A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

Gut microbiome and its clinical implications: exploring the key players in human health.

PURPOSE OF REVIEW: The human gut harbors a diverse community of microorganisms known as the gut microbiota. Extensive research in recent years has shed light on the profound influence of the gut microbiome on human health and disease. This review aims to explore the role of the gut microbiome in various clinical conditions and highlight the emerging therapeutic potential of targeting the gut microbiota for disease management. RECENT FINDINGS: Knowledge of the influence of gut microbiota on human physiology led to the development of various therapeutic possibilities such as fecal microbiota transplant (FMT), phage therapy, prebiotics, and probiotics. Recently, the U.S. FDA approved two FMT products for the treatment of recurrent Clostridioides difficile infection with ongoing research for the treatment of various disease conditions. SUMMARY: Advancement in the knowledge of the association between gut microbiota and various disease processes has paved the way for novel therapeutics.

Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 U.S. States, February 2022-May 2023.

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 U.S. States, February 1, 2022-January 31, 2023.

As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

COVID-19: disease pathways and gene expression changes predict methylprednisolone can improve outcome in severe cases.

MOTIVATION: COVID-19 has several distinct clinical phases: a viral replication phase, an inflammatory phase and in some patients, a hyper-inflammatory phase. High mortality is associated with patients developing cytokine storm syndrome. Treatment of hyper-inflammation in these patients using existing approved therapies with proven safety profiles could address the immediate need to reduce mortality. RESULTS: We analyzed the changes in the gene expression, pathways and putative mechanisms induced by SARS-CoV2 in NHBE, and A549 cells, as well as COVID-19 lung versus their respective controls. We used these changes to identify FDA approved drugs that could be repurposed to help COVID-19 patients with severe symptoms related to hyper-inflammation. We identified methylprednisolone (MP) as a potential leading therapy. The results were then confirmed in five independent validation datasets including Vero E6 cells, lung and intestinal organoids, as well as additional patient lung sample versus their respective controls. Finally, the efficacy of MP was validated in an independent clinical study. Thirty-day all-cause mortality occurred at a significantly lower rate in the MP-treated group compared to control group (29.6% versus 16.6%, P = 0.027). Clinical results confirmed the in silico prediction that MP could improve outcomes in severe cases of COVID-19. A low number needed to treat (NNT = 5) suggests MP may be more efficacious than dexamethasone or hydrocortisone. AVAILABILITY AND IMPLEMENTATION: iPathwayGuide is available at https://advaitabio.com/ipathwayguide/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Utility of microbiologic testing in surveillance bronchoscopy following lung transplantation: A retrospective cohort study.

BACKGROUND: The utility of surveillance bronchoscopy (SB) for the clinical management of lung transplant recipients (LTRs) is undefined. This study evaluates the role of SB in the monitoring and care of LTRs. METHODS: We retrospectively analyzed all LTRs who had SB at Henry Ford Hospital in Detroit, Michigan between August 2014 and August 2019. Bronchoscopies performed for clinical symptoms, new radiographic abnormalities, and to assess stents or acute rejection were excluded. A total of 107 LTRs and 449 bronchoscopies were analyzed. The primary outcome was the rate of change in clinical care based on microbiologic and pathologic test results. Secondary outcomes were rates of microbiologic and pathologic test positivity and rates of adverse effects. RESULTS: The most common microbiologic tests performed on bronchoalveolar lavage were bacterial (96.9%), fungal (95.3%), and acid-fast bacillus (95.1%) stains and cultures. Of 2560 microbiologic tests, 22.0% were positive and resulted in therapy changes for 2.9%. Positive galactomannan, acid-fast bacillus tests, and Pneumocystis jirovecii antigen/polymerase chain reaction did not result in therapy changes. Of the 370 transbronchial biopsies performed, 82.2% were negative for acute rejection and 13% were positive for A1/A2 rejection. Immunosuppressive therapy changes occurred after 15.8% with reduction in immunosuppression due to positive microbiologic tests in 16.9%. Adverse events occurred in 8.0% of patients. CONCLUSION: Diagnostic stewardship is warranted when performing SB in LTRs.

Bridging the gap: An approach to reporting antimicrobial stewardship metrics specific to solid organ transplant recipients.

BACKGROUND: This study seeks to describe inpatient antimicrobial use (AU) utilizing the National Healthcare Safety Network-AU (NHSN-AU) framework among solid organ transplant recipients (SOTr) within 12 months after transplant. METHODS: This cross-sectional study included SOTr ≥ 18 years of age who underwent transplantation from January 2015 to December 2016 at a Midwestern US transplant center. Inpatient AU was followed for 12 months post-transplant. Hospital days present up to 12 months post-transplant, AU variables, and Clostridioides difficile infection (CDI) occurrences were analyzed. RESULTS: The cohort of 530 SOTr included 225 kidney (42.5%), 171 liver (32.3%), 45 lung (8.5%), 40 heart (7.5%), 39 multivisceral (7.4%), seven small bowel (1.3%), and three pancreas (0.6%) transplants. Total days of therapy (DOT) were 22 782 among the cohort, with a median of 5 days [interquartile range [IQR], 1-12]. Lung and liver transplants had the most total DOT (6571 vs. 5569 days), while lungs and small bowels had the highest median DOT (13 [IQR, 2-56] vs. 12 [IQR, 2-31]). The facility-wide DOT/1000 days were lowest in pancreas and highest in lung transplants (5.3 vs. 428.1). Small bowel transplants received the most resistant-Gram-positive infection and hospital-onset infection agents for facility-wide DOT/1000 days present. Pancreas and kidney transplants accounted for the most high-risk CDI agents. CDI occurred in 34 patients, with kidney and liver transplants experiencing 13 each. CONCLUSION: This study represents one of the first reports of AU in SOTr utilizing the NHSN-AU framework. More studies are needed for further peer-to-peer comparison of AU in this complex patient population.

SARS-CoV-2 neutralizing antibodies for COVID-19: Outcomes for bamlanivimab versus bamlanivimab-etesevimab combination in a racially diverse cohort of patients with significant comorbidities.

WHAT IS KNOWN AND OBJECTIVE: Anti-spike monoclonal antibodies (MAB) including bamlanivimab (BAM) and bamlanivimab/etesevimab (BAM/E) have shown reduced hospitalization rates for non-severe coronavirus disease 2019 (COVID-19) in clinical trials. Recent data have provided real-world hospitalization rates for high-risk patients treated with BAM, however, data on a similar cohort treated with BAM/E are lacking. METHODS: This retrospective cohort study evaluated outpatients ≥18 years with laboratory-confirmed mild/moderate COVID-19 who received MAB from 1 December 2020 to 19 April 2021. Use of BAM monotherapy changed to BAM/E combination on 27 March 2021. Primary outcome was overall rate of COVID-19 related-hospitalization, including comparison of hospitalization rates between MAB-formulation groups. Secondary outcomes were 30-day mortality and length of stay (LOS). RESULTS AND DISCUSSION: The population included 643 patients (BAM and BAM/E); median age was 58 years, 43% were male, median BMI was 33 kg/m2 , and 24% self-identified as Black. Patients in the BAM/E combination group were significantly younger with higher median BMI and a longer time from symptom onset to infusion. The incidence of 30-day COVID-19 related hospitalization was similar between patients receiving either BAM or BAM/E combination (7.8% and 7.2%, respectively). WHAT IS NEW AND CONCLUSION: This study represents the first such publication of real-world BAM/E hospitalization outcomes. Hospitalization rates utilizing BAM/E were comparable to BAM in our real-world study.

Rapid Reorganization of an Academic Infectious Diseases Program During the Coronavirus Disease 2019 Pandemic in Detroit: A Novel Unit-based Group Rounding Model.

The surge of coronavirus disease 2019 (COVID-19) hospitalizations at our 877-bed quaternary care hospital in Detroit led to an emergent demand for Infectious Diseases (ID) consultations. The traditional 1-on-1 consultation model was untenable. Therefore, we rapidly restructured our ID division to provide effective consultative services. We implemented a novel unit-based group rounds model that focused on delivering key updates to teams and providing unit-wide consultations simultaneously to all team members. Effectiveness of the program was studied using Likert-scale survey data. The survey captured data from the first month of the Detroit COVID-19 pandemic. During this period there were approximately 950 patients hospitalized for treatment of COVID-19. The survey of trainees and faculty reported an overall 95% positive response to delivery of information, new knowledge acquisition, and provider confidence in the care of COVID-19 patients. This showed that the unit-based consult model is a sustainable effort to provide care during epidemics.

Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well described. METHODS: We performed a multicenter cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients. RESULTS: Four hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (interquartile range [IQR] 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [adjusted odds ratio [aOR] 3.0, 95% confidence interval [CI] 1.7-5.5, P < .001], congestive heart failure [aOR 3.2, 95% CI 1.4-7.0, P = .004], chronic lung disease [aOR 2.5, 95% CI 1.2-5.2, P = .018], obesity [aOR 1.9, 95% CI 1.0-3.4, P = .039]) and presenting findings (lymphopenia [aOR 1.9, 95% CI 1.1-3.5, P = .033], abnormal chest imaging [aOR 2.9, 95% CI 1.1-7.5, P = .027]) were independently associated with mortality. Multiple measures of immunosuppression intensity were not associated with mortality. CONCLUSIONS: Mortality among SOT recipients hospitalized for COVID-19 was 20.5%. Age and underlying comorbidities rather than immunosuppression intensity-related measures were major drivers of mortality.

Systematic review and meta-analysis of effectiveness of treatment options against SARS-CoV-2 infection.

Treatment options for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) are limited with no clarity on efficacy and safety profiles. We performed a systematic review and meta-analysis of studies on patients ≥18 years reporting data on therapeutic interventions in SARS-CoV-2. Primary outcome was all-cause mortality and secondary outcomes were rates of mechanical ventilation, viral clearance, adverse events, discharge, and progression to severe disease. Pooled rates and odds ratios (OR) were calculated. Twenty-nine studies with 5207 patients were included. Pooled all-cause mortality in intervention arm was 12.8% (95% confidence interval [CI]: 8.1%-17.4%). Mortality was significantly higher for studies using hydroxychloroquine (HCQ) for intervention (OR: 1.36; 95% CI: 0.97-1.89). Adverse events were also higher in HCQ subgroup (OR: 3.88; 95% CI: 1.60-9.45). There was no difference in other secondary outcomes. There is a need for well-designed randomized clinical trials for further investigation of every therapeutic intervention for further insight into different therapeutic options.

Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19.

BACKGROUND: There is no proven antiviral or immunomodulatory therapy for coronavirus disease 2019 (COVID-19). The disease progression associated with the proinflammatory host response prompted us to examine the role of early corticosteroid therapy in patients with moderate to severe COVID-19. METHODS: We conducted a single pretest, single posttest quasi-experiment in a multicenter health system in Michigan from 12 March to 27 March 2020. Adult patients with confirmed moderate to severe COVID were included. A protocol was implemented on 20 March 2020 using early, short-course, methylprednisolone 0.5 to 1 mg/kg/day divided in 2 intravenous doses for 3 days. Outcomes of standard of care (SOC) and early corticosteroid groups were evaluated, with a primary composite endpoint of escalation of care from ward to intensive care unit (ICU), new requirement for mechanical ventilation, and mortality. All patients had at least 14 days of follow-up. RESULTS: We analyzed 213 eligible subjects, 81 (38%) and 132 (62%) in SOC and early corticosteroid groups, respectively. The composite endpoint occurred at a significantly lower rate in the early corticosteroid group (34.9% vs 54.3%, P = .005). This treatment effect was observed within each individual component of the composite endpoint. Significant reduction in median hospital length of stay was also observed in the early corticosteroid group (5 vs 8 days, P < .001). Multivariate regression analysis demonstrated an independent reduction in the composite endpoint at 14-days controlling for other factors (adjusted odds ratio: 0.41; 95% confidence interval, .22 - .77). CONCLUSIONS: An early short course of methylprednisolone in patients with moderate to severe COVID-19 reduced escalation of care and improved clinical outcomes. CLINICAL TRIALS REGISTRATION: NCT04374071.

Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study.

Solid organ transplant recipients (SOTr) with coronavirus disease 2019 (COVID-19) are expected to have poorer outcomes compared to nontransplant patients because of immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 nonkidney organs) were compared to 100 consecutive hospitalized nontransplant controls. Twelve of 47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs 57% P = .0007), diabetes (66% vs 33% P = .0007), and hypertension (94% vs 72% P = .006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs 17%, P < .0001) was more frequent in SOTr. Primary composite outcome (escalation to intensive care unit, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs 48%, odds ratio [OR] 0.72 confidence interval [CI] [0.33-1.58] P = .42), despite more comorbidities in SOTr. Acute kidney injury requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] P = .007). Multivariate analysis demonstrated that increasing age and clinical severity were associated with mortality. Transplant status itself was not associated with mortality.

Activity of cefepime/zidebactam against MDR Escherichia coli isolates harbouring a novel mechanism of resistance based on four-amino-acid inserts in PBP3.

BACKGROUND: Recent reports reveal the emergence of Escherichia coli isolates harbouring a novel resistance mechanism based on four-amino-acid inserts in PBP3. These organisms concomitantly expressed ESBLs or/and serine-/metallo-carbapenemases and were phenotypically detected by elevated aztreonam/avibactam MICs. OBJECTIVES: The in vitro activities of the investigational antibiotic cefepime/zidebactam and approved antibiotics (ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam and others) were determined against E. coli isolates harbouring four-amino-acid inserts in PBP3. METHODS: Whole-genome sequenced E. coli isolates (n = 89) collected from a large tertiary care hospital in Southern India (n = 64) and from 12 tertiary care hospitals located across India (n = 25) during 2016-18, showing aztreonam/avibactam MICs ≥1 mg/L (≥4 times the aztreonam epidemiological cut-off) were included in this study. The MICs of antibiotics were determined using the reference broth microdilution method. RESULTS: Four-amino-acid inserts [YRIK (n = 30) and YRIN (n = 53)] were found in 83/89 isolates. Among 83 isolates, 65 carried carbapenemase genes [blaNDM (n = 39), blaOXA-48-like (n = 11) and blaNDM + blaOXA-48-like (n = 15)] and 18 isolates produced ESBLs/class C ß-lactamases only. At least 16 unique STs were noted. Cefepime/zidebactam demonstrated potent activity, with all isolates inhibited at ≤1 mg/L. Comparator antibiotics including ceftazidime/avibactam and imipenem/relebactam showed limited activities. CONCLUSIONS: E. coli isolates concurrently harbouring four-amino-acid inserts in PBP3 and NDM are an emerging therapeutic challenge. Assisted by the PBP2-binding action of zidebactam, the cefepime/zidebactam combination overcomes both target modification (PBP3 insert)- and carbapenemase (NDM)-mediated resistance mechanisms in E. coli.

Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab.

Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. This was a retrospective observational cohort study conducted at a five hospital health system in Michigan, United States. Adult patients with confirmed COVID-19 that were admitted to the hospital and received tocilizumab for cytokine storm from March 1, 2020 through April 3, 2020 were included. Patients were grouped into survivors and non-survivors based on 28 day in-hospital mortality. Study day 0 was defined as the day tocilizumab was administered. Factors independently associated with in-hospital survival at 28 days after tocilizumab administration were assessed. Epidemiologic, demographic, laboratory, prognostic scores, treatment, and outcome data were collected and analyzed. Clinical response was collected and defined as a decline of two levels on a six-point ordinal scale of clinical status or discharged alive from the hospital. Of the 81 patients included, the median age was 64 (58-71) years and 56 (69.1%) were male. The 28 day in-hospital mortality was 43.2%. There were 46 (56.8%) patients in the survivors and 35 (43.2%) in the non-survivors group. On study day 0 no differences were noted in demographics, clinical characteristics, severity of illness scores, or treatments received between survivors and non-survivors. C-reactive protein was significantly higher in the non-survivors compared to survivors. Compared to non-survivors, recipients of tocilizumab within 12 days of symptom onset was independently associated with survival (adjusted OR: 0.296, 95% CI: 0.098-0.889). SOFA score ≥8 on day 0 was independently associated with mortality (adjusted OR: 2.842, 95% CI: 1.042-7.753). Clinical response occurred more commonly in survivors than non-survivors (80.4% vs. 5.7%; p < 0.001). Improvements in the six-point ordinal scale and SOFA score were observed in survivors after tocilizumab. Early receipt of tocilizumab in patients with severe COVID-19 was an independent predictor for in-hospital survival at 28 days.

Proceeding report of the Second Symposium on Hidradenitis Suppurativa Advances (SHSA) 2017.

The 2nd Annual Symposium on Hidradenitis Suppurativa Advances (SHSA) took place on 03-05 November 2017 in Detroit, Michigan, USA. This symposium was a joint meeting of the Hidradenitis Suppurativa Foundation (HSF Inc.) founded in the USA, and the Canadian Hidradenitis Suppurativa Foundation (CHSF). This was the second annual meeting of the SHSA with experts from different disciplines arriving from North America, Europe and Australia, in a joint aim to discuss most recent innovations, practical challenges and potential solutions to issues related in the management and care of Hidradenitis Suppurativa patients. The last session involved clinicians, patients and their families in an effort to educate them more about the disease.

Outcomes of Fecal Microbiota Transplantation for Clostridium difficile Infection in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) has recently been shown to be a promising therapy for recurrent and refractory Clostridium difficile infections (CDI) despite lack of protocol standardization. Patients with inflammatory bowel disease (IBD) present a particular challenge to CDI therapy as they are reported to have worse clinical outcomes, including higher colectomy rates and increased mortality. We aimed to assess the outcomes of FMT for recurrent CDI in patients with IBD at our healthcare system. METHODS: We constructed a retrospective cohort of all patients who underwent FMT at our healthcare system between December 2012 and May 2014. Patients with concurrent IBD were identified. We evaluated the differences in demographic and clinical characteristics, along with the outcomes to FMT between patients with IBD as compared to the general population. RESULTS: Over the study period, 201 patients underwent FMT of which 20 patients had concurrent IBD. Patients with IBD were younger but did not differ from the general population in terms of CDI risk factors or disease severity. The response to FMT and rate of CDI relapse in the IBD group were not statistically different compared to the rest of the cohort. The overall response rate in the IBD population was 75% at 12 weeks. Of the patients who failed FMT 4 of 5 patients had active or untreated IBD. CONCLUSION: Fecal microbiota transplantation provides a good alternative treatment option with high success rates for recurrent or refractory Clostridium difficile infection in patients with well-controlled IBD who fail standard antimicrobial therapy.