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

Phramongkutklao College of Medicine and Hospital

Status: Unknown

Conditions: Critical Illness; Drug Resistance; Carbapenem-Resistant Enterobacteriaceae Infection; Treatment Outcomes; Clinical Outcomes; Septic Shock; Sepsis

Treatments: Other: Standard antibiotic regimens; Other: Combined antibiotic regimens

Study type: Interventional

Funder types: Other

Identifiers

NCT04516395

Q011h/63

Details and patient eligibility

About

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

Full 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.

Enrollment: 102 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

102 participants in 2 patient groups

Optimal antibiotic combination regimens

Experimental group

Description:

The patients in the groups will be given the optimal antibiotic combination regimens.

Treatment:

Other: Combined antibiotic regimens

Standard antibiotic regimens

Other group

Description:

The patients in the groups will be given the standard antibiotic regimens.

Treatment:

Other: Standard antibiotic regimens