Resistance to rifampin

Intranasal S. aureus increases the risk of S. aureus exit-site infections, tunnel infections, peritonitis, and subsequent catheter loss.49 Several measures have been used to decrease the risk of peritonitis caused by S. aureus, including mupirocin cream applied daily around the exit site, intranasal mupirocin cream twice daily for 5 days each month, or rifampin 300 mg orally twice daily for 5 days, repeated every 3 months.49 Mupirocin use is preferred over rifampin to prevent the development of resistance to rifampin, although mupirocin resistance has also been reported.49 Other measures that have been used to decrease both S. aureus and P. aeruginosa infections include gentamicin cream applied twice daily and ciprofloxacin otic solution applied daily to the exit site.49... 

Three studies have addressed the possibility of inducing cross-resistance to Mycobacterium tuberculosis during the use of rifaximin. In an experimental guinea pig model of M. tuberculosis, rifaximin was administered in an effort to induce resistance among M. tuberculosis strains of human origin. Not only did no resistance develop, crossresistance to rifampin also did not occur [17, 18]. In another approach, M. tuberculosis strains were subjected to subinhibitory concentrations of rifaximin. No induction of resistance or cross-resistance to rifampin occurred... 

The use of an antagonistic antimicrobial combination does not preclude other potential beneficial interactions. For example, rifampin may antagonize the action of anti-staphylococcal penicillins or vancomycin against staphylococci. However, the aforementioned antimicrobials may prevent the emergence of resistance to rifampin. 

Cooksey RC, Holloway BP, Oldenburg MC, Listenbee S, Miller CW. Evaluation of the invader assay, a linear signal amplification method, for identification of mutations associated with resistance to rifampin and isoniazid in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2000 44(5) 1296-1301. 

Rifabutin resembles rifampin but may be effective in infections resistant to rifampin. 

Chromosomal mutation develops readily in most bacteria exposed to rifampin and leads to a high level of resistance. These mutants show stable changes in RNA polymerase that prevent binding. Resistance to rifampin is not transferable and there is no cross-resistance with other antibiotics. 

Isoniazid, the mainstay in virtually any regimen to treat M. tuberculosis, penetrates the CSF with or without meningeal inflammation and achieves concentrations of more than 30 times the MIC of M. tuberculosis (MICs of 0.05 to 0.2 mg/L)." Rifampin s penetration of CSF approximates only 20% of sernm concentrations in the presence of meningeal inflammation. M. tuberculosis typically is so exquisitely sensitive to rifampin, however, that the low penetration ratio is of little clinical significance. However, the incidence of M. tuberculosis resistance to rifampin has increased, necessitating empirical multiple-antibiotic regimens. 

Answer E. For antitubercular activity, isoniazid (INH) must first be metabolically activated via a catalase present in mycobacteria. A decrease in expression of the cat G gene that encodes this enzyme is the mechanism of high-level resistance to INH. Low-level resistance occurs via mutations in the inh A gene that codes for an enzyme involved in synthesis of mycolic acids. Mutations in the gene that codes for DNA-dependent RNA polymerase is an important mechanism of resistance to rifampin and related antibiotics. 

Rifabutin has better activity against MAC organisms than rifampin and is active in vitro against MAC bacteria isolated from HIV-infected (typically M. avium and non-HIV-infected individuals (-40% M. intracellulare. Rifabutin also inhibits the growth of many strains o/M. tuberculosis. Cross-resistance between rifampin and rifabutin is common in M. tuberculosis, although some strains are resistant to rifampin yet sensitive to rifabutin. Most M. avium strains resistant to rifampin are still sensitive to rifabutin. 

Within a few days of initiation of treatment for tuberculosis, laboratory staining results of Ivy Sharer s sputum confirmed the diagnosis of pulmonary tuberculosis caused by M. tuberculosis. Therefore, the multidrug therapy, which included the antibiotic rifampin, was continued. Rifampin binds to the RNA polymerases of several bacteria. M. tuberculosis rapidly develops resistance to rifampin through mutations that result in an RNA polymerase that cannot bind the complex structure. Simultaneous treatment with a drug that works through a different mechanism decreases the selective advantage of the mutation and the rate at which resistance develops. 

Organism exhibits intermediate resistance to rifampin (rifampicin) concentration (disc) 15 yg. Organism is susceptible to rifampin (rifampicin) concentration (NOT disc) 20 yg/ml. 

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