scholarly journals The immune response in Acinetobacter baumannii pneumonia

2016 ◽  
Vol 19 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Cristina Anca Tudor ◽  
◽  
Cristian Boros ◽  
Raluca Petre ◽  
Adriana Elena Nica ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Tract ◽  
Acinetobacter Baumannii ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Lower Respiratory Tract ◽  
Defense Mechanism ◽  
Immunocompromised Patients ◽  
Common Site ◽  
Acinetobacter Baumanii

Acinetobacter baumannii is a bacterium that is commonly causes of nosocomial infections, the most common site of infection and colonization is the lower respiratory tract. Although it is present more often in immunocompromised patients, the defense mechanism against infection with Acinetobacter baumanii remains incomplete elucidated. Among the virulence factors involved in infection with Acinetobacter baumanii are production and release of exopolysaccharide, and ability to biofilm formation in tissues. Understanding of virulence mechanisms is important for early initiation of treatment.

scholarly journals DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study

2021 ◽  
Author(s):  
Roy F Chemaly ◽  
Francisco M Marty ◽  
Cameron R Wolfe ◽  
Steven J Lawrence ◽  
Sanjeet Dadwal ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Tract ◽  
Primary Endpoint ◽  
Lower Respiratory Tract ◽  
Parainfluenza Virus ◽  
Controlled Study ◽  
Solid Organ ◽  
Immunocompromised Patients ◽  
Post Hoc Analysis ◽  
Post Hoc

Abstract Background There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Methods Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. Results A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012). Conclusions The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877.

scholarly journals The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

2019 ◽  
Vol 55 (4) ◽  
pp. 224-235
Author(s):  
Lisa Avery ◽  
Charles Hoffmann ◽  
Karen M. Whalen
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Adverse Reactions ◽  
Immunocompromised Patients ◽  
Syncytial Virus

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain >10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy.

scholarly journals The Role of the Immune Response in the Pathogenesis of Bronchiectasis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Paul T. King
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Therapeutic Potential ◽  
Small Airways ◽  
Upper Respiratory Tract ◽  
Causative Factors ◽  
Triggering Factor

Bronchiectasis is a prevalent respiratory condition characterised by permanent and abnormal dilation of the lung airways (bronchi). There are a large variety of causative factors that have been identified for bronchiectasis; all of these compromise the function of the immune response to fight infection. A triggering factor may lead to the establishment of chronic infection in the lower respiratory tract. The bacteria responsible for the lower respiratory tract infection are usually found as commensals in the upper respiratory tract microbiome. The consequent inflammatory response to infection is largely responsible for the pathology of this condition. Both innate and adaptive immune responses are activated. The literature has highlighted the central role of neutrophils in the pathogenesis of bronchiectasis. Proteases produced in the lung by the inflammatory response damage the airways and lead to the pathological dilation that is the pathognomonic feature of bronchiectasis. The small airways demonstrate infiltration with lymphoid follicles that may contribute to localised small airway obstruction. Despite aggressive treatment, most patients will have persistent disease. Manipulating the immune response in bronchiectasis may potentially have therapeutic potential.

A SIR2 family protein impacts biofilm formation by post-translational modifications in Acinetobacter baumannii

2020 ◽  
Author(s):  
Brandon Robin ◽  
Sebastien Massier ◽  
Anaïs Potron ◽  
Jean-Baptiste Vuillemenot ◽  
Salomé Sauvage ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Therapeutic Targets ◽  
World Health ◽  
Protein Acetylation ◽  
Acinetobacter Baumanii ◽  
Post Translational Modifications ◽  
Bacterial Physiology ◽  
Global Dynamic ◽  
Biofilm Development

<p><em>Acinetobacter baumannii</em> is one of the most problematic opportunist pathogen responsible for many infections worldwide (1). Besides its high capacities to acquire antibiotic resistance mechanisms, it also presents high adhesion abilities on any types of abiotic or living surfaces leading to biofilm development, a mode of growth conferring an additional protection against various treatments and allowing the infection relapse (2). <em>A. baumannii</em> has been recently ranked on the global priority pathogens list established by the World Health Organization for which there is an urgent need for new treatments. One interesting way to identify new therapeutic targets to eradicate this pathogen is the characterization of its post-translational modifications (PTMs) (3). The functions and extents of PTMs remain largely unknown in prokaryotic cells compared to eukaryotic cells. Lysine acetylation is an attractive and prevalent PTM in bacteria. An increasing number of investigations have been dedicated to identify acetylated proteins by proteomics. Some studies have shown that acetylation can play a pivotal role in bacterial virulence, resistance, or biofilm (4). Enzymes involved in acetylation addition (lysine acetyltranferase KAT) or removal (lysine deacetylase KDAC) would provide a better mechanistic understanding of bacterial physiology and therefore could be considered as potential therapeutic targets. So far, little information is available on these enzymes in <em>A. baumannii</em> (5). Recently, in a global dynamic proteome study of<em> A. baumannii</em> ATCC 17978 strain grown in sessile mode, we highlighted the highest protein fold change for a protein belonging to the Sir2-like family which may possess a KDAC activity (6). The aim of the current study was to evaluate the involvement of this protein in <em>A. baumannii</em> physiology. For this purpose, a gene deletion approach was carried out to perform different phenotype tests (drugs and oxidative stress resistance, virulence assays, motility and biofilm formation) on wild-type and mutant strains. We compared, in biofilm mode of growth, acetylomes of the WT and the mutant. Our results demonstrated more than twice acetylated proteins in mutant in comparison to the WT. Of interest, biofilm formation in mutant was sensibly decreased. These different results suggest a potential involvement of this protein in <em>A. baumannii</em> biofilm formation.</p> <p> </p> <p>(1) Antunes et al. Acinetobacter baumannii: evolution of a global pathogen. Pathog. Dis. 71(2014), 292-301.</p> <p>(2) Espinal et al. Effect of biofilm formation on the survival of Acinetobacter baumannii on dry surfaces. J. Hosp. Infect. 80(2012), 56–60.</p> <p>(3) Richters. Targeting protein arginine methyltransferase 5 in disease. Future Med. Chem. 9(2017), 2081-2098.</p> <p>(4) VanDrisse and Escalante-Semerena. Protein acetylation in bacteria. Annu. Rev. Microbiol. 73(2019), 111-132.</p> <p>(5) Carabetta and Cristea. Regulation, function, and detection of protein acetylation in bacteria. J. Bacteriol. 199(2017), e00107-17.</p> <p>(6) Kentache et al. Global dynamic proteome study of a pellicle-forming Acinetobacter baumanii strain. Mol. Cell. Proteomics. 16(2017), 100-112.</p>

scholarly journals Staphylococcus aureus Arsenal To Conquer the Lower Respiratory Tract

mSphere ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Mariane Pivard ◽  
Karen Moreau ◽  
François Vandenesch
Keyword(s):  
Staphylococcus Aureus ◽  
Respiratory Tract ◽  
Virulence Factors ◽  
Lower Respiratory Tract ◽  
Defense Mechanisms ◽  
Future Research ◽  
Epithelial Barrier ◽  
Content Type ◽  
Wide Range ◽  
The Impact

ABSTRACT Staphylococcus aureus is both a commensal and a pathogenic bacterium for humans. Its ability to induce severe infections is based on a wide range of virulence factors. S. aureus community-acquired pneumonia (SA-CAP) is rare and severe, and the contribution of certain virulence factors in this disease has been recognized over the past 2 decades. First, the factors involved in metabolism adaptation are crucial for S. aureus survival in the lower respiratory tract, and toxins and enzymes are required for it to cross the pulmonary epithelial barrier. S. aureus subsequently faces host defense mechanisms, including the epithelial barrier, but most importantly the immune system. Here, again, S. aureus uses myriad virulence factors to successfully escape from the host’s defenses and takes advantage of them. The impact of S. aureus virulence, combined with the collateral damage caused by an overwhelming immune response, leads to severe tissue damage and adverse clinical outcomes. In this review, we summarize step by step all of the S. aureus factors implicated in CAP and described to date, and we provide an outlook for future research.

scholarly journals Investigation of the effect of N-Acetylcysteine on colistin mic values in Acinetobacter Baumannii strains isolated from clinical samples

2021 ◽  
Vol 38 (4) ◽  
pp. 471-473
Author(s):  
Fahriye EKŞİ ◽  
Mehmet ERİNMEZ
Keyword(s):  
Respiratory Tract ◽  
Acinetobacter Baumannii ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Clinical Samples ◽  
Chronic Obstructive ◽  
Identification System ◽  
Lower Respiratory Tract Infections ◽  
Broth Microdilution Method ◽  
Tract Infections

Acinetobacter baumannii is an opportunistic pathogen which colonize inpatients and cause severe infections, septic shock and death. With emergence of multi-drug resistant gramnegative species and being effective in A. baumannii infections, colistin becomes a treatment option again. N-acetylcysteine (NAC), is a mucolitic agent which used commonly in lower respiratory tract infections especially patients who have cronic respiratory disorders like Chronic obstructive pulmonary disease, cystic fibrosis and bronchiectasis. In this study we aim to investigate the effect of NAC, which commonly added in lower respiratory tract infections tratment regime, on MIC values colistin used in A. baumanni tratment. Fifty A.baumannii isolates were included in the study. The isolates were identified by automated identification system. With broth microdilution method, we investigated and compared the MIC (minimum inhibitory concentration) values of colistin and NAC+Colistin combination. Colistin MIC50 value is 0.25 μg/mL and MİK90 value is 1 μg/mL, NAC+Colistin combination MIC50 value is 0.25 μg/mL and MİK90 value is 1 μg/mL. The screening for the effectiveness of clinical drugs may provide clinical strategy to improve treatment outcomes of A. baumannii and reduce hospitalization days.

scholarly journals Impact of a Cross-Kingdom Signaling Molecule of Candida albicans on Acinetobacter baumannii Physiology

2015 ◽  
Vol 60 (1) ◽  
pp. 161-167 ◽  
Author(s):  
Xenia Kostoulias ◽  
Gerald L. Murray ◽  
Gustavo M. Cerqueira ◽  
Jason B. Kong ◽  
Farkad Bantun ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Cell Membrane ◽  
Acinetobacter Baumannii ◽  
Biofilm Formation ◽  
Defense Mechanism ◽  
Membrane Integrity ◽  
Efflux Pumps ◽  
Signaling Molecule ◽  
Content Type ◽  
Antagonistic Interactions

ABSTRACTMultidrug-resistant (MDR)Acinetobacter baumanniiis an opportunistic human pathogen that has become highly problematic in the clinical environment. Novel therapies are desperately required. To assist in identifying new therapeutic targets, the antagonistic interactions betweenA. baumanniiand the most common human fungal pathogen,Candida albicans, were studied. We have observed that theC. albicansquorum-sensing molecule, farnesol, has cross-kingdom interactions, affecting the viability ofA. baumannii. To gain an understanding of its mechanism, the transcriptional profile ofA. baumanniiexposed to farnesol was examined. Farnesol caused dysregulation of a large number of genes involved in cell membrane biogenesis, multidrug efflux pumps (AcrAB-like and AdeIJK-like), andA. baumanniivirulence traits such as biofilm formation (csuA,csuB, andompA) and motility (pilZandpilH). We also observed a strong induction in genes involved in cell division (minD,minE,ftsK,ftsB, andftsL). These transcriptional data were supported by functional assays showing that farnesol disruptsA. baumanniicell membrane integrity, alters cell morphology, and impairs virulence characteristics such as biofilm formation and twitching motility. Moreover, we showed thatA. baumanniiuses efflux pumps as a defense mechanism against this eukaryotic signaling molecule. Owing to its effects on membrane integrity, farnesol was tested to see if it potentiated the activity of the membrane-acting polymyxin antibiotic colistin. When coadministered, farnesol increased sensitivity to colistin for otherwise resistant strains. These data provide mechanistic understanding of the antagonistic interactions between diverse pathogens and may provide important insights into novel therapeutic strategies.

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