Trial of MRSA Polymerase Chain Reaction for Pneumonia

February 8, 2023 updated by: Richard Wunderink, Northwestern University

Rapid Diagnostic Testing to Guide Antibiotic Therapy in Drug Resistant Pneumonia

The purpose of this study is to conduct a randomized clinical trial to compare an antibiotic strategy based on a novel diagnostic test, polymerase chain reaction (PCR) to usual care, in critically ill adults with pneumonia suspected to be caused by methicillin resistant staphylococcus aureus (MRSA). The investigators hypothesize that when automated PCR is used to guide antibiotic therapy, antibiotic exposure will be reduced in critically ill subjects with pneumonia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Bacterial resistance to antibiotics is a major problem in intensive care units (ICUs). The Centers for Disease Control (CDC) estimate drug resistant infections affect more than 2 million individuals nationwide and cause 23,000 deaths annually. In a recent executive order, the President of the United States called for improved antibiotic stewardship and the development of rapid diagnostic tests to identify antibiotic resistant infections. In ICU patients with pneumonia, guidelines advocate the routine use of broad spectrum antibiotics in most patients. In large part this is because diagnostic testing for pneumonia is too insensitive and too slow to inform decision making about appropriate antibiotics. Overuse of broad spectrum antibiotics promotes drug resistance by selecting for antibiotic resistant bacterial strains. This proposal will apply a new diagnostic test, polymerase chain reaction (PCR), to rapidly identify a drug resistant pathogen, methicillin resistant staphylococcus aureus (MRSA) to reduce inappropriate antibiotics in ICU patients with suspected pneumonia.

MRSA is an important cause of drug resistant pneumonia associated with high mortality. Methicillin resistance in Staphylococcus aureus (SA) results from acquisition of the mecA gene located in the mobile element staphylococcal cassette chromosome mec (SCCmec). MRSA pneumonia requires specific antibiotic therapy, treatment guidelines recommend addition of empiric antibiotics against MRSA in patients admitted to the ICU with risk factors for DRPs. The investigators prior work demonstrates that there is significant overlap of MRSA risk factors with risk factors for other DRPs, which potentially leads to the overuse of anti-MRSA antibiotics. Globally, MRSA pneumonia occurs in an estimated 2-6% of ICU patients. By contrast, empiric anti-MRSA therapy is prescribed in the majority of ICU patients with suspected pneumonia. The investigators have shown that at their own institution, the prevalence of MRSA is 5.5%, but empiric anti-MRSA therapy is prescribed in 89.5% of ICU patients with pneumonia. The large gap between empiric antibiotic therapy for MRSA pneumonia and actual cases of MRSA pneumonia is due to the lack of specificity of DRP risk factors, and the time delay of bacterial cultures. Overuse of antibiotics against MRSA has adverse consequences for patients, including new hospital acquired infections (HAIs), increased hospital length of stay (LOS), and higher cost.

Faster and more accurate diagnostic tests for MRSA, such as PCR, have the potential to reduce antibiotic exposure and improve patient outcomes. The time delay of bacterial cultures and the lack of specificity of DRP risk factors is a major limitation to the treatment of pneumonia, particularly in ICUs where the rapid delivery of appropriate antibiotics could be life saving. PCR has the potential to change the paradigm of empiric antibiotics by increasing diagnostic certainty and reducing the time to diagnosis or exclusion of a resistant pathogen. However, molecular diagnostic tests have not yet been validated for routine clinical practice.

The goal of this trial is to compare conduct a clinical trial to compare a PCR guided approach to MRSA therapy to usual care to determine if 1) an antibiotic strategy that utilizes rapid automated PCR reduces antibiotic-days in ICU subject with suspected pneumonia, 2) To compare the safety of an antibiotic strategy that relies on rapid automated PCR to usual care, and 3) To compare costs of the rapid automated PCR based strategy to routine microbiologic cultures.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adults aged 18 years and older with known or suspected pneumonia who are endotracheally intubated and mechanically ventilated
  2. Can receive bronchoalveolar lavage (BAL) while intubated
  3. Have received 24 hours or less of MRSA therapy (the antibiotics vancomycin or linezolid) prior to study enrollment

Exclusion Criteria:

  1. More than 24 hours of MRSA therapy therapy (the antibiotics vancomycin or linezolid),
  2. Subjects with extra pulmonary infection requiring treatment with vancomycin or linezolid
  3. Neutropenic fever
  4. Chronic airway infection
  5. Patient/surrogate refusal
  6. Subjects in whom BAL is deemed unsafe by the treating physician
  7. Treating physician refusal to discontinue antibiotics to treat MRSA if PCR negative
  8. Prisoners
  9. Pregnant women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: Usual care
In the usual care arm, antibiotic therapy against methicillin resistant Staphylococcus aureus (MRSA) will be given at the discretion of the care team. If bacterial cultures are negative for MRSA at 72 hours, the treating physician will be prompted to discontinue MRSA therapy.
EXPERIMENTAL: Polymerase Chain Reaction
In subjects randomized to the polymerase chain reaction (PCR) arm, antibiotic therapy against methicillin resistant Staphylococcus aureus (MRSA) will be determined by the results of the PCR test. In subjects who are clinically stable, results from the PCR must be available prior to the administration of MRSA therapy. Subjects with a positive MRSA PCR will be administered MRSA therapy. In subjects with a negative MRSA PCR, MRSA therapy will be withheld. In subjects randomized to the automated PCR arm who are clinically unstable, empiric MRSA therapy will be allowed until the PCR is completed. In these cases of unstable subjects, empiric MRSA therapy will be discontinued if the PCR is negative.
Other: Polymerase Chain Reaction (PCR)
Respiratory samples called bronchoalveolar lavage (BAL) gathered from subjects in the PCR arm will be tested for the presence of MRSA using the Cepheid Xpert® Assay. Xpert® is a qualitative in vitro test designed for rapid detection and differentiation of Staphylococcus aureus (SA) and methicillin resistant Staphylococcus aureus (MRSA) using PCR amplification. MRSA is identified by the mecA gene and staphylococcal cassette chromosome mec (SCCmec). Xpert® Assay is approved by the Federal Drug Administration to detect MRSA in soft tissue samples. Once the PCR is completed, the results will be relayed to the treating physician, and antibiotic therapy (vancomycin or linezolid) will be started or stopped based on the study protocol. All BAL samples will be sent for routine bacterial cultures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Days of anti-MRSA antibiotic therapy
Time Frame: 14 days
days for initially suspected MRSA pneumonia
14 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: 28 days post randomization
All cause mortality
28 days post randomization
Organ dysfunction
Time Frame: 28 days post randomization
Days alive and organ dysfunction free for 28 days (based on daily SOFA score)
28 days post randomization
Renal Organ dysfunction
Time Frame: 28 days post randomization
Days alive and renal organ dysfunction free for 28 days (based on daily SOFA renal organ score)
28 days post randomization
Days of subsequent anti-MRSA treatment
Time Frame: 28 days post randomization
total days of vancomycin or linezolid treatment
28 days post randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (ACTUAL)

February 28, 2017

Study Completion (ACTUAL)

May 3, 2019

Study Registration Dates

First Submitted

January 4, 2016

First Submitted That Met QC Criteria

January 18, 2016

First Posted (ESTIMATE)

January 21, 2016

Study Record Updates

Last Update Posted (ACTUAL)

February 10, 2023

Last Update Submitted That Met QC Criteria

February 8, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STU00202148

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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