Antiinfective Drugs Lecture Notes PDF

ANTIINFECTIVE DRUGS Chapter 12 Page 226  ANTIMICROBIALS An antimicrobial is a chemical substance that has the capacity, in diluted solutions, to kill (biocidal activity) or inhibit the growth (biostatic activity) of microbes MICROORGANISMS SUCH AS B...

ANTIINFECTIVE DRUGS Chapter 12 Page 226  ANTIMICROBIALS An antimicrobial is a chemical substance that has the capacity, in diluted solutions, to kill (biocidal activity) or inhibit the growth (biostatic activity) of microbes MICROORGANISMS SUCH AS BACTERIA …..Antibiotics FUNGI …..Antifungals VIRUSES …..Antivirals PROTOZOA …..Antiprotozoals PARASITES …..Antiparasitics  ANTIBIOTICS “…any substance antagonistic to life.” “An antibiotic is a chemical substance which is produced by one microorganism and which , in dilute solution, can inhibit or destroy other microorganisms.” ANTIBIOTICS 1. Mechanisms of Action 2. Classification 3. Effectiveness A. Susceptibility B. Penetration C. Tolerable (by patient) 4. Resistance 5. Residue 6. Withdrawal Time THEY KILL or CONTROL THESE GUYS ! 1. GENERAL MECHANISMS OF ANTIMICROBIAL ACTION A Disruption of the development of the microbial cell wall www.newageimagery.com B Damaging the cell membrane in static/adult populations medicineworld.org C Interference with microbial protein synthesis edouard.decastro.name D Inhibition of nucleic acid production png E Disruption of microbial metabolic activity gopaultech.com Cell wall synthesis DNA gyrase DNA-directed RNA polymerase RNA elongation Cycloserine Quinolones Nalidixic acid Rifampin Vancomycin Ciprofloxacin Actinomycin Streptovaricins Bacitracin Novobiocin Penicillins Cephalosporins Protein synthesis Monobactams (50S inhibitors) Carbapenems Erythromycin (macrolides) DNA Chloramphenicol Clindamycin Folic acid metabolism Lincomycin Trimethoprim THF mRNA Sulfonamides Protein synthesis Ribosomes (30S inhibitors) DHF 50 50 50 Tetracyclines 30 30 30 Spectinomycin Streptomycin Gentamicin Cytoplasmic membrane Kanamycin structure and function Amikacin Polymyxins Nitrofurans Lipid Daptomycin biosynthesis Protein synthesis Platensimycin (tRNA) PABA Cytoplasmic Cell wall membrane Mupirocin Puromycin © 2012 Pearson Education, Inc.  2. CLASSIFICATION OF ANTIBIOTICS: 1) Type of microorganism it fights 2) Whether it kills the microorganism Spectrum of action : or only prevents it from – “is the range of bacteria for which the replicating & proliferating agent is effective” A) Bactericidal antibiotics kill the bacteria. Narrow-spectrum antibiotics work only on EITHER Gram +’ve OR Gram -’ve bacteria (not both!) Broad-spectrum antibiotics work on both gram +’ve B) Bacteriostatic antibiotics inhibit the growth or AND gram -’ve bacteria , but not necessarily ALL! replication of bacteria.  SPECTRUM KILL or INHIBIT Capacity (types of Bacteria) Photo Practical Pharmacology for Veterinary Technicians Clip Art Library  BACTERICIDAL VS BACTERIOSTATIC The drug does the ‘killing’ Temporarily inhibit the growth of bacteria, but Often must be at a higher once the drug is removed [ ] or longer treatment the organism can begin to time multiply again Depends more on a functional immune system to ultimately defeat the organism www.slate.com savvykidsmoms.biz 3. EFFECTIVENESS OF ANTIBIOTICS: ‘3’ MAJOR CONTRIBUTING FACTORS A. Organism must be susceptible to the antimicrobial drug. B. The antimicrobial must be able to penetrate the site of infection in high enough concentration to kill or inhibit the microorganism. C. Patient must be able to tolerate the treatment. 3 A1) SUSCEPTIBILITY: CULTURE & SENSITIVITY -indicates a disk coated with antibiotic ex: penicillin , sulpha , cephalexin etc. -indicates no growth of bacteria Start with a blank growth media, P Su and streak out the sample ; for example it could be an ear swab from a dog or a milk sample from a dairy cow. Tet Qui Key P =penicillin Su =sulph Qui=quinolone Photograph on page 228 of text. Tet =tetracycline  Nutrient Inoculate plate agar plate with a liquid culture of a test organism Discs containing antimicrobial agents are placed on surface Incubate for 24–48 h Test organism shows susceptibility to some agents, indicated by inhibition of bacterial growth around discs (zones of inhibition) © 2012 Pearson Education, Inc. 3 A2) SUSCEPTIBILITY: MIC MIC = Minimum Inhibitory Concentration MIC represents the lowest concentration of drug at which growth of the bacterium is inhibited Page 228 & 229 in textbook demonstrates the broth dilution susceptibility method microbeonline.com 3 A2) SUSCEPTIBILITY: MIC TIME DEPENDENT KILLING OR CONCENTRATION DEPENDENT KILLING Time : penicillin , cephalosporins, clindamycin, erythromycin versus Concentration : aminoglycosides , quinolones 3 A2) SUSCEPTIBILITY: MIC 1.2 1 Concentrations here have toxic effects 0.8 Drug Plasma Concentration [blood] 0.6 Therapeutic range of concentrations 0.4 MIC 0.2 Concentrations here are ineffective 0 Time NOTE: For each bacterial strain the MIC for antimicrobial drugs characteristically varies 3 A2) SUSCEPTIBILITY: MIC MIC = Minimum Inhibitory Concentration Bacteria & other pathogens typically have an MIC for almost all drugs… However, the concentrations required to kill or inhibit the bacteria may be so high that the host animal would suffer serious side effects Must consider the Maximum Tolerated Dose (MTD) 3 A2) SUSCEPTIBILITY: MIC Thus…if a bacterial strain has an MIC for an antimicrobial that IS LOW ENOUGH to not produce significant side effects in the host, then the bacteria is said to be sensitive to the drug Thus…if a bacterial strain has an MIC for an antimicrobial that is HIGHER then the drug’s MTD concentration, the bacteria are said to be resistant to that particular antibiotic.  3 B) PENETRATE TO THE SITE OF INFECTION In other words does the drug reach the target tissue??? Already know BBB , eye , mammary tissue Also meninges , CSF , prostate 3 C) PATIENT MUST BE ABLE TO TOLERATE THE TREATMENT Debilitated patients : Neonatal & Geriatric Compromised patients: kidney function , liver function 4. RESISTANCE TO ANTIBIOTICS: Resistance is created when bacteria develop the ability to survive in the presence of an antibiotic drug; they pass this resistance on to subsequent generations of bacteria. Canadian Animal Health Inspection Agency ”As little as possible, as much as necessary.” HOW THE BACTERIA DEVELOPS RESISTANCE TO AN ANTIBIOTIC 1. Genetic mutation in the DNA of the bacteria. It is passed to subsequent generations by what is called vertical transmission of resistance. 2. Acquire resistance as a result of spontaneous mutations of chromosomes 3. Where one bacteria transfer resistance to other unrelated bacteria by sharing a piece of DNA called a R plasmid. This process is known as horizontal transmission of resistance. BACTERIAL RESISTANCE More resistant bacterium 10 µg/ml Less resistant If concentrations achieved at infection Bacterium site are 7 µg/ml, the bacteria in 1 µg/ml the general population are killed, but the more resistant one is not! The resistant bacteria have survived and replicated, thus the next time the same antibiotic is used against them Selection it will be more difficult to kill them because this population Pressure has an MIC 10 X that of the original strain!!! TIME DEPENDENT / CONCENTRATION DEPENDENT 1. Antibiotics reduce diversity of commensal bacteria. 2. Increase prevalence of resistance genes. 3. Changes can be persistent. 5. ANTIBIOTIC RESIDUE: www.rissington.com “An antibiotic residue is the presence of a drug, chemical or its metabolites in animal tissue or food products, resulting from either administration of that drug or chemical to an animal or contamination of food products during food processing.” Antibiotic residues can cause allergic reactions in people or can produce resistant bacteria that can be transferred to people who consume these products Withdrawal times for antibiotics are aimed at eliminating antibiotic residues in food producing animals. 6. WITHDRAWAL TIMES Antibiotic is metabolized to a non-functional unit It is eliminated from the body Withdrawal times vary