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Background Community-acquired pneumonia (CAP) is a leading cause of hospital admissions and antimicrobial use. Clinical practice guidelines recommend switching from intravenous (IV) to oral antibiotics once patients are clinically stable. Methods We conducted a retrospective cohort study of adults admitted with CAP and initially treated with IV antibiotics at 642 US hospitals from 2010 through 2015. Switching was defined as discontinuation of IV and initiation of oral antibiotics without interrupting therapy. Patients switched by hospital day 3 were considered early switchers. We compared length of stay (LOS), in-hospital 14-day mortality, late deterioration (intensive care unit [ICU] transfer), and hospital costs between early switchers and others, controlling for hospital characteristics, patient demographics, comorbidities, initial treatments, and predicted mortality. Results Of 378 041 CAP patients, 21 784 (6%) were switched early, most frequently to fluoroquinolones. Patients switched early had fewer days on IV antibiotics, shorter duration of inpatient antibiotic treatment, shorter LOS, and lower hospitalization costs, but no significant excesses in 14-day in-hospital mortality or late ICU admission. Patients at a higher mortality risk were less likely to be switched. However, even in hospitals with relatively high switch rates, Conclusions Although early switching was not associated with worse outcomes and was associated with shorter LOS and fewer days on antibiotics, it occurred infrequently. Even in hospitals with high switch rates

Objective:Clostridioides difficile infection (CDI) is the most common cause of gastroenteritis, and community-acquired pneumonia (CAP) is the most common infection treated in hospitals. American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) CAP guidelines recommend empiric therapy with a respiratory fluoroquinolone or cephalosporin plus macrolide combination, but the CDI risk of these regimens is unknown. We examined the association between each antibiotic regimen and the development of hospital-onset CDI.Methods:We conducted a retrospective cohort study using data from 638 US hospitals contributing administrative including 177 also contributing microbiologic data to Premier, Inc. We included adults admitted with pneumonia and discharged from July 2010 through June 2015 with a pneumonia diagnosis code who received ≥3 days of either empiric regimen. Hospital-onset CDI was defined by a diagnosis code not present on admission and positive laboratory test on day 4 or later or readmission for CDI. Mixed propensity-weighted multiple logistic regression was used to estimate the associations of CDI with antibiotic regimens.Results:Our sample included 58,060 patients treated with either cephalosporin plus macrolide (36,796 patients) or a fluoroquinolone alone (21,264 patients) and with microbiological data; 127 (0.35%) patients who received cephalosporin plus macrolide and 65 (0.31%) who received a fluoroquinolone developed CDI. After adjustment for patient demographics, comorbidities, risk factors for antimicrobial resistance, and hospital characteristics, CDI risks were similar for fluoroquinolones versus cephalosporin plus macrolide (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.70–1.38).Conclusion:Among patients with CAP at US hospitals, CDI was uncommon, occurring in ∼0.33% of patients. We did not detect a significant association between the choice of empiric guideline recommended antibiotic therapy and the development of CDI.

Background:Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.Methods:We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.Results:Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).Conclusions:In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

Despite recent guidance from the Centers for Disease Control and Prevention (CDC) allowing institutions to relax in-facility masking strategies and due to our evolving understanding of respiratory pathogen transmission during the coronavirus disease 2019 (COVID-19) pandemic, we propose an updated standard for universal precautions in healthcare settings: permanently including universal masking in routine patient-care interactions. Such a practice prioritizes safety for patients, healthcare providers (HCPs), and visitors.

Objective: To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy. Design: We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures. Setting: This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals. Participants: Adults hospitalized for CAP. Exposure: Risk factors for resistant infection. Results: Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%–30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model. Conclusions: Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.

Background Choice of empiric therapy for pneumonia depends on risk for antimicrobial resistance. Models to predict resistance are derived from blood and respiratory culture results. We compared these results to understand if organisms and resistance patterns differed by site. We also compared characteristics and outcomes of patients with positive cultures by site. Methods We studied adult patients discharged from 177 US hospitals from July 2010 through June 2015, with principal diagnoses of pneumonia, or principal diagnoses of respiratory failure, acute respiratory distress syndrome, respiratory arrest, or sepsis with a secondary diagnosis of pneumonia, and who had blood or respiratory cultures performed. Demographics, treatment, microbiologic results, and outcomes were examined. Results Among 138 561 hospitalizations of patients with pneumonia who had blood or respiratory cultures obtained at admission, 12 888 (9.3%) yielded positive cultures: 6438 respiratory cultures, 5992 blood cultures, and 458 both respiratory and blood cultures. Forty-two percent had isolates resistant to first-line therapy for community-acquired pneumonia. Isolates from respiratory samples were more often resistant than were isolates from blood (54.2% vs 26.6%; P < .001). Patients with both culture sites positive had higher case-fatality, longer lengths of stay, and higher costs than patients who had only blood or respiratory cultures positive. Among respiratory cultures, the most common pathogens were Staphylococcus aureus (34%) and Pseudomonas aeruginosa (17%), whereas blood cultures most commonly grew Streptococcus pneumoniae (33%), followed by S. aureus (22%). Conclusions Patients with positive respiratory tract cultures are clinically different from those with positive blood cultures, and resistance patterns differ by source. Models of antibiotic resistance should account for culture source.

Background The Infectious Diseases Society of America recommends pneumococcal urinary antigen testing (UAT) when identifying pneumococcal infection would allow for antibiotic de-escalation. However, the frequencies of UAT and subsequent antibiotic de-escalation are unknown. Methods We conducted a retrospective cohort study of adult patients admitted with community-acquired or healthcare-associated pneumonia to 170 US hospitals in the Premier database from 2010 to 2015, to describe variation in UAT use, associations of UAT results with antibiotic de-escalation, and associations of de-escalation with outcomes. Results Among 159 894 eligible admissions, 24 757 (15.5%) included UAT performed (18.4% of intensive care unit [ICU] and 15.3% of non-ICU patients). Among hospitals with ≥100 eligible patients, UAT proportions ranged from 0% to 69%. Compared to patients with negative UAT, 7.2% with positive UAT more often had a positive Streptococcus pneumoniae culture (25.4% vs 1.9%, P < .001) and less often had resistant bacteria (5.2% vs 6.8%, P < .05). Of patients initially treated with broad-spectrum antibiotics, most were still receiving broad-spectrum therapy 3 days later, but UAT-positive patients more often had coverage narrowed (38.4% vs 17.0% UAT-negative and 14.6% untested patients, P < .001). Hospital rate of UAT was strongly correlated with de-escalation following a positive test. Only 3 patients de-escalated after a positive UAT result were subsequently admitted to ICU. Conclusions UAT is not ordered routinely in pneumonia, even in ICU. A positive UAT result was associated with less frequent resistant organisms, but usually did not lead to antibiotic de-escalation. Increasing UAT and narrowing therapy after a positive UAT result are opportunities for improved antimicrobial stewardship.

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.

Objective:Viruses are more common than bacteria in patients hospitalized with community-acquired pneumonia. Little is known, however, about the frequency of respiratory viral testing and its associations with antimicrobial utilization.Design:Retrospective cohort study.Setting:The study included 179 US hospitals.Patients:Adults admitted with pneumonia between July 2010 and June 2015.Methods:We assessed the frequency of respiratory virus testing and compared antimicrobial utilization, mortality, length of stay, and costs between tested versus untested patients, and between virus-positive versus virus-negative patients.Results:Among 166,273 patients with pneumonia on admission, 40,787 patients (24.5%) were tested for respiratory viruses, 94.8% were tested for influenza, and 20.7% were tested for other viruses. Viral assays were positive in 5,133 of 40,787 tested patients (12.6%), typically for influenza and rhinovirus. Tested patients were younger and had fewer comorbidities than untested patients, but patients with positive viral assays were older and had more comorbidities than those with negative assays. Blood cultures were positive for bacterial pathogens in 2.7% of patients with positive viral assays versus 5.3% of patients with negative viral tests (P < .001). Antibacterial courses were shorter for virus-positive versus -negative patients overall (mean 5.5 vs 6.4 days; P < .001) but varied by bacterial testing: 8.1 versus 8.0 days (P = .60) if bacterial tests were positive; 5.3 versus 6.1 days (P < .001) if bacterial tests were negative; and 3.3 versus 5.2 days (P < .001) if bacterial tests were not obtained (interaction P < .001).Conclusions:A minority of patients hospitalized with pneumonia were tested for respiratory viruses; only a fraction of potential viral pathogens were assayed; and patients with positive viral tests often received long antibacterial courses.

Background.Healthcare-associated pneumonia (HCAP) is an entity distinct from community-acquired pneumonia (CAP). HCAP has a higher case-fatality rate, due either to HCAP organisms or to the health status of HCAP patients. The contribution of HCAP criteria to case-fatality rate is unknown.Methods.We conducted a retrospective review of adult patients admitted with a diagnosis of pneumonia from July 2007 through November 2011 to 491 US hospitals. HCAP was defined as having at least 1 of the following: prior hospitalization within 90 days, hemodialysis, admission from a skilled nursing facility, or immune suppression. We compared characteristics of patients with CAP and patients with HCAP and explored the contribution of HCAP criteria to case-fatality rate in a hierarchical generalized linear model.Results.Of 436,483 patients hospitalized with pneumonia, 149,963 (34.4%) had HCAP. Compared to CAP patients, HCAP patients were older, had more comorbidities, and were more likely to require intensive care unit (ICU) care. In-hospital case-fatality rate was higher among patients with HCAP, compared to those with CAP (11.1% vs 5.1%, P < .001). After adjustment for demographics, comorbidities, presence of other infections, early ICU admission, chronic and acute medications, early tests and therapies, and length of stay, HCAP remained associated with increased case-fatality rate (odds ratio [OR], 1.35 [95% confidence interval (CI), 1.32-1.39]); odds of death increased for each additional HCAP criterion (OR [95% CI]: 1 criterion, 1.27 [1.23-1.31], 2 criteria, 1.55 [1.49-1.62], and 3 or more criteria, 1.88 [1.72-2.06]).Conclusions.After adjustment for differences in patient characteristics, HCAP was associated with greater case-fatality rate than CAP. This difference may be due to HCAP organisms or to HCAP criteria themselves.

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.

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.

Influenza infection most commonly affects the upper and lower respiratory tracts, but can involve extrapulmonary sites, including the myocardium. We report on a case of myocarditis caused by documented 2009 pandemic H1N1 influenza in a previously healthy adult, and review the literature on influenza myocarditis.

Staphylococcus aureus (SA) is becoming increasingly resistant to antibiotics in hospitals and the community. Long-term outcomes following susceptible and resistant SA infection have not been studied. We performed a retrospective matched pair analysis of all patients with positive culture for meticillin-resistant SA (MRSA) or meticillin-susceptible SA (MSSA) from any site to assess the outcomes of infection. Data were collected for length of hospitalisation and in-hospital mortality, as well as longer-term outcomes including all-cause mortality, number of rehospitalisations and subsequent cultures for SA during the year following infection. Twelve months after their initial SA infection, 42% of patients were dead. There were no differences between the groups in short-term mortality, length of hospitalisation, number of subsequent hospitalisations and cultures for SA during the year following infection. Following discharge, however, MRSA infection was associated with higher mortality than MSSA at three months (32% vs 18% P=0.02), six months (42% vs 22% P=0.002) and 12 months (51% vs 32% P=0.005). In conclusion, SA infection is associated with a high one-year all-cause mortality. Most deaths occur after discharge. The likelihood of dying during the year following infection is higher for patients with MRSA infection than for those with MSSA infection.