细菌对抗生素的耐药发生率在逐年上升,特别是近些年来,耐药株已发展多个种属,特别是革兰阳性球菌,经常是对不同类的多种抗生素产生耐药,而且对那些已受到耐药株感染的病例,可供选择的药物治疗非常有限.细菌对β-内酰胺类抗生素(包括青...细菌对抗生素的耐药发生率在逐年上升,特别是近些年来,耐药株已发展多个种属,特别是革兰阳性球菌,经常是对不同类的多种抗生素产生耐药,而且对那些已受到耐药株感染的病例,可供选择的药物治疗非常有限.细菌对β-内酰胺类抗生素(包括青霉素和头孢菌素类)耐药在很多年前就已经产生了,而现在由葡萄球菌和肺炎球菌产生的耐药已变得相当普遍.且这种耐药常常是伴随着对大环内酯类(一类用于替代青霉素的重要常用抗菌药)的耐药.虽然大环内酯类-林可酰胺类-链阳性菌素B类(macrolide-lincosamide-streptogramin group B,MLSB)抗生素可用于治疗耐青霉素致病菌导致的呼吸道感染,但耐MLSB类抗生素的病原菌正在全球范围内蔓延,威胁着这些药物的应用.展开更多
msrA encodes an efflux protein in Staphylococcus spp.that confers inducible resistance to macrolides,such as erythromycin(ERY),but not telithromycin(TEL).Thus,msrA+S.aureus remain susceptible to TEL.Production of msrA...msrA encodes an efflux protein in Staphylococcus spp.that confers inducible resistance to macrolides,such as erythromycin(ERY),but not telithromycin(TEL).Thus,msrA+S.aureus remain susceptible to TEL.Production of msrAis regulated by a 320-bp upstream region,presumably by translational attenuation,similar to regulation of erm.We investigated whether ERY could induce TEL resistance in msrA+S.aureus.MICs of ERY and TEL were determined by broth microdilution(BMD).Inducible TEL resistance was detected by a BMD checkerboard panel containing combinations of ERY and TEL and by a D-test where an ERY disk was placed 15mm from a TEL disk on a blood agar plate.Blunting of the TEL zones of inhibition proximal to the ERY disk indicated inducible resistance and no blunting indicated no inducible resistance.Approximately 400bp of the upstream regulatory region and 200bp of msrA were amplified by PCR and sequenced.The TEL MICs for 10 msrA+isolates ranged from 0.06-2g/mL(MIC90=0.25g/mL);ERY MICs were all≥32g/mL.All isolates showed an increase in TEL MICs of>2doubling dilutions(MIC90>4g/mL)in the presence of ERY;All were also positive by D-test.For 9isolates(initial TEL MIC<1g/mL),constitutive TEL resistance was selected by plating cells on Mueller-Hinton agar with 2g/mL TEL.All 9isolates grew on the selective media and were resistant to TEL(MIC ranged 2-8g/mL).Mutation to constitutive resistance occurred at a rate of 8×10-7 to 2.4×10-6.Eight of the 9resistant isolates had a single nucleotide substitution in the upstream regulatory region relative to the parent strain.Specifically,six isolates had a G to T mutation at position-222;one had a C to A mutation at-228;And one had a C to A mutation at-247.Transformation of the msrAgene with above point mutation in regulatory region into S.aureus RN4220conferred the strain resistant(MIC=8g/mL)to the telithromycin while transformants with the wild-type msrAgene remained susceptible(MIC=1g/mL)to telithromycin.展开更多
Background The emergence of bacterial resistance to commonly used antibiotics, such as macrolides, is complicating the management of respiratory tract infections （RTIs）. Telithromycin, a ketolide antimicrobial struc...Background The emergence of bacterial resistance to commonly used antibiotics, such as macrolides, is complicating the management of respiratory tract infections （RTIs）. Telithromycin, a ketolide antimicrobial structurally related to macrolides, is approved for the treatment of community-acquired RTIs, and shows lower pathogen resistance rates. The purpose of this study was to compare the efficacy and safety of telithromycin with clarithromycin, a macrolide routinely used as therapy for RTIs. Methods We performed a meta-analysis of relevant randomized-controlled trials （RCTs） identified in PubMed, the Cochrane Library, Embase, CNKI and VIP databases. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure time in the per-protocol population, and the primary safety outcome was drug related adverse effects. Results Seven RCTs, involving 2845 patients with RTIs, were included in the meta-analysis. Oral telithromycin and clarithromycin showed a similar clinical treatment success in modified intention to treat and per-protocol population （cure and improvement） （odds ratios （ORs）： 0.84, 95% confidence intervals （C/）： 0.64-1.11 and OR： 1.14, 95% CI： 0.71-1.85, respectively）. Similar findings were obtained for secondary efficacy outcomes： clinical treatment success at a late post- therapy visit （OR： 0.92, 95% CI： 0.57-1.48） and microbiological treatment success at the test-of-cure time （OR： 1.14; 95% CI： 0.71-1.85）. The safety outcome analysis indicated telithromycin had a similar risk of drug-related adverse effect and serious adverse effect with clarithromycin. Conclusions Our findings indicate that oral telithromycin and clarithromycin have similar treatment efficacy and adverse effect. The advantages of lower antimicrobial resistance rates, once-daily short-duration dosing and reported lower health- care costs make oral telithromycin a useful option for the empiric management of mild-to-moderate RTIs.展开更多
文摘细菌对抗生素的耐药发生率在逐年上升,特别是近些年来,耐药株已发展多个种属,特别是革兰阳性球菌,经常是对不同类的多种抗生素产生耐药,而且对那些已受到耐药株感染的病例,可供选择的药物治疗非常有限.细菌对β-内酰胺类抗生素(包括青霉素和头孢菌素类)耐药在很多年前就已经产生了,而现在由葡萄球菌和肺炎球菌产生的耐药已变得相当普遍.且这种耐药常常是伴随着对大环内酯类(一类用于替代青霉素的重要常用抗菌药)的耐药.虽然大环内酯类-林可酰胺类-链阳性菌素B类(macrolide-lincosamide-streptogramin group B,MLSB)抗生素可用于治疗耐青霉素致病菌导致的呼吸道感染,但耐MLSB类抗生素的病原菌正在全球范围内蔓延,威胁着这些药物的应用.
文摘msrA encodes an efflux protein in Staphylococcus spp.that confers inducible resistance to macrolides,such as erythromycin(ERY),but not telithromycin(TEL).Thus,msrA+S.aureus remain susceptible to TEL.Production of msrAis regulated by a 320-bp upstream region,presumably by translational attenuation,similar to regulation of erm.We investigated whether ERY could induce TEL resistance in msrA+S.aureus.MICs of ERY and TEL were determined by broth microdilution(BMD).Inducible TEL resistance was detected by a BMD checkerboard panel containing combinations of ERY and TEL and by a D-test where an ERY disk was placed 15mm from a TEL disk on a blood agar plate.Blunting of the TEL zones of inhibition proximal to the ERY disk indicated inducible resistance and no blunting indicated no inducible resistance.Approximately 400bp of the upstream regulatory region and 200bp of msrA were amplified by PCR and sequenced.The TEL MICs for 10 msrA+isolates ranged from 0.06-2g/mL(MIC90=0.25g/mL);ERY MICs were all≥32g/mL.All isolates showed an increase in TEL MICs of>2doubling dilutions(MIC90>4g/mL)in the presence of ERY;All were also positive by D-test.For 9isolates(initial TEL MIC<1g/mL),constitutive TEL resistance was selected by plating cells on Mueller-Hinton agar with 2g/mL TEL.All 9isolates grew on the selective media and were resistant to TEL(MIC ranged 2-8g/mL).Mutation to constitutive resistance occurred at a rate of 8×10-7 to 2.4×10-6.Eight of the 9resistant isolates had a single nucleotide substitution in the upstream regulatory region relative to the parent strain.Specifically,six isolates had a G to T mutation at position-222;one had a C to A mutation at-228;And one had a C to A mutation at-247.Transformation of the msrAgene with above point mutation in regulatory region into S.aureus RN4220conferred the strain resistant(MIC=8g/mL)to the telithromycin while transformants with the wild-type msrAgene remained susceptible(MIC=1g/mL)to telithromycin.
文摘Background The emergence of bacterial resistance to commonly used antibiotics, such as macrolides, is complicating the management of respiratory tract infections （RTIs）. Telithromycin, a ketolide antimicrobial structurally related to macrolides, is approved for the treatment of community-acquired RTIs, and shows lower pathogen resistance rates. The purpose of this study was to compare the efficacy and safety of telithromycin with clarithromycin, a macrolide routinely used as therapy for RTIs. Methods We performed a meta-analysis of relevant randomized-controlled trials （RCTs） identified in PubMed, the Cochrane Library, Embase, CNKI and VIP databases. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure time in the per-protocol population, and the primary safety outcome was drug related adverse effects. Results Seven RCTs, involving 2845 patients with RTIs, were included in the meta-analysis. Oral telithromycin and clarithromycin showed a similar clinical treatment success in modified intention to treat and per-protocol population （cure and improvement） （odds ratios （ORs）： 0.84, 95% confidence intervals （C/）： 0.64-1.11 and OR： 1.14, 95% CI： 0.71-1.85, respectively）. Similar findings were obtained for secondary efficacy outcomes： clinical treatment success at a late post- therapy visit （OR： 0.92, 95% CI： 0.57-1.48） and microbiological treatment success at the test-of-cure time （OR： 1.14; 95% CI： 0.71-1.85）. The safety outcome analysis indicated telithromycin had a similar risk of drug-related adverse effect and serious adverse effect with clarithromycin. Conclusions Our findings indicate that oral telithromycin and clarithromycin have similar treatment efficacy and adverse effect. The advantages of lower antimicrobial resistance rates, once-daily short-duration dosing and reported lower health- care costs make oral telithromycin a useful option for the empiric management of mild-to-moderate RTIs.
