Characteristics and Outcomes of Patients Treated with Intravenous Colistin for Multidrug-Resistant Gram-Negative Bacterial Infections

Background: Multidrug-resistant (MDR) Gram-negative rod (GNR) infections are emerging in hospitals with increasing frequency. Some of these bacteria are resistant to all commonly used antibiotics with the possible exception of the polymyxins. Accordingly, colistin (polymyxin E), which was shelved in the 1970s because it was considered more nephrotoxic than the aminoglycosides, is being increasingly utilized as the only treatment option for some severe GNR infections. Many doctors and pharmacists have little or no experience using this potentially life-saving yet also potentially toxic antibiotic.

Objective: To describe the characteristics and outcomes of patients treated with intravenous (IV) colistin.

Methods: Retrospective cohort study of all patients treated with IV colistin at two Midwestern hospitals, one a county hospital with a burn unit and level 1 trauma center and the other a university, tertiary care hospital, both affiliated with the same medical school.

Results: During the study period 120 patients were treated with IV colistin. The trend over time increased from 3 in 2001 to 27 in 2008. The mean (SD) age of the patients was 44 (15) years with 25% being non-white and 39% female. Thirty-eight percent were burn patients, 12% were cystic fibrosis (CF) patients, and 50% other. Sixteen percent of patients had severe hypotension, and 65% were mechanically ventilated. The mean predicted mortality rate from the MPM II score on the colistin start date was 21%. Twelve percent of patients received colistin empirically, whereas 88% received it based on a positive culture result, with Acinetobacter (n=92) and/or Pseudomonas (n=39) accounting for all cases. Types of infections included bacteremia (48%), wound (40%), pneumonia (23%), and urinary tract (17%). The mean (SD) length of colistin therapy was 14 (13) days with a range of 68 days. The mean creatinine (Cr) at start of therapy was 1.2 mg/dL, mean peak Cr 2.0 mg/dL, and mean Cr at end of therapy 1.6 mg/dL. The mean (SD) change in Cr was 0.8 (1.0) mg/dL with a range of 6.0 mg/dL. Severe renal dysfunction was associated with longer duration of colistin therapy. The majority of patients with a significant rise in Cr (normal to >3.0 mg/dL) were on colistin for >14 days. Hospital mortality was 29% with significant differences between burn patients (27%), CF patients (7%), and other patients (36%).

Conclusions: MDR Acinetobacter and MDR Pseudomonas were the predominant indications for IV colistin in this study. Empiric use was uncommon. Mild to moderate renal dysfunction often occurred during therapy but appeared to trend back toward baseline by end of therapy. Severe renal dysfunction was unusual. The mortality of patients treated with IV colistin was very high, likely reflecting the severity of the underlying infections and co-morbidities. CF patients treated with IV colistin had lower hospital mortality compared to other patients.