ESICM 2010

Authors and Affiliations

  • Qin Lu
    • 1
  • Cassio Girardi
    • 1
    • 7
  • Mao Zhang
    • 1
    • 8
  • Belaïd Bouhemad
    • 1
  • Kamel Louchahi
    • 2
  • Olivier Petitjean
    • 2
  • Frédéric Wallet
    • 3
  • Marie-Helene Becquemin
    • 4
  • Gilles Le Naour
    • 5
  • Charles-Hugo Marquette
    • 6
  • Jean-Jacques Rouby
    • 1
    • 9
  1. 1.Multidisciplinary Intensive Care Unit, Department of Anesthesiology and Critical Care MedicineLa Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, UPMC Univ Paris 06ParisFrance
  2. 2.Department of PharmacologyAvicenne Hospital, Assistance Publique-Hôpitaux de ParisBobignyFrance
  3. 3.DHURE and INSERM U 416, University School of MedicineLilleFrance
  4. 4.Explorations Fonctionelles Respiratoires UPRES 2397, La Pitié-Salpêtrière HospitalParisFrance
  5. 5.Department of PathologyLa Pitié-Salpêtrière HospitalParisFrance
  6. 6.EA4319 University Nice Sophia AntipolisNiceFrance
  7. 7.Department of AnesthesiologyFederal University of São Paulo Escola Paulista de MedicinaSão PauloBrazil
  8. 8.Department of Emergency MedicineSchool of Medicine, Second Affiliated Hospital, Zhejiang UniversityHangzhouChina
  9. 9.Réanimation Polyvalente, Département d’Anesthésie-Réanimation Hôpital Pitié-SalpêtrièreParisFrance