Antibiotics, mycobacteria

The cell walls of mycobacteria contain three structures peptidoglycan, an arabinogalactan polysaccharide and long chain hydroxy fatty acids (mycolic acids) which are all covalently linked. Additional non-covalently attached lipid components found in the wall include glycolipids, various phospholipids and waxes. The lipid-rich nature of the mycobacterial wall is responsible for the characteristic acid-fastness on staining and serves as a penetration barrier to many antibiotics. Isoniazid and ethambutol have long been known as specific antimycobacterial agents but their mechanisms of action have only recently become more clearly understood. 

Mycobacteria are also killed in vitro, as expected from an antibiotic sharing the properties of the rifamycin family [24], In a study by Soro et al. [25], the MIC of rifaximin was determined for five Mycobacterium tuberculosis isolates from patients with tuberculosis. MIC concentrations were studied at 6, 20, 90 and 270 pg/ml, respectively. No resistant organisms were found. Growing M. tuberculosis in the presence of varying doses of rifaximin did not induce the occurrence of rifampicin-resistant strains [25]. In addition to this, experimental tubercular infection in the guinea pig was found not to be affected by an oral treatment course with rifaximin, therefore confirming the lack of absorption of the molecule after oral administration [26],... 

Ansamycins, like the macrolides, are synthesized by condensation of a number of acetate and propionate units. These antibiotics, which are produced by several genera of the Actinomy-cetales, display a characteristic core aromatic ring structure. Amongst the best-known family members are the rifamycins, which are particularly active against Gram-positive bacteria and mycobacteria. They have been used, for example, in the treatment of Mycobacterium tuberculosis. 

The aminoglycoside (see Section II.c) streptomycin was the first antimycobacterial antibiotic. It has activity against extracellular mycobacteria with a high growth rate. The macrolide antibiotics azithromycin and clarithromycin (see Section Il.d.l) were approved for the treatment of disseminated mycobacterial infections due to Mycobacterium avium complex. 

All mycobacteria produce (3-lactamase. In vitro, several (3-lactamase-resistant antibiotics or a combination of a (3-lactam with (3-lactamase inhibitors, such as clavulanic acid, are active against M tuberculosis and nontubercu-lous mycobacteria. However, the activity of (3-lactam agents against intracellular mycobacteria is generally poor. The (3-lactam agents may be useful in the treatment of MDR tuberculosis in combination with other antitubercular drugs but never as monotherapy. 

Rifampin is a semisynthetic derivative of rifamycin, an antibiotic produced by Streptomyces mediterranei. It is active in vitro against gram-positive and gram-negative cocci, some enteric bacteria, mycobacteria, and chlamydia. Susceptible organisms are inhibited by less than 1 mcg/mL. Resistant mutants are present in all microbial populations at... 

Capreomycin is a peptide protein synthesis inhibitor antibiotic obtained from Streptomyces capreolus. Daily injection of 1 g intramuscularly results in blood levels of 10 mcg/mL or more. Such concentrations in vitro are inhibitory for many mycobacteria, including multidrug-resistant strains of M tuberculosis. 

Antibacterial Spectrum. Hawley reported that various species and strains of the genera Staphylococcus, Streptococcus, Neisseria, Bacillus, Clostridium, and Corynebacterium are inhibited by nisin (Hawley 1957A, B). Mattick and Hirsch (1947) added actinomycetes, pneumococci, mycobacteria, and Erysipelothrix to this list. The nisin concentration required for complete inhibition is organism specific and ranges from 0.25 to 500 units per milliliter. Inhibition of L. casei by antibiotics from S. lactis and S. cremoris was observed by Baribo and Foster (1951). Inhibition of Propionibacterium by nisin but not of coliform bacteria was reported by Galesloot (1957). 

Biological Properties. The in vitro activity is such that oligosaccharides, in general, are highly potent, but are narrow-spectrum antibiotics. Everninomicins are active against a wide variety of gram-positive aerobes and anaerobes Neisseria, Mycoplasma, and some Mycobacteria. Comparatively, nambamycin is less potent Ilian everninomicin D. 

Herrmann M, Bohlendorf B, Irschik H, Reichenbach H, Hofle G (1998) Maracin and Maracen New Types of Ethynyl Vinyl Ether and a-Chloro Divinyl Ether Antibiotics from Sorangium cellulosum with Specific Activity Against Mycobacteria. Angew Chem Int Ed 37 1253... 

J Trias. Antibiotic transport in mycobacteria. In N Georgopapadakou, ed. Drug Transport in Antimicrobial and Anticancer Chemotherapy. New York Marcel Dek-ker, 1995, pp 269-288. 

S. pyrocinia produces [118] an antifungal antibiotic pyrrolnitrin (140) active against mycobacteria. The antimycobacterial activity can be well correlated with the presence of the halogen and nitro group in the aromatic ring. 

Determination of Minimum Inhibitory Concentration of Antibiotics and Non-Antibiotics by Tube Dilution of Different Strains of Mycobacteria... 

In these tests, MIC represented the smallest concentration of antibiotic/non-antibiotic that completely inhibited growth. Fourteen strains of mycobacteria were used for this study (Table 32). The drugs, namely, Streptomycin and Ri-fampicin, were used at the following concentrations ( xg/ml) in Kir diner s liquid medium [51] 0.12, 0.25, 0.5, 1.0, 1.5, and 2.0, with one drug-free control for methdilazine the concentrations (pg/ml) was 1,2.5,5.0,7.5,10.0,12.5, and 15. 

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