ABSTRACT
Obstructive sleep apnea (OSA) is closely related to many cardiovascular diseases, including hypertension, coronary heart disease, arrhythmia, heart failure and coronary revascularization. Continuous positive airway pressure (CPAP) therapy is still controversial in the prognosis of patients with obstructive sleep apnea complicated with cardiovascular disease. This method has not been fully confirmed by recent large randomized controlled trials except for its positive effects on controlling hypertension and atrial fibrillation.
ABSTRACT
<p><b>BACKGROUND</b>Extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) is one of the most popular pathogens that cause refractory respiratory tract infection. The genetic environment, including insertion sequences and the types of promoter, plays a key role in exploration of the mechanism of prevalence and dismission of the ESBL-producing K. pneumoniae isolates. The aim of the investigation was to target analysis the genetic environment and promoter sequences of blaCTX-M, blaSHV and blaTEM, the most popular β-lactamase genes harbored by ESBL-producing K. pneumoniae isolates.</p><p><b>METHODS</b>From February 2010 to July 2011, 158 of 416 K. pneumoniae isolates producing ESBL from patients with lower respiratory tract infection were collected from seven tertiary hospitals from Beijing, Anhui, Fujian, Liaoning, Hebei and Inner Mongolia Autonomous Region in China. The genetic environment including promoters of 10 types of blaCTX-M, 18 types of blaSHV and 2 types of blaTEM were analyzed by amplification and direct sequencing with various sets of PCR primers.</p><p><b>RESULTS</b>ISEcp1 was located upstream of the 5' end of the blaCTX-M gene in 130 (97.0%) out of 134 K. pneumoniae isolates harboring blaCTX-M and provided a conserved promoter to blaCTX-M. A non-coding sequence preceded by kdpC and recF was identified in all of the blaSHV genes except blaSHV-12 and blaSHV-2a. IS26 was also found upstream of 1 blaCTX-M-15, 10 blaSHV-1 strains, 4 blaTEM-1 and all of the blaSHV-2, blaSHV-2a, blaSHV-5 and blaSHV-12. Eighty-seven of 91 strains harboring blaTEM-1 carried a copy of Tn2 and IS26-blaTEM-1 fragments were also detected in 4 strains. With respect to K. pneumoniae, the genetic environment of blaCTX-M-38, blaSHV-142 and blaTEM-135 were firstly elaborated, and four kinds of novel genetic environment of blaCTX-M-3, blaCTX-M-15 and blaTEM-1 have been detected as well.</p><p><b>CONCLUSIONS</b>Perfective implementation of the genetic environment information of bgr;-lactamase gene needs to be further explored and supplemented. ISEcp1 and IS26 elements are widespread upstream of the blaCTX-M, blaSHV and blaTEM genes and contribute to horizontal transmission and genetic expression.</p>
Subject(s)
Humans , Anti-Bacterial Agents , Pharmacology , Bacterial Proteins , Genetics , Metabolism , China , Drug Resistance, Multiple, Bacterial , Genetics , Klebsiella pneumoniae , Genetics , Microbial Sensitivity Tests , Promoter Regions, Genetic , Genetics , beta-Lactamases , Genetics , MetabolismABSTRACT
<p><b>BACKGROUND</b>The extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae has increasingly become a major contributor to nosocomial infections and can exhibit multiple antibiotic resistance. Previous studies have focused on the resistance genes in ESBL-producing strains, and the resistance-associated genetic environment of non-ESBL-producing strains has been ignored until now. Here, we investigated the occurrence and characteristics of non-ESBL-producing K. pneumoniae, which potentially carries unexpressed resistance genes.</p><p><b>METHODS</b>K. pneumoniae strains were collected from five medical institutions in China from February 2010 to August 2013. The VITEK-2 ESBL detection system was used as a primary screen to identify the ESBL-producing phenotype, and the three primary types of ESBL-associated genes (CTX, SHV, and TEM) were detected by polymerase chain reaction (PCR) to confirm the strains presenting with a non-ESBL-producing phenotype. mRNA expression in the non-ESBL-producing strains was further screened by reverse-transcription PCR (RT-PCR) to validate their transcriptional efficiency.</p><p><b>RESULTS</b>Out of 224 clinically isolated antibiotic-sensitive K. pneumoniae strains with a non-ESBL-producing phenotype, 5 (2.2%) were identified to carry inactivated ESBL blaSHV genes with intact upstream promoter regions and resistance gene sequences. Interestingly, three of the five antibiotic-sensitive K. pneumoniae strains containing ESBL blaSHV genes still exhibited mRNA transcription of blaSHV, while the other two exhibited no mRNA transcription.</p><p><b>CONCLUSION</b>These findings suggest that inactivated ESBL genes exist in non-ESBL-producing antibiotic-sensitive K. pneumoniae strains, which have the potential to transform the strain into an ESBL phenotype if an inappropriate application or overdose of antibiotics is implemented during clinical management.</p>