PCR to Guide Antibiotic Therapy for Pneumonia

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.

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