INDUCTION OF MRSA BIOFILM BY LOW-DOSE β-LACTAM ANTIBIOTICS: SPECIFICITY, PREVALENCE AND DOSE-RESPONSE EFFECTS

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-associated infections. The formation of adherent clusters of cells known as biofilms is an important virulence factor in MRSA pathogenesis. Previous studies showed that subminimal inhibitory (sub-MIC) concentrations of methicillin induce biofilm formation in the community-associated MRSA strain LAC. In this study we measured the ability sub-MIC concentrations of eight other β-lactam antibiotics and six non-β-lactam antibiotics to induce LAC biofilm. All eight β-lactam antibiotics, but none of the non-β-lactam antibiotics, induced LAC biofilm. The dose-response effects of the eight β-lactam antibiotics on LAC biofilm varied from biphasic and bimodal to near-linear. We also found that sub-MIC methicillin induced biofilm in 33 out of 39 additional MRSA clinical isolates, which also exhibited biphasic, bimodal and linear dose-response curves. The amount of biofilm formation induced by sub-MIC methicillin was inversely proportional to the susceptibility of each strain to methicillin. Our results demonstrate that induction of biofilm by sub-MIC antibiotics is a common phenotype among MRSA clinical strains and is specific for β-lactam antibiotics. These findings may have relevance to the use of β-lactam antibiotics in clinical and agricultural settings

Ureaplasma septic polyarthritis in a young woman with neuromyelitis optica receiving rituximab

© 2021 BMJ Publishing Group. All rights reserved. We report a case of septic polyarthritis caused by Ureaplasma urealyticum in a woman with neuromyelitis optica who was receiving rituximab. Her case exemplifies some of the unique characteristics of invasive Ureaplasma infections that can lead to delayed diagnosis as well as treatment challenges including recurrence following antibiotic discontinuation

Challenges in conducting research on sexual violence and HIV and methods to overcome them

Background: Studies have implicated sexual violence as a potential correlate of HIV acquisition in women. Characterizing how violence affects the female immune system may provide insight into the biological mechanisms of HIV transmission and ultimately improve global HIV prevention strategies. Little research has been done in this domain, and the obstacles to investigation can be daunting. We describe methodological challenges encountered and solutions. explored while implementing a study of dysregulation of immune biomarkers in pre- and postmenopausal women following sexual assault. Methods: We compared immune biomarkers indicative of HIV susceptibility between women who had experienced forced vaginal penetration during the preceding 12 weeks (cases) and women who had never experienced forced or coerced vaginal penetration (controls). Participants provided blood, cervicovaginal lavage and cervical swab samples for biomarker analysis at one or five visits, depending on study arm. In addition, some participants completed a computer self-administered interview at each visit. Results: From July 2014 to June 2016, we enrolled 24 cases (21 pre-menopausal and 3 postmenopausal) and 30 controls (25 pre-menopausal and 5 post-menopausal). Challenges included accessing and defining sexual assault survivors, ensuring participant well-being during research engagement, reducing selection and information bias, collecting and processing biological samples, and adjusting for confounders such as reproductive tract infections and emotional and physical abuse. Use of sensitive, mature, and highly trained research staff in conjunction with well-articulated community and medical partnerships were key methods to overcoming challenges while promoting the safety and welfare of vulnerable study participants. Conclusions: Research into the relationships between sexual assault, immune biomarkers and HIV is possible though not without challenges. Moreover, many survivors of sexual assault welcome the chance to help other women at risk for violence. This field of research would benefit from the development of multi-site consortia, which would allow for the combined accrual of larger study populations to clarify the individual and interacting effects of various causal factors

Challenges in Conducting Research on Sexual Violence and HIV and Approaches to Overcome Them.

Studies have implicated sexual violence as a strong correlate of HIV acquisition in women. Characterizing how such violence affects the female immune system may provide insight into the biological mechanisms of HIV transmission and ultimately improve global HIV prevention strategies. Little research has been carried out in this domain, and the obstacles to investigation can be daunting. Here, we describe methodological challenges encountered and solutions explored while implementing a study of dysregulation of immune biomarkers potentially indicative of increased HIV susceptibility in women following sexual assault. Challenges included accessing sexual assault survivors and defining sexual assault, promoting study participant well-being during research engagement, reducing selection and information bias, collecting and processing biological samples, and adjusting for confounders such as reproductive tract infections and emotional and physical abuse. We found that many survivors of sexual assault welcomed the attention from study staff and felt empowered by the opportunity to help other women at risk for violence. Well-trained research staff and well-articulated community and medical partnerships were key methods to overcoming challenges while promoting the safety and welfare of vulnerable study participants

Impact of Sexual Violence on Chemokines in the Female Genital Tract: Risk of HIV acquisition

Sexual violence is a known risk factor in HIV acquisition and transmission, and may cause dysregulation of genital immune microenvironment. IP-10, MCP-1 and MIP-3α are chemokines that act as chemo-attractants for macrophages and T-cells. Since macrophages and T-cells are targets for HIV, increase in these chemokines may lead to an increased risk of HIV infection in women experiencing sexual violence. Cases were defined as women who had experienced non-consensual vaginal intercourse in the last 3 months (n=42) and controls, defined as women who had no history of sexual violence, were recruited from the local Washington DC community (n=63). Cervical-vaginal lavage (CVL) samples were collected by washing the cervical-vaginal tract with 10 mL of sterile saline. Premenopausal women were asked to return 4 more times over 8 weeks to collect information about their menstrual cycle. Post-menopausal women were asked to return as well to match premenopausal women. Samples were analyzed by standard Enzyme Linked Immunosorbent Assay (ELISA) (R&D Systems) for three chemokines, MCP-1, IP-10, and MIP-3α according to manufacturer’s protocol. Data was analyzed using GraphPad Prism (version 5.04) and SAS version 9.4. Multiple visits were treated as distinct records for analysis. We observed MIP-3α to have significantly lower levels (p\u3c0.0001) in Cases compared to Controls. In addition, MIP-3α levels were also affected by menopausal status showing significantly lower values for both premenopausal Cases (p=0.0004) and post-menopausal Cases (p=0.0147) relative to their respective Control groups. The results from MCP-1 was different, showing a significantly (p=0.0196) lower concentration in Cases compared to Controls. Stratifying by menopausal status, we found significantly lower levels of MCP-1 in post-menopausal Cases (p=0.0297). We also found that MCP-1 levels were decreased among pre-menopausal Cases but these results were not statistically significant. Analysis of IP-10 levels in CVL revealed no statistically significant differences in between Cases and Controls or between premenopausal and postmenopausal status. Our results indicate that sexual violence may cause immunological changes in the genital tract microenvironment in a manner that might enhance risk of HIV infection. All three chemokines that we analyzed function to attract T-cells and macrophages to an area of localized inflammation caused by damage to tissues or infection. Additionally, menopausal status might alter the immune environment further and therefore should be considered in studies involving women’s health and HIV