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Ruxolitinib (RUX) is a kinase inhibitor used in the treatment of various medical conditions and its mechanism of action involves suppression of the immune system. While beneficial in treatment of polycythemia vera, myelofibrosis and other indications, it can also increase a patient’s susceptibility to various infections, including bacterial, viral and fungal. We present a case of a patient being treated with RUX who presented with a disseminated fungal infection. This case emphasises the need for vigilance of endemic fungal infections in individuals who are on RUX therapy. [ABSTRACT FROM AUTHOR]

Introduction: Immunocompromised patients infected with influenza exhibit prolonged viral shedding and higher risk of resistance. Optimized treatment strategies are needed to reduce the risk of antiviral resistance. This phase IIIb, randomized, double-blind study (NCT00545532) evaluated conventional-dose or double-dose oseltamivir for the treatment of influenza in immunocompromised patients. Methods: Patients with primary or secondary immunodeficiency and influenza infection were randomized 1:1 to receive conventional-dose oseltamivir (75 mg adolescents/adults [≥ 13 years]; 30–75 mg by body weight in children [1–12 years]) or double-dose oseltamivir (150 or 60–150 mg, respectively), twice daily for an extended period of 10 days. Nasal/throat swabs were taken for virology assessments at all study visits. Co-primary endpoints were safety/tolerability and viral resistance. Secondary endpoints included time to symptom alleviation (TTSA) and time to cessation of viral shedding (TTCVS). Results: Of 228 patients enrolled between February 2008 and May 2017, 215 (199 adults) were evaluable for safety, 167 (151 adults) for efficacy, and 152 (138 adults) for resistance. Fewer patients experienced an adverse event (AE) in the conventional-dose group (50.5%) versus the double-dose group (59.1%). The most frequently reported AEs were nausea, diarrhea, vomiting, and headache. Fifteen patients had post-baseline resistance, more commonly in the conventional-dose group (n = 12) than in the double-dose group (n = 3). In adults, median TTSA was similar between arms, while median TTCVS was longer with conventional dosing. Conclusions: Oseltamivir was well tolerated, with a trend toward better safety/tolerability for conventional dosing versus double dosing. Resistance rates were higher with conventional dosing in this immunocompromised patient population. Trial Registration: ClinicalTrials.gov identifier: NCT00545532. Funding: F. Hoffmann-La Roche Ltd. [ABSTRACT FROM AUTHOR]

Severe Strongyloides stercoralis, such as hyperinfection syndrome, carries a high mortality risk. Even with appropriate treatment, patients may experience infectious complications and failure of therapy. Currently, there are no Food and Drug administration--approved parenteral therapies available for treatment in patients who develop gastrointestinal complications from hyperinfection, including small bowel obstruction. A veterinary form of ivermectin is available as a subcutaneous injection, although current literature in humans is limited. We report on the successful treatment of two surviving immunocompromised patients with S. stercoralis hyperinfection syndrome after prompt recognition and initiation of veterinary subcutaneous ivermectin therapy. [ABSTRACT FROM AUTHOR]

Clostridium difficile is an important cause of nosocomial acquired antibiotic-associated diarrhea causing an estimated 453,000 cases with 29,000 deaths yearly in the U.S. Both antibiotic resistance and toxin expression of C. difficile correlate with the severity of C. difficile infection (CDI). In this report, a total of 139 C. difficile isolates from patients diagnosed with CDI in Tampa General Hospital (Florida) in 2016 were studied for antibiotic resistance profiles of 12 types of antibiotics and toxin production. Antibiotic resistance determined by broth microdilution method showed that strains resistant to multi-antibiotics are common. Six strains (4.32%) showed resistance to six types of antibiotics. Twenty strains (14.39%) showed resistance to five types of antibiotics. Seventeen strains (12.24%) showed resistance to four types of antibiotics. Thirty-nine strains (28.06%) showed resistance to three types of antibiotic. Thirty-four strains (24.46%) showed resistance to two types of antibiotics. While, all isolates were susceptible to metronidazole, and rifaximin, we found that one isolate (0.72%) displayed resistance to vancomycin (MIC ≥ 8μg/ml), and another one was resistant to fidaxomicin (MIC >1μg/ml). The percentage of isolates resistant to cefoxitin, ceftriaxone, chloramphenicol, ampicillin, clindamycin, erythromycin, gatifloxacin, and moxifloxacin was 75.54, 10.79, 5.76, 67.63, 82.70, 45.32, 28.06, and 28.78%, respectively. Toxin profiling by PCR showed the isolates include 101 (72.66%) A+B+CDT-strains, 23 (16.55%) A+B+CDT+ strains, 3 (2.16%) A-B+CDT+ strains, 1 (0.72%) A-B+CDT-strains, and 11 (7.91%) A-B-CDT-strains. Toxin production determined by ELISA using supernatants of bacterial culture harvested at 12, 24, 48, and 72 h of post inoculation (hpi) showed that the toxins were mainly produced between 48 and 72 hpi, and toxin B (TcdB) was produced faster than toxin A (TcdA) during the experimental time (72 hpi). In addition, the binary-positive strains were likely to yield more toxins compared to the binary-negative strains. This work contributes to the current understanding of the antibiotic resistance and virulence of C. difficile clinical strains. [ABSTRACT FROM AUTHOR]

Background Clostridium difficile infection (CDI) is a major infectious disease focus for which fecal microbiota transplantation (FMT) has been used with success in various patient populations. Methods We conducted a retrospective study of FMT in immunocompetent and immunocompromised patients to review outcomes at our center, with a focus on identifying risk factors for FMT failure in solid organ transplant (SOT) patients. FMT was conducted using universal banked frozen stool via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per our institutional protocol. Results Thirteen patients were included in the analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these, 6 patients had a history of SOT and were primarily abdominal organ recipients. All immunocompetent patients experienced success with FMT, while 3 immunocompromised SOT patients experienced failure. Two patients who failed FMT had a second FMT, which was successful in one patient and failed in the second patient. No adverse events were noted with FMT administration. A predictor of FMT failure was antimicrobial exposure pre-FMT. Conclusions This study highlights the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised patients. Antimicrobial exposure prior to FMT was an identified risk factor for FMT failure. The use of sequential FMT in SOT patients may be considered but ultimately requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Physicians rely on blood culture to diagnose bloodstream infections (BSI) despite its limitations. As new technologies emerge for rapid BSI diagnosis, optimization of their application to patient care requires an understanding of clinicians’ perspectives on BSI diagnosis and how a rapid test would influence medical decisions. Methods: We administered a 26-question survey to practitioners in infectious diseases/microbiology, critical care, internal medicine, and hematology/oncology services in USA and Germany about current standards in diagnosing and treating BSI and a hypothetical rapid BSI test. Results: Responses from 242 providers had roughly equal representation across specialties. For suspected BSI patients, 78% of practitioners would administer empiric broad spectrum antibiotics although they estimated, on average, that 31% of patients received incorrect antibiotics while awaiting blood culture results. The ability of blood culture to rule in or rule out infection was very/extremely acceptable in 67% and 36%, respectively. Given rapid test results, 60–87% of practitioners would narrow the spectrum of antimicrobial therapy depending on the microorganism detected, with significantly higher percentages when resistance determinants were also tested. Over half of respondents felt a rapid test would be very/extremely influential on clinical practice. Conclusions: Limitations of blood culture were perceived as a barrier to patient care. A rapid test to diagnose BSI would impact clinical practice, but the extent of impact may be limited by prevailing attitudes and practices. Opportunities exist for interventions to influence practitioners’ behaviors in BSI management particularly with emergence of newer diagnostic tests. [ABSTRACT FROM AUTHOR]

A 30-year-old man with history of neonatal hydrocephalus requiring ventriculoperitoneal shunt placement presented with Mycobacterium abscessus shunt infection despite no shunt manipulation over 10 years prior to presentation. Cure was not achieved until complete removal of all CNS shunt foreign body was performed despite initial adequate antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Background: Approaches to treatment-experienced HIV-infected patients with persistent low-level viremia are limited by current commercial resistance genotyping assays when the viral load (VL) is <500 copies/mL. The best intervention to achieve virologic suppression in this population is unclear. Methods: This is a case control retrospective chart review study of 149 HIV-infected patients with a VL of 50 to 1000 copies/mL. Patients were in either regimen unchanged group or intervention group (intensification of regimen or switch without guidance from resistance testing). End point was VL < 100 copies/mL. Results: At 6 months post change, 30.8% of patients with intervention versus 36.6% with no intervention achieved a complete virologic suppression. There were no statistically significant differences between these 2 groups (P = .254). The majority of patients without regimen change eventually progressed to complete virologic failure. Conclusion: Patients with persistent low levels of viremia are likely to progress to have virologic failure. This supports the adoption of a more proactive approach to treatment and more sensitive technique to identify drug resistance. [ABSTRACT FROM PUBLISHER]

Background Nocardia species can cause localized or disseminated disease in humans. Infection results from direct inoculation or inhalation. In recent years, several new species have been identified via molecular methods. Further speciation is crucial as each organism has its own spectrum of disease and unique antibiotic susceptibility patterns. Immunosuppression, alcoholism, and certain lung diseases are well-established risk factors for nocardiosis. In fact, cases have incremented in association with increasing population of immunocompromised hosts as well as improved methods for detection and identification. Thus, Nocardia species may be considered opportunistic pathogens. Nocardia bejingensis was first isolated in 2001 by Wang et al from sewage soil in China. The first human infections were reported in Asia. Subsequently, cases were reported in Europe and a few cases have been described in the United States but it has been infrequently cited in the literature. Thus, not much is known about its spectrum of disease. Methods The primary objective of this study was to determine the risk factors and clinical manifestations of Nocardia bejingensis infection via retrospective chart review of 6 cases identified in Tampa General Hospital and Moffitt Cancer Center within a 5-year period. We aimed to evaluate the treatment used and the antibiotic susceptibility patterns of the isolates. Results All patients were immunocompromised (1/3 HIV/AIDS, 1/3 hematologic malignancy, 1/3 solid-organ transplant). Most were male (67%) and mean age of 48. The majority had lung involvement (67%). Thecal sac infection and femur osteomyelitis (OM) were atypical manifestations. Localized disease predominated. Combination therapy was preferred. Trimethoprim-sulfamethoxazole (TMP-SMX), Ceftriaxone, and carbapenems were mostly used. All isolates were susceptible to TMP-SMX. See Table 1. Conclusion This case series depicts clinical features, risk factors, and epidemiology of Nocardia bejingensis infections. Our observations suggest that it is a novel pathogen in the United States, affecting mainly immunocompromised hosts. Early detection, appropriate antibiotics, and surgery were keys in successful management. However, further studies are needed to further elucidate its pathogenesis. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Strongyloides stercoralis is a nematode endemic to the tropical and subtropical regions. In the United States, it is mostly found at southeastern states. Most infections are asymptomatic but disseminated and fatal infections have been reported in immunocompromised patients. At our institution, universal screening through Strongyloides antibody detection in serum among solid-organ transplant candidates began since 2010 and all seropositive candidates are treated before transplantation. We previously determined our incidence to be about 5%. The aim of this study was to determine demographic characteristics and risk factors that can be used for more cost-effective targeted screening. Methods We performed a retrospective cohort study of patients who underwent transplant evaluation from 2014 to 2016. A total of 228 charts were reviewed for Strongyloides serology status, eosinophilia, demographics and risk factors. Chi-square and Fisher exact tests were used to do a comparative analysis between Strongyloides seropositive and seronegative cohorts. Results We identified 113 seropositive (SP) patients and 115 seronegative (SN) patients. There were more males in the seropositive group (79%) compared with seronegative group (62%) (P = 0.005). Caucasians predominated in both groups (SP 71% vs. SN 57%; P = 0.286). No significant difference was found between both groups with regards to occupation with soil or water contact (SP 38% vs. SN 30%; P = 0.281), birthplace outside USA or travel outside of United States (SP 31% vs. SN 36%; P = 0.732). Eosinophilia occurred less in the seropositive group compared with the seronegative group (SP 16% vs. SN 30%; P = 0.030). Conclusion The study did not find any statistically significant difference in the demographic characteristics or risk factors that can be used for prediction of Strongyloides seropositivity among solid-organ transplant candidates. Hence, our institution will continue universal screening for Strongyloides stercoralis for all our transplant candidates. Our findings further question donor screening for Strongyloides that uses a similar questionnaire which may not be reliable to identify those infected with this parasite. This would put recipients at risk for a donor-transmitted infection. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]