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

NCT04516395 | Unknown

• 1 other identifier: Q011h/63
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Mortality

  Within 14 and 28/30 days after discharge

• Length of stay

  up to 12 weeks

• Physician acceptance rates

  up to 72 hours after reporting the bacterial culture results

• Microbiological outcomes

  Before discharge

Study Arms (2)

Optimal antibiotic combination regimens

EXPERIMENTAL

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

Other: Combined antibiotic regimens

Standard antibiotic regimens

OTHER

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

Other: Standard antibiotic regimens

Interventions

Combined antibiotic regimens OTHER

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

Optimal antibiotic combination regimens

Standard antibiotic regimens OTHER

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

Standard antibiotic regimens

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Phramongkutklao College of Medicine and Hospital: lead

Study Sites (1)

Phramongkutklao hospital

Bangkok, 10400, Thailand

Location

Related Publications (9)

• 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 Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.

  PMID: 26903338 RESULT

• 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. No abstract available.

  PMID: 29276050 RESULT

• 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. Implementing an Antibiotic Stewardship Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016 May 15;62(10):e51-77. doi: 10.1093/cid/ciw118. Epub 2016 Apr 13.

  PMID: 27080992 RESULT

• Asin-Prieto E, Rodriguez-Gascon 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.

  PMID: 25737147 RESULT

• Rodriguez-Bano J, Gutierrez-Gutierrez 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):e00079-17. doi: 10.1128/CMR.00079-17. Print 2018 Apr.

  PMID: 29444952 RESULT

• 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):257-264. doi: 10.1093/cid/ciw741. Epub 2016 Nov 9.

  PMID: 28013264 RESULT

• 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.

  PMID: 31765385 RESULT

• 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.

  PMID: 30761114 RESULT

• Gutierrez-Gutierrez B, Salamanca E, de Cueto M, Hsueh PR, Viale P, Pano-Pardo JR, Venditti M, Tumbarello M, Daikos G, Canton R, Doi Y, Tuon FF, Karaiskos I, Perez-Nadales E, Schwaber MJ, Azap OK, Souli M, Roilides E, Pournaras S, Akova M, Perez F, Bermejo J, Oliver A, Almela M, Lowman W, Almirante B, Bonomo RA, Carmeli Y, Paterson DL, Pascual A, Rodriguez-Bano J; REIPI/ESGBIS/INCREMENT Investigators. Effect of appropriate combination therapy on mortality of patients with bloodstream infections due to carbapenemase-producing Enterobacteriaceae (INCREMENT): a retrospective cohort study. Lancet Infect Dis. 2017 Jul;17(7):726-734. doi: 10.1016/S1473-3099(17)30228-1. Epub 2017 Apr 22.

  PMID: 28442293 RESULT

MeSH Terms

Conditions

Sepsis; Shock, Septic; Critical Illness

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Disease Attributes

Study Officials

• Wichai Santimaleeworagun

  Silpakorn University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wichai Santimaleeworagun, PhD

CONTACT

663547600; Swichai1234@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: August 18, 2020
• Study Start: September 1, 2020
• Primary Completion: March 1, 2021
• Study Completion: April 1, 2021
• Last Updated: August 26, 2020

Record last verified: 2020-08

Locations

TH (1)