Dose Optimization by Pharmacokinetic/Pharmacodynamic of Antibiotics to Improve Clinical Outcome of Carbapenem Resistant Klebsiella Pneumoniae Bloodstream Infections in Critically Ill Patients at Phramongkutklao Hospital

Phase 4

Recruiting

• Conditions: Carbapenem Resistant Klebsiella Pneumoniae
• Interventions: Drug: Dose-adjustment by PKPD

• Registration Number: NCT05862402
• Lead Sponsor: Phramongkutklao College of Medicine and Hospital

Brief Summary

The patients who infected with Carbapenem resistant Klebsiella pneumoniae were high mortality rate. Appropriate antibiotics therapy adjusted by Pharmacokinetic/Pharmacodynamic plays an important role in determining outcomes in Critically ill patients. Consequently, standard antibiotics dose may not be adequate to achieve pharmacokinetic/pharmacodynamic target in Critically ill patients. The purpose of this study is to compare the clinical outcomes between the critically ill patients who received antibiotics dose adjusted by pharmacokinetic/pharmacodynamic using Monte Carlo simulation and historical critically ill patients who received antibiotics from standard practice.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-04
• Study First Submitted: 2023-04-26
• Study Start: 2023-05-07
• Study First Submitted QC: 2023-05-07
• Last Update Submitted: 2023-05-07
• Study First Posted: 2023-05-17
• Last Update Posted: 2023-05-17
• Primary Completion: 2024-05-31
• Study Completion: 2024-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

1. 20 years and older who admitted at Phramongkutklao Hospital

2. Patients who was diagnosed blood stream infection with CRKP between April 10th, 2023 to March 31st, 2024 (Prospective study) and January 1st, 2012 to March 31st, 2023 (Retrospective study); Historical group

3. Patients who had signs and symptoms at least 1 criteria following:

   3.1. Patients who had signs and symptoms of Systemic Inflammatory Response Syndrome (SIRS) at least 2 criteria:

   • Temperature above 38 oC or below 36 oC
   • Heart rate more than 90 beats/min
   • Respiratory rate more than 20 /min or PaCO2 less than 32 mmHg (4.3 kPa)
   • White blood cell more than 12,000 cell/mm3 or less than 4,000 cell/mm3 3.2. Patients who was diagnosed sepsis or SOFA score or qSOFA score at least 2 score 3.3. Patients who was diagnosed septic shock or who had hypotension with adequate fluid and need for vasopressor to maintain mean arterial pressure over 65 mmHg and serum lactate above 2 mmol/L

4. Patients who received antibiotics at least 48 hours which are as follow:

   • Ceftazidime-Avibactam or
   • Combination antibiotics (eg. Meropenem-Colistin, Imipenem-Colistin, Tigecycline-Amikacin, Tigecycline- Gentamicin, Tigecycline-Meropenem or Tigecycline-Colistin)

Exclusion Criteria

1. Patients who were pregnancy or breastfeeding
2. Patients who had drug allergy (eg. Ceftazidime-Avibactam, Tigecycline, Amikacin, Gentamicin, Imipenem, Meropenem or Colistin)
3. Patients who not to received resuscitation.
4. Patients who were end stage cancer.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Dose-adjustment by PKPD	Dose antibiotics adjusted by pharmacokinetic and pharmacodynamic using Monte Carlo simulation

Primary Outcome Measures

Name	Time	Method
Mortality	14 day	Alive or death

Secondary Outcome Measures

Name	Time	Method
Mortality	30 days	Alive or death
Duration of ventilator	Assessed with in 30 days	Time interval (day) of ventilator
Ventilator free day	30 days	Day alive and free of ventilator
Vasopressor or Inotropic drug free day	30 days	Day alive and free of vasopressor or inotropic drug
Microbiological cure rate	14 days	Evaluated culture of bloodstream
Hospital length of stay	With in 30 days	Time interval (day) from hospital admission (after enrolled) to hospital discharge or death from any cause
ICU length of stay	With in 30 days	Time interval (day) from ICU admission (after enrolled) to ICU discharge or death from any cause
Clinical cure rate	Through treatment completion or with in 30 days	Evaluated sign and symptoms of infection or culture no growth
Duration of vasopressor or Inotropic agents	With in 30 days	Time interval (day) from time of vasopressor or Inotropic agents initiation to time to vasopressor or Inotropic agents discontinuation
Procalcitonin	14 days	Evaluated serum procalcitonin
Adverse event	Day 0, 5, 7 and finish course of Antibiotics or discharge	Evaluated side effect (eg. seizure, liver impairment, renal impairment)

Trial Locations

Locations (1)

Phramongkutklao Hospital; 🇹🇭 Ratchathewi, Bangkok, Thailand