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Objectives To evaluate the safety and efficacy of two dosing regimens of oral ibrexafungerp (formerly SCY-078), a novel orally bioavailable β-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.

The Accelerate Pheno and BacT/Alert Virtuo systems may improve bacteremia management. Here, we evaluated the impact of both devices on outcomes in patients with sepsis and concurrent Gram-negative bacteremia. This quasiexperimental study included a retrospective preimplementation and a prospective postimplementation group. Patients ≥18 years old with Gram-negative bacteremia were included. Patients with neutropenia, pregnant patients, those who were transferred from an outside hospital with active bloodstream infections, and those with polymicrobial bacteremia were excluded. Blood culture incubation in the BacT/Alert 3D device and microdilution antimicrobial susceptibility testing from culture plate growth were used prior to implementation of the BacT/Alert Virtuo and Accelerate Pheno systems. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) identification directly from blood culture was used pre- and postimplementation. Time to Gram stain results, identification, susceptibility reporting, initiation of narrow-spectrum Gram-negative therapy at 72 h, 30-day inpatient mortality, sepsis resolution, and length of hospital stay were evaluated. A total of 116 patients were included (63 preimplementation, 53 postimplementation). Median times to Gram stain and susceptibility results were significantly shorter postimplementation (P

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.

Background The Centers for Disease Control and Prevention and New York State Department of Health recently identified the Capital District of New York (CDNY) as an emerging endemic area for blastomycosis. However, no clinical or epidemiological description of blastomycosis in the CDNY has been published. Methods We performed a retrospective analysis of blastomycosis cases at Albany Medical Center (AMC) and Albany Stratton Veterans Affairs Medical Center (VAMC) from January 1, 2000, through June 1, 2019. Patients were identified via an institution-approved informatics system at the hospital's microbiology laboratory. Results We identified 20 patients diagnosed with blastomycosis over the past 2 decades. There was a nearly 9-fold increase in the annual number of cases in 2016–2019 compared with 2000–2015. The majority of patients resided in the CDNY (90%), and 65% lived within the Mohawk River valley. Most cases (85%) were assumed to be malignancies or non-mycotic infections prior to diagnosis, with median time between presentation and diagnosis of 53 days. Conclusions Our data support recent reports that blastomycosis is an emerging disease in the CDNY. Most patients were misdiagnosed as malignancy or non-mycotic infection, which led to treatment delays.

Combination therapy with vancomycin and piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) compared with monotherapy with either agent. This retrospective, matched cohort study was conducted to assess the comparative incidence of AKI due to combination therapy in patients receiving vancomycin and TZP in combination or as monotherapy. Patients aged ≥18 years admitted to Albany Medical Center (Albany, NY) between September 2013 and August 2014 who had received therapy for at least two consecutive days were included. Patients who were pregnant, neutropenic, had AKI on admission or with cystic fibrosis were excluded. Patients were matched on baseline risk of AKI. The main outcome of interest was AKI, defined as an increase in serum creatinine of ≥0.3 mg/L or ≥50% within 48 h. Secondary outcomes evaluated were length of hospital and ICU stay and inpatient mortality associated with AKI. The risk of AKI was 7.0%, 8.5% and 26.8% in the vancomycin monotherapy, TZP monotherapy and combination groups, respectively (P0.001). In the multivariate analysis, combination therapy was independently associated with an increased odds of AKI (adjusted odds ratio = 4.406, 95% confidence interval 1.472-13.188) compared with vancomycin monotherapy. The excess risk of combination therapy was 11.3%. In this matched cohort study, there was an increased incidence of AKI in patients receiving vancomycin and TZP combination therapy. Further research is needed to determine the individual strategies to best prevent inpatient AKI in patients receiving this combination therapy.

Background Blood cultures are approximately 50% sensitive for diagnosing invasive candidiasis. The T2Candida nanodiagnostic panel uses T2 magnetic resonance and a dedicated instrument to detect Candida directly within whole blood samples. Methods Patients with Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, or Candida krusei candidemia were identified at 14 centers using diagnostic blood cultures (dBCs). Follow-up blood samples were collected concurrently for testing by T2Candida and companion cultures (cBCs). T2Candida results are reported qualitatively for C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis. T2Candida and cBCs were positive if they detected a species present in the dBC. Results Median time between collection of dBC and T2Candida/cBC samples in 152 patients was 55.5 hours (range, 16.4-148.4). T2Candida and cBCs were positive in 45% (69/152) and 24% (36/152) of patients, respectively (P < .0001). T2Candida clinical sensitivity was 89%, as positive results were obtained in 32/36 patients with positive cBCs. Combined test results were both positive (T2+/cBC+), 21% (32/152); T2+/cBC-, 24% (37/152); T2-/cBC+, 3% (4/152); and T2-/cBC-, 52% (79/152). Prior antifungal therapy, neutropenia, and C. albicans candidemia were independently associated with T2Candida positivity and T2+/cBC- results (P values < .05). Conclusions T2Candida was sensitive for diagnosing candidemia at the time of positive blood cultures. In patients receiving antifungal therapy, T2Candida identified bloodstream infections that were missed by cBCs. T2Candida may improve care by shortening times to Candida detection and species identification compared to blood cultures, retaining sensitivity during antifungal therapy and rendering active candidemia unlikely if results are negative. Clinical Trials Registration NCT01525095.

Purpose Antimicrobial stewardship programs (ASPs) can be aided by using rapid diagnostics (RDT). However, there are limited data evaluating the impact of ASPs and RDT on sepsis outcomes in the setting of the new Sepsis-3 guidelines. This study evaluates the impact of a low-resource method for ASPs with RDT on sepsis outcomes. Methods This was a prospective, quasi-experimental study with a retrospective double pretest. Patients ≥ 18 years old with sepsis and concurrent bacteremia or fungemia were included; patients who were pregnant, had polymicrobial septicemia or who were transferred from an outside hospital were excluded. In the first pretest (O1), polymerase chain reaction was used to identify Staphylococcal species from positive blood cultures, and traditional laboratory techniques were used to identify other species. Matrix-assisted laser desorption ionization time-of-flight mass spectroscopy and FilmArray were implemented in the second pretest (O2), and twice daily blood culture review was implemented in the posttest (O3). Results A total of 394 patients (157 in O1, 176 in O2, 61 in O3) were enrolled. Clinical response was 73.2%, 83.5%, and 88.5% in O1, O2, and O3, respectively, p = 0.013. By Cox regression, the O3 was associated with improved time to clinical response (hazard ratio, 1.388; 95% confidence interval, 1.004-1.919) as compared with O1. Mortality, hospital length of stay, and intensive care unit length of stay were unchanged between groups. Conclusion Twice-daily blood culture review may be useful for implementing rapid diagnostics within low-resource ASPs. Further research is needed to identify the optimal method of blood culture follow-up within low-resource settings.

To report use of intravenous foscarnet or cidofovir for the treatment of refractory acute retinal necrosis (ARN).Retrospective chart review.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).Cases of HSV or VZV ARN that worsen despite intravenous acyclovir treatment may respond to intravenous foscarnet or cidofovir.

Background Blastomycosis is a commonly misdiagnosed infection caused by Blastomyces spp. It is not reportable in New York State (NYS), but where reportable, yearly incidence is 1–2/100,000 persons. In October 2017, a physician notified the NYS Department of Health (NYSDOH) of six blastomycosis cases seen during April 2016–July 2017 in the nonendemic eastern upstate area known as the Capital District (CD). NYSDOH investigated to determine the possibility of locally acquired blastomycosis. Methods NYS hospital blastomycosis discharge codes from the January 2007–December 2016 Statewide Planning and Research Cooperative System dataset were reviewed. To better understand illness in the area of highest incidence, NYSDOH contacted CD physicians to identify patients diagnosed with blastomycosis during April 2016–February 2018. Chart reviews and interviews were conducted to obtain travel and disease progression details. Results During 2007–2016, there were 279 blastomycosis diagnoses in NYS. Mean annual blastomycosis diagnoses during 2007–2015 was 24 (incidence: 0.1/100,000 persons); in 2016, there were 59 blastomycosis diagnoses (incidence: 0.3/100,000 persons). A CD county had the highest state incidence, with a rate increase from 2.0/100,000 persons during 2007–2015 to 4.1/100,000 persons during 2016. CD physicians provided contact and clinical information for the six initially-identified patients and two additional patients seen during April 2016–February 2018. All experienced delays in diagnosis, seven lacked travel history, two had cutaneous blastomycosis, three had pulmonary blastomycosis, and three had disseminated blastomycosis. One died from blastomycosis and another required long-term ventilator support. Seven cases were identified by culture or histopathology; the diagnostic method for one was unknown. Conclusion One CD county had blastomycosis rates similar to known endemic areas; patients lacked travel history to endemic areas, indicating locally acquired blastomycosis might have occurred. To improve prompt diagnosis, NYS clinicians and laboratorians should consider blastomycosis in patients with pneumonia, even without travel history to endemic areas. Further evaluation is needed to determine whether the endemic area of NYS has expanded. Disclosures All authors: No reported disclosures.

Background Blood cultures (BC) are the diagnostic gold standard for candidemia, but sensitivity is Methods Candidemic adults were identified at 14 centers by diagnostic BC (dBC). Follow-up blood samples were collected from all patients (pts) for testing by T2 and companion BC (cBC). T2 was run-in batch at a central lab; results are reported qualitatively for three groups of spp. (Candida albicans/C. tropicalis (CA/CT), C. glabrata/C. krusei (CG/CK), or C. parapsilosis (CP)). T2 and cBC were defined as positive (+) if they detected a sp. identified in dBC. Results 152 patients were enrolled (median age: 54 yrs (18–93); 54% (82) men). Candidemia risk factors included indwelling catheters (82%, 125), abdominal surgery (24%, 36), transplant (22%, 33), cancer (22%, 33), hemodialysis (17%, 26), neutropenia (10%, 15). Mean times to Candida detection/spp. identification by dBC were 47/133 hours (2/5.5 d). dBC revealed CA (30%, 46), CG (29%, 45), CP (28%, 43), CT (11%, 17) and CK (3%, 4). Mean time to collection of T2/cBC was 62 hours (2.6 d). 74% (112) of patients received antifungal (AF) therapy prior to T2/cBC (mean: 55 hours (2.3 d)). Overall, T2 results were more likely than cBC to be + (P Conclusion T2 was sensitive for diagnosing candidemia at the time of + cBC, and it was significantly more like to be + than cBC among AF-treated patients. T2 is an important advance in the diagnosis of candidemia, which is likely to be particularly useful in patients receiving prophylactic, pre-emptive or empiric AF therapy. Disclosure D. P. Kontoyiannis, Pfizer: Research Contractor, Research support and Speaker honorarium; Astellas: Research Contractor, Research support and Speaker honorarium; Merck: Honorarium, Speaker honorarium; Cidara: Honorarium, Speaker honorarium; Amplyx: Honorarium, Speaker honorarium; F2G: Honorarium, Speaker honorarium; L. Ostrosky-Zeichner, Astellas: Consultant and Grant Investigator, Consulting fee and Research grant; Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium; Pfizer: Grant Investigator and Speaker’s Bureau, Grant recipient and Speaker honorarium; Scynexis: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient; Cidara: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; S. Apewokin, T2 biosystems: Investigator, Research support; Astellas: Scientific Advisor, Consulting fee