CHAPTER 21 BACTERIA Paul Ehrlich the cell membranes German physician and bacteriologist Observed that some cells dye stained some cells but not other indicating a fundamental difference in o Helps spark the idea that some bacteria would kill some cells and not others Discovered the cure for syphilis by researching effective arsenic compounds This drug was Salvarsan o Toxin termed the magic bullet but killed Terponema HISTORY AND DEVELOPMENT Discovery of Antimicrobial Drugs o Ehrlich discovered the first antimicrobial with Salvarsan o Domagk discovered a red dye that was affective against strep infections in animals It only is affective with the blood enzyme split the Prontosil molecule into sulfanilamide which acted against the infection Termed the sulfa drug o Chemotheraputic agent any chemical that combats a disease o Antimicrobial drug treat a microbial infection Discovery of antibiotics Penicillium o Alexander Fleming while observing staph that was being inhibited by a mold species In his lifetime he proved the effectiveness but was never able to purify penicillin o Ernst Chain and Howard Florey purified penicillin 10 years later Put in affect large scale operation by being able to study the structure of the drug Used in large scale in the war Penicillin G was found to be the most effective First antibiotic o Selman Waksman Discovered strepomysin by isolating bacteria in soil Development of New Generation Drugs o Concern of super drugs via overuse and pathogen adaptability o Scientists are able to change the properties of one microbial agent Ex penicillin g into ampicillin FEATURES OF ANTIMICROBIAL DRUGS Commercial Production o Can come from the lab soil bacteria and fungi o Semi synthetic when the drug is chemically altered after being grown and isolated in the lab o Grow strain in broth medium in fermentation tank o Incubate to maximum antibiotic concentration o Extract drug from medium o Purify drug them chemically modifed o Meaning causing greater harm to the microbe than to the body o Interfere with essential biological processes of the microorganism but not the host o Expressed in a therapeutic index the lowest toxic does to the patient divided by the dose used for therapy Selective toxicity When an agent has a high therapeutic index like penicillin a large amount can be administered without fear of toxins in the blood becoming high Bactracin pencillin beta lactams vancomysin Antimicrobial Action Spectrum of Activity o Bacteriostatic inhibit growth of organisms but when removed growth can will resume o Bacteriocidal sterilizing and fully kill microbial life o Broad spectrum antibiotics ones that kill a wide range of species Can disrupt the normal flora in the body o Narrow spectrum target a small number of species Kills less of the normal flora in the body Effects of Combinations of Antimicrobial Drugs o Some drugs when used in combo with each other have neg effects Bacteriostatic agents limit the effects of drugs that kill rapidly dividing cells o Antagonistic when one drug has a negative effect on the performance of another o Synergistic one drug enhances the ability of another o Additive drugs that are neutral and have no effect on the other Tissue Distribution Metabolism and Excretion of the Drug o Drugs have different characteristics that impede effectiveness If they can pass through CSF or whether or not they are able to be stable at pH o Half life the amount of time needed to eliminate of the drug from the body Depends on size and frequency of the dosage Adverse Effects o Allergic Reactions o Toxic Efects Can result in fever rash or anaphylactic shock Aplastic anemia a condition caused by toxic levels of chloramphenicol in which the body cannot make RBCs and WBCs o Suppression of the Normal Microbiota Antibiotic associated colitis caused by the growth of toxin producing C Difficilie This is normal flora but when other flora is suppressed this bacteria will become dominant in the culture and cause illness o Resistance to Antimicrobials Innate intrinstic resistance when bacteria is inherently resistant to certain drug effects Acquired resistance when new genes create the resistance Mechanisms of Action of Antibacterial Drugs Beta lactam drugs that inhibit cell wall synthesis Inhibit PBP pencillin binding proteins enzymes Inhibit synthesis by makeing prokaryotic ribosomes targets Have a b lactam ring Each class of drug binds to a particular position on the ribosomes to block translation Bacteriocidal and inhibits cell wall synthesis Vary in spectrum against Gram and Resistance is due to the synthesis of B lactamanses enzyme that breaks the beta lactam ring o Natural Penicillins Narrow spectrum Work against Gram and come gram o Penicillinase resistance penicillin o Broad spectrum Side chains prevent inactivation from penicillinases Modified side chains for broad spectrum o Extended spectrum Better against Pseudomonas o Penicillins and beta lactamase inhibitor Combination penicillin drug enzyme inhibitor Augmentin amoxicillin clavulanic acid Structures resistant to inactivation from b lactamnases o Cephalosporin Chemically modified to produce several generations of related cephlosporins Cefactor cephalexin Gram negative bacteria o Vancomycin Blocks PG peptide chains Used against penicillinR Gram bercause cannot cross gram negative outer membrane By IV only poor absorption from GI tract Levels needto be monitored in blood VanR most by alterations in the sidechain of the NAM molecule Protein Synthesis Inhibitors o Macroslides Erythromyosin clarithromycin azithromysin Reversibly bind to the 50S ribome Effective against cariety of gram and mycobacterium Resistance via Modification of rRNA target Production of enzyme that modifies drug Inhibition of nucleic acid sythesis o Rifamycins Block bacterial RNA polymerase and therefore transcription Anti Gr Primarily used to treat TB and leprosy and meningitis Resistance is due to a mutation in the RNA polymerase gene o Fluoroquinolones Inhibittopoisomerase DNA gyrase which is responsible for DNA supercoiling Ciprofloxacin Effective against Gram positive and Gram negative bacteria Resistance due to alteration of DNA gyrase Inhibtion of metabolic pathways o Relatively few drugs o Most useful for folic acid synthesis o sulfonamides o Trimethoprim sulfa drugs group of related compounds inhibit both types of gram resistance is due to plasmid coding for enzyme with low affinity for the drug Used for UTIs along with sulfa The