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.

Colistin 復習してみよう

以下 UpToDate とハンドサーチより


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. 
Crit. Care Med. 2015 Mar; 43(3):527-33.
The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis
  • A significant improvement in clinical response (odds ratio, 1.57; 95% CI, 1.14-2.15; p = 0.006; I2 = 37%), microbiological eradication (odds ratio, 1.61; 95% CI, 1.11-2.35; p = 0.01; I2 = 0%), and infection-related mortality (odds ratio, 0.58; 95% CI, 0.34-0.96; p = 0.04; I2 = 46%) was observed with the addition of aerosolized colistin to i.v. treatment, whereas the addition of aerosolized colistin did not affect overall mortality (odds ratio, 0.74; 95% CI, 0.54-1.01; p = 0.06; I2 = 25%) or nephrotoxicity (odds ratio, 1.18; 95% CI, 0.76-1.83; p = 0.45; I2 = 0%).
Int. J. Antimicrob. Agents 2014 Dec; 44(6):477-85.
Colistin for the treatment of ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: a systematic review and meta-analysis.
  • The clinical cure rate of colistin was comparable with that of β-lactam antibiotics (OR=1.00, 95% CI 0.68-1.47). 
  • Compared with IV colistin alone, AS plus IV colistin exhibited a better clinical cure (OR=2.12, 95% CI 1.40-3.20). 
  • Compared with colistin monotherapy, colistin combined therapy did not appear to provide a better clinical cure (OR=1.38, 95% CI 0.81-2.33).
Antimicrob. Agents Chemother. 2013 Oct; 57(10):5104-11.
Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems.
Clin. Infect. Dis. 2012 Mar 1; 54(5):670-80.
What is the efficacy and safety of colistin for the treatment of ventilator-associated pneumonia? A systematic review and meta-regression.
  • Treatment with colistin vs controls did not affect hospital mortality (OR, 0.92; 95% CI, .50-1.67; P = .78; I(2) = 34.59%) or nephrotoxicity (OR, 1.14; 95% CI, .59-2.20; P = .69; I(2) = 0%). 
Clin. Infect. Dis. 2013 Aug; 57(3):349-58.
Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.
  •  In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit.death and length of hospitalization.
J. Antimicrob. Chemother. 2010 Dec; 65(12):2645-9.
Randomized controlled trial of nebulized colistimethate sodium as adjunctive therapy of ventilator-associated pneumonia caused by Gram-negative bacteria.
  • Favourable clinical outcome was 51.0% in the CMS group and 53.1% in the control group (P = 0.84). 
J. Infect. 2008 Jun; 56(6):432-6
Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia.
  • Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group, respectively. Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS).
Colistin 耐性
J Antimicrob Chemother. 2007;59(4):786.
Colistin-resistant isolates of Klebsiella pneumoniae emerging in intensive care unit patients: first report of a multiclonal cluster.
  • Selective pressure due to extensive or inadequate colistin use may lead to the emergence of colistin resistance among K. pneumoniae isolates, jeopardizing treatment options in the ICU, potentially increasing morbidity and mortality of critically ill patients and necessitating prudent use of colistin.
Antimicrob Agents Chemother. 2011 Feb;55(2):593-9. Epub 2010 Nov 29.
Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan.
  • Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. 
  • This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission
Clin Microbiol Infect. 2013 Jan;19(1):E23-30. Epub 2012 Nov 9.
High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality.
  • In-hospital mortality was 25.8%. 
  • Multivariate analysis adjusted for appropriate treatment, combination therapy and infectious-source removal, showed that Charlson comorbidity score, intensive-care unit onset of infection, bacteraemia and infection due to a colistin-resistant CR-KP strain were independent risk factors for mortality

J Clin Microbiol. 2015 Oct;53(10):3341-4. Epub 2015 Jul 22.
Large Nosocomial Outbreak of Colistin-Resistant, Carbapenemase-Producing Klebsiella pneumoniae Traced to Clonal Expansion of an mgrB Deletion Mutant.
  • We describe a large hospital outbreak (93 bloodstream infections) of colistin-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates which was mirrored by increased colistin consumption. The outbreak was mostly traced to the clonal expansion of an mgrB deletion mutant of an ST512 strain that produced KPC-3.