Beta-lactam plus Macrolide vs Fluoroquinolone for Empiric Therapy of Hospitalized Patients with CAP: Results from the University of Louisville Pneumonia Study

Background Current guidelines recommend a β-lactam plus a macrolide or fluoroquinolone monotherapy as initial empiric antibiotic therapy for treatment of patients hospitalized with community-acquired pneumonia (CAP). Multiple studies have shown different results comparing the two regimens for the treatment of CAP. Our objective, in a city-wide prospective study, was to compare outcomes among hospitalized patients with CAP who received empiric treatment either with a β-lactam plus a macrolide or fluoroquinolone monotherapy. Methods This was a propensity score matched case-control study of the University of Louisville Pneumonia Study. It was a prospective population-based cohort study of all hospitalized adults with CAP. Patients were divided into two groups and propensity score matched based on empiric therapy; a β-lactam plus a macrolide compared to fluoroquinolone monotherapy. Study outcomes were time to clinical stability, length of stay, and in-hospital, 30-day and 1-year mortality. Stratified Cox proportional hazards regression was performed to analyze continuous variable differences between groups. Conditional logistic regression was performed to analyze dichotomous variable differences in mortality. Results An association was not found between the two groups for time to clinical stability (aHR: 1.06; 95% CI: 0.93-1.22), length of stay (aHR: 1.14; 95% CI: 0.99-1.32) or mortality. Conclusion The present study did not show any difference in short or long-term outcomes for hospitalized patients with CAP who were treated with either a β-lactam plus a macrolide or fluoroquinolone monotherapy. Hence, our study does not support the superiority of one treatment over other

Impact of Pooling Samples on Analytic Sensitivity of a Real-Time Reverse Transcriptase PCR Assay for SARS CoV-2

During the COVID-19 pandemic, laboratories experienced periods of shortages for certain critical materials required to meet the high demand for SARS-CoV-2 testing. The U.S. Food & Drug Administration provided a template for molecular diagnostic testing, including guidance for a specimen pooling process in order to evaluate performance of the SARS-CoV-2 nucleic acid amplification assay. This study aimed to evaluate the testing of pooled specimens consisting of four nasopharyngeal swab specimens using the Luminex ARIES® nucleic acid amplification platform. Results indicated that there was a loss of analytic sensitivity with pooled nasopharyngeal swab samples, demonstrating that this approach should be balanced against material shortages and the clinical utility of a less sensitive assay

Association of Urine Levels of C-Reactive Protein with Clinical Outcomes in Patients with Pneumonia: A Pilot Study

Finding relevant biomarkers as a potential predictor of severity for patients hospitalized with community acquired pneumonia (CAP), in addition to the clinical scoring system, could advance progress towards more effective patient management. The inflammatory marker, C-reactive protein (CRP), which is elevated in the pathogenesis of many infectious diseases, may be a key biomarker target for CAP. Previous studies have shown that serum CRP may be a useful diagnostic marker for pneumonia in hospitalized patients with acute respiratory symptoms. The main aims of this study were to determine the correlation between serum and urine CRP levels in hospitalized patients with CAP, and any correlation with patient outcomes. Our laboratory employed a commercially available human high sensitive CRP ELISA kit to check the level of CRP in the corresponding patient urine sample. The results showed that there was a positive correlation between patient serum and urine CRP levels. In addition, we showed the correlation of urine CRP levels with certain patient comorbidities, time to clinical stability, length of patient hospital stay, and mortality

The Population Affected by the Syndemic of COVID-19 and Poverty is More Likely to be Hospitalized with SARS-CoV-2 Pneumonia

Background Lockdown measures to control COVID-19 have exacerbated the poverty epidemic. We hypothesized that the synergistic interaction of COVID-19 and poverty epidemics favors the development of more severe forms of COVID-19 in the population living in poverty. To test this hypothesis, we assessed whether an ecological association exists between the geographic distribution of hospitalized patients with SARS-CoV-2 pneumonia and markers of poverty in the city of Louisville, KY. Methods Using the geomasked home addresses of hospitalized patients with SARS-CoV-2 pneumonia in the city of Louisville, a kernel density heatmap was created. Kuldorff’s spatial scan statistic was used to calculate areas of increased risk for SARS-CoV-2 pneumonia hospitalization. Heat maps were created for census tract–level demographics according to income, age, race, and ethnicity to assess whether an ecological association exists with the spatial distribution of SARS-CoV-2 pneumonia hospitalization. Results Four areas of increased risk of hospitalization due to SARS-CoV-2 pneumonia were identified in the western and central sections of the city, with relative risks (RRs) ranging from 2.3 to 3.2 (p Conclusions Residents from low-income areas are almost three times more likely to develop SARS-CoV-2 pneumonia requiring hospitalization. Current efforts to decrease the number of COVID-19 hospitalizations through vaccination of populations at risk should be concentrated in city areas with a low-income level population

Severity of disease and mortality for hospitalized patients with community-acquired viral pneumonia compared to patients with community-acquired bacterial pneumonia

Background: There exists a large body of literature to help identify, diagnose, treat, and manage community-acquired pneumonia (CAP). Despite this, there is little data that directly compares the clinical syndromes and complications of pure bacterial pneumonia to pure viral pneumonia. Our study compares the clinical presentation, morbidity and mortality of viral vs. bacterial etiologies of CAP. Methods: This was a secondary data analysis of the Community-Acquired Pneumonia Organization (CAPO) international study database. Data was collected concerning patient demographics, physical examination findings, laboratory findings, radiological findings, severity of illness, and clinical outcomes and stratified according to the two study groups, CAVP and CABP. A microbiological diagnosis of CABP was based on the isolation of a bacterium from a respiratory sample, blood culture and/or identification of a urinary antigen for Streptococcus or Legionella; microbiological diagnosis of CAVP was based on polymerase chain reaction or antigen detection from respiratory samples. Results: Our study included 1,913 patients. Of these, 286 (15.0%) had viral infection, while 1,627 (85.0%) had CAVP. We found that bacterial CAP patients are older, more frequently male, and suffer from a higher proportion of comorbidities when compared to viral CAP patients. Comparison of physical exam findings and laboratory values failed to find a clinically significant difference between bacterial and viral CAP patients. When comparing severity of illness, bacterial CAP patients had greater frequency of PSI ≥ class IV; however, viral CAP patients more frequently needed ICU admission, ventilator support, vasopressor support, and had higher rate of in hospital mortality. Conclusions: Our study confirms the extreme difficulty differentiating CABP from CAVP using demographics, physical exam, or x-ray findings. We found no major clinical or laboratory findings distinguishing CABP from CAVP. The increased severity of illness of CAVP compared to bacterial etiologies shows that PSI scores may not be an accurate indicator of severity of disease. More studies are needed to identify the best process of care for patients with CAP, including the potential benefits of routine respiratory viral panel testing and empiric antiviral therapy

Characteristics and Clinical Outcomes of Hospitalized Patients with Community-Acquired Pneumonia who are Active Intravenous Drug Users

Background: Intravenous drug users (IVDU) have a 10-fold increased risk of community-acquired pneumonia (CAP) compared to the general population. There is scarce data available evaluating the clinical outcomes of IVDU hospitalized patients with CAP and that data mostly focuses on mortality. The objective of this study was to evaluate the clinical characteristics, incidence and outcomes of hospitalized patients with CAP in active intravenous drug users in Louisville, Kentucky. Methods: This was a secondary data analysis of the University of Louisville Pneumonia study. IVDU patients were propensity score matched to a non-IVDU group. Study outcomes were time to clinical stability (TCS), length of stay (LOS), mortality at discharge, and mortality at 1 year. Stratified Cox proportional hazard regression was performed to evaluate TCS and LOS. Conditional logistic regression was performed to evaluate mortality. Statistical significance was defined as p ≤ 0.05. Results:From a total of 8,284 hospitalized patients with CAP reviewed, 113 patients were matched per group. Median (IQR) age for the IVDU was 33 (28-43) versus 36 (28-48) for the matched non-IVDU group (p Conclusions: This study shows that active IVDU hospitalized patients with CAP do not have worse outcomes when compared with non-IVDU hospitalized patients with CAP. Patients in the IVDU group were significantly younger. Since severity scores commonly used are heavily influenced by age, these will not likely be useful tools to assist the physicians with the site for care and management

Assessment of Pneumonia Severity Indices as Mortality Predictors

BACKGROUND The leading cause of infectious disease death in the United States is community-acquired pneumonia (CAP). Several pneumonia severity indices exist and are widely used as tools to assist physicians regarding site of care based on risk of death. However, limited data exists that discerns which of the most commonly used severity scores is the best predictor of mortality across multiple time points. The objective of this study is to determine the best mortality predictor at different time points between four of the most commonly used pneumonia severity scores. METHODS This was a secondary analysis of a prospective, multicenter, population-based, observational study of patients hospitalized with CAP in the city of Louisville, KY. The severity indices used were the American Thoracic Society (ATS) criteria, the Pneumonia Severity Index (PSI), the British Thoracic Society criteria (CURB-65), Quick Sepsis-Related Organ Failure Assessment (QSOFA), and direct ICU admission to represent physician discretion. The accuracy, kappa statistic, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the ability to predict in-hospital, 30-day, 6-month, and 1-year mortality. 95% confidence intervals for each variable were generated by bootstrapping with random sampling and resampling of the subjects 1000 times. In addition, the area under the curve (AUC) was calculated for each severity score and mortality time point. RESULTS There were 6013 eligible patients included in this analysis with data collected between the years 2014 and 2016. At each time point, the QSOFA had the highest sensitivity and NPV, while the PSI had the highest specificity and PPV. QSOFA had the highest accuracy for in-hospital mortality, 30-day mortality, and 6-month mortality, and the CURB-65 had highest mortality for 1-year mortality. The QSOFA had the highest kappa statistic for in-hospital mortality, the CURB-65 had the highest kappa statistic for 30-day mortality, and the PSI had the highest kappa statistic for 6-month and 1-year mortality. The AUC was highest for the ATS criteria for in-hospital mortality, and was highest for the PSI at the remaining time points. CONCLUSIONS The results of this study show that QSOFA and the PSI are the most reliable severity indices for mortality predictions based on these measures. QSOFA was found, on average, to have the highest accuracy, sensitivity, and NPV. Additionally, PSI was found, on average, to have the highest kappa statistic, specificity, and PPV. The AUC, on average, was best with PSI as the predictor. QSOFA is most capable of making true negative predictions and the PSI is the most capable of making true positive predictions across the four time points

Comparing Outcomes for Community-Acquired Pneumonia Between Females and Males: Results from the University of Louisville Pneumonia Study

Introduction: Male sex is currently considered to be a risk factor for worsened community-acquired pneumonia (CAP) outcomes compared to female sex; hence, female sex equates to a lower score on the Pneumonia Severity Index. There is no recent update on sex-based outcomes of patients with CAP. The objective of this study was to compare the outcomes of CAP between females and males. Methods: This was a secondary analysis of the University of Louisville Pneumonia Study database. It was a prospective population-based cohort study of all hospitalized adults with CAP who were residents of Jefferson County in the city of Louisville, Kentucky. The study included data from June 1, 2014, to May 31, 2016, and data from October 1, 2016, to May 31, 2017. The study population was divided into two groups: females and males. Results: Female patients had a 13% lower mortality at one year compared to males (aHR 1.13 [95% CI 1.05–1.23], P=0.002). There was no significant difference in mortality between the two groups during hospitalization or at 30-day or six-month follow-up. The median time to discharge for both female and male patients hospitalized with CAP was five days (interquartile range [IQR] 3, 9 days). The median time to clinical stability for both female and male patients hospitalized with CAP was two days (IQR 1, 4 days). Conclusion: This study shows that female patients had significantly lower one-year mortality compared to males. There was no significant difference between females and males in time to clinical stability or length of stay. Further investigation is needed to examine whether risk factors associated with female and male sex predict outcomes among hospitalized patients due to CAP

International Infection Control Training Partnerships: Experiences from the Egypt-University of Louisville Collaboration

Background: Healthcare-associated infection (HAI) is a global challenge that represent opportunities for international collaboration. Both the United States and Egypt prioritize HAI reduction as activities of public health importance. These shared priorities provide a foundation for interactive education and training. Objective: In the fall 2018, The United States Agency for International Development (USAID) sought a US training site where a delegation of physicians and nurses from Egypt could receive experiential training regarding HAI and prevention. The objectives of this review are to: 1) outline the training components used for the US-Egypt collaboration held at the University of Louisville in Kentucky; 2) describe the immersive and experiential approaches used to promote interprofessional education in infection control; and 3) identify some of the successes and challenges of this cultural and practice collaboration. Methods: The course curriculum consisted of a 10-day agenda that provided classroom training, live simulation, role playing, and healthcare facility visits all supporting immersive and experiential learning. Evaluation methods were based upon Kirkpatrick’s Model and included individual self-assessments, daily course evaluations, a summative course evaluation, pre-and post-course testing, and action learning plans. Results: The Egyptian cohort consisted of twenty-six physicians and nurses representing twenty-six different healthcare facilities across the country. Participants rated the course highly but had a strong desire for more interactive experiences at the hospitals. Comparing pre- and post-course knowledge, overall knowledge improved in both the physician and nurse groups. Conclusions: Results from this collaboration demonstrate an ability to provide an organized infection prevention and control training course that reached the University of Louisville team goals and met the stated expectations of the course sponsors. Both the University of Louisville team and the Egyptian delegation indicated that a longer planning horizon would have been beneficial

The Community-Acquired Pneumonia Organization (CAPO) Cloud-Based Research Platform (the CAPO-Cloud): Facilitating Data Sharing in Clinical Research

Background: Pneumonia is a costly and deadly respiratory disease that afflicts millions every year. Advances in pneumonia care require significant research investment and collaboration among pneumonia investigators. Despite the importance of data sharing for clinical research it remains difficult to share datasets with old and new investigators. We present CAPOCloud, a web-based pneumonia research platform intended to facilitate data sharing and make data more accessible to new investigators. Methods: We establish the first two use cases for CAPOCloud to be the automatic subsetting and constraining of the CAPO database and the automatic summarization of the database in aggregate. We use the REDCap data capture software and the R programming language to facilitate these use cases. Results: CAPOCloud allows CAPO investigators to access the CAPO clinical database and explore subsets of the data including demographics, comorbidities, and geographic regions. It also allows them to summarize these subsets or the entire CAPO database in aggregate while preserving privacy restrictions. Discussion: CAPOCloud demonstrates the viability of a research platform combining data capture, data quality, hypothesis generation, data exploration and data sharing in one interface. Future use cases for the software include automated univariate hypothesis testing, automated bivariate hypothesis testing, and principal component analysis