7 research outputs found
Clonal diversity and genetic profiling of antibiotic resistance among multidrug/carbapenem-resistant Klebsiella pneumoniae isolates from a tertiary care hospital in Saudi Arabia
Abstract Background The nexus between resistance determinants, plasmid type, and clonality appears to play a crucial role in the dissemination and survival of carbapenem-resistant Klebsiella pneumoniae (CRKP). The incidence of infections involving CRKP in Saudi Arabia is increasing and there is a need for detailed molecular profiling of this pathogen for CRKP surveillance and control. Methods The resistance determinants of 71 non-redundant CRKP isolates were investigated by polymerase chain reaction (PCR) and sequencing. Plasmid typing was performed using PCR-based replicon typing and the clonality of isolates was determined by multilocus sequence typing. Capsular polysaccharide synthesis genes and other virulence factors were examined using multiplex PCR. Diversity was calculated using DIVEIN, clonal relationship was determined using eBURST, and phylogenetic analysis was performed using SplitsTree4. Results A polyclonal OXA-48 gene alone was the most common carbapenemase detected in 48/71 (67.6%) isolates followed by NDM-1 alone in 9/71 (12.7%) isolates. Coproduction of OXA-48 and NDM-1 was observed in 6/71 (8.5%) isolates. Both carbapenemase genes could be transferred into an Escherichia coli recipient. CTX-M-15 was the most abundant extended-spectrum β-lactamase gene detected in 47/71 (66.2%) isolates, whereas clone-specific CTX-M-14 (ST-199 and -709) was found in 15/71 (21%) isolates. Sixty-seven of 71 isolates were positive for one or more plasmid replicons. The replicons detected were: IncFII; IncFIIK; IncFIA; IncFIB; L/M; IncI1; and IncN. FIIK and L/M were predominant, with 69 and 67% positivity, respectively. All isolates were negative for the magA (K1), rmpA, and K2 genes and presented a non-hypermucoviscous phenotype. Conclusion A polyclonal CRKP reservoir of sequence types (STs)-37, − 199, and − 152 was observed and ST-152 appeared to be a “frequent carrier” of the NDM-1 gene. ST-199, a singleton not previously reported, showed a sequence diversity suggestive of positive selection. A significant association was evident between resistance determinants and the clonal types of K. pneumoniae: all ST-152 isolates were positive for NDM-1 but negative for OXA-48; ST-199 isolates were positive for OXA-48 but negative for NDM-1; and ST-709 and -199 isolates were positive for CTX-M-14. The incidence of certain clonal types in large numbers predicts an outbreak-like situation and warrants stringent surveillance and infection control
Literature Review: Role of Budesonide with Surfactant on Preterm Infants
This review analyzes the advocacy of budesonide-booster and surfactant in treating respiratory disorders in preterm neonates. Premature labor leads to respiratory distress syndrome [RDS] because of inadequate surfactant production and immature lungs, which in turn raises the probability of chronic lung disorders like BPD. However, while promoting lung function and oxygenation as provided in exogenous surfactant therapy is effective, it does not meet the processes causing inflammation to reduce pulmonary complications in the long run. Budesonide, a highly selective anti-inflammatory glucocorticosteroid, can be used as an adjuvant to surfactant treatment because of its ability to act on the lungs with minimal systemic effects directly. Studies from PubMed and Embase also show that when combined, budesonide and surfactant have beneficial effects in decreasing the severity of RDS, enhancing lung function, and reducing the prevalence of BPD in premature infants. However, these promising results should be further investigated in terms of the determination of optimal dosing, administration time, and therapeutic application concerning safety issues in the long term. This combined strategy has valuable prospects for enhancing the respiratory prognosis in premature newborns
Multi-drug carbapenem-resistant Klebsiella pneumoniae infection carrying the OXA-48 gene and showing variations in outer membrane protein 36 causing an outbreak in a tertiary care hospital in Riyadh, Saudi Arabia
SummaryObjectivesTo investigate the genes of antibiotic resistance among isolates from the first reported carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in a tertiary care hospital, Riyadh, Saudi Arabia.MethodsAntimicrobial susceptibility testing was performed on bacterial isolates using the Microscan Walkaway system (Siemens, Germany) and was confirmed by Etest (AB Biodisk, Sweden). bla-CTX-M, -SHV, -TEM, -OXA-48, OXA-A,B,C,D, -KPC, -NDM, -VIM, -IMP, integron 1, and outer membrane proteins(Omp)-35 and Omp-36 were investigated by PCR amplification and direct sequencing of PCR products. Isolates were sequence-typed by multilocus sequence typing (MLST).ResultsAll isolates were resistant to cefotaxime, ceftazidime, cefepime, ciprofloxacin, and piperacillin–tazobactam, and 91% (21 out of 23) were resistant to amikacin and gentamicin. All isolates except two from a single patient were resistant to one of the carbapenems. CTX-M and SHV genes were detected in all isolates, CTX-M-15 and SHV-1 types being predominant among these extended-spectrum beta-lactamases (ESBLs). TEM-1 was found in all except one isolate (isolate 3). Significantly, the OXA-48 gene was also found in all isolates. OXA-D-gene was found in three out of 23 isolates. KPC, NDM, OXA-A, -B, -C, VIM, and IMP genes were absent in all isolates. Disruption of the Omp-36 gene due to insertion of transposon IS903 and/or IS4 was detected in four out of 23 isolates, and some unique variations were also observed in this gene, including an insertion of two amino acids in the L3 region of Omp-36 in one isolate (isolate 3) and a mutation resulting in a premature stop codon in another isolate (isolate 25). MLST revealed ST29 to be the predominant sequence type (17 out of 23 isolates, 74%). Three were ST709 and one each was ST37 and ST111; one isolate had an unknown ST.ConclusionsThis is probably the first reported outbreak of multidrug/carbapenem-resistant Klebsiella infection involving the OXA-48 gene from Saudi Arabia. Although the presence of ESBLs such as OXA, CTX-M, TEM, and SHV are predictable reasons for resistance, variations in the Omp-36 gene might also have precipitated this phenomenon. Disruption of the Omp-36 sequence by large insertional elements, the insertion of two amino acids in a very crucial part of this protein, and the presence of a premature stop codon in one isolate might have rendered this protein incomplete and non-functional. The study also demonstrated that more than one type of clone was responsible for this reported apparent outbreak and that ST29, a clone not reported from this region before, was the major clone responsible
Additional file 3: of Clonal diversity and genetic profiling of antibiotic resistance among multidrug/carbapenem-resistant Klebsiella pneumoniae isolates from a tertiary care hospital in Saudi Arabia
Individual diversity graphs. Diversity graphs for each of the seven multilocus sequence typing loci sequences i.e., gapA, mdh, pgi, phoE, rpoB, infB, and tonB. (PNG 92Â kb
Biallelic HMGXB4 loss-of-function variant causes intellectual disability, developmental delay, and dysmorphic features
Background: HMGXB4 (additionally known as HMG2L1) is a non-histone DNA-binding protein that contains a single HMG-box domain. HMGXB4 was originally described in Xenopus where it was seen to negatively regulate the Wnt/β-catenin signaling pathway. Materials and methods: In this study, we conducted a genetic and clinical evaluation of a single family with three affected individuals suffering from intellectual disability (ID), global developmental delay (GDD) and dysmorphic facial features.Whole genome sequencing (WGS) and Sanger sequencing were performed on the affected individuals' DNA to identify genetic variations. Additionally, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess gene expression in both the affected and unaffected individuals in the family. Result: WGS identified a homozygous frameshift variant c.1193_1196del p. (Lys398Argfs × 25) in exon 5 of the HMGXB4 gene (OMIM 604702), which completely segregated the disease phenotype in the family. Furthermore, RT-qPCR revealed a substantial decrease in the HMGXB4 gene expression in the affected individuals as compared to the unaffected individuals of the family. Conclusions: The current study is the first evidence linking a genetic variant in the HMGXB4 gene to ID, GDD, and dysmorphic facial features. Therefore, it is possible that HMGXB4 contributes significantly to developmental milestones and may be responsible for neurodevelopmental disorders in humans
Prevalence of Dietary Supplements Use among Gymnasium Users
Background. Several studies showed that regular gymnasium users use various dietary supplements without comprehension of their potential risks. Objective. To determine the prevalence and dietary supplement intake and assess the awareness of supplement use among regular gymnasium users in Riyadh, Saudi Arabia. Methods. A descriptive cross-sectional study was conducted among regular gymnasium users in Riyadh, Saudi Arabia, between April 2015 and June 2015. A validated structured questionnaire was used. Results. The study included 299 participants. Of these 113 (37.8%) were dietary supplements users and this was more common among males than females (44.7% versus 16.4%). Gender based analysis showed that males were exercising more frequently than females and the type of cardiovascular exercise was more among them. The most commonly used supplements were whey protein (22.1%), amino acids (16.8%), multivitamins (16.8%), creatine (11.5%), and omega 3 (11.5%). The reasons for taking dietary supplements were to improve body shape (47.7%), increase health (44.2%), and improve performance (41.5%). Conclusion. Most of the information about supplements was obtained from unreliable sources. More studies are needed to better understand supplements use and their impact on health in Saudi Arabia
Prevalence of Dietary Supplements Use among Gymnasium Users
Background. Several studies showed that regular gymnasium users use various dietary supplements without comprehension of their potential risks. Objective. To determine the prevalence and dietary supplement intake and assess the awareness of supplement use among regular gymnasium users in Riyadh, Saudi Arabia. Methods. A descriptive cross-sectional study was conducted among regular gymnasium users in Riyadh, Saudi Arabia, between April 2015 and June 2015. A validated structured questionnaire was used. Results. The study included 299 participants. Of these 113 (37.8%) were dietary supplements users and this was more common among males than females (44.7% versus 16.4%). Gender based analysis showed that males were exercising more frequently than females and the type of cardiovascular exercise was more among them. The most commonly used supplements were whey protein (22.1%), amino acids (16.8%), multivitamins (16.8%), creatine (11.5%), and omega 3 (11.5%). The reasons for taking dietary supplements were to improve body shape (47.7%), increase health (44.2%), and improve performance (41.5%). Conclusion. Most of the information about supplements was obtained from unreliable sources. More studies are needed to better understand supplements use and their impact on health in Saudi Arabia
