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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04516395
• Other study ID #: Q011h/63
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2020
• Est. completion date: April 2021

Study information

• Verified date: August 2020
• Source: Phramongkutklao College of Medicine and Hospital
• Contact: Wichai Santimaleeworagun, PhD
• Phone: 663547600
• Email: Swichai1234[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 102
• Est. completion date: April 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carbapenem-Resistant Enterobacteriaceae Infection
• Clinical Outcomes
• Communicable Diseases
• Critical Illness
• Drug Resistance
• Enterobacteriaceae Infections
• Infection
• Sepsis
• Septic Shock
• Treatment Outcomes

Intervention

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

Locations

Country	Name	City	State
Thailand	Phramongkutklao hospital	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Phramongkutklao College of Medicine and Hospital

Country where clinical trial is conducted

Thailand, 

References & Publications (9)

Asín-Prieto E, Rodríguez-Gascón A, Isla A. Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents. J Infect Chemother. 2015 May;21(5):319-29. doi: 10.1016/j.jiac.2015.02.001. Epub 2015 Feb 12. Review. — View Citation

Barlam TF, Cosgrove SE, Abbo LM, MacDougall C, Schuetz AN, Septimus EJ, Srinivasan A, Dellit TH, Falck-Ytter YT, Fishman NO, Hamilton CW, Jenkins TC, Lipsett PA, Malani PN, May LS, Moran GJ, Neuhauser MM, Newland JG, Ohl CA, Samore MH, Seo SK, Trivedi KK. — View Citation

Demidenko E, Miller TW. Statistical determination of synergy based on Bliss definition of drugs independence. PLoS One. 2019 Nov 25;14(11):e0224137. doi: 10.1371/journal.pone.0224137. eCollection 2019. — View Citation

Gutiérrez-Gutiérrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Paño-Pardo JR, Venditti M, Tumbarello M, Daikos G, Cantón R, Doi Y, Tuon FF, Karaiskos I, Pérez-Nadales E, Schwaber MJ, Azap ÖK, Souli M, Roilides E, Pournaras S, Akova M, Pérez F, Bermejo — View Citation

Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, Pascual A. Treatment of Infections Caused by Extended-Spectrum-Beta-Lactamase-, AmpC-, and Carbapenemase-Producing Enterobacteriaceae. Clin Microbiol Rev. 2018 Feb 14;31(2). pii: e00079-17. doi: 10.1128/ — View Citation

Sheu CC, Chang YT, Lin SY, Chen YH, Hsueh PR. Infections Caused by Carbapenem-Resistant Enterobacteriaceae: An Update on Therapeutic Options. Front Microbiol. 2019 Jan 30;10:80. doi: 10.3389/fmicb.2019.00080. eCollection 2019. Review. — View Citation

Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International C — View Citation

Tamma PD, Goodman KE, Harris AD, Tekle T, Roberts A, Taiwo A, Simner PJ. Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis. 2017 Feb 1;64(3): — View Citation

Tillotson G. A crucial list of pathogens. Lancet Infect Dis. 2018 Mar;18(3):234-236. doi: 10.1016/S1473-3099(17)30754-5. Epub 2017 Dec 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical improvement or failure	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.	up to 8 weeks
Secondary	Mortality	All cause mortality	Within 14 and 28/30 days after discharge
Secondary	Length of stay	The duration of a hospitalization	up to 12 weeks
Secondary	Physician acceptance rates	The rates of physicians' acceptance of an recommended optimal regimen	up to 72 hours after reporting the bacterial culture results
Secondary	Microbiological outcomes	Bacterial response in cultures after the treatment	Before discharge

External Links

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