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The Quantiferon-Cytomegalovirus (QF-CMV) assay was introduced to predict CMV infection and inform prophylaxis duration in our lung transplant recipients (LTR) from 2012. The aims of this retrospective cohort study were to review our QF-CMV experience, understand factors associated with positive results and further explore its predictive utility.LTR with QF-CMV testing performed at 5 months post-transplant were included. Patients receiving QF-directed prophylaxis (5 or 11 months) were compared to those receiving our prior standard of care (5 months). Outcomes were CMV infection1,000 IU/mL in blood and/or bronchoalveolar lavage fluid. Factors associated with positive QF-CMV results were identified. Patients were compared based on serostatus, QF-CMV results and prophylaxis duration.Our cohort included 263 LTR (59 D+/R-, 204 R+). QF-directed prophylaxis was used in 195 of 263 (74%) and was associated with reduced CMV infection (84/195, 43% vs 41/68, 60%, p.001). Patients receiving extended prophylaxis experienced less CMV if negative and/or indeterminate (43% vs 70%, p.01) or positive (10% vs 51%, p.01). Only 5 of 59 (8%) D+/R- patients were QF-CMV positive compared to 155 of 204 (76%) R+ patients (adjusted OR 0.03, 0.01-0.07, p.001). After controlling for prophylaxis duration, only D+/R- serostatus remained independently associated with CMV infection (adjusted HR 4.90, 95% CI 2.68-9.00, p.0001).QF-CMV results were strongly correlated with serostatus, with D+/R- patients unlikely to test positive while receiving prophylaxis. Extended prophylaxis was associated with delayed onset, reduced frequency and severity of CMV infection across all subgroups. After accounting for serostatus, the incremental predictive value of QF-CMV in this cohort was limited.

Limited data exist to describe sex-based differences in the severity of cytomegalovirus (CMV) infection after solid organ transplant (SOT). We sought to identify if a difference exists in likelihood of tissue-invasive disease between male and female SOT recipients and to understand how age affects this relationship.A retrospective cohort of 180 heart, liver, and kidney recipients treated for CMV was examined. A logistic regression model was developed to assess the relationship between female sex and CMV type (noninvasive vs. invasive). A secondary regression analysis looked at the relationship of invasive CMV with a variable combining sex with age above or below 50.There were 37 cases of proven or probable invasive CMV, occurring in 30% of females versus 16% of males. After adjustment for potential confounders, females with CMV infection were significantly more likely to have invasive disease (odds ratio (OR) 2.69, 95% confidence interval (CI) 1.25-5.90, p = .01). Females 50 years or older were at particular risk compared with males under 50 years (adjusted OR 4.54, 95% CI 1.33-18.83, p = .02).Female SOT recipients with CMV in our cohort were more likely than males to have tissue-invasive disease, with the highest risk among older females. Further prospective studies are warranted to explore underlying immunologic mechanisms.

The >30 mutated residues in the Omicron spike protein have led to its rapid classification as a new SARS-CoV-2 variant of concern. As a result, Omicron may escape from the immune system, decreasing the protection provided by COVID-19 vaccines. Preliminary data shows a weaker neutralizing antibody response to Omicron compared to the ancestral SARS-CoV-2 virus, which can be increased after a booster vaccine. Here, we report that CD8+ T cells can recognize Omicron variant epitopes presented by HLA-A*02:01 in both COVID-19 recovered and vaccinated individuals, even 6 months after infection or vaccination. Additionally, the T cell response was stronger for Omicron variant epitopes after the vaccine booster. Altogether, T cells can recognize Omicron variants, especially in vaccinated individuals after the vaccine booster.One-Sentence SummaryCD8+ T cells response against Omicron variant epitopes is stronger after the vaccine booster.

BACKGROUND Optimizing immunosuppression in lung transplant recipients (LTR) is crucially important in minimizing the risk of infection and rejection. Quantiferon®-Monitor (QFM) is a candidate immune function biomarker which has not yet been rigorously evaluated in the lung transplant setting. The aim of this prospective cohort study was to explore relationships between QFM results, immunosuppression, and infection/rejection in LTR. METHODS QFM, which measures interferon-γ after stimulation with innate and adaptive immune antigens, was tested before and at 2, 6, 12, 24 and 52 weeks post-transplant. Immunosuppression relationships were assessed with linear mixed effects models. Clinical outcomes were analyzed based on the preceding QFM result. RESULTS Eighty LTR were included. Median pre-transplant QFM levels were 171 IU/mL (IQR 45-461), decreasing to 3 IU/mL (IQR 1-8) at 2 weeks post-transplant then progressively recovering toward baseline with time from transplant. Prednisolone was strongly inversely associated with QFM level (0.1 mg/kg dose increase correlating with 88 IU/mL QFM decrease, 95% CI 61-114, P

Objectives Primary objective: To determine the efficacy of a candidate antiviral on time to virological cure compared to standard of care within 14 days of randomisation Secondary objectives: • To determine the safety of the antiviral • To determine the clinical benefit of the antiviral over placebo according to the WHO 7-point ordinal scale • To determine the clinical benefit of the antiviral over placebo on time to resolution of clinical symptoms • To determine the effect of the antiviral over placebo on biomarkers of inflammation and immune activation Trial design This is a multi-centre, triple-blind, randomised placebo controlled phase II, 2-arm trial with parallel-group design with allocation ratio 1:1. Participants Inclusion Criteria: • Provision of informed consent by the participant • Age ≥18 years • Confirmed SARS-CoV-2 by nucleic acid testing in the past 5 days • COVID-19 related symptom initiation within 5 days • Female patients of childbearing potential must have a negative pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 1 week following the last dose of study treatment. Exclusion criteria: • Known allergy to the study medication • Is on another clinical trial investigating an antiviral treatment for COVID-19 • Pregnancy • Patients with severe hepatic dysfunction equivalent to Grade C in the Child-Pugh classification • Patients with renal impairment requiring dialysis • Is deemed by the Investigator to be ineligible for any reason Participants will be recruited from, and the study visits will take place at Alfred Hospital, Monash Health, Austin Health in Victoria, Australia for hospitalised participants as well as recruitment in the community in participants homes for eligible people not requiring hospitalisation. Intervention and comparator The first candidate antiviral is favipiravir Arm 1: Favipiravir 1800 mg favipiravir BD on Day 1 followed by 800 mg BD favipiravir for the next 13 days. Arm 2: Placebo Main outcomes Primary outcome: Time to virological cure as defined by 2 successive throat (or combined nose/throat) swabs negative for SARS-CoV-2 by nucleic acid testing during the 14 days after enrolment. Randomisation Randomisation performed at the Alfred Hospital Clinical Trials Pharmacy using computer generated block-randomisation lists with 6 participants per block. Within each block half of the participants will be randomised to the candidate antiviral and the other half to placebo. Randomisation is stratified by study site, with participants enrolled in the community considered as a study site. Blinding (masking) Study participants, study investigators and the study statistician will be blinded to treatment allocation. Numbers to be randomised (sample size) The study aims to recruit 190 people (95/arm) with the first candidate antiviral favipiravir Trial Status Protocol version 2.0 Dated 31-Jul-2020. Recruitment will take place between July 2020 and December 2020. Trial registration clinicaltrials.gov NCT04445467 First posted 24-Jun-2020 Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Cytomegalovirus (CMV) infection can be a challenging clinical problem in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis. Clinical presentation is difficult to distinguish from an underlying disease flare. A number of diagnostic modalities are now available and when combined can aid clinicians in the identification of patients who are most likely to benefit from antiviral therapy. The aim of this article is to review the available literature and outline a practical approach to the diagnosis and management of CMV in patients with IBD. This article is protected by copyright. All rights reserved.

Uncomplicated urinary tract infection is one of the most common indications for antibiotic use in the community. However, the Gram-negative organisms that can cause the infection are becoming more resistant to antibiotics. Many multidrug resistant organisms retain susceptibility to two old antibiotics, nitrofurantoin and fosfomycin. Advantages over newer drugs include their high urinary concentrations and minimal toxicity. Fosfomycin is a potential treatment option for patients with uncomplicated urinary tract infection due to resistant organisms. Nitrofurantoin may be more effective and can be used for urinary infections in pregnant women.

Extraintestinal infection with Clostridium difficile has been reported but remains uncommon. Treatment of this unusual complication is complex given the limitations of current therapeutic options. Here we report a novel case of recurrent extraintestinal C. difficile infection that occurred following fecal microbiota transplantation. Using whole genome sequencing, we confirmed recrudescence rather than reinfection was responsible. The patient ultimately responded to prolonged, targeted antimicrobial therapy informed by susceptibility testing.

Background Recurrent cytomegalovirus (CMV) disease in solid organ transplant recipients frequently occurs despite effective antiviral therapy. We previously demonstrated that patients with lymphopenia before liver transplantation are more likely to develop posttransplant infectious complications including CMV. The aim of this study was to explore absolute lymphocyte count (ALC) as a predictor of relapse following treatment for CMV disease. Methods We performed a retrospective cohort study of heart, liver, and kidney transplant recipients treated for an episode of CMV disease. Our primary outcome was time to relapse of CMV within 6 months. Data on potential predictors of relapse including ALC were collected at the time of CMV treatment completion. Univariate and multivariate hazard ratios (HRs) were calculated with a Cox model. Multiple imputation was used to complete the data. Results Relapse occurred in 33 of 170 participants (19.4%). Mean ALC in relapse-free patients was 1.08 ± 0.69 vs 0.73 ± 0.42 × 103 cells/μL in those who relapsed, corresponding to an unadjusted hazard ratio of 1.11 (95% confidence interval, 1.03-1.21; P = .009, n = 133) for every decrease of 100 cells/μL. After adjusting for potential confounders, the association between ALC and relapse remained significant (HR, 1.11 [1.03-1.20]; P = .009). Conclusions Low ALC at the time of CMV treatment completion was a strong independent predictor for recurrent CMV disease. This finding is biologically plausible given the known importance of T-cell immunity in maintaining CMV latency. Future studies should consider this inexpensive, readily available marker of host immunity.

New on-demand multiplex molecular respiratory viral diagnostics offer superior performance although can be expensive and some platforms cannot process multiple specimens simultaneously. We performed a retrospective study reviewing results of patients tested for respiratory viruses following introduction of a two-stage testing algorithm incorporating an initial screen with Sofia® immunoassay then secondary Biofire Filmarray®, and compared to a period when only Filmarray® was used. Of 2976 testing episodes, 1814 underwent initial Sofia® then follow-up FilmArray®. A diagnosis of influenza was made by Sofia® in 282 patients, and by FilmArray® in an additional 163 (median time to result 1.12 hours versus 3.46 hours, P

Background Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid organ transplantation (SOT). While recurrent infection occurs in up to 30% of patients, its impact on mortality is unclear. The aim of this study was to explore the relationship between recurrent CMV infection and long-term survival in SOT recipients. Methods We performed a retrospective cohort study of SOT recipients who completed treatment for an episode of CMV infection. Patients were followed until death, loss to follow-up or 10 years following CMV treatment completion. Univariable and multivariable hazard ratios (HR) were calculated, treating relapse and rejection following CMV as time-varying. Results About 79 kidney, 52 heart, 34 liver, and 5 liver-kidney transplant recipients were included. About 62/170 died, at a median of 3.8 years (IQR 0.8-6.6 years). Median follow-up among the 108 survivors was 7.4 years (IQR 3.7-10 years). Recurrent CMV infection occurred in 49/170 (29%), 67% within 6 months of treatment completion. Mortality among those who relapsed was 39% (19/49) vs 36% (43/121) in those who remained relapse-free (unadjusted HR 1.59, 95% CI 0.92-2.75, P = .10). After adjusting for age and transplanted organ, findings were similar (HR 1.68, 95% CI 0.93-3.04, P = .09). Conclusions Mortality following CMV remains high even in the valganciclovir era. Although our findings suggest a possible increased risk of death among patients with recurrent CMV, these did not reach statistical significance. The complex nature of these patients, multiple potential confounders, and limited statistical power made detection of small effects difficult. Larger prospective studies evaluating the clinical impact of strategies to reduce recurrence are needed.

The disease burden, risk factors and clinical sequelae of CMV reactivation in patients with rheumatologic conditions is poorly understood. We have described a cohort with underlying rheumatic disease and CMV, and compared a subgroup with systemic lupus erythematosus (SLE) to controls to identify potential risk factors for CMV reactivation. Adults with rheumatic disease and CMV infection from 2000–2015 were identified. SLE cases were matched 3:1 with controls based on age, sex and year of admission, and compared. Fourteen patients were included (6 SLE, 4 rheumatoid arthritis, 2 sarcoidosis, 1 psoriatic arthritis, 1 microscopic polyangiitis). Seven had viremia alone, the remainder tissue-invasive disease. Thirteen received glucocorticoids prior to CMV reactivation. Fever was the most common symptom, and coinfections were seen in eight including four with bacteremia. Thirteen received antiviral therapy (median 33 days), four died during hospitalization. Six patients with underlying SLE and CMV reactivation were compared to 18 SLE controls. Cases received more glucocorticoids prior to admission (median 36.5 vs. 2.5 mg/day, p = 0.006), had longer hospitalizations (median 47 vs. 7 days, p = 0.006) and more coinfections (67% vs. 17%, p = 0.04). There were no significant differences in symptoms at presentation. CMV reactivation occurs in patients with rheumatologic disease, can result in severe clinical sequelae, and is difficult to distinguish from a flare of the underlying disease. Patients with CMV received higher doses of glucocorticoids and developed more co-infections. CMV should be considered during the evaluation of a febrile illness in this complex patient population.

Avibactam, a novel β-lactamase inhibitor, has recently been co-formulated with ceftazidime and approved for use in patients with complicated intra-abdominal and urinary tract infections, where no better treatment alternative exists. The basis for its FDA approval has been the extensive clinical experience with ceftazidime and the demonstration in vitro and in animal models that the addition of avibactam reverses resistance to ceftazidime in extended-spectrum β-lactamase and some carbapenemase-producing Enterobacteriaceae. Early clinical data are promising, with efficacy demonstrated in patients with complicated intra-abdominal and urinary tract infections. This review will summarize the in vitro, animal and clinical data available on this agent to date.

Broad-range polymerase chain reaction (PCR) is increasingly used in patients with culture-negative infections; however, few studies have assessed the diagnostic utility of this test in this context. We performed a retrospective cohort study of patients who had clinical specimens sent for broad-range PCR, aiming to evaluate performance and determine impact on patient management. Organisms were identified in 21/71 samples. High numbers of polymorphonuclear leukocytes on Gram stain (odds ratio [OR], 4.17; P = .04) and acute inflammation on histopathology (OR, 5.69; P = .02) were significantly associated with a positive result. Management was altered in 18 patients, 11 with positive and 7 with negative results. Overall, broad-range PCR assay had the highest impact in patients with microscopic evidence of inflammation. Physicians ordering this complex, difficult to interpret, and expensive test should carefully consider all available clinical information on an individualized basis to optimize its performance.

Purpose Determining the optimal level of immunosuppression in lung transplant (LT) recipients is challenging. The Quantiferon®-Monitor (QFM) is a novel immune function assay that measures interferon-γ after stimulation with ligands for the innate & adaptive immune system. The aim of this prospective cohort study was to assess the relationships between immunosuppression and QFM results, and the clinical utility of QFM as a predictor of infection/rejection in LT. Methods QFM was tested pre & at 2, 6, 12, 24 & 52 weeks post-LT. Standard immunosuppression included tacrolimus , azathioprine , prednisone & basiliximab in patients with limited renal reserve. Patients were assessed over 1yr for rejection & infection. Results 80 LT patients were recruited from 2015-17 (median age 61, 60% male, 86% bilateral LT and 50% received basiliximab). Pre-transplant QFM results were lower in patients receiving glucocorticoids (median 67 IU/mL, IQR 9-244 vs. 314, 67-499, p=0.01) and those testing cytomegalovirus (CMV) seronegative (71, 5-262 vs. 230, 58-499, p=0.01). QFM values decreased significantly post-transplant then progressively increased (Figure). Trough tacrolimus levels & prednisone doses were associated with post-transplant QFM levels (p viremia occurred in 44% (>1000 copies/mL in 15%), respiratory viral infections in 40% & positive BAL bacterial cultures in 64%. 9 patients (11%) experienced rejection, 4 within 30 days post-transplant. 76% were readmitted & 5 died within 1 yr. QFM results at 2 & 6 weeks were not associated with any of these outcomes. Conclusion Our study demonstrated an association between tacrolimus levels, prednisolone dose & QFM results but was underpowered to detect differences in clinical outcomes. CMV serostatus appeared to have an impact on QFM results both pre- & post-transplant.

Background Cytomegalovirus (CMV) is a major contributor to morbidity and mortality in solid organ transplant recipients (SOTRs). Ganciclovir and valganciclovir are highly effective antiviral drugs with a well-established role in primary prophylaxis and treatment of CMV disease. Our objective in this study was to examine the effect of secondary prophylaxis (SP) on the risk of relapse in SOTRs following an episode of CMV disease. Methods We performed a retrospective cohort study of SOTRs from 1995 to 2015 and used propensity score-based inverse probability of treatment weighting methodology to control for confounding by indication. A weighted Cox model was created to determine the effect of SP on time to relapse within 1 year of treatment completion. Results Fifty-two heart, 34 liver, 79 kidney, and 5 liver-kidney transplant recipients who completed treatment for an episode of CMV infection/disease were included. A total of 120 (70.6%) received SP (median duration, 61 days; range, 5-365) and 39 (23%) relapsed. SP was protective against relapse from 0 to 6 weeks following treatment completion (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.05-0.69). However, after 6 weeks, risk of relapse did not significantly differ between the 2 groups (HR, 1.18; 95% CI, 0.46-2.99). Conclusions Our findings demonstrate that use of SP following treatment of CMV disease did not confer long-term protection against relapse, although it did delay relapse while patients were receiving antivirals. This suggests that SP has limited clinical utility in the overall prevention of recurrent CMV disease.

Background Cytomegalovirus (CMV) remains a significant contributor to morbidity and mortality following solid-organ transplantation (SOT). While relapse after treatment completion can occur in up to 30% of patients, the effect of this on mortality is not clear. The aim of this study was to explore the impact of recurrent CMV disease on long-term survival in SOT recipients. Methods We performed a retrospective cohort study of heart, liver and kidney transplant recipients who completed treatment for an episode of CMV disease. Data on potential confounders were collected from the time of CMV treatment completion. Censoring occurred at the time of death, loss to follow-up or 10 years. Univariable and multivariable hazard ratios (HR) were calculated using a Cox model, treating relapse and rejection following CMV as time-varying covariates. Results Seventy-nine kidney, 52 heart, 34 liver and five liver-kidney transplant recipients were included. Sixty-two of 170 died, at a median of 3.8 years (interquartile range [IQR] 0.8–6.6 years). Median follow-up amongst the 108 survivors was 7.4 years (IQR 3.7–10 years) although 22 (13%) were censored before 3 years. CMV relapse occurred in 49/170 (29%), 67% within 6 months of treatment completion. Overall mortality amongst those who relapsed was 39% (19/49) vs. 36% (43/121) in those who remained relapse free. On univariable analysis, CMV relapse was not associated with a significantly increased risk of death (unadjusted HR 1.59, 95% CI 0.92–2.75, P = 0.10). After controlling for age and transplanted organ type, findings were similar (adjusted HR 1.68, 95% CI 0.93–3.04, P = 0.09). Conclusion Mortality rates following CMV remain high even in the valganciclovir era. In our study, we did not identify a significant relationship between the development of recurrent CMV disease and death. However, the complex nature of these patients, multiple layers of potential confounding and limited statistical power of our cohort make detection of small effects difficult. Future prospective studies evaluating the clinical efficacy of strategies to reduce recurrence are needed to further assess this relationship. Disclosures D. Snydman, Merck: Board Member, Consulting fee and Grant recipient; Shire: Board Member, Consulting fee; Takeda: Board Member, Consulting fee; Chimerix: Board Member, Consulting fee; Seres Therapeutics: Grant Investigator, Grant recipient; Actelion: Grant Investigator, Grant recipient; Moderna: Board Member, Consulting fee; Summit: Grant Investigator, Grant recipient; Tetraphase: Grant Investigator, Grant recipient.

Our data demonstrate that symptomatic respiratory virus infection is strongly associated with development of chronic lung allograft dysfunction. With multiple new respiratory antivirals currently in clinical trial, this association offers a potentially intervenable risk factor for a highly morbid process.

Infective endocarditis due to Candida sp. has a high mortality rate. Traditionally, management involves early surgery and prolonged amphotericin ± flucytosine. We report a case of Candida parapsilosis bileaflet mitral valve endocarditis cured with anidulafungin and fluconazole, and review the role of echinocandins in the management of Candida endocarditis.

Eggerthella lenta bacteremia is uncommon and generally associated with abdominal sepsis. The organism and its clinical significance have not been well characterized due to historical difficulties with identification. We report a case of severe infection in a paraplegic man complicated by psoas abscess, osteomyelitis, and meningitis and discuss treatment challenges.

Background Reactivation of latent cytomegalovirus infection can occur in nonimmunocompromised individuals during critical illness and may be associated with increased morbidity and mortality. However, few studies have focused on patients undergoing major surgery. Our aim was to explore risk factors for and outcomes following CMV reactivation in nonimmunocompromised post-operative patients. Methods We performed a retrospective case–control study of nonimmunocompromised patients with CMV reactivation following major surgery from 2004 to 2016. Cases included patients testing positive for CMV by viral load, viral culture or histopathology. Controls were matched to cases 2:1 by age, sex, type and year of surgery. Groups were compared using conditional logistic regression. Results 16 patients with CMV were matched to 32 controls. Median age was 65 (range 34–84) and 50% were male. The most common surgeries were abdominal (44%) and cardiac (25%). Median time from surgery to CMV diagnosis was 32 days (range 17–93). Patients had a range of clinical symptoms including fever (94%), hepatitis (75%), bone marrow suppression (56%) and gastrointestinal symptoms (56%). All except one were treated with antiviral therapy. Despite having similar baseline Charlson comorbidity scores, cases were more likely to return to surgery within 3 months (odds ratio, OR 6.31; 95% CI, 1.29–30.74), require renal replacement therapy (OR 18.54, 2.36–145.6), total parenteral nutrition (OR 33.0, 6.60–262.37) and corticosteroids (OR 18.78, 4.5–103.9). Length of stay was increased (median 51 vs. 8 days, P = 0.005), coinfections were more common (OR 15.10, 1.89–120.8), and in-hospital mortality was significantly higher (38% vs. 0%, P < 0.01). Conclusion Reactivation of CMV occurs in nonimmunocompromised patients post-operatively and is associated with poor outcomes including other infections and mortality. Potential risk factors include prolonged length of stay, development of surgical complications, and prolonged use of corticosteroids. It is not clear from our study if CMV reactivation is a surrogate marker of severe illness and postoperative complications, or if CMV reactivation plays a causative role in the development of these adverse outcomes. Disclosures D. Snydman, Merck: Board Member, Consulting fee and Grant recipient. Shire: Board Member, Consulting fee. Takeda: Board Member, Consulting fee. Chimerix: Board Member, Consulting fee. Seres Therapeutics: Grant Investigator, Grant recipient. Actelion: Grant Investigator, Grant recipient. Moderna: Board Member, Consulting fee. Summit: Grant Investigator, Grant recipient. Tetraphase: Grant Investigator, Grant recipient.

Background While there are emerging reports of cytomegalovirus (CMV) disease in patients with underlying rheumatic conditions, the disease burden, risk factors and clinical sequelae in this population are poorly understood. We sought to describe a cohort of patients with underlying rheumatic disease and CMV infection, then compare those with systemic lupus erythematosus (SLE), the largest subgroup, using case–control methodology to identify risk factors for reactivation and differences in outcomes. Methods Adults with rheumatic disease and CMV reactivation diagnosed by viral load, viral culture or histopathology from Tufts Medical Center between 2000 and 2015 were identified. Due to SLE cases comprising 43% of the total, these patients were matched 3:1 with SLE controls based on age, sex and year of admission. Results Fourteen patients with rheumatic disease and CMV were included (six SLE, four rheumatoid arthritis, two sarcoid, one psoriatic arthritis, one microscopic polyangiitis). Seven patients had viremia alone and the remainder had tissue-invasive disease (four gastrointestinal, three pulmonary). Thirteen (93%) received corticosteroids within 3 months prior to CMV reactivation. Fever (86%) was the most common symptom. Coinfections were seen in eight (57%), including four with bacteremia. Thirteen (93%) were treated with antiviral therapy for a median of 33 days (range 13–171). Relapse occurred in three patients and four died during hospitalization. Six patients with underlying SLE and CMV reactivation were compared with 18 controls. Cases received significantly more corticosteroids during the 8-week period prior to admission (median 36.5 vs. 2.5 mg/day, P = 0.006), had longer hospitalizations (median 46.5 vs. 6.5 days, P = 0.006) and more frequent co-infections (67% vs. 17%, P = 0.04). There were no significant differences in symptoms at presentation. Conclusion CMV reactivation occurs in patients with rheumatic disease, and can result in severe clinical sequelae that may be difficult to distinguish from a flare of the underlying disease. Patients with CMV were more likely to have received high doses of corticosteroids, and developed more co-infections during their hospitalization. Clinicians should consider this diagnosis during the evaluation of a febrile illness in the rheumatologic population. Disclosures D. Snydman, Merck: Board Member, Consulting fee and Grant recipient; Shire: Board Member, Consulting fee; Takeda: Board Member, Consulting fee; Chimerix: Board Member, Consulting fee; Seres Therapeutics: Grant Investigator, Grant recipient; Actelion: Grant Investigator, Grant recipient; Moderna: Board Member, Consulting fee; Summit: Grant Investigator, Grant recipient; Tetraphase: Grant Investigator, Grant recipient.

Objectives As the optimal administration time for fosfomycin peri-procedural prophylaxis is unclear, we sought to determine optimal administration times for fosfomycin peri-procedural prophylaxis. Methods Plasma, peripheral zone and transition zone fosfomycin concentrations were obtained from 26 subjects undergoing transurethral resection of the prostate (TURP), following a single oral dose of 3 g of fosfomycin. Population pharmacokinetic modelling was completed with the Nonparametric Adaptive Grid (NPAG) algorithm (Pmetrics package for R), with a four-compartment model. Plasma and tissue concentrations were simulated during the first 24 h post-dose, comparing these with EUCAST susceptibility breakpoints for Escherichia coli, a common uropathogen. Results Non-compartmental-determined pharmacokinetic values in our population were similar to those reported in the package insert. Predicted plasma concentrations rapidly increased after the first hour, giving more than 90% population coverage for organisms with an MIC ≤4 mg/L over the first 12 h post-dose. Organisms with higher MICs fared much worse, with organisms at the EUCAST breakpoint being covered for Conclusions Until more precise plasma and tissue data are available, we recommend that fosfomycin prophylaxis be given 1–4 h prior to prostate biopsy. We do not recommend fosfomycin prophylaxis for subjects with known organisms with MICs >4 mg/L.

Eggerthella lenta is an emerging pathogen that has been underrecognized due to historical difficulties with phenotypic identification. Until now, its pathogenicity, antimicrobial susceptibility profile, and optimal treatment have been poorly characterized. In this article, we report the largest cohort of patients with E. lenta bacteremia to date and describe in detail their clinical features, microbiologic characteristics, treatment, and outcomes. We identified 33 patients; the median age was 68 years, and there was no gender predominance. Twenty-seven patients (82%) had serious intra-abdominal pathology, often requiring a medical procedure. Of those who received antibiotics (28/33, 85%), the median duration of treatment was 21.5 days. Mortality from all causes was 6% at 7 days, 12% at 30 days, and 33% at 1 year. Of 26 isolates available for further testing, all were identified as E. lenta by both commercially available matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) systems, and none were found to harbor a vanA or vanB gene. Of 23 isolates which underwent susceptibility testing, all were susceptible to amoxicillin-clavulanate, cefoxitin, metronidazole, piperacillin-tazobactam, ertapenem, and meropenem, 91% were susceptible to clindamycin, 74% were susceptible to moxifloxacin, and 39% were susceptible to penicillin.

Historically, Streptococcus pyogenes was a common cause of endocarditis and infected aortic aneurysm. Today, endovascular infections due to this organism have become exceedingly rare. We report the first case of aortic aneurysm infection due to S. pyogenes treated with initial endoluminal repair, review previous reports and discuss current treatment options.

Background. Multidrug-resistant gram-negative bacterial (MDR-GNB) infections of the prostate are an increasing problem worldwide, particularly complicating transrectal ultrasound (TRUS)–guided prostate biopsy. Fluoroquinolonebased regimens, once the mainstay of many protocols, are increasingly ineffective. Fosfomycin has reasonable in vitro and urinary activity (minimum inhibitory concentration breakpoint ≤64 µg/mL) against MDR-GNB, but its prostatic penetration has been uncertain, so it has not been widely recommended for the prophylaxis or treatment of MDR-GNB prostatitis. Methods. In a prospective study of healthy men undergoing a transurethral resection of the prostate for benign prostatic hyperplasia, we assessed serum, urine, and prostatic tissue (transition zone [TZ] and peripheral zone [PZ]) fosfomycin concentrations using liquid chromatography–tandem mass spectrometry, following a single 3-g oral fosfomycin dose within 17 hours of surgery. Results. Among the 26 participants, mean plasma and urinary fosfomycin levels were 11.4 ± 7.6 µg/mL and 571 ± 418 µg/mL, 565 ± 149 minutes and 581 ± 150 minutes postdose, respectively. Mean overall prostate fosfomycin levels were 6.5 ± 4.9 µg/g (range, 0.7–22.1 µg/g), with therapeutic concentrations detectable up to 17 hours following the dose. The mean prostate to plasma ratio was 0.67 ± 0.57. Mean concentrations within the TZ vs PZ prostate regions varied significantly (TZ, 8.3 ± 6.6 vs PZ, 4.4 ± 4.1 µg/g; P= .001). Only 1 patient had a mean prostatic fosfomycin concentration of

Background Bloodstream infections are a major cause of morbidity and mortality worldwide, with favorable clinical outcomes associated with early optimal antibiotic selection. Rapid diagnostics have become a key part in achieving this. Biofire Filmarray® was introduced at our institution for rapid blood culture (BC) identification, coupled with antimicrobial stewardship (AS) interventions. We aimed to assess the impact of this test on time to adequate antimicrobial therapy in a setting with pre-existing effective AS interventions. Methods An observational retrospective chart review, pre and post study was performed. We reviewed adult positive BC before and after implementation of Biofire. Outcomes were: (1) time from BC result reported to health care provider to start of adequate antimicrobial therapy,(2) time to stopping antimicrobial therapy in BC thought to be contaminants, (3) time to any change in antimicrobial therapy and (4) a composite outcome of outcomes 1 and 2. A univariate Cox proportional hazards model was performed. Results 326 positive BC were analyzed, 173 before and 153 after Biofire implementation. At the time of healthcare provider notification, 77 were not on adequate antimicrobials, with median time to adequate therapy of 6.98 hours. (IQR 3.93–23.96) before and 6.1 hours. (IQR 1.84–20.95) after implementation, P = 0.48. There were 75 BC classified as contaminants and median time to stopping antimicrobials was 48.28 (IQR 18.56–89.36) vs. 45.25 hours. (IQR 15.12–100.60), P = 0.61. Time to any change in any antimicrobial therapy was similar with a median of 13.05 (IQR 4.00–36.77) vs. 10.90 hours. (IQR 2.97–31.10), P = 0.87. Analysis of the composite outcome revealed a median of 23.95 (6.29–58.50) vs. 14.82 (IQR 4.07–44.79) hours. (Hazard ratio 1.33, 95% confidence interval 0.96–1.84, P = 0.09). Conclusion Implementation of the Biofire Filmarray® did not have a statistically significant effect on our composite outcome of time to adequate therapy and time to discontinuation in the case of contaminants. Our findings suggests that when added to other effective AS surveillance and interventions, the magnitude of the clinical impact of rapid PCR diagnostics for BC identification is minimal. Disclosures D. R. Snydman, Merck: Scientific Advisor, Consulting fee; Shire: Scientific Advisor, Consulting fee

Background Over the past decade, detection of bacterial and fungal DNA by universal polymerase chain reaction (PCR) has been increasingly used for organism identification in culture negative tissue samples. Few studies have assessed the diagnostic utility of this test in real-world clinical practice. The aim of this study was to assess the clinical performance of this test by examining available clinical information, test results and the impact on patient management. Methods We performed a single-center retrospective cohort study of patients who had clinical specimens sent for universal PCR from August 2013 to April 2016. Clinical data were extracted from medical records. Odds ratios were calculated and patients testing positive/negative were compared with univariate logistic regression. Sensitivity, specificity, positive predictive value and negative predictive values were calculated by comparing the test result with a gold standard composite final clinical diagnosis determined by 3 independent reviewers based on all available clinical information. Results 71 tissue samples were included, of which 21(29.6%) were positive. 12 bacteria, 3 mycobacteria and 7 fungi were identified. The number of leukocytes in the gram stain (odds ratio, OR 1.57, P = 0.04) and presence of inflammation on histopathological examination (OR 5.69, P = 0.02) were found to be significantly associated with a positive result. The sensitivity, specificity, positive predictive value, and negative predictive values were 56%, 95%, 91% and 70% respectively. Management was altered in 22 patients, 9 of whom had a positive and 13 had a negative result. Conclusion These findings suggest that the universal PCR assay has significant clinical utility, but the yield of this test can be optimized by careful patient/specimen selection. Utility was highest in patients with microscopic evidence of inflammation by gram stain or histopathlogical examination. Specificity was high. The use of this complex, difficult to interpret, and expensive test should be limited to infectious disease physicians incorporating all available clinical information to optimize performance. Disclosures All authors: No reported disclosures.

Background Cytomegalovirus (CMV) is a major contributor to morbidity and mortality in solid organ transplant recipients (SOTRs). Ganciclovir and valganciclovir are highly effective antiviral drugs with a well-established role in primary prophylaxis and treatment of CMV disease. Our objective in this study was to examine the effect of secondary prophylaxis (SP) on the risk of relapse in SOTRs following an episode of CMV disease. Methods We performed a retrospective cohort study of SOTRs from 1995 to 2015 and used propensity score-based inverse probability of treatment weighting methodology to control for confounding by indication. A weighted Cox model was created to determine the effect of SP on time to relapse within 1 year of treatment completion. Results Fifty-two heart, 34 liver, 79 kidney, and 5 liver-kidney transplant recipients who completed treatment for an episode of CMV infection/disease were included. A total of 120 (70.6%) received SP (median duration, 61 days; range, 5-365) and 39 (23%) relapsed. SP was protective against relapse from 0 to 6 weeks following treatment completion (hazard ratio [HR], 0.19; 95% confidence interval [CI], 0.05-0.69). However, after 6 weeks, risk of relapse did not significantly differ between the 2 groups (HR, 1.18; 95% CI, 0.46-2.99). Conclusions Our findings demonstrate that use of SP following treatment of CMV disease did not confer long-term protection against relapse, although it did delay relapse while patients were receiving antivirals. This suggests that SP has limited clinical utility in the overall prevention of recurrent CMV disease.

We describe a case of faecal microbiota transplantation (FMT) used for severe binary toxin-positive Clostridium difficile infection in an intensive care setting. The patient was admitted to the ICU of a tertiary hospital and failed traditional maximal pharmacological management. Adjunctive therapy with FMT given through gastroscopy resulted in resolution of the C. difficile-related symptoms. Although there is a growing experience with FMT for recurrent C. difficile infection, published evidence in severe disease is very limited. In a landscape of increasingly severe C. difficile infection, adjunctive FMT may be considered a useful early treatment option.