Acinetobacter Infections Clinical Trial
Official title:
Prospective Observational Study, Impact of Plasma Levels of Colistin in Patients With Carbapenem Resistant Acinetobacter Baumannii Infection
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.
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.
With regard to the bactericidal activity of colistin, the unbound area under the
concentration-time curve/minimum inhibitory concentration (fAUC/MIC) is important, and
adequate exposure to the drug has been known to be important for curative effect, but it is
still controversial what the optimal dose and interval are. Although the drug has been used
long, the accurate measuring of colistin blood concentration became possible only in the mid
2000s and, therefore, pharmacokinetic research on the drug has been conducted relatively
recently and there is increasing interest in the validity of established uses, adequate uses,
therapeutic drug monitoring, etc. Two of the established uses of the drug are intravenous
administration of 2.5~5mg/kg/day divided into 2~4 times to patients with normal renal
function, adjusting the dose and interval of administration according to renal function
(package insert), and the administration of loading dose followed by 2~3 times of
administration depending on renal function. The major side effects of colistin are
nephrotoxicity and neurotoxicity, and according to a recent study, the incidence of
nephrotoxicity caused by colistin was 30~60%. Renal insufficiency is more frequent when
vancomycin is used together in VAP. Renal insufficiency is known to be reversible, but some
cases require dialysis. Known risk factors of renal insufficiency include cumulative CMS
dose, combined use of drugs inducing renal insufficiency, female, and age.
There have been ex vivo studies for assessing the bactericidal effect of colistin for
exploring its adequate uses and case studies for evaluating the risk factors of
nephrotoxicity, one of the major side effects yet there are still controversial issues
related to the drug. Furthermore, as most of these studies were conducted with Western
subjects, their results are hardly applicable to Koreans as they are. Thus, this study
purposed to examine the adequate range of therapeutic concentration for Korean people.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02688322 -
Pharmacodynamics Modeling to Optimize Dosage Regimens of Sulbactam in Patients With Acinetobacter Infections
|
Phase 4 | |
Completed |
NCT03622918 -
Colistin-rifampin Combination and Colistin Monotherapy in Extensively Drug-resistant Acinetobacter Baumannii
|
N/A | |
Enrolling by invitation |
NCT05880069 -
Clinical Outcomes in Patients With Infection by Resistant Microorganism
|
||
Completed |
NCT00524563 -
Clinical Outcomes and Global Epidemiology -Data Coordinating Center
|
||
Terminated |
NCT05210387 -
Seven Versus 14 Days of Antibiotic Therapy for Multidrug-resistant Gram-negative Bacilli Infections
|
N/A | |
Completed |
NCT02573064 -
Impact of Treatment With Colistin on Mortality Bacteremia Multiresistant Acinetobacter Baumannii Sensitive Colistin in Patients Critical
|
N/A | |
Recruiting |
NCT05586815 -
Efficacy of Colistin Monotherapy Versus Colistin Plus Minocycline for Carbapenem-Resistant A. Baumannii Infection
|
Phase 4 | |
Completed |
NCT00524290 -
Multinational Study of Acinetobacter Bloodstream Infection: Clinical Outcomes and Global Epidemiology-PITT Protocol
|
||
Completed |
NCT00462579 -
Risk Factors for Carbapenem-resistant Acinetobacter Baumannii
|