Assessing Patient Acceptance of an Automated Algorithm to Identify Ciswomen for HIV Pre-Exposure Prophylaxis.

The use of HIV pre-exposure prophylaxis (PrEP) in cisgender women (ciswomen) lags far behind their need. Data elements from the electronic medical record (EMR), including diagnosis of a sexually transmitted infection (STI), can be incorporated into automated algorithms for identifying clients who are most vulnerable to HIV and would benefit from PrEP. However, it is unknown how women feel about the use of such technology. In this study, we assessed women's attitudes and opinions about an automated EMR-based HIV risk algorithm and determined if their perspectives varied by level of HIV risk. Respondents were identified using best practice alerts or referral to a clinic for STI symptoms from January to December 2021 in Chicago, IL. Participants were asked about HIV risk factors, their self-perceived HIV risk, and their thoughts regarding an algorithm to identify ciswomen who could benefit from PrEP. Most of the 112 women who completed the survey (85%) thought they were at low risk for HIV, despite high rates of STI diagnoses. The majority were comfortable with the use of this algorithm, but their comfort level dropped when asked about the algorithm identifying them specifically. Ciswomen had mixed feelings about the use of an automated HIV risk algorithm, citing it as a potentially helpful and empowering tool for women, yet raising concerns about invasion of privacy and potential racial bias. Clinics must balance the benefits of using an EMR-based algorithm for ciswomen with their concerns about privacy and bias to improve PrEP uptake among particularly vulnerable women.

Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging.

BACKGROUND: People living with HIV (PLWH), even when viral replication is controlled through antiretroviral therapy (ART), experience persistent inflammation. This inflammation is partly attributed to intestinal microbial dysbiosis and translocation, which may lead to non-AIDS-related aging-associated comorbidities. The extent to which living with HIV - influenced by the infection itself, ART usage, sexual orientation, or other associated factors - affects the biological age of the intestines is unclear. Furthermore, the role of microbial dysbiosis and translocation in the biological aging of PLWH remains to be elucidated. To investigate these uncertainties, we used a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PLWH on ART and people living without HIV (PLWoH) as controls. RESULTS: PLWH exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to PLWoH. Investigating the relationship between microbial translocation and biological aging, PLWH had decreased levels of tight junction proteins in the intestines, along with increased microbial translocation. This intestinal permeability correlated with faster biological aging and increased inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PLWH had higher abundance of specific pro-inflammatory bacteria, such as Catenibacterium and Prevotella. These bacteria correlated with accelerated biological aging. Conversely, the intestines of PLWH had lower abundance of bacteria known for producing the anti-inflammatory short-chain fatty acids, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbe-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid. CONCLUSIONS: We identified specific microbial compositions and microbiota-related metabolic pathways that are intertwined with intestinal and systemic biological aging. This microbial signature of biological aging is likely reflecting various factors including the HIV infection itself, ART usage, sexual orientation, and other aspects associated with living with HIV. A deeper understanding of the mechanisms underlying these connections could offer potential strategies to mitigate accelerated aging and its associated health complications. Video Abstract.

Comparative antimicrobial use in coronavirus disease 2019 (COVID-19) and non-COVID-19 inpatients from 2019 to 2020: A multicenter ecological study.

OBJECTIVE: We sought to determine whether increased antimicrobial use (AU) at the onset of the coronavirus disease 2019 (COVID-19) pandemic was driven by greater AU in COVID-19 patients only, or whether AU also increased in non-COVID-19 patients. DESIGN: In this retrospective observational ecological study from 2019 to 2020, we stratified inpatients by COVID-19 status and determined relative percentage differences in median monthly AU in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (March-December 2020) and the pre-COVID-19 period (March-December 2019). We also determined relative percentage differences in median monthly AU in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period. Statistical significance was assessed using Wilcoxon signed-rank tests. SETTING: The study was conducted in 3 acute-care hospitals in Chicago, Illinois. PATIENTS: Hospitalized patients. RESULTS: Facility-wide AU for broad-spectrum antibacterial agents predominantly used for hospital-onset infections was significantly greater in COVID-19 patients versus non-COVID-19 patients during the COVID-19 period (with relative increases of 73%, 66%, and 91% for hospitals A, B, and C, respectively), and during the pre-COVID-19 period (with relative increases of 52%, 64%, and 66% for hospitals A, B, and C, respectively). In contrast, facility-wide AU for all antibacterial agents was significantly lower in non-COVID-19 patients during the COVID-19 period versus the pre-COVID-19 period (with relative decreases of 8%, 7%, and 8% in hospitals A, B, and C, respectively). CONCLUSIONS: AU for broad-spectrum antimicrobials was greater in COVID-19 patients compared to non-COVID-19 patients at the onset of the pandemic. AU for all antibacterial agents in non-COVID-19 patients decreased in the COVID-19 period compared to the pre-COVID-19 period.

Distinct Intestinal Microbial Signatures Linked to Accelerated Biological Aging in People with HIV.

Background: People with HIV (PWH), even with controlled viral replication through antiretroviral therapy (ART), experience persistent inflammation. This is partly due to intestinal microbial dysbiosis and translocation. Such ongoing inflammation may lead to the development of non-AIDS-related aging-associated comorbidities. However, there remains uncertainty regarding whether HIV affects the biological age of the intestines and whether microbial dysbiosis and translocation influence the biological aging process in PWH on ART. To fill this knowledge gap, we utilized a systems biology approach, analyzing colon and ileal biopsies, blood samples, and stool specimens from PWH on ART and their matched HIV-negative counterparts. Results: Despite having similar chronological ages, PWH on ART exhibit accelerated biological aging in the colon, ileum, and blood, as measured by various epigenetic aging clocks, compared to HIV-negative controls. Investigating the relationship between microbial translocation and biological aging, PWH on ART had decreased levels of tight junction proteins in the colon and ileum, along with increased microbial translocation. This increased intestinal permeability correlated with faster intestinal and systemic biological aging, as well as increased systemic inflammation. When investigating the relationship between microbial dysbiosis and biological aging, the intestines of PWH on ART had higher abundance of specific pro-inflammatory bacterial genera, such as Catenibacterium and Prevotella. These bacteria significantly correlated with accelerated local and systemic biological aging. Conversely, the intestines of PWH on ART had lower abundance of bacterial genera known for producing short-chain fatty acids and exhibiting anti-inflammatory properties, such as Subdoligranulum and Erysipelotrichaceae, and these bacteria taxa were associated with slower biological aging. Correlation networks revealed significant links between specific microbial genera in the colon and ileum (but not in feces), increased aging, a rise in pro-inflammatory microbial-related metabolites (e.g., those in the tryptophan metabolism pathway), and a decrease in anti-inflammatory metabolites like hippuric acid and oleic acid. Conclusions: We identified a specific microbial composition and microbiome-related metabolic pathways that are intertwined with both intestinal and systemic biological aging in PWH on ART. A deeper understanding of the mechanisms underlying these connections could potentially offer strategies to counteract premature aging and its associated health complications in PWH.

A Rare Case of Locally Contracted Cutaneous Corynebacterium diphtheriae.

A 32-year-old man with a history of intravenous heroin use and housing instability presented with three years of worsening left forearm and wrist "infection," which had progressed over the past few months with worsening purulence, pain, and deformity. In the emergency department, he was afebrile with stable vitals. Superficial cultures drawn demonstrated polymicrobial growth, including heavy growth of Corynebacterium diphtheriae. He was treated with vancomycin and then IV penicillin to complete 10 days of therapy. Given the uncharacteristic appearance of the lesion, a biopsy was recommended, but the patient left against medical advice. Later, the diphtheria isolate was identified as C. diphtheriae var. mitis by the Centers for Disease Control and Prevention (CDC). This describes an atypical case of cutaneous diphtheria, a disease that is infrequently seen in the United States due to the high prevalence of routine vaccination.

Development of a predictive model for identifying women vulnerable to HIV in Chicago.

INTRODUCTION: Researchers in the United States have created several models to predict persons most at risk for HIV. Many of these predictive models use data from all persons newly diagnosed with HIV, the majority of whom are men, and specifically men who have sex with men (MSM). Consequently, risk factors identified by these models are biased toward features that apply only to men or capture sexual behaviours of MSM. We sought to create a predictive model for women using cohort data from two major hospitals in Chicago with large opt-out HIV screening programs. METHODS: We matched 48 newly diagnosed women to 192 HIV-negative women based on number of previous encounters at University of Chicago or Rush University hospitals. We examined data for each woman for the two years prior to either their HIV diagnosis or their last encounter. We assessed risk factors including demographic characteristics and clinical diagnoses taken from patient electronic medical records (EMR) using odds ratios and 95% confidence intervals. We created a multivariable logistic regression model and measured predictive power with the area under the curve (AUC). In the multivariable model, age group, race, and ethnicity were included a priori due to increased risk for HIV among specific demographic groups. RESULTS: The following clinical diagnoses were significant at the bivariate level and were included in the model: pregnancy (OR 1.96 (1.00, 3.84)), hepatitis C (OR 5.73 (1.24, 26.51)), substance use (OR 3.12 (1.12, 8.65)) and sexually transmitted infections (STIs) chlamydia, gonorrhoea, or syphilis. We also a priori included demographic factors that are associated with HIV. Our final model had an AUC of 0.74 and included healthcare site, age group, race, ethnicity, pregnancy, hepatitis C, substance use, and STI diagnosis. CONCLUSIONS: Our predictive model showed acceptable discrimination between those who were and were not newly diagnosed with HIV. We identified risk factors such as recent pregnancy, recent hepatitis C diagnosis, and substance use in addition to the traditionally used recent STI diagnosis that can be incorporated by health systems to detect women who are vulnerable to HIV and would benefit from preexposure prophylaxis (PrEP).

Immune Reconstitution Inflammatory Syndrome Reaction in Patient on Long-Term Prednisone.

Immune reconstitution inflammatory syndrome (IRIS) can be triggered in many ways. IRIS has been recognized during tuberculosis (TB) therapy, especially in patients newly initiated on antiretroviral therapy for HIV or those taken off immunosuppressives such as tumor necrosis factor-alpha inhibitors. However, there are still many triggers of IRIS that are less understood. This case report describes a patient with scrofula that was concerning for TB reactivation, who then had subsequent IRIS. The patient had been consistently using low-dose long-term prednisone for suppression of his polymyalgia rheumatica. It is suspected that the IRIS reaction could be due to an interaction between rifampin and prednisone causing decreased efficacy of its immunosuppressive effects.

Utility of the Signal-to-Cutoff Ratio and Antigen Index from Fourth- and Fifth-Generation HIV-1/HIV-2 Antigen/Antibody Assays for the Diagnosis of Acute HIV Infection: Applicability for Real-Time Use for Immediate Initiation of Antiretroviral Therapy.

Identification of individuals with acute HIV infection (AHI) and rapid initiation of antiretroviral therapy (ART) are priorities for HIV elimination efforts. Fourth- and fifth-generation HIV-1/HIV-2 antigen (Ag)/antibody (Ab) combination assays can quickly identify patients with AHI, but false-positive results can occur. Confirmatory nucleic acid amplification testing (NAAT) may not be rapidly available. We reviewed the data for 127 patients with positive fourth-generation ARCHITECT and fifth-generation Bio-Plex immunoassay results who had negative or indeterminate confirmatory Ab testing results, which yielded 38 patients with confirmed AHI and 89 patients with false-positive results. The receiver operating characteristic (ROC) curves showed excellent discriminatory power, with an area under the curve (AUC) for the signal-to-cutoff (S/CO) ratio of 0.970 (95% confidence interval [CI], 0.935 to 1.00) and an AUC for the Ag index (AI) of 0.968 (95% CI, 0.904 to 1.00). A threshold of 3.78 for the S/CO ratio would maximize the sensitivity (96.3%) and specificity (93.4%). The threshold for AI was 2.83 (sensitivity of 100% and specificity of 96.4%). The S/CO ratio was significantly correlated with the viral load (Spearman correlation coefficient, 0.486 [P = 0.014]), but the AI was not. The viral loads were all high, with a median of >2.8 million copies/mL. Two false-positive results with AI and S/CO ratio values markedly higher than the medians were observed, indicating that biological false-positive results can occur. Review of the S/CO ratio or AI may be used to improve the accuracy of AHI diagnosis prior to confirmatory NAAT results being available.

Effectiveness of an electronic health record model for HIV pre-exposure prophylaxis.

Pre-exposure prophylaxis (PrEP) to prevent human immunodeficiency virus (HIV) is extremely effective when taken correctly, though grossly under-prescribed for at-risk patients. We initiated a best practice advisory (BPA) in the Epic electronic medical record (EMR) to identify patients who met criteria for PrEP use. We evaluated this model to determine its effectiveness in identifying patients and its use by providers for increasing prescription of PrEP. The BPA fired 145 times with five total new PrEP prescriptions. Over half of the patients identified were cisgender women, a group that is both under prescribed PrEP and missed by prior EMR PrEP algorithms. Half of the patients were African American, a group at high risk of HIV infection. Though the model was effective at identifying patients, provider initiation of PrEP or acknowledgment of the BPA was low. Further education of providers regarding PrEP usage and expansion of BPA messages are needed to increase rates of PrEP initiation.

Bacterial Sinusitis in the COVID-19 Era: A Reminder for Antibiotic Stewardship.

The COVID-19 pandemic has necessitated the trial of novel treatment regimens to improve clinical outcomes. However, the liberal use of antibiotic and steroid therapy during this period may have also contributed to unintended consequences including the development of multidrug-resistant (MDR) bacterial infections. In this report, we discuss the case of a 76-year-old woman treated with an extended course of steroids for COVID-19 infection. The patient then developed MDR bacterial sinusitis requiring multiple courses of antibiotics complicated by medication side effects. Thus, this case highlights the continued importance of discretion in long-term steroid use and antibiotic stewardship.

Evolution of an Electronic Health Record Based-Human Immunodeficiency Virus (HIV) Screening Program in an Urban Emergency Department for Diagnosing Acute and Chronic HIV Infection.

BACKGROUND: Since 2006, Centers for Disease Control and Prevention guidelines recommend routine opt-out human immunodeficiency virus (HIV) testing among sexually active 13- to 64-year-olds. Earlier diagnosis and treatment of HIV infection reduces morbidity and mortality and can limit transmission to others. OBJECTIVE: Our aim was to increase HIV testing, diagnosis, and linkage to care in the emergency department (ED). METHODS: Beginning May 4, 2015, we utilized our electronic health record (EHR) to enhance HIV testing in patients seen in the Rush University Medical Center emergency department in Chicago, IL, who were 13-64 years of age, did not have HIV listed on their problem list, and did not have an HIV antigen/antibody (Ag/Ab) test in the EHR within the past rolling 12-month period. Strategies included use of a "Best Practice Advisory" and later auto-order screening linked to a complete blood count order. RESULTS: Our baseline HIV test rate was 2.5% of the target population by age (average of 93 tests per month). From May 4, 2015 to January 31, 2019, 137,749 patients of 240,091 ED visits met our test criteria and 23,588 (17.1% of the target population) HIV Ag/Ab tests were performed, resulting in 164 positive tests. We identified 18 acute seroconverters, 51 new chronically infected persons, and 95 known infected, many of who had not disclosed their status. Our positive test rate was 0.70%, which dropped to 0.29% if only newly diagnosed individuals were counted. CONCLUSIONS: EHR enhancements in a large urban ED identifies both newly diagnosed acute and chronically HIV-infected persons. Identification of previously diagnosed patients offers an opportunity to relink them to care.

Extended antibiotic resistance in carbapenemase-producing Klebsiella pneumoniae: A case series.

Infections caused by carbapenemase-producing Klebsiella pneumoniae resistant to tigecycline, colistin, or aminoglycosides are a growing health concern. In our retrospective chart review, we noted increased resistance to colistin compared with tigecycline, despite limited prior use of colistin. This may affect the choice of presumptive antibiotics used in these hard to treat infections. Improved infection control and antimicrobial stewardship practices are essential to prevent the spread of these multidrug-resistant organisms.

Health-care worker vaccination for influenza: strategies and controversies.

Influenza infections cause significant morbidity and mortality throughout the world, and vaccination rates of health-care workers remain well below target goals. Strategies for increasing vaccination rates include mandatory vaccination of health-care workers, mandatory declination, employee incentives, intensive education, increased access to vaccines, and the use of social media to inform employees of the safety and efficacy of vaccination. While these strategies in combination have been shown to be effective in increasing vaccination rates, personal and religious objections, as well as the potential for infringing on individual autonomy, remain challenges in our efforts to bring health-care worker vaccination rates up to target goals.

Influenza virus resistance to neuraminidase inhibitors: implications for treatment.

Oseltamivir and Zanamivir are the two main Neuraminidase inhibitors used for the treatment of Influenza. Oseltamivir resistance has been identified in non-pandemic influenza viruses, as well as H1N1 pandemic Influenza A viruses. Resistance is associated with increased morbidity, and poorer outcomes in severely immunocompromised hosts. Newer neuraminidase inhibitors, increased vaccination and combination therapy may be alternatives for the treatment of Influenza in this setting.

Vibrio furnissii: an unusual cause of bacteremia and skin lesions after ingestion of seafood.

Vibrio furnissii in the blood is rarely reported, which may explain why clinical features of bloodstream infections with this organism have not been described. We describe a patient who developed skin lesions and V. furnissii bacteremia and was successfully treated with fluoroquinolones. V. furnissii may be a serious pathogen in patients with underlying comorbidities who are exposed to seafood.

Treatment of severe cases of pandemic (H1N1) 2009 influenza: review of antivirals and adjuvant therapy.

Three worldwide influenza pandemics were reported in the 20th century: in 1918, 1957 and 1968. All three pandemics were caused by different sub-types of Influenza A viruses: H1N1, H2N2 and H3N2 respectively. In early March 2009, the first cases of influenza -like illness (ILI) were reported from Mexico. This strain was identified as influenza A/ H1N1 strain. Pandemic (H1N1) 2009 influenza most commonly causes a self-limited illness, however, significant morbidity and mortality were reported in the young, the obese and in pregnant women. The drugs of choice for treatment and prophylaxis of pandemic (H1N1) 2009 influenza are the neuraminidase inhibitors, Oseltamivir and Zanamivir. While a few cases of Oseltamivir-resistance are reported, these isolates still retained their susceptibility to the inhaled Neuraminidase inhibitor, Zanamivir. Pandemic (H1N1) 2009 influenza virus is routinely resistant to the adamantanes: Amantadine and Rimantadine. These agents should not be used for the treatment or prophylaxis of pandemic (H1N1) 2009 influenza. The FDA recently approved the emergency use of Peramivir, an intravenous neuraminidase inhibitor, for the treatment of patients with severe influenza. We discuss the use of available antivirals, as well as the effectiveness of adjunctive therapies with immunomodulatory and anti-inflammatory agents, such as immunoglobulins and statins, for the treatment and management of patients with severe H1N1 influenza. This review summarizes the recent patents for the use of antivirals in treatment of severe influenza.