Kollef, Marin H.

Abstract Background Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) remain significant causes of morbidity and mortality among patients admitted to a medical facility. Consensus guidelines for the treatment of HAP/VAP recommend patients with certain risk factors be empirically treated with an anti-methicillin resistant Staphylococcus aureus (MRSA) and anti-pseudomonal antibiotic. The most commonly utilized anti-pseudomonal agents at BJC hospitals include cefepime, followed by piperacillin/tazobactam and meropenem. The purpose of this study is to determine if there is a difference in clinical outcomes between cefepime and the other most commonly used anti-pseudomonal antibiotics, piperacillin/tazobactam or meropenem, at these institutions for the treatment of HAP/VAP. Methods This retrospective, multicenter cohort study included adult patients with HAP/VAP who received cefepime, meropenem, or piperacillin/tazobactam. Major exclusion criteria included patients that received antibiotics within 48 hours of hospital admission or less than 48 hours of empiric antibiotics. The primary outcome was in-hospital mortality. Secondary outcomes included change in initial antibiotic, mechanical ventilation-free days, ICU length of stay, hospital length of stay, hospital readmission, and new C. difficile infection. Results Of 1,117 included patients, 1,008 patients received cefepime and 109 received meropenem or piperacillin/tazobactam. Incidence of in-hospital mortality was not observed to be significantly different among empiric Gram-negative regimens (cefepime group 19.4% vs. meropenem or piperacillin/tazobactam 22%, p=0.521. Change in initial antibiotic, ICU length of stay, and hospital length of stay were observed to be significantly higher in the cefepime group. Conclusion We observed no difference in in-hospital mortality between cefepime and piperacillin/tazobactam or meropenem. However, there was a significantly higher incidence of change in initial antibiotic, ICU length of stay, and hospital length of stay observed in the cefepime group, though additional research is needed to corroborate these observations. Disclosures Kevin Betthauser, PharmD, La Jolla Pharmaceutical Company: Advisor/Consultant|La Jolla Pharmaceutical Company: Grant/Research Support Paul Juang, Pharm.D., Merck & Co: Grant/Research Support

IMPORTANCE: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection, accounting for 22% of all nosocomial infections. The available studies to date have not attempted to assess whether confounding factors may account for the observed difference in mortality for the two forms of nosocomial pneumonia associated with mechanical ventilation, namely ventilated HAP (vHAP) and ventilator-associated pneumonia (VAP). OBJECTIVES: To determine if vHAP is an independent predictor of mortality among patients with nosocomial pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Single-center retrospective cohort study conducted at Barnes-Jewish Hospital, St. Louis, MO, between 2016 and 2019. Adult patients with a pneumonia discharge diagnosis were screened and patients diagnosed with vHAP and VAP were included. All patient data was extracted from the electronic health record. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day all-cause mortality (ACM). RESULTS: One thousand one-hundred twenty unique patient admissions were included (410 vHAP, 710 VAP). Thirty-day ACM was greater for patients with vHAP compared with VAP (37.1% vs 28.5%; p = 0.003). Logistic regression analysis identified vHAP (adjusted odds ratio [AOR], 1.77; 95% CI, 1.51–2.07), vasopressor use (AOR, 2.34; 95% CI, 1.94–2.82), Charlson Comorbidity Index (1-point increments) (AOR, 1.21; 95% CI, 1.18–1.24), total antibiotic treatment days (1-d increments) (AOR, 1.13; 95% CI, 1.11–1.14), and Acute Physiology and Chronic Health Evaluation II score (1-point increments) (AOR, 1.04; 95% CI, 1.03–1.06) as independent predictors of 30-day ACM. The most common bacterial pathogens identified as causes of vHAP and VAP were Staphylococcus aureus, Enterobacterales species, and Pseudomonas aeruginosa. CONCLUSIONS AND RELEVANCE: In this single-center cohort study with low rates of initial inappropriate antibiotic therapy, vHAP had greater 30-day ACM compared with VAP after adjusting for potential confounding variables including disease severity and comorbidities. This finding suggests that clinical trials enrolling patients with vHAP need to account for this outcome difference in their trial design and data interpretation.