Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting.

BACKGROUND: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2. METHODS: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs. RESULTS: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001). CONCLUSIONS: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

A Risk-Based Clinical Decision Support System for Patient-Specific Antimicrobial Therapy (iBiogram): Design and Retrospective Analysis.

BACKGROUND: There is a pressing need for digital tools that can leverage big data to help clinicians select effective antibiotic treatments in the absence of timely susceptibility data. Clinical presentation and local epidemiology can inform therapy selection to balance the risk of antimicrobial resistance and patient risk. However, data and clinical expertise must be appropriately integrated into clinical workflows. OBJECTIVE: The aim of this study is to leverage available data in electronic health records, to develop a data-driven, user-centered, clinical decision support system to navigate patient safety and population health. METHODS: We analyzed 5 years of susceptibility testing (1,078,510 isolates) and patient data (30,761 patients) across a large academic medical center. After curating the data according to the Clinical and Laboratory Standards Institute guidelines, we analyzed and visualized the impact of risk factors on clinical outcomes. On the basis of this data-driven understanding, we developed a probabilistic algorithm that maps these data to individual cases and implemented iBiogram, a prototype digital empiric antimicrobial clinical decision support system, which we evaluated against actual prescribing outcomes. RESULTS: We determined patient-specific factors across syndromes and contexts and identified relevant local patterns of antimicrobial resistance by clinical syndrome. Mortality and length of stay differed significantly depending on these factors and could be used to generate heuristic targets for an acceptable risk of underprescription. Combined with the developed remaining risk algorithm, these factors can be used to inform clinicians' reasoning. A retrospective comparison of the iBiogram-suggested therapies versus the actual prescription by physicians showed similar performance for low-risk diseases such as urinary tract infections, whereas iBiogram recognized risk and recommended more appropriate coverage in high mortality conditions such as sepsis. CONCLUSIONS: The application of such data-driven, patient-centered tools may guide empirical prescription for clinicians to balance morbidity and mortality with antimicrobial stewardship.

Public Health Role of Academic Medical Center in Community Outbreak of Hepatitis A, San Diego County, California, USA, 2016-2018.

During 2016-2018, San Diego County, California, USA, experienced one of the largest hepatitis A outbreaks in the United States in 2 decades. In close partnership with local healthcare systems, San Diego County Public Health led a public health response to the outbreak that focused on a 3-pronged strategy to vaccinate, sanitize, and educate. Healthcare systems administered nearly half of the vaccinations delivered in San Diego County. At University of California San Diego Health, the use of informatics tools assisted with the identification of at-risk populations and with vaccine delivery across outpatient and inpatient settings. In addition, acute care facilities helped prevent further disease transmission by delaying the discharge of patients with hepatitis A who were experiencing homelessness. We assessed the public health roles that acute care hospitals can play during a large community outbreak and the critical nature of ongoing collaboration between hospitals and public health systems in controlling such outbreaks.

Tuberculosis infection risk, preventive therapy care cascade and incidence of tuberculosis disease in healthcare workers at Maputo Central Hospital.

BACKGROUND: Mozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established. METHODS: This study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated. RESULTS: Of 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35-49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p < 0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10 mm, and among those with a skin test result ≥10 mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14 mm was 63.6%, and for those with a quantitative skin test result ≥15 mm it was 82.2%. CONCLUSIONS: There is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

Annual N95 respirator fit-testing: an unnecessary burden on healthcare.

US regulations mandate annual N95 mask fit testing for healthcare workers, but the optimal testing interval is unknown. In our study using data from 12,565 healthcare workers, the probability of survival free from fit-test failure after 3 years was 99.4%, suggesting that less frequent fit testing every 3 years would be safe.

Assessing past versus present severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection: A survey of criteria for discontinuing precautions in asymptomatic patients testing positive on admission.

Infection prevention program leaders report frequent use of criteria to distinguish recently recovered coronavirus disease 2019 (COVID-19) cases from actively infectious cases when incidentally positive asymptomatic patients were identified on routine severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing. Guidance on appropriate interpretation of high-sensitivity molecular tests can prevent harm from unnecessary precautions that delay admission and impede medical care.

Stethoscope barriers narrative review; It's time for a strategy unfriendly to multi-drug resistant organisms (MDROs).

The current standard of stethoscope hygiene doesn't eliminate the transmission of harmful pathogens, including multi-drug resistant organisms (MDROs). In the era of the increasing prevalence of MDRO infections, the use of new systems providing touch free barriers may improve patient safety versus traditional stethoscope cleaning practices with chemical agents. Our purpose was to provide a narrative literature review regarding barriers as an improvement over the current standard of care for stethoscope hygiene. Searching PubMed, articles were identified if they were in English and published after 1990, using the search term "stethoscope barrier", or if they were from a previously published stethoscope hygiene article using "author's name + stethoscope". Included articles evaluated or discussed stethoscope barriers. Of 28 manuscripts identified, 15 met the inclusion criteria. Barriers were considered superior to alternatives if they were single use, disposable, applied in a touch free fashion, were impervious to pathogens, provided an aseptic patient contact, and were acoustically invisible. Use of a practitioner's personal stethoscope with a disposable diaphragm barrier should be recommended as a new standard of care as this represents an improvement in patient safety and patient experience when compared to the disposable stethoscope or isopropyl alcohol stethoscope diaphragm cleaning.

Hepatitis C Virus Micro-elimination Among People With HIV in San Diego: Are We on Track?

Background: Rising incidence of hepatitis C virus (HCV) among people with HIV (PWH) in San Diego County (SDC) was reported. In 2018, the University of California San Diego (UCSD) launched a micro-elimination initiative among PWH, and in 2020 SDC launched an initiative to reduce HCV incidence by 80% across 2015-2030. We model the impact of observed treatment scale-up on HCV micro-elimination among PWH in SDC. Methods: A model of HCV transmission among people who inject drugs (PWID) and men who have sex with men (MSM) was calibrated to SDC. The model was additionally stratified by age, gender, and HIV status. The model was calibrated to HCV viremia prevalence among PWH in 2010, 2018, and 2021 (42.1%, 18.5%, and 8.5%, respectively), and HCV seroprevalence among PWID aged 18-39 years, MSM, and MSM with HIV in 2015. We simulate treatment among PWH, weighted by UCSD Owen Clinic (reaching 26% of HCV-infected PWH) and non-UCSD treatment, calibrated to achieve the observed HCV viremia prevalence. We simulated HCV incidence with observed and further treatment scale-up (+/- risk reductions) among PWH. Results: Observed treatment scale-up from 2018 to 2021 will reduce HCV incidence among PWH in SDC from a mean of 429 infections/year in 2015 to 159 infections/year in 2030. County-wide scale-up to the maximum treatment rate achieved at UCSD Owen Clinic (in 2021) will reduce incidence by 69%, missing the 80% incidence reduction target by 2030 unless accompanied by behavioral risk reductions. Conclusions: As SDC progresses toward HCV micro-elimination among PWH, a comprehensive treatment and risk reduction approach is necessary to reach 2030 targets.

The dose-response relationship of peginterferon alfa-2a and ribavirin in the treatment of patients coinfected with HIV-HCV.

PURPOSE: The relationship between peginterferon/ribavirin exposure and the probability of achieving a sustained virologic response (SVR) in HIV-HCV coinfected patients is not well described. We conducted a retrospective analysis of HIV-HCV coinfected patients randomized to 48 weeks of treatment with peginterferon alfa-2a (40 kD) 180 µg/week and ribavirin 800 mg/day in the multinational APRICOT study to define optimal exposure thresholds. METHOD: Actual drug exposure was estimated in 287 patients, taking into consideration dose reductions for adverse events or laboratory abnormalities. RESULTS: SVR overall and SVR in those completing treatment was, respectively, 29% and 37% among HCV genotype-1 patients and 59% and 68% among genotype non-1 patients. No patients with ≤40% exposure to ribavirin achieved an SVR. Receiver operating characteristic analysis identified that threshold exposures to both drugs of >75% (genotype-1) and >60% (genotype non-1) are associated with SVR. An existing generalized additive model populated with data from HCV monoinfected patients was updated to predict an overall SVR of 37% if genotype-1 patients received ribavirin 1000 or 1200 mg/day but at the cost of a higher incidence of anemia (23%). CONCLUSION: Completion of scheduled treatment and exceeding certain thresholds for exposure to peginterferon alfa 2a (40 kD) and ribavirin is associated with higher SVR rates.

Reliability and predictive validity of a hepatitis-related symptom inventory in HIV-infected individuals referred for Hepatitis C treatment.

BACKGROUND: We aimed to determine the reliability and validity of a hepatitis symptom inventory and to identify predictors of hepatitis C (HCV) treatment initiation in a cohort of HIV-infected patients. METHODS: Prospective clinic based study that enrolled patients referred for HCV therapy consideration. A hepatitis symptom inventory and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to HIV/HCV individuals. The symptom inventory was factor analyzed and subscale reliability estimated with Cronbach's alpha. Predictive validity was evaluated using generalized estimating equations (GEE). Predictors of HCV treatment were identified using logistic regression. RESULTS: Between April 2008 to July 2010, 126 HIV/HCV co-infected patients were enrolled in the study. Factor analysis using data from 126 patients yielded a three-factor structure explaining 60% of the variance for the inventory. Factor 1 (neuropsychiatric symptoms) had 14 items, factor 2 (somatic symptoms) had eleven items, and factor 3 (sleep symptoms) had two items, explaining 28%, 22% and 11% of the variance, respectively. The three factor subscales demonstrated high intrinsic consistency reliability. GEE modeling of the 32 patients who initiated HCV therapy showed that patients developed worsening neuropsychiatric and somatic symptoms following HCV therapy with stable sleep symptoms. Bivariate analyses identified the following as predictors of HCV therapy initiation: lower HIV log10 RNA, lower scores for neuropsychiatric, somatic and sleep symptoms, lower CES-D scores and white ethnicity. In stepwise multiple logistic regression analysis, low neuropsychiatric symptom score was the strongest independent predictor of HCV therapy initiation and HIV log10 RNA was inversely associated with a decision to initiate HCV treatment. CONCLUSIONS: A 41-item hepatitis-related symptom inventory was found to have a clinically meaningful 3-factor structure with excellent internal consistency reliability and predictive validity. In adjusted analysis, low neuropsychiatric symptom scores and controlled HIV infection were independent predictors of HCV treatment initiation. The usefulness of the HCV symptom inventory in monitoring HCV treatment should be evaluated prospectively.

The Impact of an Inpatient Nurse-Triggered Sepsis Alert on Antimicrobial Utilization.

INTRODUCTION: A nurse-triggered sepsis alert called "Code Sepsis" was implemented for early recognition and management of sepsis. The researchers analyzed its impact on antimicrobial use and identified factors associated with infection as source of Code Sepsis. METHODS: The medical records of hospitalized patients with Code Sepsis between January 1 and June 30, 2018, were reviewed. Patients were classified as "Infection" when probable or definitive infection was identified or "No Infection" when a probable or definitive noninfectious source was identified. Patients were categorized as "Escalation" with addition or change to broader-spectrum antimicrobials or "No Escalation" with no change or change to narrower-spectrum antimicrobials. Escalation was classified as "Indicated" with appropriate escalation or "Not Indicated" with inappropriate escalation. Logistic regression model was used to identify factors associated with Infection as Code Sepsis trigger. RESULTS: Code Sepsis was activated in 529 patients, with Escalation in 246 (46.5%) and No Escalation in 283 (53.5%) patients. Escalation was Indicated in 157 (63.8%) and Not Indicated in 89 (36.2%) patients. Infection was identified in 356 (67.3%) and No Infection in 173 (32.7%) patients. History of HIV (odds ratio [OR] = 2.75, p = 0.03), temperature > 38.3°C or < 36°C (OR = 2.63, p < 0.01), and respiratory rate > 20/minute (OR = 1.56, p = 0.02) were associated with Infection, while surgery within 3 days (OR = 0.30, p < 0.01) was associated with No Infection. CONCLUSION: One hospital system's Code Sepsis inadvertently identified patients without infections and led to antimicrobial overuse. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock only, the organization hopes to optimize resource utilization and improve patient outcomes.

Screening for Sexually Transmitted Infections During Hepatitis C Treatment to Predict Reinfection Among People With HIV.

BACKGROUND: Little is known about the risk of hepatitis C virus (HCV) reinfection among people with HIV (PWH) in the direct-acting antiviral (DAA) era. We evaluate HCV reinfection rates in the DAA era and characterize presustained virologic response (SVR) behavioral risk factors associated with reinfection among PWH at the University of California, San Diego (UCSD). METHODS: Observational longitudinal cohort of PWH treated with DAAs between 2014 and July 2019 who achieved SVR and had at least 1 subsequent HCV viral load measurement. HCV reinfection was defined as new HCV viremia after SVR. We examined whether screening for sexually transmitted infections (STIs) and substance use during the pre-SVR period could identify patients at greater risk for reinfection using exact Poisson regression to compare reinfection incidence rates between those with and without pre-SVR STIs and positive urine drug screens. RESULTS: Eight out of 200 PWH were reinfected with HCV a median ~26 weeks after SVR over 328.1 person-years of follow-up (PYFU), for an incidence rate of 2.44/100 PYFU. The observed HCV reinfection rate was highest among men who have sex with men who inject drugs (MSM IDU; 4.63/100 PFYU) and those aged 30-39 years (6.80/100 PYFU). Having a positive gonorrhea/chlamydia test during the pre-SVR period was a predictor of HCV reinfection. CONCLUSIONS: The HCV reinfection rate in the DAA era is similar to the rate observed in the interferon era in San Diego in PWH. STI screening during HCV treatment may help determine those at higher risk for HCV reinfection.

Hepatitis C Knowledge and Recent Diagnosis Affect Hepatitis C Treatment Willingness in Persons Living With HIV.

BACKGROUND: We assessed the impact of health literacy and hepatitis C (HCV) knowledge on HCV treatment willingness among people living with HIV (PLWH) at an academic HIV clinic. METHODS: Cross-sectional analysis of PLWH coinfected with HCV who completed health literacy, HIV literacy, and HCV knowledge inventories. We estimated the prevalence of low health literacy, HIV knowledge, and HCV knowledge sampled from 3-comparison groups: PLWH not referred for HCV, referred but who "not showed" to the HCV clinic, and referred and attended the HCV clinic. We used mixed-model linear and logistic regression to ascertain predictors of low health literacy, HIV knowledge, HCV knowledge, and predictors of willingness to start HCV treatment. RESULTS: We enrolled 151 PLWH; 17% were female, 38% non-White, and 60% without a high-school education. Approximately, 68% were men who have sex with men, of whom 62% used intravenous drugs. The prevalence of low health, HIV knowledge, and HCV knowledge was 10%, 32%, and 29%, respectively. Predictors of low health literacy were being Hispanic, cirrhotic, and not completing high-school education. Low HCV knowledge was observed in female, non-White, and those diagnosed with HCV for a decade. In adjusted analyses, PLWH living with HCV for a decade (OR: 0.23) were less likely to be very willing to be treated for HCV. By contrast, those with high HCV knowledge were more likely to be very willing to receive treatment (OR: 1.27). CONCLUSION: Low HCV knowledge and living with HCV for at least a decade are under-recognized negative predictors for PLWH's willingness to receive HCV treatment. CLINICAL TRIALS REGISTRATION: ClinicaTrials.gov identifier: NCT20170991.

SARS-CoV-2 detection status associates with bacterial community composition in patients and the hospital environment.

BACKGROUND: SARS-CoV-2 is an RNA virus responsible for the coronavirus disease 2019 (COVID-19) pandemic. Viruses exist in complex microbial environments, and recent studies have revealed both synergistic and antagonistic effects of specific bacterial taxa on viral prevalence and infectivity. We set out to test whether specific bacterial communities predict SARS-CoV-2 occurrence in a hospital setting. METHODS: We collected 972 samples from hospitalized patients with COVID-19, their health care providers, and hospital surfaces before, during, and after admission. We screened for SARS-CoV-2 using RT-qPCR, characterized microbial communities using 16S rRNA gene amplicon sequencing, and used these bacterial profiles to classify SARS-CoV-2 RNA detection with a random forest model. RESULTS: Sixteen percent of surfaces from COVID-19 patient rooms had detectable SARS-CoV-2 RNA, although infectivity was not assessed. The highest prevalence was in floor samples next to patient beds (39%) and directly outside their rooms (29%). Although bed rail samples more closely resembled the patient microbiome compared to floor samples, SARS-CoV-2 RNA was detected less often in bed rail samples (11%). SARS-CoV-2 positive samples had higher bacterial phylogenetic diversity in both human and surface samples and higher biomass in floor samples. 16S microbial community profiles enabled high classifier accuracy for SARS-CoV-2 status in not only nares, but also forehead, stool, and floor samples. Across these distinct microbial profiles, a single amplicon sequence variant from the genus Rothia strongly predicted SARS-CoV-2 presence across sample types, with greater prevalence in positive surface and human samples, even when compared to samples from patients in other intensive care units prior to the COVID-19 pandemic. CONCLUSIONS: These results contextualize the vast diversity of microbial niches where SARS-CoV-2 RNA is detected and identify specific bacterial taxa that associate with the viral RNA prevalence both in the host and hospital environment. Video Abstract.

The role of barriers to care on the propensity for hepatitis C virus nonreferral among people living with HIV.

: Twenty-five percent of HIV/hepatitis C virus (HCV) coinfected patients were not referred for HCV treatment despite unrestricted access in California to direct-acting antivirals (DAA) in 2018. Having unstable housing and ongoing drug use directly affected HCV treatment nonreferral. However, psychiatric history and alcohol use impacted HCV treatment nonreferral through the mediation of not being engaged in HIV care. Achieving HCV elimination requires DAA treatment outside conventional health settings, including substance rehabilitation centers, mental health crisis houses, and homeless shelters.

Aseptic Barriers Allow a Clean Contact for Contaminated Stethoscope Diaphragms.

OBJECTIVE: To determine whether a single-use stethoscope diaphragm barrier surface remains aseptic when placed on pathogen-contaminated stethoscopes. METHODS: From May 31 to August 5, 2019, we tested 2 separate barriers using 3 different strains of 7 human pathogens, including extended-spectrum ß-lactamase-producing Escherichia coli, methicillin-resistant Staphylococcus aureus, and vancomycin resistant Enterococcus faecium. RESULTS: For all diaphragms with either of the 2 barriers tested, no growth was recorded for any of the pathogens. Stethoscopes with aseptic barriers remained sterile for up to 24 hours. These single-use barriers also provided aseptic surfaces when stethoscope diaphragms were inoculated with human specimens, including saliva, stool, urine, and sputum. CONCLUSION: Disposable aseptic diaphragm barriers may provide robust and efficient solutions to reduce transmission of pathogens via stethoscopes.