Antimicrobial Chemotherapy

1. Antimicrobial Chemotherapy

2. Resistance to antimicrobial drugs:- There are many mechanism by which micro-organisms might exhibit resistance. A-Microorganisms Produce enzymes that destroy the active drug ex: staph resistant to penicillin G produce B-lactamase enzyme that destroy the drug. B-Microorganisms change their permeability to the drug ex: Tetracycline's accumulates in susceptible bacteria but not resistant bacteria. C-Microorganisms develop an altered structural target for the drug ex: Chromosomal resistance to aminoglycosdes is in the30s subunit of bacterial ribosome's that serves as a binding site in susceptible organism.

3. D-Microorganisms develop an altered metabolic pathway that by passes the reaction inhibited by the drug ex: some sulfonamide-resistant bact. Do not require extracelluar PABA (P-amino-benzoiacid) for biosynthesis of folic acid, but like mammalian cells they can utilize performed folic acid. E- Microorganisms develop an altered enzymes that is much less affected by drug as in trimethoprim resistant bact.

4. 1-Non genetic origin:- Origin of drug resistance Active replication of bacteria is usually required for most anti bacterial drug action. Thus M.O that are metabolically inactive (non multiplying may be resistant to drug. However their off spring are fully susceptible. T.B- survive in tissues for many years after infection restrained by the hosts defense and don’t multiply. Such M.O are resistant to treatment, but of they start to multiply (like following corticosteroid treatment of the patients) they are fully susceptible to same drug. Penicillin susceptible organism may change to L-from lacking cell wall and become resistant to penicillin (the cell wall inhibitor). M.O: May infect the host at sites where the antimicrobials are not active as like(gentamicin is not effective in treating Salmonella enteric fevers because Salmonella is intracellular).

5. 2-Genetic origin: *Chromosomal resistance:-develops a Result of spontaneous mutation in a chromosomal locus that control susceptibility to drugs (code for a number of drug receptors) as -Erythromyecin -Lincomycin -aminoglycosides *Extra chromosomal resistance:- bacteria also contain extra chromosomal genetic elements called plasmids (circular DNA molecules may exist free in bacterial cytoplasm organism integrated into the bacteria chromosome. R-Factors:- are class of plasmids that carry genes for resistance to antimicrobial resistance drug plasmid genes for antimicrobial resistance control the formation of enzymes that destroy antimicrobial drug.

6. Genetic material and plasmids can be transferred by the following mechanisms: 1-Transduction: Plasmids DNA is enclosed in a bacterial virus (bacteriophage) and transferred by the virus to another bacteria of the same spp. Ex: the plasmid carrying the gene for β lactamase production (in staph) can be transferred from a P-resistant to susceptible. If carried by suitable bacteriophage . 2- Transformation: naked DNA passes from one bacterial cell of a spp to another cell thus altering its genotype. This occur in laboratory manipulation or spontaneously. 3-Bacterial conjucation:- a unilateral transferring of genetic material between bacteria of the same or different genera occur during a mating process. This is mediated by a fertility (F) factor that result in the extension of sex pili from the donor (F+) cell to the recipient. Plasmid or other DNA will transfer through these tubules from donor to recipient cell such a resistance transfer factor (RTF) is the commonest method of spread of multidrug resistance in G-ve bacteria.

7. 4- Transposition: a transfer of short DNA sequence (transposons) occur between one plasmid and anther or between plasmid and apportion of the bacterial chromosome within a bact. Cell. Cross resistance: Microorganisms resistance to a certain drug may also be resistance to anther drug that share a mechanism of action. This exist mainly between agents that are closely related chemically eg, different aminoglycosides ). Selection of antibiotics : it depends on:- 1-Etiological diagnosis (the causative microorganism). 2- Susceptibility test of organism to the antibiotic in the lab.

8. Antimicrobial activity in vitro: Antim .activity is measured in vitro in order to determine: 1-The potency of an antibacterial agent in solution. 2-its conc. in body fluid or tissues. 3-The sensitivity of a given M.O to known conc. Of the drug. Measurement of antimicrobial activity: A-Dilution method : graded amounts of antimicrobial substance are incorporated into liquid or solid bacteriologic media. Then the media is inoculated with test bacteria and inoculated. The end point is taken as that amount of antimicrobial sub.required to inhibit the growth of or kill the test bacteria. B-Diffusion method: a fitter paper disk containing measured quantities of drug is placed on a solid media that have been heavy seeded with the test organism, after incubation. The diameter of the clear zone surrounding the deposit of drug in taken as a measure of inhibitory power of the drug against the test organism.

9. Disk Diffusion Test Determination of MIC Str Tet Ery 4 2 1 0 8 Tetracycline (μg/ml) Chl Amp MIC = 2 μg/ml Antibiotic Susceptibility Testing

11. Antibiotic resistant bacteria

12. References: • 1- Jawetz, Melnick, & Adelberg’s.( 2013). Medical Microbiology (Twenty-Sixth Edition). • 2- Kenneth Todar. (2008).Todar’s Online Textbook of Bacteriology ,University of Wisconsin.

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