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Background Little is known regarding the rate and clinical outcomes of asymptomatic carriers of SARS‐CoV‐2 among patients with cancer. Detection of asymptomatic carriers is important in this population given the use of myelosuppressive and immunomodulating therapies. Understanding the asymptomatic carrier rate will help to develop mitigation strategies in this high‐risk cohort. Methods Retrospective cohort analysis of an asymptomatic screening protocol which required patients receiving infusional anti‐cancer therapy to undergo a symptom/exposure screen and SARS‐CoV‐2 PCR testing 24–96 h prior to their infusion. The primary outcome of this analysis was the rate of asymptomatic SARS‐CoV‐2 infection. Secondary outcomes included the rate of COVID‐19‐related hospitalization and mortality and delays in oncologic therapy. Results Among a cohort of 2691 cancer patients who underwent asymptomatic screening, 1.6% (N = 43/2691) of patients were found to be SARS‐CoV‐2 positive on asymptomatic screening. 11.6% (N = 5/43) of the cohort ultimately developed COVID‐19‐related symptoms. Four patients required hospitalization for complications of COVID‐19 infection. No patient died from COVID‐related complications. 97.7% (N = 42/43) had their anti‐cancer therapy delayed or deferred with a median delay of 21 days (range: 7–77 days). Conclusions Overall, among a cohort of active cancer patients receiving anti‐cancer therapy, an asymptomatic SARS‐CoV2 PCR‐based screening protocol detected a small cohort of asymptomatic carriers. The majority of these patients remained asymptomatic on long‐term follow‐up and outcomes were much more favorable compared to previously described outcomes of cancer patients with symptomatic COVID‐19 infection., Little is known about the rate of asymptomatic SARS‐CoV‐2 carriers among cancer patients. Here, we examined a cohort of active cancer patients who underwent asymptomatic SARS‐CoV‐2 PCR screening prior to their infusion therapy. We found a low rate of asymptomatic carriers (1.6%) among this cohort and this asymptomatic cohort had favorable longterm infectious outcomes.

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.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.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), temperature38.3°C or36°C (OR = 2.63, p0.01), and respiratory rate20/minute (OR = 1.56, p = 0.02) were associated with Infection, while surgery within 3 days (OR = 0.30, p0.01) was associated with No Infection.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.

Resurgence of Covid-19 in Vaccinated Health Workers From March through July 2021, a total of 227 health care workers at UCSD, 57% of whom were fully vaccinated, tested positive for SARS-CoV-2; the ...

Objective To evaluate whether Clostridioides (formerly Clostridium) difficile–contaminated stethoscope diaphragms remained aseptic by the placement of an aseptic diaphragm barrier. Methods On November 1, 2019, fresh cultures of C difficile were diluted to 107 colony-forming units (CFU)/mL and used to inoculate 16 stethoscope diaphragms; 8 had an aseptic diaphragm barrier applied and 8 served as nonbarrier controls. Contaminated stethoscopes were anaerobically incubated, then swabbed at 15 and 30 minutes, 2 and 4 hours, and 1, 2, 3, and 7 days after inoculation and subsequently plated onto blood, chocolate, and cycloserine-cefoxitin fructose agar. Plates were incubated for 48 hours and on November 9, 2019, the resulting colonies were manually counted. Statistical analyses (RStudio, version 1.0.153) used analysis of variance with post hoc Tukey honestly significant difference. Results Overall, mean colony count was 33 CFU on stethoscopes without barriers vs zero on those with barriers (P≤.05). Growth was greatest at 48 hours, with colony counts as high as 160 CFU. The presence of the barrier resulted in no growth in 100% of stethoscope diaphragms for up to 1 week. Conclusion We found that stethoscope diaphragm barriers provide an aseptic patient contact point, thus reducing the potential for transmission of C difficile during the physical examination. In critical care environments, in which many hospitals use acoustically inferior disposable stethoscopes, the option of a disposable aseptic stethoscope barrier may allow high-quality auscultation while reducing the potential for pathogen transmission.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., For patients with acute COVID-19 pneumonia who require oxygen support, the International Task Force made suggestions for remdesivir and dexamethasone, but against hydroxychloroquine. Post-discharge management of COVID-19 survivors is a research priority. https://bit.ly/32B96uI

Objective:To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients.Design:Retrospective cohort study.Setting:Eight tertiary-care referral general hospitals in California.Methods:We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment.Results:For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15–1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, −25%; IQR, −20% to −29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%–105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, −15%; IQR, −14% to −21%) and decreased the SIR at all hospitals (median, −8%; IQR, −4% to −11%).Conclusions:For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.

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 β-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.

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.

SARS-CoV-2 Vaccine and Infection in Health Workers After more than 36,500 health care workers at the University of California received at least one dose of vaccine, 71% of 379 workers with positive...

Fifty-four consecutive persons with HIV co-infected with hepatitis C virus (HCV) and liver decompensation were treated with direct-acting antivirals (DAA). The HCV treatment was delivered using a multidisciplinary HIV-coinfection model of care integrating sub-specialty services in 3 countries. Of those treated, 91% (95% confidence interval, 80.1 to 95.9) achieved sustained viral response, and only one person died during treatment. Our study provides evidence that HIV providers achieve excellent outcomes when treating patients with histories of decompensated liver disease, with characteristics similar to those studied using a multidisciplinary HIV-centered approach. © The Author(s) 2021.

Background As of June 2, 2020, 67,113 cases and 321 deaths due to Coronavirus Disease 19 (COVID-19) have been reported in healthcare personnel (HCP) in the United States. Given the close contact of HCP with individuals with COVID-19, it is important to quantify the risk of acquiring COVID-19 in the healthcare setting. Methods We conducted a retrospective cohort study of HCP exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at our academic medical center from March 15, 2020 to May 16, 2020. Exposure during the study period was defined as having contact with patients or other HCP with COVID-19 within 6 feet of distance for at least 90 seconds when HCP’s eyes, nose, or mouth were not covered. HCP with exposures were monitored for symptoms consistent with COVID-19 for 14 days from last exposure and those who developed symptoms were tested for SARS-CoV-2 using RT-PCR. Results We identified 33 exposure events; 19 of which were patient-to-HCP exposures and 14 of which were HCP-to-HCP exposures. These 33 events resulted in 959 exposed HCP among whom 238 (25%) developed one or more symptoms of COVID-19 and required SARS-CoV-2 RT-PCR testing. Testing was performed at 7.1 ± 5.0 (mean ± SD) days from exposure. Of the 238 HCP who were tested, 82% were female and 49% were registered nurses (Table 1). Five HCP tested positive for SARS-CoV-2 by RT-PCR, but one was presumed to have acquired the disease from a household member with confirmed COVID-19. Among the four HCP who were infected due to occupational exposure, three were nurses while one was an environmental service worker (Table 1). Conclusion Despite exposures among HCP, the risk of acquiring symptomatic COVID-19 in the healthcare setting was low with less than 1% of HCP with occupational exposure subsequently diagnosed with COVID-19. With the definition of exposure now changed to at least 15 minutes of close contact without personal protective equipment, we anticipate fewer exposures at our healthcare facility and that much of COVID-19 transmission affecting HCP are due to community exposures. Disclosures All Authors: No reported disclosures

Background Early reports have indicated widespread empiric antimicrobial usage in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As data regarding bacterial complications in patients with Coronavirus Disease 2019 (COVID-19) are limited and emerging, it is important to delineate the burden of complications with bacterial pneumonia in patients with COVID-19 and its implication on antimicrobial usage. Methods We conducted a retrospective cohort study of all hospitalized patients diagnosed with COVID-19 based on detection of SARS-CoV-2 on RT-PCR from March 1, 2020 to May 10, 2020. Data were collected retrospectively to determine the presence of bacterial pneumonia among patients hospitalized with COVID-19 and to identify demographics, comorbidities, or laboratory values that may help to distinguish patients with bacterial pneumonia. Fisher’s exact test was used to analyze categorical data and Student’s t test was used to analyze differences between means. Results Among 99 patients hospitalized with COVID-19 during the study period, complication with bacterial pneumonia was seen in 17 (17%) based on sputum, tracheal aspirate or lower respiratory tract cultures performed 8.9 ± 7.8 (mean ± SD) days from the detection of SARS-CoV-2 on RT-PCR. Staphylococcus aureus was the causative organism in 8 (47%) cases while Enterobacteriaceae were isolated in 7 (41%) cases, Burkholderia cepacia in one (6%) and Rahnella aqualitis in one (6%) case. There were no significant differences in demographics, comorbidities, or laboratory findings between patients with or without complication with bacterial pneumonia. However, those with complication with bacterial pneumonia were more likely to be intubated (24% vs. 88%, p< 0.01), on vasopressors (23% vs. 82%, p < 0.01), and require intensive care unit admission (37% vs. 94%, p< 0.01). Conclusion Nosocomial and ventilator-associated pneumonia were commonly seen among hospitalized patients with COVID-19 requiring intubation and intensive care use admission. With complications of bacterial pneumonia common among critically-ill patients infected with SARS-CoV-2, widespread antimicrobial usage may increase the selective pressure for antibiotic resistance in this patient population. Disclosures All Authors: No reported disclosures

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.

Synergistic effects of bacteria on viral stability and transmission are widely documented but remain unclear in the context of SARS-CoV-2. We collected 972 samples from hospitalized patients with coronavirus disease 2019 (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 contextualized the massive microbial diversity in this dataset through meta-analysis of over 20,000 samples. Sixteen percent of surfaces from COVID-19 patient rooms were positive, with the highest prevalence in floor samples next to patient beds (39%) and directly outside their rooms (29%). Although bed rail samples increasingly resembled the patient microbiome over time, SARS-CoV-2 was detected less there (11%). Despite viral surface contamination in almost all patient rooms, no health care workers contracted the disease, suggesting that personal protective equipment was effective in preventing transmissions. SARS-CoV-2 positive samples had higher bacterial phylogenetic diversity across human and surface samples, and higher biomass in floor samples. 16S microbial community profiles allowed for high SARS-CoV-2 classifier accuracy in not only nares, but also forehead, stool, and floor samples. Across distinct microbial profiles, a single amplicon sequence variant from the genus Rothia was highly predictive of SARS-CoV-2 across sample types and had higher prevalence in positive surface and human samples, even compared to samples from patients in another intensive care unit prior to the COVID-19 pandemic. These results suggest that bacterial communities may contribute to viral prevalence both in the host and hospital environment., One Sentence Summary: Microbial classifier highlights specific taxa predictive of SARS-CoV-2 prevalence across diverse microbial niches in a COVID-19 hospital unit.

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.

The stethoscope has long been at the center of patient care, as well as a symbol of the physician–patient relationship. While advancements in other diagnostic modalities have allowed for more efficient and accurate diagnosis, the stethoscope has evolved in parallel to address the needs of the modern era of medicine. These advancements include sound visualization, ambient noise reduction/cancellation, Bluetooth (Bluetooth SIG Inc, Kirkland, Wash) transmission, and computer algorithm diagnostic support. However, despite these advancements, the ever-changing climate of infection prevention, especially in the wake of the COVID-19 pandemic, has led many to question the stethoscope as a vector for infectious diseases. Stethoscopes have been reported to harbor bacteria with contamination levels comparable with a physician's hand. Although disinfection is recommended, stethoscope hygiene compliance remains low. In addition, disinfectants may not be completely effective in eliminating microorganisms. Despite these risks, the growing technological integration with the stethoscope continues to make it a highly valuable tool. Rather than casting our valuable tool and symbol of medicine aside, we must create and implement an effective method of stethoscope hygiene to keep patients safe.

Background Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, was declared a global pandemic by the World Health Organization in March 2020. Case presentation We report a case of a 51-year-old Chinese woman who was evacuated from Wuhan, China and diagnosed with coronavirus disease 2019 infection at a Southern California quarantine facility. Her clinical course was notable for high fevers, night sweats, productive cough, transient leukopenia, lymphopenia, thrombocytopenia, and transaminitis. Evolving hypoxia and infiltrates on chest imaging warranted the trial of an investigational antiviral drug - remdesivir. Our patient recovered and was discharged after 2 weeks of hospitalization. Conclusions This case highlights our patient’s clinical course, including diagnostic work-up, medical management, and challenges in defining non-infectivity in a relatively unknown disease.

Objective To describe the implementation of technological support important for optimizing clinical management of the COVID-19 pandemic. Materials and Methods Our health system has confirmed prior and current cases of COVID-19. An Incident Command Center was established early in the crisis and helped identify electronic health record (EHR)-based tools to support clinical care. Results We outline the design and implementation of EHR-based rapid screening processes, laboratory testing, clinical decision support, reporting tools, and patient-facing technology related to COVID-19. Discussion The EHR is a useful tool to enable rapid deployment of standardized processes. UC San Diego Health built multiple COVID-19-specific tools to support outbreak management, including scripted triaging, electronic check-in, standard ordering and documentation, secure messaging, real-time data analytics, and telemedicine capabilities. Challenges included the need to frequently adjust build to meet rapidly evolving requirements, communication, and adoption, and to coordinate the needs of multiple stakeholders while maintaining high-quality, prepandemic medical care. Conclusion The EHR is an essential tool in supporting the clinical needs of a health system managing the COVID-19 pandemic.

Background: The County of San Diego Health and Human Services (SDHHSA) established a goal to vaccinate 1.9 million residents as quickly as possible to attain vaccine induced herd immunity. This strategy would minimize the emergence of more transmissible variants, to which some vaccines may be less effective. With this strategy in mind, UC San Diego Health (UCSDH) collaborated with the local health authorities and the San Diego Padres to build a superstation in downtown San Diego in the parking lot of a baseball stadium. Methods: Building on the experience of rapidly vaccinating the UCSDH workforce in mid-December 2020, UCSDH and SDHHSA partnered to more efficiently distribute SARS-CoV-2 vaccine in San Diego County by building a vaccine superstation. The San Diego Padres offered their parking lot as the site; it was centrally located, easily accessible, quick to set up, and semipermanent. They also provided infrastructure support, event coordination, and internet capability. Occupying a space of ~6.5 acres, the superstation included 12 lanes serving 12 cars each, with ~3 cycles every hour, as well as a pedestrian walk-up station. Altogether, the site had the capacity for >5,000 vaccinations daily. This effort required coordination among administration, healthcare providers, IT specialists, and support staff—a daily workforce of >300 persons. The workforce needs were met using a multipronged approach, including flexible staffing, coordination of volunteers, and recruitment of previously retired providers. The private–public partnership enabled the superstation to be up and running in 5 days. Results: The operation was quickly ramped up to provide >6,000 vaccines daily. Initially only open to healthcare workers, on January 17 the superstation was expanded to persons aged >75 years, with further expansion to those aged ≥65 years on January 23. From January 11 to February 5, >100,000 individuals received their first dose of vaccine at the superstation, corresponding to ~31% of all San Diego county vaccinations. Conclusions: Vaccination of as many people as quickly as possible is essential to controlling the pandemic. Unchecked replication of SARS-CoV-2 allows increases the chance that the virus may develop mutations that render vaccines and therapeutics less effective. Our model vaccine superstation was replicated at 3 more sites around the county, the limited allocation of vaccine has been the only barrier to further expansion. A force of 10 superstations could administer a first dose to the remaining 1.6 million county residents within 32 days.Funding: NoDisclosures: None

Background: In January 2019, our large academic medical center implemented hard stops for ordering Clostridiodes difficile nucleic acid amplification testing (NAAT), and required a discussion with an infectious diseases physician if the order was placed in a clinical scenario not consistent with the 2017 IDSA/SHEA C. difficile infection (CDI) testing guidelines. Recently, some groups have expressed concerns that requiring the discontinuation of laxatives may delay the diagnosis of CDI and result in serious adverse outcomes. Methods:C. difficile testing stewardship interventions were performed at 2 hospitals within the same university health system to reduce inappropriate testing. In January 2019, a best practice advisory (BPA) was implemented to alert providers ordering C. difficile NAAT if patients had received laxatives within 24 hours, requiring a discussion with the ID physician to override the hard stop. We reviewed clinical outcomes of patients who had a BPA alert due to laxative use within the past 24 hours April 23 to October 23, 2019. Results: During the study period, there were 235 patients with a BPA because of laxative use within the past 24 hours. Moreover, 55 (23.4%) continued to experience diarrhea after the discontinuation of laxatives and were retested for CDI within 7 days. Only 8 tests returned positive, suggesting that, at most, 3.4% of cases had delayed diagnoses because of the hard stop. This finding is supported by the increase in the percentage of tests positive from 11.6% observed overall to 14.6% (8 of 55) after this intervention. There were no severe CDI cases (ICU admission, colectomy, or death) among patients who had delayed testing due to laxative use. Conclusions: In the setting of laxative use, C. difficile testing stewardship interventions with C. difficile NAAT using a hard-stop BPA are effective in reducing unnecessary testing and safe if they are used in combination with a real-time expert input of the risk of clinical disease.Funding: NoneDisclosures: None

Public reporting of Clostridioides difficile infection (CDI) using laboratory-identified events has led some institutions to revert from molecular-based tests to less sensitive testing modalities. At one academic medical center, researchers chose to use nucleic acid amplification test alone in CDI diagnosis with institutional protocols aimed at diagnostic stewardship.A single-center, quasi-experimental study was conducted to introduce and analyze the effects of various diagnostic stewardship interventions. In April 2017 an order report was created to inform providers of patients' recent bowel movements, laxative use, and prior Clostridioides difficile (CD) testing (Intervention 1). In November 2017 nursing staff were empowered to not send nondiarrheal stools for testing (Intervention 2). In February 2019, an interruptive alert was implemented to prevent testing that was not indicated (Intervention 3). CD testing rates and healthcare facility-onset CDI (HO-CDI) rates were compared before and after the interventions using one-way analysis of variance (ANOVA).At baseline, testing for CD after 3 days of admission was performed at mean ± standard deviation of 15.9 ± 1.7 tests/1,000 patient-days. After Intervention 1, it decreased to 12.1 ± 1.1 tests. This further decreased to 10.6 ± 0.8 after Intervention 2 and to 8.1 ± 0.1 after Intervention 3 (p0.001). HO-CDI cases per 10,000 patient-days declined from 12.7 ± 1.4 cases at baseline to 10.7 ± 1.2 after Intervention 1, to 8.7 ± 2.4 after Intervention 2, and to 5.8 ± 0.2 after Intervention 3 (p = 0.03).A multidisciplinary approach optimizing electronic health record support tools and leveraging nursing education can reduce both testing and HO-CDI rates while using the most sensitive testing modality.

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

Background Little is known about the influence of ongoing barriers to care in the persistence of hepatitis C virus (HCV) viremia after treatment with direct-acting antivirals (DAAs) among people living with human immunodeficiency virus (PLWH). Methods We conducted a retrospective cohort analysis of PLWH treated through the standard of care in 3 Western countries, to investigate the predictors of HCV treatment failure (clinical or virologic), defined as having a detectable serum HCV ribonucleic acid within 12 weeks after DAA discontinuation. In addition to HCV and liver-related predictors, we collected data on ongoing illicit drug use, alcohol abuse, mental illness, and unstable housing. Logistic regression analyses were used to identify predictors of HCV treatment failure. Results Between January 2014 and December 2017, 784 PLWH were treated with DAA, 7% (n = 55) of whom failed HCV therapy: 50.9% (n = 28) had a clinical failure (discontinued DAA therapy prematurely, died, or were lost to follow-up), 47.3% (n = 26) had an HCV virologic failure, and 1 (1.8%) was reinfected with HCV. Ongoing drug use (odds ratio [OR] = 2.60) and mental illness (OR = 2.85) were independent predictors of any HCV treatment failure. Having both present explained 20% of the risk of any HCV treatment failure due to their interaction (OR = 7.47; P < .0001). Predictors of HCV virologic failure were ongoing illicit drug use (OR = 2.75) and advanced liver fibrosis (OR = 2.29). Conclusions People living with human immunodeficiency virus with ongoing illicit drug use, mental illness, and advanced liver fibrosis might benefit from enhanced DAA treatment strategies to reduce the risk of HCV treatment failure.

Introduction Little is known about the rates of asymptomatic COVID-19 carriers among cancer patients. The rate of asymptomatic carriers is important to understand in this population given the use of myelosuppressive and immunomodulating therapies and the risk of transmission to other patients in shared infusion centers. At UC San Diego, in June 2020, we implemented a COVID-19 asymptomatic screening protocol in which cancer patients receiving anti-cancer therapy in an infusion center must undergo symptom-based screening and then SARS-CoV-2 PCR testing prior to their infusion. Here, we describe the results of this asymptomatic screening protocol. Methods This was a single-center retrospective analysis of patients with active cancer receiving infusional anti-cancer therapy in 5 infusion centers who underwent at least 1 asymptomatic SARS-CoV-2 PCR test between 6/1- 12/1/2020. The primary endpoint was the rate of COVID-19 positivity among asymptomatic patients. Symptomatic patients were excluded. Secondary endpoints included COVID-19-related outcomes and patterns of oncologic management for asymptomatic COVID-19 positive patients. Results A cohort of 2,202 cancer patients received at least 1 asymptomatic SARS-CoV-2 PCR test prior to receipt of infusional anti-cancer therapy. 0.95% (N=21/2202) of patients were found to be PCR-positive on asymptomatic screening. Among positive patients, 9.5% (N=2/21) had hematologic malignancies and 90.5% (N=19/21) had solid tumors. In terms of therapy, 76.2% (N=16) were treated with cytotoxic chemotherapy, 9.5% (N=2) with targeted therapy, 4.7% (N=1) with immunotherapy, and 9.5% (N=2) were on a clinical trial. With a median follow-up of 122 days from positive PCR test (range: 8-186), only 2 of 21 (9.5%) of the cohort ultimately developed COVID-related symptoms. Both patients had a diagnosis of acute leukemia and 1 patient required hospitalization for COVID-related complications. No patients died from COVID-related complications. With regards to oncologic management, 95.2% (N=20/21) of patients had their therapy delayed or deferred with a median delay of 21 days (range: 7-77 days). Only 1 patient proceeded with cytotoxic chemotherapy on schedule in the setting of adjuvant chemoradiation for oropharyngeal squamous cell carcinoma. Among the overall cohort, an additional 26 patients (1.2%) developed cases of symptomatic COVID-19 infection during the study period. Conclusions A strategy of asymptomatic screening of cancer patients receiving anti-cancer therapy in an infusion center detected an extremely low rate of asymptomatic carriers of COVID-19. This low rate of asymptomatic carriers may be due to a number of factors including multiple symptom-based screenings prior to infusion, behavior modification among patients, and/or differential immune responses to COVID-19 infection. Asymptomatic carriers in this cohort appeared to have favorable outcomes with few developing symptoms or requiring hospitalization, though the number of positive patients in our cohort is low, precluding definitive conclusions in this population. Citation Format: Justin A. Shaya, Angelo Cabal, Francesca Torriani, Joseph Califano, Scott Lippman, Assuntina Sacco, Rana R. McKay. Asymptomatic detection of COVID-19 among cancer patients receiving infusional anti-cancer therapy [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S09-04.

Background Healthcare-associated infections (HAIs), such as C. difficile colitis, pose a significant health risk. C. difficile is a spore-forming gram-positive anaerobic bacillus capable of surviving on various surfaces. While a strong emphasis has been placed on hand-washing and environmental cleaning with bleach products to limit the spread of C. difficile, stethoscope contamination has been poorly addressed. Studies have demonstrated that the stethoscope diaphragm harbors similar levels and type of contamination to one’s hands. While a non-alcohol-based solution is recommended for stethoscope hygiene in settings at risk for C. difficile, the use of an aseptic stethoscope diaphragm barrier has not been evaluated. Our purpose is to evaluate whether C. difficile-contaminated stethoscope diaphragms remain aseptic by the placement of an aseptic diaphragm barrier. Methods Fresh cultures of C. difficile were diluted to 107 CFU/mL. After inoculating 16 stethoscope diaphragms with C. difficile, 8 had an aseptic diaphragm barrier applied, and 8 served as non-barrier controls. Contaminated stethoscopes were placed in an anaerobic incubator, then swabbed at 15 and 30 minutes, 2 and 4 hours, and 1, 2, 3, and 7 days after inoculation, and subsequently plated onto blood, chocolate, and cycloserine-cefoxitin fructose agar. These plates were incubated for 48 hours, and resulting colonies were manually counted. Statistical analysis was performed (RStudio version 1.0.153) by ANOVA (Analysis of Variance) with post-hoc Tukey HSD (Honestly Significant Difference). Results Overall, mean colony count was 33 CFU on the 8 stethoscope diaphragms without barriers, vs zero on those with barriers (p≤ 0.05). Growth rates were greatest at 48 hours, with colony counts as high as 160. While stethoscope diaphragms without barriers had increasing rates of C. difficile culture growth, the presence of the barrier resulted in no growth in 100% of stethoscope diaphragms for up to 1 week after contamination (Figure 1). C. difficile colony counts from stethoscope diaphragms at time-points up to 1 week. Conclusion Aseptic barriers allow C. difficile-contaminated stethoscope diaphragms to remain without bacterial growth for up to a week. Disposable aseptic diaphragm barriers may be effective in preventing the spread of C. difficile. Disclosures William F. Peacock, MD, AseptiScope Inc. (Board Member)

Background We estimated and characterized the proportion of patients living with HIV (PLWH) who missed hepatitis C (HCV) intake appointments and subsequently failed to establish HCV care. Methods Logistic regression analyses were used to identify factors associated with missed HCV intake appointments and failure to establish HCV care among PLWH referred for HCV treatment between January 2014 and December 2017. In addition to demographics, variables included HIV treatment characteristics, type of insurance, liver health status, active alcohol or illicit drug use, unstable housing, and history of a mental health disorder (MHD). Results During the study period, 349 new HCV clinic appointments were scheduled for 202 unduplicated patients. Approximately half were nonwhite, and 80% had an undetectable HIV viral load. Drug use (31.7%), heavy alcohol use (32.8%), and MHD (37.8%) were prevalent. Over the 4-year period, 21.9% of PLWH referred for HCV treatment missed their HCV intake appointment. The proportion increased each year, from 17.2% in 2014 to 25.4% in 2017 (P = .021). Sixty-six of the 202 newly referred HCV patients (32.7%) missed their first HCV appointment, and 28 of these (42.4%) failed to establish HCV care. Having a history of MHD, CD4 Conclusions The proportion of PLWH with missed HCV appointments increased over time. HCV elimination among PLWH may require integrated treatment of MHD and substance use.

Background Clinicians are incorporating patient-reported outcomes in the management of HIV-infected persons co-infected with hepatitis C virus (HCV), but there are no validated inventories to monitor symptoms of patients during HCV therapy. Design Five-year retrospective cohort analysis of persons living with HIV (PLWH) treated for HCV. Methods The HCV symptom-inventory (HCV-SI) was administered before, during, and after HCV treatment. Discriminant validity was assessed, separately, in mixed model linear regression of HCV-SI T-scores on treatment regimens (pegylated-interferon and ribavirin; pegylated-interferon, ribavirin, and telaprevir; and interferon-free antivirals); and side effect-related premature treatment discontinuation (SE-DC). Results From the 103 patients who completed the HCV-SI, 7% were female, 26% non-white, 32% cirrhotics and 91% had undetectable HIV viral loads. Most had genotype 1 (83%) and were HCV treatment-naïve (78%). We treated 19% of patients with pegylated-interferon and ribavirin, 22% with pegylated-interferon, ribavirin, and telaprevir and 59% received interferon-free antivirals. Overall, 77% achieved a sustained virologic response, and 6% discontinued HCV treatment due to side effects. In the treatment discrimination model, compared to the no treatment period, HCV-SI scores were significantly (p

Background Balancing antimicrobial stewardship with sepsis management is a challenge. At our academic medical center, a “Code Sepsis” was implemented as a nursing driven initiative to improve early recognition and management of sepsis. Per protocol, Code Sepsis is activated in patients who meet two or more systemic inflammatory response syndrome (SIRS) criteria due to a suspected infection to allow for early implementation of the sepsis bundle, which includes laboratory testing, fluid resuscitation, and antibiotic administration (Figure 1). We analyzed the impact that Code Sepsis had on antimicrobial use among hospitalized patients over a six month period. Methods We reviewed the electronic medical records of hospitalized patients with Code Sepsis activation between January 1, 2018 and June 30, 2018 to determine whether antibiotics were “escalated” or “not escalated.” Among patients who had antibiotic escalation, escalation was classified as “indicated” or “not indicated” (Figure 2). A logistic regression model was used to identify characteristics, SIRS or organ dysfunction criteria predictive of indicated antimicrobial escalation. Results Code Sepsis was activated in 529 patients with antibiotics escalated in 247 (47%) and not escalated in 282 (53%) (Table 1). Among patients whose antibiotics were escalated, 64% (152) had an indication. In 36% (89), escalation was not indicated as Code Sepsis was due to a suspected noninfectious source, known infectious source already on appropriate antimicrobials, or a suspected infectious source in which diagnostic results had already shown the absence of the infection (Figure 2). Odds of indicated antibiotic escalation increased with the number of SIRS and organ dysfunction criteria (Table 2). Conclusion In our efforts to improve sepsis outcomes, we focused on early recognition (Code Sepsis) and intervention (sepsis bundle). However, our Code Sepsis inadvertently led to antibiotic overutilization. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock, we hope to optimize resource utilization and improve patient outcomes. Disclosures All authors: No reported disclosures.

Background.Central line-associated bloodstream infection (CLABSI) is a national target for mandatory reporting and a Centers for Medicare and Medicaid Services target for value-based purchasing. Differences in chart review versus claims-based metrics used by national agencies and groups raise concerns about the validity of these measures.Objective.Evaluate consistency and reasons for discordance among chart review and claims-based CLABSI events.Methods.We conducted 2 multicenter retrospective cohort studies within 6 academic institutions. A total of 150 consecutive patients were identified with CLABSI on the basis of National Healthcare Safety Network (NHSN) criteria (NHSN cohort), and an additional 150 consecutive patients were identified with CLABSI on the basis of claims codes (claims cohort). Ail events had full-text medical record reviews and were identified as concordant or discordant with the other metric.Results.In the NHSN cohort, there were 152 CLABSIs among 150 patients, and 73.0% of these cases were discordant with claims data. Common reasons for the lack of associated claims codes included coding omission and lack of physician documentation of bacteremia cause. In the claims cohort, there were 150 CLABSIs among 150 patients, and 65.3% of these cases were discordant with NHSN criteria. Common reasons for the lack of NHSN reporting were identification of non-CLABSI with bacteremia meeting Centers for Disease Control and Prevention (CDC) criteria for an alternative infection source.Conclusion.Substantial discordance between NHSN and claims-based CLABSI indicators persists. Compared with standardized CDC chart review criteria, claims data often had both coding omissions and misclassification of non-CLABSI infections as CLABSI. Additionally, claims did not identify any additional CLABSIs for CDC reporting. NHSN criteria are a more consistent interhospital standard for CLABSI reporting.

The government publishes 3 different public report surgical site infection (SSI) metrics, all called standardized infection ratios (SIRs), that impact perceived hospital quality. We conducted a non-random cross-sectional observational pilot study of 20 California hospitals that voluntarily submitted colon surgery and SSI data. Discordant SIR values, leading to contradictory conclusions, occurred in 35% of these hospitals.Infect Control Hosp Epidemiol2016;1–5

Highlights • 22.5% of adult patients with H1N1 developed bacterial co-infection. • Staphylococcus aureus was the most common cause of co-infection. • Bacterial and viral co-infections were associated with death in bivariate. • Patients with a bacterial co-infection had greater use of resources., Background Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. Objectives To describe the spectrum and clinical impact of co-infections. Study design Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis. Results Of 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23–0.73], p = 0.003), leukocytosis (>11 K/μl, OR 3.7 [2.2–6.2], p

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 add...

Using an inclusive HCV treatment protocol that encourages prospective engagement in care, HIV-infected patients with and without ongoing barriers to care had similar chances of HCV sustained viral response irrespective of which HCV treatment regimen was used., Background. Access to hepatitis C virus (HCV) medications for human immunodeficiency virus (HIV)-infected patients with ongoing barriers to care is restricted by healthcare payers in the absence of HCV treatment outcomes data in the era of direct-acting antivirals (DAA). Methods. Retrospective analysis of HCV treatment outcomes using interferon (IFN)-free DAA regimens and an inclusive treatment protocol in an urban HIV clinic where ongoing barriers to care (drug or alcohol use, psychiatric disease, and/or unstable housing) are common. Then, using logistic regression analysis, we compared the proportion of HIV-infected patients who achieved HCV sustained viral response (SVR) in the pegylated-IFN plus ribavirin (PEG-IFN/RBV, 2008–2011), pegylated-IFN plus ribavirin and telaprevir (PEG-IFN/RBV/PI, 2011–2013), and IFN-free DAA therapy eras (2014). Results are displayed using forest plots. Results. The proportion of patients who achieved HCV SVR in the PEG-IFN/RBV, PEG-IFN/RBV/PI, and IFN-free DAA therapy eras increased from 38.4% (95% confidence interval [CI], 23.2–53.7) and 48% (95% CI, 28.4–67.6) to 83.3% (95% CI, 70.0–96.7), respectively. Similar proportions of patients with ongoing barriers to care were treated during the PEG-IFN/RBV (25 of 39 [64%]), PEG-IFN/RBV/PI (14 of 25 [56%]), and IFN-free DAA (16 of 30 [53%]) eras. Hepatitis C virus SVR among patients with ongoing barriers to care improved from 40% (95% CI, 21–59) to 76.5% (95% CI, 56–97) in the PEG-IFN/RBV and IFN-free DAA eras, respectively. After stratification for factors associated with HCV SVR such as HCV genotype and cirrhosis, HCV SVR were similar in patients regardless of the presence of ongoing barriers to care. Conclusions. Using IFN-free DAA and an inclusive HCV treatment protocol, 76.5% of HIV/HCV-treated patients with ongoing barriers to care achieved HCV SVR.

Background: In HIV/ hepatitis C virus (HCV) coinfection, adverse events (AEs) during HCV therapy account for 12%-39% of treatment discontinuations. It is unknown whether sex influences complications. Methods: Meta-analysis to study the effect of sex and other predictors of AEs in 3 randomized trials, ACTG 5071, APRICOT, and ANRSHC02-RIBAVIC of Interferon (IFN) and Pegylated IFN (PEG), both with and without Ribavirin, in HIV/HCV coinfection. Primary endpoints were AEs requiring treatment discontinuation (AETD) or first dose modification (AEDM). Multi-covariate stratified logistic regression was used to study predictors and assess interactions with sex. Results: Twenty-one percent of 1376 subjects were women; 61% had undetectable HIV RNA; 14% were antiretroviral (ARV) therapy naive at entry; median CD4 was 485 cells per cubicmillimeter. Seventeen percent had an AETD and 50% AEDM; women had more AETD than men (24% vs. 16% P = 0.003) and AEDM (61 % vs. 48% P < 0.0001). AETD and AEDM occurred earlier in women; but the types of AETD and AEDM were similar between sexes. Seventy-four percent of AETDs and 49% of AEDMs involved constitutional AEs; 18% of AETD depression; and 26% of AEDM neutropenia. We identified interactions with sex and body mass index (BMI) (P = 0.04, continuous) and nonnucleoside reverse transcriptase inhibitor (P = 0.03); more AETDs were seen in men with lower BMI (P = 0.01) and in women on nonnucleoside reverse transcriptase inhibitors (P = 0.009). More AEDMs were seen with PEG [odds ratio (OR) = 2.07]; older age (OR = 1.48 per 10 years); decreasing BMI (OR = 1.04 per kg/m 2 ); HCV genotype 1, 4 (OR = 1.31); Ishak 5, 6 (OR = 1.42); decreasing Hgb (OR = 1.23 per g/dL); and decreasing absolute neutrophil count (1.04 per 500 cells/mm 3 ). Interactions between sex and ARV-naive status (P = 0.001) and zidovudine (P = 0.001) were identified: There were more AEDMs in ARV-naive women (P = 0.06) and ARV-experienced men (P = 0.001) and higher AEDMs in women with zidovudine (P = 0.0002). Conclusions: Although there was no difference in type of AE, AETD and AEDM were more frequent and occurred earlier in women. In women, ARV regimen may be an important predictor of AETDs during HCV therapy and should be explored as a predictor of AEs in HIV/HCV coinfection trials.

Few attempts have been made to include the oxygen enhancement ratio (OER) in treatment planning for ion beam therapy, and systematic studies to evaluate the impact of hypoxia in treatment with the beam of different ion species are sorely needed. The radiobiological models used to quantify the OER in such studies are mainly based on the dose-averaged LET estimates, and do not explicitly distinguish between the ion species and fractionation schemes. In this study, a new type of OER modelling, based on the microdosimetric kinetic model, taking into account the specificity of the different ions, LET spectra, tissues and fractionation schemes, has been developed. The model has been benchmarked with published in vitro data, HSG, V79 and CHO cells in aerobic and hypoxic conditions, for different ion irradiation. The model has been included in the simulation of treatments for a clinical case (brain tumour) using proton, lithium, helium, carbon and oxygen ion beams. A study of the tumour control probability (TCP) as a function of oxygen partial pressure, dose per fraction and primary ion type has been performed. The modelled OER depends on both the LET and ion type, also showing a decrease for an increased dose per fraction with a slope that depends on the LET and ion type, in good agreement with the experimental data. In the investigated clinical case, a significant increase in TCP has been found upon increasing the ion charge. Higher OER variations as a function of dose per fraction have also been found for low-LET ions (up to 15% varying from 2 to 8 Gy(RBE) for protons). This model could be exploited in the identification of treatment condition optimality in the presence of hypoxia, including fractionation and primary particle selection.

Compounding pharmacies should be required to follow good manufacturing practices, including end-product sterility testing., Nationally distributed medications from compounding pharmacies, which typically adhere to less stringent quality-control standards than pharmaceutical manufacturers, can lead to multistate outbreaks. We investigated a cluster of 6 patients in a Maryland hospital who had Sphingomonas paucimobilis bloodstream infections in November 2007. Of the 6 case-patients, 5 (83%) had received intravenous fentanyl within 48 hours before bacteremia developed. Cultures of unopened samples of fentanyl grew S. paucimobilis; the pulsed-field gel electrophoresis pattern was indistinguishable from that of the isolates of 5 case-patients. The contaminated fentanyl lot had been prepared at a compounding pharmacy and distributed to 4 states. Subsequently, in California, S. paucimobilis bacteremia was diagnosed for 2 patients who had received intravenous fentanyl from the same compounding pharmacy. These pharmacies should adopt more stringent quality-control measures, including prerelease product testing, when compounding and distributing large quantities of sterile preparations.

Background Dyslipidemia is a frequent complication of antiretroviral therapy (ART) for patients with human immunodeficiency virus infection (HIV). The effects of ART on lipoproteins are less well-understood, and have not been investigated in a prospective study where assignment to ART is randomized. Objective To evaluate the effects of three class-sparing ART regimens on lipids and lipoproteins. Methods This was a substudy of a prospective, multicenter study of treatment-naive HIV-infected individuals randomly assigned to receive a regimen of nucleoside reverse transcriptase inhibitors (NRTIs) + the non-nucleoside reverse transcriptase inhibitor efavirenz, NRTIs + the protease inhibitor lopinavir/ritonavir, or a NRTI-sparing regimen of efavirenz + lopinavir/ritonavir. Lipoproteins were measured by nuclear magnetic resonance spectroscopy. Results Among the 82 participants, total and small low-density lipoprotein concentrations increased by a median of 152 nmol/L (interquartile range, −49 to +407 nmol/L; P P P KW P P = 0.022). High-density lipoproteins increased by a median of 6.0 nmol/L (interquartile range, 2.8–10.4 nmol/L; P P KW = 0.069). Changes were not related to changes in markers of insulin/glucose metabolism. Conclusions Total and small low-density lipoprotein concentrations increased, especially in the arms containing lopinavir/ritonavir, as did increases in total very-low-density lipoproteins. Adverse changes were especially prominent in the arm with efavirenz + lopinavir/ritonavir.

To identify baseline characteristics predictive of a sustained virological response (SVR) in patients with HIV-hepatitis C virus (HCV) co-infection treated with interferon-based therapy.A stepwise multiple logistic regression analysis was used to explore the prognostic factors associated with SVR [undetectable HCV-RNA (50 IU/ml) at the end of untreated follow-up in week 72].In all patients (n = 853), in addition to the HCV therapy received, the factors most predictive of SVR were baseline HCV-RNA [or = versus400 000 IU/ml; odds ratio (OR) 4.77; 95% confidence interval (CI) 3.15-7.22; P0.0001] and HCV genotype (OR 2.87; 95% CI 2.00-4.12; P0.0001). HIV treatment (with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor; P = 0.034), race (P = 0.027), and body mass index (P = 0.039) were also weak predictors of HCV treatment response.In the AIDS PEGASYS Ribavirin International Co-infection Trial (APRICOT), the predictors of SVR among HIV-HCV co-infected patients treated with peginterferon alfa-2a plus ribavirin were similar to those in patients with HCV mono-infection. The HCV genotype and pretreatment HCV-RNA level had the greatest influence on SVR.

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs−/anti-HBc+; anti-HBs+/ anti-HBc−; anti-HBs−/anti-HBc−. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs−/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc−; 45 (25.6%) anti-HBs−/anti-HBc−. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology. J. Med. Virol. 79: 694–700, 2007. © 2007 Wiley-Liss, Inc.

Author(s): Shah, Nirav S; Greenberg, Jared A; McNulty, Moira C; Gregg, Kevin S; Riddell, James; Mangino, Julie E; Weber, Devin M; Hebert, Courtney L; Marzec, Natalie S; Barron, Michelle A; Chaparro-Rojas, Fredy; Restrepo, Alejandro; Hemmige, Vagish; Prasidthrathsint, Kunatum; Cobb, Sandra; Herwaldt, Loreen; Raabe, Vanessa; Cannavino, Christopher R; Hines, Andrea Green; Bares, Sara H; Antiporta, Philip B; Scardina, Tonya; Patel, Ursula; Reid, Gail; Mohazabnia, Parvin; Kachhdiya, Suresh; Le, Binh-Minh; Park, Connie J; Ostrowsky, Belinda; Robicsek, Ari; Smith, Becky A; Schied, Jeanmarie; Bhatti, Micah M; Mayer, Stockton; Sikka, Monica; Murphy-Aguilu, Ivette; Patwari, Priti; Abeles, Shira R; Torriani, Francesca J; Abbas, Zainab; Toya, Sophie; Doktor, Katherine; Chakrabarti, Anindita; Doblecki-Lewis, Susanne; Looney, David J; David, Michael Z | Abstract: BackgroundInfluenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season.MethodsA retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.ResultsA total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (g65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], Pl.001), and a higher Sequential Organ Failure Assessment score (for each increase by 1 in score, 1.3 [1.2-1.4], Pl.001).ConclusionRisk factors for death among US patients with severe influenza during the 2013-2014 season, when influenza A (H1N1) pdm09 was the predominant circulating strain type, shifted in the first postpandemic season in which it predominated toward those of a more typical epidemic influenza season.

Objectives Figures Results The Impact of Direct Acting Antivirals in the Cure of HCV in HIVInfected Patients with Ongoing Barriers to Care ER. Cachay1,2, DL. Wyles1,2, L. Hill3, C. Ballard1,3, FJ. Torriani1,2, B. Colwell1,3, A. Kuo4, R. Schooley2, and Wm C. Mathews1 1Department of Medicine, Owen Clinic, UC San Diego, 2Department of Medicine, Division of Infectious Diseases, UC San Diego, 3Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, 4Department of Medicine, Division of Gastroenterology and Hepatology, UC San Diego

Background A multinational trial (APRICOT) showed that peginterferon alfa-2a (40 kDa) plus ribavirin is efficacious for treatment of HIV–HCV co-infection. The cost-effectiveness of treating these patients with peginterferon alfa-2a/ribavirin has yet to be explored from a US societal perspective. Objective To predict the cost-effectiveness of peginterferon alfa-2a/ribavirin with interferon/ribavirin (IFN/RBV) or no treatment in HIV–HCV co-infected patients. Study design A Markov model was constructed with liver progression estimates based on published literature. Sustained virological response and baseline characteristics of the reference case were based on APRICOT. Quality of life and costs in 2004 US dollars (US$) were based on literature estimates and discounted at 3%. Results Peginterferon alfa-2a/ribavirin compared with IFN/RBV or no treatment is predicted to increase quality-adjusted life-years (QALYs) by 0.73 and 0.94 years, respectively, in HCV-genotype-1 patients. The incremental cost-effectiveness ratio of peginterferon alfa-2a/ribavirin compared with IFN/RBV and no treatment for all patients is respectively US$ 2082 and 5187/QALY gained. Conclusions Anti-HCV treatment is predicted to decrease the risk of cirrhosis and increase quality-adjusted survival of HIV–HCV co-infected patients compared with IFN/RBV and no treatment. Peginterferon alfa-2a/ribavirin's cost per QALY gained relative to these options falls within the cost-effectiveness level of many health technologies commonly adopted in the US.

To investigate immune and viral contributions to the pathogenesis of immune recovery uveitis (IRU), which presents as vitritis, macular edema, or formation of epiretinal membranes, and develops in patients with acquired immunodeficiency syndrome (AIDS) who experienced cytomegalovirus (CMV) retinitis before antiretroviral treatment (ART) induced immune reconstitution.Aqueous and vitreous fluids from patients with IRU, active CMV retinitis, and control human immunodeficiency virus (HIV)-negative, noninflamed eyes were compared for presence of cytokines IL-6, IL12, interferon gamma using enzyme-linked immunosorbent assay techniques, and CMV DNA (by polymerase chain reaction).IRU eyes (11 patients, 18 samples) had the highest levels of IL-12 (median 48 pg/mL), moderate levels of IL-6 (median 146 pg/mL), and low but significant interferon gamma (median 15 pg/mL), compared to controls (P0.01). All uveitis eyes tested (9/9) were CMV DNA negative. In contrast, active CMV retinitis eyes were CMV DNA positive, had higher levels of IL-6 (median 349 pg/mL) (25 patients, 41 samples) than both control (P = 0.0001) and uveitis eyes (P = 0.048), similar levels of interferon gamma (median 27 pg/mL) to uveitis eyes, but less IL-12 (median 0 pg/mL) than uveitis eyes.Inflammatory IRU can be differentiated from active CMV retinitis by the presence of IL-12, less IL-6, and absence of detectable CMV replication.

Liver biopsy remains the gold standard in the assessment of severity of liver disease. Noninvasive tests have gained popularity to predict histology in view of the associated risks of biopsy. However, many models include tests not readily available, and there are limited data from patients with HIV/hepatitis C virus (HCV) coinfection. We aimed to develop a model using routine tests to predict liver fibrosis in patients with HIV/HCV coinfection. A retrospective analysis of liver histology was performed in 832 patients. Liver fibrosis was assessed via Ishak score; patients were categorized as 0-1, 2-3, or 4-6 and were randomly assigned to training (n = 555) or validation (n = 277) sets. Multivariate logistic regression analysis revealed that platelet count (PLT), age, AST, and INR were significantly associated with fibrosis. Additional analysis revealed PLT, age, AST, and ALT as an alternative model. Based on this, a simple index (FIB-4) was developed: age ([yr] x AST [U/L]) / ((PLT [10(9)/L]) x (ALT [U/L])(1/2)). The AUROC of the index was 0.765 for differentiation between Ishak stage 0-3 and 4-6. At a cutoff of1.45 in the validation set, the negative predictive value to exclude advanced fibrosis (stage 4-6) was 90% with a sensitivity of 70%. A cutoff of3.25 had a positive predictive value of 65% and a specificity of 97%. Using these cutoffs, 87% of the 198 patients with FIB-4 values outside 1.45-3.25 would be correctly classified, and liver biopsy could be avoided in 71% of the validation group. In conclusion, noninvasive tests can accurately predict hepatic fibrosis and may reduce the need for liver biopsy in the majority of HIV/HCV-coinfected patients.

There is a paucity of information on the safety and efficacy of lipid-lowering therapy for dyslipidemia associated with human immunodeficiency virus (HIV) and antiretroviral therapy. Our objective was to determine whether fenofibrate and pravastatin were equivalent for the treatment of combined dyslipidemia in HIV as measured by a composite of the National Cholesterol Education Project (NCEP) goals based on absolute values for low-density lipoprotein (LDL), triglycerides (TG), and high-density lipoprotein (HDL) and to compare the safety of these agents through 48 weeks. This was a randomized, open-label trial with subjects assigned to fenofibrate 200 mg (n = 88) or pravastatin 40 mg (n = 86) daily. Subjects who failed to reach the NCEP composite goal on monotherapy by week 12 received both drugs. The composite goal at week 12 was achieved in 1% of fenofibrate and 5% of pravastatin subjects. At week 16, 69/88 subjects on fenofibrate added pravastatin (FP) and 67/86 subjects on pravastatin added fenofibrate (PF). At week 48, 7% FP subjects and 3% PF subjects achieved the composite goal. Median changes in LDL/HDL/TG/non-HDL were -8/+5/-144/+50 and -14/+2/-66/+34 mg/dl in subjects receiving FP and PF, respectively. There were few adverse events and no rhabdomyolysis reported. Combination therapy with fenofibrate and pravastatin for HIV-related dyslipidemia provides substantial improvements in lipid parameters and appears safe, but is unlikely to achieve all NCEP targets for lipid levels.

To evaluate the results of a graded treatment approach in a cohort of eyes with macular complications of immune recovery uveitis.A cohort of 18 eyes of 13 patients representing all eyes with these complications at the University of California, San Diego AIDS Ocular Treatment Unit was studied. Eyes were classified into three groups and treated according to a graded protocol.Eyes with mild disease (macular edema and vision of 20/30 or better) were observed. These six eyes maintained good vision with only one dropping to 20/40. In eyes with worse macular edema and vision of 20/30 or worse (10 eyes of 9 patients), repository sub-Tenon steroid injections were used repeatedly. There were no complications of steroid use but visual improvement occurred in only 40% of eyes. Macular edema persisted. In eyes with structural macular changes, such as epiretinal membrane, vitrectomy resulted in vision improvement in three of four eyes. The cystoid macular edema persisted despite surgery.Mild cases of immune recovery uveitis and macular edema may be observed. In eyes with reduction of vision due to cystoid macular edema, there was only a modest treatment effect using repository corticosteroids. Eyes with immune recovery uveitis that develop epiretinal membrane undergo some visual improvement after removal of the membrane. The macular edema of immune recovery uveitis is resistant to corticosteroid treatment.

We studied hepatitis C virus (HCV) and human immunodeficiency virus (HIV) dynamics in 10 coinfected subjects in a trial of pegylated interferon-alpha2a (PEG-IFN) alone or combined with ribavirin (RBV), compared with IFN plus RBV for the treatment of HCV. Five subjects, 4 of whom were treated with PEG-IFN, achieved a sustained virological response, although it was delayed by >/=1 week in 3 subjects. The median treatment efficacy in blocking virion production was 99.7% in the PEG-IFN group and 60% with standard IFN. In 2 patients with detectable HIV loads before starting HCV study drugs, we observed a 1-log decrease in HIV RNA load. The estimated HCV virion half-life was longer in the HIV-coinfected subjects, which suggests that coinfection may contribute to a slower clearance of HCV. Although the early viral kinetics of coinfected subjects treated with PEG-IFN or IFN differ from those of singly infected subjects, the treatment response seems unaffected.

Purpose To determine the association between anticytomegalovirus (CMV) maintenance therapy after immune recovery and immune recovery uveitis in acquired immunodeficiency syndrome (AIDS) patients on highly active antiretroviral therapy (HAART). Design Observational cohort study. Methods Data were obtained on AIDS patients with CMV retinitis followed up at the AIDS Ocular Research Unit of University of California San Diego from November 1995 to October 1999. Immune recovery was defined as CD4 count greater than 50 cells/μl for more than 3 months. Patients with immune recovery uveitis presented with vitritis, cystoid macular edema, or epiretinal membrane. Statistical analyses were conducted to determine the risk of continued use of anti-CMV therapy after immune recovery and the relationship of developing immune recovery uveitis with the type of anti-CMV therapy. Results Forty-three patients (64 eyes) had healed CMV retinitis and had achieved immune recovery. Thirty-one patients (48 eyes) received anti-CMV therapy after immune recovery, and 20 patients (29 eyes) developed immune recovery uveitis. Per-eye analyses revealed a 3.8-fold increase in the odds of developing immune recovery uveitis with anti-CMV therapy compared with no treatment ( P = .02). If treated with cidofovir the odds were 3.3 greater than if treated with an alternative regimen ( P = .04), 4.1 greater if treated intravenously ( P = .01), and 5.2 greater than if not treated ( P = .004). If not treated with cidofovir, a nonsignificant increase in the risk (2.4) of immune recovery uveitis was found ( P = .15). Neither the potency nor the use of implants for noncidofovir treatment was related to the risk of recovery uveitis ( P > .62). Conclusions The use of cidofovir is a primary risk factor in the subsequent development of immune recovery uveitis. Ongoing treatment of healed CMV retinitis after immune recovery does not appear to protect against the development of immune recovery uveitis.

The present nonrandomized prospective study evaluated whether antimycobacterial therapy for disseminated Mycobacterium avium complex (MAC) could be withdrawn from human immunodeficiency virus-infected subjects who experienced immunologic recovery while receiving highly active antiretroviral therapy (HAART). Eligible subjects had received macrolide-based therapy for least 12 months, were asymptomatic for MAC, had received HAART for at least 16 weeks, and had CD4+ T cell counts >100 cells/microL. Forty-eight subjects were enrolled, with a median CD4+ T cell count of 240 cells/microL at the time of discontinuation of MAC therapy. Forty-seven subjects remained MAC free, whereas 1 subject developed localized MAC osteomyelitis. The median duration of follow-up while not receiving therapy was 77 weeks, and the incidence of MAC infection was 1.44/100 person-years (95% confidence interval, 0.04-8.01). Withdrawal of anti-MAC therapy appears to be safe in patients who have been treated with a macrolide-based regimen for at least 1 year and have an immunologic response on HAART.