A comparison of strategies for identifying patients at risk for carbapenem-resistant or extended ß-lactam-resistant Pseudomonas aeruginosa.

OBJECTIVES: To assess risk factors for carbapenem-resistant Pseudomonas aeruginosa (CR) and extended-ß-lactam-resistant P. aeruginosa (EBR) infection/colonization, and to develop and compare tools for predicting isolation of CR and EBR from clinical cultures. METHODS: This retrospective study analysed hospitalized patients with positive P. aeruginosa cultures between 2015 and 2021. Two case-control analyses were performed to identify risk factors and develop scoring tools for distinguishing patients with CR versus carbapenem-susceptible (CS) P. aeruginosa and EBR versus CS P. aeruginosa. The performance of institutionally derived scores, externally derived scores and the presence/absence of key risk factors to predict CR and EBR were then compared. RESULTS: A total of 2379 patients were included. Of these, 8.3% had a positive culture for CR, 5.0% for EBR and 86.7% for CS P. aeruginosa. There was substantial overlap in risk factors for CR and EBR. Institutional risk scores demonstrated modestly higher area under the ROC curve values than external scores for predicting CR (0.67 versus 0.58) and EBR (0.76 versus 0.70). Assessing the presence/absence of ≥1 of the two strongest predictors (prior carbapenem use or CR isolation within 90 days) was slightly inferior to scoring tools for predicting CR, and comparable for predicting EBR. CONCLUSIONS: Clinicians concerned about CR in P. aeruginosa should consider the likelihood of EBR when making treatment decisions. A simple approach of assessing recent history of CR isolation or carbapenem usage performed similarly to more complex scoring tools and offers a more pragmatic way of identifying patients who require coverage for resistant P. aeruginosa.

Epidemiology, clinical features and outcomes of hospitalized patients with COVID-19 by vaccination status: a multicenter historical cohort study.

INTRODUCTION: COVID-19 disease resulted in over six million deaths worldwide. Although vaccines against SARS-CoV-2 demonstrated efficacy, breakthrough infections became increasingly common. There is still a lack of data regarding the severity and outcomes of COVID-19 among vaccinated compared to unvaccinated individuals. METHODS: This was a historical cohort study of adult COVID-19 patients hospitalized in five Ascension hospitals in southeast Michigan. Electronic medical records were reviewed. Vaccine information was collected from the Michigan Care Improvement Registry. Data were analyzed using Student's t-test, analysis of variance, the chi-squared test, the Mann-Whitney and Kruskal-Wallis tests, and multivariable logistic regression. RESULTS: Of 341 patients, the mean age was 57.9 ± 18.3 years, 54.8% (187/341) were female, and 48.7% (166/341) were black/African American. Most patients were unvaccinated, 65.7%, 8.5%, and 25.8% receiving one dose or at least two doses, respectively. Unvaccinated patients were younger than fully vaccinated (p = 0.001) and were more likely to be black/African American (p = 0.002). Fully vaccinated patients were 5.3 times less likely to have severe/critical disease (WHO classification) than unvaccinated patients (p < 0.001) after controlling for age, BMI, race, home steroid use, and serum albumin levels on admission. The case fatality rate in fully vaccinated patients was 3.4% compared to 17.9% in unvaccinated patients (p = 0.003). Unvaccinated patients also had higher rates of complications. CONCLUSIONS: Patients who were unvaccinated or partially vaccinated had more in-hospital complications, severe disease, and death as compared to fully vaccinated patients. Factors associated with severe COVID-19 disease included advanced age, obesity, low serum albumin, and home steroid use.

Molnupiravir and Nirmatrelvir-Ritonavir: Oral Coronavirus Disease 2019 Antiviral Drugs.

At a crucial time with rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant globally, the United States Food and Drug Administration has issued an emergency use authorization for 2 oral antivirals, molnupiravir (in persons aged ≥18 years) and nirmatrelvir-ritonavir (Paxlovid) (in persons aged ≥12 years weighing ≥40 kg), for the outpatient treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is a human immunodeficiency virus type 1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within 5 days of symptoms onset and given for 5 days' duration. This article reviews the 2 oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.

In vitro activity of fosfomycin alone and in combination against Staphylococcus aureus with reduced susceptibility or resistance to methicillin, vancomycin, daptomycin or linezolid.

OBJECTIVES: To evaluate the activity of fosfomycin against a group of MRSA strains, including isolates with reduced susceptibility or resistance to vancomycin, daptomycin, linezolid and ceftaroline and to determine the effect of combining various combinations of antimicrobial agents used in the therapy of serious Gram-positive infections. METHODS: Broth microdilution testing was used to determine the MICs of fosfomycin, vancomycin, daptomycin, linezolid, ceftaroline and cefazolin. Isolates were selected for further evaluations to determine in vitro synergy between fosfomycin and select antimicrobial agents using chequerboard broth microdilution testing. Fosfomycin was tested in combination with vancomycin, linezolid, daptomycin, ceftaroline and cefazolin. RESULTS: Fosfomycin maintained activity against 100% of strains of vancomycin-resistant Staphylococcus aureus (VRSA) and linezolid-resistant S. aureus (LRSA), 86% of VISA and 95% of daptomycin-resistant S. aureus (DRSA) strains. The combination of fosfomycin with ceftaroline consistently demonstrated synergy among all 18 isolates against the strains tested. The next most potent combination regimen was linezolid with fosfomycin, which demonstrated synergy in 16 of the 18 strains. Daptomycin demonstrated synergy in only 7 of the 18 strains tested when combined with fosfomycin. Cefazolin demonstrated synergy in 6 of 6 strains and vancomycin demonstrated no interaction in 6 of 6 strains tested. CONCLUSIONS: Fosfomycin demonstrated excellent activity against MRSA as well as isolates with resistance or reduced activity to other anti-MRSA drugs including vancomycin, daptomycin and linezolid. When combined with linezolid or daptomycin, fosfomycin demonstrated synergy for all or most strains tested. Thus, these combinations may have potential clinical utility when treating patients with serious infections caused by MRSA.

The American Board of Internal Medicine's New Longitudinal Assessment Option and What It Means for Infectious Disease Specialists.

As members of the American Board of Internal Medicine's (ABIM) Infectious Disease (ID) Board we've heard from many of our colleagues asking for greater flexibility in maintaining their ABIM Board Certification. The ID Board-and ABIM as a whole-has engaged with the physician community over the past several years to gain a deeper understanding of what is most important to them, and how an enhanced Maintenance of Certification (MOC) program could support their commitment to keeping up with advances in medical knowledge. This article serves as an update about how ABIM has evolved its assessments over time and on our progress in developing a new longitudinal pathway that is anticipated to become available in most specialties in 2022, and will launch in ID in 2023.

Risk Factors for In-hospital Mortality from Coronavirus Disease 2019 Infection Among Black Patients-An Urban Center Experience.

BACKGROUND: Racial disparities are central in the national conversation about coronavirus disease 2019 (COVID-19) , with Black/African Americans being disproportionately affected. We assessed risk factors for death from COVID-19 among Black inpatients at an urban hospital in Detroit, Michigan. METHODS: This was a retrospective, single-center cohort study. We reviewed the electronic medical records of patients positive for severe acute respiratory syndrome coronavirus 2 (the COVID-19 virus) on qualitative polymerase chain reaction assay who were admitted between 8 March 2020 and 6 May 2020. The primary outcome was in-hospital mortality. RESULTS: The case fatality rate was 29.1% (122/419). The mean duration of symptoms prior to hospitalization was 5.3 (3.9) days. The incidence of altered mental status on presentation was higher among patients who died than those who survived, 43% vs 20.0%, respectively (P < .0001). From multivariable analysis, the odds of death increased with age (≥60 years), admission from a nursing facility, Charlson score, altered mental status, higher C-reactive protein on admission, need for mechanical ventilation, presence of shock, and acute respiratory distress syndrome. CONCLUSIONS: These demographic, clinical, and laboratory factors may help healthcare providers identify Black patients at highest risk for severe COVID-19-associated outcomes. Early and aggressive interventions among this at-risk population may help mitigate adverse outcomes.

Clinical Features and Risk Factors for In-Hospital Mortality From COVID-19 Infection at a Tertiary Care Medical Center, at the Onset of the US COVID-19 Pandemic.

BACKGROUND: Mortality from COVID-19 has been associated with older age, black race, and comorbidities including obesity, Understanding the clinical risk factors and laboratory biomarkers associated with severe and fatal COVID-19 will allow early interventions to help mitigate adverse outcomes. Our study identified risk factors for in-hospital mortality among patients with COVID-19 infection at a tertiary care center, in Detroit, Michigan. METHODS: We conducted a single-center, retrospective cohort study at a 776-bed tertiary care urban academic medical center. Adult inpatients with confirmed COVID-19 (nasopharyngeal swab testing positive by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay) from March 8, 2020, to June 14, 2020, were included. Clinical information including the presence of comorbid conditions (according to the Charlson Weighted Index of Comorbidity (CWIC)), initial vital signs, admission laboratory markers and management data were collected. The primary outcome was in-hospital mortality. RESULTS: Among 565 hospitalized patients, 172 patients died for a case fatality rate of 30.4%. The mean (SD) age of the cohort was 64.4 (16.2) years, and 294 (52.0%) were male. The patients who died were significantly older (mean [SD] age, 70.4 [14.1] years vs 61.7 [16.1] years; P < 0.0001), more likely to have congestive heart failure (35 [20.3%] vs 47 [12.0%]; P = 0.009), dementia (47 [27.3%] vs 48 [12.2%]; P < 0.0001), hemiplegia (18 [10.5%] vs 18 [4.8%]; P = 0.01) and a diagnosis of malignancy (16 [9.3%] vs 18 [4.6%]; P = 0.03).From multivariable analysis, factors associated with an increased odds of death were age greater than 60 years (OR = 2.2, P = 0.003), CWIC score (OR = 1.1, P = 0.023), qSOFA (OR = 1.7, P < 0.0001), WBC counts (OR = 1.1, P = 0.002), lymphocytopenia (OR = 2.0, P = 0.003), thrombocytopenia (OR = 1.9, P = 0.019), albumin (OR = 0.6, P = 0.014), and AST levels (OR = 2.0, P = 0.004) on admission. CONCLUSIONS: This study identified risk factor for in-hospital mortality among patients admitted with COVID-19 in a tertiary care hospital at the onset of U.S. Covid-19 pandemic. After adjusting for age, CWIC score, and laboratory data, qSOFA remained an independent predictor of mortality. Knowing these risk factors may help identify patients who would benefit from close observations and early interventions.

Predicting QT interval prolongation in patients diagnosed with the 2019 novel coronavirus infection.

INTRODUCTION: 2019 novel coronavirus (COVID-19) patients frequently develop QT interval prolongation that predisposes them to Torsades de Pointes and sudden cardiac death. Continuous cardiac monitoring has been recommended for any COVID-19 patient with a Tisdale Score of seven or more. This recommendation, however, has not been validated. METHODS: We included 178 COVID-19 patients admitted to a non-intensive care unit setting of a tertiary academic medical center. A receiver operating characteristics curve was plotted to determine the accuracy of the Tisdale Score to predict QT interval prolongation. Multivariable analysis was performed to identify additional predictors. RESULTS: The area under the curve of the Tisdale Score was 0.60 (CI 95%, 0.46-0.75). Using the cutoff of seven to stratify COVID-19, patients had a sensitivity of 85.7% and a specificity of 7.6%. Risk factors independently associated with QT interval prolongation included a history of end-stage renal disease (ESRD) (OR, 6.42; CI 95%, 1.28-32.13), QTc ≥450 ms on admission (OR, 5.90; CI 95%, 1.62-21.50), and serum potassium ≤3.5 mmol/L during hospitalization (OR, 4.97; CI 95%, 1.51-16.36). CONCLUSION: The Tisdale Score is not a useful tool to stratify hospitalized non-critical COVID-19 patients based on their risks of developing QT interval prolongation. Clinicians should initiate continuous cardiac monitoring for patients who present with a history of ESRD, QTc ≥450 ms on admission or serum potassium ≤3.5 mmol/L.

Tocilizumab: A retrospective multi-center cohort study of critically ill patients with COVID-19.

BACKGROUND: Coronavirus disease 19 (COVID-19) can have a severe presentation characterized by a dysregulated immune response requiring admission to the intensive care unit (ICU). Immunomodulatory treatments like tocilizumab were found to improve inflammatory markers and lung injury over time. We aim to evaluate the effectiveness of tocilizumab treatment on critically ill patients with severe COVID-19. MATERIALS AND METHODS: We conducted a multi-center retrospective cohort study of 154 adult patients admitted to the ICU for severe COVID-19 pneumonia between March 15 and May 8, 2020. Data were obtained by electronic medical record (EMR) review. The primary outcome of interest was mortality. RESULTS: Of 154 patients, 34 (21.4%) received tocilizumab. Compared to the non-treated group, the treated group was significantly younger, had fewer comorbidities, lower creatinine and procalcitonin levels, and higher alanine aminotransferase levels on admission. The treated group was more likely to receive supportive measures in the context of critical illness. The overall case fatality rate was 71.4%, and it was significantly lower in the treated than the non-treated (52.9 vs. 76.7%, p = 0.007). In multivariable survival analysis, tocilizumab treatment was associated with a 2.1 times lower hazard of mortality when compared to those who were not treated (hazard ratio: 0.47; 95% CI: 0.27, 0.83; p = 0.009). The prevalence of secondary infection was higher in the treated group compared to the non-treated without significant difference (p = 0.17). CONCLUSION: Tocilizumab treatment for critically ill patients with COVID-19 resulted in a lower likelihood of mortality.

How Can Malnutrition Affect Autophagy in Chronic Heart Failure? Focus and Perspectives.

Chronic heart failure (CHF) is a disease with important clinical and socio-economic ramifications. Malnutrition and severe alteration of the protein components of the body (protein disarrangements), common conditions in CHF patients, are independent correlates of heart dysfunction, disease progression, and mortality. Autophagy, a prominent occurrence in the heart of patients with advanced CHF, is a self-digestive process that prolongs myocardial cell lifespan by the removal of cytosolic components, such as aging organelles and proteins, and recycles the constituent elements for new protein synthesis. However, in specific conditions, excessive activation of autophagy can lead to the destruction of molecules and organelles essential to cell survival, ultimately leading to organ failure and patient death. In this review, we aim to describe the experimental and clinical evidence supporting a pathophysiological role of nutrition and autophagy in the progression of CHF. The understanding of the mechanisms underlying the interplay between nutrition and autophagy may have important clinical implications by providing molecular targets for innovative therapeutic strategies in CHF patients.

Plazomicin: A New Aminoglycoside.

Plazomicin (ACHN-490) is a novel parenteral aminoglycoside developed to target multidrug-resistant Enterobacteriaceae. It has recently been approved by the Food and Drug Administration for the management of complicated urinary tract infections and pyelonephritis caused by susceptible organisms. When compared with meropenem, plazomicin was not inferior. The adverse-event profile for plazomicin was comparable to meropenem except for an increased additional rise in serum creatinine in the plazomicin arm compared with the meropenem arm. This review focuses on the mode of action, antimicrobial activity, pharmacokinetics, clinical indications, and safety profile of this drug. Considerations for formulary addition and its place in therapy are also discussed.

Baloxavir: A Novel Antiviral Agent in the Treatment of Influenza.

Baloxavir marboxil (formerly S-033188) is a prodrug of baloxavir acid (S-033447) and inhibits cap-dependent endonuclease, an essential protein involved in the initiation of viral transcription by cleaving capped mRNA bound to PB2. Its adverse event profile is comparable to oseltamivir but is still vulnerable to resistance. The single-dose baloxavir marboxil is an appealing antiviral regimen for the treatment of influenza among outpatients when compared with longer, twice-daily regimens of oral and inhaled neuraminidase inhibitors. This review focuses on the mode of action, antiviral activity, pharmacokinetics, clinical indications, and safety profiles of this drug. Considerations for formulary addition and its place in therapy are also discussed.

Predictors for Severe COVID-19 Infection.

BACKGROUND: COVID-19 is a pandemic disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Predictors for severe COVID-19 infection have not been well defined. Determination of risk factors for severe infection would enable identifying patients who may benefit from aggressive supportive care and early intervention. METHODS: We conducted a retrospective observational study of 197 patients with confirmed COVID-19 admitted to a tertiary academic medical center. RESULTS: Of 197 hospitalized patients, the mean (SD) age of the cohort was 60.6 (16.2) years, 103 (52.3%) were male, and 156 (82.1%) were black. Severe COVID-19 infection was noted in 74 (37.6%) patients, requiring intubation. Patients aged above 60 were significantly more likely to have severe infection. Patients with severe infection were significantly more likely to have diabetes, renal disease, and chronic pulmonary disease and had significantly higher white blood cell counts, lower lymphocyte counts, and increased C-reactive protein (CRP) than patients with nonsevere infection. In multivariable logistic regression analysis, risk factors for severe infection included pre-existing renal disease (odds ratio [OR], 7.4; 95% CI, 2.5-22.0), oxygen requirement at hospitalization (OR, 2.9; 95% CI, 1.3-6.7), acute renal injury (OR, 2.7; 95% CI, 1.3-5.6), and CRP on admission (OR, 1.006; 95% CI, 1.001-1.01). Race, age, and socioeconomic status were not independent predictors. CONCLUSIONS: Acute or pre-existing renal disease, supplemental oxygen upon hospitalization, and admission CRP were independent predictors for the development of severe COVID-19. Every 1-unit increase in CRP increased the risk of severe disease by 0.06%.

Delafloxacin activity against Staphylococcus aureus with reduced susceptibility or resistance to methicillin, vancomycin, daptomycin or linezolid.

BACKGROUND: Delafloxacin is a recently approved anionic fluoroquinolone antibiotic with broad-spectrum activity against Gram-positive and Gram-negative organisms. The drug has been approved for patients with acute bacterial skin and skin structure infections including those caused by MRSA. There are limited data available against MRSA blood isolates (MRSABIs), vancomycin-intermediate strains (VISA), vancomycin-resistant strains (VRSA), daptomycin-non-susceptible strains (DNSSA) and linezolid-resistant Staphylococcus aureus (LRSA). METHODS: Antimicrobial activity of delafloxacin, levofloxacin, vancomycin, daptomycin and linezolid was determined against 110 MRSABIs, 15 VRSA, 35 VISA, 40 DNSSA and 6 LRSA. Microdilution testing using CAMHB was used to determine MIC according to CLSI guidelines. FDA breakpoints were used to determine delafloxacin susceptibility, and CLSI breakpoints were used for all other antibiotics. PCR testing for molecular markers was performed. RESULTS: Delafloxacin demonstrated activity against MRSABIs with an MIC90 of 1 mg/L and 68% susceptibility. Against the other groups the MIC90 and susceptibility were 1 mg/L and 40%, respectively, for VISA, 4 mg/L and 7% for VRSA and 1 mg/L and 38% for DNSSA. None of the LRSA isolates was susceptible to delafloxacin. Delafloxacin was active against 94% of MRSA blood isolates that were genotype SCC IVa. For MRSABIs with a levofloxacin MIC ≥8 mg/L (55/110), suggesting multiple mutations in the QRDR, delafloxacin MIC90 was 1 mg/L with a 36.4% susceptibility rate. CONCLUSIONS: Delafloxacin demonstrates superior activity to levofloxacin against recent MRSA blood isolates, VISA, VRSA and DNSSA, and demonstrates good activity against blood isolates most commonly found in the community.

Delafloxacin: A New Anti-methicillin-resistant Staphylococcus aureus Fluoroquinolone.

Delafloxacin (ABT 492) is a new fluoroquinolone available in both oral and parenteral formulations. It has recently been approved by the Food and Drug Administration for the management of acute bacterial skin and skin structure infections. When compared to combination therapy of vancomycin and aztreonam, delafloxacin was not inferior and had a favorable adverse event profile. Furthermore, its anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and favorable clinical response in MRSA infections distinguishes it from other fluoroquinolones. This review focuses on the mode of action, antimicrobial activity, pharmacokinetics and pharmacodynamics, clinical indications, and safety profile of this drug. Considerations for formulary addition and its place in therapy are also discussed.

Elevated Cardiac Troponin in Clinical Scenarios Beyond Obstructive Coronary Artery Disease.

In this systematic review article, we aim to summarize the most up-to-date evidence regarding elevations of cardiac troponin, especially in clinical scenarios other than obstructive coronary artery disease. The accurate interpretation of raised cardiac troponin is challenging because it relies on unconfirmed postulations and dogmatic knowledge (e.g., the exclusive provenience of cardiac troponin from cardiac myocytes), based on which every troponin elevation is assumed to definitely indicate myocardial damage. Indeed, the investigation of the pathophysiologic mechanism leading to the release in the bloodstream of cardiac biomarkers should be the first step of the diagnostic process to fully understand the clinical significance of the elevated serum levels and identify the best management. A prominent effort should be put in place to identify the contribution of potential confounding factors, both cardiac and non-cardiac in etiology, with the ability to affect synthesis and clearance of cardiac biomarkers. Regardless of the underlying cause, it is well established that cardiovascular biomarkers are increasingly useful to further risk stratification and prognosticate patients. Accordingly, we sought to clarify the meaning and impact of elevated cardiac troponin in those frequently encountered real-world scenarios presenting clinicians with a diagnostic dilemma, with the final goal of facilitating the diagnosis and help optimize individually tailored treatment strategies.

Oritavancin: A Long-Half-Life Lipoglycopeptide.

Oritavancin is a lipoglycopeptide antibiotic that has been shown to be effective for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). This antibiotic has multiple mechanisms of action including inhibiting peptidoglycan cell wall synthesis and disrupting bacterial cell membrane, leading to cell death. Oritavancin is highly active against common gram-positive pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, and vancomycin-resistant enterococci. The drug is administered as a single intravenous dose of 1200 mg over 3 hours in adult patients, and because of its terminal half-life of 393 hours, repeat dosing is not required in the treatment of ABSSIs. There is a very slow elimination from tissue sites, and no dosing adjustments are required for renal or hepatic insufficiency. Two clinical trials have demonstrated noninferiority compared with vancomycin in the treatment of ABSSSIs. Other than liver enzyme elevation and the occurrence of osteomyelitis, oritavancin has been associated with adverse events similar to those of vancomycin in follow-up for up to 60 days. Patients should be monitored for osteomyelitis and alternate therapy given in the case of confirmed or suspected osteomyelitis. Although oritavancin is an attractive antibiotic to consider in the outpatient area, its efficacy and safety in the treatment of other sites of infection are yet to be established.