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BackgroundFor patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized patients with pneumonia with negative cultures.MethodsWe included adults admitted with pneumonia in 2010–2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS), and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles.ResultsOf 14 170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4. Hospital de-escalation rates ranged from 2–35% and hospital de-escalation rate quartile was not significantly associated with outcomes. At hospitals in the top quartile of de-escalation, even among patients at lowest risk for mortality, the de-escalation rates were ConclusionsA minority of eligible patients with pneumonia had antibiotics de-escalated by hospital day 4 following negative cultures and de-escalation rates varied widely between hospitals. To adhere to recent guidelines will require substantial changes in practice.

BACKGROUND The American Thoracic Society and Infectious Diseases Society of America guidelines for management of healthcare-associated pneumonia (HCAP), first published in 2005, have been controversial regarding the selection of empiric broad-spectrum antibiotics, whether the criteria for HCAP predicts the likelihood of infection with multidrug resistant organisms, and whether HCAP patients have improved outcomes when treated with empiric broad-spectrum antibiotics. METHODS A retrospective cohort study at 488 US hospitals from July 2007 to November 2011. Patients who met criteria for HCAP were included. Guideline-concordant antibiotics were assessed based on guideline recommendations. We assessed changes in hospital rates of concordant antibiotic use over time and their correlation with outcomes. RESULTS Among 149,963 patients with HCAP, 19.6% received fully guideline-concordant antibiotics, 21.7% received partially concordant antibiotics, and 58.9% received discordant antibiotics. Guideline concordance increased over time. Rates of fully or partially concordant antibiotics varied across hospitals (median 36.4%; interquartile range 25.8%-49.1%). Among patients who received discordant antibiotics, 81.5% were treated according to community-acquired pneumonia (CAP) guidelines. On average, the rate of guideline concordance increased by 2.2% per 6-month interval, while hospital level rates of mortality, excess length of stay, and progression to respiratory failure did not change. CONCLUSIONS In this large, nationally representative cohort, only 1 in 5 patients with risk factors for HCAP received treatment that was fully in accordance with guidelines, and many received CAP therapy instead. At the hospital level, increases in the use of concordant antibiotics were not associated with declines in mortality, excess length of stay, or progression to respiratory failure.

Background Influenza is a leading cause of community-acquired pneumonia (CAP). Little is known about the effect of influenza testing on antimicrobial treatment among adult patients hospitalized with CAP. We quantified prevalence of testing and impact of positivity on treatment with antibacterials, antivirals, and outcomes. Methods We included adults admitted with pneumonia in 2010–2015 to 179 US hospitals contributing to the Premier database. Patients had CAP if radiographic evidence of pneumonia and antimicrobial treatment were present on day 1. We assessed influenza testing and compared antimicrobial utilization and outcomes of patients who tested positive vs negative vs not tested. Using mixed logistic regression and gamma generalized linear mixed models, we assessed the impact of influenza testing on inpatient mortality, length of stay (LOS) and cost. Results Among 166,273 patients with CAP, 38,665 (23.2%) were tested for influenza; 11.5% of these tested positive. The influenza testing rate increased from 15.4% in 2010/7–2011/6 to 35.6% in 2014/7–2015/6, ranging from 28.8% during flu season (October–May) to 8.2% in other months. Positive tests were more common during flu season (12.2% vs. 2.8%, P < 0.001). Patients tested for influenza were younger (66.6 vs. 70.3 years), less likely admitted from SNF (5.4% vs. 7.9%), with fewer comorbidities (2.9 vs. 3.3). Of patients tested for influenza, positive patients were younger (66.3 vs. 68.8 years), less likely admitted from SNF (5.2% vs. 6.8%), with more comorbidities (2.9 vs. 2.7) (all comparisons P < 0.001). Patients testing positive more likely received antivirals, were slightly less likely to receive antibacterials (Figure 1), but received shorter antibacterial courses than negative patients (5.3 vs 6.4 days, P < 0.001). Influenza tests were associated with reduced odds of in-hospital mortality compared with no testing (adjusted OR 0.71, 95% CI 0.63–0.81) and positive vs. negative tests with reduced costs (0.95, 0.92–0.99) and LOS (0.97, 0.94–0.99) (Figure 2). Conclusion In a large US inpatient sample hospitalized for pneumonia, only 23.2% of the patients were tested for influenza, but testing varied widely by hospital. A positive influenza test was associated with antiviral treatment but had minimal impact on antibiotic prescribing. Disclosures All authors: No reported disclosures.

BACKGROUND Fluoroquinolones have equivalent oral and intravenous bioavailability, but hospitalized patients with community-acquired pneumonia (CAP) generally are treated intravenously. Our objectives were to compare outcomes of hospitalized CAP patients initially receiving intravenous vs oral respiratory fluoroquinolones. METHODS This was a retrospective cohort study utilizing data from 340 hospitals involving CAP patients admitted to a non-intensive care unit (ICU) setting from 2007 to 2010, who received intravenous or oral levofloxacin or moxifloxacin. The primary outcome was in-hospital mortality. Secondary outcomes included clinical deterioration (transfer to ICU, initiation of vasopressors, or invasive mechanical ventilation [IMV] initiated after the second hospital day), antibiotic escalation, length of stay (LOS), and cost. RESULTS Of 36 405 patients who met inclusion criteria, 34 200 (94%) initially received intravenous treatment and 2205 (6%) received oral treatment. Patients who received oral fluoroquinolones had lower unadjusted mortality (1.4% vs 2.5%; P = .002), and shorter mean LOS (5.0 vs 5.3; P < .001). Multivariable models using stabilized inverse propensity treatment weighting revealed lower rates of antibiotic escalation for oral vs intravenous therapy (odds ratio [OR], 0.84; 95% confidence interval [CI], .74-.96) but no differences in hospital mortality (OR, 0.82; 95% CI, .58-1.15), LOS (difference in days 0.03; 95% CI, -.09-.15), cost (difference in $-7.7; 95% CI, -197.4-182.0), late ICU admission (OR, 1.04; 95% CI, .80-1.36), late IMV (OR, 1.17; 95% CI, .87-1.56), or late vasopressor use (OR, 0.94; 95% CI, .68-1.30). CONCLUSIONS Among hospitalized patients who received fluoroquinolones for CAP, there was no association between initial route of administration and outcomes. More patients may be treated orally without worsening outcomes.

Viral influenza is a seasonal infection associated with significant morbidity and mortality. In the United States more than 35,000 deaths and 200,000 hospitalizations due to influenza occur annually, and the number is increasing. Children aged less than 1 year and adults aged more than 65 years, pregnant woman, and people of any age with comorbid illnesses are at highest risk. Annual vaccination is the cornerstone of prevention, but some older patients may derive less benefit from immunization than otherwise fit individuals. If started promptly, antiviral medications may reduce complications of acute influenza, but increasing resistance to amantadine and perhaps neuraminidase inhibitors underscores the need for novel prevention and treatment strategies. Pulmonary complications of influenza are most common and include primary influenza and secondary bacterial infection. Either may cause pneumonia, and each has a unique clinical presentation and pathologic basis. Staphylococcus aureus, including methicillin-resistant strains, is an important cause of secondary bacterial pneumonia with high mortality. During influenza season, treatment of pneumonia should include empiric coverage for this pathogen. Neuromuscular and cardiac complications are unusual but may manifest in persons of any age.

Objectives Guidelines for treatment of healthcare-associated pneumonia (HCAP) recommend empirical therapy with broad-spectrum antimicrobials. Our objective was to examine the association between guideline-based therapy (GBT) and outcomes for patients with HCAP. Patients and methods We conducted a pharmacoepidemiological cohort study at 346 US hospitals. We included adults hospitalized between July 2007 and June 2010 for HCAP, defined as patients admitted from a nursing home, with end-stage renal disease or immunosuppression, or discharged from a hospital in the previous 90 days. Outcome measures included in-hospital mortality, length of stay and costs. Results Of 85 097 patients at 346 hospitals, 31 949 (37.5%) received GBT (one agent against MRSA and at least one against Pseudomonas). Compared with patients who received non-GBT, those who received GBT had a heavier burden of chronic disease and more severe pneumonia. GBT was associated with higher mortality (17.1% versus 7.7%, P Conclusions Among patients who met HCAP criteria, GBT was not associated with lower adjusted mortality, length of stay or costs in any analyses. Better criteria are needed to identify patients at risk for MDR infections who might benefit from broad-spectrum antimicrobial coverage.

Background The IDSA guideline for CAP recommends Pneumococcal urinary antigen testing (UAT) in addition to blood and sputum cultures for patients with severe CAP. In controlled settings, UAT is 50–80% sensitive and >90% specific; however, its utility and performance on a large-scale in real-world use has not been assessed. It is unclear whether UAT is clinically useful or whether the results impact prescribing behavior. Methods Retrospective cohort study of adult patients admitted with CAP or HCAP from 2010 to 2015 at 170 US hospitals that submit data to Premier. Date and time-stamped administrative and microbiologic data were assessed. Patients with a principal diagnosis of pneumonia, or sepsis with a secondary diagnosis of pneumonia plus a CXR and antibiotics within the first 24 hours, were included if they had a UAT plus either a blood or respiratory culture within the first 48 hours of admission. Results Of 159,894 eligible pneumonia patients, 24,757 (15.5%) had UAT plus either blood or respiratory cultures performed. Of 1,797 (7%) who had a positive UAT, 457 (25%) also grew S. pneumoniae (SP) from blood or respiratory cultures, 1,240 (69%) had negative cultures, and 100 (6%) an organism other than SP, with S. aureus, Pseudomonas spp., and E.coli being the most common pathogens, predominantly from respiratory cultures. Among 22,960 patients with a negative UAT, 429 (2%) had a positive blood or respiratory culture for SP and 2,653 (12%) had a culture positive for another organism. UAT was performed among 18.4% of patients admitted to the ICU, and 15.3% of those admitted to wards. Among patients empirically started on broad-spectrum antibiotics, 35% who had a positive UAT were de-escalated by Day 5, compared with 49% who grew SP in blood cultures and 24% in respiratory cultures. Conclusion In a large representative US inpatient database, there was poor concordance between UAT and cultures for SP. A positive UAT decreased the probability of having a non-SP pathogen. Antibiotic de-escalation occurred more often in association with a positive blood culture for SP than for UAT or positive respiratory culture, but occurred in less than half the patients with these markers of pneumococcal pneumonia. Overall, UAT is underutilized and does not appear to have a substantial impact on clinical care. Disclosures S. Haessler, AHRQ: Investigator, Research grant; P. C. Yu, AHRQ: Investigator, Research grant; M. Rothberg, AHRQ: Investigator, Research grant