Identifying New Antimicrobials and Drug Sensitivities

Multi-drug resistance is particularly damaging. This will create superbugs that are resistant to many different antimicrobials. A common method of doing this is to have a broad-spectrum efflux pump that can pump out many antimicrobial drugs. Nosocomial infections that occur in a medical setting are much more likely to be related to multidrug resistance.

MRSA or methicillin-resistant Staphylococcus aureus is a particularly problematic organism to treat. It is resistant to methicillin and all the beta-lactamase drugs. While it was first just an opportunistic and nosocomial infection, it is now a communityassociated infection, causing about six percent of staphylococcal carrier statuses. There are now vancomycin-resistant Staphylococcus aureus infections and vancomycinresistant enterococcal infections, usually spread in the hospital setting. Resistances also exist with gram-negative organisms that make extended-spectrum beta-lactamases and carbapenem resistances seen with Enterobacter organisms. Many strains of Mycobacterium tuberculosis are resistant to multiple drugs.

IDENTIFYING NEW ANTIMICROBIALS AND DRUG SENSITIVITIES

There are tests that can be done to test whether or not an antimicrobial drug is effective against a particular organism. The most common test is the Kirby-Bauer disk diffusion test. Organisms are grown on an agar plate and then disks with antimicrobial drugs impregnated into them are placed on the disk. Antibacterial activity is identified as a clear spot called the zone of inhibition around the disk. The diameter of the disk determines the level of antibacterial activity of the drug. It cannot tell the difference between a bacteriostatic and bactericidal drug. It cannot compare one drug with another.

Dilution testing can provide the doctor with the drug’s MIC or minimal inhibitory concentration, which is the lowest concentration of a drug that will inhibit visible growth of the bacterium and minimal bactericidal concentration or MBC, which is the lowest concentration of the drug that kills more than 99.9 percent of the starting organism inoculum. The MIC will be seen by looking for cloudiness of the broth, while

the MBC is detected by checking to see how many organisms grow. The drug’s level in the serum must be at least three times the MIC to treat an infection.

The E-test will combine the Kirby-Bauer test and the dilution testing. Instead of a disk placed on the agar disk, there is a strip that has a gradient of antibacterial concentrations. There will be an elliptical zone around the strip that will determine the MIC. It will compare one drug to another but cannot say what the MBC of the drug will be. The strip is labeled with different dilutions of drug on it.

New drugs can be made against pathogens by chemically altering existing drugs until something is found to be both effective and safe. Soil, vegetation, and microbial products are tested to see if there is antimicrobial activity found in any of these sources. There is a special technique called the iChip, which grows organisms right in the actual soil to see if anything in the dirt has antimicrobial effects. Soils from around the world have been tested, but there are marine sources that have not yet been tested.