akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.


日本生まれ colistin

現代の最終兵器 colistin

でも耐性菌いるよ colistin
耐性菌どうなる⁉︎ 世界がビビる colistin
尿MDRP 保菌患者の侵襲高い尿路手術にコリスチン予防投与必要性を、紹介先の大学病院 (自施設で手術嫌だとの理由で紹介…)、尊敬する感染症内科の先生を含めて議論しましたが、使用は難しいと決断。手術出来ませんでした。


It was first isolated in Japan in 1949 from Bacillus polymyxa var. colistinus and became available for clinical use in 1959 
Colistin, or polymyxin E, is a bactericidal drug that disrupts the outer cell membrane of gram-negative rods and is primarily used for infections with Pseudomonas aeruginosa and Acinetobacter baumannii.
Acquired resistance to colistin is uncommon. However, certain gram-negative rods are intrinsically resistant. These include Burkholderia cepacia, Serratia marcescens, Moraxella catarrhalis, Proteus spp, Providencia spp, and Morganella morganii. Penetration of colistin into the cerebrospinal fluid is low when administered intravenously.
Colistin is formulated as colistimethate sodium for reconstitution for parenteral use. It is measured as grams of colistin base activity in the United States and as international units of colistimethate sodium in Europe. The recommended dosage varies by formulation and manufacturer. Dose adjustments should be made in the setting of renal dysfunction.
We do not routinely use inhaled colistin for gram-negative pneumonia, although it may be a useful adjunctive therapy in select multidrug-resistant cases. If used, it should be done with caution and must be mixed immediately prior to administration. 
The incidence of renal toxicity ranges from 8 to 58 percent, and renal impairment appears to be reversible. Neurologic toxicity, mainly paresthesias, is also associated with colistin. 
Resistance to colistin is relatively uncommon, although there have been increasing reports of colistin resistance in carbapenem-resistant gram-negative bacilli. Furthermore, the identification of plasmid-mediated resistance to colistin raises the possibility of widespread dissemination of resistance.
There are no standardized methods for colistin susceptibility testing. The broth microdilution method is preferred for susceptibility testing. E-testing correlates well with broth microdilution at low minimum inhibitory concentrations (MIC between 0.25 and 1 mg/mL) but less reliably at more extreme dilutions. The disk diffusion method cannot be used to test for resistance since polymyxins diffuse poorly in agar. Agar dilution and Vitek2 have also been used, but their reliability is unproven.
The mechanism of colistin resistance is poorly defined. Overexpression of outer membrane proteins such as OprH, induced by acidic, low-magnesium environments, appears to play a significant role. In addition, resistance has been associated with a reduction in the net negative charge of the lipid A component of LPS that reduces binding of positively charged colistin; these changes have in some cases been mediated by chromosomal mutations in the PmrAB two-component regulatory system, which affects cellular metabolism. Heteroresistance to colistin has been demonstrated in vitro.
Plasmid-mediated resistance to colistin due to an enzyme that modifies lipid A, which can be transferred in vitro to other bacterial genera, has also been described, prompting concerns that colistin resistance could become more widespread. In a study from China, a plasmid gene associated with in vitro colistin resistance was first identified through surveillance of E. coli isolated from food animals, and in 2014, was identified in 16 of 1322 clinical isolates (1.2 percent) from hospitalized patients with Enterobacteriaceae infections.
Antimicrob Agents Chemother. 2011 Feb;55(2):593-9. Epub 2010 Nov 29.
J Clin Microbiol. 2015 Oct;53(10):3341-4. Epub 2015 Jul 22.
Clin Microbiol Infect. 2013 Jan;19(1):E23-30. Epub 2012 Nov 9.
J Antimicrob Chemother. 2007;59(4):786.