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

Study Overview
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Brief Summary
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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.

Official Title
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Dose Optimization by PK/PD of Antibiotics to Improve Clinical Outcome of CRKP Bloodstream Infections in Critically Ill Patients and in Vitro Study of Monotherapy, Combination Therapy and Molecular Biology of Drug Resistance at Phramongkutklao Hospital: Prospective, Historical Controlled Study

Conditions
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Carbapenem Resistant Klebsiella Pneumoniae

Intervention / Treatment
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* Drug: Dose-adjustment by PKPD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20 years and older who admitted at Phramongkutklao Hospital 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 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 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: Patients who were pregnancy or breastfeeding Patients who had drug allergy (eg. Ceftazidime-Avibactam, Tigecycline, Amikacin, Gentamicin, Imipenem, Meropenem or Colistin) Patients who not to received resuscitation. Patients who were end stage cancer.

Ages Eligible for Study
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Minimum Age: 20 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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective study compare historical controlled study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>Dose antibiotics adjusted by pharmacokinetic and pharmacodynamic using Monte Carlo simulation | Drug: Dose-adjustment by PKPD<br>* Dose-adjustment by pharmacokinetic and pharmacodynamic using Monte Carlo simulation<br>* Other names: Antibiotics: Ceftazidime-Avibactam or Combination antibiotics (eg. Meropenem-Colistin, Imipenem-Colistin, Tigecycline-Amikacin, Tigecycline-Gentamicin, Tigecycline-Meropenem or Tigecycline-Colistin);|
| No Intervention: Control group<br>Dose antibiotics from standard care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Alive or death | 14 day | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotics, Dose optimization, Clinical outcome, CRKP, Critically ill