Decreased antimicrobial prescribing rate following academic detailing of resident physicians in outpatient clinic.

Among 37 internal-medicine resident physicians assigned to our outpatient clinic at Minneapolis Veterans' Affairs Health Care System (MVAHCS) on July 1, 2017, we designed a pre- and postintervention observational study. Our results show that in-person academic detailing around outpatient antimicrobial selection was associated with a decrease in outpatient antimicrobial prescriptions in a group of high-prescribing resident physicians.

Evaluation of Strategies to Improve Uptake of Expedited Partner Therapy for Chlamydia trachomatis Treatment in Minnesota: A Decision Analytic Model.

Background. Despite the established effectiveness of expedited partner therapy (EPT) in partner treatment of bacterial sexually transmitted infections (STI), the practice is underutilized. Objective. To estimate the relative effectiveness of strategies to increase EPT uptake (numbers of partners treated for chlamydia). Methods. We developed a care cascade model of cumulative probabilities to estimate the number of partners treated under strategies to increase EPT uptake in Minnesota. The care cascade model used data from clinical trials, population-based studies, and Minnesota chlamydia surveillance as well as in-depth interviews of health providers who regularly treat STI patients and a statewide survey of health providers across Minnesota. Results. Several strategies could improve EPT uptake among providers, including facilitating treatment payment (additional 1,932 partners treated) and implementing electronic health record reminders (additional 1,755 partners treated). Addressing concerns about liability would have the greatest effect, resulting in 2,187 additional partners treated. Conclusions. Providers expressed openness to offering EPT under several scenarios, which reflect differences in knowledge about EPT, its legality, and potential risks to patients. While addressing concerns about provider liability would have the greatest effect on number of partners treated, provider education and procedural changes could make a substantial impact. Highlights: Addressing provider concerns about expedited partner therapy (EPT) legality and its potential risks would result in the most partners treated for chlamydia.EPT alerts and electronic EPT prescriptions may also streamline partner treatment.Provider education about the legality of EPT and its potential risks and training in counseling patients on EPT could also increase uptake.

A Statewide Mixed-Methods Study of Provider Knowledge and Behavior Administering Expedited Partner Therapy for Chlamydia and Gonorrhea.

BACKGROUND: Expedited partner therapy (EPT) refers to the practice of having patients diagnosed with chlamydia or gonorrhea deliver medication directly to their partner(s) to treat them presumptively for infection. Although EPT facilitates timely treatment and prevents reinfection, it remains underused. We used findings from key informant interviews to design and implement a statewide survey to estimate knowledge and utilization of EPT and to identify barriers and facilitators to EPT among Minnesota providers. METHODS: From November to December 2020, we carried out 15 interviews with health providers who currently provide EPT and coded interviews by recurring themes. We then conducted a statewide online survey on sexually transmitted infection treatment and barriers to EPT, from December 2020 to March 2021. We disseminated the survey to all licensed Minnesota health providers, and those who reported treating bacterial sexually transmitted infections in the past year were included in the study. RESULTS: Interview themes included the importance of direct provision of partner medication, administrative/pharmacy barriers to treatment, inclusive EPT eligibility, and patient counseling. Of the 623 health providers who completed the online survey, only 70% thought EPT was legal and only 37% currently offer EPT. Of those who did not provide EPT, 78% said they would under certain circumstances. Barriers included concerns about safety/liability of prescribing without a medical examination, administrative concerns about prescriptions, and patient acceptance. CONCLUSIONS: Given that over a quarter of respondents did not know expedited partner therapy (EPT)'s legal status, improving provider education may increase EPT provision. More research is needed on system-level barriers and patient acceptance of solutions identified in this study.

Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.

The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques.

Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption.

Antiretroviral therapy (ART) suppresses HIV replication in most individuals but cannot eradicate latently infected cells established before ART was initiated. Thus, infection rebounds when treatment is interrupted by reactivation of virus production from this reservoir. Currently, one or a few latently infected resting memory CD4 T cells are thought be the principal source of recrudescent infection, but this estimate is based on peripheral blood rather than lymphoid tissues (LTs), the principal sites of virus production and persistence before initiating ART. We, therefore, examined lymph node (LN) and gut-associated lymphoid tissue (GALT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive (vRNA+) cells were detected by in situ hybridization in LTs obtained before interruption in several patients. After interruption, multiple foci of vRNA+ cells were detected in 6 of 12 individuals as soon as pVL was measureable and in some subjects, in more than one anatomic site. Minimal estimates of the number of rebounding/founder (R/F) variants were determined by single-gene amplification and sequencing of viral RNA or DNA from peripheral blood mononuclear cells and plasma obtained at or just before viral recrudescence. Sequence analysis revealed a large number of R/F viruses representing recrudescent viremia from multiple sources. Together, these findings are consistent with the origins of recrudescent infection by reactivation from many latently infected cells at multiple sites. The inferred large pool of cells and sites to rekindle recrudescent infection highlights the challenges in eradicating HIV.

Inguinal lymph node and anorectal mucosal biopsies for human immunodeficiency virus research protocols in an emerging nation: patient outcomes and lessons learned.

BACKGROUND: Lymph nodes and gut-associated lymphatic tissue are important reservoirs of the human immunodeficiency virus (HIV). Little is known about these reservoirs in different geographic populations. We report the surgical outcomes of excisional lymph node and anorectal mucosal biopsies performed internationally and describe the lessons learned. METHODS: Patients were recruited through the Joint Clinical Research Center (JCRC) in Kampala, Uganda, where procedures were performed. Studies were approved by the Institutional Review Boards of the JCRC and the University of Minnesota. Instruments and supplies were shipped to Uganda and prepared onsite. Drugs and skin preparations were purchased locally. Lymph nodes were removed through 1-3 cm incisions with ligatures on lymphovascular pedicles. Incisions were closed with subcuticular sutures and epidermal tape. Two to four pieces of anorectal mucosa were obtained through anoscopes using biopsy forceps. RESULTS: One hundred thirty-eight lymph node biopsies and 98 anorectal mucosal biopsies were performed on 71 patients. Forty-one patients were HIV-positive. Many patients had multiple procedures. Two minor complications resulted: One hematoma and one lymphocele. Despite the cost of travel and lodging, cost per biopsy was lower in Uganda compared with the United States. CONCLUSION: Invasive clinical research can be performed with minimal morbidity in emerging nations with outcomes similar to those found in the United States, but with lower cost.

Fungemia due to Lachancea fermentati: a case report.

BACKGROUND: Lachancea fermentati is an environmental yeast that is also used in the fermentation of alcoholic drinks. It has not previously been described as a human pathogen although the closely related yeast, Saccharomyces boulardii, can cause fungemia. Here we report a case of L. fermentati acting as a pathogen in a septic patient with cultures positive from blood, peritoneal fluid, bile, and sputum. CASE PRESENTATION: A 36 year-old Caucasian man was hospitalized with acute alcoholic hepatitis complicated by Escherichia coli spontaneous bacterial peritonitis. Three days after admission, he developed new fevers with sepsis requiring mechanical ventilation and vasopressor support. He was found to have a bowel perforation. Cultures from blood, peritoneal fluid, and sputum grew a difficult-to-identify yeast. Micafungin was started empirically. On hospital day 43 the yeast was identified as L. fermentati with low minimum inhibitory concentrations (by Epsilometer test) to all antifungals tested. Micafungin was changed to fluconazole to complete a 3-month course of therapy. Serial peritoneal fluid cultures remained positive for 31 days. One year after his initial hospitalization the patient had ongoing cirrhosis but had recovered from fungemia. CONCLUSION: This case demonstrates the need for clinicians to consider host factors when interpreting culture results with normally non-pathogenic organisms. In this immunocompromised host L. fermentati caused disseminated disease. We believe his hobby of brewing alcohol led to colonization with L. fermentati, which then resulted in invasive disease when the opportunity arose.