Investigation of the Correlation Between Plasma Concentration of Linezolid Antibiotic and Treatment Response and Adverse Reactions

NCT ID: NCT03126890

Last Updated: 2022-02-10

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-11-01
• Study Completion Date: 2023-12-31

Brief Summary

Linezolid is the second line agent in the treatment of MRSA and PRSP infections, and it is also the drug of choice for VRE infections. It can be an alternative option against multidrug resistant tuberculosis and non-tuberculosis mycobacterium. However, Patients who receive more than 2 weeks of treatment duration and who have renal dysfunction or severe cirrhosis may prone to experience anemia, thrombocytopenia, and leukopenia. Long-term use may also result in lactic acidosis, peripheral neuropathy and optic neuropathy due to mitochondrial toxicity. Thus, this study will analysis the medical charts in National Taiwan University Hospital (NTUH) from 2011 to 2016 to get the population demographics who use linezolid and analysis the occurrence rate of myelosuppression, neuropathy and lactic acidosis. Simultaneously, the investigators also use therapeutic drug monitoring (TDM) to prospectively evaluate the association of linezolid blood concentration and clinical efficacy and safety. The result of this study will provide physicians more information to prevent concentration-dependent adverse effects.

Detailed Description

The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP) has caused significant medical issue. With limited antimicrobial agents available, it has been an increasing challenge in infection control and disease treatment. Linezolid is the second line antibiotics in the treatment of MRSA and PRSP infections, and it is also the drug of choice for VRE infections. It can be an alternative against multidrug resistant tuberculosis and non-tuberculosis mycobacterium. Linezolid has almost 100% of bioavailability. It has excellent tissue penetration. It metabolized via non-enzymatic oxidation. Two major metabolites, aminoethoxyacetic acid (chemical name) and hydroxyethyl glycine (chemical name), are final forms before excreted through kidneys. Even though the manufacturer does not recommend dosing adjustment for patients with renal or hepatic dysfunction, recent studies demonstrated accumulation of linezolid and 2 metabolites in the body. Patients who receive more than 2 weeks of treatment duration and who have renal dysfunction or severe cirrhosis may present higher plasma linezolid concentration. Patients may experience anemia, thrombocytopenia, and leukopenia under long-term use of linezolid. However, there is lack of study on lactic acidosis, peripheral neuropathy, and optic neuropathy due to mitochondrial toxicity.

This study has two parts. This study will analysis the medical charts in NTUH from 2011 to 2016 to get the population demographics who use linezolid and the occurrence rate of myelosuppression, neuropathy and lactic acidosis. Then, followed by a prospective study which aim is to monitor the plasma peak and trough concentration of linezolid (total and free drug) and 2 metabolites by different sample collecting method (plasma, dry blood spot; DBS). If clinical necessity, the investigators may also monitor tissue fluid concentration. Clinical response and toxicity were monitored by liquid chromatography (LC) analysis. The investigators plan to evaluate the association between plasma concentration and toxicity including bone marrow suppression, peripheral neuropathy, and lactic acidosis. It is important to determine if dose adjustment in patients with renal and/or hepatic dysfunction is required. Simultaneously, the investigators want to develop DBS method which can ease patients' uncomfortable sense and simplify the drug monitor process. The result of this study will provide physicians more information to prevent concentration-dependent adverse effects.

Conditions

Myelosuppression; Lactic Acidosis; Peripheral Neuropathy

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Linezolid TDM (prospective)

Adult patients received linezolid at NTUH. This prospective cohort study will draw blood from every patient to measure the linezolid blood concentration. After blood concentration analysis by high pressure liquid chromatography (HPLC), the investigator will report the concentration to clinicians and dose adjustment is judged by clinician (not the investigators).

No interventions assigned to this group

Linezolid observation (retrospective)

Adult patients received linezolid at NTUH.

No interventions assigned to this group

Eligibility Criteria

Exclusion Criteria

Retrospective study 1. Patients without baseline complete blood count (CBC) data (RBC or Hb, WBC, platelet) before linezolid treatment. Prospective study

1. Patients with severe disease status (assess by clinicians) might die within 2 days or treatment duration less than 2 days

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shu-Wen Lin

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University Hospital

Locations

National Taiwan University Hospital

Taipei, Test2, Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Shu-Wen Lin, Pharm.D

Role: CONTACT

shuwenlin@ntu.edu.tw

886-2-33668782

Facility Contacts

Shu-Wen Lin

Role: primary

shuwenlin@ntu.edu.tw

02 - 33668782

Other Identifiers

201610008RINB

Identifier Type: -

Identifier Source: org_study_id