Colistin and polymyxin B have indistinguishable microbiological activity in vitro, but they differ in the form administered parenterally to patients. Polymyxin B is administered directly as the active antibiotic, whereas colistin is administered as the inactive prodrug, colistin methanesulfonate (CMS). CMS must be converted to colistin in vivo, but this occurs slowly and incompletely. Here we s...

OBJECTIVES Colistin susceptibility in Pseudomonas aeruginosa is associated with a lipopolysaccharide (LPS) structure that is controlled by the modulation of several two-component regulatory systems. In this study, we attempted to elucidate the role of these two-component systems in the development of colistin resistance in P. aeruginosa. METHODS pmrA-, phoP-, parR- or cprR-inactivated mutants...

Increasing antibiotic resistance in gram-negative bacteria has recently renewed interest in colistin as a therapeutic option. The increasing use of colistin necessitates the availability of rapid and reliable methods for colistin susceptibility testing. We compared seven methods of colistin susceptibility testing (disk diffusion, agar dilution on Mueller-Hinton [MH] and Isosensitest agar, Etest...

The antimicrobial activities of colistin and other antibiotics against clinical Acinetobacter baumannii and the mutant prevention concentration (MPC) of colistin against multidrug-resistant A. baumannii were studied. All 70 stains tested were sensitive to colistin. The MPC range of colistin against 30 multidrug-resistant A. baumannii stains was approximately 32 to >128 microg/ml, and the MPC at...

Colistin use has increased in response to the advent of infections caused by multidrug-resistant organisms. It is administered parenterally as an inactive prodrug, colistin methanesulfonate (CMS). Various formulations of CMS and labeling conventions can lead to confusion about colistin dosing, and questions remain about the pharmacokinetics of CMS. Since CMS does not have strong UV absorbance, ...

Dear Editor, Colistin is the last line of defense for carbapenem-resistant Enterobacteriaceae (CRE) or Acinetobacter baumannii infection [1]. Recently, a plasmid-mediated colistin resistance mechanism (mcr-1 gene) was identified in human, animal, and environmental isolates in China, and the worldwide spread of the mcr-1 gene has continuously been reported [2]. This colistin resistance mechanism...

OBJECTIVES The use of colistin in the treatment of life-threatening Gram-negative infections is associated with a high rate of nephrotoxicity that is dose limiting. This study aimed to examine the nephroprotective effect of ascorbic acid against colistin-induced nephrotoxicity. METHODS Rats were treated intravenously twice daily with saline, colistin (cumulative dose of 36.5 mg/kg), a combina...

BACKGROUND The most important concern with polymyxins (Colistin and Polymyxin B) use is nephrotoxicity. There is no prospective data comparing nephrotoxicity of these two drugs, when administered in high doses and as per current recommendations. We conducted a prospective study to compare their trend of nephrotoxicity in our patient population. METHODS Our study included adult ICU patients wh...

To the Editor—In an article recently published in the Journal, Lopez-Rojas et al [1] demonstrated that an in vitro mutant of Acinetobacter baumannii resistant to colistin had reduced in vivo fitness and decreased virulence, in terms of both mortality and survival, in a mouse model of peritoneal sepsis. They suggest that the lower in vivo bacterial fitness and decreased virulence of this mutant ...

OBJECTIVES Colistin resistance in Acinetobacter baumannii has been associated with loss of virulence and a negative impact on isolate selection. In this study, exposure of clinical isolates to suboptimal concentrations of colistin was used to explore the capacity to develop resistance by diverse mechanisms, and whether acquired resistance always reduces fitness and virulence. METHODS Twelve c...