Trial of MRSA Polymerase Chain Reaction for Pneumonia
Condition: Pneumonia; Methicillin-Resistant Staphylococcus Aureus
MeSH terms: Pneumonia; Staphylococcal Infections
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Polymerase Chain Reaction (PCR)
Intervention type(s): Other
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Pneumonia; Methicillin-Resistant Staphylococcus aureus; Polymerase Chain Reaction; Intensive care units; Drug Resistance