1. Diamantis P. Kofteridis, Christina Alexopoulou, Antonios Valachis, Sofia Maraki, Dimitra Dimopoulou Clinical Infectious Diseases 2010; 51(11):1238–1244 R2 최은용 / Pf. 이미숙 Aerosolized plus Intravenous Colistin versus Intravenous Colistin Alone for the Treatment of Ventilator-Associated Pneumonia A Matched Case-Control Study

2. VAP morbidity and mortality in ICU MDR pathogens :polymyxins antimicrobials (polymyxin B and colistin) Colistin (IV) effectiveness pneumonia ? several reports of successful treatment Aerosolized (AS) colistin VAP due to MDR pathogens Pseudomonas aeruginosa in patients with cystic fibrosis AS plus IV colistin Vs only IV colistin MDR VAP G(-) bacterium INTRODUCTION

3. Study design Retrospective case-control matching study (ratio, 1:1) University Hospital of Heraklion 11-bed medical-surgical unit January 2005–December 2008 matching criteria: age (±5 years) APACHE II score (±4 points) Materials and Methods AS-IV colistin group 6 doses of AS therapy and 3 days of IV therapy Control patients IV colistin for 3 days

4. Definitions VAP - >intubated for 48 hr -radiographic finding + least 2 Microbiological diagnosis bronchial secretions or BAL with isolation of an MDR G(-) 10 4 CFU/mL Treatment response time of discharge from the ICU or at the end of antimicrobial therapy body temperature, >38C or < 35.5C; leukocytosis (leukocyte count, 112,000 cells/mm3) or leukopenia (leukocyte count, <4000 cells/mm3); and clinical evidence suggestive of pneumonia

5. The primary end point : clinical outcome of VAP secondary end points: we evaluated microbiological outcome, VAP-related mortality, all-cause mortality, and the occurrence of adverse events during colistin treatment. Clinical outcome : clinical cure, improvement, failure, recurrence Clinical success : clinical cure or improvement Microbiological outcome : rated as eradication, persistence, recurrence, colonization VAP-related mortality : pneumonia, septic shock Nephrotoxicity NL renal fuction: cr >2 mg/dL, crcl 50% dec., renal replacement therapy renal dysfunction : inc of >50% cr, crcl of 50%dec.

6. The following variables - cause of ICU admission; duration of ICU stay; comorbidities, including chronic lung disease, malignancy, diabetes mellitus, and renal failure; antineoplastic therapy; use of systemic corticosteroids and antibiotics 1 week prior to and/ or during the infectious episode; previous surgery; length and dosage of colistin treatment; ….

7. Microbiological Testing Susceptibility : automated broth microdilution method Susceptibility to colistin : Etest methodology (susceptibility ≤ 2 mg/L; resistance ≥ 4 mg/L) and disk diffusion method with a 10ug colistin sulfate disk MDR G(-) : susceptible only to colistin if they R to all of the 6 antipseudomonal classes of antimicrobial agents for P. aeruginosa and K. Pneumoniae R to ampicillin-sulbactam and tetracycline for A. baumanii Treatment Regimen AS colistin was 2 million international units (IU) divided into 2 doses IV colistin was 9 million IU divided into 3 doses

8. Results

12. This study : AS to IV colistin  NO therapeuticbenefit ( MDR VAP G(-)) IV Vs AS colistin ? AS+ IV: study by Korbila et al,(they did not include a control arm) AS only study : A favorable clinical outcome  current guidelines do not recommend AS colistin treatment The microbiological results showed that AS therapy had no impact on bacterial growth Clinical cure : marginal benefit  multianylsis  no bedefit Discussion

13. renal dysfunction in 19% Non required renal replacement therapy renal dysfunction rate was similar  addition of AS colistin does not cause systemic adverse events. no major toxicity of colistin AS (bronchospasm, chest tightness, or apnea) AS colistin Drawback little is known about the penetration of these agents into infected tissues from the airway lumen resistant strains inhaled antibiotics : yet none

14. First, this is a singlecenter, retrospective study with a relatively small number of patients Second, relatively few P. aeruginosa and K. pneumoniae organisms Finally, we did not monitor the volume of respiratory secretions(marker of airway inflammation) Limitations

15. In conclusion, the present study has revealed that the addition of AS colistin did not add any clinical, microbiological, or survival benefit for patients with VAP caused by gram-negative MDR pathogens susceptible only to colistin. differences between the present findings  randomized, controlled trials are needed CONCLUSION