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Background Candidemia is an important cause of morbidity and mortality. Fluconazole resistance is associated with increased mortality in candidemia and thus echinocandins are recommended as first line empiric therapy. To understand the current landscape of candidemia treatment, we evaluated the epidemiology and outcomes of candidemia at our medical center, with a focus on differences in traditional azole-susceptible and non-susceptible candida species. Methods This is a retrospective cohort study including unique episodes of candidemia from 7/2017 – 12/2021 in hospitalized adult patients. We characterized candidemia episodes by species, age, hospital-onset, hospital location and critical illness. We compared traditionally azole susceptible organisms (e.g. C.albicans, C. parapsilosis, C.tropicalis) to non-susceptible (e.g. C.krusei, C.glabrata) based on antibiogram (cut off >94% susceptible) with the primary outcome of 30-day mortality. Secondary outcomes were recurrent/persistent candidemia, 90-day mortality and length of stay. Comparisons were done with χ2 or Wilcoxon rank sum tests. Logistic regression was performed to determine if azole-nonsusceptible candidemia was associated with 30-day mortality. Results 404 candidemic episodes for 389 patients were identified, of which 72% were due to azole-susceptible Candida spp. and C.glabrata and C.krusei were 23% and 5%, respectively. Critically ill patients were more likely to have azole-non-susceptible Candida spp (59 vs. 48%, p=0.04). Overall 30-day mortality was 35%, and was similar between azole-susceptible and non-susceptible groups, with no difference in other outcomes (Table 1). After adjusting for age and hospital-onset, critically ill patients with azole-non-susceptible candidemia had odds ratio of 1.5 (95% CI 0.87 – 2.7 p=0.13) for 30-day mortality. Distribution of candida species and associated 30-day mortality are found in Table 2. Demographics and Outcome Distribution of most common Candida spp. in candidemia in critically ill (n=205) Conclusion We found similar 30-day mortality rates in azole-susceptible and non-susceptible candida species since echinocandin first-line empiric therapy was implemented in guidelines. The impact on critically ill and invasive infections, including ocular involvement, needs further evaluation. Disclosures All Authors: No reported disclosures.

We aim to discuss the evidence behind combination therapy as well as to describe the novel antifungals used in the treatment for mucormycosis. In patients with advanced or refractory invasive mucormycosis, limited data support the use of combination salvage therapy with a polyene backbone plus an echinocandin. Several new antifungal agents have also shown in vitro activity against Mucorales by acting through different mechanisms. VT1161 and VT-1598 are next-generation azoles, termed tetrazoles, that target the fungal cell membrane by inhibiting the CYP51 enzyme with minimal drug-drug interactions. Fosmanogepix (APX001) is a glycosylphosphatidylinositol inhibitor with a broad spectrum of activity. Finally, MGCD290 is a histone deacetylase inhibitor that has shown synergistic effects with azoles and echinocandins. Mucormycosis is a life-threatening disease. Current guidelines recommend polyenes and certain azoles as first-line treatment along with surgical management and correction of specific host factors. For refractory mucormycosis, there are combination salvage therapy options with evidence from murine models and human case reports; however, there have been no prospective, randomized clinical trials to prove their efficacy. For those intolerant of polyenes and azoles, there are novel drug therapies that have shown in vitro activity against Mucorales, although further investigation is needed to determine if these agents should be used clinically as monotherapy or in combination with existing agents.

Diagnostic stewardship in solid organ transplant (SOT) recipients has the potential to help these vulnerable patients at risk for over-testing and overtreatment.Herein, we review potential targets for diagnostic stewardship in SOT, such as Clostridioides difficile testing, urine cultures, molecular diagnostics, as well as novel areas of diagnostic stewardship.Bundled interventions focused on appropriate C. difficile testing can result in a significant decrease in testing and clinical diagnosis of C. difficile infection without any harms related to delay in diagnosis. In otherwise stable renal transplant recipients after the first month of transplant, screening urine cultures have not been shown to improve outcomes. Novel targets that require additional study in the SOT population include noninvasive fungal diagnostics and cytomegalovirus testing strategies CONCLUSIONS: Diagnostic stewardship is an innovative approach to improve diagnosis and limit unnecessary antimicrobial use. While there has been little direct exploration of diagnostic stewardship in the SOT population, there is great potential for benefit given frequent testing with diagnostics that have imperfect sensitivity and specificity, and sometimes great cost. Diagnostic stewardship in the SOT population is indeed possible but will require a multidisciplinary effort to ensure that appropriates tests and benefits are realized.

Background Prospective audit with feedback (PAF) is an impactful strategy for antimicrobial stewardship program (ASP) activities. However, because PAF requires reviewing large numbers of antimicrobial orders on a case-by-case basis, PAF programs are highly resource intensive. The current study aimed to identify predictors of ASP intervention (ie, feedback) and to build models to identify orders that can be safely bypassed from review, to make PAF programs more efficient. Methods We performed a retrospective cross-sectional study of inpatient antimicrobial orders reviewed by the University of Maryland Medical Center’s PAF program between 2017 and 2019. We evaluated the relationship between antimicrobial and patient characteristics with ASP intervention using multivariable logistic regression models. Separately, we built prediction models for ASP intervention using statistical and machine learning approaches and evaluated performance on held-out data. Results Across 17 503 PAF reviews, 4219 (24%) resulted in intervention. In adjusted analyses, a clinical pharmacist on the ordering unit or receipt of an infectious disease consult were associated with 17% and 56% lower intervention odds, respectively (adjusted odds ratios [aORs], 0.83 and 0.44; P ≤ .001 for both). Fluoroquinolones had the highest adjusted intervention odds (aOR, 3.22 [95% confidence interval, 2.63–3.96]). A machine learning classifier (C-statistic 0.76) reduced reviews by 49% while achieving 78% sensitivity. A “workflow simplified” regression model that restricted to antimicrobial class and clinical indication variables, 2 strong machine learning–identified predictors, reduced reviews by one-third while achieving 81% sensitivity. Conclusions Prediction models substantially reduced PAF review caseloads while maintaining high sensitivities. Our results and approach may offer a blueprint for other ASPs.

The role of follow-up blood cultures (FUBCs) in gram-negative bloodstream infections to improve clinical outcomes remains controversial, especially among immunocompromised patients. Among 139 patients, FUBCs were common (117, 84.2%); however, positive FUBCs were rare (3, 2.6%). Only presence of fever was associated with a positive FUBC.

Human herpesvirus 6 (HHV-6) reactivation can occur in patients who are highly immunosuppressed, including those who have undergone hematopoietic stem cell transplantation (HSCT). HHV-6 encephalitis is a severe manifestation that is well described in the HSCT population. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy that results in severe immunosuppression. Patients undergoing CAR-T therapy may be at risk for HHV-6 encephalitis, which can be difficult to distinguish from a common adverse effect of CAR-T therapy, neurotoxicity. Herein, we describe 2 patients diagnosed with HHV-6 encephalitis after CAR-T therapy and discuss the diagnostic approach and differential diagnosis for altered mental status after CAR-T therapy. Diagnosing HHV-6 encephalitis can be difficult in this patient population as altered mental status is common after CAR-T therapy and may be attributed to CAR-T-associated neurotoxicity.

Interrupted time series segmented regression was conducted to trend antibiotic use and multidrug-resistant gram-negative (MDRGN) acquisition relative to COVID-19 in an academic hospital. Total antibiotic use and antibiotic use related to pneumonia was higher in the period after the onset of COVID-19 compared to the similar calendar period in 2019. Furthermore, MDRGN acquisition increased 3% for every increase in positive COVID-19 tests per week.

Introduction Dalbavancin is approved for acute bacterial skin and skin structure infections (ABSSSIs) but offers a potential treatment option for complicated invasive gram-positive infections. Importantly, dalbavancin’s real benefits may be in treating complicated infections in vulnerable patient populations, such as persons who inject drugs (PWID). Methods A multicenter retrospective analysis was performed from March 2014 to April 2017 to assess 30- and 90-day clinical cure and adverse drug events (ADEs) in adult patients who received ≥ 1 dose of dalbavancin for a non-ABSSSI indication. Results During the study period, 45 patients received dalbavancin, 28 for a non-ABSSSI indication. The predominant infections treated included osteomyelitis (46%), endovascular infection (25%) and uncomplicated bacteremia (14%). Half of the patients had positive Staphylococcus aureus in cultures, 29% methicillin resistant and 21% methicillin susceptible. Most patients were prescribed dalbavancin as sequential treatment with a median of 13.5 days of prior antibiotic therapy. The most common reason for choosing dalbavancin over standard therapy use was PWID (54%). Seven patients were lost to follow-up at day 30. Of the remaining evaluable patients, 30-day clinical cure was achieved in 15/21 (71%) patients. The most common reason for failure was lack of source control (4/6, 67%). At day 90, relapse occurred in two patients. Three patients had a potential dalbavancin-associated ADE: two patients with renal dysfunction and one patient with pruritus. Conclusions This study demonstrates a possible role for dalbavancin in the treatment of non-ABSSSI invasive gram-positive infections in select vulnerable OPAT patients.

Background Guidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions. Methods Panelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds. Results Thirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable. Conclusions In the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.

This is a retrospective cohort study evaluating the safety and effectiveness of biodegradable calcium sulfate antibiotic beads in vascular graft infections compared with standard of care. No differences in acute kidney injury or hypercalcemia were observed between the cohorts. Recurrence of infection did not occur in the 13-patient bead cohort compared with 14 patients who had recurrence in the 45-patient nonbead cohort with a number needed to treat of 4.0.

We identified deep diabetic foot infections by culture and conducted a case–control study examining the risk factors for moderate to severe methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PsA) diabetic foot infections. Our MRSA prevalence was lower than literature values; PsA was higher. Gangrene may be predictive of Pseudomonas infection.

Hospital-based antibiotic stewardship (AS) programs provide oversight and guidance for appropriate antimicrobial use in acute care settings. Infectious disease expertise is beneficial in the care of hospitalized patients with infections. The impact of infectious diseases consultation (IDC) on antimicrobial appropriateness in a large tertiary hospital with an established AS program was investigated. This was a cross-sectional study from October 2017 to March 2019 at a large academic hospital with an AS-directed prospective audit and feedback process and multiple IDC services. Antimicrobial appropriateness was adjudicated by an AS team member after antimicrobial start. Antimicrobial appropriateness was compared among antimicrobial orders with and without IDC using propensity score matching and multivariable logistic regression. Analyses were stratified by primary services caring for the patients. There were 10,508 antimicrobial orders from 6,165 unique patient encounters. Overall appropriateness was 92%, with higher appropriateness among patients with IDC versus without IDC (94% versus 84%; P

Antimicrobial stewardship (AS) programs are expanding efforts across the entire healthcare continuum. Antimicrobials are commonly overused in outpatient care locations, which have not received the same intensity of AS intervention as inpatient settings. Guidance for AS programs is needed on how to implement interventions and monitor for improvement. Antimicrobials prescribed in the outpatient setting are inappropriate in 23–76% of cases. Factors associated with inappropriate prescribing include older adult patients, advanced practice practitioner prescribers, and urgent care clinics. Indications such as upper respiratory infections and asymptomatic bacteriuria are common conditions in which antibiotics should not be used yet they are major contributors to inappropriate antibiotic use. Promising interventions include peer comparison and clinical decision support, but gaps remain. There is little evidence for how to limit the use of fluoroquinolones and newly approved antibiotics. Improving antibiotic use is needed in the outpatient setting and poses unique challenges for AS programs. Defining problems unique to designated outpatient centers and implementing proposed interventions targeting these problems is an effective strategy. Collaboration with State Health Departments, health insurers, and healthcare systems will be essential.

Background Urine cultures are often positive in the absence of a urinary tract infection (UTI). Pyuria is generally considered necessary to diagnose a UTI. Problem Urine cultures are often positive in the absence of UTI leading to unnecessary antibiotics. Methods Quasi-experimental pre-post study of all patient urine cultures ordered in a VA acute care hospital, emergency department (ED), and two long-term care (LTC) facilities from August 2016 to August 2018. Urine cultures performed per 100 days were compared pre- (August 2016 to July 2017) versus post-intervention (August 2017 to August 2018) using interrupted time series negative binomial regression. Intervention We examined whether reflexing to urine culture only if a urinalysis (UA) found greater than 10 WBC/hpf decreased urine culturing. Results In acute-care, reflex culturing resulted in a 39% time series regression analysis adjusted decrease in the rate of cultures performed (pre-intervention, 3.6 cultures/100 days vs. Post-intervention, 1.8 cultures/100 days, p p = 0.0015) regression analysis adjusted decrease in cultures, from 5.4/100 visits to 3.3/100 visits. In LTC, there was a small absolute, but regression analysis adjusted increase of 89% (p = 0.0018) in rates from (0.4/100 days to 0.5/100 days). Conclusion In acute care and ED, urine reflex culturing decreased the number of urine cultures performed. A small absolute increase was seen between pre-post time periods in LTC. Reflex testing generally decreases cultures and may lead to more accurate diagnoses of CAUTI.

We analyzed the effects of different cefepime MIC breakpoints on Enterobacteriaceae cefepime susceptibility and the presence of AmpC and extended-spectrum β-lactamase (ESBL) genes within the cefepime MIC interpretative categories.Using Enterobacteriaceae susceptibility data from 2013 comparisons of MIC breakpoints were performed using Pearson's chi-squared test. Molecular testing on a subset of isolates was done.Among 3784 non-duplicate clinical isolates, cefepime susceptibility decreased from 97.6% to 96.1% to 93.7% for CLSI 2013, CLSI 2014, and EUCAST 2011, respectively. In ceftriaxone non-susceptible isolates, cefepime susceptibility decreased from 79% to 66% (P0.0001) using CLSI 2013 and 2014, respectively, which was greater and statistically significant for Escherichia coli and Klebsiella spp. but not for Enterobacter spp. (P=0.06). Isolates with MIC ≤1μg/mL more often harbored AmpC (77%) than ESBL (18%) genes.Lower cefepime MIC breakpoints decrease cefepime susceptibility for isolates harboring ESBLs, while sparing the majority of those with AmpCs.

Background Outpatient antibiotic stewardship is an emerging area of interest. The COVID-19 pandemic has led to unique restrictions such as social distancing and an increase in telemedicine visits. The effects on outpatient antimicrobial prescription needs further exploration. Methods We investigated the outpatient antimicrobial prescription trend pre (January 5 to March 14 2020) and post (March 15 to May 31 2020) COVID-19 restrictions at the Veteran’s Affairs Maryland Health Care System. We compared prescribing characteristics pre and post restrictions using Chi-squared and Mann Whitney U tests. Segmented regression analysis was used to compare antimicrobial prescriptions per 1000 encounters, with a control group from the same weeks in 2019. Results There were 3,881 total antibiotics prescribed for 382501 encounters during the 16 weeks in 2020. Post-restrictions, there was a significant decrease in encounters and antibiotics per week with mean difference of -15241 and -147, for encounters and antibiotics, respectively. The mean antibiotics per 1000 encounters was slightly higher in the post-restriction group, but without statistical significance by this analysis (10.1 vs 10.4, p-value 0.48). Other notable changes post-prescription described in the Table was a decrease in macrolide and an increase in trimethoprim-sulfamethoxazole; urgent care prescriptions decreased, while primary care prescription increased; and refill prescriptions were less common, while mail prescriptions were more common. On regression analysis, we found a significant level change of +2.7 antibiotics per 1000 encounters (p=0.02) immediately after restrictions were placed, without any significant change in trend (Figure). This translates to an additional 243 antibiotics prescribed during the post-restriction weeks. This was in comparison to data from 2019 which had no significant level or trend change during the same weeks. Table 1. Characteristics of antibiotics prescribed and comparison between pre and post COVID-19 restrictions in 2020, with 2019 control. Figure 1. Segmented Regression of antibiotic prescription per 1000 encounters pre and post COVID-19 restrictions with 2019 as control group. Conclusion We found an immediate increase in antibiotics relative to encounters post COVID-19 restrictions though antibiotics and encounters were all generally decreased with azithromycin showing the most appreciable decrease. Further investigation is needed to understand these findings and the implications on the population. Disclosures All Authors: No reported disclosures

Background Staphylococcus lugdunensis is a coagulase negative Staphylococcus (CoNS) species with the potential to cause aggressive infection. Guidance surrounding S. lugdunensis bacteremia (SLB) is lacking, especially in the case of a single positive set of blood cultures. Methods We performed a multicenter, retrospective observational cohort review of adult patients with SLB from at least one blood culture set within the University of Maryland Medical System from November 2015-November 2019. Objectives were to (1) describe baseline characteristics, (2) compare available criteria for evaluating clinical significance, and (3) evaluate the clinical outcomes among patients with SLB in 1 vs ≥2 positive blood culture sets. Descriptive statistics with Chi-squared and Mann-Whitney U tests were carried out. Results There were 5,548 CoNS-positive blood culture sets, 49 (0.88%) with S. lugdunensis comprising 36 adult patients (24 with 1 positive set and 12 with ≥2 positive sets). Patients with ≥2 positive sets were more likely to be on hemodialysis (HD) (p=0.029) and to have an HD catheter present (p=0.10) (Table 1). Thirty-five of the 36 patients fulfilled at least one of the following: systemic inflammatory response syndrome (SIRS), Souvenir criteria, or clinical criteria (infectious focus on imaging and/or second positive culture site) (Table 2). Twenty-eight (78%) patients were treated with antimicrobial therapy and/or central line removal. SIRS criteria were met more often among patients with 1 positive set (p=0.05). Patients with ≥2 positive sets were more often treated with antibiotics for longer than 2 weeks (p=0.02). The mean time of positive cultures to discharge was 11 days and was longer for patients with only one set of positive blood cultures (13 vs. 6 days), although this difference was not statistically significant (p=0.29) (Table 3). Conclusion SLB was rare and occurred more frequently as a single set of positive blood cultures. Though limited by sample size, this study found similar patient characteristics, clinical significance and outcomes between patients with one set and those with ≥2 sets of blood cultures positive for S. lugdunensis. Given the potential severity of SLB, it seems prudent to treat S. lugdunensis in a single blood culture, but larger studies are needed. Disclosures All Authors: No reported disclosures

Background Staphylococcus lugdunensis is a coagulase negative Staphylococcus species and frequent human skin commensal with the potential for aggressive infection. Guidance surrounding S. lugdunensis bacteremia (SLB) from a single set of blood cultures is lacking. Methods A multicenter, retrospective cohort of patients with SLB from at least one blood culture set within the University of Maryland Medical System from 2015 to 2019 is presented. Objectives are to describe baseline characteristics, compare the clinical status and treatment course, and to evaluate the clinical outcomes among patients with SLB in single versus multiple sets. Results Thirty-six patients were included, 24 with one set of blood cultures positive for S lugdunensis and 12 with multiple sets. Baseline characteristics were similar between the groups, though patients with SLB in multiple sets were more commonly on hemodialysis (P = 0.029). Central lines were the most common source (17%). Most (97%) fulfilled systemic inflammatory response syndrome or Souvenir criteria, had an infectious focus on imaging, or had a second positive culture site. Most (78%) were treated as clinically significant. Patients with multiple positive sets were more commonly treated with antibiotics for >2 weeks (P = 0.02). Conclusions SLB was rare and occurred more frequently as a single set of positive cultures. Patient characteristics and clinical courses were similar between single and multiple set groups. Given the potential severity of S. lugdunensis bacteremia it seems prudent to treat S. lugdunensis in a single blood culture as true bacteremia, pending larger studies and guidelines.

Background Human herpesvirus 6 (HHV-6) is the most common cause of infectious encephalitis following hematopoietic stem cell transplant. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel cancer-directed immunotherapy; chemotherapy conditioning for CAR-T results in prolonged, severe immunosuppression. HHV-6 encephalitis has not been reported in patients after CAR-T therapy. Methods We report 2 cases of HHV-6 encephalitis after CAR-T therapy. Results Case 1: A 69 year old man underwent CAR-T therapy after fludarabine/cyclophosphamide (Flu/Cy) conditioning for relapsed diffuse large B cell lymphoma (DLBCL). His course was complicated by cytokine release syndrome (CRS) requiring tocilizumab and neurotoxicity requiring high dose dexamethasone. On day 29 he was febrile to 39.3℃, confused, and had difficulty speaking. Mental status (MS) worsened, so LP and MRI of the brain were performed. HHV-6 CSF PCR was positive, and ganciclovir (GCV) was started. He improved gradually over 10 days. At follow up, he reported mild short term memory difficulty but no focal deficits. Case 2: A 57 year old man underwent CAR-T therapy after Flu/Cy conditioning for refractory DLBCL. His course was complicated by CRS requiring tocilizumab. On day 6, he had difficulty concentrating, slowed thinking, stuttering and repetitive speech. MS continued to worsen, and dexamethasone and siltuximab were given for CAR-T neurotoxicity. After 1 week he was following commands. By week 3 he remained intermittently confused and agitated, so MRI and LP were performed. HHV-6 PCR was positive in the CSF. He was started on GCV and improved gradually over the next 2 weeks but remained dysarthric with slowed speech. On day 55, HHV-6 remained detectable in CSF but not quantifiable and GCV was discontinued despite persistent cognitive deficits. Table 1: Demographics and clinical characteristics of 2 patients with HHV-6 encephalitis following CAR-T therapy Conclusion Diagnosing HHV-6 encephalitis can be challenging after CAR-T therapy because altered MS is often attributed to CAR-T associated neurotoxicity. It is important to maintain a high index of suspicion for infectious causes of altered MS after CAR-T therapy, including HHV-6 encephalitis, especially in patients treated with further immunosuppression for CRS and CAR-T related neurotoxicity. Disclosures All Authors: No reported disclosures

Peer comparison has potential as an effective antimicrobial stewardship intervention in the inpatient setting. We report a new metric, days of therapy per 100 service days, for comparing antibiotic utilization. Among 14 prescribers on the primary infectious diseases service during a 6-month period, we identified 1 outlier for each anti-MRSA agent.Infect Control Hosp Epidemiol 2017;38:1506–1508

Herein we report the solid-phase synthesis of a combinatorial aryl, alkyl-triazine library and its application to biofuel production. The combination of Grignard reactions and solid supported Suzuki coupling reactions afforded unique 120 triazine compounds with high purities and minimum purification steps. Through an unbiased phenotypic screening for improved biofuel generation in oleaginous yeast, we found one diaryl triazine derivative (E4) which increased the biolipid production up to 86%.

Rapid identification of microorganisms and antimicrobial resistance is paramount for targeted treatment in serious bloodstream infections (BSI). The Verigene Gram-negative blood culture nucleic acid test (BC-GN) is a multiplex, automated molecular diagnostic test for identification of eight Gram-negative (GN) organisms and resistance markers from blood culture with a turnaround time of approximately 2 h. Clinical isolates from adult patients at the University Maryland Medical Center with GN bacteremia from 1 January 2012 to 30 June 2012 were included in this study. Blood culture bottles were spiked with clinical isolates, allowed to incubate, and processed by BC-GN. A diagnostic evaluation was performed. In addition, a theoretical evaluation of time to effective and optimal antibiotic was performed, comparing actual antibiotic administration times from chart review (“control”) to theoretical administration times based on BC-GN reporting and antimicrobial stewardship team (AST) review (“intervention”). For organisms detected by the assay, BC-GN correctly identified 95.6% (131/137), with a sensitivity of 97.1% (95% confidence interval [CI], 90.7 to 98.4%) and a specificity of 99.5% (95% CI, 98.8 to 99.8%). CTX-M and OXA resistance determinants were both detected. Allowing 12 h from Gram stain for antibiotic implementation, the intervention group had a significantly shorter duration to both effective (3.3 versus 7.0 h; P < 0.01) and optimal (23.5 versus 41.8 h; P < 0.01) antibiotic therapy. BC-GN with AST intervention can potentially decrease time to both effective and optimal antibiotic therapy in GN BSI.

To introduce the biaryl structure as a triazine functionality, we have developed a new synthetic route via the Suzuki cross-coupling reaction of resin-bound chlorotriazines. The Suzuki cross-coupling reaction was achieved using various arylboronic acids, Pd(PPh 3 ) 4 , Cs 2 CO 3 , and dioxane. With the integration of this chemistry and our previous orthogonal methodology, the triazine library is greatly expanded to a biaryl scaffold.

An HIV-infected male patient who had sex with men and with a penicillin allergy presented with liver dysfunction due to secondary syphilis and was successfully treated with doxycycline. This case highlights that syphilitic hepatitis may be overlooked in this particular population, and health care providers should be attuned to this diagnosis. Doxycycline may be an acceptable alternative to penicillin for treatment of this clinical syndrome.

With the advent of combinatorial chemistry, heterocyclic scaffolds can be efficiently used for the generation of large member libraries. Due to the pressing need for such compound libraries, unique synthesis reactions and techniques have been developed to expedite and further improve the process. Present review article summarizes synthetic strategies for the construction of purine, pyrimidine and triazine libraries in both solution and solid phase syntheses. Typical strategy includes the nucleophilc aromatic substitution, such as amination. Also, metal-mediated synthesis has been used as a driving tool in expanding the diversity of the libraries. Demonstrated biological properties of these libraries, as a rich source of bioactivities, are also highlighted.

[reaction: see text] To improve upon the previous orthogonal method for synthesis of a triazine library, an alternative strategy has been developed via oxidation-activation of the thioether to the sulfone. Through a comparison between these two methods, the sulfone strategy was demonstrated as an enhanced method in the generation of highly pure triazine library compounds.

To expand the diversity of 1,3,5-triazine libraries to aryl and alkyl functionalities through the C–C bond, we employed a novel orthogonal synthesis via Grignard monoalkylation or monoarylation of cyanuric chloride in solution to prepare aryl- or alkyl-substituted triazine building blocks. These aryl- or alkyl-substituted triazine building blocks were captured by a resin-bound amine, followed by amination and acidic cleavage with high purity. Herein, we demonstrate a novel orthogonal synthesis of a tagged aryl- and alkyl-triazine library on solid support, utilizing building blocks prepared via Grignard reaction in solution. Through incorporation of a triethylene glycol linker at one of the alternate sites on the triazine scaffold we explored an intrinsic tagged library approach.