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

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

Optimizing Antibiotic Dosing Regimens for the Treatment of Infection Caused by Carbapenem Resistant Enterobacteriaceae: the Study of in Vitro Activity of Monotherapy and Combination Therapy, PK/PD Study and Treatment Outcomes

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.

Drug Resistance, Carbapenem-Resistant Enterobacteriaceae Infection, Sepsis, Septic Shock, Critical Illness, Clinical Outcomes, Treatment Outcomes

Pharmacokinetics/Pharmacodynamics, Antibiotic combination regimens, Dose-optimization, Carbapenem-Resistant Enterobacteriaceae Infection

According to the model, it divided into two parts - retrospective chart review and prospective data collection. Single independent patient group will be divided two parts depending on over a period of time. The patients in the retrospective part received a standard treatment become a control group, while the patients in the prospective part received the intervention become an experimental group.

Combined antibiotic combinations defined as the optimal antibiotic combination regimens which are created from in vitro study and the application of PK/PD.

Standard antibiotic regimens defined as the antibiotic regimens which are generally given to the patients following to the hospital protocol.

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.

Inclusion Criteria: Any patients are diagnosed any diseases caused by CRE infection by physicians at Phramongkutklao hospital during 1/4/2018 to 30/4/2021. Any patients are more than 18 years old. 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: Patients are breast-feeding or pregnancy. Patients are insufficient or incomplete information on the medical electronic record such as patients transferred.

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Drug resistance situations from National Antimicrobial Resistance Surveillance Center Thailand (NARST) (Thai)