RESUMO
OBJECTIVES: Effective use of antibiotics is critical to control the global tuberculosis pandemic. High-dose isoniazid (INH) can be effective in the presence of low-level resistance. We performed a systematic literature review to improve our understanding of the differential impact of genomic Mycobacterium tuberculosis (Mtb) variants on the level of INH resistance. The following online databases were searched: PubMed, Web of Science and Embase. Articles reporting on clinical Mtb isolates with linked genotypic and phenotypic data and reporting INH resistance levels were eligible for inclusion. METHODS: All genomic regions reported in the eligible studies were included in the analysis, including: katG, inhA, ahpC, oxyR-ahpC, furA, fabG1, kasA, rv1592c, iniA, iniB, iniC, rv0340, rv2242 and nat. The level of INH resistance was determined by MIC: low-level resistance was defined as 0.1-0.4 µg/mL on liquid and 0.2-1.0 µg/mL on solid media, high-level resistance as >0.4µg/mL on liquid and >1.0 µg/mL on solid media. RESULTS: A total of 1212 records were retrieved of which 46 were included. These 46 studies reported 1697 isolates of which 21% (n = 362) were INH susceptible, 17% (n = 287) had low-level, and 62% (n = 1048) high-level INH resistance. Overall, 24% (n = 402) of isolates were reported as wild type and 76% (n = 1295) had ≥1 relevant genetic variant. Among 1295 isolates with ≥1 variant, 78% (n = 1011) had a mutation in the katG gene. Of the 867 isolates with a katG mutation in codon 315, 93% (n = 810) had high-level INH resistance. In contrast, only 50% (n = 72) of the 144 isolates with a katG variant not in the 315-position had high-level resistance. Of the 284 isolates with ≥1 relevant genetic variant and wild type katG gene, 40% (n = 114) had high-level INH resistance. CONCLUSIONS: Presence of a variant in the katG gene is a good marker of high-level INH resistance only if located in codon 315.
Assuntos
Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Farmacorresistência Bacteriana/genética , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Antituberculosos/administração & dosagem , Marcadores Genéticos/genética , Humanos , Isoniazida/administração & dosagem , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/isolamento & purificação , Oxirredutases/genética , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Impact has been an important rock-forming process on the moon. Electron- and ion-probe analyses of major and minor elements show that most glasses and chondrule-like particles formed by shock melting of various proportions of mainly pyroxene, plagioclase, and ilmenite. This is the first direct evidence that chondrule-like molten droplets can form in impact events. Welding and shock lithification resulted in rocks texturally similar to chondrites but composition rules out the moon as source for chondrites. Impact craters on a nickel-iron sample evidence the importance of secondary impacts by accelerated lunar matter.
RESUMO
Garnet has been identified for the first time as a meteorite mineral in the Coorara chondrite from Western Australia. It replaces olivine grains in a 1-millimeter veinlet traversing the body of the meteorite. The associated olivine has abnormally low birefringence, which suggests a highly shocked condition. Microprobe analyses do not distinguish the garnet from the associated olivine, which has the composition (Mg(.75)Fe(.25))(2) SiO(4); the garnet may have the composition Mg(3)Fe(2)Si(3)O(12) but be unresolvable from the accompanying olivine, or alternatively is nonstoichiometric. Transformation of olivine to garnet under high pressure could have significant implications for the phase composition of the Earth's mantle.
