Development of resistance

Development of Resistance. One of the principal disadvantages of sulfonamide therapy is the emergence of dmg-resistant strains of bacteria. Resistance develops by several mechanisms overproduction of PABA (38) altered permeabiUty of the organisms to sulfonamides (39) and reduced affinity of dihydropteroate synthetase for sulfonamides while the affinity for PABA is retained (40). Sulfonamides also show cross-resistance to other sulfonamides but not to other antibacterials. In plasmodia, resistance may occur by means of a bypass mechanism in which the organisms can use preformed foHc acid (41). 

Provides a coordinated crop protection industry response to the development of resistance in insect and mite pests. During the last decade, IRAC has formed several international working gi oups to provide practical solutions to mite and insect resistance problems within major crops and pesticide groups. 

In endemic areas, chemoprophylaxis has been abandoned for a variety of reasons, mainly due to sustainability problems and the risk of contributing to the development of resistance. Intermittent preventive therapy (EPT), however, appears to be an alternative to protect pregnant women (IPTp) and children during the first year of their life (IPTi). 

Meinke, LJ USDA Western corn rootworm resistance to methyl parathion-development of resistance management strategies... 

As has been demonstrated for tenofovir, when incorporated at the 3 -end of reverse transcriptase (RT)-driven DNA chain allows the PMPA residue to adopt multiple conformations [in contrast with the more rigid conformation of the 2, 3 -dideoxynucleosides (see infra) (Tuske et al. 2004). This greater flexibility in conformation may impede development of resistance to tenofovir. 

The development of resistance against HCV NS3/4 protease inhibitors will become a major challenge for the clinical use of these new compounds. Clinical trials of telaprevir (VX-950) have shown that mutations at different positions are rapidly selected (Sarrazin et al. 2005). In vitro studies indicate that cells bearing repUcons with those mutations are associated with different levels of resistance to telaprevir (< 10-fold change to >40-fold change in sensitivity). However, telaprevir-resistant mutants remain susceptible to interferon-a, at least in the replicon system. Likewise, replicon mutants that are resistant to boceprevir are still sensitive to interferon-a (Tong et al. 2006). 

Selective toxicity is also important in relation to the development of resistance or tolerance to pollutants from two distinct points of view. On the one hand, there is interest among scientists concerned with crop protection and disease control in mechanisms by which crop pests, vectors of disease, plant pathogens, and weeds develop resistance to pesticides. Understanding the mechanism should point to ways of overcoming resistance, for example, other compounds not affected by resistance mechanisms or synergists to inhibit enzymes that provide a resistance mechanism. On the other hand, the development of resistance can be a useful indication of the environmental impact of pollutants. 

The development of resistant strains of pest species of insects has been intensively studied for sound economic reasons, and there are many good examples. For further information, see Brown (1971), Georghiou and Saito (1983), McCaffery (1998), and Oppenoorth and Welling (1976). Some examples of mechanisms of insect resistance are given in Table 4.3. 

The rapid growth in the use of OPs and the proliferation of new active ingredients and formulations was not without its problems. Some OPs proved to be too hazardous to operators because of very high acute toxicity. A few were found to cause delayed neurotoxicity, a condition not caused by ChE inhibition (e.g., mipafox, lepto-phos). There was also the problem of the development of resistance, for example, by... 

Apart from the importance of OP resistance in pest control, ecotoxicologists have become interested in the development of resistance as an indication of the environmental impact of insecticides. Thus, the development of esteratic resistance mechanisms by aquatic invertebrates may provide a measure of the enviromnental impact of OPs in freshwater (Parker and Callaghan 1997). 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

Staphylococcus aureus is less sensitive to erythron rdn than are pneumococci or haemolytic streptococci, and there may be a rapid development of resistance, especially of staphylococci, in vitro. However, in vivo with successM short courses of treatment, resistance is not usually a serious clinical problem. On the other hand, resistance is likely to develop when the antibiotic is used for long periods. 

The three standard drugs used in the treatment of tuberculosis were streptomycin (considered above), -aminosalicylic acid (PAS) and isoniazid (isonicotinylhydrazide, INH synonym, isonicotinic acid hydrazine, INAH). The tubercle bacillus rapidly becomes resistant to streptomycin, and the role of PAS was mainly that of preventing this development of resistance. The current approach is to treat tuberculosis in two phases an initial phase where a combination of three dmgs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of... 

Koziarz JWP, J Veall, N Sandhu, P Kumar, B Hoecher, IB Lambert (1998) Oxygen-insensitive nitroreductases analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli. J Bacteriol 180 5529-5539. 

To prevent development of resistance and promote synergy, inhaled tobramycin or colistin is usually added to an oral fluoroquinolone for P. aeruginosa coverage.1,3 Methicillin-sensitive S. aureus (MSSA) may be treated with oral amoxiciUin-clavulanic acid, dicloxacillin, first- or second-generation cephalosporins, trimethoprim-sulfamethoxazole, or clindamycin, depending on sensitivity. Likewise, methiciUin-resistant S. aureus (MRSA) may be treated with oral trimethoprim-sulfamethoxazole, clindamycin, minocycline, or linezolid. H. influenzae often produces... 

Inhaled tobramycin (TOBI ) is typically administered to patients 6 years of age and older in alternating 28-day cycles of 300 mg nebulized twice daily, followed by a 28-day washout or off period to minimize development of resistance. Longterm intermittent administration improves pulmonary function, decreases microbial burden, and reduces the need for hospitalization for IV therapy.24,25 Due to minimal systemic absorption, pharmacokinetic monitoring is not necessary with normal renal function. Lower doses of nebulized tobramycin solution for injection have been used in younger children, and studies are underway using 300 mg twice daily in children under age 6. 

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... 

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