Risk of resistance development

The compounds are highlighted from the following viewpoints anti-HIV potency and selectivity, mechanism of action, antiviral activity spectrum, clinical or therapeutic potential, and risk of resistance development. 

Reducing the risk of resistance development, for example, for pesticides... 

In the case of pyrimidines and benzimidazoles. the first groups of fungicides against which resistance occurred quickly after market introduction, to our knowledge the risk of resistance development was not evaluated, nor was the phenomenon expected to show up. In... 

Imipenem-cilastatin is effective for a wide variety of infections, including urinary tract and lower respiratory infections intra-abdominal and gynecological infections and skin, soft tissue, bone, and joint infections. The drug combination appears to be especially useful for the treatment of infections caused by cephalosporin-resistant nosocomial bacteria, such as Citrobacter freundii and Enterobacter spp. It would be prudent to use imipenem for empirical treatment of serious infections in hospitalized patients who have recently received other P-lactam antibiotics because of the increased risk of infection with cephalosporin- and/or penicillin-resistant bacteria. Imipenem should not be used as monotherapy for infections owing to P. aeruginosa because of the risk of resistance developing during therapy. 

Resistance Prescribing tigecycline in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. 

Even if initial therapy is successful, some clinicians recommend periodically placing horses back on treatment following stress, which appears to play a role in the pathogenesis of EPM (Saville et al 2001). Other intermittent treatment regimens have also been used, such as treatment once every 2- 4 weeks or daily during the first week of every month. However, such intermittent treatment may increase the risk of the development of resistance in S. neurona and is, therefore, not recommended. Poor responses to therapy have led to the use of increased dosages of pyrimethamine and sulfadiazine in horses that do not respond clinically within 30-60 days of commencing treatment. 

There have been reports on the risk of resistant pathogen strains developing to Complex 11 inhibitors. Mutants resistant to carboxin were found to contain a single amino-acid substitution in the third cysteine-rich domain of the Ip protein. These mutations resulted in the conversion of a highly conserved His residue, located in a region of the protein associated with the [3Fe-4S] high-potential, non-heme iron sulfur-cluster (S3), to either Tyr or Leu [4]. 

Since its first commercial use in 2001, there have been no reports of reduced pathogen sensitivity to zoxamide. Laboratory studies to investigate the potential for resistance development to the benzamide class have been carried out with zoxamide [24], and zarilamide [25], a benzamide that binds to the same site as zoxamide on jS-tubulin [7]. In these studies, attempts to isolate resistant mutants in different Oomycetes using chemical mutagenesis, UV irradiation or adaptation were unsuccessful. These results suggest that the risk for resistance development to zoxamide in its commercial target pathogens is relatively low. 

When we introduce new fungicides, it is necessaiy to evaluate how quickly resistant strains can appear and increase with the use of fungicides. It is generally useful to elucidate the mode of action of newly developed products when predicting the inherent risk for resistance development, as most fungicides that have encountered resistance so far were site-specific inhibitors such as benzimidazoles, Qols and MBI-Ds. 

In conclusion, flavonoids and plant extract rich in flavonoidic compounds as antimicrobial agents present two main positive features the first is their natural origin, which means more safety for consumers, and the second is that they are considered to be low risk for resistance development by pathogenic microorganisms thus they can be considered a valuable support in the treatment of infections and may contribute to the development of new and safe antimicrobial agents. 

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