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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Carbapenem Resistant Klebsiella Pneumoniae
• Intervention / Treatment: Drug: Dose-adjustment by PKPD

• Study Type: Interventional
• Enrollment (Anticipated): 76
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sujareenoot Suya, PharmD; Phone Number: 66814738170; Email: Auensujareenoot@gmail.com
• Study Contact Backup: Name: Weerayuth Saelim, BCP; Phone Number: 66891705954; Email: Saelim_w6@su.ac.th

Study Locations

• Thailand
  • Bangkok
    • Ratchathewi, Bangkok, Thailand, 10400
      • Recruiting
      • Phramongkutklao Hospital
      • Contact: Sujareenoot Suya, PharmD; Phone Number: 66814738170; Email: Auensujareenoot@gmail.com
      • Contact: Weerayuth Saelim, BCP; Phone Number: 66891705954; Email: Saelim_w6@su.ac.th
      • Principal Investigator: Sujareenoot Suya, PharmD
      • Principal Investigator: Weerayuth Saelim, BCP
      • Sub-Investigator: Wichai Santimaleeworagun, PhD
      • Sub-Investigator: Worapong Nasomsong, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Dose antibiotics adjusted by pharmacokinetic and pharmacodynamic using Monte Carlo simulation	Drug: Dose-adjustment by PKPD; Dose-adjustment by pharmacokinetic and pharmacodynamic using Monte Carlo simulation; 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; Dose antibiotics from standard care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Phramongkutklao College of Medicine and Hospital
• Collaborators: Silpakorn University
• Investigators: Study Chair: Sujareenoot Suya, PharmD, Faculty of Pharmacy, Silpakorn University; Study Director: Weerayuth Saelim, BCP, Faculty of Pharmacy, Silpakorn University; Study Director: Wichai Santimaleeworagun, PhD, Faculty of Pharmacy, Silpakorn University; Study Director: Worapong Nasomsong, MD, Phramongkutklao College of Medicine and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): May 7, 2023
• Primary Completion (Anticipated): May 31, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: April 26, 2023
• First Submitted That Met QC Criteria: May 7, 2023
• First Posted (Actual): May 17, 2023

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Antibiotics; Clinical outcome; Critically ill; Dose optimization; CRKP
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Sepsis; Pneumonia; Critical Illness; Klebsiella Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Protein Synthesis Inhibitors; Antitubercular Agents; beta-Lactamase Inhibitors; Anti-Bacterial Agents; Antibiotics, Antitubercular; Gentamicins; Imipenem; Tigecycline; Meropenem; Colistin; Avibactam; Amikacin; Ceftazidime
• Other Study ID Numbers: PMK-0008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No