Antimicrobial Drug Resistance & New Treatment Strategies (PDF)

28.12 Antimicrobial Drug Resistance and PEXAM New Treatment Strategies Antimicrobial drug resistance – the acquired ability of a microorganism to resist the effects of a chemotherapeutic agent to which it is normally sensitive – at least five reasons that microorganisms are...

28.12 Antimicrobial Drug Resistance and PEXAM New Treatment Strategies Antimicrobial drug resistance – the acquired ability of a microorganism to resist the effects of a chemotherapeutic agent to which it is normally sensitive – at least five reasons that microorganisms are naturally resistant to certain antibiotics (Table 28.8) Organism is impermeable to antibiotic. Organism can inactivate the antibiotic. Organism may modify the target of the antibiotic. Organism may develop a resistant biochemical pathway. Organism may be able to pump out the antibiotic (efflux). omis Table 28.8  Antimicrobial drug resistance – Because antibiotic-resistant genes are in nearly every population, physicians cannot use the same antibiotic for long. (Figure 28.33) – Any use of antibiotics selects for resistance, increasing the number of resistant bacteria in any bacterial population. Overuse accelerates this process.  Antimicrobial drug resistance – Almost all pathogenic microbes have acquired resistance to some chemotherapeutic agents. – A few pathogens have developed resistance to all ㄱ known antimicrobial agents. Our immnne syslem is – Resistance can be minimized by using antibiotics the strongest ! correctly and only when needed. – Resistance to a certain antibiotic can be lost if antibiotic is not used for several years.  New Treatment Strategies – Long-term solution to antimicrobial resistance relies on the development of new antimicrobial compounds. – Modification of current antimicrobial compounds is often productive (e.g., for vancomycin in Figure 28.34) – Automated chemistry methods (combinatorial chemistry) have sped up drug discovery. – New methods of screening natural products are being used. E.g., led to the discovery of platensimycin from the soil bacterium Streptomyces platensis Example of modifications on current drug: Vancomycin. Many pathogenic strains now show intermediate drug resistance to the parent structure of vancomycin, but chemically substituting the carbonyl oxygen at the position shown in red with a methylene (=CH2) group restores much of the lost activity. Like penicillin, vancomycin prevents cross-linking of peptidoglycan and is most effective against gram-positive pathogens. Figure 28.34 – Computers can now be used to design molecules to interact with specific microbial structures. Most successful example is saquinavir. (Figure 28.35) binds to active site of HIV protease – Combinations of drugs with enzyme inhibitors (e.g., clavulanic acid inhibits - lactamase) is given with ampicillin. – Combinations of drugs can be used (e.g., ampicillin and sulbactam).  언급은 없지안 당연히 나오겠기 ? 송 Antimicrobial susceptibility tests to determine minimum inhibitory concentration antibiotics, higher the 1. Agar disc diffusion test bigger thering A standardized concentration of bacteria is spread over the surface of an agar medium 「 and then paper disks or strips impregnated with antibiotics are placed on the agar surface. After overnight incubation, an area of inhibited growth is observed surrounding the paper disks or strips. The size of the area of inhibition corresponds to the activity of the Sadgrove, 2015 antibiotic—the more susceptible the organism is to the antibiotic, the larger the area of inhibited growth. By standardizing the test conditions for the agar diffusion tests, the area of inhibition is proportional to the minimum inhibitory concentration (MIC) value.  2. Broth dilution test Serial dilutions of an antibiotic are prepared in a nutrient medium and then inoculated with a standardized concentration of the test bacterium. After overnight incubation, the lowest concentration of antibiotic that is able to inhibit the growth of the bacteria is referred to as the minimum inhibitory concentration (MIC). https://microbeonline.com/minimum-inhibitory-concentration-mic-broth-dilution-method-procedure-interpretation/