| 2017 | Drug Susceptibility of 33 Reference Strains of Slowly Growing Mycobacteria to 19 Antimicrobial Agents. | Biomed Res Int | . Slowly growing mycobacteria (SGM) are prevalent worldwide and cause an extensive spectrum of diseases. . In this study, the antimicrobial susceptibility of 33 reference strains of SGM to 19 antimicrobial agents was tested using a modified microdilution method. . Cefmetazole (32/33) and azithromycin (32/33) exhibited the highest antimicrobial activity, and dapsone (9/33) exhibited the lowest activity against the tested strains. Cefoxitin (30/33), cefoperazone (28/33), and cefepime (28/33) were effective against a high proportion of strains, and macrolides were also highly effective as well as offering the benefit of convenient oral administration to patients. Linezolid (27/33), meropenem (26/33), sulfamethoxazole (26/33), and tigecycline (25/33) showed the highest activity; clofazimine (20/33) and doxycycline (18/33) showed intermediate activity; and rifapentine (13/33), rifabutin (13/33), and minocycline (11/33) showed low antimicrobial activity, closely followed by thioacetazone (10/33) and pasiniazid (10/33), against the tested organisms. According to their susceptibility profiles, the slowly growing species and were the least susceptible to the tested drugs, whereas , , , , , and were the most susceptible. . In summary, cephalosporins and macrolides, particularly cefmetazole, azithromycin, clarithromycin, and Roxithromycin, showed good antimicrobial activity against the reference strains of SGM. |
| 2017 | Antimicrobial susceptibility and MIC distribution of 41 drugs against clinical isolates from China and reference strains of nontuberculous mycobacteria. | Int J Antimicrob Agents | To treat nontuberculous mycobacteria (NTM) infections more optimally, further research pertaining to mycobacterial susceptibility to antimicrobial agents is required. A total of 82 species of NTM reference strains and 23 species of NTM clinical isolates were included. Minimum inhibitory concentrations (MICs) for 41 drugs were determined using the microdilution method in cation-adjusted Mueller-Hinton broth. The results showed that most of the NTM were susceptible to aminoglycosides, quinolones, three macrolides (clarithromycin, azithromycin and Roxithromycin), cefmetazole, linezolid and capreomycin. Rapidly growing mycobacterium strains were additionally susceptible to cefoxitin, clofazimine, rifapentine, doxycycline, minocycline, tigecycline, meropenem and sulfamethoxazole, whereas slowly growing mycobacterium strains were additionally susceptible to rifabutin. This study on the susceptibility of NTM includes the largest sample size of Chinese clinical isolates and reference strains. NTM species-specific drug susceptibility patterns suggested that it is urgent to identify the species of NTM, to normalise the treatment of NTM infectious disease and to clarify the resistance mechanisms of NTM. |
| 2002 | [Prospects for development of new antituberculous drugs]. | Kekkaku | Tuberculosis (TB) is a growing international health concern, since it is the leading infectious cause of death in the world today. Moreover, the resurgence of TB in industrialized countries and the worldwide increase in the prevalence of Mycobacterium avium complex (MAC) infections in immunocompromised hosts have prompted the quest for new antimycobacterial drugs. In particular, the appearance of multidrug-resistant (MDR) strains of M. tuberculosis, which exhibit in vitro resistance to at least two major antituberculous drug (usually INH and RFP) and cause intractable TB, has greatly contributed to the increased incidence of TB. Because of the global health problems of TB, the increasing rate of MDR-TB and the high rate of a co-infection with HIV, the development of potent new antituberculous drugs without cross-resistance with known antimycobacterial agents is urgently needed. In this article, I reviewed the following areas. First, I briefly reviewed some new findings (mainly reported after 2000) on the pharmacological status of rifamycin derivatives (rifabutin, rifapentine, and rifalazil), fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, moxifloxacin, and others), and new macrolides (clarithromycin, azithromycin, and Roxithromycin). Second, I described other types of agents which are being developed as antimycobacterial drugs. Some of the agents discussed are already under preliminary clinical investigation, and others appear to be promising candidates for future development. In this review, the status of the development of new antimycobacterial, especially antituberculous agents including oxazolidinone (PNU-100480), 5'-nitroimidazole (CGI 17341), 2-pyridone (ABT-255), new riminophenazines, nitroimidazopyran (PA-824), new ketolides (ABT-773, telithromycin) and defensins (human neutrophil peptide-I), was examined. Third, the development of new antitubercular drugs was discussed according to the potential pharmacological target. New critical information on the whole genome of M. tuberculosis recently elucidated and increasing knowledge on various mycobacterial virulence genes will promote the progression in the identification of genes that code for new drug targets. Using such findings on mycobacterial genomes, drug development using quantitative structure-activity relationship may be possible in the near future. In this review, I described the screening of drugs that have an inhibitory activity against dTDP-rhamnose synthesis of M. tuberculosis, as a new drug target of the organism. In addition, I discussed the usefulness of antisense oligo DNAs specific to mycobacterial genes encoding certain metabolic enzymes or virulence factors that play roles in the bacterial escape from antimicrobial mechanisms of host macrophages. Fourth, I reviewed the drug vehicles which enable efficacious drug delivery to their target in vivo. The usefulness of poly (DL-lactide-co-glycolide) microsphere technology, which enables the encapsulated drugs to deliver the requested doses of them for prolonged time periods by a single shot without causing any toxicity and, moreover, enables the highly targeted delivery of the drugs to host macrophages, was discussed. Fifth, I described adjunctive immunotherapy for the management of patients with mycobacterial infections by giving certain immunomodulators in combination with antimycobacterial drugs. Adjuvant clinical trials using IL-2 or GM-CSF have been found to be efficacious to some extent in improving patients with tuberculosis or disseminated MAC infections. However, it seems that these immunopotentiating cytokines as well as IFN-gamma and IL-12 are not so promising for the therapeutic agents of mycobacterial infections because of the possible induction of immunosuppressive cytokines during adjuvant therapy and, in some cases, severe side-effect. Thus, the development of new classes of immuno-modulators other than cytokines, particularly those with no severe side-effect, is needed. This review dealt with ATP and its analogues which potentiate macrophage antimycobacterial activity via a purinergic P2X7 receptor. Finally, I described the roles of type II alveolar epithelial cells in the establishment of mycobacterial infections in the host lungs and the profiles of drug susceptibilities of M. tuberculosis and MAC organisms replicating within the type II pneumocytes. These findings are useful to precisely assess or predict the in vivo therapeutic activity of a given antimycobacterial drug from its in vitro activity. In this article, I have thoroughly reviewed the status of the development of new antimycobacterial drugs. There are a number of difficulties in the drug-design for the development of new drug formulations with increased potential for antimycobacterial effects, excellent pharmacokinetics, and tolerability. It should be emphasized that the most urgent goal of chemotherapy of tuberculosis and MAC infections, especially that associated with HIV infection, is to develop highly active, low-cost drugs which can be used not only in industrialized countries but also in developing countries, since the incidences of AIDS-associated intractable tuberculosis is rapidly increasing in the latter. |
| 2000 | Prospects for development of new antimycobacterial drugs. | J Infect Chemother | In this article, I have thoroughly reviewed the status of development of new antimycobacterial drugs, particularly fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, and moxifloxacin), new macrolides (clarithromycin, azithromycin, and Roxithromycin), rifamycin derivatives (rifabutin, rifapentine, and KRM-1648), and others. The main purpose of this review was to describe the in-vitro and in-vivo activities of these drugs against Mycobacterium tuberculosis and Mycobacterium avium complex. In addition, the therapeutic efficacy of these drugs in the clinical treatment of mycobacterial infections has also been briefly mentioned. |
| 2000 | Prospects for development of new antimycobacterial drugs, with special reference to a new benzoxazinorifamycin, KRM-1648. | Arch Immunol Ther Exp (Warsz) | In this article, I have thoroughly reviewed the status of development of new antimycobacterial drugs, in particular, rifamycin derivatives (rifabutin, rifapentine, and a new benzoxazinorifamycin, KRM-1648), fluoroquinolones (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin, sitafloxacin, moxifloxacin, and others), new macrolides (clarithromycin, azithromycin, Roxithromycin), and others. In this review, I have mainly described the in vitro and in vivo activities of these drugs against Mycobacterium tuberculosis and atypical mycobacteria, especially Mycobacterium avium complex. In addition, therapeutic efficacy of these drugs in cases of clinical treatment of mycobacterial infections have also been briefly mentioned. |
| 1998 | Susceptibilities of Legionella spp. to newer antimicrobials in vitro. | Antimicrob Agents Chemother | The in vitro activities of 13 antimicrobial agents against 30 strains of Legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC90s], < or = 0.008 microgram/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC90s, 0.03 to 0.06 microgram/ml) were more active than erythromycin A or Roxithromycin. The MIC90s of dalfopristin-quinupristin and linezolid were 0.5 and 8 micrograms/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of Legionella infections. |
| 1998 | In vitro susceptibilities of aerobic and facultative non-spore-forming gram-positive bacilli to HMR 3647 (RU 66647) and 14 other antimicrobials. | Antimicrob Agents Chemother | The comparative in vitro activity of the ketolide HMR 3647 (RU 66647) and those of structurally related macrolide-lincosamide-streptogramin compounds (erythromycin, Roxithromycin, azithromycin, clarithromycin, josamycin, lincomycin, pristinamycin, and quinupristin-dalfopristin) as well as those of benzylpenicillin, doxycycline, vancomycin, teicoplanin, levofloxacin, and rifapentine against 247 aerobic and facultative non-spore-forming gram-positive bacilli were determined by an agar dilution method. The ketolide was active against most organisms tested except Corynebacterium striatum, coryneform CDC group 12, and Oerskovia spp. The frequency of resistance to erythromycin and other macrolides as well as that to lincomycin was high. Pristinamycin and, to a lesser extent, quinupristin-dalfopristin were very active, but resistance to these agents was present in some strains of Rhodococcus equi, Listeria spp., C. striatum, Erysipelothrix rhusiopathiae, and Oerskovia spp. HMR 3647 was very active against all erythromycin-sensitive and many erythromycin-nonsusceptible strains, especially Corynebacterium minutissimum, Corynebacterium pseudodiphtheriticum, Corynebacterium amycolatum, and Corynebacterium jeikeium. In vitro resistance to benzylpenicillin was common, but doxycycline, vancomycin, and teicoplanin were very active against most organisms tested except E. rhusiopathiae, against which glycopeptide antibiotics were not active. The in vitro activity of levofloxacin was remarkable, but resistance to this agent was common for C. amycolatum, Corynebacterium urealyticum, C. jeikeium, and Oerskovia spp. strains. Rifapentine was also very active in vitro against many organisms, but resistance to this agent was always present in E. rhusiopathiae and was very common in C. striatum and C. urealyticum. |
| 1998 | In vitro susceptibilities of Bordetella pertussis and Bordetella parapertussis to two ketolides (HMR 3004 and HMR 3647), four macrolides (azithromycin, clarithromycin, erythromycin A, and roxithromycin), and two ansamycins (rifampin and rifapentine). | Antimicrob Agents Chemother | When tested by agar dilution on Mueller-Hinton agar supplemented with 5% horse blood, the ketolides HMR 3004 and HMR 3647 were slightly more active (MIC at which 90% of the isolates were inhibited [MIC90], 0.03 microg/ml) against Bordetella pertussis than azithromycin, clarithromycin, erythromycin A, and Roxithromycin. Azithromycin (MIC90, 0.06 microg/ml) was the most active compound against B. parapertussis. Rifampin and rifapentine were considerably less active. |
| 1993 | In vitro activities of new macrolides and rifapentine against Brucella spp. | Antimicrob Agents Chemother | We have tested the in vitro activities of streptomycin, rifampin, tetracyclines, trimethoprim-sulfamethoxazole, erythromycin, four new macrolides (Roxithromycin, azithromycin, clarithromycin, and dirithromycin), and rifapentine against 62 strains of Brucella spp. Azithromycin and clarithromycin were, respectively, eight- and twofold more active than erythromycins (MIC for 90% of strains = 2, 8, and 16 micrograms/ml, respectively). The activity of rifapentine was similar to that of rifampin (MIC for 90% of strains = 1 microgram/ml). |
| 1989 | [In vitro activity of clofazimine alone and in combination with amikacin, roxithromycin, rifampicin and rifapentine against Mycobacterium avium-intracellulare]. | Enferm Infecc Microbiol Clin | The activity of clofazimine, amikacin, Roxithromycin, rifampicin and rifapentine was tested, alone and in association, against Mycobacterium avium intracellulare. Clofazimine, amikacin and rifapentine were shown to be very active. With all established associations, the MIC observed for each drug alone was appreciably reduced. |