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

• Published in: Critical care medicine Vol. 37; no. 9; p. 2590
• Main Authors: Chiang, Shyh-Ren, Chuang, Yin-Ching, Tang, Hung-Jen, Chen, Chi-Chung, Chen, Chung-Hua, Lee, Nan-Yao, Chou, Chen-His, Ko, Wen-Chien
• Format: Journal Article
• Language: English
• Published: United States 01.09.2009
• Subjects: Acinetobacter baumannii - drug effects; Acinetobacter Infections - drug therapy; Animals; Anti-Bacterial Agents - administration & dosage; Carbapenems - pharmacology; Colistin - administration & dosage; Disease Models, Animal; Drug Resistance, Bacterial; Female; Mice; Mice, Inbred BALB C; Pneumonia, Bacterial - drug therapy; Pneumonia, Bacterial - microbiology; Time Factors; Trachea
• ISSN: 1530-0293
• DOI: 10.1097/CCM.0b013e3181a0f8e1

: 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. : A controlled, in vivo experimental study. : Research laboratory of a medical center. : Female BALB/c mice. : The minimal inhibitory concentrations of antibiotics were measured. Acute pneumonia was established by intratracheal inoculation with an inoculum size of 2.5 x 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. : The minimal inhibitory concentrations of colistin sulfate, imipenem/cilastatin, or sulbactam for Ab396 were 2 microg/mL, 128 microg/mL, or 32 microg/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. : 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.