Linezolid Attenuates Lethal Lung Damage during Postinfluenza Methicillin-Resistant Staphylococcus aureus Pneumonia Host Response and Inflammation

In this study, we investigated the efficacy of antibiotic therapies and the impact of S. aureus alpha-toxin in a model of lethal influenza virus and MRSA coinfection. We demonstrate that antibiotics primarily attenuate alpha-toxin-induced acute lethality, even though both alpha-toxin-dependent and -independent mechanisms significantly contribute to animal mortality after coinfection. Furthermore, we found that the protein synthesis-suppressing antibiotic linezolid has an advantageous therapeutic effect on alpha-toxin-induced lung damage, as measured by protein leak and lactate dehydrogenase (LDH) activity. Importantly, using a Panton-Valentine leucocidin (PVL)-negative MRSA isolate from patient sputum, we show that linezolid therapy significantly improves animal survival from postinfluenza MRSA pneumonia compared with vancomycin treatment. Rather than improved viral or bacterial control, this advantageous therapeutic effect is associated with a significantly attenuated proinflammatory cytokine response and acute lung damage in linezolid-treated mice. Together, our findings not only establish a critical role of alpha-toxin in the extreme mortality of secondary MRSA pneumonia after influenza but also provide support for the possibility that linezolid could be a more effective treatment than vancomycin to improve disease outcomes.
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research

Related Links:

Abstract Background: The 2019 community-acquired pneumonia guidelines recommend using recent respiratory cultures and locally validated epidemiology plus risk factor assessment to determine empirical coverage of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Objective: To develop a methodology for evaluating local epidemiology and validating local risk factors for P aeruginosa and MRSA. Methods: This multicenter, retrospective cohort evaluated adult patients admitted for pneumonia. Risk factors for MRSA and P aeruginosa were evaluated using multivariable logistic regression and repo...
Source: The Annals of Pharmacotherapy - Category: Drugs & Pharmacology Authors: Tags: Ann Pharmacother Source Type: research
Semin Respir Crit Care Med DOI: 10.1055/s-0040-1709992 Staphylococcus aureus is an emergent etiology of community-acquired pneumonia (CAP) over the past 2 decades, with severe community-acquired pneumonia (SCAP) caused by methicillin-resistant S. aureus (MRSA) leading to critical illness and death. S. aureus colonization is associated with a high incidence of pneumonia. Panton-Valentine leukocidin (PVL) is one of the most important virulence factors of S. aureus associated with serious complications. In recent years, community-associated MRSA (CA-MRSA) clones that caused infections in young adults and healthy individual...
Source: Seminars in Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Review Article Source Type: research
Abstract Patients with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) pneumonia have poor clinical outcomes and high frequency of mortality, especially in patents with postinfluenza infection. Herein, we report a case of community-acquired pneumonia with multiple organ failure in a 51-year-old patient with initial presentation of flu-like symptoms. The influenza rapid test from the specimen of nasopharyngeal swab was positive for type B influenza virus and was confirmed by real-time polymerase chain reaction. Gram stain of bronchoalveolar lavage fluid revealed gram positive cocci in gro...
Source: The American Journal of the Medical Sciences - Category: General Medicine Authors: Tags: Am J Med Sci Source Type: research
Conclusion: MCC-IMS is a promising tool for the detection of resistant strains in vitro. More resistant strains will be evaluated and presented.
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory infections Source Type: research
We report a case of a 13-year-old female who presented to the Emergency Department with altered mental status and respiratory distress following a treatment course for influenza. She was diagnosed with multifocal pneumonia and developed fulminant respiratory failure requiring ECLS. The causative organism was later found to be Methicillin-Resistant Staphylococcus Aureus (MRSA). She was maintained on ECLS for 49 days and developed secondary complications of lung necrosis, an intrathoracic hematoma, and multiple bronchopleural fistulae. She was managed non-operatively for these complications until she stabilized enough to be ...
Source: Journal of Pediatric Surgery Case Reports - Category: Surgery Source Type: research
Conclusion: Prior respiratory infection, obesity, alcoholism, and old age (>60 years) were observed to be important risk factors for severe CAP. Prospective studies should evaluate effect of weight reduction and cessation of alcohol consumption on recurrences of pneumonia in this population and on the severity of pneumonia.
Source: Lung India - Category: Respiratory Medicine Authors: Source Type: research
Clinically, meticillin-resistant Staphylococcus aureus (MRSA) ventilator-associated pneumonia (VAP) is rare. However, MRSA is a common colonizer of respiratory secretions in ventilated adults in intensive care units (ICUs). The classic clinical features of bona fide S. aureus pneumonia are well known from experience with S. aureus pneumonia with influenza. In a potential VAP (pVAP) ICU patient without the clinical findings of S. aureus pneumonia (i.e. otherwise unexplained new high fevers/chills, haemorrhagic tracheobronchitis, elastin fibres in bronchial secretions, hypotension, rapid cavitation, and thick-walled cavities...
Source: International Journal of Antimicrobial Agents - Category: Drugs & Pharmacology Authors: Tags: Letter to the Editor Source Type: research
Influenza A virus (IAV) infection is often followed by secondary bacterial lung infection, which is a major reason for severe, often fatal pneumonia. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains such as USA300 cause particularly severe and difficult-to-treat cases of IAV-associated pneumonia. CA-MRSA strains are known to produce extraordinarily large amounts of phenol-soluble modulin (PSM) peptides, which are important cytotoxins and proinflammatory molecules that contribute to several types of S. aureus infection. However, their potential role in pneumonia has remained elusive. We det...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Molecular Pathogenesis Source Type: research
ConclusionThese metabolic changes in the urine preceded the clinical severe sepsis phenotype, which suggests that detection of the extent of metabolic disruption can aid in the early identification of a sepsis phenotype in advance of clinical diagnosis. These data also support the utility of metabolomics for the development of clinical assays for the identification of patients with pediatric pneumonia at high risk for deterioration.This article is protected by copyright. All rights reserved.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: Special Issue on Precision Medicine Source Type: research
Conclusions. Despite very low prevalence of S. aureus and, specifically, MRSA, nearly one-third of adults hospitalized with CAP received anti-MRSA antibiotics. The clinical presentation of MRSA CAP overlapped substantially with pneumococcal CAP, highlighting the challenge of accurately targeting empirical anti-MRSA antibiotics with currently available clinical tools and the need for new diagnostic strategies.
Source: Clinical Infectious Diseases - Category: Infectious Diseases Authors: Tags: ARTICLES AND COMMENTARIES Source Type: research
More News: Antibiotic Therapy | Infectious Diseases | Influenza | Linezolid | MRSA | Pneumonia | Staphylococcus Aureus | Study | Superbugs | Zyvox