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1.
In vitro and in vivo activities of levofloxacin against Mycobacterium tuberculosis. 总被引:4,自引:0,他引:4
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B JI N Lounis C Truffot-Pernot J Grosset 《Antimicrobial agents and chemotherapy》1995,39(6):1341-1344
In tests with 18 drug-susceptible strains of Mycobacterium tuberculosis, the MIC at which 50% of the strains are inhibited by levofloxacin (LVFX) was one dilution less than that at which 50% of the strains are inhibited by ofloxacin (OFLO), but the MICs at which 90% of the strains are inhibited were similar. The in vivo activity of LVFX against M. tuberculosis was compared with the activities of isoniazid, OFLO, and sparfloxacin (SPFX). Mice were inoculated intravenously with 1.74 x 10(6) CFU of H37Rv, and treatments began the next day and were carried out six times weekly for 4 weeks. The severity of infection and effectiveness of treatment were assessed by survival rate, spleen weights, gross lung lesions, and enumeration of CFU in the spleen. In terms of CFU counts, the ranking of the anti-M. tuberculosis activities of the treatments used ran in the following order: LVFX (300 mg/kg of body weight) = SPFX (100 mg/kg) > isoniazid > SPFX (50 mg/kg) > OFLO (300 mg/kg) = LVFX (150 mg/kg) > OFLO (150 mg/kg) = LVFX (50 mg/kg). It seems, therefore, that the in vivo activity of LVFX is comparable to that produced by a twofold-greater dosage of OFLO. It is assumed that the maximal clinically tolerated dosage of LVFX is similar to that of OFLO, i.e., 800 mg daily, which is equivalent to 300 mg of LVFX per kg in mice. Because LVFX displayed powerful bactericidal activity, promising effects against human tuberculosis may be achieved if patients are treated with the maximal clinically tolerated dosage of LVFX. 相似文献
2.
Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis. 总被引:1,自引:0,他引:1
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The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at > or = 8.0 micrograms/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 micrograms/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4- to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections. 相似文献
3.
In vitro activities of linezolid against clinical isolates of Mycobacterium tuberculosis that are susceptible or resistant to first-line antituberculous drugs 总被引:5,自引:0,他引:5
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Alcalá L Ruiz-Serrano MJ Pérez-Fernández Turégano C García De Viedma D Díaz-Infantes M Marín-Arriaza M Bouza E 《Antimicrobial agents and chemotherapy》2003,47(1):416-417
We evaluated 117 isolates of Mycobacterium tuberculosis for susceptibility to linezolid by the proportion and E-test methods. Linezolid showed high in vitro activity, with all the strains inhibited by 相似文献
4.
Inhibitory and bactericidal activities of levofloxacin against Mycobacterium tuberculosis in vitro and in human macrophages. 总被引:1,自引:6,他引:1
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Levofloxacin exhibited twofold greater inhibitory and bactericidal activities than ofloxacin against either extracellular or intracellular tubercle bacilli. The activities of both drugs against extracellular and intracellular bacteria were about the same, despite the accumulation of the drugs in macrophages at a level four- to fivefold greater than that in the extracellular medium. The activities of both drugs against intracellular bacteria were largely associated with the short, 2-h pulsed exposures of the infected macrophages to the concentrations which correspond to those attainable in blood during the period of the maximum concentration of drug in serum. 相似文献
5.
In vitro activities of membrane-active peptides alone and in combination with clinically used antimicrobial agents against Stenotrophomonas maltophilia 总被引:2,自引:0,他引:2
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Giacometti A Cirioni O Del Prete MS Barchiesi F Fortuna M Drenaggi D Scalise G 《Antimicrobial agents and chemotherapy》2000,44(6):1716-1719
The in vitro activities of buforin II, cecropin P1, and magainin II, alone and in combination with six clinically used antimicrobial agents, against 12 clinical isolates of Stenotrophomonas maltophilia were investigated. Antimicrobial activities were measured by MIC and time-kill studies. The isolates were susceptible to the peptides at concentrations in the range of 0.50 to 16 microg/ml. Synergy was observed when the peptides were combined with polymyxin E, meropenem, ceftazidime, piperacillin, and clarithromycin. 相似文献
6.
In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis. 总被引:1,自引:4,他引:1
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The comparative in vitro activity of amoxicillin alone and in combination with clavulanic acid against 15 isolates of Mycobacterium tuberculosis was evaluated by broth dilution susceptibility testing. Amoxicillin inhibited 4 of 15 isolates at 8 micrograms/ml or less but was not bactericidal against any of the isolates at that concentration. Amoxicillin in combination with clavulanic acid was bactericidal for 14 of 15 isolates tested at an amoxicillin concentration of 4 micrograms/ml or less and a clavulanic acid concentration of 2 micrograms/ml or less. 相似文献
7.
Gatifloxacin (GAT) and moxifloxacin (MXF) were evaluated in vitro to determine their activities against Mycobacterium tuberculosis. GAT was subsequently compared in a dose range study to isoniazid (INH) in a murine tuberculosis model. GAT was somewhat less active than INH. GAT and MXF were evaluated in mice infected with M. tuberculosis and were found to have similar activities. GAT was studied alone and in combination with ethambutol, ethionamide (ETA), and pyrazinamide (PZA) and compared to INH and rifampin (RIF). GAT appears to have sufficient activity alone and in combination with ETA with or without PZA to merit evaluation for treatment of tuberculosis. 相似文献
8.
In vitro activities of free and liposomal drugs against Mycobacterium avium-M. intracellulare complex and M. tuberculosis. 总被引:2,自引:1,他引:2
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R T Mehta A Keyhani T J McQueen B Rosenbaum K V Rolston J J Tarrand 《Antimicrobial agents and chemotherapy》1993,37(12):2584-2587
We compared MICs and MBCs of various free- and liposome-incorporated antimicrobial agents against several patient isolates of Mycobacterium avium-M. intracellulare complex and certain American Type Culture Collection strains of M. avium, M. intracellulare, and Mycobacterium tuberculosis. Seven of 19 agents were selected for incorporation into liposomes. The MICs of these agents for 50 and 90% of isolates tested (MIC50s and MIC90s, respectively) ranged from 0.5 to 62 micrograms/ml. Members of the M. avium-M. intracellulare complex were resistant to killing by most of the other agents tested in the free form. However, clofazimine, resorcinomycin A, and PD 117558 showed complete killing of bacteria at concentrations ranging from 8 to 31 micrograms/ml, represented as MBC90s. Among the liposome-incorporated agents, clofazimine and resorcinomycin A had the highest killing effects (MBC90s, 8 and 16 micrograms/ml, respectively). Furthermore, both free and liposome-incorporated clofazimine had equivalent growth-inhibitory and killing effects on all American Type Culture Collection strains of M. avium, M. intracellulare, and M. tuberculosis tested. These results show that the antibacterial activities of certain drugs, particularly those of clofazimine and resorcinomycin, were maintained after the drugs were incorporated into liposomes. 相似文献
9.
In vitro activity of levofloxacin, singly and in combination with rifamycin analogs, against Mycobacterium leprae.
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The in vitro susceptibility of Mycobacterium leprae to levofloxacin was studied by using two biochemical parameters to measure the metabolic activity of the organism. Levofloxacin consistently exhibited twofold greater bactericidal activity than ofloxacin, with the MIC being 0.75 microgram/ml. When combined with one of the three rifamycin analogs, synergism was obtained with KRM-1648 and rifabutin but not with rifampin. 相似文献
10.
In vitro and in vivo activities of macrolide derivatives against Mycobacterium tuberculosis 总被引:3,自引:0,他引:3
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Falzari K Zhu Z Pan D Liu H Hongmanee P Franzblau SG 《Antimicrobial agents and chemotherapy》2005,49(4):1447-1454
Existing macrolides have never shown definitive clinical efficacy in tuberculosis. Recent reports suggest that ribosome methylation is involved in macrolide resistance in Mycobacterium tuberculosis, a mechanism that newer macrolides have been designed to overcome in gram-positive bacteria. Therefore, selected macrolides and ketolides (descladinose) with substitutions at positions 9, 11,12, and 6 were assessed for activity against M. tuberculosis, and those with MICs of < or = 4 microM were evaluated for cytotoxicity to Vero cells and J774A.1 macrophages. Several compounds with 9-oxime substitutions or aryl substitutions at position 6 or on 11,12 carbamates or carbazates demonstrated submicromolar MICs. For the three macrolide-ketolide pairs, macrolides demonstrated superior activity. Four compounds with low MICs and low cytotoxicity also effected significant reductions in CFU in infected macrophages. Active compounds were assessed for tolerance and the ability to reduce CFU in the lungs of BALB/c mice in an aerosol infection model. A substituted 11,12 carbazate macrolide demonstrated significant dose-dependent inhibition of M. tuberculosis growth in mice, with a 10- to 20-fold reduction of CFU in lung tissue. Structure-activity relationships, some of which are unique to M. tuberculosis, suggest several synthetic directions for further improvement of antituberculosis activity. This class appears promising for yielding a clinically useful agent for tuberculosis. 相似文献
11.
Intracellular activities of roxithromycin used alone and in association with other drugs against Mycobacterium avium complex in human macrophages. 总被引:1,自引:0,他引:1
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Recent reports have shown that roxithromycin possesses significant activity against atypical mycobacteria, including the Mycobacterium avium complex (MAC), and that its extracellular anti-MAC activity is further enhanced in two- or three-drug combinations with ethambutol, rifampin, amikacin, ofloxacin, and clofazimine. In accordance with the above data, the anti-MAC potential of roxithromycin used alone and in combination with the above-mentioned antituberculous drugs was screened intracellularly against five clinical MAC isolates (from both human immunodeficiency virus-positive and human immunodeficiency virus-negative patients), phagocytized by human monocyte-derived macrophages. The results showed that roxithromycin used alone and within clinically achievable levels was active against all of the MAC isolates tested. Screening of two-drug combinations showed that both rifampin and clofazimine further increased the intracellular activity of roxithromycin against all five isolates by 35 to 80% (ethambutol, ofloxacin, and amikacin resulted in increased intracellular activity against one, two, and four isolates, respectively). For the three-drug combinations, the combination of roxithromycin plus ethambutol used with rifampin or clofazimine was the most uniformly active against all five MAC isolates, with activity increases of 42 to 90%, followed by roxithromycin plus ethambutol used with amikacin, which resulted in activity increases of 15 to 90%. The overall level of intracellular killing after 5 days of drug addition, in comparison with growth in untreated controls, varied from 1 to 3 log units depending on the individual MAC isolate and/or drug combination used. 相似文献
12.
Williams K Minkowski A Amoabeng O Peloquin CA Taylor D Andries K Wallis RS Mdluli KE Nuermberger EL 《Antimicrobial agents and chemotherapy》2012,56(6):3114-3120
Novel oral regimens composed of new drugs with potent activity against Mycobacterium tuberculosis and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. As part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, several 3- and 4-drug combinations containing new agents currently in phase 2/3 trials (TMC207 [bedaquiline], PA-824 and PNU-100480 [sutezolid], and/or clofazimine) proved superior to the first-line regimen of rifampin, pyrazinamide, and isoniazid. TMC207 plus PNU-100480 was the most effective drug pair. In the second experiment, in which 3- and 4-drug combinations composed of TMC207 and pyrazinamide plus rifapentine, clofazimine, PNU-100480, or both rifapentine and clofazimine were evaluated, the rank order of drugs improving the sterilizing activity of TMC207 and pyrazinamide was as follows: rifapentine plus clofazimine ≥ clofazimine ≥ rifapentine > PNU-100480. The results revealed potential new building blocks for universally active short-course regimens for drug-resistant tuberculosis. The inclusion of pyrazinamide against susceptible isolates may shorten the duration of treatment further. 相似文献
13.
目的 研究替比培南(TBM)及联用-内酰胺酶抑制剂对结核分枝杆菌体外抑菌效果,分析菌株抗结核药物耐药表型和基因型与TBM药物敏感性的关联性。方法 选取128株抗结核药物敏感(DS)和耐多药/广泛耐药(M/XDR)结核分枝杆菌临床分离株,其中96株(75.0%)属于北京家族,32株(25.0%)属于非北京家族。采用96孔微孔板显色法检测菌株药物敏感性(最小抑菌浓度)。采用2检验分析菌株对TBM及联用不同抑制剂组合物的耐药率差异。结果 TBM/克拉维酸(CLA)的抑菌活性最高(MIC90,2 g/ml),其次为TBM/阿维巴坦(AVI)(MIC90,4 g/ml),分别有2株和5株耐药。不同耐药类型菌株中,DS菌株的TBM,TBM/AVI和TBM/CLA耐药率均高于M/XDR菌株,但差异均无统计学意义(P0.05)。不同基因型菌株中,北京基因型菌株TBM耐药率(60.4%)显著高于非北京基因型菌株(37.5%)(2=5.09,P=0.024),差异有统计学意义(P0.05),而二者对TBM/AVI的耐药率差异无统计学意义(P0.05)。结论 TBM联用CLA或AVI具有良好的体外抑制结核分枝杆菌效果,北京基因型与TBM耐药表型之间存在关联性,尚不能确定抗结核药物多重耐药表型与TBM耐药是否有相关性。 相似文献
14.
In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.
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T Hirata H Saito H Tomioka K Sato J Jidoi K Hosoe T Hidaka 《Antimicrobial agents and chemotherapy》1995,39(10):2295-2303
The in vitro and in vivo activities of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium tuberculosis were studied. The MIC at which 50% of the isolates are inhibited (MIC50) and the MIC90 of KRM for 30 fresh isolates of M. tuberculosis measured by the BACTEC 460 TB System were 0.016 and 2 micrograms/ml, respectively. These values were much lower than those for rifampin (RMP), which were 4 and >128 micrograms/ml, respectively, and considerably lower than those for rifabutin (RBT), which were 0.125 and 8 micrograms/ml, respectively. A correlational analysis of the MICs of these drugs for the clinical isolates revealed the presence of cross-resistance of the organisms to KRM and either RMP or RBT although the MICs of KRM were distributed over a much lower range than were those of the other two drugs. KRM and RMP at concentrations of 1 to 10 micrograms/ml almost completely inhibited the bacterial growth of RMP-sensitive strains (H37Rv, Kurono, and Fujii) of M. tuberculosis phagocytosed in macrophage-derived J774.1 cells. KRM was more active than RMP in inhibiting the growth of the RMP-resistant (MIC = 8 micrograms/ml) Kurata strain but failed to show such an effect against the RMP-resistant (MIC >128 micrograms/ml) Watanabe stain. When KRM was given to M. tuberculosis-infected mice at dosages of 5 to 20 mg/kg of body weight by gavage, one daily six times per week from day 1 after infection, it was much more efficacious than RMP against infections induced in mice by the RMP-sensitive Kurono strain, as measured by a reduction of rates of mortality, a reduction of the frequency and extent of gross lung lesions, histopathological changes in lung tissues, and a decrease in the bacterial loads in the lungs and spleens of infected mice. KRM also displayed significant therapeutic efficacy against infection induced by the RMP-resistant Kurata strain, while neither KRM nor RMP was efficacious against infection by the RMP-resistant Watanabe strain. In the case of infection with the Kurono strain, the efficacy of the drugs in prolonging the time of survival was in the order KRM, RBT, RMP. KRM was much more efficacious than RMP, when given at 1- to 4-week intervals. These findings suggest that KRM may be useful for the clinical treatment of tuberculosis contracted through RMP-sensitive strains, even when it is administered at long intervals. 相似文献
15.
In vitro and in vivo activities of the nitroimidazole CGI 17341 against Mycobacterium tuberculosis. 总被引:2,自引:0,他引:2
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D R Ashtekar R Costa-Perira K Nagrajan N Vishvanathan A D Bhatt W Rittel 《Antimicrobial agents and chemotherapy》1993,37(2):183-186
CGI 17341 (2-ethyl-5-nitro-2,3-dihydro[2-1b]imidazo-oxazole) is a novel orally active representative of the 5-nitroimidazole series of antimicrobial agents. At concentrations ranging from 0.1 to 0.3 micrograms/ml, CGI 17341 inhibited the drug-susceptible and multi-drug-resistant strains of Mycobacterium tuberculosis. CGI 17341 had no cross-resistance with isoniazid, rifampin, streptomycin, or ethambutol. While the in vitro activity of CGI 17341 against M. tuberculosis was comparable to those of isoniazid and rifampin, it was superior to those of streptomycin, ciprofloxacin or norfloxacin, and oxazolidinone DuP 721. The MIC of CGI 17341 was not affected when the pH of the medium was decreased from 6.8 to 5.6, while four- to sixfold increases in the MICs of ciprofloxacin and isoniazid were observed. In mice infected with M. tuberculosis, the 50% effective dose for CGI 17341 was 7.7 mg/kg of body weight (95% confidence limits, 3.5 and 10.27) when administered on days 11 and 12 postinfection. CGI 17341 gave a dose-dependent (r = 0.995) and significant increase in the survival time. Our data indicate that the 5-nitroimidazole CGI 17341 is a promising and novel antituberculosis compound with potent in vitro and in vivo activities. Further investigations on this compound are warranted. 相似文献
16.
17.
In vitro activities of tritrpticin alone and in combination with other antimicrobial agents against Pseudomonas aeruginosa
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Cirioni O Giacometti A Silvestri C Della Vittoria A Licci A Riva A Scalise G 《Antimicrobial agents and chemotherapy》2006,50(11):3923-3925
The in vitro activity of the cathelicidin tritrpticin was investigated against multidrug-resistant Pseudomonas aeruginosa. The isolates were susceptible to the peptide at concentrations of 0.50 to 8 mg/liter. Tritrpticin completely inhibits lipopolysaccharide procoagulant activity at a 10 microM concentration. Fractionary inhibitory concentration indexes (0.385, 0.312, and 0.458) demonstrated synergy between the peptide and beta-lactams. 相似文献
18.
In vitro and ex vivo activities of antimicrobial agents used in combination with clarithromycin, with or without amikacin, against Mycobacterium avium. 总被引:1,自引:0,他引:1
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L Fattorini B Li C Piersimoni E Tortoli Y Xiao C Santoro M L Ricci G Orefici 《Antimicrobial agents and chemotherapy》1995,39(3):680-685
MICs of clarithromycin, amikacin, isoniazid, rifabutin, ciprofloxacin, sparfloxacin, ethambutol, and clofazimine were determined for six isolates of Mycobacterium avium complex (MAC) from AIDS patients both by the radiometric method and by an ex vivo model of infection in human macrophages. The median MICs in macrophages were similar or slightly lower than values found in broth, except for amikacin, which had slightly higher MICs inside the cells. Combinations of clarithromycin with other antimicrobial agents showed that clarithromycin-clofazimine and clarithromycin-rifabutin were synergistic on five of six strains while clarithromycin-amikacin and clarithromycin-isoniazid were antagonistic on one and two strains, respectively. The addition of amikacin made the combinations of clarithromycin-clofazimine and clarithromycin-ethambutol synergistic against all the MAC strains. In the macrophage model, the combination of clarithromycin-clofazimine (mean survival, 21%) and clarithromycin-rifabutin (mean survival, 29%) showed a strong reduction in viable counts compared with single drugs, while clarithromycin-amikacin was less active than single drugs alone. In general, the addition of amikacin did not improve the activity of the combinations, except for clarithromycin-isoniazid-amikacin (mean survival, 19%), which was significantly more active than either clarithromycin-isoniazid or clarithromycin-amikacin. The use of the macrophage model can suggest new combinations of antimicrobial agents with anti-MAC activity which, on the basis of their in vitro effectiveness, would probably be disregarded for assay in animal models. 相似文献
19.
Bacteriostatic and bactericidal activities of gentamicin alone and in combination with clarithromycin against Mycobacterium avium.
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L B Heifets P J Lindholm-Levy R D Comstock 《Antimicrobial agents and chemotherapy》1992,36(8):1695-1698
The inhibitory activity of gentamicin against Mycobacterium avium depended on the pH of the medium, and the broth-determined MICs for 90% of strains were 5.0 micrograms/ml at pH 7.4, 9.5 micrograms/ml at pH 6.8, and greater than 16.0 micrograms/ml at pH 5.0. The MBCs were two- to eightfold higher than the MICs. The combined effect of gentamicin and clarithromycin was additive, and the MICs and MBCs of each drug were either the same as those in the single-drug tests or reduced twofold. 相似文献
20.
A. Santos R. Cremades J. C. Rodríguez E. Garcia-Pachon M. Ruiz G. Royo 《Journal of infection and chemotherapy》2010,16(1):64-67
Interest in Mycobacterium fortuitum has increased since it was recognized as an emergent pathogen. The objective of this study was to screen a large number of
drug combinations in order to evaluate the activity of classical and new potentially useful antibiotics against M. fortuitum. Twenty M. fortuitum clinical isolates were studied with 51 combinations of two drugs and 47 combinations of three drugs belonging to different
families: fluoroquinolones, linezolid, macrolides, rifamycins, aminoglycosides, and carbapenems. Activity was determined in
Mueller Hinton broth by seeing whether the cultures were negative after 4 days of incubation with the combination of antibiotics.
The most active drugs were moxifloxacin and gatifloxacin, which were active against 15 of the 20 strains studied, followed
by amikacin (14 of the 20). The combinations of gatifloxacin with rifampicin or rifabutin, moxifloxacin with rifampicin or
amikacin, and ciprofloxacin with amikacin were the most useful against M. fortuitum, as they showed activity in 18 of the 20 strains studied. Linezolid, imipenem, and ertapenem showed poor activity in this
experimental model when they were used on their own. Larger studies, both in vitro and in vivo, should be done to confirm
the true usefulness of the new fluoroquinolones, alone or in combination, in the treatment of M. fortuitum. 相似文献