Journal
ACS INFECTIOUS DISEASES
Volume 1, Issue 11, Pages 568-575Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.5b00085
Keywords
polymyxin; colistin; nephrotoxicity; Gram-negative bacteria; multidrug-resistance
Categories
Funding
- National Institute of Allergy and Infectious Diseases of National Institutes of Health [R01 AI098771]
- Australian National Health and Medical Research Council (NHMRC) [1026109]
Ask authors/readers for more resources
Polymyxin B and colistin are currently used as a last-line treatment for multidrug-resistant Gram-negative bacteria. However, very little is known about the pharmacological differences between polymyxin B-1 polymyxin B-2, colistin A, and colistin B, the major cyclic lipopeptide components present in polymyxin B and colistin products. Here, we report on the in vitro and in vivo antimicrobial activity and toxicity of these major lipopeptide components. All four lipopeptides had comparable minimum inhibitory concentrations (MICs) (<0.125-4 mg/L) against a panel of clinical Gram-negative isolates. They also had comparable in vivo antimicrobial activity (Delta log(10) colony forming units (CFU)/mL > -3) and nephrotoxicity (mild to moderate histological damage) in mouse models. However, polymyxin B-1, and colistin A showed significantly higher (>3-fold) in vitro apoptotic effect on human kidney proximal tubular HK-2 cells than polymyxin B-2 and colistin B, respectively. Compared to the commercial polymyxin and colistin products, the individual lipopeptide components had slightly more in vivo antimicrobial activity. Our results highlight the need to reassess pharmacopoeial standards for polymyxin B and colistin and to standardize the composition of the different commercial products of polymyxin antibiotics.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available