Optimizing Antibiotic Dosing Regimens for the Treatment of Infection Caused by Carbapenem Resistant Enterobacteriaceae

Not Applicable

• Conditions: Critical Illness; Sepsis; Carbapenem-Resistant Enterobacteriaceae Infection; Septic Shock; Clinical Outcomes; Treatment Outcomes; Drug Resistance
• Interventions: Other: Standard antibiotic regimens; Other: Combined antibiotic regimens

• Registration Number: NCT04516395
• Lead Sponsor: Phramongkutklao College of Medicine and Hospital

Brief Summary

The purpose of this study is to evaluate the treatment outcomes in patients with CRE infections.

Detailed Description

Antibiotic resistance is one of the major problems because of global burden. Resistant pathogens are non-susceptible to available antibiotics, causing of high clinical mortality (clinical impact) and high budget (economic impact), whereas new antibiotics in drug development are fewer. Carbapenem-Resistant Enterobacteriaceae (CRE) are categorized into one of the critical groups in World Health Organization's lists. In Thailand, the spread of CRE have been risen continuously since 2011.

Diverse actions are designed to address antibiotic resistance with limited resources, known as antimicrobial stewardship programs (ASPs). Dose-optimization by using PK/PD (Pharmacokinetics/Pharmacodynamics) application is recommendation of supplemental strategies in clinical routine practice. The benefit of the strategy is to reduce inappropriate antibiotic use and provide minimum resistance as well as maximum the success of clinical treatment.

Antibiotic combination regimens have a role for the CRE treatment. However, current evidence in clinical study is not concluded which the best or optimal combined antibiotics are. The reasons may be that combined antibiotics often vary among different sites of infection, causative pathogens, the patterns of local antimicrobial susceptibility and patient comorbidity. As the results, the antibiotic combination regimens for the treatment any infections caused by CRE is needed for further investigation. The anticipated result is to fill the limited data of the appropriate antibiotic regimens for individual Thai patients.

Study Timeline

• Study First Submitted: 2020-07-20
• Status Verified: 2020-08
• Study First Submitted QC: 2020-08-14
• Study First Posted: 2020-08-18
• Last Update Submitted: 2020-08-22
• Last Update Posted: 2020-08-26
• Study Start: 2020-09
• Primary Completion: 2021-03
• Study Completion: 2021-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

1. Any patients are diagnosed any diseases caused by CRE infection by physicians at Phramongkutklao hospital during 1/4/2018 to 30/4/2021.

2. Any patients are more than 18 years old.

3. Any patients have at least 1 criterion as following 3.1 Any patients have at least 2 of the signs and symptoms of Systemic inflammatory response syndrome (SIRS), including

   • Fever (temperature > 38 °C) or hypothermia (temperature < 36°C)
   • Tachypnea (heart rate > 90 beats per minute)
   • Respiratory rate > 20 beats per minute or Paco2 < 32 mm Hg (4.3 kPa)
   • White blood cell count > 12,000 cells per millilitre (leukocytosis) or < 4,000 cells per milliliter (leukopenia) 3.2. Any patients are diagnosed with sepsis or have ≥ 2 points of Sequential Organ Failure Assessment (SOFA) Score or qSOFA (Quick SOFA) Score.

3.3. Any patients are diagnosed with septic shock or are received vasopressors (eg, dopamine, norepinephrine, epinephrine, vasopressin, phenylephrine), mean arterial pressure (MAP) < 65 mm Hg, and lactate > 2 mmol/L (18 mg/dL) 3.4 Any patients are received mechanical ventilation 3.5 Any patients are admitted at ICU ward.

Exclusion Criteria

1. Patients are breast-feeding or pregnancy.
2. Patients are insufficient or incomplete information on the medical electronic record such as patients transferred.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Standard antibiotic regimens	Standard antibiotic regimens	The patients in the groups will be given the standard antibiotic regimens.
Optimal antibiotic combination regimens	Combined antibiotic regimens	The patients in the groups will be given the optimal antibiotic combination regimens.

Primary Outcome Measures

Name	Time	Method
Clinical improvement or failure	up to 8 weeks	* Clinical improvement was defined as resolution of the signs and symptoms of the infection with no change or addition antibiotic therapy at the end of treatment course, excepting de-escalation to a narrower spectrum antibiotic.; * Clinical failure was defined as the signs and symptoms of the infection being more serious with change or addition antibiotic therapy against CRE.

Secondary Outcome Measures

Name	Time	Method
Microbiological outcomes	Before discharge	Bacterial response in cultures after the treatment
Mortality	Within 14 and 28/30 days after discharge	All cause mortality
Length of stay	up to 12 weeks	The duration of a hospitalization
Physician acceptance rates	up to 72 hours after reporting the bacterial culture results	The rates of physicians' acceptance of an recommended optimal regimen

Trial Locations

Locations (1)

Phramongkutklao hospital; 🇹🇭 Bangkok, Thailand