Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pra...

/pdf/diagnosis-and-treatment-of-adults-with-community-acquired-4u8h6pikis.pdf

Diagnosis and Treatment of Adults with Community-acquired Pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America

Antimicrobial-resistant ESKAPE ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. The acquisition of antimicrobial resistance genes by ESKAPE pathogens has reduced the treatment options for serious infections, increased the burden of disease, and increased death rates due to treatment failure and requires a coordinated global response for antimicrobial resistance surveillance. This looming health threat has restimulated interest in the development of new antimicrobial therapies, has demanded the need for better patient care, and has facilitated heightened governance over stewardship practices.

Antimicrobial resistance in ESKAPE pathogens

ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are among the most common opportunistic pathogens in nosocomial infections. ESKAPE pathogens distinguish themselves from normal ones by developing a high level of antibiotic resistance that involves multiple mechanisms. Contemporary therapeutic strategies which are potential options in combating ESKAPE bacteria need further investigation. Herein, a broad overview of the antimicrobial research on ESKAPE pathogens over the past five years is provided with prospective clinical applications.

https://onlinelibrary.wiley.com/doi/epdf/10.1002/advs.201901872

Considerations and Caveats in Combating ESKAPE Pathogens against Nosocomial Infections

People infected with the SARS-CoV-2 virus, which causes COVID-19, can develop severe respiratory failure and require a ventilator to keep breathing, but this does not happen to every infected individual. Measuring a blood protein called suPAR (soluble urokinase plasminogen activator receptor) may help identify patients at the greatest risk of developing severe respiratory failure and requiring a ventilator. Previous investigations have suggested that measuring suPAR can identify pneumonia patients at highest risk for developing respiratory failure. The protein can be measured by taking a blood sample, and its levels provide a snapshot of how the body’s immune system is reacting to infection, and of how it may respond to treatment. Anakinra is a drug that forms part of a class of medications called interleukin antagonists. It is commonly prescribed alone or in combination with other medications to reduce pain and swelling associated with rheumatoid arthritis. Kyriazopoulou et al. investigated whether treating COVID-19 patients who had developed pneumonia with anakinra could prevent the use of a ventilator and lower the risk of death. The findings show that treating COVID-19 patients with an injection of 100 milligrams of anakinra for ten days may be an effective approach because the drug combats inflammation. Kyriazopoulou et al. examined various markers of the immune response and discovered that anakinra was able to improve immune function, protecting a significant number of patients from going on a ventilator. The drug was also found to be safe and cause no significant adverse side effects. Administering anakinra decreased of the risk of progression into severe respiratory failure by 70%, and reduced death rates significantly. These results suggest that it may be beneficial to use suPAR as an early biomarker for identifying those individuals at highest risk for severe respiratory failure, and then treat them with anakinra. While the findings are promising, they must be validated in larger studies.

An open label trial of anakinra to prevent respiratory failure in COVID-19.

Community-acquired pneumonia (CAP) is the leading cause of death among infectious diseases and an important health problem, having considerable implications for healthcare systems worldwide. Despite important advances in prevention through vaccines, new rapid diagnostic tests and antibiotics, CAP management still has significant drawbacks. Mortality remains very high in severely ill patients presenting with respiratory failure or shock but is also high in the elderly. Even after a CAP episode, higher risk of death remains during a long period, a risk mainly driven by inflammation and patient-related co-morbidities. CAP microbiology has been altered by new molecular diagnostic tests that have turned viruses into the most identified pathogens, notwithstanding uncertainties about the specific role of each virus in CAP pathogenesis. Pneumococcal vaccines also impacted CAP etiology and thus had changed Streptococcus pneumoniae circulating serotypes. Pathogens from specific regions should also be kept in mind when treating CAP. New antibiotics for CAP treatment were not tested in severely ill patients and focused on multidrug-resistant pathogens that are unrelated to CAP, limiting their general use and indications for intensive care unit (ICU) patients. Similarly, CAP management could be personalized through the use of adjunctive therapies that showed outcome improvements in particular patient groups. Although pneumococcal vaccination was only convincingly shown to reduce invasive pneumococcal disease, with a less significant effect in pneumococcal CAP, it remains the best therapeutic intervention to prevent bacterial CAP. Further research in CAP is needed to reduce its population impact and improve individual outcomes.

/pdf/burden-of-community-acquired-pneumonia-and-unmet-clinical-11r964o7ok.pdf

Burden of Community-Acquired Pneumonia and Unmet Clinical Needs

Background Omadacycline, a new once-daily aminomethylcycline antibiotic agent that can be administered intravenously or orally, reaches high concentrations in pulmonary tissues and is acti...

https://www.nejm.org/doi/suppl/10.1056/NEJMoa1800201/suppl_file/nejmoa1800201_appendix.pdf

Omadacycline for Community-Acquired Bacterial Pneumonia

FUNDING AND DISCLOSURES BACKGROUND METHODS A Phase 3, Randomized, Double-Blind, Multi-Center Study to Compare the Safety and Efficacy of IV to Oral Omadacycline to Moxifloxacin for the Treatment of Adult Patients With CABP (The OPTIC Study) Roman Stets, MD, PhD1; Monica Popescu, MD2; Joven Gonong, MD3; Ismail Mitha, MD4; William Nseir, MD5; Andrzej Madej, MD, PhD6; Courtney Kirsch, BS7; Anita Das, PhD7; Lynne Garrity-Ryan, PhD7; Judith N. Steenbergen, PhD7; Amy Manley, BS7; Paul B. Eckburg, MD7; Stephen Villano, MD7; Evan Tzanis, BA7; Paul McGovern, MD7; Evan Loh, MD7 Poster 1883

A Phase 3 Randomized, Double-blind, Multi-center Study to Compare the Safety and Efficacy of IV to Oral Omadacycline to Moxifloxacin for the Treatment of Adult Subjects with CABP (The OPTIC Study)

Abstract Background Delafloxacin (DLX) is a fluoroquinolone, approved in the United States for treatment of ABSSSI. DLX has no preclinical signals for QT prolongation and has no QT prolongation in a validated challenge study. Risk of QT prolongation is a consideration in antibiotic selection for elderly hospitalized CABP patients. A Phase 3 CABP trial with DLX was analyzed with a focus on age and gender. Methods Data on age and gender were reviewed from a multicenter, randomized, double-blind trial of adults with CABP. Patients were randomized 1:1 to DLX or moxifloxacin (MOX) treatment for 5–10 days. Patients received a minimum of 3 days of IV treatment, then were switched to oral at MD discretion. A key clinical endpoint was the investigator-assessment at Test of Cure (TOC) 5–10 days after the end of treatment. Clinical success was defined as complete or near resolution of signs and symptoms and no further antibiotics needed Results In the overall study, 859 patients were randomized with a mean age of 60 years (55.5% <65, 44.5% ≥65, 21.2% ≥75; range 18–93); 58.7% were male; 25.4% and 1.4% were PORT class IV and V; 28.6% multi-lobar pneumonia. Table shows the comparison of DLX and MOX clinical response at TOC in the Intent to Treat (ITT) population. Overall, DLX was well tolerated, with similar related adverse events (AE) between treatment groups regardless of age (< 65: 16.7% DLX, 13.3% MOX; ≥ 65: 13.4% DLX, 11.7% MOX) or gender (male: 16.0% DLX, 11.1% MOX; female 14.0% DLX, 14.9% MOX). The most common treatment-related AEs for DLX were diarrhea and transaminase elevations which were mild-to-moderate and did not routinely lead to discontinuation. There were no reports of potential QT prolongation on DLX. Conclusion Based on age and gender, DLX had comparable outcomes to MOX in clinical success at TOC. DLX was also well tolerated regardless of age or gender. DLX may offer a promising alternative in the treatment of CABP including elderly patients. Disclosures All authors: No reported disclosures.

/pdf/2234-outcomes-by-age-and-gender-from-a-global-phase-3-study-4fj5fuw6vk.pdf

Andrzej Madej

Papers

Omadacycline for Community-Acquired Bacterial Pneumonia

A Phase 3 Randomized, Double-blind, Multi-center Study to Compare the Safety and Efficacy of IV to Oral Omadacycline to Moxifloxacin for the Treatment of Adult Subjects with CABP (The OPTIC Study)

2234. Outcomes by Age and Gender from a Global Phase 3 Study of Delafloxacin (DLX) in Community-Acquired Bacterial Pneumonia (CABP)