Antimicrobial Agents PDF

Antimicrobial agents  1) Introduction Common terminologies  Chemotherapy  Is the use of chemical agents (either synthetic or natural) to destroy infective agents and to inhibit the growth of malignant or cancerous cells.  Antimicrobial agents  Chemical agent...

Antimicrobial agents  1) Introduction Common terminologies  Chemotherapy  Is the use of chemical agents (either synthetic or natural) to destroy infective agents and to inhibit the growth of malignant or cancerous cells.  Antimicrobial agents  Chemical agents/drugs (synthetic or natural) which are used for treating bacterial, fungal and viral infection either by killing or inhibiting the causative agent in vivo (in the host body).  Includes antibiotics and chemical antimicrobial agents. 2 Introduction….  Antibiotics  Are substances produced by various species of microorganisms (bacteria, fungi) that suppress the growth of other microorganisms.  E.g. Tetracycline, Penicillin, Streptomycin etc.  Chemical antimicrobial agents  Which are synthesized synthetically from different chemicals in the laboratory.  E.g. Sulphonamides, Metronidazole, Quinolones etc. NB:- Antibiotics may have a cidal (killing) effect or a static (inhibitory) effect on a range of microbes. Introduction….  Bactericidal  When antimicrobial agents lead to the death of the susceptible bacteria.  E.g. Penicillin’s, Cephalosporin, Glycopeptides and Aminoglycosides.  Bacteriostatic  When, at usual dosages, they prevent the active multiplication of bacteria.  E.g. Chloramphenicol, Tetracycline, and Erythromycin. Introduction…. Broad spectrum is applied to antibacterial with activity against a wide range of Gram positive and Gram negative bacteria. E.g. Tetracycline, Sulphonamides etc. Narrow spectrum Antibiotics those with activity against one or few types of bacteria. E.g. Vancomycin against Staphylococci and Enterococci.  Spectrum of Activity Narrow Spectrum Wide Spectrum Introduction….  Laboratory Terms  Antimicrobial sensitivity testing  Measuring the ability of an antimicrobial agent to inhibit or kill pathogens (bacteria) in vitro.  Using for selecting effective antimicrobial drugs.  Susceptible  The organism is killed or inhibited by given levels of antibiotics.  Resistant  The organism not killed or inhibited by given level of antibiotics.  Minimal Inhibitory Concentration(MIC)  Minimum concentration of antibiotics needed to inhibit visual growth of the organism. 7 Introduction…. Source of Antibiotics  Antibiotics are low-molecular weight substances that are produced as secondary metabolites by certain groups of microorganisms.  Natural 1) Bacteria  Streptomyces  Actinomycetes  Bacillus 2) Fungi (Molds)  Penicillium  Cephalosporium Microbial source of some antibiotics Microbial source of some antibiotics Introduction….  Ideal Qualities of antimicrobial agents 1) kill or inhibit the growth of pathogens. 2) Cause no damage to the host. 3) Cause no allergic reaction to the host. 4) Stable when stored in solid or liquid form. 5)Remain in specific tissues in the body long enough to be effective. 6) kill the pathogens before they mutate and become resistant to it. 7) It should not eliminate the normal flora of the host. 8) It should be nontoxic to the host and without undesirable side effects. 9) It should be inexpensive and easy to produce. 10) It should be able to reach the part of the human body where the infection is occurring.  Basic Classes of Antibiotics 1) β-lactams (Cell wall biosynthesis) Penicillins  Penicillin G  Ampicillin/amoxicillin  Flucloxacillin/cloxacillin  Piperacillin  Carbapenem Cephalosporins  Cefazolin, Cephalexin, Cephalothin (1st generation)  Cefaclor, Cefamandole, & Cefuroxime ( 2nd generation)  Cefotaxime, Ceftazidime, Ceftriaxone (3rd generation)  Cefepime ( 4th generation) Basic Classes of Antibiotics… 2) Glycopeptide (Cell wall biosynthesis)  Vancomycin  Teicoplanin 3) Aminoglycosides (Protein synthesis)  Gentamycin  Neomycin  Streptomycin  Amikacin  Kanamycin Basic Classes of Antibiotics… 4) Macrolides (Protein synthesis)  Erythromycin  Clarithromycin  Azithromycin 5) Quinolones (Nucleic acid synthesis)  Ciprofloxacin  Nalidixic acid 6) Sulfonamides (Folic acid metabolism)  Sulfamethoxazole  Trimethoprim 2) Mechanisms of antimicrobial drugs action 1) Inhibition of cell wall synthesis. 2) Inhibition of cell membrane function. 3) Inhibition of protein synthesis. 4) Inhibition of nucleic acid synthesis. 5) Antimetabolities Antibiotic Modes of Action Antibiotic Modes of Action Antimicrobial drug Resistance. Clinical resistance ◦ Resistance of bacteria to the concentration of anti-infective agents maintained at the infection site in the macroorganism. Natural resistance ◦ Resistance characteristic of a bacterial species, genus, or family. Acquired resistance ◦ Strains of sensitive taxa can acquire resistance by way of changes in their genetic material. Antimicrobial drug resistant Clinical consequence of Antibiotic Resistance i) Therapeutic failures and relapse ii) Facilitates spread in the hospital under “antibiotic pressure” iii) Need to use more costly and toxic agents iv) The emergence of untreatable pathogens. Etc.. Antimicrobial drug resistant….  Reasons for antibiotics resistance  Practices Contributing to Misuse of Antibiotics  Inappropriate specimen selection and collection  Inappropriate clinical tests  Failure to use stains/smears  Failure to use cultures and susceptibility tests  Inappropriate Antibiotic Use  Use of antibiotics with no clinical indication (eg, for viral infections)  Use of broad spectrum antibiotics when not indicated  Inappropriate choice of empiric antibiotics  Inappropriate Drug Regimen  Inappropriate dose - ineffective concentration of antibiotics at site of infection  Inappropriate route - ineffective concentration of antibiotics at site of infection Antimicrobial drug resistant…. Control of antibiotic resistance i) Increased awareness on how resistance occurs ii) Use of drugs only for serious disease and if given in sufficiently high dose. iii) Use of combined therapy iv) Sensitivity test should recommend. etc…… 4) Antimicrobial Sensitivity Testing Used for measuring the ability of the drug to inhibit or kill pathogens in vitro. ◦ So that it is used for selecting effective antimicrobial drugs. Itwill control the use of antibiotics in clinical practice. Testing will assist the clinicians in the choice of drugs for the treatment of infections. 22 Antimicrobial Sensitivity Testing…  Sensitivity test is performed: 1) For organisms with variable antibiotic sensitivity (un predictable sensitivity) E.g. Shigella species. 2) For non responding patients after taking adequate therapy. 3) For patients whose immune system is depressed. 4) For relapsing cases (reappearance of disease) Antimicrobial Sensitivity Testing… Sensitivity Testing Techniques 1) A dilution technique 2) A disk diffusion technique 1) Dilution technique for sensitivity test  Agar or broth media.  Principle: Graded amounts of antimicrobial agents are incorporated into liquid or solid bacteriology media.  The media are subsequently inoculated with test bacteria and incubated. 24 Antimicrobial Sensitivity Testing… The end point is taken as that smallest amount of antimicrobial agent required to inhibit the growth of the test bacteria minimum inhibitory concentration (MIC) or to kill the test bacterial minimum bactericidal concentration (MBC). Tube Dilution Test Antimicrobial Sensitivity Testing… 2) Disk Diffusion Sensitivity Testing  Principle: A disk of blotting paper is impregnated with a known volume and appropriate concentration of an antimicrobial agent, and this is placed on a plate of sensitivity testing agar uniformly inoculated with the test organism.  The antimicrobial diffuses from the disc into the medium and the growth of the test organism is inhibited at a distance from a disc that is related to the sensitivity of the organism. 27 Antimicrobial Sensitivity Testing… Strains sensitive to the antimicrobial agent are inhibited at a distance from the disc, where as resistant strains have smaller zones of inhibition or grow up to edge of the disc. The zone of inhibition is measured by clippers or ruler and values are matched (compared) with the predetermined standard values and reported as susceptible, Intermediate and resistant. 29 Antimicrobial Sensitivity Testing… Interpretation of Zone Size Using the interpretative chart, interpret the zones sizes of each antimicrobial and report the organisms as Resistant  A pathogen reported as ‘resistant’ implies that the infection it has caused will not respond to treatment with the drug to which it is resistant irrespective of dose or site of infection. 30 Antimicrobial Sensitivity Testing… Intermediate (moderately sensitive)  A pathogen reported as intermediately sensitive suggests that the infection it has caused is likely to respond to treatment when the drug is used in larger doses than normal or when the drug is concentrated at the site of infection.  Consideration should be given to using other drugs that may provide more optimal therapy. Antimicrobial Sensitivity Testing… Sensitive (Susceptible)  A pathogen reported as sensitive suggests that the infection it has caused is likely to respond to treatment when the drug is used in normal recommended doses.  NB: It is necessary to report the first and second choice of antibiotics for a patient’s infection unless the strain is resistant. 32  Susceptibility Testing Methods Incubate plate Inoculate Place disks 18-24 hr, 35 C MH plate on agar plate Measure and record zone of inhibition around each disk Antibacterial Agents Listed by Mechanism of Action