Biological activity of a new class of rifamycins Spiro-piperidyl-rifamycins.

Sanfilippo, A.; Bruna, C. Della; Marsili, L; Morvillo, Enza; Pasqualucci, C.R.; Schioppacassi, G; Ungheri, D.

doi:10.7164/antibiotics.33.1193

Cited by 43 publications

(15 citation statements)

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“…Ansamycin (LM427; spiropiperidyl rifamycin) has been reported as having substantial in vitro activity against mycobacteria, especially against Mycobacterium avium complex (12,17). This antimycobacterial agent is widely used in the United States as an experimental drug, primarily for the treatment of disseminated M. avium infection in acquired immune deficiency syndrome patients.…”

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confidence: 99%

Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods

Heifets¹,

Iseman²,

Lindholm-Levy³

et al. 1985

Antimicrob Agents Chemother

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A radiometric method to determine the MIC of ansamycin (LM427) for Mycobacterium avium complex clinical isolates has been developed. It is based on a comparison of the conventional growth curve determination and the radiometric detection of growth (growth index) in the same liquid medium (7H12 broth). This new method requires less time and labor than does a conventional determination of MIC in liquid medium (CFU). Other advantages of this method include relatively short periods of exposure of the drug to 3TC and the composition of 7H12 broth, which has practically no substrates which could absorb or bind the drug. Thus, a more accurate estimation of the MIC in this medium can be expected than by the conventional agar dilution (proportion) method. The MICs of ansamycin appeared to be higher in agar plates than in 7H12 broth. More than 70% of the isolates had a broth-determined MIC one to three times lower than the average peak concentration of ansamycin achieved in sera of patients. The wide range of MICs suggests the importance of testing susceptibility in broth with many concentrations in addition to, or rather than in, agar plates with concentrations of 2.0 or 1.0 ,ug/ml only. Taking into account relatively low levels of ansamycin in sera of patients, it would be appropriate to compare the MICs with the levels in serum to make the outcome of chemotherapy more predictable.Ansamycin (LM427; spiropiperidyl rifamycin) has been reported as having substantial in vitro activity against mycobacteria, especially against Mycobacterium avium complex (12, 17). This antimycobacterial agent is widely used in the United States as an experimental drug, primarily for the treatment of disseminated M. avium infection in acquired immune deficiency syndrome patients. However, the clinical effect of this treatment is so far unknown. This use of ansamycin is based on in vitro studies which indicated that a high percentage of M. avium complex strains were inhibited by 1.0 and 2.0 pug of ansamycin per ml incorporated into 7H10 or 7H11 agar medium. However, several major questions remain to be answered about the utility of this compound in such infections. It is not known whether there is any correlation between the MIC of this drug for the infecting organism in vitro and the clinical (in vivo) study were to determine the range of MICs of ansamycin for M. avium clinical isolates in liquid medium, to establish the validity of determining the MIC in 7H12 broth with the radiometric growth index (GI) by comparing such data with the growth curve in the same cultures, to compare results obtained in liquid medium and by the agar dilution method, and to compare the range of MICs with ascertained levels of ansamycin in sera of patients.We have very limited information about the clinical effects of ansamycin, and only a few of the patients from whom isolates were taken for this study have been treated with ansamycin. Therefore, this report does not present any data regarding the correlation between the results of in vitro testing and the clini...

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confidence: 99%

Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods

Heifets¹,

Iseman²,

Lindholm-Levy³

et al. 1985

Antimicrob Agents Chemother

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“…The spiro-piperidyl-rifamycins are a new class (1) of rifamycin S antibiotics endowed w i t h antibacterial activity (2,3). In a recent paper Marsili et al (1) described many derivativem of rifamycin and among these the spiro-piperidyl compounds Iw 118 and rifabutin (LM 427) showed a promising activity against atypical Mycobacterium tubercolosis strains ( The requirement of radioactive derivatives to assist disposition, metabolism and pharmacokinetics 6tudies in laboratory animals, prompted us to prepare these substances in a suitable labelled form.…”

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Synthesis of carbon‐14 labelled spiro‐piperidyl‐rifamycins (LM 118) and rifabutin (LM 427)

Fontana¹,

Giarda²,

Vioglio³

et al. 1987

Labelled Comp Radiopharmac

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“…Ansamycin is a derivative of rifamycin SV (4,7,12). Its in vitro activity against Mycobacterium avium complex was reported by Woodley and Kilburn (21), Ungheri et al (20), Cynamon (3), and Heifets and Iseman (5).…”

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Two Groups of Mycobacterium avium Complex Strains Determined According to the Susceptibility to Rifampicin and Ansamycin

Tsukamura

1987

Microbiology and Immunology

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Mycobacterium avium complex strains previously not exposed to any antituberculosis agents could be divided into two groups according to their susceptibility to rifampicin and ansamycin; one group susceptible to 80 ,ugiml rifampicin and to 1.25 ,ugiml ansamycin, and another resistant to these concentrations. In each group, the ratio of the minimal inhibitory concentration of ansamycin against that of rifampicin was greatly different depending on the strain. This naturally occurring resistance to rifampicin and ansamycin was frequently correlated to naturally occurring resistance to ethambutol, kanamycin, enviomycin, kitasamycin, and minocycline, but not correlated to that to isoniazid and sulfadimethoxine. Ansamycin was more active than rifampicin against M. bovis, M. kansasii, M. marinum, M. xenopi, and M. haemophilum.Ansamycin is a derivative of rifamycin SV (4, 7, 12). Its in vitro activity against Mycobacterium avium complex was reported by Woodley and Kilburn (21), Ungheri et al (20), Cynamon (3), and Heifets and Iseman (5). It inhibited the growth of the M. avium complex strains at concentrations of 1 to 2 ,ug/ml in the 7H-10 agar, 7H-10 broth, or 7H-11 agar medium (3,5,20,21). Therefore, ansamycin is at present the most promising agent for the treatment of disease due to the M. avium complex, which is resistant to most antituberculosis agents. However, the cross-resistance relationship between rifampicin and ansamycin (both are derivatives of rifamycin SV) is not yet clear. Employing the 7H-11 agar medium, Heifets and Iseman (5) reported that all strains that were susceptible to 1.0 ,ug/ml rifampicin were susceptible to 0.5 ,ug/ml ansamycin and 20% of the strains, which were naturally resistant to 10 dug/ml rifampicin, were susceptible to 0.5 iug/ml ansamycin. Only 10% of the latter strains were resistant to 2.0 eug/ml ansamycin. Their finding suggests that the cross-resistance relationship between these two agents is only partial. The present study has been carried out to clarify the cross-resistance relationship. 615

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Biological activity of a new class of rifamycins Spiro-piperidyl-rifamycins.

Cited by 43 publications

References 1 publication

Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods

Determination of ansamycin MICs for Mycobacterium avium complex in liquid medium by radiometric and conventional methods

Synthesis of carbon‐14 labelled spiro‐piperidyl‐rifamycins (LM 118) and rifabutin (LM 427)

Two Groups of Mycobacterium avium Complex Strains Determined According to the Susceptibility to Rifampicin and Ansamycin

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