A comparison of clinical outcomes associated with dosing metronidazole every 8 hours versus every 12 hours: a systematic review and metaanalysis.

Background: Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around 8 hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites have led to the consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods: Using the PRISMA checklist, we searched five databases to systematically identify all relevant studies published up to June 16, 2023. Results: The final analysis included two published retrospective cohort studies of hospitalized adult patients: a single site study (n = 200) and a multisite study (n = 85) of "good" quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Metaanalysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% confidence interval: 47.6% lower to 6.4 times higher risk, P = 0.34) and inverse-variance method (risk ratio: 1.87; 95% confidence interval: 0.52-6.65, P = 0.34). Conclusions: This review suggests that dosing metronidazole every 12 hours is as effective as every-8-hour dosing for hospitalized patients with anaerobic infections. These encouraging findings would benefit from validation by a multicenter randomized controlled trial since there would be many benefits to a 12-hour dosing interval while achieving similar clinical outcomes with traditional dosing. The studies in this systematic review excluded patients with Clostridioides difficile and central nervous system and amebiasis infections, so the findings do not apply to these infection types.

Assessment of the impact of centralized bioMérieux BACT/ALERT® VIRTUO® blood culture system (VIRTUO) implementation on outcomes in patients with gram-negative bacteremia.

BACKGROUND: We evaluated pre- and postimplementation of Virtuo on outcome in patients with gram-negative bacteremia using a quasiexperimental time-in-motion design. METHODS: Becton Dickinson BACTEC™ 9000 series (Bactec) (2018) and Virtuo system (2020) were utilized in a decentralized and centralized process, respectively. Data collected in August-December in 2018 and 2020 were analyzed with SPSS (ver 28). RESULTS: For 185 patients in each time period, patient age, gender, length of hospitalization were not different. However, blood culture (BC) volume was significantly lower in 2020 (7.1 ± 2.6 mL) compared to 2018 (8.9 ± 1.9 mL). Time from BC draw and time from pathogen identification (ID) to treatment change were both significantly faster in 2020 (52.9 ± 38.3 hours; 15.1 ± 27.4 hours), compared to 2018 (65.0 ± 46.3 hours; 23.8 ± 33.8), respectively. CONCLUSIONS: Replacement of decentralized Bactec with centralized Virtuo, resulted in significant improvement in management of patients gram-negative bacteremia.

Sex and Race Disparities in Hepatocellular Carcinoma Surveillance in Patients With Chronic Hepatitis B During COVID-19: A Single-Center Retrospective Review.

Background: The management of patients with chronic hepatitis B (CHB) is complex and spans multiple medical specialties. As a result of this complexity, patients with CHB often do not receive adequate monitoring including hepatocellular carcinoma (HCC) surveillance with abdominal ultrasonography. Previous studies have identified multiple factors associated with decreased HCC surveillance. We aimed to identify the impact of race and sex on HCC surveillance in patients with CHB. Methods: We performed a single health system chart review between January 2018 and January 2022. Differences between sex and race were evaluated using the Chi-square test and Fisher's exact test, and continuous variables were analyzed using analysis of variance (ANOVA). Results: A total of 248 patient records between January 2018 and January 2022 were evaluated. In total 37% of females were adequately screened for HCC in any of the 6-month time frames compared to 26% of males. During the coronavirus disease 2019 (COVID-19) surge, surveillance rates were reduced in both men and women. During the first 6 months of the COVID-19 surge, there was a significant difference in screening between men and women (19% vs. 35%, P = 0.026). There was a decrease in HCC screening across all races during the COVID-19 surge; however, no significant difference when comparing races was found. Conclusion: Men received less HCC surveillance compared to women. These differences were more pronounced during the COVID-19 pandemic surge. Obtaining appropriate surveillance is important and retrospective evaluations can help us determine the presence of health-related social needs so that progress can be made toward achieving health equity.

Diagnosis and Outcomes of Fungal Co-Infections in COVID-19 Infections: A Retrospective Study.

The SARS-CoV-2 pandemic has resulted in a public health emergency with unique complications such as the development of fungal co-infections. The diagnosis of fungal infections can be challenging due to confounding imaging studies and difficulty obtaining histopathology. In this retrospective study, 173 patients with COVID-19 receiving antifungal therapy due to concern for fungal co-infection were evaluated. Patient characteristics, clinical outcomes, and the utility of fungal biomarkers were then evaluated for continuation of antifungal therapy. Data were collected from the electronic health record (EPIC) and analyzed using SPSS (version. 28, IBM, Inc., Armonk, NY, USA) Data are presented as mean ± SD or percentages. A total of 56 COVID-19 patients were diagnosed with fungal co-infection and 117 COVID-19 + patients had no fungal infection. Significantly fewer female patients were in the fungal+ group compared to COVID-19 control patients (29% in fungal+ compared to 51% in controls p = 0.005). Fungal diagnostics were all significantly higher in fungal+ patients. These include 1,4-beta-D-glucan (BDG), fungal culture, and bronchoalveolar lavage galactomannan (BAL GM). Intensive care unit hospitalization, mechanical ventilation, and mortality in fungal+ patients with COVID-19 were significantly higher than in control patients. Finally, significantly more fungal+ patients received voriconazole, isavuconazonium, or amphotericin B therapies, whereas control patients received significantly more short-course fluconazole. COVID-19+ patients with fungal co-infection were significantly more likely to be in the ICU and mechanically ventilated, and they result in higher mortality compared to control COVID-19 patients. The use of fungal diagnostics markers were helpful for diagnosis.

Structural Determinants of Indole-2-carboxamides: Identification of Lead Acetamides with Pan Antimycobacterial Activity.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), is one of the leading causes of death in developing countries. Non-tuberculous mycobacteria (NTM) infections are rising and prey upon patients with structural lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis. All mycobacterial infections require lengthy treatment regimens with undesirable side effects. Therefore, new antimycobacterial compounds with novel mechanisms of action are urgently needed. Published indole-2-carboxamides (IC) with suggested inhibition of the essential transporter MmpL3 showed good potency against whole-cell M.tb, yet had poor aqueous solubility. This project focused on retaining the required MmpL3 inhibitory pharmacophore and increasing the molecular heteroatom percentage by reducing lipophilic atoms. We evaluated pyrrole, mandelic acid, imidazole, and acetamide functional groups coupled to lipophilic head groups, where lead acetamide-based compounds maintained high potency against mycobacterial pathogens, had improved in vitro ADME profiles over their indole-2-carboxamide analogs, were non-cytotoxic, and were determined to be MmpL3 inhibitors.

Improving understanding and utilization of the antibiogram among medical residents.

In this quality improvement project, we sought to increase the understanding and utilization of the antibiogram among physicians in family medicine, internal medicine, and surgery residency programs at a Midwest Academic Healthcare institution. Through simple, inexpensive measures the comfort with, access to, and utilization of the antibiogram can be improved.

COVID-19 Mortality and Therapeutics in Nebraska and Southwest Iowa during Early Pandemic.

Different pharmacotherapeutics have been introduced, and then stopped or continued, for the treatment of SARS-CoV-2. We evaluated the risks associated with mortality from SARS-CoV-2 infection. METHODS: Data was concurrently or retrospectively captured on COVID-19 hospitalized patients from 6 regional hospitals within the health system. Demographic details, the source of SARS-CoV-2 infection, concomitant disease status, as well as the therapeutic agents used for treating SARS-CoV-2 (e.g., antimicrobials, dexamethasone, convalescent plasma, tocilizumab, and remdesivir) were recorded. Discrete and continuous variables were analyzed using SPSS (ver. 27). Logistic regression identified variables significantly correlated with mortality. RESULTS: 471 patients (admitted from 1 March 2020 through 15 July 2020) were reviewed. Mean (±SD) age and body weight (kg) were 62.5 ± 17.7 years and 86.3 ± 27.1 kg, respectively. Patients were Caucasian (50%), Hispanic (34%), African-American (10%), or Asian (5%). Females accounted for 52% of patients. Therapeutic modalities used for COVID-19 illness included remdesivir (16%), dexamethasone (35%), convalescent plasma (17.8%), and tocilizumab (5.8%). The majority of patients returned home (62%) or were transferred to a skilled nursing facility (23%). The overall mortality from SARS-CoV-2 was 14%. Logistic regression identified variables significantly correlated with mortality. Intubation, receipt of dexamethasone, African-American or Asian ethnicity, and being a patient from a nursing home were significantly associated with mortality (x2 = 86.36 (13) p < 0.0005). CONCLUSIONS: SARS-CoV-2 infected hospitalized patients had significant mortality risk if they were intubated, received dexamethasone, were of African-American or Asian ethnicity, or occupied a nursing home bed prior to hospital admission.

Targeted Immuno-Antiretroviral to Promote Dual Protection against HIV: A Proof-of-Concept Study.

The C-C motif chemokine receptor-5 (CCR5) expression on the T-cell surface is the prime barrier to HIV/AIDS eradication, as it promotes both active human immunodeficiency virus (HIV)-infection and latency; however, antiretrovirals (ARVs) suppress plasma viral loads to non-detectable levels. Keeping this in mind, we strategically designed a targeted ARVs-loaded nanoformulation that targets CCR5 expressing T-cells (e.g., CD4+ cells). Conceptually, CCR5-blocking and targeted ARV delivery would be a dual protection strategy to prevent HIV infection. For targeting CCR5+ T-cells, the nanoformulation was surface conjugated with anti-CCR5 monoclonal antibodies (CCR5 mAb) and loaded with dolutegravir+tenofovir alafenamide (D+T) ARVs to block HIV replication. The result demonstrated that the targeted-ARV nanoparticle's multimeric CCR5 binding property improved its antigen-binding affinity, prolonged receptor binding, and ARV intracellular retention. Further, nanoformulation demonstrated high binding affinity to CCR5 expressing CD4+ cells, monocytes, and other CCR5+ T-cells. Finally, the short-term pre-exposure prophylaxis study demonstrated that prolonged CCR5 blockage and ARV presence further induced a "protective immune phenotype" with a boosted T-helper (Th), temporary memory (TM), and effector (E) sub-population. The proof-of-concept study that the targeted-ARV nanoformulation dual-action mechanism could provide a multifactorial solution toward achieving HIV "functional cure."

Beta-Lactam vs. Fluoroquinolone Monotherapy for Pseudomonas aeruginosa Infection: A Systematic Review and Meta-Analysis.

INTRODUCTION: Pseudomonas aeruginosa (PA) is a leading cause of healthcare-associated infections. A variety of antibiotic classes are used in the treatment of PA infections, including beta-lactams (BLs) and fluoroquinolones (FQs), given either together in combination therapy or alone in monotherapy. A systematic review and meta-analysis were performed to evaluate the therapeutic efficacy of BL agents versus FQ agents as active, definitive monotherapy in PA infections in adults. METHODS: Comprehensive literature searches of the Medline and Scopus electronic databases, alongside hand searches of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar, were performed without a time restriction to identify studies published in English comparing BL and FQ agents given as monotherapy for PA infection in hospitalized adults for which mortality, bacteriological eradication, or clinical response was evaluated. One reviewer screened search results based on pre-defined selection criteria. Two reviewers independently assessed included studies for methodological quality using NIH assessment tools. Two fixed-effects meta-analyses were performed. RESULTS: A total of 368 articles were screened, and six studies involving 338 total patients were included in the meta-analysis. Upon evaluation of methodological quality, two studies were rated good, three fair, and one poor. A meta-analysis of three studies demonstrates FQ monotherapy is associated with significantly improved survival compared to BL monotherapy for patients with PA bacteremia (OR, 3.65; 95% CI, 1.27-10.44; p = 0.02). A meta-analysis of three studies demonstrates FQ monotherapy is associated with equivalent bacteriological eradication compared to BL monotherapy for PA pneumonia or skin and soft tissue infection (RD, 0.07; 95% CI, -0.09 to 0.24; p = 0.39). CONCLUSION: The meta-analyses demonstrate FQ monotherapy significantly improves survival in PA bacteremia and is associated with similar rates of bacteriological eradication in pneumonia and skin and soft tissue infection caused by PA compared to BL monotherapy. However, more research is needed to make meaningful clinical recommendations.

Bamlanivimab use in mild-to-moderate COVID-19 disease: A matched cohort design.

STUDY OBJECTIVE: Our objective was to determine if bamlanivimab (LY-CoV555; BAM), a monoclonal antibody for mild-to-moderate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2, prevented emergency department (ED) visits, hospitalizations for SARS-CoV-2, or death within 60 days of a positive SARS-CoV-2 viral test. DESIGN: Patient propensity matching was performed for BAM administration to get two discrete groups of patients; those who received BAM (N = 117) and those who did not (N = 117). SETTING: Outpatients (N = 2107) eligible to receive BAM from November 1 to December 31, 2020, were identified. PATIENTS: A total of 144 of 2107 patients with mild-to-moderate SARS-CoV-2 received BAM INTERVENTION: Eligible patients had mild-to-moderate SARS-CoV-2 disease, a positive SARS-CoV-2 test, and risk factor(s) for progression to severe SARS-CoV-2 infection. All patients were reviewed for subsequent ED visits, subsequent hospitalization, and death. MEASUREMENTS AND MAIN RESULTS: Patients (N = 234) were matched, 117 in each group. Median (interquartile range) age was 72 (65-80) years. Forty-seven percent of patients were male. Twenty-one patients who received BAM were subsequently seen in the ED compared to 34 untreated patients (18.0% vs. 29.1%; p = 0.045). Fourteen BAM-treated patients were subsequently hospitalized post-BAM infusion compared to 27 untreated patients (12.0% vs. 23.1%; p = 0.025). Finally, there were no mortalities in the BAM group, however, eleven patients in the untreated group died (0.0% vs. 9.4%; p < 0.001). The number needed to treat (NNT) is 11 patients to prevent one mortality event. CONCLUSIONS: BAM infusion for mild-to-moderate SARS-CoV-2 infection in outpatients significantly prevented subsequent ED visits, hospitalizations, and death from SARS-CoV-2.

A Concept Evaluation Study of a New Combination Bictegravir plus Tenofovir Alafenamide Nanoformulation with Prolonged Sustained-Drug-Release Potency for HIV-1 Preexposure Prophylaxis.

The antiretroviral treatment (ART) approach is the best-prescribed approach to date for preexposure prophylaxis (PrEP) for high-risk individuals. However, the daily combination antiretroviral (cARV) regimen has become cumbersome for healthy individuals, leading to nonadherence. Recent surveys showed high acceptance of parenteral sustained-release ART enhancing PrEP adherence. Our approach is to design a parenteral nanoparticle (NP)-based cARV sustained-release (cARV-SR) system as long-acting HIV PrEP. Here, we report a new combination of two potent ARVs (tenofovir alafenamide fumarate [TAF] and bictegravir [BIC]) loaded as a nanoformulation intended as a cARV-SR for PrEP. The BIC+TAF NPs were fabricated by using a standardized in-house methodology. In vitro intracellular kinetics, cytotoxicity, and HIV-1 protection studies demonstrated that BIC+TAF encapsulation prolonged drug retention, reduced drug-associated cytotoxicity, and enhanced HIV protection. In human peripheral blood mononuclear cells, nanoformulated BIC+TAF demonstrated significant (P < 0.05) improvement in the drug's selectivity index by 472 times compared to the BIC+TAF in solution. In vivo pharmacokinetic study of BIC, TAF, and respective drug metabolites in female BALB/c mice after single subcutaneous doses of BIC+TAF NPs demonstrated plasma drug concentrations of BIC and tenofovir above the intracellular 50% inhibitory concentration during the entire 30-day study period and prolonged persistence of both active drugs in the HIV target organs, including the vagina, colon, spleen, and lymph nodes. This report demonstrates that the encapsulation of BIC+TAF in a nanoformulation improved its therapeutic selectivity and the in vivo pharmacokinetics of free drugs. Based on these preliminary studies, we hypothesize that cARV-SR has potential as an innovative once-monthly delivery treatment for PrEP.

Bictegravir Plus Tenofovir Alafenamide Nanoformulation as a Long-Acting Pre-Exposure Prophylaxis Regimen: Application of Modeling to Design Non-Human Primate Pharmacokinetic Experiments.

Bictegravir (BIC) and tenofovir alafenamide fumarate (TAF), two potent anti-HIV drugs, had been nanoformulated (nBIC-TAF) to achieve once-a-month PrEP coverage. In-vivo mouse experiments for nBIC-TAF exhibited favorable subcutaneous (SC) pharmacokinetics. To probe the clinical suitability of the nBIC-TAF, as the next step, we intend to study nBIC-TAF in non-human primates (NHP), as the best preclinical model to foster clinical trials. Before entering an expensive NHP study, however, we seek to improve our a priori understanding about nBIC-TAF in higher species, having just mouse data. The mechanism-based pharmacokinetic modeling (MBPK) has been used as an appropriate method for pharmacokinetic modeling and interspecies scaling for nanoformulations. Via the use of MBPK, in this work, we created a model for nBIC-TAF able to predict plasma concentration-time curves in NHP. BIKTARVY is a daily oral combination of BIC, TAF, and emtricitabine (Gilead Science, CA), approved for HIV therapy. Using BIKTARVY equivalent dosages (from their NHP studies), we predicted that, following just one SC dose of nBIC-TAF in NHP, both BIC and tenofovir will have detectable and above in vitro efficacy levels for 28 days. Furthermore, the MBPK was able to provide a mechanistic explanation regarding the long-acting mechanism characterizing nBIC-TAF: nanoparticles stores in the SC space from which drugs slowly dissociate. Dissociated drugs in the SC space then buffer the plasma pool over time, yielding an extended-release effect in the plasma. Overall, we predicted for nBIC-TAF a promising long-acting pharmacokinetic in NHP, potentially usable as monthly PrEP. These results will help investigators to gain confidence for facing regulatory submissions at early stages.

Implementation of a Health-System Wide Antimicrobial Stewardship Program in Omaha, NE.

The Centers for Medicare and Medicaid Services (CMS) have mandated that acute care and critical access hospitals implement an Antimicrobial Stewardship (AMS) Program. This manuscript describes the process that was implemented to ensure CMS compliance for AMS, across a 14-member health system (eight community hospitals, five critical access hospitals, and an academic medical center) in the Omaha metro area, and surrounding cities. The addition of the AMS program to the 14-member health system increased personnel, with a 0.5 full-time equivalent (FTE) infectious diseases (ID) physician, and 2.5 FTE infectious diseases trained clinical pharmacists to support daily AMS activities. Clinical decision support software had previously been implemented across the health system, which was also key to the success of the program. Overall, in its first year, the AMS program demonstrated a $1.2 million normalized reduction (21% total reduction in antimicrobial purchases) in antimicrobial expenses. The ability to review charts daily for antimicrobial optimization with ID pharmacist and physician support, identify facility specific needs and opportunities, and to collect available data endpoints to determine program effectiveness helped to ensure the success of the program.

Effect of antimicrobial stewardship with rapid MALDI-TOF identification and Vitek 2 antimicrobial susceptibility testing on hospitalization outcome.

We sought to evaluate time for bacterial culture and initiation of appropriate therapy for patients, from 2017 (without rapid diagnostic test (RDT) and Antimicrobial Stewardship Program (ASP)) and 2018 (with RDT and ASP). Time to identification (ID) was significantly faster in 2018 (2018 24.9 ±â€¯14.4, 2017 33.8 ±â€¯17 h, P = 0.001). Time to antimicrobial susceptibility test (AST) results was significantly faster for patients in 2018 compared to 2017 (18.2 ±â€¯14 h compared to 28.5 ±â€¯14.9 h, P < 0.001). Length of hospital stay for enrolled patients was significantly shorter in 2018 compared to 2017 (2018 10.7 ±â€¯11.1 days and 2017 15.5 ±â€¯18.1 days, P = 0.05). Length of antimicrobial therapy for enrolled patients was significantly shorter for 2018 (2018 6.7 ±â€¯3.8 d vs. 2017 8.8 ±â€¯7.8 d, P = 0.036). These results demonstrate MALDI-TOF/Vitek 2 leads to an average 21.5 h faster ID and AST results that can be acted upon by ASP for antimicrobial recommendations.

Correction to: Pharmacokinetic and Tissue Distribution Profile of Long Acting Tenofovir Alafenamide and Elvitegravir Loaded Nanoparticles in Humanized Mice Model.

There are errors in the published article (Volume 34, Number 12, pp. 2749-2755). The errors occurred in pharmacokinetic study design of materials and methods section on page 2750-51.

A potential long-acting bictegravir loaded nano-drug delivery system for HIV-1 infection: A proof-of-concept study.

Bictegravir (BIC), a newly FDA-approved integrase strand transfer inhibitor (INSTI), as a single tablet regimen has proven efficacious in treating HIV-1 and SIV viruses, with reduced resistance. BIC clinical trials have not investigated its prophylaxis potency. This study investigates the HIV prevention potency of a novel long-acting BIC nano-formulation aimed to improve adherence. Poly (lactic-co-glycolic acid) loaded BIC nanoparticles (BIC NPs) were formulated using an oil-in-water emulsion methodology. BIC NPs were <200 nm in size, with 47.9 ±â€¯6.9% encapsulation efficiency. A novel, sensitive and high throughput LC-MS/MS method was used to estimate intracellular pharmacokinetics (PK) of BIC NPs and compared to BIC solution demonstrated prolonged intracellular BIC retention. BIC NPs safety was assessed based on cytotoxicity. Further, in-vitro prevention study of BIC NPs vs BIC solution was assessed against HIV-1NLX and HIV-1ADA on TZM-bl cell line and PBMCs, respectively. BIC nanoencapsulation demonstrated elevated cellular cytotoxicity concentration (CC50: 2.25 µM (BIC solution) to 820.4 µM (BIC NPs)] and lowers HIV-1 inhibitory concentration [EC50: 0.604 µM (BIC solution) to 0.0038 µM (BIC NPs)) thereby improving selectivity index (SI) from 3.7 (BIC solution) to 215,789 (BIC NP) for TZM-bl cells. Comparable results in PBMCs were obtained where BIC NPs improved SI from 0.29 (BIC solution) to 523.33 (BIC NPs). This demonstrates long-acting BIC nano-formulation with sustained drug-release potency, improved BIC cytotoxicity and enhanced HIV-1 protection compared to BIC in solution.

A review of CCR5 antibodies against HIV: current and future aspects.

HIV is one of the most devastating viral infections the world has ever encountered. Ever since HIV was first identified in the 1980s, it has claimed millions of lives worldwide. There has been tremendous research and development in the diagnosis, prevention and treatment of HIV. Small molecules have been shown to reduce the virus to nondetectable level in human plasma, however, there are reservoirs of latent virus that reemerge if antiretroviral therapy is stopped. There is no vaccine to prevent or cure HIV. A significant amount of research has been reported in the literature regarding antibodies for CCR5, a HIV entry host receptor. This report describes the role of CCR5 antibody in HIV prevention/treatment and how antibody-conjugated nanoparticles could be a future strategy with the potential to effectively eradicate the virus from the human system.

Ceftaroline fosamil for the treatment of Gram-positive endocarditis: CAPTURE study experience.

BACKGROUND: The clinical experience of ceftaroline fosamil (CPT-F) therapy for Gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the USA. METHODS: Data, including patient demographics, medical history, risk factors, microbiological aetiology and clinical outcomes, were collected by review of patient charts between September 2013 and February 2015. RESULTS: Patients (n=55) with Gram-positive endocarditis were treated with CPT-F. The most common risk factors were intravascular devices (43.6%), diabetes mellitus (40.0%) and injection drug use (38.2%). The most commonly isolated pathogens were meticillin-resistant Staphylococcus aureus (MRSA; 80%), meticillin-susceptible S. aureus (MSSA; 7.3%) and coagulase-negative staphylococci (7.3%). CPT-F was given as first-line therapy in 7.3% of patients and as second-line or later therapy in 92.7% of patients, and as monotherapy in 41.8% of patients and as concurrent therapy in 58.2% of patients. Clinical success was observed in 82.6% (19/23) of patients treated with CPT-F as monotherapy. In patients treated with CPT-F as first-line therapy or second-line or later therapy, 75.0% (3/4) and 70.6% (36/51) achieved success, respectively. Clinical success was observed in 77.3% (34/44) of patients with MRSA and 25% (1/4) of patients with MSSA. Two patients discontinued treatment with CPT-F due to an adverse event. CONCLUSIONS: CPT-F treatment was associated with a high rate of clinical success in patients with Gram-positive infective endocarditis, including those with risk factors and infections caused by MRSA. A high rate of clinical success was observed in patients treated with CPT-F used as first- line therapy or second-line or later therapy, or as monotherapy or in combination with other antibiotics.

Indole-2-Carboxamides Are Active against Mycobacterium abscessus in a Mouse Model of Acute Infection.

Nontuberculous mycobacteria (NTM) pathogens particularly infect patients with structural lung disorders. We previously reported novel indole-2-carboxamides (ICs) that are active against a wide panel of NTM pathogens. This study discloses in vivo data for two lead molecules (compounds 5 and 25) that were advanced for efficacy studies in Mycobacterium abscessus-infected mouse models. Oral administration of the lead molecules showed a statistically significant reduction in the bacterial loads in lung and spleen of M. abscessus-infected mice.