Prospective Observational Pilot-study for the Evaluation of the Nephro- an Neurotoxicity in the Anti-infectious Therapy With Inhalative Colistin Therapy for Patients With Ventilator-associated Pneumonia (VAP)

Study Overview
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Brief Summary
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Multi-Drug resistant pathogens (MDR) are reported worldwide with increasing incidence, especially in intensive care settings. One of the drugs which are effective against MDRs, is colistin (polymyxin E). This agent has been reintroduced in response to the increase of MDR pathogens and might be used more often in the future. Data on safety regarding the most important side effects are not sufficiently available. l This study evaluates the toxicity in patients who receive aerosolized colistin.

Detailed Description
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There is growing evidence that patients in the ICU setting have a special risk profile for consecutive colonization and possible infection due to MDR pathogens. One therapy option is the use of inhalative colistin, as this agent has been demonstrated to be effective against these pathogens. Data on pharmacodynamics or - kinetics are transferred from older studies or from other patient populations. For patients with pulmonary colonization or infection due to an MDR pathogen the systemic resorption of the drug is not known, consequently systemic side effects including kidney or neural damage are not predictable. This study focus on patients with inhalative colistin therapy and uses therapeutic drug monitoring to determine the rate of systemic resorption of colistin. For the evaluation of neurotoxicity function of peripheral nerves (neve conduction velocity) and of the eighth cranial nerve is monitored. Nephrotoxicity is estimated by creatinine level (-clearance) and the RIFLE criteria.

Official Title
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Prospective Observational Pilot-study for the Evaluation of the Nephro- an Neurotoxicity in the Anti-infectious Therapy With Inhalative Colistin Therapy for Patients With Ventilator-associated Pneumonia (VAP)

Conditions
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Infection Resistant to Multiple Drugs

Intervention / Treatment
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* Other: TDM, Monitoring of Neuro-and Nephropathology


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: invasive ventilated patients (male and female) with assumed or assured bacteria with an elevated resistance pattern found in a tracheal or bronchial secretion with or without clinical signs of infection indicated colistin co-therapy or eradication-attempt with inhalative colistin (β-Lactam) therapy according to the standard operation procedure (SOP) of the hospital Exclusion criteria: Consent of the patient or of the patient´s legal representative can´t be obtained soon Age < 18 years Included within another, prospective clinical antibiotics-study Hypersensitivity to colistin or polymyxin B Patients with cystic fibrosis Present letter of attorney or patient´s provision, which precludes a priori the participation in studies Missing consent for storage of pseudonymised data in context of the study The patient is in an institution due to a court injunction or administrative order

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Colistin inhalative<br>Adult ICU patients with invasive ventilation with assumed or assured bacteria with an elevated resistance pattern found in a tracheal or bronchial secretion with or without clinical signs of infection indicated colistin co-therapy or eradication-attempt with inhalative colistin (β-Lactam) therapy according to the standard operation procedure (SOP) of the hospital Patients included into the study group receive additional TDM, Monitoring of Neuro-and Nephropathology | Other: TDM, Monitoring of Neuro-and Nephropathology<br>* Therapeutic drug monitoring of serum levels and Monitoring of Neuro- and Nephropathology<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy) | Adverse events are measured based on validated criteria: creatinine-clearance and RIFLE-criteria Neuromonitoring (nerve conduction velocity, EEG) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of colistin and β-Lactam antibiotics | Colistin-concentration in serum following inhalative therapy (in mg/L) 2 hours and 8 hours of application and in steady state on day 3 of therapy | 3 days | 
| Serum levels of colistin and β-Lactam antibiotics (e.g. Meropenem)in mg/L | Serum drug levels in mg/L 2hours, 8 hours and 3 days (steady state) after therapy induction | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colistin, MDR, inhalative therapy