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This study aimed to determine the stool specimen collection and Clostridioides difficile (C. difficile) testing frequency from inpatients and long-term care facility (LTCF) residents with new-onset diarrhea.A cross-sectional study was conducted in all wards of 9 adult hospitals (3532 beds) and 14 LTCFs (1205 beds) in Louisville, Kentucky to identify new-onset diarrhea (≥3 loose stools in the past 24 h and not present in the preceding 24 h) among Louisville adults via electronic medical record review, nurse interviews, and patient interviews during a 1-2 week observation period in 2018-2019.Among Louisville-resident inpatients, 167 patients with 9731 inpatient-days had new-onset diarrhea (1.7/100 inpatient-days). Stool specimens were collected from 32% (53/167); 12 (23%) specimens were laboratory-confirmed for C. difficile infection (CDI) (12.3 cases/10,000 inpatient-days). Among LTCF residents, 63 with 10,402 LTCF resident-days had new-onset diarrhea (0.6/100 LTCF resident-days). Stool specimens were collected from 32% (20/63); 9 (45%) specimens were laboratory-confirmed for CDI (8.6 cases/10,000 LTCF resident-days).New-onset diarrhea was common among inpatients and LTCF residents. Only one-third of patients with new-onset diarrhea had a stool specimen collected and tested for C. difficile-indicative of a potential CDI underdiagnosis-although, further studies are needed to confirm the extent of CDI underdiagnosis.

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.

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.

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.

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

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.

Summary Background The American Thoracic Society and Infectious Diseases Society of America provide guidelines for management of hospital-acquired, ventilator-associated, and health-care-associated pneumonias, consisting of empirical antibiotic regimens for patients at risk for multidrug-resistant pathogens. We aimed to improve compliance with these guidelines and assess outcomes. Methods We implemented a performance-improvement initiative in four academic medical centres in the USA with protocol-based education and prospective observation of outcomes. Patients were assessed for severity of illness and followed up until death, hospital discharge, or day 28. We included patients in intensive-care units who were at risk for multidrug-resistant pneumonia and were treated empirically. Findings 303 patients at risk for multidrug-resistant pneumonia were treated empirically, and prescribed treatment was guideline compliant in 129 patients and non-compliant in 174 patients. 44 (34%) patients died before 28 days in the compliance group and 35 (20%) died in the non-compliance group. Five patients in the compliance group and seven in the non-compliance group were lost to follow-up after day 14. Kaplan-Meier estimated survival to 28 days was 65% in the compliance group and 79% in the non-compliance group (p=0·0042). This difference persisted after adjustment for severity of illness. Median length of stay and duration of mechanical ventilation did not differ between groups. Compliance failures included non-use of dual treatment for Gram-negative pathogens in 154 patients and absence of meticillin-resistant Staphylococcus aureus coverage in 24 patients. For patients in whom pathogens were subsequently identified, empirical treatment was active in 79 (81%) of 97 of patients receiving compliant therapy compared with 109 (85%) of 128 of patients receiving non-compliant therapy. Interpretation Because adherence with empirical treatment was associated with increased mortality, we recommend a randomised trial be done before further implementation of these guidelines. Funding Pfizer, US Medical.