Activities of pefloxacin and ciprofloxacin against Mycobacterium leprae in the mouse

Because ciprofloxacin and pefloxacin are fluoroquinolones active against many mycobacterial species, both drugs were tested against Mycobacterium leprae in the mouse foot-pad system. Preliminary pharmacokinetic studies in the mouse showed that after a single oral dose of 150 mg/kg ciprofloxacin the peak serum concentration was 3.6 micrograms/ml, and after 50 mg/kg or 150 mg/kg pefloxacin peak serum concentrations were, respectively, 9.2 micrograms/ml and 16.9 micrograms/ml, the half-lives for serum elimination being about 2 hr for both drugs. The activity of daily 50 mg/kg and 150 mg/kg ciprofloxacin and pefloxacin against M. leprae was then tested in mice infected with 5 X 10(3) M. leprae. The growth of M. leprae was not prevented in mice treated continuously with either 50 mg/kg or 150 mg/kg ciprofloxacin, indicating that this drug had no or a limited bacteriostatic effect at the dosages used. In mice treated continuously with 50 mg/kg pefloxacin, growth of M. leprae was not prevented, but at monthly harvests the number of bacilli in the foot pads remained less than those of control mice (p less than 0.05). No growth of M. leprae occurred in mice treated continuously with 150 mg/kg pefloxacin. In mice treated for only 3 months with daily 150 mg/kg pefloxacin, the growth-delay that followed the stopping of the drug was 126 days, suggesting that approximately 99% of the M. leprae were killed. The pharmacokinetics of pefloxacin being more favorable in man than in the mouse, pefloxacin appears a possible drug for the chemotherapy of leprosy.     

Comparative in vitro and in vivo activity of fleroxacin and ofloxacin against various mycobacteria.

In vitro antimicrobial activity of fleroxacin (6,8- difluoro-1-(2-fluoroethyl)-1, 4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid) and ofloxacin against representative pathogenic mycobacteria was evaluated by the agar dilution method, using 7H11 agar medium. Fleroxacin showed appreciable antimicrobial activity against Mycobacterium tuberculosis (MIC90 = 6.25 mg/l), M. kansasii (MIC90 = 3.13 mg/l), and M. fortuitum (MIC90 = 6.25 mg/l), whereas M. marinum, M. scrofulaceum, M. avium, M. intracellulare, and M. chelonae were highly resistant to the agent. The activity of fleroxacin was comparable to that of ofloxacin. Fleroxacin showed antimicrobial activity against M. intracellulare phagocytosed in murine peritoneal macrophages at a concentration of 10 mg/l in the culture medium, but its activity was considerably lower than that of ofloxacin. On the other hand, the therapeutic activity of fleroxacin against M. fortuitum infection induced in mice was higher than that of ofloxacin. Neither fleroxacin nor ofloxacin was efficacious against M. intracellulare infection. Fleroxacin significantly depressed the growth of M. leprae in the mouse footpad.     

Activity of ofloxacin against Mycobacterium leprae in the mouse

Mice inoculated with 4800 Mycobacterium leprae in the left hind foot pad were treated from day 62 to day 150 after infection with 50 mg or 150 mg of ofloxacin per kg body weight, 150 mg pefloxacin per kg, or 50 mg prothionamide per kg. These drugs were administered by esophageal cannula 5 days weekly with dapsone (0.01 g per 100 g diet). Multiplication of M. leprae in the treated and in untreated control mice was assessed by monthly harvests. The treatment of mice with the smaller dosage ofloxacin, with pefloxacin, prothionamide, or dapsone uniformly resulted in a delay of multiplication of 4 months, compared to the multiplication of M. leprae in the untreated controls. The delay of multiplication (4 months) being 1 month longer than the duration of drug administration (3 months), all of the treatments may be considered as bacteriopausal or moderately bactericidal. In contast with these results, treatment of mice with 150 mg ofloxacin per kg resulted in no growth of the organisms whatever as late as 18 months after inoculation, strongly suggesting that, in that dosage, ofloxacin had killed all of the M. leprae. Such a profound killing activity has been observed only with rifampin. Although the pharmacokinetic characteristics of ofloxacin are different in man from those in the mouse, the daily dosage of 150 mg ofloxacin per kg body weight in the mouse is equivalent to 400 mg per day in man which is the usual therapeutic dosage; thus, the results obtained in the mouse may be extrapolated to man. Therefore, ofloxacin appears a very promising drug for the chemotherapy of leprosy.     

Ofloxacin for the treatment of leprosy

Among the major commercially available fluoroquinolones, ciprofloxacin was inactive against M. leprae in mice; pefloxacin was active, 50 mg/kg daily showed bacteriostatic activity but 150 mg/kg daily displayed bactericidal activity; ofloxacin was more active than pefloxacin, 50 mg/kg daily exerted the same level of bactericidal effect as pefloxacin 150 mg/kg daily, and ofloxacin 150 mg/kg displayed profound killing activity. Two clinical trials with 6 months of pefloxacin and/or ofloxacin in 31 previously untreated lepromatous patients have been completed. Pefloxacin 400 mg twice daily or 800 mg once daily or ofloxacin 400 mg once daily were equally effective; definite clinical improvement with drastically decrease of morphological index to the baseline were observed in all patients at 2 months after beginning of treatment; about 99.99%, or 4 "logs", of organisms viable on Day 0 were killed by 22 doses of either pefloxacin or ofloxacin. The side effects from the two trials were rare and mild, and the patients tolerated extremely well the combinations of pefloxacin/ofloxacin plus multidrug therapy (MDT) regimen for multibacillary leprosy recommended by WHO. The amount of rifampicin-resistant mutants in lepromatous patients before treatment are no more than 4 "logs", thus, all rifampicin-resistant mutants may be eliminated by 22 doses of either pefloxacin or ofloxacin. It is, therefore, possible that the combination of ofloxacin and rifampicin may considerably shorten the required duration of MDT.     

In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis.

The in vitro and in vivo activities of sparfloxacin (AT-4140) against M. tuberculosis are reported. The MICs of sparfloxacin for 50% and 90% of 18 clinical isolates were, respectively, 0.25 and 0.5 mg/l, one or two dilutions lower than that of ciprofloxacin and ofloxacin. In mice infected intravenously with 0.1 mg M. tuberculosis H37Rv strain, the minimal effective dosage of sparfloxacin, as assessed by survival rate, spleen enlargement and gross lung lesions, was 12.5 mg/kg. The activities of various regimens were in the following rank order: INH 25 mg/kg = sparfloxacin 50-100 mg/kg greater than ofloxacin 300 mg/kg greater than (or =) sparfloxacin 25 mg/kg greater than sparfloxacin 12.5 mg/kg greater than (or =) ofloxacin 200 mg/kg greater than ofloxacin 100 mg/kg greater than (or =) negative control. Therefore, on a weight to weight basis, sparfloxacin was six to eight-fold more active against M. tuberculosis infection in mice than ofloxacin. In addition, WIN 57273, a new broad-spectrum fluoroquinolone, at a dosage of 100 mg/kg daily, was inactive against M. tuberculosis infection.     

Antimycobacterial activity of a newly synthesized fluoroquinolone, Y-26611]

Y-26611, a newly developed fluoroquinolone having a morpholine moiety at the 7 position was examined for in vitro antimycobacterial activity by the agar dilution method using 7H11 medium. The MIC90 values of Y-26611 were as follows: Mycobacterium tuberculosis (25 strains), 0.4 micrograms/ml; M. kansasii (19 strains), 6.25 micrograms/ml; M. marinum (10 strains), 25 micrograms/ml; M. scrofulaceum (19 strains), 50 micrograms/ml; M. avium (18 strains), 50 micrograms/ml; M. intracellulare (31 strains), greater than 100 micrograms/ml; M. fortuitum (20 strains), 0.4 micrograms/ml; M. chelonae subsp. abscessus (15 strains), greater than 100 micrograms/ml; and M. chelonae subsp. chelonae (20 strains), 100 micrograms/ml. The MICs against M. tuberculosis and M. fortuitum were lower than those of ofloxacin (OFLX), although it had somewhat higher MICs against M. avium complex than OFLX. Antimicrobial activity of Y-26611 against M. tuberculosis phagocytosed in cultured murine peritoneal macrophages were somewhat lower, as compared to that of OFLX. When M. fortuitum-infected (iv) A/J mice were treated with Y-26611 by gavage at doses of 0.5-2 mg/mouse, once daily, six times per week, from day 1 for up to 4 weeks after infection, mice were protected from death and the number of CFU recovered from their visceral organs, such as the lungs, spleen and kidneys were reduced. The therapeutic efficacy of Y-26611 was similar as that of OFLX.     

氯法齐明抗结核分枝杆菌的体内外活性研究

目的 评价氯法齐明(clofazimine,CLF)在体外及体内抗结核分枝杆菌的活性,为临床应用提供依据.方法 应用微孔板指示剂法,测定氯法齐明对结核分枝杆菌标准株H37Rv及临床分离耐多药结核分枝杆菌(30株)的MIC;建立小鼠静脉感染H37Rv的结核病模型(105 CFU/只),根据氯法齐明的不同剂量,分为3个治疗组:20 mg/kg,每周给药5次(CLF-1组);10 mg/kg,每周给约5次(CLF-2组);20 mg/kg,每周给药2次(CLF-3组);治疗30 d后进行肺、脾组织活菌计数,应用单冈素方差分析,比较氯法齐明在小鼠体内的抗结核分枝杆菌活性.结果 氯法齐明对结核分枝杆菌H37Rv的MIC为0.12～0.24 μg/ml;对30株耐多药结核分枝杆菌临床分离株的MIC为0.12～1.92 μg/ml.在小鼠结核病治疗模型中,3个治疗组的小鼠肺活菌计数分别较空白对照组降低2.92、1.78和1.39 lg CFU,均具有统计学意义(F=74.09,P＜0.01).结论 氯法齐明具有较好的体外及体内抗结核分枝杆菌活性,值得进一步研究.     

Anti-Mycobacterium leprae activity of several quinolones studied in the mouse.

The anti-Mycobacterium leprae activity of several fluoroquinolones (A-56619, A-56620, ofloxacin, fleroxacin, lomefloxacin, temafloxacin, tosufloxacin, and PD-117596) was studied in the mouse. In a dosage of 150 mg/kg administered daily, A-56619 is active and A-56620 is inactive against M. leprae. Ofloxacin administered daily for 2 weeks at 300 mg/kg is bactericidal. The minimal effective dose of PD-117596, lomefloxacin and temafloxacin is less than 37.5 mg/kg. When administered at 300 mg/kg at monthly intervals temafloxacin, PD-117596, and ofloxacin are bacteriostatic; while fleroxacin and lomefloxacin are bactericidal. Tosufloxacin is less active than the other quinolones included in the present study.     

左旋氧氟沙星单体与左旋氧氟沙星凝胶的体外抗结核活性研究

目的观察卡波姆凝胶与左旋氧氟沙星联合体外抗结核作用和支气管介入的安全性。方法手工法、仪器法分别测定卡波姆凝胶与左旋氧氟沙星药物的最小抑菌浓度(MIC)和最小杀菌浓度(MBC)及家兔经支气管介入的安全性试验。结果左旋氧氟沙星的卡波姆凝胶对H37Rv标准株、牛型结核分枝杆菌、草分枝杆菌MIC值分别为0.5mg/L、0.5mg/L、1.0mg/L,MBC值分别为1.0mg/L、1.0mg/L和1.5mg/L;左旋氧氟沙星的卡波姆凝胶与左旋氧氟沙星单体MIC、MBC值无显著差异;家兔动物实验表明该药无任何毒副作用。结论左旋氧氟沙星凝胶具有与左旋氧氟沙星单体相同的抗结核菌药效,卡波姆基质不影响左旋氧氟沙星的抗菌活性;以卡波姆为基质的左旋氧氟沙星凝胶应用安全。     

Combination of ofloxacin and amikacin in the treatment of sternotomy wound infection

Mycobacterium fortuitum infection of soft tissue and wound (postoperative or otherwise) has been well reported in medical literature. In 1987, ten patients in our hospital with various cardiac diagnoses requiring open-heart surgery developed M fortuitum infection at the sternotomy site. As successful chemotherapy, in addition to surgical debridement, relies on in vitro susceptibility testing, ofloxacin and amikacin were thus assessed and found to have very satisfactory MIC. For the former: 1.25 mg/L for eight isolates, 2.5 mg/L for one isolate, and greater than 20 mg/L for one isolate were found. For the latter: 1 mg/L for six isolates, 2 mg/L for two isolates, and 4 mg/L and 8 mg/L for the remaining two isolates were found, respectively. These patients were given ofloxacin (300 mg once daily to 1,200 mg daily in divided doses) for three to six months and 500 mg amikacin daily (in two divided doses intravenously or intramuscularly) for three to eight weeks. The clinical outcome was favorable except for one patient who died of bacteremia due to M fortuitum coupled with many medical complications. Encouraged by these preliminary results, a future prospective study with ofloxacin as single agent for soft tissue, particularly postoperative sepsis due to M fortuitum, will be planned.     

圣露丸的抗结核作用初步实验研究

目的 评价中药圣露丸的体外及小鼠结核病模型中的抗结核活性。方法 在7H9液体培养基、7H10固体培养基中分别测定圣露丸对结核分枝杆菌标准株H37Rv的最低抑菌浓度(MIC)。气溶胶感染方式采用结核分枝杆菌标准株H37Rv先后感染SPF级BALB/C小鼠46只和36只,分别建立小鼠急性结核病模型。均为感染第10天开始给予药物治疗,随机分组,每组10只。其中圣露丸组每只小鼠每次剂量为3g/kg;异烟肼(INH)组,每次剂量为25mg/kg,同时设无药空白对照组。各组均口服灌胃给药,每周给药5次,分别给予3周和6周药物治疗。治疗结束后次日处死各组小鼠,称重,无菌操作下解剖,做肺组织活菌计数。结果 圣露丸在7H9液体培养基中对H37Rv的MIC为2.5mg/ml,在7H10固体培养基中对H37Rv的MIC为<5mg/ml。小鼠感染及治疗过程中各组耐受性良好,无死亡。给予3周共计15次(每次给予“圣露丸”3g/kg)剂量治疗后,圣露丸组小鼠全肺的CFU为 (6.81±0.71)lg CFU,较空白对照组降低0.39lg CFU。应用圣露丸治疗6周后,圣露丸组的小鼠全肺的CFU为 (4.33±0.51)lg CFU,较空白对照组降低1.10lg CFU。结论 在本研究条件建立的小鼠结核病模型中,中药圣露丸显示出抗结核活性,值得进一步研究。     

Study of the in vitro susceptibility of M. tuberculosis to ofloxacin in Spain. Spanish Study Group of M. tuberculosis resistance.

The aim of this study was to determine the proportion of antituberculosis ofloxacin resistance among Mycobacterium tuberculosis strain isolates in Spain. Over a period of one month, 213 M. tuberculosis strains collected from 14 different hospitals were studied, including strains both susceptible and resistant to primary antituberculosis drugs. In 28.1% of the strains, a minimum inhibitory concentration (MIC) for ofloxacin of 0.25 microg/ml was obtained; in 43.6% the MIC was 0.5 microg/ml; in 22.06% it was 1 microg/ml; and in 6.1% it was > or =2 microg/ml. Ofloxacin currently seems to be an effective antimicrobial in vitro against susceptible or multiresistant strains of M. tuberculosis in human immunodeficiency virus (HIV)-negative or HIV-positive patients in Spain.     

鸟分枝杆菌复合群对16种抗感染药物药敏试验的分析

目的 通过比较3种新型喹诺酮类药物(西他沙星、加替沙星和莫西沙星)与其他13种抗感染药物对鸟分枝杆菌复合群(MAC)分离株的体外活性,初步探讨喹诺酮类药物用于治疗MAC疾病的可能性.方法 琼脂梯度稀释法测定上述16种抗感染药物对MAC分离株的最低抑菌浓度(MIC),比较其能抑制90%菌株生长的MIC(MIC90).结果 与胞内分枝杆菌相比,鸟分枝杆菌菌株的MIC范围分布更广,且MIC90多高于胞内分枝杆菌.4种大环内酯类药物中,克拉霉素对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,分别为32和16 mg/L;4种利福霉素类化合物中利福拉齐对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,分别为0.5和0.25 mg/L;5种喹诺酮类药物中西他沙星对鸟分枝杆菌和胞内分枝杆菌的MIC90最低,均为4 mg/L,加替沙星和莫西沙星均为8 mg/L.2株克拉霉素敏感株(MIC=0.5 mg/L)对其他抗感染药物均接近或达到MIC范围的下限,3株克拉霉素不敏感株(MIC=64 mg/L)对除喹诺酮类以外的抗感染药物均接近MIC范围的上限.结论 利福拉齐、西他沙星、加替沙星和莫西沙星对MAC分离株具有较强的体外活性.     

氯法齐明对不同耐药类型结核分枝杆菌的体外抑菌活性研究

目的 评价氯法齐明对不同耐药类型的MTB临床分离菌株的体外抑菌活性,为临床应用提供依据.方法 应用微孔板观察法,测定氯法齐明对MTB标准株H37Rv及临床分离敏感、单耐药、多耐药、耐多药和广泛耐药菌株各15株的MIC,并将氯法齐明对不同耐药类型的MTB菌株体外活性与异烟肼、利福平、阿米卡星、卷曲霉素和氧氟沙星进行比较.结果 氯法齐明对敏感菌株的MIC(0.06～4.00mg/L)高于异烟肼(0.06～0.25 mg/L)和利福平(0.06～0.25 mg/L),与氧氟沙星(0.06～2.00mg/L)、阿米卡星(0.06～4.00mg/L)和卷曲霉素(0.50～4.00mg/L)相似;氯法齐明对单耐药菌株的MIC(0.03～4.00mg/L)与异烟肼(0.06～0.25 mg/L)和利福平(0.06～0.25 mg/L)相似,低于氧氟沙星(0.25～8.00mg/L)、阿米卡星(0.06～4.00mg/L)和卷曲霉素(0.50～8.00mg/L);氯法齐明对耐多药菌株的MIC(0.06～8.00mg/L)与阿米卡星(0.25～8.00mg/L)相似,优于氧氟沙星(0.125～8.00mg/L)和卷曲霉素(0.50～8.00mg/L);氯法齐明对广泛耐药菌株的MIC(0.03～8.00mg/L)明显优于其他药物.结论 氯法齐明对MTB菌株,尤其是耐多药和广泛耐药MTB菌株,均有较好的体外抑菌活性.

Abstract：

Objective To study the in vitro antituberculous activities of clofazimine (CLF) to different drug-resistant types of Mycobacterium tuberculosis.Methods The minimal inhibitory concentration (MIC) of CLF and isoniazid (INH), rifampicin (RFP), ofloxacin (OFLX), amikacin (AK), and capreomycin (CPM) against sensitive, single-drug resistant (SDR), poly-drug resistant (PDR), multi-drug resistant (MDR), and extensive-drug resistant (XDR) Mycobacterium tuberculosis strains isolated clinically were determined by microplate assays.Results The MICs of CLF for sensitive, SDR, PDR, MDR and XDR strains of clinically isolated Mycobacterium tuberculosis were 0.06 -4.00 mg/L, 0.03 -4.00 mg/L, 0.06 -8.00 mg/L, 0.06 - 8.00 mg/L, 0.03 - 8.00 mg/L.For the sensitive group, the MIC of CLF ( 0.06 -4.00 mg/L) was higher than that of INH (0.06 -0.25 mg/L) and RFP (0.06 -0.25 mg/L), while there was no significant difference among OFLX (0.06 -2.00 mg/L), AK (0.06 -4.00 mg/L), and CPM (0.50 -4.00 mg/L).For the single-drug resistant group, there was no significant difference among CLF (0.03-4.00 mg/L), INH (0.06-0.25 mg/L), and RFP (0.06-0.25 mg/L), but the MIC of CLF was lower than that of OFLX ( 0.25 - 8.00 mg/L), AK ( 0.06 - 4.00 mg/L ), and CPM ( 0.50 - 8.00 mg/L).For the MDR group, there was no significant difference between CLF (0.06 -8.00 mg/L) and AK (0.25 - 8.00 mg/L), but the MIC of CLF was lower than that of OFLX (0.125 - 8.00 mg/L) and CPM (0.50 -8.O0 mg/L).For the XDR group, the MIC of CLF (0.03 -8.00 mg/L) was lower than that of others.Conclusion CLF showed good in vitro activity against Mycobacterium tuberculosis, especially MDR and XDR strains.     

Single daily-dose ofloxacin monotherapy for Mycobacterium fortuitum sternotomy infection

Infection of sternotomy wounds due to Mycobacterium fortuitum-chelonei complex postoperatively was noted in ten patients in 1987 and six patients in 1988 in our hospital. The first ten patients were treated with a combination of ofloxacin and amikacin, successfully in nine. In the six later patients, five had M fortuitum infection and one had M chelonei infection. In those five we used single daily-dose ofloxacin, 600 mg, in three with rapid clinical response and bacteriologic cure. The MIC of ofloxacin for these three isolates ranged from 0.32 mg/L to 1.25 mg/L, and peak serum level of ofloxacin assessed by high-performance liquid chromatography ranged from 4.1 mg/L to 8.0 mg/L. Monotherapy with ofloxacin is recommended for M fortuitum infection of wound and soft tissue, with in vitro susceptibility studies as a guide, pending further reinforcing clinical evidence.     

左氧氟沙星的抗结核作用研究

目的 以氧氟沙星（ＯＦＬＸ）为对照,通过药效学、药代动力学、临床试验三方面评价左氧氟沙星（ＬＶＬＸ）的抗结核作用。方法 采用二倍稀释法测定最低抑菌浓度氏杀菌浓度,以半数动物存活时间为指标比较药物对实验性结核病的疗效。高效液相色谱法测定健康志愿者口服３００ｍｇＬＶＬＸ或６００ｍｇＯＦＬＸ血药浓度,求两药各药代动力学参数并进行ｔ检验。将１３８例初、复治菌阳性结核患者随机分入ＬＶＬＸ治疗组或ＯＦＬＸ对照     

Antimycobacterial activities of a new quinolone, sparfloxacin]

Sparfloxacin (SPFX), a new quinolone, was studied its in vitro and in vivo activities against various mycobacteria, especially Mycobacterium intracellulare. SPFX exhibited a potent in vitro activity against M. tuberculosis, M.kansasii and M.fortuitum with MIC90 values of 0.2, 6.25 and 1.6 micrograms/ml, respectively, and the potency of SPFX was higher than that of ofloxacin (OFLX). M.marinum, M.scrofulaceum, M.avium, M.intracellulare, M.chelonae (subsp. abscessus and chelonae) were resistant to SPFX. SPFX inhibited the growth of M. intracellulare in 7H9 broth when added at the concentration of 0.2 microgram/ml and rapidly killed the organisms at the dose of 1 microgram/ml. The activity of SPFX was higher than that of OFLX. SPFX exhibited a greater antimicrobial activity against M.intracellulare phagocytosed by murine peritoneal macrophages than did OFLX. SPFX exhibited a weak therapeutic activity against M.intracellulare infection induced in mice, on the basis of the rate of bacterial elimination in the host lungs and spleen, but such an efficacy was not noted for OFLX. SPFX combined with rifampicin (RFP), or in combination with RFP and kanamycin yielded a slightly increased therapeutic efficacy, based on the degree of pulmonary gross lesions in host animals or CFU of organisms in the lungs and spleen.     

Antimycobacterial activities of rifamycin derivatives

The Standard Initial Chemotherapy, chemotherapeutic activity of which depends mostly on the two potent bactericidal drugs, INH and RFP, has made a remarkable progress in the treatment of tuberculosis. However, certain difficult situations still remain in the treatment of resistant diseases, mostly in retreatment cases especially resistant to INH and/or RFP, and of the patients who are not able to continue the Standard Regimens because of side effects and/or severe complications with various organ dysfunctions. It is evident that presently available antituberculosis drugs are not potent enough to deal satisfactorily with the above situations, and besides, there has been unsatisfactory chemotherapeutic efficacy against infections caused by Mycobacterium avium complex. The above matters strongly urge our effort to develop new antimycobacterial agents. In the present review, in vitro and in vivo activities of newly synthesized rifamycin derivatives (3'-hydroxy-5'-alkylpiperazinyl-benzoxazinorifamycins, KRMs) were discussed. Of a total of 158 newly synthesized compounds, five (KRM-1648, KRM-1657, KRM-1668, KRM-1674, KRM-2312) were selected due to significantly lower MICs than those of RFP against M. tuberculosis H37Rv and M. intracellulare 31F093T. The MIC90s of these compounds were 16 to 32 times lower than MIC90 of RFP against RFP-susceptible clinical isolates (20 strains) of M. tuberculosis, and 100 times or more lower than MIC90s of RFP against 20 disease-associated M. avium complex strains.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro activity of linezolid against clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains from Beijing, China

The in vitro activity of linezolid was evaluated against 84 clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, isolated from the center for tuberculosis research and treatment of the Chinese army. Linezolid showed excellent activity, with minimum inhibitory concentrations (MICs) of 0.125-0.5 μg/mL against all tested isolates. There were no differences in the MIC(50) and MIC(90) of linezolid between susceptible, isoniazid-resistant, MDR, and XDR. Indeed, all of the groups displayed identical MIC(90) values of 0.25 μg/mL, which is lower than previously reported in similar studies. We conclude that linezolid may be a more effective drug against M. tuberculosis and may play an important role in treating drug-resistant tuberculosis in China.     

微孔板Alamar blue显色法检测结核分枝杆菌氧氟沙星耐药性的研究

目的 评价微孔板Alamar blue显色法检测结核分枝杆菌氧氟沙星耐药性的可行性。方法 用微孔板Alamar blue显色法对78株结核分枝杆菌检测氧氟沙星的最小抑菌浓度,记录获得结果时间,利用ROC曲线确定氧氟沙星的最佳耐药阈值,并和传统的药物敏感性实验罗氏培养基比例法进行比较。结果 微孔板Alamar blue显色法获得结果平均时间为8 d,氧氟沙星的最佳耐药阈值为2 μg/mL,以罗氏培养基比例法为金标准,氧氟沙星的灵敏度和特异度分别为88.6%和94.1%。结论 微孔板Alamar blue显色法是一种简便、敏感、快速的药物敏感性检测方法,可用于结核分枝杆菌氧氟沙星耐药性的快速检测。