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Colistin, the most widely used polymyxin antibiotic, was originally introduced in the late 1950s before the establishment of the present-day drug approval process. Originally shelved due to toxicity concerns, colistin, in the form of its inactive prodrug colistin methanesulfonate, has undergone a renaissance in the past 15 years. Unfortunately, this is not because of an improved adverse-effect profile but because colistin is among the only remaining antibiotics with activity against multidrug-resistant gram-negative bacilli. Pharmacokinetic and pharmacodynamic data are limited to guide the appropriate use of colistin; however, important advances have occurred over the past 5 years. Since its reintroduction, published reports regarding colistin have produced discordant results in terms of both efficacy and safety. Because the efficacy and toxicity of colistin are dose dependent, the impact of discordant dosing recommendations cannot be understated. This review highlights the issues leading to differing and often conflicting dosing recommendations, reviews the recent pharmacokinetic advances, and provides recommendations for the optimal use of colistin. [ABSTRACT FROM AUTHOR]

Study Objective. To determine clinical and microbiologic success in patients receiving adjunctive aerosolized antibiotics for the treatment of ventilator-associated pneumonia (VAP). Design. Retrospective medical record review. Setting. Level I trauma intensive care unit of a large academic medical center. Patients. Forty-nine patients (mean ± SD age 42 ± 19 yrs) who received aerosolized antibiotics for the treatment of a total of 60 episodes of VAP caused by Pseudomonas aeruginosa and/or Acinetobacter baumannii between January 2001 and July 2007. Measurements and Main Results. Patients were identified by using an existing database of patients with documented VAP at the study center. To receive a diagnosis of VAP, patients had to have bacterial growth of 105 or more colony-forming units/ml from a bronchoscopic bronchoalveolar lavage and new or changing infiltrate on chest radiograph, plus at least two of the following: abnormal body temperature (> 38°C or < 36°C), abnormal white blood cell count (> 10 or < 4 x 10³/mm³, or > 10% immature bands), or macroscopically purulent sputum. By reviewing patient data, we evaluated clinical and microbiologic success using standard definitions. The median (interquartile range) Injury Severity Score and admission Acute Physiology and Chronic Health Evaluation II score were 40 (29-45) and 17 (9-21), respectively. Pseudomonas aeruginosa, A. baumannii, or both were isolated in 45, 14, and 1 episode(s), respectively. Eighteen VAP episodes included additional bacteria. Aerosolized tobramycin, amikacin, and colistimethate were used in 44, 9, and 9 episodes, respectively. Systemic antibiotics were used in 59 (98%) of the 60 episodes. Clinical success was achieved in 36 (73%) of the 49 first episodes of VAP, 8 (73%) of 11 subsequent episodes, 17 (85%) of 20 episodes that were failing intravenous monotherapy, and 30 (79%) of 38 episodes with multidrug-resistant P. aeruginosa or A. baumannii. Microbiologic success was achieved in 29 (71%) of 41 evaluable episodes. Six patients died from VAE Conclusion. Treatment with adjunctive aerosolized antibiotics was associated with a good response rate in critically ill trauma patients with VAP due to nonfermenting gram-negative bacilli. It is noteworthy that episodes of VAP that followed intravenous therapy failure and/or that were due to multidrug-resistant organisms responded well. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses polymyxins.