PCR to Guide Antibiotic Therapy for Pneumonia
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|ClinicalTrials.gov Identifier: NCT02660554|
Recruitment Status : Active, not recruiting
First Posted : January 21, 2016
Last Update Posted : April 23, 2018
|Condition or disease||Intervention/treatment||Phase|
|Pneumonia Methicillin-Resistant Staphylococcus Aureus||Other: Polymerase Chain Reaction (PCR)||Not Applicable|
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 (Clinical Trial)|
|Actual Enrollment :||45 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Clinical Trial to Compare Early Pneumonia Diagnosis Using Polymerase Chain Reaction to Usual Care in Critically Ill Adults|
|Study Start Date :||January 2016|
|Actual Primary Completion Date :||February 28, 2017|
|Estimated Study Completion Date :||December 31, 2018|
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.
- Days of anti-MRSA antibiotic therapy [ Time Frame: 14 days ]days for initially suspected MRSA pneumonia
- Mortality [ Time Frame: 28 days post randomization ]All cause mortality
- Organ dysfunction [ Time Frame: 28 days post randomization ]Days alive and organ dysfunction free for 28 days (based on daily SOFA score)
- 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)
- Days of subsequent anti-MRSA treatment [ Time Frame: 28 days post randomization ]total days of vancomycin or linezolid treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02660554
|United States, Illinois|
|Northwestern Memorial Hospital|
|Chicago, Illinois, United States, 60611|
|Principal Investigator:||Richard G Wunderink, MD||Northwestern University|