ABSTRACT
Resumen La fibrosis quística es una enfermedad hereditaria autosómica recesiva que se origina por mutaciones en el gen regulador de conductancia transmembranal de la fibrosis quística (CFTR, cystic fibrosis transmembrane conductance regulator). El CFTR es una proteína que transporta iones a través de la membrana de las células epiteliales pulmonares. La pérdida de su función conlleva la producción de un moco pegajoso y espeso, donde se pueden establecer y adaptar diversos patógenos bacterianos que contribuyen a la pérdida gradual de la función pulmonar. En este artículo de revisión se dará evidencia de los mecanismos moleculares que utilizan Pseudomonas aeruginosa y Burkholderia cenocepacia para sobrevivir y persistir en el ambiente pulmonar. Adicionalmente, se describirán las nuevas estrategias de terapia a base de moduladores de la función del CFTR.
Abstract Cystic fibrosis is an autosomal recessive inherited disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). CFTR is a protein that transports ions across the membrane of lung epithelial cells. Loss of its function leads to the production of thick sticky mucus, where various bacterial pathogens can establish and adapt, contributing to the gradual loss of lung function. In this review, evidence of the molecular mechanisms used by Pseudomonas aeruginosa and Burkholderia cenocepacia to survive and persist in the pulmonary environment will be provided. Additionally, new therapeutic strategies based on CFTR function modulators will be described.
ABSTRACT
OBJECTIVES: To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation. METHODS: We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013. RESULTS: From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection. CONCLUSION: The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Young Adult , Lung Transplantation/adverse effects , Burkholderia cepacia/isolation & purification , Burkholderia Infections/etiology , Cystic Fibrosis/microbiology , Phylogeny , Time Factors , Brazil/epidemiology , DNA, Bacterial , Prospective Studies , Regression Analysis , Risk Factors , Lung Transplantation/mortality , Treatment Outcome , Burkholderia Infections/mortality , Cystic Fibrosis/surgery , Cystic Fibrosis/complications , Cystic Fibrosis/mortality , Kaplan-Meier Estimate , Contraindications, Procedure , Intensive Care Units , Length of StayABSTRACT
Objective To identify the risk factors of Burkholderia cenocepacia associated nosocomial lower respiratory tract infections (NLRTIs),and to investigate the drug resistance of Burkholderia cenocepacia strains.Methods A total of 138 patients with Burkholderia cenocepacia associated NLRTIs and 40 patients with non-Burkholderia cenocepacia associated NLRTIs were enrolled in the study.All patients were collected from the Second Affiliated Hospital of Wenzhou Medical University during January 2009 and December 2012.Clinical data and results of drug sensitivity tests were retrospectively reviewed.Chi-square test and Logistic regression analysis were performed to identify the risk factors of Burkholderia cenocepacia associated NLRTIs.Results Logistic regression analvsis showed that combination use of 2 or more antimicrobial agents,mechanical ventilation,stay in intensive care unit (ICU) for more than two weeks,use of antacid H2 antagonist and deep venous puncture were the independent risk factors of Burkholderia cenocepacia associated NLRTIs (OR =6.315,5.957,5.254,4.585 and 2.017,P ＜0.05).Burkholderia cenocepacia strains were sensitive to levofloxacin,ceftazidime and sulfamethoxazole; More than 40％ strains were resistant to cefotaxime,ceftriaxone,cefepime,aztreonam and tetracycline; And nearly 100％ strains were resistant to gentamicin,amikacin and tobramycin.Conclusion Burkholderia cenocepacia associated NLRTIs are more likely to occur in patients with combination use of 2 or more antimicrobial agents,mechanical ventilation,and those who stay in ICU for more than two weeks,or received antacid and deep venous punctures,and most Burkholderia cenocepacia strains are multiple drug resistant.
ABSTRACT
OBJECTIVE To study 39 kinds of resistant-related genes in a pan-resistant Burkholderia cenocepacia(BCE) strain,in the sputum from a severe hepatitis B patient.METHODS To detect the susceptibility to antimicrobial agents by MIC,16S rRNA,39 resistant-related genes including 29 ?-lactamases genes,6 aminoglycoside-modifying enzymes(AMEs) genes,chlorhexidine/sulfadiazine resistant gene(qacE△1-sul1),integron(intⅠ1,2,3),et al,of 1 strain of BCE in the sputum from a severe hepatitis B patient,were measured by PCR,and verified by DNA sequencing.RESULTS The strain was BCE conformed by 16S rRNA-PCR-DNA sequencing.It was susceptible to ceftazidime,cefepime,ciprofloxacin,levofloxacin,and trimethoprim/sulfamethoxazole,but resistant to piperacillin,aztreonam,cefotaxime,cefoxitin,meropenem,imipenem,nitrofurantoin,gentamicin and amikacin.There were positive of 6 kinds of resistant-related genes(blaTEM-116,aac(6′)-Ⅰb,aac(3)-Ⅰ,ant(2″)-Ⅰ,ant(3″)-Ⅰ,and intⅠ1),28 kinds of ?-lactamases genes,2 kinds of AMEs genes(aac(6′)-Ⅱ and aac(3)-Ⅱ),2 kinds genes of intⅠ(intⅠ2 and intⅠ3) were negative.CONCLUSIONS The multi-resistant BCE is with its multiple resistant mechanisms,and mainly relates to 6 kinds of resistant-related genes(blaTEM-116,aac(6′)-Ⅰb,aac(3)-Ⅰ,ant(2″)-Ⅰ,ant(3″)-Ⅰ and intⅠ1.