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Background Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease from nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. Methods This prospective study enrolled adults aged ≥18 years hospitalized with radiographically confirmed CAP between October 2013 and September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). Results Among 12 055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13- and PCV20-unique serotypes were associated with 37.7% (n = 559) and 27.0% (n = 400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. Conclusions The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine., A novel urinary antigen detection assay substantially increased detection of non-pneumococcal conjugate vaccine 13 (PCV13) serotypes included in an investigational PCV20 among US adults with community-acquired pneumonia (CAP). PCV20 may address the burden of CAP due to the additional serotypes.

Background Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. Methods This observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. Results Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status. Conclusions After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.

Community acquired pneumonia (CAP) carries high morbidity, mortality, and economic burden, which is even higher in adults diagnosed with chronic obstructive pulmonary disease (COPD). While several studies have assessed the clinical burden and mortality risk of CAP and COPD, very few studies focus on CAP burden from a COPD patient perspective. Individuals recently diagnosed with CAP and with pre-existing COPD were recruited through the COPD Foundation. The CAP Burden of Illness Questionnaire (CAP-BIQ), a content validated questionnaire assessing CAP symptomatology, duration of symptoms and CAP impact on work, activities and family, was administered at baseline and at 30-days follow-up. Of the 490 participants recruited, 481 had data sufficient for analysis. The prevalence of respiratory-related symptoms was very high (>90%) at the time of diagnosis with other generalized symptoms such as fatigue, trouble sleeping, headaches and confusion present in more than 60% of participants. Mean duration of symptoms varied from approximately 2 weeks for headaches and fever to more than a month for fatigue, wheezing, dyspnea, and cough. Employed participants missed an average of 21 days of work and those not employed missed 36 days of usual activities. Over 84% required help from family, friends or care givers. CAP is a serious and burdensome condition for people with COPD, a condition that can impair activities for weeks, frequently requires care from family or friends, and includes lingering symptoms. The patient-reported impact of CAP reported in this study underscores the need for prevention strategies in this population.

Background:Clostridioides difficile infection (CDI), caused by toxigenic C. difficile and predominately manifested by moderate-to-severe diarrhea, is an important cause of morbidity and mortality in long-term care facilities (LTCFs). However, for CDI to be diagnosed in an LTCF resident, an LTCF resident with diarrhea must have a stool specimen collected for CDI diagnostic testing. The objective of this study was to define the frequency of stool specimen collection and testing for CDI in adult LTCF residents with diarrhea in Louisville, Kentucky. Methods: A cross-sectional study was conducted in 14 (31%) of the 45 LTCFs in Louisville (adults aged ≥18 years; population, 599,276) to identify LTCF residents with diarrhea and to observe the frequency of stool specimen collection for CDI diagnosis. For 14 consecutive days in February 2019, each LTCF was visited to identify new onset diarrhea (≥3 loose stools in 24 hours) by interviews of nursing staff. For residents with diarrhea, staff reviewed electronic medical records to determine whether a stool specimen was collected for CDI diagnosis and interviewed nurses about potential noninfectious causes of diarrhea. Results: The 14 participating LTCFs have 1,208 beds (median, 86 beds and 43 occupied beds per participating LTCF). Among 743 LTCF residents (with 10,402 patient days of surveillance), new-onset diarrhea was identified in 63 residents (21% male; median age 75 years); 0.6 diarrhea cases per 100 patient days (diarrhea attack rate, 0.6% per day). Nurses indicated that 16 (25%) of the 63 residents with diarrhea had a potential noninfectious cause of diarrhea (11 laxatives, 3 feeding tube, 1 colostomy, and 1 gastric surgery). Stool specimens were collected for CDI testing from 20 of 63 of residents (32%) with diarrhea; none with potential noninfectious cause of diarrhea and from 20 of 47 other residents (42%) with diarrhea. Of 20 stool specimens tested, 9 (47%) yielded toxigenic C. difficile (8.6 CDI cases per 10,000 patient days). During this survey, none of the 63 LTCF residents with diarrhea were transferred to a hospital or other healthcare facility. Conclusions: Diarrhea was common among LTCF residents, and toxigenic C. difficile was frequently identified in stool specimens collected from LTCF residents with diarrhea. The majority of non–laxative-receiving LTCF residents with diarrhea did not have a stool specimen collected for CDI diagnosis. The low frequency of CDI diagnostic testing of LTCF residents with diarrhea indicates that CDI may be underdiagnosed in these LTCFs and suggests that the CDI disease burden may be larger than currently appreciated.Funding: Pfizer Vaccines provided support for this study.Disclosures: Frederick Angulo, Kimbal D. Ford, Joann Zamparo, Elisa Gonzalez, Sharon Gray, David Swerdlow, and Catia Ferreira all report salary from Pfizer.

Background: Although Clostridioides difficile infections (CDIs) are associated with significant morbidity and mortality, CDI disease burden may be underestimated if a high proportion of inpatients with diarrhea do not have stool specimens collected for CDI diagnostic testing. The objective of this study was to define the frequency of stool specimen collection and testing for CDI in adult hospitalized patients with diarrhea. Methods: A cross-sectional study was conducted in all 9 adult hospitals (total, 3,532 beds) in Louisville (adult aged ≥18 years; population 599,276) to identify patients with diarrhea and to observe the frequency of stool specimen collection for CDI diagnosis. For 7 consecutive days in December 2018, each ward was visited to identify new onset diarrhea (>3 loose stools in 24 hours) among Louisville adults: first via electronic medical record (EMR) review, then by nurse interviews, and finally by interviewing patients. For patients with diarrhea, research staff reviewed EMRs to determine whether a stool specimen was collected for CDI diagnosis, and they interviewed nurses about potential noninfectious causes of diarrhea. Results: Among 2,565 hospitalized adults (with 14,042 patient days), research staff identified 167 patients (47% men; median age, 64 years) with new onset diarrhea, 1.2 diarrhea cases per 100 patient days. Patients with diarrhea were initially ascertained by EMR review (50%), nurse interviews (42%) or patient interviews (8%); all cases identified by patient interviews were identified by nurses the following day (but many cases identified by nurses were never identified by EMR review). Nurses indicated that 67 cases had a potential noninfectious cause of diarrhea (eg, laxatives, feeding tube, colostomy, liquid diet, etc). Stool specimens were collected by hospital staff for CDI testing from 53 of 167 patients (32%) with diarrhea; 10 of 67 patients (15%) with diarrhea for whom nurses reported potential noninfectious causes of diarrhea (laxative use, enteric feeding, or gastric survey) in the past 24 hours; and 43 of 100 patients (43%) with diarrhea with no reported potential noninfectious causes of diarrhea. Stool collection frequency was similar on weekdays and weekends. Conclusions: The low frequency of CDI diagnostic testing of hospitalized patients with diarrhea indicates that CDI may be underdiagnosed in these hospitals and suggests, given that only 32% of patients with diarrhea had a stool specimen collected, that the CDI disease burden may be 3 times larger than currently appreciated. New-onset diarrhea occurred in >1% of patients each day; the most effective method for identifying patients with diarrhea was via nurse interviews.Funding: Pfizer Vaccines supported this study.Disclosures: Frederick Angulo, Kimbal D. Ford, Joann Zamparo, Elisa Gonzalez, Sharon Gray, David Swerdlow, and Catia Ferreira all report salary from Pfizer.

Background: Complicated skin and skin structure infections (cSSSIs) due to Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), are associated with significant morbidity. Re-ducing MRSA carriage has been a focus of infection control interventions. The prevalence of MRSA colonization after successful treatment of a MRSA cSSSI is unknown. Methods: Secondary analysis of a randomized controlled trial comparing linezolid and vancomycin for the treatment of MRSA cSSSI. Adult patients that had a colonization culture, confirmed MRSA cSSSI, received at least one dose of study treatment, and had an outcome recorded at end of study. Patient, clinical characteristics and prevalence of colonization were compared by treatment regimens. A multivariate regression model identified predictors of MRSA colonization at EOS. Results: There were 456 patients evaluated. The prevalence of MRSA colonization was higher for vancomycin treated patients compared to linezolid treated patients at end of treatment (EOT) (28% vs. 5%, p < 0.001) and EOS (34% vs. 22%, p < 0.01). Independent predictors of colonization at EOS after treatment for a MRSA cSSSI included diagnosis, primarily driven by abscess, black race, treatment with vancomycin, MRSA mixed infection and male gender. Conclusion: Patients treated with linezolid for a cSSSI had less MRSA colonization at EOT and EOS compared to those treated with vancomycin. Multiple independent predictors of MRSA colonization were identified. Additional studies evaluating the relationship of MRSA colonization after treatment of cSSSI are needed.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of invasive surgical site infection (SSI) in the USA. Antimicrobial prophylaxis for SSI typically includes a cephalosporin. Vancomycin is used to provide MRSA coverage, but the timing of administration is challenging. Linezolid is an attractive agent for SSI prophylaxis, particularly for the prevention of SSI due to MRSA.We developed a decision-analytic model to evaluate linezolid use for cardiothoracic SSI prophylaxis. A theoretical cohort of 10,000 cardiothoracic surgery patients was followed through 2 stages: (1) occurrence of SSI, and (2) mortality after SSI. All patients were administered cefuroxime, vancomycin, or linezolid between 1 and 180 min prior to surgical incision. SSIs were categorized into 3 pathogen categories: (1) methicillin-susceptible Gram-positive, (2) methicillin-resistant Gram-positive, and (3) other organisms. The most effective strategy resulted in the fewest SSIs. Assumptions for antibiotic effectiveness, impact of administration time, and pathogens were based on the published literature.Compared with cefuroxime, there was a 1% increase in the total number of SSIs in the linezolid group (mean SSI increase = 7), while there was a 12% increase in the vancomycin group (mean SSI increase = 86). Linezolid prophylaxis resulted in fewer SSIs due to methicillin-resistant Gram-positive infections (n = 108) compared with cefuroxime (n = 200, 46% reduction in the linezolid group) and vancomycin (n = 119, 9% reduction in the linezolid group).This simulation indicates that linezolid may offer benefits for SSI prophylaxis over existing prophylactic agents, particularly for the prevention of SSI due to Gram-positive methicillin-resistant pathogens.

Background Vaccines are one of the most important public health interventions. Understanding factors associated with vaccine acceptance is critical. The objectives of this study were to evaluate the impact of the three constructs of the Theory of Planned Behavior (TPB) on the intention to be vaccinated among healthy individuals being seen for pre-travel care, and to evaluate if behavioral intention was associated with vaccine acceptance. Methods We surveyed individuals seeking vaccination at the University of Louisville Vaccine and International Health and Travel Clinic. Linear and two stage least squares regression models were used to define the associations between constructs of the TPB and the intention to be vaccinated, as well as the association between the intention to be vaccinated and vaccine acceptance. Results A total of 183 individuals were included in the analysis. None of the constructs of the TPB were associated with intention to be vaccinated. Behavioral intention was not associated with vaccination acceptance. Conclusions This study suggests that the TPB does not predict the intention to get vaccinated among individuals attending our Vaccine and International Health and Travel Clinic. It will be critical to define better predictors of vaccine uptake in healthy, low-risk individuals to increase vaccine acceptance.

SummaryObjectiveTo compare demographic and clinical characteristics, and methicillin-resistant Staphylococcus aureus (MRSA) strain characteristics, in patients with early-onset (EO) and late-onset (LO) MRSA nosocomial pneumonia.MethodsThis was a retrospective analysis of data from a multicenter observational study of nosocomial pneumonia patients admitted between November 2008 and July 2010. Laboratory analyses performed on MRSA isolates included confirmation of antimicrobial susceptibility and heteroresistance to vancomycin, USA typing, staphylococcal cassette chromosome (SCC) mec typing, and detection of Panton–Valentine leukocidin (PVL) genes.ResultsWe identified 134 patients; 42 (31%) had EO MRSA pneumonia and 92 (69%) had LO MRSA pneumonia. The patients in the LO group were more likely to have risk factors for multidrug-resistant pathogens (98% vs. 76%, p

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial pneumonia. To characterize pathogen-derived and host-related factors in intensive care unit (ICU) patients with MRSA pneumonia, we evaluated the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. We performed multivariate regression analyses of 28-day mortality and clinical response using univariate analysis variables at a P level of mec types II (64.1%) and IV (33.1%), and agr I (36.7%) and II (61.8%). Panton-Valentine leukocidin (PVL) was present in 21.9%, and vancomycin heteroresistance was present in 15.9%. Mortality occurred in 37.1% of patients; factors in the univariate analysis were age, APACHE II score, AIDS, cardiac disease, vascular disease, diabetes, SCC mec type II, PVL negativity, and higher vancomycin MIC (all P values were P < 0.001) and age (OR, 1.024; 95% CI, 1.003 to 1.046; P = 0.02). Clinical failure occurred in 36.8% of 201 evaluable patients; the only independent predictor was APACHE II score (OR, 1.082; 95% CI, 1.031 to 1.136; P = 0.002). In summary, APACHE II score (mortality, clinical failure) and age (mortality) were the only independent predictors, which is consistent with severity of illness in ICU patients with MRSA pneumonia. Interestingly, our univariate findings suggest that both pathogen and host factors influence outcomes. As the epidemiology of MRSA pneumonia continues to evolve, both pathogen- and host-related factors should be considered when describing epidemiological trends and outcomes of therapeutic interventions.

Background. Patients with community-acquired pneumonia (CAP) infected with methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the Panton-Valentine leukocidin (PVL) gene have severe clinical presentation and poor clinical outcomes. Antibiotics that suppress toxin production have been suggested for the management of these patients. The objective of this study was to compare the severity of disease and clinical outcomes of patients with hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) infected with MRSA carrying the PVL gene with those patients infected with MRSA strains that do not carry the PVL gene. Methods. This was a multicenter observational study of patients with HAP and VAP. MRSA isolates were subjected to genetic analysis to define the presence of the PVL gene, the USA type and the staphylococcal cassette chromosome mec type. Severity of disease was evaluated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. The primary clinical outcome was mortality at hospital discharge. Results. Atotalof109casesofMRSAHAP/VAPwereevaluated.TheincidenceofPVL 1 MRSA was 27%. APACHE II score at diagnosis of HAP/VAP was 21 6 8f or PVL 1 MRSA and 20 6 6f or PVL 2 MRSA (P 5 .67). Mortality was 10% (3/29) for patients with PVL 1 MRSA versus 10% (8/80) for patients with PVL 2 MRSA (P . .99). Conclusions. In patients with HAP or VAP due to MRSA, severity of disease and clinical outcomes are not influenced by the presence of the PVL gene. Therapeutic strategies directed to block PVL exotoxin may not impact outcomes in these patients.

Introduction In 2005 the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) published guidelines for managing hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP). Although recommendations were evidence based, collective guidelines had not been validated in clinical practice and did not provide specific tools for local implementation. We initiated a performance improvement project designated Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) at four academic centers in the United States. Our objectives were to develop and implement the project, and to assess compliance with quality indicators in adults admitted to intensive care units (ICUs) with HAP, VAP, or HCAP. Methods The project was conducted in three phases over 18 consecutive months beginning 1 February 2006: 1) a three-month planning period for literature review to create the consensus pathway for managing nosocomial pneumonia in these ICUs, a data collection form, quality performance indicators, and internet-based repository; 2) a six-month implementation period for customizing ATS/IDSA guidelines into center-specific guidelines via educational forums; and 3) a nine-month post-implementation period for continuing education and data collection. Data from the first two phases were combined (pre-implementation period) and compared with data from the post-implementation period. Results We developed a consensus pathway based on ATS/IDSA guidelines and customized it at the local level to accommodate formulary and microbiologic considerations. We implemented multimodal educational activities to teach ICU staff about the guidelines and continued education throughout post-implementation. We registered 432 patients (pre- vs post-implementation, 274 vs 158). Diagnostic criteria for nosocomial pneumonia were more likely to be met during post-implementation (247/257 (96.1%) vs 150/151 (99.3%); P = 0.06). Similarly, empiric antibiotics were more likely to be compliant with ATS/IDSA guidelines during post-implementation (79/257 (30.7%) vs 66/151 (43.7%); P = 0.01), an effect that was sustained over quarterly intervals (P = 0.0008). Between-period differences in compliance with obtaining cultures and use of de-escalation were not statistically significant. Conclusions Developing a multi-center performance improvement project to operationalize ATS/IDSA guidelines for HAP, VAP, and HCAP is feasible with local consensus pathway directives for implementation and with quality indicators for monitoring compliance with guidelines.

In an effort to decrease the gap between the current management of pneumonia in the ICU and the recommendations by the 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), we developed, implemented and evaluated an ICU hospital-acquired pneumonia performance improvement (PI) project by adapting these guidelines in four academic hospitals.

We developed an ICU performance improvement project to evaluate patients with ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP), and healthcare-associated pneumonia (HCAP) using the 2005 American Thoracic Society/Infectious Diseases Society of America guidelines. Below is a descriptive analysis of the patients enrolled and their outcomes.

Introduction Controversy exists regarding optimal treatment for ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA). The primary objective of this study was to compare clinical success of linezolid versus vancomycin for the treatment of patients with MRSA VAP. Methods This was a multicenter, retrospective, observational study of patients with VAP (defined according to Centers for Disease Control and Prevention criteria) due to MRSA who were treated with linezolid or vancomycin. MRSA VAP was considered when MRSA was isolated from a tracheal aspirate or bronchoalveolar lavage. Clinical success was evaluated by assessing improvement or resolution of signs and symptoms of VAP by day 14. After matching on confounding factors, logistic regression models were used to determine if an association existed between treatment arm and clinical success. Results A total of 188 patients were evaluated (101 treated with linezolid and 87 with vancomycin). The mean ± standard deviation Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21 ± 11 for linezolid- and 19 ± 9 for vancomycin-treated patients (P = 0.041). Clinical success occurred in 85% of linezolid-treated patients compared with 69% of vancomycin-treated patients (P = 0.009). After adjusting for confounding factors, linezolid-treated patients were 24% more likely to experience clinical success than vancomycin-treated patients (P = 0.018). Conclusions This study adds to the evidence indicating that patients with MRSA VAP who are treated with linezolid are more likely to respond favorably compared with patients treated with vancomycin.