MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis.

OBJECTIVES: To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable ß-glucan synthase inhibitor, in subjects with invasive candidiasis versus the standard of care (SOC) and to identify the dose to achieve target exposure (15.4 µM·h) in >80% of the intended population. METHODS: In a multinational, open-label study, patients with documented invasive candidiasis were randomized to receive step-down therapy to one of three treatment arms: two dosing regimens of novel oral ibrexafungerp or the SOC treatment following initial echinocandin therapy. Plasma samples were collected to evaluate exposure by population pharmacokinetic (PK) modelling. Safety was assessed throughout the study and global response at the end of treatment. RESULTS: Out of 27 subjects enrolled, 7 received ibrexafungerp 500 mg, 7 received ibrexafungerp 750 mg and 8 received the SOC. Five did not meet criteria for randomization. Population PK analysis indicated that an ibrexafungerp 750 mg regimen is predicted to achieve the target exposure in ∼85% of the population. The rate of adverse events was similar among patients receiving ibrexafungerp or fluconazole. Similar favourable response rates were reported among all groups: 86% (n = 6) in the ibrexafungerp 750 mg versus 71% (n = 5) in both the fluconazole and ibrexafungerp 500 mg treatment arms. The one subject treated with continued micafungin had a favourable global response. CONCLUSIONS: The oral ibrexafungerp dose estimated to achieve the target exposure in subjects with invasive candidiasis is 750 mg daily. This dose was well tolerated and achieved a favourable global response rate, similar to the SOC.

Is Blastomycosis Endemic in Upstate New York?: A Case Report and Review of Literature.

CASE: We describe a case of biopsy-proven blastomycosis in a patient residing in Upstate New York with osseous and skin lesions and no pulmonary or constitutional symptoms. The patient had a rapid resolution of symptoms after the initiation of antifungal treatment, followed by curettage and cementation of her distal femoral lesion. CONCLUSIONS: Orthopaedic surgeons should be aware of the presence of blastomycosis in nonendemic areas, especially since bone involvement may be the predominant manifestation. Tissue should be submitted for both histologic and microbiologic analysis. Antifungal therapy and surgical management if needed can result in a good outcome.

Treatment of Refractory Acute Retinal Necrosis with Intravenous Foscarnet or Cidofovir.

PURPOSE: To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN). METHODS: Retrospective chart review. RESULTS: Four immunocompetent men aged 45-90 years presented with ARN from 2008-2014. One patient with two prior episodes of herpes simplex virus (HSV) ARN developed ARN after 6 years of antiviral prophylaxis. His condition worsened on acyclovir followed by intravenous foscarnet but responded to intravenous cidofovir (final VA in involved eye 20/20). Another patient with HSV ARN had received prolonged acyclovir prophylaxis for HSV keratitis; ARN improved after switching from acyclovir to intravenous foscarnet (final VA 20/125). Two patients with varicella zoster virus (VZV) ARN initially responded to acyclovir but developed fellow eye involvement 2-8 weeks later that worsened on acyclovir but responded to intravenous foscarnet (fellow eye final VA 20/20, 20/40). CONCLUSIONS: Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.

The spread of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae to upstate New York.

Klebsiella pneumoniae carbapenemases (KPCs) have previously been identified in distinct geographic locations. We report the spread of KPC-2 to upstate New York. Our intention is to alert clinicians to problems encountered in identifying KPC-containing isolates. Possible errors as a result of inferring susceptibility of untested carbapenems from the routine antibiogram using agar-based methodology or microdilution testing are discussed.

Successful treatment of Fusarium endophthalmitis with voriconazole and Aspergillus endophthalmitis with voriconazole plus caspofungin.

PURPOSE: To report successful treatment of exogenous Fusarium and Aspergillus endophthalmitis with new antifungal agents. DESIGN: Interventional case report. METHODS: Treatment of two cases is reviewed. RESULTS: A 64-year-old man developed post-cataract Fusarium moniliforme endophthalmitis. Infection persisted despite removal of the intraocular lens, three vitrectomies, and five intravitreal injections of amphotericin. Inflammation resolved and vision improved from 20/80 to 20/40 on 6 months of oral voriconazole. A 55-year-old man developed post-cataract intraocular inflammation. After three vitrectomies and removal of the intraocular lens, Aspergillus fumigatus endophthalmitis was diagnosed. Intravitreal amphotericin and systemic voriconazole were given, but one week later there were early signs of recurrence. Intravenous caspofungin was added and the eye improved. Caspofungin was continued for 6 weeks and voriconazole for 6 months. Vision improved from counting fingers to 20/80 at 6 months and 20/25 at 23 months. CONCLUSION: Voriconazole is a promising new therapy for Fusarium and Aspergillus endophthalmitis. Caspofungin may act synergistically with voriconazole in treating Aspergillus endophthalmitis.

Community associated methicillin resistant Staphylococcus aureus causing Fournier's gangrene and genital infections.

PURPOSE: We identified an emerging infectious disease of the genitoperineum caused by community associated, methicillin resistant Staphylococcus aureus. MATERIALS AND METHODS: We report our experience with severe genital infections caused by community associated, methicillin resistant S. aureus occurring in 3 individuals who lacked any of the risk factors associated with traditional methicillin resistant S. aureus infection. Two cases were limited to scrotal abscesses that required only incision and drainage plus antimicrobial therapy. To our knowledge the third case represents the first and only reported case to date of Fournier's gangrene caused by community associated, methicillin resistant S. aureus. RESULTS: The prevalence of community associated, methicillin resistant S. aureus complicated skin and skin structure infections is increasing throughout the United States and other countries. Community associated, methicillin resistant S. aureus contains unique virulence factors but retains sensitivity to various nonbeta-lactam antibiotics. Historical risk factors associated with methicillin resistant S. aureus appear not to apply to infections associated with community associated, methicillin resistant S. aureus. Infections due to the latter cause have been identified in healthy individuals of all ages, races and ethnicities. Surgical and antimicrobial approaches to management are presented. CONCLUSIONS: Community associated, methicillin resistant S. aureus infections of the genitoperineum are likely to increase in incidence, necessitating heightened awareness on the part of the urologist.

Identification of dengue virus in respiratory specimens from a patient who had recently traveled from a region where dengue virus infection is endemic.

Dengue is the most important arthropod-borne viral disease, and it is a major public health problem in subtropical and tropical regions. The virus is transmitted to humans by the bite of infected female mosquitoes of the genus Aedes. The global resurgence of dengue is thought to be due to failure to control the Aedes populations, uncontrolled urbanization, population growth, climate change, and increased airplane travel. In this paper we describe the methods used to detect dengue virus infection in a patient who presented to a hospital in New York State. The patient was a 21-year-old female who had recently traveled from Thailand. Serologic testing, viral culture, and molecular methods, including reverse transcription-PCR (RT-PCR) and real-time RT-PCR, were tools used for diagnosis. Enzyme-linked immunosorbent assay and immunofluorescence assay of serum specimens indicated flavivirus infection. Conventional RT-PCR and sequencing, in addition to real-time RT-PCR of serum samples and nasal and throat swabs from the patient, confirmed dengue virus 1 (DEN-1) infection. A cytopathic effect was observed in virus cultures of the acute-phase serum samples and nasal swabs. DEN-1 was subsequently detected by RT-PCR from cell culture supernatants and by direct fluorescent-antibody assay staining of the cell culture monolayer. We show that a multipronged approach to the laboratory diagnosis of dengue infections can be used to successfully diagnose and differentiate the dengue virus serotypes. In addition, we show that both dengue viral RNA and infectious virus can be detected in respiratory specimens from an infected patient.