Clinical trial NCT05862402: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Carbapenem Resistant Klebsiella Pneumoniae
Keywords: Antibiotics
Dose optimization
Clinical outcome
CRKP
Critically ill
Lead sponsor: Phramongkutklao College of Medicine and Hospital
Sponsor class: OTHER
Collaborators: name: Silpakorn University
First posted: 2023-05-17
Enrollment: 76
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective study compare historical controlled study
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mortality
timeFrame: 14 day
Secondary outcomes:
measure: Mortality
timeFrame: 30 days
measure: Microbiological cure rate
timeFrame: 14 days
measure: Hospital length of stay
timeFrame: With in 30 days
measure: ICU length of stay
timeFrame: With in 30 days
measure: Clinical cure rate
timeFrame: Through treatment completion or with in 30 days
measure: Duration of vasopressor or Inotropic agents
timeFrame: With in 30 days
measure: Duration of ventilator
timeFrame: Assessed with in 30 days
measure: Ventilator free day
timeFrame: 30 days
measure: Vasopressor or Inotropic drug free day
timeFrame: 30 days
measure: Procalcitonin
timeFrame: 14 days
measure: Adverse event
timeFrame: Day 0, 5, 7 and finish course of Antibiotics or discharge
Other outcomes:
Locations:
city: Ratchathewi
country: Thailand
facility: Phramongkutklao Hospital
state: Bangkok
Study officials:
affiliation: Faculty of Pharmacy, Silpakorn University
name: Sujareenoot Suya, PharmD
role: STUDY_CHAIR
affiliation: Faculty of Pharmacy, Silpakorn University
name: Weerayuth Saelim, BCP
role: STUDY_DIRECTOR
affiliation: Faculty of Pharmacy, Silpakorn University
name: Wichai Santimaleeworagun, PhD
role: STUDY_DIRECTOR
affiliation: Phramongkutklao College of Medicine and Hospital
name: Worapong Nasomsong, MD
role: STUDY_DIRECTOR
References: