细菌对利福定的耐药性与细菌包膜屏障的关系

选用大肠杆菌k-12及其耐利福定菌株,利用同位素示踪技术研究发现利福定明显抑制~3H-尿苷掺入敏感菌,而耐药菌掺入则不受抑制,加用膜通透剂EDTA后,~3H-尿苷掺入耐药菌受到明显的抑制;~3H-利福定透入耐药菌的量明显低于透入敏感菌的量,用EDTA后,透入耐药菌中的~3H-利福定显著增加。结果提示:细菌包膜屏障通透性降低使药物进入菌体减少是细菌对利福定耐药的重要机制之一。     

结核杆菌耐利福定与细菌RNA聚合酶变异关系的研究

选用结核杆菌H_(37)Rv,于体外诱导筛选获得耐利福定(1250μg/ml)菌株,检测了利福定抗结核杆菌活性及其与6种常用抗结核药物的交叉耐药性;以~3H-尿苷进行掺入实验,发现利福定明显抑制~3H-尿苷掺入敏感菌,而对掺入耐药菌则无抑制;提取及分析结核杆菌RNA聚合酶,发现敏感菌酶活性受利福定明显抑制,耐药菌酶活性则未见抑制。结果提示:结核杆菌耐利福定与耐药菌RNA聚合酶改变有关。     

利福定耐药机制探讨—耐药菌及敏感菌的形态学比较

本文报道利福定耐药及敏感细菌的形态学比较。扫描电镜见大肠杆菌耐药菌菌体变短,表面较敏感菌坚实、粗糙;透射电镜观察见耐药菌外膜增厚,电子密度增加。敏感菌以利福定(100μg/ml)处理4h后,光镜下可见菌体变得模糊,出现溶解现象;透射电镜见胞质疏松、核糖体减少并出现空泡。耐药菌经药物处理后无明显改变,但用药时加用EDTA,则出现与敏感菌类似的改变。该结果支持利福定耐药性与细菌包膜屏障改变有关。     

中国利福霉素药理学的研究进展

新利福霉素产生菌的发现:利福霉素是一组结构相似而复杂的大环抗生素,由地中海链霉菌及诺卡氏菌产生.1970年代初.四川抗菌素工业研究所在中国桂林泥塘土壤中发现产生利福霉素的小单孢菌(S-190)为国际首创.新利福霉素的研究:中国对国产利福霉素SV及1974年上市的利福平(RFP)的临床前及临床药理进行了深入的研究.利福定(R-761)是一个新的半合成药物,具有抗结核作用强及血药浓度比利福平高两倍的优点.利福喷丁(R-773)是一个长效利福霉素,其半衰期为32.8小时,分别比利福平及利福定长5倍及2倍.体外利福喷丁对结核杆菌的抗菌作用比利福平强,但比利幅定弱.小鼠体内实验表明它的抗结核作用比利福平及利福定强.品型及生物利用度的研究:从丁醇获得的利福平晶型Ⅰ和SVⅢ及丙酮制成的品型们Ⅱ常稳定,具有良好的解离度及生物利用度.而乙醇SVl结晶则非常不稳定,生物利用度低,仅为晶型Ⅰ、SVⅢ和Ⅱl/3.利福定的1、IV晶型有良好的生物利用度,但晶型Ⅱ则甚差.作用机理的研究:同位素前体参入实验发现利福霉素类的RFP、H、R-751、R-761及R-773抑制细菌RNA合成,但对DNA及蛋白质合成的影响较小.R-751对M607的RNA合成也有非常显著的抑制作用.利福霉素还有明显的后效作用,其强度:利福喷丁>利福定>利福平.经药物处理细菌的超微结     

利福霉素类抗生素耐药性与突变细菌包膜屏障的关系

利福霉素是治疗结核、麻风等有效药物之一。近年来,随着新利福霉素衍生物的不断发展与临床滥用,又引起了新的问题——耐药性。国外研究证明,这类药物的耐药性与RNA多聚酶的突变有关,但耐药性与色膜屏障的关系至今尚无定论。本文采用国产利福平(RFP)、利福定(RFD)和利福喷丁霉素(DL-473)通过同位素示踪、电镜和电镜自显影对细菌形态、结构、药物分布以及包膜组份等进行了突变耐药机理初步研究,结果简介于下:     

利福霉素的药理与临床

利福霉素的药效动力学目前已知Rif抗菌机制是,抑制细菌RNA聚合酶;而其抗肿瘤作用是,抑制病毒逆向转录酶和DNA聚合酶,这三种酶统称Rif的靶酶。 Rif和细菌RNA聚合酶,容易形成稳定的复合物,使RNA合成停止。利用RNA之放射性前体物之一~3H尿苷掺入菌体速度,可以间接测定菌体RNA聚合酶活性;研究中发现利福定(RFD)和利福平(RFP)与     

新的利福霉素衍生物环戊哌嗪利福霉素对金黄色葡萄球菌的体内外抗菌作用

本文选择50株临床分离的金黄色葡萄球菌,比较了利福平、利福定及新的利福霉素衍生物环戊哌嗪利福霉素的体外抗菌活力,并试验了利福平、利福定、环戊哌嗪利福霉素及青霉素对实验性金黄色葡萄球菌感染小     

反相高效液相色谱法研究家兔体内利福定对地塞米松代谢动力学的影响

已知利福平是一种肝微粒体酶诱导剂,我们在临床药学工作中发现,与利福平结构相似的另一强效抗菌药利福定与糖皮质激素联用时,可使后者的临床疗效显著降低。因此,推测利福定也可能有肝微粒体酶诱导作用,从而加速糖皮质激素的肝脏代谢,降低其治疗有效浓度。本实验从药物相互作用的角度,研究家兔体内利福定对地塞米松代谢动力学的影响。     

利福定片剂的生物有效性

利福定(异丁基哌嗪力复霉素,R-76-1)系利福霉素类衍生物,自1976年研制成功并投放市场以来,多年的临床实践表明,利福定对结核杆菌及麻风杆菌具有与利福平相似的抗菌作用,吸收好,毒副反应小,疗效高,抗菌能力较利福平强,治疗费用低,因而受到广大患者的青睐。目前利福定已在我国的抗痨药物方面占有重要地位。利福定在生产过程中由于结晶的条件不同,出现Ⅰ、Ⅱ、Ⅲ、Ⅳ四种晶型,业已证明不同晶型在人工胃肠液中溶解度亦不同,Ⅰ、Ⅴ型溶解度好,Ⅱ、Ⅲ型较差,血浓和尿药排泄量也有相似的规     

利福定片生产工艺对其生物利用度的影响

利福定为一多晶型化合物。但各种晶形的生物利用度有差别。利福定片生产工艺可影响晶形的转化,因而对其生物效价影响甚大,利福定片选用全粉末直接压片法有较高的生物效价。     

Gentamicin-susceptibility of various pathogens isolated from clinical materials]

We studied on the antibacterial activity of gentamicin against various pathogens isolated from clinical materials mainly isolated during 1974 and 1975, comparing with other antibiotics. Beta hemolytic streptococci, pneumococci and enterococci are less susceptible to gentamicin than staphylococci. Staph, aureus and Staph. epidermidis resistant to various antibiotics are very susceptible to gentamicin, and no resistant strain to this drug was found. Haemophilus influenzae, H. parainfluenzae and H. parahaemolyticus are very susceptible to gentamicin, and there is no resistant strain to this drug. Escherichia coli, Klebsiella, Citrobacter, Serratia and five species of Proteus are more susceptible to gentamicin and tobramycin than dibekacin and amikacin. A few resistant or less susceptible strains to gentamicin are found in E. coli, Citrobacerr, Serratia, Pr. morganii and Pr. rettgeri. Pr. inconstans is less susceptible to gentamicin than other species of Proteus. Antibacterial activity of gentamicin against Pseudomonas aeruginosa is very strong, but dibekacin and tobramycin are stronger. Gentamicin-resistant strains of Pseudomonas aeruginosa are now rather few.     

呼吸道感染常见细菌分泌MPT64蛋白或其抗原类似物情况分析

目的:进一步确证呼吸道感染常见细菌分泌结核分枝杆菌MPT64蛋白或抗原类似物的情况,为结核病试验诊断研究提供循证依据。方法:选取2019年3月至2020年12月清远市清新区人民医院送检的合格痰标本80株培养分离株,依细菌分离时间先后将样本分为训练集样本组50株和测试集样本组30株。取ATCC25923金黄色葡萄球菌、A...     

In vitro activity of clinafloxacin against fluoroquinolone resistant Spanish clinical isolates.

The in vitro activity of clinafloxacin against 162 ciprofloxacin-resistant clinical isolates was determined. Isolates were selected when their MIC to ciprofloxacin was 2 mg/l (intermediate) or > 2 mg/l (resistant). The following strains were tested: 61 Escherichia coli, 12 Klebsiella pneumoniae, 7 Proteus mirabilis, 21 Serratia marcescens, 4 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 21 Staphylococcus. aureus (resistant to methicillin) and 15 Enterococcus spp. Clinafloxacin, ciprofloxacin, ofloxacin and norfloxacin activities were evaluated by agar dilution using Müeller-Hinton agar according to NCCLS recommendations. Of the 162 isolates, 16 (9.8%) were intermediate and 146 (90.1%) resistant to ciprofloxacin. 95 of the 162 strains (58.6%) were susceptible, 27 (16.7%) intermediately susceptible, and 40 strains (24.7%) were resistant to clinafloxacin. The percentage susceptible to clinafloxacin was 65.6% for E. coli, 75% for K. pneumoniae, 71.4% for P. mirabilis, 28.6% for S. marcescens, 75% for E. cloacae, 33.3% for P. aeruginosa, 90.5% for S. aureus and 40% for Enterococcus spp. Clinafloxacin was active against 58.6% of the ciprofloxacin-resistant clinical isolates tested. It was particularly active against S. aureus strains resistant to both ciprofloxacin and methicillin.     

Distribution and changes in the susceptibility of bacteria isolated from clinical samples. II

In vitro activity of antimicrobial agents such as ABPC, SBPC, MPC, CEZ, CTM, CMZ, CTX, CMX, CZX, LMOX, CPZ, CFS and GM against major clinical isolates, S. aureus, S. pyogenes, E. coli, K. pneumoniae, P. mirabilis, C. freundii, Enterobacter spp., S. marcescens, P. vulgaris and P. aeruginosa, was examined. In this paper, we will report the susceptibility of S. aureus, S. pyogenes, E. coli, K. pneumoniae and P. mirabilis during a three-year period, 1981 to approximately 1983. CEZ- and GM-resistant S. aureus has markedly increased and occupied 24% and 18%, respectively, in 1983. CMZ and CFS have showed potent activity against CEZ-resistant S. aureus. It seems that the abuse of third generation-cephems and new oral cephalosporins is closely related with the increase of cephems-resistant S. aureus. The penicillin- and cephem-resistant strains of S. pyogenes could not be found in our study. Quite a few strains of E. coli, K. pneumoniae and P. mirabilis are resistant to penicillins, and also there is no appreciable change in susceptibility. Some strains of E. coli, K. pneumoniae and P. mirabilis showed low susceptibility to CPZ, but all strains showed high susceptibility and no change in susceptibility to third generations, and these strains showed no tendency to decrease in susceptibility to GM.     

氧氟沙星和托氟沙星在氟喹诺酮耐药大肠杆菌中的蓄积(英文)

目的:研究大肠杆菌耐药菌株蓄积亲水性氟喹诺酮药物氧氟沙星和疏水性药物托氟沙星的机制有无差异。方法:荧光测定法检测菌体内的药物蓄积量和主动外排;SDS-PAGE法分析细菌外膜蛋白。结果:氧氟沙星在Ecs与JF701的蓄积量基本一致,在JF703中较JF701低1/2,但在4株耐药菌的蓄积量较这些敏感菌低5—7倍;托氟沙星在氟喹诺酮耐药和敏感菌株中的蓄积则未见显著差异。加入质子载体DNP后5,10min,细菌中托氟沙星的蓄积缓慢下降,氧氟沙星的蓄积增加,尤其在耐药菌株明显。氧氟沙星的蓄积增加与其对细菌的MIC呈正相关(r分别为0.9623和0.8006)。此外,Ecs中OmpF和OmpC完整;R2、R256和R5、R6分别发生OmpF和OmpC缺失。结论:OmpF缺失和药物主动外排可导致氧氟沙星,而不是托氟沙星在菌体内的蓄积减少。     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1998). III. Secular changes in susceptibility

Susceptibilities to various antimicrobial agents were examined for Enterococcus faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas aeruginosa that were isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June 1998 to May 1999, and the results were compared with those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and complicated UTIs. Among E. faecalis strains, those with low susceptibilities to almost drugs have increased in the latest period. All 5 S. aureus strains isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM). Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to GM, and on the contrary the resistant strains have increased with the MIC90 of 256 micrograms/ml or above. Among S. aureus strains isolated from complicated UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the latest period compared to those during period of 1996-1997, and the MIC90s of them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4 micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from uncomplicated and complicated UTIs have been lower 2-3 classes in the latest period than those in 1997. Among Klebsiella spp. strains isolated from uncomplicated UTIs, those with low susceptibilities to almost cephems had increased in 1997, but few of them were detected in the latest study. The sensitive strains of P. aeruginosa to almost drugs have increased during the latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa were the best in our history. The sensitive strains of P. aeruginosa to ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have increased in the latest period.     

The resistance of recent clinical isolates against isepamycin, other aminoglycosides and injectable beta-lactams

Clinical isolates collected from clinical facilities across Japan in 1998 were tested against five aminoglycosides and three beta-lactams. The resistance of 50 strains each of methicillin sensitive Staphylococcus aureus, methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, Enterobacter sp., Serratia sp., Pseudomonas aeruginosa and Proteus sp. (P. mirabilis 25 strains and P. vulgaris 25 strains) to the aminoglycosides isepamicin (ISP), amikacin (AMK), gentamicin, tobramycin and dibekacin, and to the beta-lactams imipenem, ceftazidime and piperacillin (all three known to be effective against P. aeruginosa) were investigated using a micro liquid dilution method with the following results: 1. ISP was effective against all strains except for 14% of MRSA, 2% of Proteus sp., and 4% of P. aeruginosa. 2. Six strains of MRSA were resistant to all eight drugs; however, in these cases ISP exhibited a relatively low minimum inhibitory concentration (MIC) compared to the other compounds. 3. Four strains of MRSA were resistant to all drugs except ISP. MRSA was the only isolate to demonstrate a resistance to seven or more drugs. 4. Twenty-one strains of MRSA and 1 strain of P. aeruginosa were resistant to six drugs; however, all of these were susceptible to both ISP and AMK. 5. Against all strains tested, ISP generally exhibited a lower MIC compared to AMK. These results suggest that, even ten years after its entering the market, ISP is still an aminoglycoside having a high anti-bacterial activity against a wide range of clinical isolates.     

Antibacterial Activity of the Crude Extracts and Fractionated Constituents of Myrtus communis

The antibacterial activity of methanol crude extract of Myrtus communis L. (Myriaceae) was evaluated against 10 laboratory strains of microorganisms, including 6 Gram positive (Staphylococcus aureus, Micrococcus luteus, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Listeria monocytogenes) and 4 Gram negative bacteria (Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa and Campylobacter jejuni). The crude extract inhibited the growth of all tested bacteria except C. jejuni. The inhibition zone diameter for 0.5 mg/ml of the crude extract (fraction M) varies from 18 mm for S. aureus to 8 mm for S. agalactiae, and minimum inhibitory concentrations (MIC) range from 0.1 for S. aureus and M. luteus to over 2 mg/ml for E. coli. Further extraction of fraction M with diethyl ether, ethyl acetate, and ethanol results in 6 different fractions (M1-M6). These fractions were screened for antibacterial activity against the non-fastidious bacteria (S. aureus, M. luteus, E. coli, P. vulgaris, and P. aeruginosa). The diethyl ether extracted fraction (fraction M1) showed the highest level of activity in comparison to fraction M and other fractions. The MIC for S. aureus and M. luteus were reduced from 0.1 in the fraction M to 0.025 mg/ml in fraction M1 and for E. coli and P. aeruginosa was reduced from over 1 mg/ml in fraction M to 0.1 mg/ml in fraction M1. Essential oil was also active against the tested bacteria, and M. luteus showed the highest level of sensitivity (MIC 1 : 1600). The presence of antibacterial activity in different fractions and essential oil indicates that the extract possesses different compounds, which have different activities.