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Intratracheal colistin sulfate for BALB/c mice with early pneumonia caused by carbapenem-resistant Acinetobacter baumannii

Chiang, Shyh-Ren MD; Chuang, Yin-Ching MD; Tang, Hung-Jen MD; Chen, Chi-Chung MS; Chen, Chung-Hua MD; Lee, Nan-Yao MD; Chou, Chen-His PhD; Ko, Wen-Chien MD

doi: 10.1097/CCM.0b013e3181a0f8e1
Laboratory Investigations

Objectives: To study the efficacy of intratracheal colistin sulfate therapy in a murine model of acute pneumonia caused by a clinical CRAB strain, Ab396. Colistin therapy has currently achieved a favorable outcome in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections, but parenteral colistin may have limited therapeutic efficacy for CRAB pneumonia.

Design: A controlled, in vivo experimental study.

Setting: Research laboratory of a medical center.

Subjects: Female BALB/c mice.

Interventions: The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 × 107 colony-forming units Ab396 plus 10% porcine mucin into the lungs of mice, verified by histopathological examinations, and then treated with or without antibiotics. Mice received intratracheal saline treatment as a control group, intraperitoneal administration (IP) imipenem/cilastatin plus sulbactam (IP IS group, 80/80 mg/kg and 40 mg/kg every 8 hrs, n = 30), IP colistin sulfate (IP CS group, 150,000 U/kg every 8 hrs, n = 30), and intratracheal colistin sulfate (intratracheal CS group, 75,000 U/kg every 8 hrs, n = 30) at 2 hrs after intratracheal inoculation of Ab396.

Measurements and Main Results: The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 μg/mL, 128 μg/mL, or 32 μg/mL, respectively. Compared with the mice in the control, IP IS, and IP CS groups, those in intratracheal CS group had a significantly favorable outcome at 72 hrs after infection (survival rate = 0%, 10%, 0% and 100%, respectively; all p < .001, log-rank test). Furthermore, intratracheal therapy decreased significantly the bacterial loads in the lungs and normalized the wet lung/body weight ratios in mice with acute pneumonia.

Conclusions: The intratracheal colistin sulfate therapy led to more favorable outcomes than therapies by IP colistin sulfate or imipenem/cilastatin plus sulbactam in mice with early CRAB pneumonia.

From the Departments of Internal Medicine (S-RC, Y-CC, H-JT) and Medical Research (Y-CC, C-CC), Chi Mei Medical Center, Tainan, Taiwan; Department of Medicine (C-HChen), En Chu Kong Hospital, Taipei County, Taiwan; and the Department of Internal Medicine (N-YL, W-CK), Institute of Clinical Pharmacy (C-HChou), National Cheng Kung University Hospital, Tainan, Taiwan.

The authors have not disclosed any potential conflicts of interest.

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© 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins