1477 - Impact Of Resistance Thresholds On Mortality In Hospital-Acquired And Ventilator-Associated Pneumonia

Background: Hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) represent a significant source of morbidity and mortality in hospitalized patients. Numerous studies demonstrate mortality benefit with appropriate empiric therapy. Choosing the right empiric coverage is paramount; however, this decision becomes more challenging as rates of antibiotic resistance rise. Most recent HAP/VAP guidelines use an arbitrary population resistance rate of 20% to recommended methicillin-resistant Staphylococcus aureus (MRSA) coverage and double-coverage of resistant gram negative bacilli (GNB). Using this threshold has led to overuse of broad spectrum antimicrobials. The goal of this study is to mathematically explore the impact of this threshold on patient outcomes and link population resistance rates to individual mortality risk.

Methods: We used the concept of excess morality risk (EMR) to develop a theoretical simulation model based for HAP/VAP caused by GNB and MRSA empirically treated with piperacillin-tazobactam and vancomycin. EMR is the product of the proportion of HAP/VAP caused by GNB/MRSA, the rate of antibiotic (piperacillin-tazobactam/ methicillin) resistance in GNB and Staphylococcus aureus isolates and the difference in mortality between discordant and appropriate antibiotic therapy. Model parameters were obtained from large surveillance networks and published clinical trials.

Results: At the HAP/VAP guideline threshold of 20% methicillin resistance in SA isolates, the EMR was 0.3%; when the model included only culture positive patients, EMR was 0.6%. At a threshold of 20% resistance to piperacillin-tazobactam in GNB isolates, EMR was 1.9% and 3.1% when culture-negative patients were excluded. EMR increased as baseline risk of failure with discordant therapy increased (e.g. critically ill patients, ventilated HAP).Risk Difference of Death for Staphylococcus aureus Isolates
Risk Difference of Death for Gram Negative Bacilli


Conclusion: This model offers a mathematical exploration of the individual excess risk for death in patients with HAP/VAP caused by GNB/MRSA because of discordant therapy. The objectivity of the model would better allow clinicians, guideline authors, and health policy makers to weigh excess risk versus possible harms of broad-spectrum therapy when developing population resistance thresholds cutoffs for empiric therapy recommendations.