scholarly journals Clinafloxacin for Treatment of Burkholderia cenocepacia Infection in a Cystic Fibrosis Patient

2015 ◽  
Vol 60 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Akshu Balwan ◽  
David P. Nicolau ◽  
Minkey Wungwattana ◽  
Jonathan B. Zuckerman ◽  
Valerie Waters
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Cystic Fibrosis Patient ◽  
Respir Crit ◽  
Burkholderia Cenocepacia ◽  
Content Type ◽  
Link Type ◽  
Potential Therapeutic Role ◽  
Established Infection

ABSTRACTRespiratory infection withBurkholderia cenocepaciais associated with accelerated decline in lung function and increased mortality in cystic fibrosis (CF) patients (A. M. Jones, M. E. Dodd, J. R. W. Govan, V. Barcus, C. J. Doherty, J. Morris, and A. K. Webb, Thorax 59:948–951, 2004,http://dx.doi.org/10.1136/thx.2003.017210).B. cenocepaciaoften possesses innate resistance to multiple antimicrobial classes, making eradication uncommon in established infection (P. B. Davis, Am J Respir Crit Care Med 173:475–482, 2006,http://dx.doi.org/10.1164/rccm.200505-840OE). We report the use of clinafloxacin in a CF patient with advancedB. cenocepaciainfection, present pharmacokinetic (PK) data, and discuss the potential therapeutic role of clinafloxacin in patients with this condition.

The role of Akkermansia muciniphila in obesity, diabetes and atherosclerosis

2021 ◽  
Vol 70 (10) ◽  
Author(s):  
Alka Hasani ◽  
Saba Ebrahimzadeh ◽  
Fatemeh Hemmati ◽  
Aytak Khabbaz ◽  
Akbar Hasani ◽  
...  
Keyword(s):  
Type Species ◽  
Anaerobic Bacteria ◽  
Regulatory System ◽  
Content Type ◽  
Akkermansia Muciniphila ◽  
Link Type ◽  
Animal Trials ◽  
Obesity And Diabetes ◽  
Underlying Mechanisms

Alteration in the composition of the gut microbiota can lead to a number of chronic clinical diseases. Akkermansia muciniphila is an anaerobic bacteria constituting 3–5% of the gut microbial community in healthy adults. This bacterium is responsible for degenerating mucin in the gut; its scarcity leads to diverse clinical disorders. In this review, we focus on the role of A. muciniphila in diabetes, obesity and atherosclerosis, as well as the use of this bacterium as a next-generation probiotic. In regard to obesity and diabetes, human and animal trials have shown that A. muciniphila controls the essential regulatory system of glucose and energy metabolism. However, the underlying mechanisms by which A. muciniphila alleviates the complications of obesity, diabetes and atherosclerosis are unclear. At the same time, its abundance suggests improved metabolic disorders, such as metabolic endotoxemia, adiposity insulin resistance and glucose tolerance. The role of A. muciniphila is implicated in declining aortic lesions and atherosclerosis. Well-characterized virulence factors, antigens and cell wall extracts of A. muciniphila may act as effector molecules in these diseases. These molecules may provide novel mechanisms and strategies by which this bacterium could be used as a probiotic for the treatment of obesity, diabetes and atherosclerosis.

The role of Staphylococcus lugdunensis as a pathogen in children: a multicentre retrospective study

2021 ◽  
Vol 70 (5) ◽  
Author(s):  
Noa Hurvitz ◽  
Lea Ohana Sarna Cahan ◽  
Itai Gross ◽  
Daniel Grupel ◽  
Orli Megged ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Blood Culture ◽  
Otitis Media ◽  
Paediatric Population ◽  
Blood Stream ◽  
Staphylococcus Lugdunensis ◽  
Content Type ◽  
Link Type ◽  
Putative Role

Introduction: Staphylococcus lugdunensis (SL), a tube coagulase negative Staphylococcus , is known to be pathogenic in adults, causing mainly skin infections. Gap Statement: Previous studies assessing SL's role in paediatric populations are sparse and are mainly limited to case reports. Aim: Present the clinical characteristics consistent with SL infections and its putative role as a pathogen in the paediatric population. Methodology: A retrospective multicentre study was conducted in four paediatric medical centres in Israel. Patients with isolates of SL presenting between 2009–2019 were included. Results: SL was isolated from 40 patients. Average (±SD) age at presentation was 5.9 (±6.2) years, with 22 (55 %) being female. Skin, soft tissue and musculoskeletal infections were the most common (n=20, 50%) followed by ear infections (n=13, 32.5%). Five cases of urine isolates and two isolates from blood culture samples were also reported. Skin abscess was the most common infection among skin and soft tissue isolates, reported in 17 children (85%) with SL being the only pathogen in 15 (75%). Otitis media was the most common ear infection accounting for 12 (92%) of all cases with SL as the only isolate reported in 6 (46%). Five cases of SL isolates from urine specimens were reported, all of which with poor growth of bacteria and normal urinalysis. Two cases of SL growth in blood culture were found in children presenting with signs and symptoms consistent with invasive blood stream infection. Conclusions: In the paediatric population, studied infections caused by SL are increasingly observed. The results of this study highlight its role as a pathogen in soft tissue infections and its putative role in otitis media and invasive blood stream infections. However, the role of SL as an uropathogen was not established.

scholarly journals Stenotrophomonas maltophilia phenotypic and genotypic features through 4-year cystic fibrosis lung colonization

2020 ◽  
Author(s):  
Eliana Alcaraz ◽  
Daniela Centrón ◽  
Gabriela Camicia ◽  
María Paula Quiroga ◽  
José Di Conza ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Adult Patient ◽  
Virulence Factors ◽  
Stenotrophomonas Maltophilia ◽  
Type Species ◽  
Mutation Frequency ◽  
Content Type ◽  
Link Type ◽  
Clonal Relatedness ◽  
Over Time

Introduction. Stenotrophomonas maltophilia has emerged as one of the most common multi-drug-resistant pathogens isolated from people with cystic fibrosis (CF). However, its adaptation over time to CF lungs has not been fully established. Hypothesis. Sequential isolates of S. maltophilia from a Brazilian adult patient are clonally related and show a pattern of adaptation by loss of virulence factors. Aim. To investigate antimicrobial susceptibility, clonal relatedness, mutation frequency, quorum sensing (QS) and selected virulence factors in sequential S. maltophilia isolates from a Brazilian adult patient attending a CF referral centre in Buenos Aires, Argentina, between May 2014 and May 2018. Methodology. The antibiotic resistance of 11 S. maltophilia isolates recovered from expectorations of an adult female with CF was determined. Clonal relatedness, mutation frequency, QS variants (RpfC–RpfF), QS autoinducer (DSF) and virulence factors were investigated in eight viable isolates. Results. Seven S. maltophilia isolates were resistant to trimethoprim–sulfamethoxazole and five to levofloxacin. All isolates were susceptible to minocycline. Strong, weak and normomutators were detected, with a tendency to decreased mutation rate over time. XbaI PFGE revealed that seven isolates belong to two related clones. All isolates were RpfC–RpfF1 variants and DSF producers. Only two isolates produced weak biofilms, but none displayed swimming or twitching motility. Four isolates showed proteolytic activity and amplified stmPr1 and stmPr2 genes. Only the first three isolates were siderophore producers. Four isolates showed high resistance to oxidative stress, while the last four showed moderate resistance. Conclusion. The present study shows the long-time persistence of two related S. maltophilia clones in an adult female with CF. During the adaptation of the prevalent clones to the CF lungs over time, we identified a gradual loss of virulence factors that could be associated with the high amounts of DSF produced by the evolved isolates. Further, a decreased mutation rate was observed in the late isolates. The role of all these adaptations over time remains to be elucidated from a clinical perspective, probably focusing on the damage they can cause to CF lungs.

Identification of Crp as a novel regulator of the Std fimbrial expression in Salmonella

Microbiology ◽  
2021 ◽  
Author(s):  
Karine Dufresne ◽  
France Daigle
Keyword(s):  
Wild Type Strain ◽  
Distal Region ◽  
Transcriptional Factor ◽  
Major Influence ◽  
Wild Type ◽  
Content Type ◽  
Link Type ◽  
Serovar Typhimurium ◽  
Metabolic Regulators

The Salmonella enterica serovar Typhi genome contains 14 putative fimbrial systems. The Std fimbriae belong to the chaperone-usher family and its regulation has not been investigated in S. Typhi. Several regulators of Std were previously identified in the closely related serovar Typhimurium. We hypothesize that regulators of S. Typhimurium may be shared with S. Typhi, but that several other regulators remain to be discovered. Here, we describe the role of more than 50 different candidate regulators on std expression. Three types of regulators were investigated: known regulators in S. Typhimurium, in silico predicted regulators and virulence/metabolic regulators. Expression of std was determined in the regulator mutants and compared with the wild-type strain. Overall, 21 regulator mutations affect std promoter expression. The role of Crp, a newly identified factor for std expression, was further investigated. Crp acted as an activator of std expression on a distal region of the std promoter region. Together, our results demonstrate the major influence of Crp as a novel transcriptional factor on std promoter expression and later production of Std fimbriae in Salmonella .

Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus

2022 ◽  
Vol 71 (1) ◽  
Author(s):  
Bailey F. Keefe ◽  
Luiz E. Bermudez
Keyword(s):  
Cystic Fibrosis ◽  
Host Cell ◽  
Biofilm Formation ◽  
Type Species ◽  
Divalent Cations ◽  
Mycobacterium Abscessus ◽  
Content Type ◽  
Link Type ◽  
Populations At Risk

Introduction. Pulmonary infections caused by organisms of the Mycobacterium abscessus complex are increasingly prevalent in populations at risk, such as patients with cystic fibrosis, bronchiectasis and emphysema. Hypothesis. M. abscessus infection of the lung is not observed in immunocompetent individuals, which raises the possibility that the compromised lung environment is a suitable niche for the pathogen to thrive in due to the overproduction of mucus and high amounts of host cell lysis. Aim. Evaluate the ability of M. abscessus to form biofilm and grow utilizing in vitro conditions as seen in immunocompromised lungs of patients. Methodology. We compared biofilm formation and protein composition in the presence and absence of synthetic cystic fibrosis medium (SCFM) and evaluated the bacterial growth when exposed to human DNA. Results. M. abscessus is capable of forming biofilm in SCFM. By eliminating single components found in the medium, it became clear that magnesium works as a signal for the biofilm formation, and chelation of the divalent cations resulted in the suppression of biofilm formation. Investigation of the specific proteins expressed in the presence of SCFM and in the presence of SCFM lacking magnesium revealed many different proteins between the conditions. M. abscessus also exhibited growth in SCFM and in the presence of host cell DNA, although the mechanism of DNA utilization remains unclear. Conclusions. In vitro conditions mimicking the airways of patients with cystic fibrosis appear to facilitate M. abscessus establishment of infection, and elimination of magnesium from the environment may affect the ability of the pathogen to establish infection.

scholarly journals Complete Genome Sequence of Pseudomonas aeruginosa Strain AA2 (LMG 27630), an Early Isolate Recovered from the Airway of a German Cystic Fibrosis Patient

2020 ◽  
Vol 9 (26) ◽  
Author(s):  
Andrea Sass ◽  
Tom Coenye
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Respiratory Tract ◽  
Cystic Fibrosis Patient ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Opportunistic Pathogen ◽  
Content Type ◽  
Airway Infections ◽  
Early Isolate

ABSTRACT Pseudomonas aeruginosa is an opportunistic pathogen that is able to cause various infections, including airway infections in cystic fibrosis patients. Here, we present the complete closed and annotated genome sequence of P. aeruginosa AA2, an isolate obtained early during infection of the respiratory tract of a German cystic fibrosis patient.

scholarly journals In Vitro Activity of a Novel Glycopolymer against Biofilms of Burkholderia cepacia Complex Cystic Fibrosis Clinical Isolates

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Vidya P. Narayanaswamy ◽  
Andrew P. Duncan ◽  
John J. LiPuma ◽  
William P. Wiesmann ◽  
Shenda M. Baker ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Burkholderia Cepacia ◽  
Laser Scanning Microscopy ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Confocal Laser ◽  
Content Type ◽  
Biofilm Removal ◽  
Increased Risk

ABSTRACT Burkholderia cepacia complex (Bcc) lung infections in cystic fibrosis (CF) patients are often associated with a steady decline in lung function and death. The formation of biofilms and inherent multidrug resistance are virulence factors associated with Bcc infection and contribute to increased risk of mortality in CF patients. New therapeutic strategies targeting bacterial biofilms are anticipated to enhance antibiotic penetration and facilitate resolution of infection. Poly (acetyl, arginyl) glucosamine (PAAG) is a cationic glycopolymer therapeutic being developed to directly target biofilm integrity. In this study, 13 isolates from 7 species were examined, including Burkholderia multivorans, Burkholderia cenocepacia, Burkholderia gladioli, Burkholderia dolosa, Burkholderia vietnamiensis, and B. cepacia. These isolates were selected for their resistance to standard clinical antibiotics and their ability to form biofilms in vitro. Biofilm biomass was quantitated using static tissue culture plate (TCP) biofilm methods and a minimum biofilm eradication concentration (MBEC) assay. Confocal laser scanning microscopy (CLSM) visualized biofilm removal by PAAG during treatment. Both TCP and MBEC methods demonstrated a significant dose-dependent relationship with regard to biofilm removal by 50 to 200 μg/ml PAAG following a 1-h treatment (P < 0.01). A significant reduction in biofilm thickness was observed following a 10-min treatment of Bcc biofilms with PAAG compared to that with vehicle control (P < 0.001) in TCP, MBEC, and CLSM analyses. PAAG also rapidly permeabilizes bacteria within the first 10 min of treatment. Glycopolymers, such as PAAG, are a new class of large-molecule therapeutics that support the treatment of recalcitrant Bcc biofilm.

scholarly journals Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Uta Düesberg ◽  
Julia Wosniok ◽  
Lutz Naehrlich ◽  
Patience Eschenhagen ◽  
Carsten Schwarz
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Aspergillus Fumigatus ◽  
Age Groups ◽  
Antibiotic Use ◽  
Lower Lung ◽  
Lung Infections ◽  
The Impact

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

scholarly journals Rapid Emergence of Resistance to Linezolid and Mutator Phenotypes in Staphylococcus aureus Isolates from an Adult Cystic Fibrosis Patient

2013 ◽  
Vol 57 (10) ◽  
pp. 5186-5188 ◽  
Author(s):  
Asmaa Tazi ◽  
Jeanne Chapron ◽  
Gerald Touak ◽  
Magalie Longo ◽  
Dominique Hubert ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Cystic Fibrosis Patient ◽  
Therapeutic Option ◽  
Clinical Isolates ◽  
23S Rrna ◽  
Mutator Phenotype ◽  
Content Type ◽  
Emergence Of Resistance ◽  
Rapid Emergence

ABSTRACTLinezolid has emerged as an important therapeutic option for the treatment ofStaphylococcus aureusin patients with cystic fibrosis. We report the rapid emergence, upon treatment with linezolid, of linezolid-resistantS. aureusclinical isolates through the accumulation of resistance-associated 23S rRNA mutations, together with acquisition of an altered mutator phenotype.

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