Clinical utility of point-of-care glucose testing in the assessment of gestational diabetes: Prospective cohort study.

OBJECTIVE: To assess the clinical utility of point-of-care (POC) capillary blood glucose (CBG) testing in the assessment of gestational diabetes mellitus (GDM) during oral glucose tolerance test (OGTT). DESIGN: Prospective cohort study. SETTING: Antenatal clinics at King's College Hospital. POPULATION: Women screened for GDM between March and June 2020. METHODS: The CBG was measured using the POC StatStrip® test and the venous plasma glucose (VPG) was measured by Roche analyser (Cobas 8000 c702). GDM was diagnosed based on the 2015 National Institute for Health and Clinical Excellence (NICE) Clinical Guideline criteria. The two methods were compared statistically using Analyse-It 5.40.2. MAIN OUTCOME MEASURES: Diagnostic sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the POC StatStrip® test, compared with VPG measured by reference laboratory method. RESULTS: A total of 230 women were included. The number and percentage of women with glucose concentrations above the GDM threshold using the POC StatStrip® test versus laboratory VPG measurement was 15 (6.5%) versus eight (3.4%) at fasting and 105 (45.6%) versus 72 (31.1%) at 2 h, respectively. The sensitivity and specificity values (and 95% CIs) for the POC StatStrip® test were 88% (52%-99%) and 97% (93%-98%) at fasting and 97% (91%-99%) and 79% (71%-84%) at 2 h, respectively. However, the specificity and the NPV for the POC StatStrip® test for concentrations of ≤5.0 mmol/L at fasting or <7.5 mmol/L at 2 h were 100%, and the sensitivity and the PPV for concentrations of >9.5 mmol/L at 2 h were 100%. CONCLUSIONS: In our cohort the POC measurement of CBG cannot entirely replace the laboratory method for the OGTT; however, it can be used to rule out/rule in GDM for glucose concentrations of ≤5.0 mmol/L at fasting or <7.5/>9.5 mmol/L at 2 h.

Antifungal Activity of Efinaconazole Compared to Fluconazole, Itraconazole, and Terbinafine against Terbinafine- and Itraconazole-Resistant and -Susceptible Clinical Isolates of Dermatophytes, Candida, and Mold.

BACKGROUND: Recently, an increasing number of resistant-to-terbinafine dermatophytosis cases have been reported. Thus, identifying an alternative antifungal agent that possesses a broad-spectrum activity, including against resistant strains, is needed. METHODS: In this study, we compared the antifungal activity of efinaconazole to fluconazole, itraconazole, and terbinafine against clinical isolates of dermatophyte, Candida, and molds using in vitro assays. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each antifungal was quantified and compared. Both susceptible and resistant clinical isolates of Trichophyton mentagrophytes (n=16), T. rubrum (n=43), T. tonsurans (n=18), T. violaceum (n=4), Candida albicans (n=55), C. auris (n=30), Fusarium sp., Scedosporium sp., and Scopulariopsis sp. (n=15 for each) were tested. RESULTS: Our data shows that efinaconazole was the most active antifungal, compared to the other agents tested, against dermatophytes with MIC50 and MIC90 (Concentration that inhibited 50% and 90% of strains tested, respectively) values of 0.002 and 0.03 µg/ml, respectively. Fluconazole, itraconazole and terbinafine showed MIC50 and MIC90 values of 1 and 8 µg/ml, 0.03 and 0.25 µg/ml, and 0.031 and 16 µg/ml, respectively. Against Candida isolates, efinaconazole MIC50 and MIC90 values were 0.016 and 0.25 µg/ml, respectively, whereas fluconazole, itraconazole and terbinafine had MIC50 and the MIC90 values of 1 and 16 µg/ml, 0.25 and 0.5 µg/ml, and 2 and 8 µg/ml, respectively. Against various mold species, efinaconazole MIC values ranged from 0.016 and 2 µg/ml, compared to 0.5 to greater than 64 µg/ml for the comparators. CONCLUSIONS: efinaconazole showed superior potent activity against a broad panel of susceptible and resistant dermatophyte, Candida, and mold isolates.

Development of obstetric-hepatology services: defining optimal care and impact of pregnancy counselling on patient experience.

Objective: Prepregnancy counselling (PPC) is an important aspect of care for women with chronic liver disease (CLD) and liver transplantation (LT), yet its impact has not been well described. This study aims to assess the experience of women attending a joint obstetric-hepatology PPC clinic in a single-centre unit. Design/methods: A retrospective questionnaire-based study in a tertiary unit within the UK where patients who attended the PPC clinic between March 2016 and July 2021 were invited to participate by filling in a questionnaire. Descriptive data and free-text content were subsequently analysed. Results: 108 women attended the PPC clinic over a 5-year period. Overall, 58/108 (54%) completed the questionnaire. Principal concerns regarding pregnancy included fears around deterioration in health (66%), maternal death (24%), pregnancy loss (66%), medication effects (60%) and disease transmission (36%). 17/58 (14%) patients felt the presence of multiple doctors was intimidating, however, perceptions improved by the end of the consultation.Overall, 44/58 (76%) respondents felt the clinic helped them reach a decision about pursuing pregnancy. Almost all respondents would recommend the clinic to others. There were no major differences in pregnancy outcomes between those that received PPC and those that did not. Conclusion: The PPC clinic facilitates a personalised approach to care and is well received by patients with CLD/LT. It is difficult to elucidate whether attendance alone impacts on pregnancy outcomes; registry data may be better placed at addressing this important question.

In Vivo Skin Colonization and Decolonization Models for Candida auris.

Candida auris infections present a critical problem to the healthcare system in many parts of the world. This yeast clinically manifests as a disseminated candidiasis which can be life-threating for susceptible individuals, as well as cutaneous and wound infections. Moreover, C. auris can colonize the skin and act as a nidus of infection. Importantly, this emerging yeast unlike other Candida spp. has demonstrated multidrug resistance; thus its eradication can be challenging. Animal models are important to gain insight into the pathogenesis of this infection, as well as play a significant role in drug development. In this chapter, we describe two C. auris animal models: a cutaneous infection guinea pig model and a skin decolonization mouse model.

An Immunocompromised Mouse Model of Candida auris Systemic Infection.

With the recent emergence of multidrug-resistant Candida auris, there is an urgent need for new antifungal compounds with novel pharmacodynamic and pharmacokinetic properties that can treat systemic fungal infections caused by this emerging yeast. Historically, testing the efficacy of treatment for disseminated candidiasis was accomplished using a diverse array of in vivo animal models, including mice which offer an advantage both in their similarities to humans and their lower cost of maintenance. However, in order to create effective in vivo models for testing new antifungal compounds designed to treat systemic infections, it is important that these models also mimic several of the relevant predisposing conditions that can lead to disseminated candidiasis. Here, we describe an immunocompromised mouse model of hematogenously disseminated C. auris infection, which may have utility to test the efficacy of candidate antifungal compounds.

Sarecycline Demonstrated Reduced Activity Compared to Minocycline against Microbial Species Representing Human Gastrointestinal Microbiota.

Prolonged use of broad-spectrum tetracycline antibiotics such as minocycline and doxycycline may significantly alter the gut and skin microbiome leading to dysbiosis. Sarecycline, a narrow-spectrum tetracycline-class antibiotic used for acne treatment, is hypothesized to have minimal impact on the gastrointestinal tract microbiota. We evaluated the effect of sarecycline compared to minocycline against a panel of microorganisms that reflect the diversity of the gut microbiome using in vitro minimum inhibitory concentration (MIC) and time-kill kinetic assays. Compared to minocycline, sarecycline showed less antimicrobial activity indicated by higher MIC against 10 of 12 isolates from the Bacteroidetes phylum, three out of four isolates from Actinobacteria phylum, and five of seven isolates from the Firmicutes phylum, with significantly higher MIC values against Propionibacterium freudenreichii (≥3 dilutions). In time-kill assays, sarecycline demonstrated significantly less activity against Escherichia coli compared to minocycline at all time-points (p < 0.05). Moreover, sarecycline was significantly less effective in inhibiting Candida tropicalis compared to minocycline following 20- and 22-h exposure. Furthermore, sarecycline showed significantly less activity against Lactobacillus paracasei (recently renamed as Lacticaseibacillus paracasei subsp. paracasei) (p = 0.002) and Bifidobacterium adolescentis at 48 h (p = 0.042), when compared to minocycline. Overall, sarecycline demonstrated reduced antimicrobial activity against 79% of the tested gut microorganisms, suggesting that it is less disruptive to gut microbiota compared with minocycline. Further in vivo testing is warranted.

Multiprofessional cross-site working between a level 1 and a level 3 neonatal unit: a retrospective cohort study.

OBJECTIVE: To assess the association of short-term neonatal outcomes with cross-site working of multiple healthcare professional teams between a level 3 and a level 1 neonatal unit. DESIGN: Retrospective cohort study. SETTING: A level 1 neonatal unit in London. PATIENTS: All infants admitted to the neonatal unit, between 2010 and 2021. INTERVENTIONS: The clinical service was rearranged in 2014 with the introduction of cross-site working between the level 1 unit and a level 3 unit of neonatal doctors, nurses and allied healthcare professionals. MAIN OUTCOME MEASURES: Admission of infants with a temperature less than 36°C, length of stay and time to first consultation by a senior team member. RESULTS: A total of 4418 infants were admitted during the study period. The percentage of infants delivered at a gestation below 32 weeks was higher in the pre-cross-site period (8.9%) compared with the cross site period (3.6%, p<0.001). The percentage of infants with an Apgar score less than 8 at 10 min was higher in the pre-cross-site period (6.2%) compared with the cross-site period (3.4%, p=0.001). More infants were admitted with a temperature less than 36°C in the pre-cross site period (12.3%) compared with the cross site period (3.7%, p<0.001). The median (IQR) duration of time to first consultation by a senior team member was higher in the pre-cross-site period (1 (0.5-2.6) hours) compared with the cross-site period (0.5 (0.2-1.3) hours) (p<0.001). The median (IQR) length of stay was 4 (2-11) days in the pre-cross-site period and decreased to 2 (1-4) days in the cross-site period (p<0.001). CONCLUSIONS: Cross-site working was associated with lower rates of admission hypothermia, shorter duration of stay and earlier first senior consultation.

Efficacy of Voriconazole, Isavuconazole, Fluconazole, and Anidulafungin in the Treatment of Emerging Candida auris Using an Immunocompromised Murine Model of Disseminated Candidiasis.

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo. MICs for anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 µg/ml, respectively. Significant in vivo efficacy was observed in the anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to that in the untreated group (P values of <0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacies against C. auris, whereas isavuconazole did not show significant in vivo activity.

Do Antifungals and Local Anesthetic Affect the Efficacy of Antibiotic Dipping Solution?

BACKGROUND: The rates of infection after inflatable penile prosthesis (IPP) range from 1% to 3%; however, with changes in antibiotic practice intraoperatively and the incorporation of local anesthetic dips, it is unclear whether this incidence of infection is affected. AIM: To evaluate whether the utilization of local anesthetic dips and antifungal solutions affect the efficacy of previously established dips across multiple species and strains. METHODS: Strains of four different species of bacteria and one fungus were prepared in a standardized confluency. A standardized, and sterile protocol was used to punch out 6mm circular discs from the reservoir of a Coloplast Titan device. The discs were submerged in a standardized concentration of antimicrobials (combinations of Bactrim, Rifampin + Gentamicin, Vancomycin, Zosyn, and Amphotericin B) and plated. The zone of inhibition (ZOI) was measured at 24, 48, and 72 hours. Five repetitions of each organism was performed (>1700 discs), and the mean ZOI was calculated. Saline and DMSO were used as control on each plate. OUTCOMES: Main outcome was the ZOI identified with each antibiotic solution, and the secondary outcome was the efficacy of the antibiotic over the course of 72 hours. RESULTS: Difference in antibiotic efficacy was seen when each bacterial species was evaluated separately, with rifampin and gentamicin having less efficacy towards all organisms other than S. epidermidis. When looking specifically at the Candida species, amphotericin B was significantly better than other antibiotic solutions. In regards to efficacy of antibiotics over 72 hours, all treatment groups showed a decrease in ZOI over time. However, treatment groups that included rifampin demonstrated the ability to inhibit S. aureus and S. epidermidis over the 72-hour period. CLINICAL IMPLICATIONS: To improve clinical practice and alleviate concerns that incorporation of local anesthetic and antifungals may decrease the efficacy of antibiotic solutions. STRENGTHS AND LIMITATIONS: A major strength of the study is that it is the most robust and scientifically sound study performed on this topic with approximately 1700 repetitions. It is also the first study of its kind to include a wide spectrum of bacterial and fungal strains and antibiotic solutions along with temporal data on drug elution over a 72-hour period. A limitation of the study is the in vitro model, and this needs to be validated in a clinical setting. CONCLUSIONS: Dipping prosthetics in antifungal and local anesthetic does not decrease the efficacy of the antimicrobials. The drug elution capabilities of the hydrophilic coating lasts primarily for 24-48hours. Mishra K, Bukavina L, Long L, et al. Do Antifungals and Local Anesthetic Affect the Efficacy of Antibiotic Dipping Solution?. J Sex Med 2021;18:966-973.

In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris.

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo AmBisome showed MIC50 and MIC90 values of 1 and 2 µg/ml, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg treatment group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data show that AmBisome has significant antifungal activity against C. auris infection in vitro and in vivo.

Safety and efficacy of in vitro fertilisation in patients with chronic liver disease and liver transplantation recipients.

BACKGROUND & AIMS: Chronic liver disease and liver transplantation (LT) can delay both timing and ability of women to conceive. With increased awareness and availability of in vitro fertilisation (IVF), the need for accurate counselling is paramount. To date, minimal data exist on outcomes of IVF in patients with chronic liver disease, cirrhosis, or post-LT. We report the largest experience of IVF in women with liver-related subfertility (LRSF). METHODS: A retrospective analysis was performed on 42 women with LRSF who had undergone 57 IVF cycles between 1990 and 2019. RESULTS: Forty-two women with LRSF received IVF; 9 cycles in 6 women with cirrhosis, 14 cycles in 11 women post-LT, and 34 cycles in 25 women without cirrhosis. The main aetiologies of liver disease included HBV, HCV, and autoimmune hepatitis (AIH). Of 57 IVF cycles evaluated, 43 (75%) resulted in successful implantation. Eight (2 post-LT, 3 with cirrhosis, 4 without cirrhosis) resulted in miscarriage. The live birth rate (LBR) was 74% (32/43). Two of 9 (22%) patients with cirrhosis, 4/14 (29%) patients who were post-LT, and 6/34 (18%) patients without cirrhosis had unsuccessful IVF attempts. Nine of 57 (16%) IVF cycles resulted in new liver enzyme derangement during therapy, which improved after treatment completion. Six pregnancies (2 in patients who were post-LT, 4 without cirrhosis) were complicated by obstetric cholestasis (OC). Ovarian hyperstimulation syndrome (OHSS) was rare (n = 3, 7%). One patient with AIH-related cirrhosis decompensated after initiating IVF, warranting discontinuation of therapy. There were no maternal deaths. Three women developed a hypertensive disorder of pregnancy. Half the pregnancies resulted in premature deliveries (range 27-36 weeks). CONCLUSIONS: In selected cases, IVF in women with LRSF can be successful. However, patients should be counselled on the potential increased risks of OHSS, OC, and prematurity. LAY SUMMARY: Women with liver disease or those who have had a liver transplant can experience difficulties getting pregnant. In this study, we look at whether alternative approaches to achieve pregnancy are harmful in these women. Overall, there were no significant issues with the use of in vitro fertilisation in women with liver disease, but they need to be aware of potential risks, such as early delivery of the baby.

A Second-Generation Fungerp Analog, SCY-247, Shows Potent In Vitro Activity against Candida auris and Other Clinically Relevant Fungal Isolates.

Due to the increase of antifungal drug resistance and difficulties associated with drug administration, new antifungal agents for invasive fungal infections are needed. SCY-247 is a second-generation fungerp antifungal compound that interferes with the synthesis of the fungal cell wall polymer ß-(1,3)-d-glucan. We conducted an extensive antifungal screen of SCY-247 against yeast and mold strains compared with the parent compound ibrexafungerp (IBX; formerly SCY-078) to evaluate the in vitro antifungal properties of SCY-247. SCY-247 demonstrated similar activity to IBX against all of the organisms tested. Moreover, SCY-247 showed a higher percentage of fungicidal activity against the panel of yeast and mold isolates than IBX. Notably, SCY-247 showed considerable antifungal properties against numerous strains of Candida auris Additionally, SCY-247 retained its antifungal activity when evaluated in the presence of synthetic urine, indicating that SCY-247 maintains activity and structural stability under environments with decreased pH levels. Finally, a time-kill study showed SCY-247 has potent anti-Candida, -Aspergillus, and -Scedosporium activity. In summary, SCY-247 has potent antifungal activity against various fungal species, indicating that further studies on this fungerp analog are warranted.

A Second-Generation Fungerp Analog, SCY-247, Shows Potent In Vivo Activity in a Murine Model of Hematogenously Disseminated Candida albicans.

Echinocandins are a first-line therapy for Candida infections through their ability to inhibit the synthesis of polymer ß-(1,3)-d-glucan. However, there has been an emergence of multidrug-resistant fungal species necessitating the development of novel antifungal agents to combat invasive fungal infections. SCY-247, a second-generation glucan synthase inhibitor of the triterpenoid class (fungerps), is currently being developed as a potential therapy option. We determined the pharmacokinetics (PKs) of SCY-247 following oral (gavage) administration in mice and evaluated the efficacy of SCY-247 in a murine model of hematogenously disseminated candidiasis caused by Candida albicans Plasma concentrations of SCY-247 were measurable through the last collected time point in all dose groups. Mean concentrations of SCY-247 increased with dose levels, with concentrations of SCY-247 higher after multiple doses than after a single dose. Treatment with SCY-247 resulted in decreased fungal burden and improvement in survival rates against C. albicans disseminated infection. Treatment with 10 mg/kg of body weight of SCY-247 showed a significant reduction in CFU compared with the untreated control (3-log decrease on average) (P = 0.008). Similarly, 40 mg/kg SCY-247 demonstrated a statistically significant reduction in kidney CFU compared with untreated mice (average log CFU ± SD of 2.38 ± 2.58 versus 6.26 ± 0.51; P = 0.001). Mice treated with SCY-247 at 40 mg/kg exhibited a 100% survival rate at the end of the study, contrasted with 62.5% (5 of 8) survival rate in untreated mice. The results of this investigation indicate that SCY-247 is a promising novel anti-fungal agent with activity against Candida infections.

Pregnancy in Liver Transplantation.

Pregnancy after liver transplantation (LT) is increasingly common and is a frequent scenario that transplant physicians, obstetricians, and midwives encounter. This review summarizes the key issues surrounding preconception, pregnancy-related outcomes, immunosuppression, and breastfeeding in female LT recipients. Prepregnancy counseling in these patients should include recommendations to delay conception for at least 1-2 years after LT and discussions about effective methods of contraception. Female LT recipients are generally recommended to continue immunosuppression during pregnancy to prevent allograft rejection; however, individual regimens may need to be altered. Although pregnancy outcomes are overall favorable, there is an increased risk of maternal and fetal complications. Pregnancy in this cohort remains high risk and should be managed vigilantly in a multidisciplinary setting. We aim to review the available evidence from national registries, population-based studies, and case series and to provide recommendations for attending clinicians.

Antimicrobial Activity of Silver Containing Crosslinked Poly(Acrylic Acid) Fibers.

: Bacterial and fungal pathogens have caused serious problems to the human health. This is particularly true for untreatable infectious diseases and clinical situations where there is no reliable treatment for infected patients. To increase the antimicrobial activity of materials, we introduce silver nanoparticle (NP) patches in which the NPs are incorporated to the surface of smooth and uniform poly(acrylic acid) (PAA) nanofibers. The PAA nanofibers were thermally crosslinked with ethylene glycol via heat treatment through a mild method. The characterization of the resulting PAA-silver NP patches was done using scanning electron microscopy (SEM), UV spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). To demonstrate the antimicrobial activity of PAA, we incorporated the patches containing the silver NPs into strains of fungi such as Candida albicans (C. albican) and bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA). The PAA-silver fibers achieved zones of inhibition against C. albicans and MRSA indicating their antimicrobial activity against both fungi and bacteria. We conclude that silver NP patches exhibited multiple inhibitory actions for the interruption and blockage of activity fungal and bacterial strains, which has the potential as an antimicrobial agent in infectious diseases. Moreover, the proposed material has the potential to be used in antimicrobial textile fabrics, food packaging films, and wound dressings.

A pilot, layerwise, ex vivo evaluation of the antifungal efficacy of amorolfine 5% nail lacquer vs other topical antifungal nail formulations in healthy toenails.

BACKGROUND: Studies investigating the penetration of amorolfine through the nail have shown the highest concentration in the uppermost layer and measurable antifungal activity even in the lower layers of the nail. OBJECTIVES: This pilot, ex vivo study compared the penetration of antifungal concentrations of amorolfine 5% nail lacquer in different layers of healthy, human cadaver toenails with that of terbinafine 10% nail solution, ciclopirox 8% nail lacquer and naftifine 1% nail solution. Moreover, the effect of nail filing prior to application on the penetration of amorolfine 5% was assessed. METHODS: Unfiled (n = 3) and filed (n = 3) nails were used for each antimycotic agent and amorolfine 5% nail lacquer, respectively. Twenty-four hours after topical application, the nails were sliced (10 µm), solubilised and added to agar plates seeded with Trichophyton rubrum. Zones of growth inhibition were measured. RESULTS: Only amorolfine penetrated the nails at sufficient concentrations to inhibit growth of T rubrum at different nail depths. In contrast, the comparators did not show antifungal efficacy. Nail filing resulted in larger zones of inhibition for amorolfine compared with those of intact nails. CONCLUSIONS: Unlike its comparators, a single application of amorolfine 5% nail lacquer resulted in antifungal efficacy within the nail plate. Nail filing increased the antifungal efficacy of amorolfine 5% nail lacquer.

Small-molecule AgrA inhibitors F12 and F19 act as antivirulence agents against Gram-positive pathogens.

Small-molecule antivirulence agents represent a promising alternative or adjuvant to antibiotics. These compounds disarm pathogens of disease-causing toxins without killing them, thereby diminishing survival pressure to develop resistance. Here we show that the small-molecule antivirulence agents F12 and F19 block staphylococcal transcription factor AgrA from binding to its promoter. Consequently, toxin expression is inhibited, thus preventing host cell damage by Gram-positive pathogens. Broad spectrum efficacy against Gram-positive pathogens is due to the existence of AgrA homologs in many Gram-positive bacteria. F12 is more efficacious in vitro and F19 works better in vivo. In a murine MRSA bacteremia/sepsis model, F19 treatment alone resulted in 100% survival while untreated animals had 70% mortality. Furthermore, F19 enhances antibiotic efficacy in vivo. Notably, in a murine MRSA wound infection model, combination of F19 with antibiotics resulted in bacterial load reduction. Thus, F19 could be used alone or in combination with antibiotics to prevent and treat infections of Gram-positive pathogens.

Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model.

Background: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration. Objectives: Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis. Methods: Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 107C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day. Results: Rezafungin had significantly lower average log10 cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log10 cfu/g of tissue compared with micafungin-treated mice on day 10. Conclusions: Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis.

Female perpetrated sexual offences reported to a London sexual assault referral centre.

A gender specific approach to understanding female sex offenders is important for developing prevention and treatment strategies, yet research to date is limited. While it is recognised that females often offend with another person, there has been little attempt to look beyond the two groupings of solo and co-offending and study females who offend in larger groups. Furthermore, very few studies have looked at the victims of these crimes and all of these have focussed on child victims only. The present work describes demographic and assault related characteristics of victims of all ages reporting a sexual assault by a female perpetrator to the Havens sexual assault referral centres in London, UK, in a five year period, with the aim of identifying victim, perpetrator and offence patterns in solo, pair and group sexual assaults. 47 cases were identified, just 0.66% of the total cases seen, and victims ranged from 3 to 59 years of age. Female perpetrators actively participated in the sexual and physical violence in many cases and were often involved in other ways, such as facilitating the offence, procuring the victim and filming the assault. Victims of solo perpetrators were mostly children who reported an assault by a teacher or childminder. Victims of pairs were older and all perpetrators were male/female pairs, usually reportedly in a romantic relationship. Victims of groups were more often strangers to the perpetrators and these assaults were often very violent. These findings are discussed in relation to current knowledge and suggestions are made for further research.

In Vitro and In Vivo Evaluation of the Antifungal Activity of APX001A/APX001 against Candida auris.

Candida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality. C. auris strains often demonstrate high fluconazole and amphotericin B MIC values, and some strains are resistant to all three major antifungal classes. We evaluated the susceptibility of 16 C. auris clinical strains, isolated from a wide geographical area, to 10 antifungal agents, including APX001A, a novel agent that inhibits the fungal protein Gwt1 (glycosylphosphatidylinositol-anchored wall transfer protein 1). APX001A demonstrated significantly lower MIC50 and MIC90 values (0.004 and 0.031 µg/ml, respectively) than all other agents tested. The efficacy of the prodrug APX001 was evaluated in an immunocompromised murine model of disseminated C. auris infection. Significant efficacy (80 to 100% survival) was observed in all three APX001 treatment groups versus 50% survival for the anidulafungin treatment group. In addition, APX001 showed a significant log reduction in CFU counts in kidney, lung, and brain tissue (1.03 to 1.83) versus the vehicle control. Anidulafungin also showed a significant log reduction in CFU in the kidneys and lungs (1.5 and 1.62, respectively) but did not impact brain CFU. These data support further clinical evaluation of this new antifungal agent.