Clinical Trial: Impact of Plasma Levels of Colistin in Patients With Carbapenem Resistant Acinetobacter Baumannii Infection

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Prospective Observational Study, Impact of Plasma Levels of Colistin in Patients With Carbapenem Resistant Acinetobacter Baumannii Infection

Brief Summary: This study purposed to examine the adequate range of therapeutic concentration for Korean people by observing curative effects, side effects, blood concentration, etc. in treating CRAB-infected patients with colistin.

Detailed Summary:

Acinetobacter baumanii usually causes pneumonia and sepsis, and is susceptible to antibiotics such as ampicillin/sulbactam and carbapenem, but it easily becomes tolerant and there are few other drugs usable. Particularly in Korean patients with ventilator-associated pneumonia (VAP), the percentage of carbapenem-resistant Acinetobacter baumannii (CRAB) is increasing recently.

Colistin (polymyxin E) is antibiotic of polymyxin line used to multidrug-resistant gram-negative bacteria such as Klebsiella pneumonia, Pseudomonas aeruginosa, and Acinetobacter baumannii, and it produces bactericidal action by destroying bacterial cell membrane. Colistin was antibiotic isolated from Bacillius polymyxa subspecies colistinus first in Japan in 1949, and has long been used in clinic since 1959, but its use through intravenous infusion decreased in the 1970s due to acute kidney injury and neurotoxicity. Recently, however, it is being used more frequently for hospital infection by multidrug-resistant gram-negative bacteria and, as a result, various studies are being conducted on colistin.

Colistin consists of over 30 different polymyxin compounds including colistin A (polymyxin E1) and colistin B (polymyxin E2), and colistimethate sodium (CMS) and colistin sulfate are used. In Korea, it is usually administered intravenously in the form of CMS, which is an inactive precursor. In the body, CMS is metabolized into various metabolites including colistin or is discharged through urine. In contrast, active metabolite colistin is hardly discharged through urine, and is removed through non-renal elimination, but the accurate extracorporeal elimination mechanism is still unknown. CMS reaches the peak serum concentration in 10 minutes from intravenous administration, and its half-life is 2.2 hours while the half-life of colistin 18.5 hours.

Sponsor: DongGuk University

Current Primary Outcome: Difference in plasma drug concentration between patients with nephrotoxicity and those without [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. Nephrothoxicity was determined during colistin use. ]

- Criteria for diagnosing nephrotoxicity: Creatinine clearance (CrCL) decreases to 50% of the baseline value or serum creatinine concentration (SCr) doubles, or renal replacement therapy is required.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Difference in plasma drug concentration between patients showing clinical cure or improvement and those of treatment failure [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. Clinical outcome was determined at the final day of colistin use. ]

    Criteria for clinical cure/improvement:

    • Clinical cure: The symptoms and signs of infection have disappeared completely at the end of treatment.
    • Clinical improvement: The symptoms and signs of infection have disappeared partially at the end of treatment.
  • Difference in plasma drug concentration according to microbiological response [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. ]
    - Microbiological response: Pathogens are not cultured at the end of treatment.
  • Difference in plasma drug concentration according to in-hospital mortality [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-5wks. ]
  • Difference in plasma drug concentration according to the RIFLE Criteria for nephrotoxicity [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. ]
  • Risk factors associated with nephrotoxicity [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. ]
    Use of NSAIDS or other antibiotics, age and sex etc. associated with nephrotoxicity will be analyzed.
  • Difference in plasma drug concentration between patients with abnormality of liver function. [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3ks. ]
  • Difference in plasma drug concentration between patients with abnormality of thrombocytopenia. [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3ks. ]
  • Difference in plasma drug concentration between patients with abnormality of neuropathy. [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3ks. ]


Original Secondary Outcome: Same as current

Information By: DongGuk University

Dates:
Date Received: June 3, 2015
Date Started: May 2015
Date Completion: December 2016
Last Updated: June 23, 2015
Last Verified: June 2015