Cumulative tenofovir exposure among patients with human immunodeficiency virus/hepatitis B co-infection with differential viral suppression.

This case-control study explored cumulative tenofovir exposure among patients with HIV/HBV co-infection with HIV viral suppression. Among patients taking tenofovir disoproxil fumarate, median TFV-DP levels in dried blood spots were ∼3-fold lower among patients with incomplete HBV viral suppression (n=4) compared to those with complete suppression (n=5) (516 vs.1456 fmol/punch).

A 7-year analysis of attributable costs of healthcare-associated infections in a network of community hospitals in the southeastern United States.

We calculated the attributable cost of several healthcare-associated infections in a community hospital network: central-line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), hospital-onset Clostridioides difficile infections (CDI-HOs) (43 hospitals); surgical site infections (SSIs) (40 hospitals). From 2016 to 2022, the total cost of CLABSIs, CAUTIs, CDI-HOs, and SSIs was $420,012,025.

Risk Factors for Recurrence of Community-Onset Urinary Tract Infections Caused by Extended-Spectrum Cephalosporin-Resistant Enterobacterales.

Background: Extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) are an increasingly important cause of community-onset urinary tract infections (UTIs), including recurrent infections. We evaluated risk factors for recurrence among patients with community-onset ESCrE UTI. Methods: This retrospective cohort study included adults with community-onset ESCrE UTI in the Duke University Health System from April 2018 through December 2021. ESCrE UTI recurrence by the same species was assessed 14-180 days (ie, 6 months) after completion of antibiotic treatment. We evaluated the relationships between candidate risk factors and time to recurrence using Cox proportional hazards regression models. Results: Among 1347 patients with community-onset ESCrE UTI, 202 (15.0%) experienced recurrent infection during the 6-month follow-up period. Independent risk factors for recurrence included neurogenic bladder (adjusted hazard ratio [aHR], 1.8 [95% confidence interval {CI}, 1.2-2.6]; P = .005), prior history of UTI (aHR, 2.4 [95% CI, 1.7-3.3]; P < .001), and fluoroquinolone nonsusceptibility of the index UTI (aHR, 1.5 [95% CI, 1.1-2.1]; P = .02). Klebsiella pneumoniae infection was associated with recurrence in univariate analysis (HR, 1.6 [95% CI, 1.1-2.1]; P = .007) but not multivariate analysis (aHR, 1.4 [95% CI, 1.0-1.9]; P = .06). Inappropriate initial or definitive antibiotic therapy was not predictive of ESCrE UTI recurrence. Conclusions: Recurrence of community-onset ESCrE UTI was common and associated with several patient and pathogen-level risk factors. Future studies should evaluate microbial risk factors for recurrence and improve the management of ESCrE UTI.

Characterization of resistance to newer antimicrobials among carbapenem-resistant Klebsiella pneumoniae in the post-acute-care setting.

We assessed susceptibility patterns to newer antimicrobial agents among clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from patients in long-term acute-care hospitals (LTACHs) from 2014 to 2015. Meropenem-vaborbactam and imipenem-relebactam nonsusceptibility were observed among 9.9% and 9.1% of isolates, respectively. Nonsusceptibility to ceftazidime-avibactam (1.1%) and plazomicin (0.8%) were uncommon.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination in staff common areas and impact on healthcare worker infection: Prospective surveillance during the coronavirus disease 2019 (COVID-19) pandemic.

We prospectively surveyed SARS-CoV-2 RNA contamination in staff common areas within an acute-care hospital. An increasing prevalence of surface contamination was detected over time. Adjusting for patient census or community incidence of coronavirus disease 2019 (COVID-19), the proportion of contaminated surfaces did not predict healthcare worker COVID-19 infection on study units.

Risk Factors for Colistin-Resistant Carbapenem-Resistant Klebsiella pneumoniae in the Postacute Care Setting.

We assessed risk factors for colistin resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) from 375 patients in long-term acute care hospitals. Recent colistin or polymyxin B exposure was associated with increased odds of colistin resistance (adjusted odds ratio = 1.11 per day of exposure, 95% confidence interval = 1.03-1.19, P = .007).

The Impact of Reported ß-Lactam Allergy on Clinical Outcomes and Antibiotic Use Among Solid Organ Transplant Recipients.

Background: Reported ß-lactam allergies (BLAs) are common and frequently inaccurate, but there are limited data on the clinical implications of BLA among solid organ transplant (SOT) recipients. We examined the impact of BLA on clinical outcomes and antibiotic use among SOT recipients. Methods: This retrospective cohort study included adult patients undergoing single-organ heart, kidney, liver, lung, or pancreas transplant at a United States academic medical center from 1 April 2017 to 31 December 2020. Demographic and clinical data were collected from the electronic health record. Multivariate median regression was performed to evaluate the association between BLA and days alive and out of the hospital in the first 180 days posttransplant (DAOH180). Multivariate logistic regression was performed to evaluate the association between BLA and antibiotic use. Results: Among 1700 SOT recipients, 285 (16.8%) had a BLA at the time of transplant. BLA was not associated with DAOH180 (adjusted median difference, -0.8 days [95% confidence interval {CI}, -2.7 to 1.2]; P = .43). Patients with BLA were more likely to receive intravenous vancomycin (adjusted odds ratio [aOR], 1.8 [95% CI, 1.3-2.6]; P < .001), clindamycin (aOR, 9.9 [95% CI, 5.1-18.9]; P < .001), aztreonam (aOR, 19.6 [95% CI, 5.9-64.4]; P < .001), fluoroquinolones (aOR, 3.8 [95% CI, 2.8-5.0]; P < .001), or aminoglycosides (aOR, 3.9 [95% CI, 2.5-6.2]; P < .001). Conclusions: BLA was associated with use of ß-lactam alternative antibiotics but not DAOH180 among SOT recipients.

SARS-CoV-2 RNA persists on surfaces following terminal disinfection of COVID-19 hospital isolation rooms.

We evaluated the effect of terminal cleaning on SARS-CoV-2 RNA contamination of COVID-19 isolation rooms in an acute care hospital. SARS-CoV-2 RNA was detected on 32.1% of room surfaces after cleaning; the odds of contamination increased with month. The prevalence of elevated high-touch surface contamination was lower in terminally cleaned rooms than patient-occupied rooms.

Real-world clinical outcomes of meropenem/vaborbactam for treatment of carbapenem-resistant Enterobacterales infections.

OBJECTIVES: Real-world data regarding the effectiveness of meropenem/vaborbactam (MVB) in the treatment of carbapenem-resistant Enterobacterales (CRE) infections remain limited. In this retrospective case series, we describe the outcomes of patients who received MVB for serious CRE infections. METHODS: This study included adult patients with MVB-susceptible CRE infection who received ≥48 h of MVB. Clinical and microbiological outcomes were ascertained via chart review. RESULTS: Among 15 patients with CRE infection who were treated with MVB, 9 (60.0%) had a positive clinical response. Among five patients with CRE bone and joint infection, three (60.0%) experienced a positive clinical response. One patient developed a microbiologically confirmed recurrent CRE infection and one patient developed Clostridioides difficile infection. CONCLUSION: MVB was well tolerated and effective for the majority of patients in this case series.

Knowledge, Perceptions, and Attitudes Regarding Antibiotic Use for Lower Respiratory Tract Infections: Insights from Patients in Sri Lanka.

Antibiotic resistance is an emerging global public health threat. One of the main drivers of this threat is the inappropriate use of antibiotics. In Sri Lanka, antibiotic consumption is increasing, but little is known locally about how patients perceive antibiotics. We conducted a qualitative study to gain a better understanding of the knowledge, perceptions, and attitudes of patients regarding antibiotics and antibiotic resistance. Semi-structured interviews involving 18 patients with lower respiratory tract infection (LRTI) admitted to a large, public tertiary care hospital in southern Sri Lanka were conducted. Interviews were analyzed to identify themes regarding the patients' knowledge of LRTI etiology and treatment, perceptions and attitudes toward LRTI treatment, including antibiotics, and patient-physician communication. Most patients mentioned multiple care visits and the use of multiple pharmaceuticals prior to admission. Patients sought a quick resolution to their ailments and frequently visited several private physicians to obtain a satisfying answer. Self-medication was also common. Patients reused prescriptions for antibiotics, kept antibiotics for later use after prematurely stopping their course of treatment, and bought over-the-counter antibiotics. Patients' knowledge of disease etiology and antibiotics was poor. Only a few patients were aware of antibiotic resistance. Despite the desire to receive more information regarding disease and treatment, patient-provider communication was limited and mainly confined to prescription instructions. This qualitative study performed in Sri Lanka suggests that inappropriate use of antibiotics is a multifactorial problem. To improve antibiotic use, a multifactorial approach that includes educating the public, increasing awareness among physicians, and implementing systems-level changes to restrict access to antibiotics is urgently needed.

Point-prevalence survey of outpatient antibiotic prescription at a tertiary medical center in Sri Lanka: opportunities to improve prescribing practices for respiratory illnesses.

BACKGROUND: Inappropriate antibiotic use is linked to the spread of antimicrobial resistance worldwide, but there are limited systemic data on antibiotic utilization in low- and middle-income countries. The purpose of this study was to evaluate the prevalence and patterns of antibiotic prescription in an ambulatory care setting in Sri Lanka. METHODS: This cross-sectional survey was conducted at the Outpatient Department of a public tertiary medical center in Southern Province, Sri Lanka from February to April 2019. Among consecutive outpatients presenting for care, questionnaires were verbally administered to a systematic random sample to capture information about patient demographics, illness characteristics, and visit outcomes. Prescription data were obtained from the outpatient pharmacy's electronic prescribing system. RESULTS: Of 409 surveyed patients, 146 (35.7%) were prescribed an antibiotic. The most frequently prescribed agents were amoxicillin (41 patients, 28.1% of antibiotic recipients) and first-generation cephalosporins (38, 26.0%). Respiratory indications were the most common reason for antibiotic use, comprising 69 (47.3%) of all antibiotic prescriptions. Antibiotics were prescribed for 66.1% of patients presenting with cough and 78.8% of those presenting with rhinorrhea or nasal congestion. Among all antibiotic recipients, 6 (4.1%) underwent diagnostic studies. CONCLUSIONS: A high prevalence of antibiotic prescription was observed, in particular for treatment of respiratory conditions. These data support the need for improved antimicrobial stewardship in the Sri Lankan outpatient setting.

A uropathogenic E. coli UTI89 model of prostatic inflammation and collagen accumulation for use in studying aberrant collagen production in the prostate.

Bacterial infection is one known etiology of prostatic inflammation. Prostatic inflammation is associated with prostatic collagen accumulation and both are linked to progressive lower urinary tract symptoms in men. We characterized a model of prostatic inflammation using transurethral instillations of Escherichia coli UTI89 in C57BL/6J male mice with the goal of determining the optimal instillation conditions, understanding the impact of instillation conditions on urinary physiology, and identifying ideal prostatic lobes and collagen 1a1 prostatic cell types for further analysis. The smallest instillation volume tested (50 µL) distributed exclusively to the bladder, 100- and 200-µL volumes distributed to the bladder and prostate, and a 500-µL volume distributed to the bladder, prostate, and ureter. A threshold optical density of 0.4 E. coli UTI89 in the instillation fluid was necessary for significant (P < 0.05) prostate colonization. E. coli UTI89 infection resulted in a low frequency, high volume spontaneous voiding pattern. This phenotype was due to exposure to E. coli UTI89, not catheterization alone, and was minimally altered by a 50-µL increase in instillation volume and doubling of E. coli concentration. Prostate inflammation was isolated to the dorsal prostate and was accompanied by increased collagen density. This was partnered with increased density of protein tyrosine phosphatase receptor type C+, procollagen type I-α1+ copositive cells and decreased density of α2-smooth muscle actin+, procollagen type I-α1+ copositive cells. Overall, we determined that this model is effective in altering urinary phenotype and producing prostatic inflammation and collagen accumulation in mice.

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: urethral histology.

The National Institutes of Health leveled new focus on sex as a biological variable with the goal of understanding sex-specific differences in health and physiology. We previously published a functional assessment of the impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology (Ruetten H, Wegner KA, Zhang HL, Wang P, Sandhu J, Sandhu S, Mueller B, Wang Z, Macoska J, Peterson RE, Bjorling DE, Ricke WA, Marker PC, Vezina CM. Am J Physiol Renal Physiol 317: F996-F1009, 2019). Here, we measured and compared five characteristics of urethral histology (urethral lumen diameter and area, epithelial cell count, epithelial and rhabdosphincter thickness, epithelial cell area, and total urethral area) in male and female 9-wk-old C57BL/6J mice using hematoxylin and eosin staining. We also compared male mice with castrated male mice, male and female mice treated with the steroid 5α-reductase inhibitor finasteride or testosterone, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that reduce prostate lobe mass. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed urethral histology, but none feminized male urethral histology (increased urethral epithelial area). Exogenous testosterone caused increased epithelial cell count in intact females but did not masculinize female urethral histology (decrease epithelial area). Our results lay a critical foundation for future studies as we begin to parse out the influence of hormones and cellular morphology on male and female urinary function.

IL-17A Contributes to Lung Fibrosis in a Model of Chronic Pulmonary Graft-versus-host Disease.

BACKGROUND: Chronic pulmonary graft-versus-host disease (cpGVHD) after hematopoietic cell transplant (HCT) manifests as progressive airway and parenchymal lung fibrosis. On the basis of our prior data, mice that undergo allogeneic HCT with Tbet-knockout donors (AlloTbet) have increased lung Th17 cells and IL-17A and develop fibrosis resembling human cpGVHD. The role of IL-17A in posttransplant pulmonary fibrosis remains incompletely understood. We hypothesized that IL-17A is necessary for development of murine cpGVHD in this model. METHODS: AlloTbet mice received weekly intraperitoneal anti-IL-17A or IgG (200 µg/mouse) starting 2 weeks post-HCT and were sacrificed after week 5. Histologic airway and parenchymal fibrosis were semiquantitatively graded in a blinded fashion. Lung cells and proteins were measured by flow cytometry, ELISA, and multicytokine assays. RESULTS: Anti-IL-17A modestly decreased airway and parenchymal lung fibrosis, along with a striking reduction in pulmonary neutrophilia, IL-6, MIP-1α, MIP-1ß, CXCL1, and CXCL5 in AlloTbet mice. Additionally, anti-IL-17A decreased CCL2, inflammatory monocytes and macrophages, and Th17 cells. CONCLUSIONS: In the setting of murine AlloHCT with Tbet donors, IL-17A blockade decreases fibrotic features of cpGVHD. This may be mediated by the observed reduction in neutrophils or specific lung monocyte and macrophage populations or alternatively via a direct effect on fibroblasts. Collectively, our results further suggest that anti-IL-17A strategies could prove useful in preventing alloimmune-driven fibrotic lung diseases.

Insight and Resources From a Study of the "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology.

The purpose of this symposium report is to summarize information from a session 3 oral presentation at the Society of Toxicologic Pathology Annual Symposium in Raleigh, North Carolina. Mice are genetically tractable and are likely to play an important role in elucidating environmental, genetic, and aging-related mechanisms of urinary dysfunction in men. We and others have made significant strides in developing quantitative methods for assessing mouse urinary function and our collaborators recently showed that aging male mice, like men, develop urinary dysfunction. Yet, it remains unclear how mouse prostate anatomy and histology relate to urinary function. The purpose of this report is to share foundational resources for evaluating mouse prostate histology and urinary physiology from our recent publication "Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology: Functional Assessment." We will begin with a review of prostatic embryology in men and mice, then move to comparative histology resources, and conclude with quantitative measures of rodent urinary physiology.

Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment.

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter "baseline" of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles (Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

A temporal and spatial map of axons in developing mouse prostate.

Prostate autonomic and sensory axons control glandular growth, fluid secretion, and smooth muscle contraction and are remodeled during cancer and inflammation. Morphogenetic signaling pathways reawakened during disease progression may drive this axon remodeling. These pathways are linked to proliferative activities in prostate cancer and benign prostate hyperplasia. However, little is known about which developmental signaling pathways guide axon investment into prostate. The first step in defining these pathways is pinpointing when axon subtypes first appear in prostate. We accomplished this by immunohistochemically mapping three axon subtypes (noradrenergic, cholinergic, and peptidergic) during fetal, neonatal, and adult stages of mouse prostate development. We devised a method for peri-prostatic axon density quantification and tested whether innervation is uniform across the proximo-distal axis of dorsal and ventral adult mouse prostate. Many axons directly interact with or innervate neuroendocrine cells in other organs, so we examined whether sensory or autonomic axons innervate neuroendocrine cells in prostate. We first detected noradrenergic, cholinergic, and peptidergic axons in prostate at embryonic day (E) 14.5. Noradrenergic and cholinergic axon densities are uniform across the proximal-distal axis of adult mouse prostate while peptidergic axons are denser in the periurethral and proximal regions. Peptidergic and cholinergic axons are closely associated with prostate neuroendocrine cells whereas noradrenergic axons are not. These results provide a foundation for understanding mouse prostatic axon development and organization and, provide strategies for quantifying axons during progression of prostate disease.

Public Awareness of HIV Pre-Exposure Prophylaxis in Durham, North Carolina: Results of a Community Survey.

BACKGROUND Adoption of HIV pre-exposure prophylaxis (PrEP) remains limited among populations at greatest risk for HIV acquisition. This study aims to assess awareness of PrEP among individuals in Durham, North Carolina, which has one of the highest rates of HIV diagnoses in the state.METHOD In 2015-2016, we administered a survey including questions to assess PrEP awareness to individuals at multiple venues throughout Durham, North Carolina.RESULTS A total of 139 respondents were surveyed. The majority were male (66%) and black/African American (75%); 21% were Hispanic/Latino. There were an estimated 53 men who have sex with men (MSM), of which 18 (33%) were black MSM M 24 years of age. Overall, only 53/138 (38%) respondents were aware of PrEP. Awareness was reported among 33/52 (63%) MSM respondents, 29/46 (63%) black MSM, and 10/17 (59%) black MSM M 24 years of age. In multivariate analysis, non-heterosexual orientation, health-insured status, and prior HIV testing were significantly associated with PrEP awareness. Ninety-four (69%) of 137 respondents reported prior HIV testing.LIMITATIONS Limitations include non-random sampling and limited sample size. Further research needs to be done in other areas of North Carolina, and assessment of PrEP acceptability and uptake needs to be performed.CONCLUSION This study reveals low overall awareness of PrEP in Durham, North Carolina, indicating that expanded outreach is necessary to increase public awareness and encourage adoption of PrEP among all demographics at risk for HIV.

Predicting Mortality for Adolescent and Adult Patients with Fever in Resource-Limited Settings.

Febrile illnesses are a major cause of mortality in sub-Saharan Africa. Early identification of patients at increased risk of death may avert adverse outcomes. We aimed to independently evaluate the performance of the Modified Early Warning Score, quick Sequential Organ Failure Assessment (qSOFA) score, and Integrated Management of Adolescent and Adult Illness (IMAI) emergency signs and severity criteria to predict in-hospital mortality among a prospective cohort of febrile patients in Tanzania. We evaluated 419 patients aged ≥ 10 years in the period 2007-2008. Of the 44 patients who died, 31 (70.5%) were human immunodeficiency virus (HIV) infected. On univariate analysis, in-hospital mortality was associated with HIV infection, oxygen saturation < 90%, respiratory distress, Glasgow Coma Scale < 15, neck stiffness, unconsciousness, convulsions, hemoglobin < 9 g/dL, absence of a systemic syndrome, and neurologic syndrome. A qSOFA score ≥ 2, the presence of at least one, two, or three IMAI emergency signs, and IMAI severe respiratory distress syndrome without shock were significantly associated with in-hospital mortality. The criterion "presence of at least one IMAI emergency sign" showed a good diagnostic accuracy, as highlighted by the high sensitivity, low negative likelihood ratio, and wide area under the receiver operating characteristics curve. The remaining scores showed a poor performance in predicting fatal outcomes in our study population. Further studies are needed to validate our findings and to derive early warning scores that have good clinical performance in settings throughout sub-Saharan Africa.

HIV Preexposure Prophylaxis Implementation at Local Health Departments: A Statewide Assessment of Activities and Barriers.

BACKGROUND: Expanding access to HIV preexposure prophylaxis (PrEP) could help reduce rates of HIV infection in the United States. This study characterizes activities and barriers to PrEP implementation at local health departments (LHDs) in North Carolina (NC), which contains a large rural population. METHODS: In May 2016, a web-based survey was distributed to health directors of all county and district health departments in NC to assess PrEP-related activities, perceived barriers to PrEP implementation, and desired PrEP-related resources. RESULTS: Of 85 LHDs in NC, 56 (66%) responded to the survey. Of these, 2 (4%) reported PrEP prescribing and 7 (13%) externally referred for PrEP services. Among the 54 departments not prescribing PrEP, the most frequently cited reasons were cost concerns (n = 25, 46%), lack of formal prescribing protocols (n = 21, 39%), and belief that PrEP would be better managed at primary care or specialty clinics (n = 19, 35%). Among the 47 departments not prescribing or referring clients for PrEP, the most frequently cited reasons for the lack of PrEP referral were the absence of local PrEP providers (n = 29, 62%), lack of PrEP knowledge among staff (n = 13, 28%), and perceived lack of PrEP candidates (n = 12, 26%). The most frequently requested PrEP-related resources included training to help identify PrEP candidates (n = 39, 70%) and training on PrEP prescribing and management (n = 38, 68%). CONCLUSIONS: PrEP prescribing and referral among LHDs in NC remains extremely limited. Increased PrEP-related training and support for LHD-based providers could enhance PrEP access, especially in rural and underserved areas.