Impact of Accelerate Pheno and BacT/Alert Virtuo on Clinical Processes and Outcomes in Patients with Sepsis and Concurrent Gram-Negative Bacteremia.

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 < 0.001). The postimplementation group had an improved hazard ratio for narrow-spectrum Gram-negative therapy at 72 h (hazard ratio [HR], 2.685 [95% confidence interval {CI}, 1.348 to 5.349]), a reduced hazard ratio for 30-day inpatient mortality (adjusted HR [aHR], 0.150 [95% CI, 0.026 to 0.846]), and improved sepsis resolution (92.5% versus 77.8% [P = 0.030]). The length of hospital stay was unchanged after implementation. We conclude that implementation of the BacT/Alert Virtuo and Accelerate Pheno systems improved microbiology laboratory processes, antibiotic utilization processes, and clinical outcomes. These data support the use of rapid diagnostics in sepsis with concurrent Gram-negative bacteremia.

Nanotechnology Fundamentals Applied to Clinical Infectious Diseases and Public Health.

Nanotechnology involves the discovery and fabrication of nanoscale materials possessing unique physicochemical properties that are being employed in industry and medicine. Infectious Diseases clinicians and public health scientists utilize nanotechnology applications to diagnose, treat, and prevent infectious diseases. However, fundamental principles of nanotechnology are often presented in technical formats that presuppose an advanced knowledge of chemistry, physics, and engineering, thereby limiting the clinician's grasp of the underlying science. While nanoscience is technically complex, it need not be out of reach of the clinical practitioner. The aim of this review is to introduce fundamental principles of nanotechnology in an accessible format, describe examples of current clinical infectious diseases and public health applications, and provide a foundation that will aid understanding of and appreciation for this burgeoning and important field of science.

Blastomycosis in the Capital District of New York State: A Newly Identified Emerging Endemic Area.

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.

Concurrent Diagnosis of Acute Myeloid Leukemia and COVID-19: A Management Challenge.

The emergence of coronavirus disease 2019 (COVID-19) has created new challenges in the management of serious diseases. We describe a 41-year-old male who presented with fever, watery diarrhea, and epistaxis. Initial workup revealed pancytopenia with >50% blasts on the peripheral smear raising suspicion of acute myeloid leukemia (AML) (later confirmed by bone marrow biopsy as AML with myelodysplasia-related changes) and a positive polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the extraordinary risk, he was treated with remdesivir and convalescent plasma for COVID-19. On admission day 8, repeat PCR for SARS-CoV-2 returned negative and the patient was deemed stable for chemotherapy. Therefore, induction was done with liposomal daunorubicin and cytarabine. However, he did not respond to the therapy and was started on re-induction therapy with decitabine and venetoclax. In our discussion, we review the current principles of treatment of patients with concurrent COVID-19 and AML.

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.

Streptococcus pyogenes peritonitis: a rare, lethal imitator of appendicitis.

Streptococcus pyogenes is a common cause of infection. Since 2010, the Centers for Disease Control has noted a 24% rise in invasive S. pyogenes infections with a mortality rate of 10%. We present a case series and review of the English literature. Two patients presented with findings concerning for appendicitis, each underwent laparoscopic appendectomies. Both had diffuse peritoneal inflammation without appendicitis, cultures grew S. pyogenes and both recovered with appropriate antibiotics. Thirty cases were identified in a review of the English literature. The average age was 27 years, 75% were in women, 9% were immunocompromised, 15% had rashes and 88% underwent surgical intervention. Previous work identified female gender, immunosuppression and preceding varicella infection as risk factors for invasive S. pyogenes. Given the similarities to appendicitis, early suspicion can influence antibiotic therapy and possibly improve outcomes.

Time to clinical response in sepsis associated with an algorithm for blood-culture pathogen identification using matrix-assisted laser desorption ionization time-of-flight mass spectroscopy.

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.

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.

Comparative incidence and excess risk of acute kidney injury in hospitalised patients receiving vancomycin and piperacillin/tazobactam in combination or as monotherapy.

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 (P < 0.001). 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.

Detecting Infections Rapidly and Easily for Candidemia Trial, Part 2 (DIRECT2): A Prospective, Multicenter Study of the T2Candida Panel.

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.

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.

Intracytoplasmic granulocytic morulae counts on confirmed cases of ehrlichiosis/anaplasmosis in the Northeast.

OBJECTIVES: To characterize the number of granulocytes needed to count on peripheral smear to identify diagnostic anaplasmosis morulae. METHODS: Retrospective case study where the peripheral smears of 14 confirmed cases of anaplasmosis were examined. The granulocytes were counted up to 100 and 200 until a morula was identified. The mean counts of three pathologists were calculated to determine the minimum number of granulocytes needed to count for identifying diagnostic morulae. RESULTS: Morulae were identified before a count of 100 granulocytes in 11 (78.6%) cases and between 100 and 200 granulocytes in 3 (21.4%) cases. All 14 (100%) cases had morulae identified before counting 200 granulocytes. CONCLUSIONS: Peripheral smears are a useful, cost-effective, and time-effective tool for diagnosing anaplasmosis. In positive cases, diagnostic morulae can be identified with a count of 200 granulocytes.

Evaluation of an early step-down strategy from intravenous anidulafungin to oral azole therapy for the treatment of candidemia and other forms of invasive candidiasis: results from an open-label trial.

BACKGROUND: Hospitalized patients are at increased risk for candidemia and invasive candidiasis (C/IC). Improved therapeutic regimens with enhanced clinical and pharmacoeconomic outcomes utilizing existing antifungal agents are still needed. METHODS: An open-label, non-comparative study evaluated an intravenous (i.v.) to oral step-down strategy. Patients with C/IC were treated with i.v. anidulafungin and after 5 days of i.v. therapy had the option to step-down to oral azole therapy (fluconazole or voriconazole) if they met prespecified criteria. The primary endpoint was the global response rate (clinical + microbiological) at end of treatment (EOT) in the modified intent-to-treat (MITT) population (at least one dose of anidulafungin plus positive Candida within 96 hours of study entry). Secondary endpoints included efficacy at other time points and in predefined patient subpopulations. Patients who stepped down early (≤ 7 days' anidulafungin) were identified as the "early switch" subpopulation. RESULTS: In total, 282 patients were enrolled, of whom 250 were included in the MITT population. The MITT global response rate at EOT was 83.7% (95% confidence interval, 78.7-88.8). Global response rates at all time points were generally similar in the early switch subpopulation compared with the MITT population. Global response rates were also similar across multiple Candida species, including C. albicans, C. glabrata, and C. parapsilosis. The most common treatment-related adverse events were nausea and vomiting (four patients each). CONCLUSIONS: A short course of i.v. anidulafungin, followed by early step-down to oral azole therapy, is an effective and well-tolerated approach for the treatment of C/IC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00496197.

Necrotizing fasciitis.

Necrotizing fasciitis is a rare but life-threatening soft-tissue infection characterized by rapidly spreading inflammation and subsequent necrosis of the fascial planes and surrounding tissue. Infection typically follows trauma, although the inciting insult may be as minor as a scrape or an insect bite. Often caused by toxin-producing, virulent bacteria such as group A streptococcus and associated with severe systemic toxicity, necrotizing fasciitis is rapidly fatal unless diagnosed promptly and treated aggressively. Necrotizing fasciitis is often initially misdiagnosed as a more benign soft-tissue infection. The single most important variable influencing mortality is time to surgical débridement. Thus, a high degree of clinical suspicion is necessary to avert potentially disastrous consequences. Orthopaedic surgeons are often the first to evaluate patients with necrotizing fasciitis and as such must be aware of the presentation and management of this disease. Timely diagnosis, broad-spectrum antibiotic therapy, and aggressive surgical débridement of affected tissue are keys to the treatment of this serious, often life-threatening infection.

Fungal vertebral osteomyelitis due to Scedosporium apiospermum after near-drowning.

Near-drowning predisposes one to infection by the fungus Scedosporium apiospermum, and brain abscess is the most common consequence. Vertebral osteomyelitis due to this organism is exceedingly rare. The authors report on a 43-year-old man who developed fungal spondylodiscitis several weeks after a near-drowning event. The rare nature of this infection led to a delay in diagnosis. A combination of surgical debridement, instrumentation, and antifungal therapy resulted in an excellent outcome at 1 year of follow-up.

Sarcoidal granulomatous tenosynovitis of the hands occurring in an organ transplant patient.

Six years after kidney-pancreas transplant, a 47-year-old white man developed multiple subcutaneous and tenosynovial nodules of hands and wrists, limiting mobility. Biopsy of multiple nodules showed fibrosing, sarcoidal granulomas, some of which contained pigmented material. Microbiology, immunohistochemistry, scanning electron microscopy with backscattered electron imaging and energy dispersive X-ray analysis and polymerase chain reaction assays failed to show any infectious agents or foreign material. There was no historical, clinical or laboratory evidence of systemic sarcoidosis. It is not known whether the donor had sarcoidosis. Despite empiric antimycobacterial therapy and ongoing immunosuppressive therapy (corticosteroids, mycophenolate, cyclosporine), the man has progressively developed more nodules, limiting hand function. Sarcoidosis occurring in non-donor tissue post-transplantation is an exceedingly rare complication of transplantation. We discuss this case and review the literature on sarcoidal tenosynovitis and sarcoidosis occurring post-transplantation.

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.

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.