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Infections Resistant to Multiple DrugsMDRO NetworkNCT03646227

Multi-Drug Resistant Organism Network

An observational study of Infections Resistant to Multiple Drugs and Bacterial Infections, run by Duke University at 4 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
How many people
6,496 participants
Where
4 sitesin 4 countries
Study dates
16 Jun 2016to 30 May 2020
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

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.

Who may be able to join

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

Who cannot join

  • 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.

Trial locations and contacts

4 sites in 4 countries.

4 sites in 4 countries

United States1 site

  • Duke Clinical Research Institute

    Durham, North Carolina, 27705

Other trials in United States

Australia1 site

  • The University of Queensland Centre for Clinical Research

    Herston, Queensland, 4029

Other trials in Australia

China1 site

  • Huashan Hospital

    Shanghai, Shanghai Municipality, 200040

Other trials in China

Colombia1 site

  • Universidad El Bosque

    Bogotá

Other trials in Colombia

About this study

Official title: Multi-Drug Resistant Organism Network - MDRO Network

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.

Read the detailed description

This is a prospective multi-center study. At each hospital, study personnel will screen the microbiology laboratory logs to identify all patients found to have a MDRO isolate from one or more anatomical sites during hospitalization. For each patient identified, designated site personnel will access the patient's medical record and use web-based data entry to enter the relevant data into the electronic case report form (eCRF) in the study's centralized database.

A sample of all MDRO isolates (bacterial isolates) will be sent to a central research laboratory for molecular analysis which will include strain typing. In addition, the mechanism of resistance will be determined by performing PCR and/or Whole Genome Sequencing.

Aim 1. Identification of target population and high volume centers. The prevalence of specific MDRO is extremely variable in various patient populations. In addition, over time, prevalence patterns for specific MDRO tend to change. The data collection carried out under this protocol will provide real-time data on which patients are the target population for any trial directed against MDRO infection. Also, the data collected will indicate which geographic areas and which centers have the highest incidence of MDRO infections. This will facilitate rational site selection for future trials.

Aim 2. Provide data on impact of potential inclusion/exclusion criteria on enrollment in future trials.

Detailed clinical data will be collected to guide the future development of clinical trials. The eCRF is designed to collect data on the most common barriers to enrollment in clinical trials. Data can then be used in the design of future trials to be presented to pharmaceutical companies, as well as to regulators from the FDA, to provide a rationale for requesting exceptions in inclusion/exclusion criteria. This will result in clinical trials that are more readily generalizable.

Aim 3. Provide data on expected outcomes of patients with MDRO infections for power and sample size calculations for future trials.

In the MDRO network, detailed outcomes data will be collected. Data will include survival and microbiologic clearance outcomes when available. In addition, anatomical site specific clinical symptomatic outcomes, modeled on FDA guidance documents, will be documented. Data obtained will aid in guiding the design of future clinical trials by providing data needed for power and sample size calculations.

All hospitalized patients, including pediatric patients, who have an MDRO isolated from a clinical culture will be included. Patients who have a positive culture for MDRO that is obtained outside the hospital setting will not be included, to ensure the ability to collect MDRO isolates and sufficient clinical data. Overall enrollment is expected to be 7000.

This study will request a waiver of informed consent, consistent with CFR Title 45 part 46.116(d). The study does not involve direct interaction with human subjects. The medical records of patients admitted to the hospital will be screened and data collected from those records according this protocol. The patients will not be approached to obtain information, no intervention is being tested. MDRO isolates will be obtained from existing standard of care microbial testing.

Being tested
Standard of Care
Keywords
Carbapenem-resistant enterobacteriaceae (CRE), Carbapenem-resistant Pseudomonas aeruginosa (CRPA), Klebsiella pneumoniae, Acinetobacter baumannii (CRAb), Bloodstream infection (BSI), Microbiological characterization
Medical subject headings
Bacterial Infections, Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Standard of CareOther

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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 1 year from index culture date

  2. 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.

    Measured: At 90 days after discharge from the index hospitalization

  3. 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.

    Measured: On the day of index culture

  4. 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.

    Measured: At collection of the MDRO isolates

  5. Length of Stay

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

    Measured: Up to 1 year from index culture date

  6. 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.

    Measured: Up to 1 year from index culture date

  7. 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.

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

  8. Survival Status

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

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

  9. Readmission Status

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

    Measured: 90 days after discharge from index hospitalization.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2018
  2. Study start16 Jun 2016
  3. Primary completion30 May 2020
  4. Study completion30 May 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case only
Time perspective
Prospective
Enrolment
6,496 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03646227
Sponsor's protocol ID
Pro00071149
Other IDs
UM1AI104681
Acronym
MDRO Network
Status last verified
Mar 2023
First submitted
15 Aug 2018
Last updated
6 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The resulting SAP and results will be shared and discussed within the MDRO Publications Committee for the purpose of manuscript developing, and to inform the design of future clinical trials.

Publications

  • Clatworthy AE, Pierson E, Hung DT. Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol. 2007 Sep;3(9):541-8. doi: 10.1038/nchembio.2007.24.

    PubMed 17710100

  • 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.

    PubMed 21474585

  • 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.

    PubMed 23142195

  • 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.

    PubMed 26289307

  • 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.

    PubMed 17278083

  • 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.

    PubMed 15699079

  • 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.

    PubMed 18538699

  • 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.

    PubMed 24798270

  • 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.

    PubMed 15312219

  • 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.

    PubMed 10075272

  • 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.

    PubMed 3558716

  • Jabbour JF, Kadri H, Jabra E, Hindy JR, Haddad SF, Kanafani ZA, Zahreddine NK, Abou Fayad AG, Komarow L, Li Y, Jiang J, Araj GF, Matar GM, Doi Y, Fowler VG Jr, Paterson DL, Satlin MJ, van Duin D, Kanj SS. Distinct molecular epidemiology and outcomes of carbapenem-resistant gram-negative infections in Lebanon: insights from the MDRO network. BMC Infect Dis. 2026 Jul 7. doi: 10.1186/s12879-026-13946-8. Online ahead of print.

    PubMed 42414940

  • 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.

    PubMed 39667036

  • 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.

    PubMed 39236214

  • 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.

    PubMed 37738153

Questions about this trial

What is this clinical trial studying?

An observational study of Infections Resistant to Multiple Drugs and Bacterial Infections, run by Duke University at 4 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States, Australia, China, Colombia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disposition at Discharge (time frame: Up to 1 year from index culture date). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03646227, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2023.

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