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

Phramongkutklao College of Medicine and Hospital

Status and phase: Enrolling; Phase 4

Conditions: Carbapenem Resistant Klebsiella Pneumoniae

Treatments: Drug: Dose-adjustment by PKPD

Study type: Interventional

Funder types: Other

Identifiers

NCT05862402

PMK-0008

Details and patient eligibility

About

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.

Enrollment: 76 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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76 participants in 2 patient groups

Intervention group

Experimental group

Description:

Dose antibiotics adjusted by pharmacokinetic and pharmacodynamic using Monte Carlo simulation

Treatment:

Drug: Dose-adjustment by PKPD

Control group

No Intervention group

Description:

Dose antibiotics from standard care