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Background In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL). Objective To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection Methods COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment. Results Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37–10.63), vitality (MTD, 6.81; 95% CI, 1.88–11.75), and mental health (MTD, 5.17; 95% CI, 0.52–9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29–5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12. Conclusion HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL.

Hepatitis C virus (HCV) reinfection after successful treatment may reduce the benefits of cure among people who inject drugs.To evaluate the rate of HCV reinfection for 3 years after successful treatment among people receiving opioid agonist therapy (OAT).A 3-year, long-term, extension study of persons enrolled in the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) study (ClinicalTrials.gov: NCT02105688).55 clinical trial sites in 13 countries.Aged 18 years and older with chronic HCV infection with genotypes 1, 4, or 6 receiving stable OAT.No treatments were administered.Serum samples were assessed for HCV reinfection. Urine drug screening was performed.Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. The rate of HCV reinfection was 1.7 [95% CI, 0.8 to 3.0] per 100 person-years; 604 person-years of follow-up). A higher rate of reinfection was seen among people with recent injecting drug use (1.9 [95% CI, 0.5 to 4.8] per 100 person-years; 212 person-years). Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up.Participants were required to be 80% adherent to OAT at baseline and may represent a population with higher stability and lower risk for HCV reinfection. Rate of reinfection may be underestimated because all participants did not continue in the long-term extension study; whether participants who discontinued were at higher risk for reinfection is unknown.Reinfection with HCV was low but was highest in the first 24 weeks after treatment completion and among people with ongoing injecting drug use and needle-syringe sharing.Merck SharpDohme Corp., a subsidiary of MerckCo., Inc.

Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or intramuscular vaccine injection. In a non-randomized observational study, we measured antibodies against the SARS-CoV-2 RBD in plasma and saliva from convalescent or vaccinated individuals and tested their neutralizing potential using a replication competent rVSV-eGFP-SARS-CoV-2. We found IgG and IgA anti-RBD antibodies as well as neutralizing activity in convalescent plasma and saliva. Two doses of mRNA vaccination (BNT162b2 or mRNA-1273) induced high levels of IgG anti-RBD in saliva, a subset of whom also had IgA, and significant neutralizing activity. We detected anti-RBD IgG and IgA with significant neutralizing potential in the plasma of single dose Ad26.COV2.S vaccinated individuals, and we detected slight amounts of anti-RBD antibodies in matched saliva. The role of salivary antibodies in protection against SARS-CoV-2 infection is unknown and merits further investigation. This study was not designed to, nor did it study the full kinetics of the antibody response or protection from infection, nor did it address variants of SARS-CoV-2.

Objectives: Levofloxacin and amiodarone are both known to prolong the QT interval. This study was conducted to estimate the risk of cardiac events in patients receiving concomitant levofloxacin and amiodarone. Methods: The study included patients who were admitted to a large academic community medical center from 1/2012 to 12/2015 and received both levofloxacin and amiodarone at some point during their hospitalization. Patients received concomitant or non-concomitant levofloxacin and amiodarone during hospitalization. The primary outcome was the occurrence of cardiac events during therapy. The secondary outcome was the proportion of patients with an electrocardiogram performed before and after initiation of therapy. Odds ratios for cardiac events were calculated using a multivariable logistic regression model with and without adjusting for the study variables. The concomitant group was further evaluated for predictors of the primary outcome using multivariable logistic regression. Results: This study included 240 patients, 164 (68.3%) of whom received concomitant levofloxacin and amiodarone. Concomitant medication therapy was associated with a greater than six-fold increased risk of cardiac events after adjusting for the study variables (Odds Ratio = 6.20; 95% Confidence Interval = 1.34–28.62). Conclusions: Patients receiving concomitant amiodarone and levofloxacin experienced a five-fold increase in cardiac events compared to patients given either medication alone. Keywords: Levofloxacin, Amiodarone, Cardiac risk, Cardiac death, QT interval

Background Coronavirus disease 2019 (COVID-19) has become a global pandemic. Clinical characteristics regarding secondary infections in patients with COVID-19 have been reported, but detailed microbiology, risk factors, and outcomes of secondary bloodstream infections (sBSIs) in patients with severe COVID-19 have not been well described. Methods We performed a multicenter case-control study including all hospitalized patients diagnosed with severe COVID-19 and blood cultures drawn from 1 March 2020 to 7 May 2020 at 3 academic medical centers in New Jersey. Data collection included demographics, clinical and microbiologic variables, and patient outcomes. Risk factors and outcomes were compared between cases (sBSI) and controls (no sBSI). Results A total of 375 hospitalized patients were included. There were 128 sBSIs during the hospitalization. For the first set of positive blood cultures, 117 (91.4%) were bacterial and 7 (5.5%) were fungal. Those with sBSI were more likely to have altered mental status, lower mean percentage oxygen saturation on room air, have septic shock, and be admitted to the intensive care unit compared with controls. In-hospital mortality was higher in those with an sBSI versus controls (53.1% vs 32.8%, P = .0001). Conclusions We observed that hospitalized adult patients with severe COVID-19 and sBSI had a more severe initial presentation, prolonged hospital course, and worse clinical outcomes. To maintain antimicrobial stewardship principles, further prospective studies are necessary to better characterize risk factors and prediction modeling to better understand when to suspect and empirically treat for sBSIs in severe COVID-19.

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused significant health and economic havoc around the globe. One of the early agents targeted for repurposing to treat and prevent COVID-19 was hydroxychloroquine (HCQ). In this systematic review and meta-analysis, HCQ is evaluated for its potential role in decreasing mortality in hospitalized patients with COVID-19. We searched PubMed, Web of Science, and medRxiv databases using combinations of the terms “COVID-19”, “SARS-CoV-2”, “coronavirus”, “hydroxychloroquine”, and “mortality”. Articles were selected for further review based on the content of their abstracts. Studies were excluded if they were of poor methodological quality, were not based in the inpatient setting, or did not have available data to assess the primary outcome of death between patients treated with HCQ versus standard of care. Once the final dataset was compiled, a meta-analysis using the random-effects model was performed. Our search identified 14 studies involving 24780 patients of whom 12707 patients were on HCQ alone or in combination with other adjuvant therapies. HCQ alone or in combination with other drugs did not significantly decrease mortality in hospitalized patients with COVID-19 (odds ratio [OR], 0.95; 95% CI, 0.72–1.26; p = 0.732; I2 = 91.05). Similar findings were observed in all subgroup analyses. HCQ did not significantly impact mortality in hospitalized patients with COVID-19. Additional well-designed studies are essential due to the heterogeneity in available studies.

PurposeThe novel coronavirus disease 2019 (COVID-19) worldwide pandemic has placed a significant burden on hospitals and healthcare providers. The immune response to this disease is thought to lead to a cytokine storm, which contributes to the severity of illness. There is an urgent need to confirm whether the use of tocilizumab provides a benefit in individuals with COVID-19.MethodsA single-center propensity-score matched cohort study, including all consecutive COVID-19 patients, admitted to the medical center who were either discharged from the medical center or expired between March 1, 2020, and May 5, 2020, was performed. Patients were stratified according to the receipt of tocilizumab for cytokine storm and matched to controls using propensity scores. The primary outcome was in-hospital mortality.ResultsA total of 132 patients were included in the matched dataset (tocilizumab=66; no tocilizumab=66). Approximately 73% of the patients were male. Hypertension (55%), diabetes mellitus (31%), and chronic pulmonary disease (15%) were the most common comorbidities present. There were 18 deaths (27.3%) in the tocilizumab group and 18 deaths (27.3%) in the no tocilizumab group (odds ratio, 1.0; 95% confidence interval, 0.465 – 2.151; p=1.00). Advanced age, history of myocardial infarction, dementia, chronic pulmonary disease, heart failure, and malignancy were significantly more common in patients who died.ConclusionThe current analysis does not support the use of tocilizumab for the management of cytokine storm in patients with COVID-19. Use of this therapeutic agent should be limited to the context of a clinical trial until more evidence is available.

Background Studies have had conflicting results regarding the influence of acid-suppression medications (ASMs) during hospitalization on the recurrence of Clostridioides difficile infection (CDI). Methods A systematic review and meta-analysis investigating the association between recurrent CDI and ASM use in inpatients was performed. Relevant literature was identified using Medline, Google Scholar, and Web of Science. All human studies were considered regardless of publication date. Case-control and cohort studies and clinical trials were included if they contained the necessary information to calculate appropriate statistics related to the objective of this study. Review articles, meta-analyses, and commentaries were excluded; however, their references were searched to identify any studies missed. The random-effects model was selected since significant heterogeneity in study design was identified. To evaluate the sensitivity of the analysis various subgroup analyses were performed. Results Our search identified 9 studies involving 5668 patients of whom 1003 (17.7%) developed recurrent CDI. Patients on ASM were 64% more likely to develop recurrent CDI than patients not on ASM (OR, 1.64; 95% CI, 1.13–2.38; P = .009; I2 = 79.54%). Proton pump inhibitor (PPI) use was associated with an 84% increased risk of recurrent CDI versus no ASM (OR, 1.84; 95% CI, 1.18–2.85; P = .007; I2 = 83.4%). Conclusions ASM use during hospitalization was associated with a 64% increase in recurrent CDI. The association was greater with PPI use. Due to significant heterogeneity in the analyses, additional studies are essential to further elucidate iatrogenic effects of ASM. Unnecessary PPI use should be discontinued.

The shift from volume-based to value-based reimbursement has created a need for quantifying clinical performance of infectious diseases (ID) physicians. Nationally recognized ID specialty-specific quality measures will allow stakeholders, such as patients and payers, to determine the value of care provided by ID physicians and will promote clinical quality improvement. Few ID-specific measures have been developed; herein, we provide an overview of the importance of quality measurement for ID, discuss issues in quality measurement specific to ID, and describe standards by which candidate quality measures can be evaluated. If ID specialists recognize the need for quality measurement, then ID specialists can direct ID-related quality improvement, quantify the impact of ID physicians on patient outcomes, compare their performance to that of peers, and convey to stakeholders the value of the specialty.

S282T in NS5B is the primary amino acid substitution associated with resistance to sofosbuvir (SOF) but has rarely been detected in patients treated with a SOF-based regimen. Here, the emergence and fitness of the S282T substitution in virologic failure patients administered SOF-based regimens across the SOF and ledipasvir (LDV)/SOF phase 2 and 3 programs was evaluated. Plasma samples collected at baseline and at virologic failure were amplified and deep sequenced (1% cutoff). To date, over 12,000 patients have been treated in SOF or LDV/SOF phase 2 and 3 studies. Of these, deep sequencing was available at baseline in 8598 patients (62.4% genotype [GT] 1, 10.7% GT2, 20.9% GT3, and 6.0% GT4-6) and at virologic failure in 901 patients. In the 8598 patients, no S282T substitution was detected at baseline; at virologic failure, 10 of the 901 (1%) patients had S282T detected. The SOF-based regimen associated with treatment-emergent S282T was SOF monotherapy in two patients, retreatment with LDV/SOF in prior LDV/SOF failures in three patients, LDV/SOF for 8 weeks in 1 GT1 patient, LDV/SOF for 12 weeks in 1 patient each with GT3, GT4, and GT5, and LDV/SOF + ribavirin for 12 weeks in 1 GT6 patient. Nine of 10 patients with emergent S282T received an SOF-based retreatment regimen, eight of whom achieved sustained virologic response 12 weeks after treatment and one of whom failed retreatment. Conclusion: The emergence of S282T substitution was rare in patients who fail SOF-based regimens. Successful retreatment of prior SOF failure patients is possible in the presence of S282T substitution with SOF in combination with various direct-acting antiviral agents. (Hepatology Communications 2017;1:538-549).

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL

Fever of unknown origin (FUO) continues to present a clinical conundrum for even expert practitioners. The syndrome of FUO has over 200 possible etiologies. Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with only 1,200 US adult cases reported annually. Fever, night sweats, and weight loss, otherwise known as B symptoms, are common early symptoms of BL. Nerve palsy, especially isolated hypoglossal nerve palsy (IHNP), is rarely seen as a presenting sign in any pathological condition. A case report of FUO and IHNP as the presenting manifestations of BL is presented. The rarity of IHNP and its clinical features delayed the recognition of this syndrome and emphasizes the value of a thorough understanding of the physical examination and the association of unusual clinical findings with a readily identifiable clinical syndrome.

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

Background: In elderly individuals aged ≥65 years with hepatitis C virus (HCV) infection, efficacious and safe HCV therapy is complicated by frequent comorbidities and concomitant medications. The aim of this analysis was to evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in people aged ≥65 years. Methods: This is an integrated retrospective analysis of EBR/GZR administered for 12 weeks in participants with HCV genotype 1 or 4 infection enrolled in 12 Phase 2/3 clinical trials. The primary end point was sustained virologic response 12 weeks after completing therapy (SVR12; HCV RNA below the lower limit of quantification). Results: Most participants aged ≥65 years were receiving ≥1 concomitant medication (322/339; 95.0%) and had ≥1 comorbidity (334/339; 99%). SVR12 rates were 95.3% (323/339) in participants aged ≥65 years and 95.4% (2,041/2,139) in those aged

Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naive and prior null-responder HCV genotype (GT) 1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12 or 24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naive and treatment-experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence or absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily+sofosbuvir 400 mg once daily for 12 or 8 weeks. The primary efficacy endpoint was SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. Enrolled were 310 patients, who were randomized and received treatment (n = 155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% confidence interval 94%-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% confidence interval 76-89%]) was not superior to the historical control (83%). The most frequent adverse events were nausea, headache, and fatigue (12-week arm: 15% [23/155], 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an adverse event. One (1%, 12-week arm) and three (2%, 8-week arm) patients experienced a serious adverse event (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected patients without cirrhosis, including those with Q80K. (Hepatology 2016;64:370-380)

The repurposing of colchicine for the treatment of COVID-19 was suggested based in its immunomodulatory, anti-inflammatory, and anti-viral properties. We performed a single-center propensity score matched cohort study, including all consecutive COVID-19 patients admitted to a community hospital between 1 March 2020 and 30 May 2020. Patients were stratified according to the receipt of colchicine. The primary endpoint was defined as in-hospital death within 28-days follow-up. Secondary endpoints included favorable change in the Ordinal Scale for Clinical Improvement on days 14 and 28 versus baseline, proportion of patients not requiring supplemental oxygen on days 14 and 28, and proportion of patients discharged by day 28. In total data for 303 PCR positive COVID-19 patients were extracted and 66 patients were included in the 1:1 matched cohort study. At the end of the 28 day follow-up, patients receiving colchicine were approximately five times more likely to be discharged (odds ratio, 5.0, 95% confidence interval, 1.25&ndash, 20.1, p = 0.023) and when comparing mortality, there were 3 deaths (9.1%) in patients receiving colchicine versus 11 deaths (33.3%) in the groups receiving standard of care (odds ratio, 0.20, 95% confidence interval, 0.05&ndash, 0.80, p = 0.023). These observations warrant further investigation in large controlled clinical trials.

Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance’s scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society’s governing board.

BACKGROUND: The fixed-dose combination of EBR 50 mg, an NS5A inhibitor, and GZR 100 mg, an NS3/4 protease inhibitor (EBR/GZR), is a highly effective and well-tolerated all-oral, once-daily regimen in diverse populations of hepatitis C virus (HCV) genotype (GT)1-, 4-, or 6-infected patients, including PWID on OAT. However, data on HCV reinfection rates after successful treatment are limited. AIMS: To determing the rate of reinfections following sucessful HCV therapy with EBR and GZR in PWID receiving OAT METHODS: The double-blind, placebo-controlled CO-STAR study evaluated the efficacy of EBR/GZR for 12 weeks in treatment-naïve HCV GT1-/4-/6-infected patients receiving OAT. Patients were randomized 2:1 to an immediate treatment group (ITG) or a deferred treatment group. HCV reinfection was evaluated among ITG patients with undetectable HCV RNA at end of treatment (EOT). In patients with recurrent viremia following EOT, population sequencing and phylogenetic analysis were performed on baseline and post-treatment samples to distinguish relapse from reinfection. RESULTS: Three hundred one patients were randomized, with 201 in the ITG (76% GT1a; 20% cirrhotic; 8% HIV+). Baseline OAT included methadone (81%) and buprenorphine (19%), and 46% had detectable illicit drugs, excluding marijuana. Post-treatment viremia was detected in 18 patients, with 12 virologic failures and 6 probable reinfections (5 through follow-up week (FW)12 and 1 at FW24). Three patients identified as reinfections had subsequent clearance of HCV RNA. Estimated reinfection incidence per 100 person-years from EOT through FW12 is 10.5 (95% CI: 3.42, 24.6), and from EOT through FW24 is 3.4 (95% CI: 1.3,7.5). Follow-up analysis to determine if any probable reinfections were due to relapse of nondominant baseline variants rather than reinfection will be presented. CONCLUSIONS: Several HCV reinfection cases were detected among PWID on OAT following successful EBR/GZR therapy. Further follow-up is required to determine the natural course of HCV reinfection in the setting of interferon-free HCV treatment and the impact of viral persistence following reinfection on long-term response rates in this population. FUNDING AGENCIES: Merck Pharmaceuticals

Background Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. Objective To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. Design Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). Setting 48 U.S. sites. Patients 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. Measurements Sustained virologic response at 12 weeks (SVR12). Results In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with velpatasvir, 25 mg; 83% (25 of 30) with velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with velpatasvir, 100 mg; and 81% (25 of 31) with velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with velpatasvir, 25 mg; 88% (22 of 25) with velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with velpatasvir, 100 mg; and 88% (23 of 26) with velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. Limitation The study was open-label, no inferential statistics were planned, and sample sizes were small. Conclusion Twelve weeks of sofosbuvir, 400 mg, and velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. Primary funding source Gilead Sciences.

Background & aims We conducted an open-label, randomized, phase 3 trial to determine the efficacy and safety of sofosbuvir and ribavirin, with and without peginterferon-alfa, in treatment-experienced patients with cirrhosis and hepatitis C virus (HCV) genotype 2 infection and treatment-naive or treatment-experienced patients with HCV genotype 3 infection. Methods The study was conducted at 80 sites in Europe, North America, Australia, and New Zealand Patients were randomly assigned (1:1:1) to groups given sofosbuvir and ribavirin for 16 weeks (n = 196); sofosbuvir and ribavirin for 24 weeks (n = 199); or sofosbuvir, peginterferon-alfa, and ribavirin for 12 weeks (n = 197). The primary end point was the percentage of patients with HCV RNA Results Rates of SVR12 among patients with genotype 2 HCV were 87% and 100%, for those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 94% for those receiving sofosbuvir, peginterferon, and ribavirin for 12 weeks. Rates of SVR12 among patients with genotype 3 HCV were 71% and 84% in those receiving 16 and 24 weeks of sofosbuvir and ribavirin, respectively, and 93% in those receiving sofosbuvir, peginterferon, and ribavirin. On-treatment virologic failure occurred in 3 patients with HCV genotype 3a receiving sofosbuvir and ribavirin for 24 weeks. The most common adverse events were fatigue, headache, insomnia, and nausea. Overall, 1% of patients discontinued treatment due to adverse events. Conclusions Among patients with genotype 3 HCV infection, including a large proportion of treatment-experienced patients with cirrhosis, the combination of sofosbuvir, peginterferon, and ribavirin for 12 weeks produces high rates of SVR. Treatment-experienced patients with cirrhosis and genotype 2 HCV infection had high rates of SVR in all groups. EudraCT ID 2013-002641-11.

Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate.EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917.The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening antiretrovirals, and 169 (15%) had previous virological failure on a non-darunavir regimen. The study regimen was non-inferior to the control for virological rebound cumulative through week 48 (19 [2·5%] of 763 patients in the study group vs eight (2·1%) of 378 patients in the control group; difference 0·4%, 95% CI -1·5 to 2·2; p0·0001). No resistance to any study drug was observed. Numbers of discontinuations related to adverse events (11 [1%] of 763 patients in the study group vs four [1%] of 378 patients in the control group) and grade 3-4 adverse events (52 [7%] patients vs 31 [8%] patients) were similar between the two groups. There was a small non-clinically relevant but statistically significant (0·2 [SD 1·1] vs 0·1 [1·1], p=0.010) difference between the two groups in change from baseline in total cholesterol to HDL-cholesterol ratio. Only one serious adverse event (pancreatitis in the study group) was deemed as possibly related to the study regimen.Our findings show the safety and efficacy of single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide as a potential switch option for the treatment of HIV-1 infection in adults with viral suppression.Janssen.

People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was sustained virologic response (HCV RNA below the limit of quantitation [15 IU/mL]) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part C, SVR12 was achieved by 23/24 (96%) participants treated for 16 weeks with ribavirin (GT1, 2/2 [100%]; GT2, 13/14 [93%]; GT3, 8/8 [100%]). One participant with GT2 infection discontinued study medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus ribavirin due to serious adverse events of vomiting and tachycardia. The presence of baseline resistance-associated substitutions had no impact on SVR12. No participant who completed treatment in either study experienced virologic failure.Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor-containing therapy. (Hepatology 2017;66:1794-1804).

Background & Aims Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) after 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). Methods In 2 phase 3, open-label trials, patients with HCV infection who had not been treated previously with a direct-acting antiviral agent were assigned randomly to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the noninferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a noninferiority margin of 5%. POLARIS-3, which enrolled patients infected with HCV genotype 3 who had cirrhosis, compared rates of SVR in both groups with a performance goal of 83%. Results In POLARIS-2, 95% (95% confidence interval [CI], 93%–97%) of patients had an SVR to 8 weeks of sofosbuvir-velpatasvir-voxilaprevir; this did not meet the criterion to establish noninferiority to 12 weeks of sofosbuvir-velpatasvir, which produced an SVR in 98% of patients (95% CI, 96%–99%; difference in the stratum-adjusted Mantel–Haenszel proportions of -3.2%; 95% CI, -6.0% to -0.4%). The difference in the efficacy was owing primarily to a lower rate of SVR (92%) among patients with HCV genotype 1a infection receiving 8 weeks of sofosbuvir-velpatasvir-voxilaprevir. In POLARIS-3, 96% of patients (95% CI, 91%–99%) achieved an SVR in both treatment groups, which was significantly superior to the performance goal. Overall, the most common adverse events were headache, fatigue, diarrhea, and nausea; diarrhea and nausea were reported more frequently by patients receiving voxilaprevir. In both trials, the proportion of patients who discontinued treatment because of adverse events was low (range, 0%–1%). Conclusions In phase 3 trials of patients with HCV infection, we did not establish that sofosbuvir-velpatasvir-voxilaprevir for 8 weeks was noninferior to sofosbuvir-velpatasvir for 12 weeks, but the 2 regimens had similar rates of SVR in patients with HCV genotype 3 and cirrhosis. Mild gastrointestinal adverse events were associated with treatment regimens that included voxilaprevir. ClinicalTrials.gov numbers: POLARIS-2, NCT02607800; and POLARIS-3, NCT02639338.

Summary Elbasvir (EBR; HCV NS5A inhibitor) and grazoprevir (GZR; HCV NS3/4A protease inhibitor) are approved as a fixed-dose combination to treat patients chronically infected with HCV genotypes 1 and 4. During the development program and supported by in vitro potency, the efficacy of EBR + GZR was assessed in HCV GT3-infected patients. This study's aim was to determine the efficacy and tolerability of 12 or 18 weeks of EBR+GZR with ribavirin (RBV) in treatment-naive, non-cirrhotic HCV GT3-infected patients. Randomized patients received open-label EBR (50 mg once daily) + GZR (100 mg once daily) + RBV. The primary efficacy objective was to evaluate the sustained virologic response rates 12 weeks after the end of all study therapy (SVR12). SVR12 rates (95% confidence interval) were 45.0% (23.1, 68.5) and 57.1% (34.0, 78.2) after treatment with EBR+GZR+RBV for 12 weeks or 18 weeks, respectively. On-treatment virologic failure was observed in 41% (17/41) of patients. At virologic failure, resistance-associated substitutions (RASs) with a >5 fold shift in potency occurred in the NS3 region in 6 (35%) patients and in the NS5A region in 16 (94%) patients. The most common RAS at virologic failure was Y93H in NS5A which was identified in 13/17 (76%) patients. The efficacy of EBR+GZR+RBV was suboptimal in HCV GT3-infected patients due to a high rate of on-treatment virologic failure and treatment emergent RASs which demonstrates an inadequate barrier to the development of GT3 resistance. However, rapid viral clearance demonstrated the antiviral activity of EBR+GZR+RBV in GT3-infected patients. This article is protected by copyright. All rights reserved.

Rapidly evolving healthcare delivery and payment systems offer an excellent opportunity for infectious disease physicians. Our unique competencies position us in a way that meets the challenge the country is facing to provide high-value, cost-effective care., The uncertainties of healthcare payment and delivery reform on income and care process have created a sense of foreboding, concern, and fear that a career in medicine is not what it used to be and that a career in infectious diseases in particular may no longer be viable. Fears have been raised that the need for infectious diseases consultation and management will be curtailed because we provide cognitive services that are not perceived as being needed in a health system filled with intensivists, hospitalists, and skilled nursing facility physicians. Now is the time for us to reframe our role in the health system that is evolving to a process of care focused on population health and patient safety that pays providers for value they bring to achieve those goals. Specific suggestions are made to enhance the infectious diseases physician's profile with the intent of encouraging debate, discussion, and action.

Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea.Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).

The Hepatitis C Task Force includes: Mark D. Boldt, RN, CNP, Minnesota Gastroenterology; Joel V. Brill, MD, AGAF, Predictive Health; Gary L. Davis, MD, Baylor University Medical Center Dallas(retired); Stuart C. Gordon, MD, AGAF, Henry Ford Health System; Arthur Y. Kim, MD, FIDSA, Massachusetts General Hospital; Lawrence R. Kosinski, MD, MBA, AGAF, Illinois Gastroenterology Group; Arnold G. Levy, MD, Capital Digestive Care; Ronald G. Nahass, MD, MHCM, FIDSA, ID Care; and John I. Allen, MD, MBA, AGAF (Chair), Yale School of Medicine.

Background Previous studies, largely based on chart reviews with small sample sizes, have demonstrated that infectious diseases (ID) specialists positively impact patient outcomes. We investigated how ID specialists impact mortality, utilization, and costs using a large claims dataset. Methods We used administrative fee-for-service Medicare claims to identify beneficiaries hospitalized from 2008 to 2009 with at least 1 of 11 infections. There were 101 991 stays with and 170 336 stays without ID interventions. Cohorts were propensity score matched for patient demographics, comorbidities, and hospital characteristics. Regression models compared ID versus non-ID intervention and early versus late ID intervention. Risk-adjusted outcomes included hospital and intensive care unit (ICU) length of stay (LOS), mortality, readmissions, hospital charges, and Medicare payments. Results The ID intervention cohort demonstrated significantly lower mortality (odds ratio [OR], 0.87; 95% confidence interval [CI], .83 to .91) and readmissions (OR, 0.96; 95% CI, .93 to .99) than the non-ID intervention cohort. Medicare charges and payments were not significantly different; the ID intervention cohort ICU LOS was 3.7% shorter (95% CI, -5.5% to -1.9%). Patients receiving ID intervention within 2 days of admission had significantly lower 30-day mortality and readmission, hospital and ICU length of stay, and Medicare charges and payments compared with patients receiving later ID interventions. Conclusions ID interventions are associated with improved patient outcomes. Early ID interventions are also associated with reduced costs for Medicare beneficiaries with select infections.

Background Hepatitis C virus (HCV) infection is common in persons who inject drugs (PWID). Objective To evaluate elbasvir-grazoprevir in treating HCV infection in PWID. Design Randomized, placebo-controlled, double-blind trial. (ClinicalTrials.gov: NCT02105688). Setting Australia, Canada, France, Germany, Israel, the Netherlands, New Zealand, Norway, Spain, Taiwan, the United Kingdom, and the United States. Patients 301 treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection who were at least 80% adherent to visits for opioid agonist therapy (OAT). Intervention The immediate-treatment group (ITG) received elbasvir-grazoprevir for 12 weeks; the deferred-treatment group (DTG) received placebo for 12 weeks, no treatment for 4 weeks, then open-label elbasvir-grazoprevir for 12 weeks. Measurements The primary outcome was sustained virologic response at 12 weeks (SVR12), evaluated separately in the ITG and DTG. Other outcomes included SVR24, viral recurrence or reinfection, and adverse events. Results The SVR12 was 91.5% (95% CI, 86.8% to 95.0%) in the ITG and 89.5% (95% CI, 81.5% to 94.8%) in the active phase of the DTG. Drug use at baseline and during treatment did not affect SVR12 or adherence to HCV therapy. Among 18 patients with posttreatment viral recurrence through 24-week follow-up, 6 had probable reinfection. If the probable reinfections were assumed to be responses, SVR12 was 94.0% (CI, 89.8% to 96.9%) in the ITG. One patient in the ITG (1 of 201) and 1 in the placebo-phase DTG (1 of 100) discontinued treatment because of an adverse event. Limitation These findings may not be generalizable to PWID who are not receiving OAT, nor do they apply to persons with genotype 3 infection, a common strain in PWID. Conclusion Patients with HCV infection who were receiving OAT and treated with elbasvir-grazoprevir had high rates of SVR12, regardless of ongoing drug use. These results support the removal of drug use as a barrier to interferon-free HCV treatment for patients receiving OAT. Primary funding source Merck & Co.

Background & AimsThe best regimen to re-treat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus genotype 1 infection.MethodsWe performed an open-label trial at 32 sites in the United States and at 2 sites in New Zealand of 197 patients with genotype 1 hepatitis C virus infection, with or without compensated cirrhosis, who were treatment-naive or were treated previously with a DAA. Between March 2, 2015, and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6–12 weeks, plus ribavirin for 1 treatment group consisting of treatment-naive patients with cirrhosis. The primary end point was sustained virologic response 12 weeks after treatment (SVR12).ResultsAmong treatment-naive patients without cirrhosis, 71% (24 of 34; 95% confidence interval [CI], 53–85) achieved SVR12 after 6 weeks of treatment and 100% (36 of 36; 95% CI, 90%–100%) achieved SVR12 after 8 weeks of treatment. Among treatment-naive patients with cirrhosis, 94% (31 of 33; 95% CI, 80–99) achieved SVR12 after 8 weeks of treatment and 81% (25 of 31; 95% CI, 63–93) achieved SVR12 after 8 weeks of treatment with ribavirin. Among DAA-experienced patients treated for 12 weeks, 100% without cirrhosis (31 of 31; 95% CI, 89–100) and 100% with cirrhosis (32 of 32; 95% CI, 89–100) achieved SVR12. The most common adverse events were headache, diarrhea, fatigue, and nausea. One patient (

Background The pattern of hepatitis C virus (HCV) transmission routes in sub-Saharan Africa (SSA) has not been previously well characterized. A recent meta-analysis reported a general population HCV prevalence of 5.4% and HIV co-infection prevalence of 3.6% in SSA, with considerable regional variation. Methods A cross-sectional study was performed in Kumasi, Ghana. Subjects were recruited from patients attending an STI clinic at a government-supported health center. Subjects completed a survey emphasizing known risk factors for HCV, including sexual behaviors, to capture potential routes of exposure. Surveys were administered in Twi, the local language, with the assistance of trained interpreters. Blood samples were collected and tested for HCV antibodies using DiaSpot Anti-HCV Rapid Screen Tests (USA). Data were analyzed using univariate analysis and logistic regression using SAS 9.4. Results Of the total 312 subjects, 15 were HCV positive (prevalence 4.8%). The HIV-HCV co-infection prevalence was 5.5%. After adjusting for age and sex, statistically significant associated risk factors for HCV infection (P < 0.05) include no/low level of education vs. tertiary (OR 5.0), northern region of birth vs. central region (OR 7.3), and traditional body scarring (OR 4.1). Rough sexual practices, ie dry sex, sores, were also explored and were associated with HCV infection (P = 0.02). Post-hoc stratified analysis of HIV-infected individuals (n = 201) was performed to identify risk factors among those with HCV co-infection. Significant risk factors (P < 0.05) in this sub-population include northern region of origin (OR 12.4) and traditional scars or marks (OR 4.6). Conclusion Two risk factors for HCV infection, ie region of birth and traditional scarring, were significant in both the total clinic population and HIV co-infected individuals suggesting cultural practices are contributing to an increased risk of infection. Among HCV positive individuals, rough sexual practices were significant risk factors; whereas, IV-drug abuse was not. While HCV treatment exists, it is not currently available in West Africa; therefore, it is critical to identify risk factors to best target education programs and screening of populations to limit disease spread. Disclosures All authors: No reported disclosures.

Background An abrupt change in baseline CDI from 2016 to 2017 prompted a response team task force including senior administration, the CMO, infection prevention, environmental services, laboratory, pharmacy, emergency department (ED), and nursing to address the problem. Methods Hospital-acquired (HA) and community-acquired (CA) CDI cases were tracked using an epidemic curve and institutional case mapping. A multipronged intervention was implemented that included molecular typing of isolates, quarterly terminal cleaning of the ED, improved CDI screening and testing, intensified antimicrobial stewardship (AS) with mandatory education for key clinicians, and rigorously enhanced enforcement of hand hygiene with secret observers and directed feedback. Pre-, mid-, and fully-implemented intervention HA and CA CDI rates were observed. Results Ninety-five percent of CA CDI and 98% of all patients who developed HA CDI were admitted through the ED. Cases of CDI were distributed throughout the hospital. The genotyping did not identify a single strain outbreak. Sixteen percent of all CDI samples (23% of CA and 9% of HA cases) sent to the DOH tested positive for BINAP1. Preintervention rates of HA CDI were found to be lower than mid-intervention rates (2.4, 95% CI= 1.5–3.1 vs. 4.3, 95% CI= 1.13–7.37). HA CDI rates after full-intervention in fourth quarter 2017 and first quarter 2018 trended toward baseline (2.1, 95% CI = 0–5.93) but had not achieved statistical improvement (Figure 1). A significant correlation between HA CDI rates and CA CDI rates was not found (r = 0.241, P < 0.5), suggesting that HA CDI rates were not driven by CA CDI rates. Hospital and ED hand hygiene improved significantly; hospital preintervention = 0.84 vs. intervention = 0.91, P < 0.01; ED hand hygiene preintervention = 0.72 vs. intervention = 0.86, P < 0.04. No statistically significant changes in antimicrobial use were noted. Conclusion A rapid, aggressive team-based approach for a CDI outbreak successfully reversed a rising rate and SIR. Although no one specific intervention was clearly responsible for the reversal, we did observe a statistically significant increase in hand hygiene. This outbreak and its management illustrate the importance of active surveillance and a rapid team-based response to CDI outbreaks. Disclosures All authors: No reported disclosures.

Recent developments in health care have focused efforts on both the national and local levels to reduce unnecessary health care costs and the number of hospital stays while increasing the quality of care, particularly in the context of hospital-associated infections. Infectious diseases specialists who contract to oversee infection-control and antibiotic-stewardship programs are uniquely positioned to play a pivotal role in helping hospitals to prosper in this new environment. This article will detail the available data supporting the value of infectious diseases specialists in their roles of directing antimicrobial-management and infection-control programs, maintaining health care workers' well-being, and minimizing exposure. The evidence in support of the influence of infectious diseases specialists to achieve cost-savings, decrease the length of hospital stays, and improve outcomes is robust and can be used as the framework for negotiating appropriate compensation from hospital management for these activities. Presenting this information in an amicable but definitive framework may be the linchpin to the overall success of the movement to improve quality of care while minimizing hospital costs and antimicrobial use. Developing this ability is critical to infectious diseases specialists' success as they redefine their role in the quality-of-care and risk-management arenas.

Purpose Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of this study was to identify whether currently prescribed doses of cefoxitin achieve adequate and sustained plasma and tissue concentrations in obese patients undergoing sleeve gastrectomy. Methods A prospective evaluation of plasma and tissue cefoxitin concentrations in patients undergoing sleeve gastrectomy was performed. On the day of the surgical procedure, venous blood samples (5 mL) were collected just before cefoxitin administration and then at 5, 30, 60, 120, and 240 minutes after dose administration. In addition, subcutaneous adipose tissue was collected from the surgical site at the time of surgical incision and at closure. Cefoxitin concentrations in the collected samples were quantified by using an HPLC–ultraviolet method. A standard noncompartmental analysis was performed for each individual cefoxitin plasma concentration–time profile. In addition, the ratio of tissue to plasma concentration was calculated for all patients. Findings Plasma and tissue pharmacokinetics of cefoxitin were evaluated in 6 patients undergoing sleeve gastrectomy. The mean age and BMI were 48.7 (6.2) years and 42.8 (7.1) kg/m 2 , respectively. At the time of surgical closure, subcutaneous adipose tissue concentrations of cefoxitin were subtherapeutic ( Implications Current dosing strategies for cefoxitin in obese surgical patients may be inadequate, and there is an urgent need to define the appropriate dosage.

Background: Current medical center practice allows for the automatic conversion of all piperacillin/tazobactam orders from intermittent to extended infusion (EI). Objective: To compare the clinical and cost impact of empirical extended-infusion piperacillin/tazobactam. Methods: All consecutive patients treated with piperacillin/tazobactam for >48 hours were reviewed for inclusion. Patients were stratified into 2 groups: (1) traditional infusion (TI), preprotocol implementation, and (2) EI, postprotocol implementation. Patient demographics and primary and secondary diagnoses were extracted from the hospital discharge database. All patients were assessed for the primary end point of all cause 14-day in-hospital mortality. Secondary outcomes included length of hospital stay, duration of antibiotic therapy, cost per treatment course, and occurrence of Clostridium difficile infection. Results: A total of 2150 patients were included (EI = 632; TI = 1518). After adjusting for comorbidity, length of stay, and age, 14-day in-hospital mortality was similar between groups (odds ratio = 1.16; 95% CI = 0.85-1.58; P = 0.37). Length of stay was similar between the EI group versus TI (mean ± SD: 12.5 ± 9.58 days vs 11.8 ± 9.58 days, respectively; P = 0.10) after adjusting for age and Chalson-Deyo comorbidity index. Total cost per treatment course was reduced in the EI group by 13% compared with the TI group ($565.90 ± $257.70 vs $648.30 ± $349.20, respectively; P < 0.0001). Conclusion: Automatic substitution of EI for TI piperacillin/tazobactam is safe and associated with significant cost savings. EI piperacillin/tazobactam was not associated with a reduction in mortality or length of stay.