Determining if the prognostic nutritional index can predict outcomes in community acquired bacterial pneumonia.

BACKGROUND: The Prognostic Nutritional Index (PNI) uses albumin levels and total lymphocyte count to predict the relationship between immune-nutritional state and prognosis in a variety of diseases, however it has not been studied in community acquired bacterial pneumonia (CABP). We conducted a historical cohort study to determine if there was an association between PNI and clinical outcomes in patients with CABP. METHODS: We reviewed 204 adult patients with confirmed CABP, and calculated admission PNI and Neutrophil-to-Lymphocyte Ratio (NLR). A comparative analysis was performed to determine the association of these values, as well as other risk factors, with the primary outcomes of 30-day readmissions and death. RESULTS: Of the 204 patients, 56.9% (116) were male, 48% (98) were black/African American and the mean age was 63.2 ± 16.1 years. The NLR was neither associated with death nor 30-day readmission. The mean PNI in those who survived was 34.7 ± 4.5, compared to 30.1 ± 6.5, in those who died, p < 0.001. From multivariable analysis after controlling for the Charlson score and age, every one-unit increase in the PNI decreased the risk of death by 13.6%. The PNI was not associated with readmissions. CONCLUSIONS: These findings suggest that poor immune and nutritional states, as reflected by PNI, both contribute to mortality, with a significant negative correlation between PNI and death in CABP. PNI was predictive of mortality in this patient cohort; NLR was not. Monitoring of albumin and lymphocyte count in CABP can provide a means for prevention and early intervention.

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.

A comparison of coronavirus disease 2019 (COVID-19) versus influenza during the pandemic: Can we distinguish COVID-19 from flu?

We conducted a retrospective chart review examining the demographics, clinical history, physical findings, and comorbidities of patients with influenza and patients with coronavirus disease 2019 (COVID-19). Older patients, male patients, patients reporting fever, and patients with higher body mass indexes (BMIs) were more likely to have COVID-19 than influenza.

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.

A case of Gemella morbillorum native valve endocarditis and results of in vitro susceptibility testing.

We present a case of a 48 years old male with Gemella morbillorum native mitral valve endocarditis. Due to poor growth of the organism, antimicrobial susceptibility test (AST) could not be performed using the CLSI approved method. AST was determined using Etest© strips and the patient was successfully treated with mitral valve replacement and intravenous ceftriaxone.

Follicular B-Cell Lymphoma and Particulate Matter Associated with Environmental Exposure to Wood Dust.

BACKGROUND In humans, wood dust is a carcinogen. Indeed, a strong association between wood dust and lung cancer risk has been reported in woodworkers, as well as in the general population. CASE REPORT The patient was a 58-year-old man with follicular B-cell lymphoma. In the 10 years preceding the cancer diagnosis, he lived within 1/4 mile of a paper mill, where wood was processed. Computed tomography of the chest, abdomen, and pelvis revealed right hilar, mediastinal, abdominal, and retroperitoneal lymphadenopathy, bilateral pleural effusions, and a large soft-tissue mass infiltrating the small bowel mesentery. Analysis of the pleural fluid revealed the presence of a web of thin filopodia-like filaments, which trapped clusters of mesothelial cells and atypical lymphocytes. Single tubular filaments, morphologically similar to tunneling nanotubes, were seen originating from atypical lymphocytes and reaching neighboring cells. Furthermore, long, thick, cylindrical fibers of unknown nature, probably from the external environment, were also observed. CONCLUSIONS Because the patient lived in an unhealthy environment for many years, the possibility that his clinical condition was related to exposure to toxic emissions should be entertained. Considered in this context, the foreign fibers in his pleural fluid could be a direct consequence of inhalation of contaminants in the polluted air.

Do risk factors at the time of hospital admission differ by sex for in-hospital mortality from coronavirus disease 2019 (COVID-19)?

Background: Sex-disaggregated data for coronavirus disease 2019 (COVID-19) reported higher hospitalized fatality rates among men than women. Objective: To determine whether the risk factors for in-hospital mortality from COVID-19, present at the time of hospital admission, differed by patient sex. Design and setting: Single-center, retrospective cohort study at a tertiary-care urban academic center. Methods: We reviewed the electronic medical records of patients positive for COVID-19 via qualitative polymerase chain reaction (PCR) assay, admitted between March 8 and June 14, 2020. Patients were stratified by sex to assess the association of variables present on admission with in-hospital mortality. Results: The overall inpatient case fatality rate (CFR) was 30.4% (172 of 565). The CFR among male patients was higher than among female patients: 99 (33.7%) versus 73 (26.9%), respectively (P = .08). Among males, comorbid conditions associated with in-hospital mortality were chronic pulmonary disease (P = .02) and connective tissue disease (P = .03). Among females, these comorbid conditions were congestive heart failure (P = .03), diabetes with complication (P = .05), and hemiplegia (P = .02). Variables that remained independently associated with death in males included age >70 years, public insurance, incremental increase in quick sepsis-related organ failure assessment (qSOFA) and C-reactive protein (CRP), lymphocytopenia, and thrombocytopenia. Among females, variables that remained independently associated with mortality included public insurance, incremental increase in Charlson weighted index of comorbidity (CWIC) score, qSOFA, and CRP. Conclusions: Risk factors for in-hospital mortality by sex included public insurance type, incremental increase in qSOFA and CRP in both sexes. For male patients, older age, lymphocytopenia and thrombocytopenia were also associated with mortality, whereas a higher Charlson score was associated with in-hospital mortality in female patients.

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.

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.

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.

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.

Clinical Experience with Telavancin: Real-World Results from the Telavancin Observational Use Registry (TOUR™).

BACKGROUND: Telavancin-a lipoglycopeptide antibacterial agent active against Gram-positive pathogens including methicillin-sensitive and -resistant Staphylococcus aureus (MRSA)-is approved in the USA for once-daily intravenous use. This registry study captured patient characteristics, prescribing patterns, and treatment outcomes associated with telavancin use in real-world clinical practice. OBJECTIVE: This prospective, multicenter, observational study will characterize current real-world practice patterns for the use of telavancin in the USA by describing demographic and clinical conditions, examining the process of care and rationale for use, and describing the clinical effectiveness and selected safety outcomes among patients treated with telavancin. METHODS: The Telavancin Observational Use Registry (TOUR™) is an observational multicenter registry study. Clinical data-including patient demographics, pathogens, telavancin dosing and treatment duration, and adverse events-along with investigators' assessments of outcome, were collected through retrospective medical chart review. RESULTS: Data from 1063 patients were collected from 45 US sites. Of these patients, 29.4% were ≥ 65 years of age [mean age ± standard deviation, 55.2 ± 15.4 years; median age (interquartile range), 57.0 (46.0-66.0)], 53.4% were male, and 83.4% were White. The primary infections in these patients included complicated skin and skin-structure infection (48.7%), bone and joint infections (27.4%), bacteremia and endocarditis (14.2%), and lower respiratory tract infections (8.5%). The predominant pathogen identified was MRSA (37.7%). The mean telavancin dose and duration of treatment were 741.7 ± 194.3 mg and 17 ± 17 days, respectively. Of the 964 (90.7%) patients for whom an end-of-treatment assessment was available, 77.7% had a positive clinical response, 10.1% failed treatment, and 12.2% had indeterminate outcomes. CONCLUSIONS: Real-world data collected from the TOUR study show once-daily telavancin is being used for the treatment of a variety of Gram-positive infections with generally positive clinical outcomes.

Real-world use of telavancin in the treatment of osteomyelitis.

This is a retrospective analysis of patients with osteomyelitis who received telavancin at some time during their treatment course. The primary outcome was the percent of patients cured or improved at the end of telavancin therapy (EOTT). The secondary outcome was the percent of patients cured or improved three months after discontinuation of telavancin therapy. There were 32 cases of osteomyelitis with methicillin-resistant Staphylococcus aureus identified in 17 (56.7%), methicillin-sensitive Staphylococcus aureus 2(6.6%), coagulase negative staphylococci 6 (20.0%) and other pathogens, 5 (16.7%). At EOTT, 87.5% of patients had their osteomyelitis cured and 94.6% had the infection cured at three months after telavancin was completed. The most common adverse events associated with telavancin were gastrointestinal in nature (nausea (25.8%), vomiting (9.7%) and diarrhea (3.2%)) followed by metallic taste (6.5%). A favorable outcome was achieved for many patients receiving the antimicrobial regimen that included telavancin for the treatment of osteomyelitis.

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.

VISA-Daptomycin non-susceptible Staphylococcus aureus frequently demonstrate non-susceptibility to Telavancin.

Telavancin was evaluated against S. aureus isolates with reduced susceptibility to other antimicrobial agents using two broth microdilution methods and Etest® strips. The three methods provided comparable results. Differences in telavancin susceptibility versus non-susceptibility were noted mainly in the VISA-daptomycin non-susceptible group of isolates. In this group the percent susceptibility was 38% for the Etest® method and 50% and 54% for the 2 broth microdilution methods. All differences in susceptibility were within one 2-fold dilution.

Endoscopic Treatment of Colonic Duplication Cyst: A Case Report and Review of the Literature.

Colonic duplication cysts are a rare congenital abnormality commonly presenting before two years of age. In adults, it has been rarely reported, most often as an incidental finding. We report a case of 42-year-old female complaining of constipation and lower abdominal pain. Patient's CT scan of the abdomen showed a cystic lesion at hepatic flexure and the diagnosis was confirmed endoscopically using endoscopic ultrasound (EUS). The cyst was treated employing hot snare to expose the cyst cavity. On our literature search, there have been no reported cases of colonic duplication cyst treated endoscopically. We here discuss incidence, diagnosis, characteristics, and treatment of duplication cysts with special emphasis on endoscopic therapy.