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

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

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21 Citations (Scopus)

Abstract

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 × 10 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.

Original languageEnglish
Pages (from-to)2590-2595
Number of pages6
JournalCritical care medicine
Volume37
Issue number9
DOIs
Publication statusPublished - 2009 Sep

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

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