Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026916 (MAC)
 5,226 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A standardized clarithromycin susceptibility test for Mycobacterium genavense is reported. The BACTEC radiometric broth dilution test method recommended for Mycobacterium avium complex was modified to develop a reliable and reproducible procedure. Test development involved optimization of medium pH and inoculum densities for antibiotic vials as well as growth control vials. MIC control organisms included Mycobacterium simiae, Mycobacterium avium, and Mycobacterium xenopi. Growth control vials required two to three inoculum dilutions, which varied for each species. Clarithromycin MICs and MBCs for 12 isolates and 1 colonial variant of M. genavense ranged from < or = 0.06 to 0.25 microg/ml.
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PMID:Standardized BACTEC method to measure clarithromycin susceptibility of Mycobacterium genavense. 950 6

Antimycobacterial drugs acting efficiently against Mycobacterium avium complex have in common low MICs and MBC/MIC ratios. The recently reported clinical efficacy of some of the newer drugs is also clearly linked to their pharmacokinetic properties such as higher serum level and/or intracellular concentrations and half-life. In the present investigation, comparative postantibiotic effects (PAEs) of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin were investigated. Bacteria were exposed to MIC, MIC x 4 and MIC x 8 concentrations of each drug for 2 h, the drug was removed by centrifugation and cells were thoroughly washed and resuspended in drug-free medium. Growth was compared to control organisms which underwent a similar treatment (but without drugs) and PAEs were assessed using the equation "T-C", where T equals the time required for colony counts to increase by 1 log10 in test samples after antibiotic exposure and C equals the time for 1 log10 growth in control. Our results underlined two distinct patterns concerning PAE: pattern I included drugs for which PAE (in hours) was dose-dependent and varied (for MIC, MIC x 4 and MIC x 8 concentrations) for amikacin (10.3 +/- 1.7, 14.7 +/- 1.9 and 17.7 +/- 4.1), rifampin (28.0 +/- 7.6, 62.0 +/- 18.5 and 71.0 +/- 3.2) and clarithromycin (2.6 +/- 1.0, 15.0 +/- 4.0 and 22.0 +/- 4.0), whereas pattern II included drugs with a stable PAE, relatively independent of the drug concentrations: sparfloxacin (11.0 +/- 2.5, 12.3 +/- 6.4 and 13.0 +/- 2.1) and clofazimine (26.0 +/- 2.8, 28.8 +/- 2.5 and 27.3 +/- 1.3). These results may be useful for guidance in scheduling of drug administration in M. avium-infected AIDS patients overburdened with too many drugs given for various opportunistic infections.
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PMID:Postantibiotic effect of amikacin, rifampin, sparfloxacin, clofazimine and clarithromycin against Mycobacterium avium. 976 52

The susceptibilities of 40 strains of various Mycoplasma species to 10 classes of antimicrobial agents were compared in vitro by a broth microdilution method. The strains tested comprised 20 strains of four AIDS-associated species--M. penetrans (1 strain), M. fermentas (5 strains), M. pirum (6 strains) and M. genitalium (8 strains)--nine strains of the urogenital tract species M. hominis and 11 strains of M. pneumoniae. The results demonstrated wide variation in the susceptibilities of the different Mycoplasma spp. to different classes of antimicrobial agent. All the mycoplasmas were susceptible or highly susceptible to the fluoroquinolones, with sparfloxacin the most active, and to the diterpine antibiotic tiamulin. M. pneumoniae and M. genitalium strains were also highly susceptible to the macrolides, particularly azithromycin and had similar antibiotic susceptibility patterns to most other antimicrobial agents. However, all strains of M. genitalium were resistant to streptomycin (MIC 250->500 mg/L) whereas all M. pneumoniae isolates, except the MAC strain, were susceptible (MICs 1.25-12.5 mg/L). M. pirum isolates varied considerably in their susceptibility to macrolides (MIC range versus azithromycin 0.0025->100 mg/L). M. fermentans strains were susceptible to the tetracyclines, lincosamides and mupirocin, but varied in susceptibility to aminoglycosides. Most M. hominis strains were susceptible to the tetracyclines and all were susceptible to clindamycin and mupirocin. M. penetrans GTU 54 was susceptible to azithromycin, the tetracyclines and lincosamides as well as to the fluoroquinolones and tiamulin.
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PMID:Comparative susceptibilities of various AIDS-associated and human urogenital tract mycoplasmas and strains of Mycoplasma pneumoniae to 10 classes of antimicrobial agent in vitro. 985 48

During a randomized study of clarithromycin plus clofazimine with or without ethambutol in patients with AIDS and Mycobacterium avium complex (MAC) bacteremia, eight participants received additional antimycobacterial drugs following the detection of a clarithromycin-resistant isolate (MIC, > 8 micrograms/mL). A macrolide (seven received clarithromycin, one azithromycin) and clofazimine were continued; additional treatment included various combinations of ethambutol, ciprofloxacin, amikacin, and rifabutin. After the detection of a resistant isolate and before receipt of additional antimycobacterials, the median peak MAC colony count in blood was 105 cfu/mL (range, 8-81,500 cfu/mL). After additional antimycobacterials, the median nadir MAC colony count was 5 cfu/mL (range, 0-110 cfu/mL). Five (63%) of eight patients had a > or = 1 log10 decrease, including two who achieved negative blood cultures; all of these responses occurred in patients originally assigned to clarithromycin plus clofazimine. Treatment of clarithromycin-resistant MAC bacteremia that emerges during clarithromycin-based treatment can decrease levels of bacteremia and transiently sterilize blood cultures.
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PMID:Successful short-term suppression of clarithromycin-resistant Mycobacterium avium complex bacteremia in AIDS. California Collaborative Treatment Group. 1002 84

Despite the development of several agents, new classes of antimicrobials with activity against the Mycobacterium avium complex (MAC) are needed. Based on a broad screening of compounds, we found that mefloquine has MICs of 8 to 16 microg/ml by the BACTEC system and 16 microg/ml by broth microdilution for five MAC strains tested. An expansion of the screening with broth microdilution to 24 macrolide-susceptible strains and 6 macrolide-resistant strains determined that the MIC for all strains was 16 microg/ml. To determine the intracellular activity of mefloquine, U937 macrophage monolayers infected with MAC strain 101, 100, or 109 (serovars 1, 8, and 4) were treated with mefloquine daily, and the number of intracellular bacteria was quantitated after 4 days. Significant growth inhibition against the three MAC strains at concentrations greater than or equal to 10 microg/ml (P < 0.05) was obtained. Due to the encouraging anti-MAC activity, in vivo efficacy in beige mice infected with MAC 101 was evaluated. Animals were treated with 5, 10, 20, or 40 mg/kg of body weight daily, three times a week, twice a week, or once a week for 4 weeks, and bacteria were quantitated in blood, liver, and spleen. No toxicity was observed with any of the treatment regimens. Mefloquine had borderline bactericidal activity at a dosage of 40 mg/kg daily (100% inhibition compared with a 1-week control), and significant inhibition was obtained at dosages of 40 mg/kg three times a week, as well as 20 mg/kg daily. Mefloquine had no significant effect on bacteremia. A combination of mefloquine and ethambutol showed significantly more activity than did either drug alone in liver, spleen, and blood; the combination was also bactericidal against M. avium. Although safety is a potential concern, mefloquine and related compounds deserve further investigation as anti-MAC therapies.
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PMID:Mefloquine is active in vitro and in vivo against Mycobacterium avium complex. 1042 5

The genetics of the ciliate Tetrahymena thermophila are richer than for most other eukaryotic cells, because Tetrahymena possesses two genomes: a germline (micronuclear) genome that follows a Mendelian model of genetic transmission and a somatic (macronuclear) genome, derived from the micronuclear genome by fragmentation, which follows a different genetic transmission model called phenotypic assortment. While genetic markers in the micronucleus fall into classical linkage groups under meiotic recombination and segregation, the same markers in the macronucleus fall into coassortment groups (CAGs) under phenotypic assortment by the random distribution of MAC chromosome pieces. We set out to determine whether genomic mapping in the macronucleus by genetic means is feasible. To investigate the relationship between the micronuclear map and coassortment groups, we systematically placed into CAGs all of the markers lying on chromosome 1L that are also found in the macronucleus. Sixteen CAGs were identified, 7 of which contain at least two loci. We have concluded that CAGs represent a fundamental genetic feature of the MAC. The MIC and MAC maps on 1L are colinear; that is, CAGs consist exclusively of markers that map to a continuous segment in a given region of the micronuclear map, with no intervening markers from other CAGs. These findings provide a solid foundation for exploiting the MAC chromosome pieces to build a physical map of the Tetrahymena genome.
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PMID:Tetrahymena macronuclear genome mapping: colinearity Of macronuclear coassortment groups and the micronuclear map on chromosome 1l. 1075 60

Current Japanese clinical practice involves the usage of large amounts of new macrolides such as clarithromycin and roxithromycin for the treatment of diffuse panbronchiolitis, Helicobacter pylori and Mycobacterium avium complex infections. In this study, the phenotypes, genotypes, and macrolide resistance mechanisms of macrolide-inactivating Escherichia coli recovered in Japan from 1996 to 1997, were investigated. The isolation rate of erythromycin A highly-resistant E. coli (MIC > or = 1,600 microg/ml) in Japan slightly increased from 0.5% in 1986 to 1.2% in 1997. In six macrolide-resistant strains, recovered from the strains collected for this study during 1996 to 1997, the inactivation of macrolide could be detected with or without added ATP in the assay system. The appearance of erythromycin A-inactivating enzyme independent of ATP was novel from Japanese isolates, and the 1H NMR spectra of oleandomycin hydrolyzed by the three ATP-independent isolates were examined. It was clearly shown that the lactone ring at the position of C-13 was cleaved as 13-H signal in aglycon of oleandomycin upper shifted. These results suggested the first detection of macrolide-lactone ring-hydrolase from clinical isolates in Japan. These results suggested the first detection of an ATP-independent macrolide-hydrolyzing enzyme from Japanese clinical isolates. Substrate specificity of the macrolide-hydrolyzing enzyme was determined with twelve macrolides including the newer members of this group and it was found that not only erythromycin A but also the new macrolides, such as clarithromycin, roxithromycin, and azithromycin were inactivated. The NMR data, broad spectrum of activity, and independence of co-enzyme supported our naming of the enzyme as a macrolide esterase. PCR methodology was employed to detect an ereB-like gene from the 3 isolates producing macrolide esterase, and one of these was subsequently shown to contain both ereB-like and ermB-like genes. It was also clearly shown that the other three isolates, which inactivated macrolide in the presence of ATP, had an mphA-like gene.
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PMID:Macrolide esterase-producing Escherichia coli clinically isolated in Japan. 1090 16

Resistance to clarithromycin in breakthrough Mycobacterium avium complex (MAC) isolates typically occurs 3 to 4 months after the initiation of monotherapy in bacteremic AIDS patients. It has been suggested that continuation of clarithromycin therapy still results in clinical and microbiological improvement. To study this paradox, C57BL/6 beige mice were infected with a clarithromycin-resistant (MIC, > or =128 microg/ml) strain of MAC 101 (CLA-R MAC 101) and treated with 200 mg of clarithromycin per kg of body weight/day alone or in combination with ethambutol (100 mg/kg/day) for 2 weeks. Mice infected with a clarithromycin-susceptible strain of MAC 101 had bacterial loads reduced by 90% in the liver and 91% in the spleen (P<0.05, compared with the control). Clarithromycin treatment of CLA-R MAC 101 resulted in a 65% reduction of bacterial loads in the liver (P = 0.009) and a 71% reduction in the spleen (P = 0.009), compared with the results for the untreated control. CLA-R MAC 101 and MAC 101 (isogenic strains) had comparable growth rates in murine tissue, ruling out a loss of virulence of CLA-R MAC 101. Strains of MAC currently defined as macrolide resistant may still respond to treatment with an agent such as clarithromycin within infected tissues.
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PMID:Clarithromycin-resistant mycobacterium avium is still susceptible to treatment with clarithromycin and is virulent in mice. 1099 34

Moxifloxacin activity against Mycobacterium avium complex (MAC) was evaluated in vitro against 25 strains. The MIC was determined to range from 0.125 to 2.0 microg/ml. In addition, U937 macrophage monolayers infected with MAC strain 101 (serovar 1) were treated with moxifloxacin (0.25 to 8 microg/ml) daily, and the number of intracellular bacteria was quantitated after 4 days. Moxifloxacin showed inhibitory activity at 0.5 microg/ml and higher. To assess the activity of moxifloxacin containing regimens in vivo, we infected C57BL bg(+)/bg(+) mice with 3 x 10(7) MAC strain 101 bacteria intravenously. One week later treatment was begun with the following: (i) moxifloxacin (50 mg/kg/day or 100 mg/kg/day), ethambutol (100 mg/kg/day), or a combination of moxifloxacin and ethambutol; or (ii) moxifloxacin (100 mg/kg/day), azithromycin (200 mg/kg/day), or rifabutin (40 mg/kg/day) as oral monotherapy; or (iii) all permutations of two-drug therapy or all three drugs in combination. All groups contained at least 14 animals, and the control group received the drug vehicle. After 4 weeks, quantitative blood cultures were obtained and the number of bacteria in liver and spleen was quantitated. Moxifloxacin, ethambutol, and azithromycin were active as single agents in liver, spleen, and blood. Rifabutin showed inhibitory activity only in the blood. Two-drug combinations containing azithromycin were no more active than azithromycin alone. Similarly, the three-drug combination was not more active than azithromycin alone in the spleen. Rifabutin did not add to the activity of any other single agent or two-drug combination. Moxifloxacin at both concentrations in combination with ethambutol was significantly more active than each drug alone.
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PMID:Activity of moxifloxacin by itself and in combination with ethambutol, rifabutin, and azithromycin in vitro and in vivo against Mycobacterium avium. 1112 Sep 69

The antimicrobial activities of levofloxacin, clarithromycin and KRM-1648 against Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) residing in Mono Mac 6 human macrophage-like cells (MM6-Mphis) and A-549 human type II alveolar epithelial cells (A-549 cells) were studied. We measured the antimicrobial activity of test drugs in terms of effects on the behaviour of intracellular organisms during a 7-day cultivation of MTB- or MAC-infected cells in the medium containing the drugs at Cmax doses. Microbicidal action of levofloxacin against intracellular MTB within A-549 cells was markedly less than its activity against the same organisms in MM6-Mphis. The same effect was also noted for the action of KRM-1648 against MAC organisms but this did not occur with clarithromycin. The MIC of KRM-1648 for MAC multiplying within A-549 cells was 32 times larger than that for MAC residing in MM6-Mphis. These findings indicate that MTB and MAC organisms replicating in the type II lung epithelial cells resist the action of certain antimycobacterial agents such as quinolones and rifamycin derivatives but not when the organisms are contained in macrophages. It appears that the antimicrobial action of certain drugs against intracellular mycobacteria is differentially manifested depending on the types of host cells, i.e. professional phagocytes (MM6-Mphis) or non-professional phagocytes (A-549cells), in which the organisms are contained.
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PMID:Antimicrobial activities of levofloxacin, clarithromycin, and KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium complex replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines. 1118 10


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