HAP/VAP Diagnosis in Critically Ill Septic Patients Using a Multiplex PCR Array (LIGHTNING)

HAP/VAP Diagnosis in Critically Ill Septic Patients Using a Multiplex PCR Assay: A Multicenter Randomized Open-Label Trial. THE LIGHTNING STUDY

Multicenter, randomized, controlled, open-label trial to assess if semiquantitative multiplex PCR assay, as compared to conventional microbiology, can reduce the percentage of patients without microbiological diagnosis in the first 24 hours from HAP/VAP suspicion, thus allowing early de-escalation.

Hospital-acquired pneumonia and ventilator-associated pneumonia are leading cause of morbidity and mortality in Intensive Care Unit due to the underlining clinical conditions of critically ill patients and the high rate of multidrug resistance among causative agents. In patients with sepsis and septic shock, early and appropriate antibiotics are essential for improving clinical outcome, often requiring the use of broad-spectrum combinations. The optimal use of antimicrobials is part of current implementation programs aimed to reduce the administration of not-necessary antibiotics, the bio-ecologic pressure and the possible side effects . In this context the application of rapid, molecular microbiological tests on respiratory samples is of overwhelming interest, due to the potential of reducing the time to inappropriate antibiotic therapy and of prompting de-escalation. During last years a new Multiplex PCR Assay for pneumonia diagnosis (Film-Array Pneumonia Panel Plus, BioFire, Salt Lake City, UT, USA) has been implementing in the clinical practice, showing very high rates of negative and positive predictive values. The hypothesis is that molecular test on lower respiratory tract samples may reduce the time to microbiological diagnosis, thus allowing early antibiotic de-escalation.

Patients with suspected HAP or VAP in which lower tract respiratory samples are analyzed with new multiplex PCR assay (Film-array Pneumonia Panel Plus)

Patients with suspected HAP or VAP in which lower tract respiratory samples are analyzed with standard culture

Within 1 hour from HAP or VAP suspicion, quantitative tracheal aspirate or bronchoalveolar lavage will be performed to confirm the diagnosis. Clinicians will be encouraged to perform BAL whenever possible

The lower tract respiratory samples will be analyzed with Multiplex PCR assay (Film-array Pneumonia Plus).

The lower tract respiratory samples will be analyzed using convention microbiological methods (including conventional Gram stain and semiquantitative culture on both selective/differential and screening agar media)

When HAP or VAP are suspected, blood samples from peripheral vein will be collected and analyzed with conventional microbiological methods

Proportion of patients where a microbiological diagnosis of HAP/VAP is not avaiable within the first 24 hours

Proportion of patients in which antibiotic therapy has been modified from broad-spectrum empirical to targeted, due to microbiological results

Period of time from empirical antibiotic therapy initiation to modification due to microbiological results

Proportion of patients in the interventional group, in which microbiological diagnosis is concordant when assessed with PCR array and standard culture

Inclusion Criteria: Suspicion of HAP/VAP (clinical/radiological/laboratory criteria); Availability to perform tracheal aspirates or broncoalveolar lavage within 1 hour from clinical suspicion Life expectancy ≥ 48 hours Signed written informed consent. Exclusion Criteria: Pregnancy, Concomitant participating in other interventional trial Refusal to sign informed consent