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Karina Calvopiña Punyawee Dulyayangkul Kate J. Heesom Matthew B. Avison 《Molecular microbiology》2020,113(2):492-503
The β-lactam antibiotic ceftazidime is one of the handful of drugs with proven clinical efficacy against the important opportunistic human pathogen Stenotrophomonas maltophilia. Here, we show that mutations in the energy transducer TonB, encoded by smlt0009 in S. maltophilia, confer ceftazidime resistance and smlt0009 mutants have reduced uptake of ceftazidime. This breaks the dogma that β-lactams enter Gram-negative bacteria only by passive diffusion through outer membrane porins. We also show that ceftazidime-resistant TonB mutants are cross-resistant to fluoroquinolone antimicrobials and a siderophore-conjugated lactivicin antibiotic designed to target TonB-dependent uptake. This implies that attempts to improve the penetration of antimicrobials into S. maltophilia by conjugating them with TonB substrates will suffer from the fact that β-lactams and fluoroquinolones coselect resistance to these novel and otherwise promising antimicrobials. Finally, we show that smlt0009 mutants already exist among S. maltophilia clinical isolates and have reduced susceptibility to siderophore-conjugated lactivicin, despite the in vitro growth impairment seen in smlt0009 mutants selected in the laboratory. 相似文献
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Saichin Isipradit Maytinee Sirimaharaj Puwat Charukamnoetkanok Oraorn Thonginnetra Warapat Wongsawad Busaba Sathornsumetee Sudawadee Somboonthanakij Piriya Soomsawasdi Umapond Jitawatanarat Wongsiri Taweebanjongsin Eakkachai Arayangkoon Punyawee Arame Chinsuchee Kobkoonthon Pannet Pangputhipong 《PloS one》2014,9(12)
Background
The majority of vision loss is preventable or treatable. Population surveys are crucial for planning, implementation, and monitoring policies and interventions to eliminate avoidable blindness and visual impairments. This is the first rapid assessment of avoidable blindness (RAAB) study in Thailand.Methods
A cross-sectional study of a population in Thailand age 50 years old or over aimed to assess the prevalence and causes of blindness and visual impairments. Using the Thailand National Census 2010 as the sampling frame, a stratified four-stage cluster sampling based on a probability proportional to size was conducted in 176 enumeration areas from 11 provinces. Participants received comprehensive eye examination by ophthalmologists.Results
The age and sex adjusted prevalence of blindness (presenting visual acuity (VA) <20/400), severe visual impairment (VA <20/200 but ≥20/400), and moderate visual impairment (VA <20/70 but ≥20/200) were 0.6% (95% CI: 0.5–0.8), 1.3% (95% CI: 1.0–1.6), 12.6% (95% CI: 10.8–14.5). There was no significant difference among the four regions of Thailand. Cataract was the main cause of vision loss accounted for 69.7% of blindness. Cataract surgical coverage in persons was 95.1% for cut off VA of 20/400. Refractive errors, diabetic retinopathy, glaucoma, and corneal opacities were responsible for 6.0%, 5.1%, 4.0%, and 2.0% of blindness respectively.Conclusion
Thailand is on track to achieve the goal of VISION 2020. However, there is still much room for improvement. Policy refinements and innovative interventions are recommended to alleviate blindness and visual impairments especially regarding the backlog of blinding cataract, management of non-communicative, chronic, age-related eye diseases such as glaucoma, age-related macular degeneration, and diabetic retinopathy, prevention of childhood blindness, and establishment of a robust eye health information system. 相似文献
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