Multi-Drug Resistant Organism Network

NCT03646227 | Completed

• 2 other identifiers: Pro00071149UM1AI104681
• Study Type: observational
• Target: 6,496
• Locations: 4 countries
• Sites: 4

Brief Summary

This study is specifically designed to provide observational data which can be used to help in the design of future randomized clinical trials on both therapeutics and diagnostics for MDRO infections. To this end, clinical and epidemiological data will be collected on patients who have MDRO isolated from clinical cultures during hospitalization, as well as descriptions of the outcomes of patients treated with various antimicrobial regimens. Molecular and microbiological characterization will also be performed on MDRO isolates. These data will include a detailed clinical and epidemiological description of patients including identifying potential barriers to enrollment in future trials. In addition, data will be collected on species, strain type, and mechanism of drug resistance of the causative organism. Knowing the molecular characteristics will further inform future trial design as not all diagnostics detect and not all therapeutics are active against the same mechanisms of resistance.

Conditions

Infections Resistant to Multiple Drugs; Bacterial Infections

Keywords

Carbapenem-resistant enterobacteriaceae (CRE); Carbapenem-resistant Pseudomonas aeruginosa (CRPA); Klebsiella pneumoniae; Acinetobacter baumannii (CRAb); Bloodstream infection (BSI); Microbiological characterization

Outcome Measures

Primary Outcomes (9)

• Disposition at Discharge

  The disposition at discharge is a composite of different locations, to which the subject is discharged (skilled nursing facility, home, long term acute care facility, transfer to another hospital, death, or hospice) and it is used to compare patient outcomes based on MDRO collected form the subject.

  Up to 1 year from index culture date

• Charlson Score

  Components of the Charlson Score are collected from the medical record and the Charlson comorbidity index is calculated to determine chronically ill subjects.

  At 90 days after discharge from the index hospitalization

• Pitt Bacteremia Score

  Components of the Pitt Bacteremia Score are collected from the medical record and the Pitt bacteremia score is calculated to determine acutely ill subjects.

  On the day of index culture

• Source of positive culture

  The differences in outcomes based on the anatomic source of the positive culture are determined. The anatomic sources collected are blood, respiratory, urine, wound, abdominal, and other, which is collected from the medical record.

  At collection of the MDRO isolates

• Length of Stay

  The length of stay is determined by the hospital admission and discharge dates, which is collected from the medical record.

  Up to 1 year from index culture date

• ICU Admissions

  The total number ICU days during the index hospitalization will be collected from the medical record to determine high risk populations and exposure.

  Up to 1 year from index culture date

• Antibiotic Summary

  All antibiotics administered during the hospital stay will be collected from the medical record. The antibiotic name, duration of therapy, frequency of dosing, dosage, and reason for discontinuation will be collected for the antibiotics of interest.

  Only during hospitalization and up to one year from index culture date

• Survival Status

  Survival status will be collected through 90 days after discharge from index hospitalization, up to one year, to determine mortality.

  90 days from discharge or up to one year from index hospitalization.

• Readmission Status

  Readmission data will be collected through 90 days after discharge from index hospitalization to determine readmission.

  90 days after discharge from index hospitalization.

Interventions

Standard of Care OTHER

There is no prescribed intervention for this study. Standard of care will be captured in the eCRF.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cohorts will be constructed for each MDRO of eligible patients by investigating hospitalized patients who have an MDRO isolated in clinical cultures from any anatomical site. This study will be conducted under a waiver of informed consent to facilitate universal inclusion. All patients who are admitted to one of the participating hospitals and who have an MDRO - as defined in the specific sub-study protocol (Appendices) - isolated in a clinical culture are targeted for inclusion.

You may qualify if:

• Hospitalized patients.
• Must have at least one multi-drug resistant organism isolated from a clinical culture while hospitalized.

You may not qualify if:

• Patients who do not have a positive culture during hospitalization.
• Patients who's only positive culture was obtained outside of hospital admission.
• Patients who have cystic fibrosis and a CRPa infection.

Sponsors & Collaborators

• Duke University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (4)

Duke Clinical Research Institute

Durham, North Carolina, 27705, United States

Location

The University of Queensland Centre for Clinical Research

Herston, Queensland, 4029, Australia

Location

Huashan Hospital

Shanghai, Shanghai Municipality, 200040, China

Location

Universidad El Bosque

Bogotá, Colombia

Location

Related Publications (16)

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• Infectious Diseases Society of America (IDSA); Spellberg B, Blaser M, Guidos RJ, Boucher HW, Bradley JS, Eisenstein BI, Gerding D, Lynfield R, Reller LB, Rex J, Schwartz D, Septimus E, Tenover FC, Gilbert DN. Combating antimicrobial resistance: policy recommendations to save lives. Clin Infect Dis. 2011 May;52 Suppl 5(Suppl 5):S397-428. doi: 10.1093/cid/cir153. No abstract available.

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• Vardakas KZ, Rafailidis PI, Konstantelias AA, Falagas ME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug? J Infect. 2013 May;66(5):401-14. doi: 10.1016/j.jinf.2012.10.028. Epub 2012 Nov 6.

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• Zasowski EJ, Rybak JM, Rybak MJ. The beta-Lactams Strike Back: Ceftazidime-Avibactam. Pharmacotherapy. 2015 Aug;35(8):755-70. doi: 10.1002/phar.1622.

  PMID: 26289307 BACKGROUND

• Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2(Suppl 2):S27-72. doi: 10.1086/511159. No abstract available.

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• American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. doi: 10.1164/rccm.200405-644ST. No abstract available.

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• Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control. 2008 Jun;36(5):309-32. doi: 10.1016/j.ajic.2008.03.002. No abstract available.

  PMID: 18538699 BACKGROUND

• van Duin D, Perez F, Rudin SD, Cober E, Hanrahan J, Ziegler J, Webber R, Fox J, Mason P, Richter SS, Cline M, Hall GS, Kaye KS, Jacobs MR, Kalayjian RC, Salata RA, Segre JA, Conlan S, Evans S, Fowler VG Jr, Bonomo RA. Surveillance of carbapenem-resistant Klebsiella pneumoniae: tracking molecular epidemiology and outcomes through a regional network. Antimicrob Agents Chemother. 2014 Jul;58(7):4035-41. doi: 10.1128/AAC.02636-14. Epub 2014 May 5.

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• Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P; Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004 Aug;8(4):R204-12. doi: 10.1186/cc2872. Epub 2004 May 24.

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• Chow JW, Yu VL. Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. Int J Antimicrob Agents. 1999 Jan;11(1):7-12. doi: 10.1016/s0924-8579(98)00060-0.

  PMID: 10075272 BACKGROUND

• Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8.

  PMID: 3558716 BACKGROUND

• Jiang J, Komarow L, Hill C, Boutzoukas AE, Hanson B, Arias CA, Bonomo RA, Evans S, Doi Y, Satlin MJ, Weston G, Cober E, Valderrama-Beltran SL, Mendoza SS, Liu Z, Fries BC, Tambyah PA, Chambers HF, Fowler VG Jr, van Duin D, Kreiswirth BN, Chen L. Molecular Epidemiology and Clinical Characterization of Carbapenemase-Producing Enterobacter Species From an International Cohort. J Infect Dis. 2025 Jul 11;231(6):1489-1501. doi: 10.1093/infdis/jiae616.

  PMID: 39667036 DERIVED

• Boutzoukas AE, Mackow N, Giri A, Komarow L, Hill C, Chen L, Doi Y, Satlin MJ, Arias C, Wang M, Mora Moreo L, Herc E, Cober E, Weston G, Patel R, Bonomo RA, Fowler V, van Duin D. Increased mortality in hospital- compared to community-onset carbapenem-resistant enterobacterales infections. J Antimicrob Chemother. 2024 Nov 4;79(11):2916-2922. doi: 10.1093/jac/dkae306.

  PMID: 39236214 DERIVED

• Wang M, Ge L, Chen L, Komarow L, Hanson B, Reyes J, Cober E, Alenazi T, Zong Z, Xie Q, Liu Z, Li L, Yu Y, Gao H, Kanj SS, Figueroa J, Herc E, Cordova E, Weston G, Ananth Tambyah P, Garcia-Diaz J, Kaye KS, Dhar S, Munita JM, Salata RA, Vilchez S, Stryjewski ME, Villegas Botero MV, Iovleva A, Evans SR, Baum K, Hill C, Kreiswirth BN, Patel R, Paterson DL, Arias CA, Bonomo RA, Chambers HF, Fowler VG Jr, Satlin MJ, van Duin D, Doi Y; Multi-Drug Resistant Organism Network Investigators. Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions. Clin Infect Dis. 2024 Feb 17;78(2):248-258. doi: 10.1093/cid/ciad556.

  PMID: 37738153 DERIVED

• Wang M, Earley M, Chen L, Hanson BM, Yu Y, Liu Z, Salcedo S, Cober E, Li L, Kanj SS, Gao H, Munita JM, Ordonez K, Weston G, Satlin MJ, Valderrama-Beltran SL, Marimuthu K, Stryjewski ME, Komarow L, Luterbach C, Marshall SH, Rudin SD, Manca C, Paterson DL, Reyes J, Villegas MV, Evans S, Hill C, Arias R, Baum K, Fries BC, Doi Y, Patel R, Kreiswirth BN, Bonomo RA, Chambers HF, Fowler VG Jr, Arias CA, van Duin D; Multi-Drug Resistant Organism Network Investigators. Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study. Lancet Infect Dis. 2022 Mar;22(3):401-412. doi: 10.1016/S1473-3099(21)00399-6. Epub 2021 Nov 9.

  PMID: 34767753 DERIVED

• van Duin D, Arias CA, Komarow L, Chen L, Hanson BM, Weston G, Cober E, Garner OB, Jacob JT, Satlin MJ, Fries BC, Garcia-Diaz J, Doi Y, Dhar S, Kaye KS, Earley M, Hujer AM, Hujer KM, Domitrovic TN, Shropshire WC, Dinh A, Manca C, Luterbach CL, Wang M, Paterson DL, Banerjee R, Patel R, Evans S, Hill C, Arias R, Chambers HF, Fowler VG Jr, Kreiswirth BN, Bonomo RA; Multi-Drug Resistant Organism Network Investigators. Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. Lancet Infect Dis. 2020 Jun;20(6):731-741. doi: 10.1016/S1473-3099(19)30755-8. Epub 2020 Mar 6.

  PMID: 32151332 DERIVED

Related Links

• Antibacterial Resistance Leadership Group (ARLG)

Biospecimen

Retention: SAMPLES WITHOUT DNA

A sample of all MDRO isolates (bacterial isolates) will be sent to a central research laboratory for molecular and microbiological characterization. In addition, antimicrobial susceptibility testing, determination of mechanisms of antibiotic resistance, and strain typing will be performed.

MeSH Terms

Conditions

Bacterial Infections; Sepsis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• David van Duin, MD. PhD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

• Robert Bonomo, MD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2018
• First Posted: August 24, 2018
• Study Start: June 16, 2016
• Primary Completion: May 30, 2020
• Study Completion: May 30, 2020
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Starting January 2017 through November 2019
• Access Criteria: Must have an executed CDA and sub-award with ARLG/Duke for this specific purpose.

Locations

CO (1); AU (1); CN (1); US (1)