Optimizing Dosing of Colistin for Infections Resistant to All Other Antibiotics, Approved NIH Protocol Dated 12.06.07(DMID Protocol #07-0036)

NCT00235690 | Completed DMC

• 2 other identifiers: IRB# 0509011NIH
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

More than 80 patients at the University of Pittsburgh Medical Center have been infected with Pseudomonas aeruginosa, lacking susceptibility to all commercially available antibiotics except "colistin". This antibiotic was developed in the 1960s and preliminary pharmacokinetic studies were performed at that time. Dosing recommendations, on the basis of these pharmacokinetic studies, are listed in the drug's product information. However, there are no dosing recommendations for patients requiring renal replacement therapy (either intermittent hemodialysis or continuous venovenous hemofiltration). Furthermore, the science of antibiotic dosing ("pharmacodynamics") has changed significantly since the 1960s and it is quite possible that the dosing recommendations listed in the product information are not optimal. Furthermore, even though physicians refer to "colistin" administration, the only intravenous form of the drug is colistin methanesulfonate (CMS). CMS is converted in the body to colistin. Both CMS and colistin have different pharmacokinetic and antimicrobial activities. For this reason, we, the investigators at the University of Pittsburgh, are performing a pilot study of the pharmacokinetics of intravenous CMS/colistin in patients requiring this antibiotic for clinical purposes. Plasma concentrations will be determined around a CMS/colistin dose once the drug has reached steady state. Concentrations in pulmonary epithelial lining fluid will also be determined in patients with pneumonia. Microbiologic and clinical endpoints will be determined and will be correlated with these concentrations. The measurement of CMS and colistin levels will be determined by a laboratory in Australia which developed these assays. A submission is being made to the National Institutes of Health (NIH) for funding of a multicenter study which will address this research question with a greater sample size. The study proposed here is a pilot study in order to prove the feasibility of the research approach and to provide preliminary data for the NIH proposal.

Conditions

Bacteremia; Pseudomonas Infections

Outcome Measures

Primary Outcomes (1)

• To provide pharmacokinetic data on intravenous (IV) CMS/colistin

  5 years

Secondary Outcomes (1)

• Determine if CMS/colistin dosing is suboptimal in ill patients

  5 years

Study Arms (1)

blood draws

OTHER

all patients enrolled will have PK blood samples obtained around a colistin dosing

Procedure: Blood draws; Other: Blood draw

Interventions

Blood draws PROCEDURE

PK samples obtained around a clinical dosing of colistin

blood draws

Blood draw OTHER

PK blood samples will be obtained around a clinical dosing of colistin

blood draws

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females greater than 18 years of age.
• All patients will remain in the hospital for pharmacokinetic sampling.
• All subjects must be on the medication colistin as part of their standard of care.
• All individuals approached for participation shall be able to read and comprehend English.

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Nation RL, Garonzik SM, Li J, Thamlikitkul V, Giamarellos-Bourboulis EJ, Paterson DL, Turnidge JD, Forrest A, Silveira FP. Updated US and European Dose Recommendations for Intravenous Colistin: How Do They Perform? Clin Infect Dis. 2016 Mar 1;62(5):552-558. doi: 10.1093/cid/civ964. Epub 2015 Nov 25.

  PMID: 26607424 DERIVED

MeSH Terms

Conditions

Bacteremia; Pseudomonas Infections

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gram-Negative Bacterial Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Fernanda Silveira, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2005
• First Posted: October 10, 2005
• Study Start: June 1, 2008
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: December 17, 2015

Record last verified: 2015-12

Locations

US (1)