Chapter 12: Drugs, Microbes, Host- The Elements of Chemotherapy *******TEST 3

goal of antimicrobial therapy

administer a drug to an infected person that destroys the infective agent without harming the host's cells

ideal antimicrobial drug

selectively toxic to microbe but not host cell, not broken down prematurely, not subject to resistance, assists activities of host's defenses

antibiotics

common metabolic products of aerobic bacteria and fungi

selectively toxic

drugs should kill or inhibit microbial cells without simultaneously damaging host tissues

mechanisms of drug action

inhibition of cell wall synthesis, breakdown of the cell membrane structure or function, interference with functions of DNA and RNA, and inhibition of protein synthesis, blockage of key metabolic pathways

narrow spectrum drugs

effective on a small range of microbes, targets a specific cell component only found in certain microbes

broad spectrum drugs

greatest range of activity, target cell components common to most pathogens

antibiotics that effect cell walls

block synthesis of peptidoglycan, causing cell to lyse, penicillin, cephalosporin, carbapenem, non-beta-lactam

antibiotics that disrupt membrane function

polymyxins interact with phospholipids and cause leakage, particularly in gram-negative bacteria, amphotericin B and nystatin

drugs that effect nucleic acid synthesis

may block synthesis of nucleotides, inhibit replication, or stop transcription, chloroquine

drugs that block protein synthesis

antimicrobics usually have a selective action against prokaryotes; can also damage the eukaryotic mitochondria, tetracycline, aminoglycoside drugs, chloramphenicol, macrolides

drugs that affect metabolic pathways

competitive inhibition: drug competes with normal substrate for enzyme's active site, sulfonamides, trimethoprim

synergistic effect

the effects of a combination of antibiotics are greater than the sum of the effects of the individual antibiotics, sulfonamides, trimethoprim

penicillin structure

thiazolidine ring, beta-lactam ring, variable side chain dictating microbial activity

mrsa ca

Staphylococcus aureus (resistant to beat-lactam drugs)

diseases od s. aureus

normal skin/nose inhabitant but can cause: boils, ssss, impetigo, food poisoning, pneumonia, septicemia

mrsa infection categories

hospital associated mrsa, community associated mrsa

ca mrsa

boil or abcess (red, swollen, painful, pus or other drainage), can be septicemic or pneumonia (sob, chills, fever, death), as more serious infections

transmission: entryt hrough cuts or scrapes

ha mrsa infections

transmission: autoinoculation or via human hands, start as small red bumps that resemble pimples, boils or spider bites, can quickly turn into deep, painful abscesses that require surgical draining, bacteria can remain confined to the skin, can also burrow deep into the body, causing potentially life-threatening infections in bones, joints, surgical wounds, the bloodstream, heart valves and lungs

risk factors

ha: current or recent hospitalization

ca: young age, contact sports, haring towels or athletic equipment, weakened immune system, crowded or unsanitary conditions

mrsa epidemiology

86% healthcare associated

tx

draining of abscess or boil, may not need antibiotics, susceptible to vancomycin, trimethoprim-sulfamethoxazole anddoxycycline, severe infections: vancomycin intravenously

visa/vrsa

Vancomycin Intermediate Staphylococcus aureus, Vancomycin Resistant Staphylococcus aureus (VRSA) are specific types ofantimicrobial-resistant bacteria.• As of October 2010, VISA/VRSA aresusceptible to several FDA approved drugs, generally hospital associated

mrsa prevention

proper hand washing, prevention of nosocomial infections, promptly shower after exercising, keep cuts and scraps clean and covered, avoid sharing personal items (towels, washcloths, razors, clothes, uniforms), wash sheets and towels with hot water and bleach

cephalosporins

1/3 of all antibiotics administered, synthetically altered beta-lactam structure, relatively broad-spectrum, resistant to most penicillinases, cause fewer allergic reactions, some are given orally; many must be administered parenterally

4 generations of cephalosporins

first generation: most effective against gram-positive cocci and few gram-negative

second generation: more effective against gram-negative bacteria

third generation: broad-spectrum activity against enteric bacteria with beta-lactamases

fourth generation: widest range, both gram-negative and gram-positive

beta-lactam drug

type of drug that binds to the enzyme that forms peptidoglycan cross-links in cell walls

walking pneumonia ca

Mycoplasma pneumoniae

walking pneumonia s&s

gradual and insidious onset of several days to weeks, fever, malaise, headache, scratchy sore throat, persistent, slowly worsening dry cough, sore chest and tracheal tenderness, chest cold, normal lung findings with early infection but rhonchi, rales, and/or wheezes several days later

walking pneumonia pathogenesis

person-to-person transmission by contact with respiratory secretions, icp 1-4 wks, prolonged paroxysmal cough due to the inhibition of ciliary movement, gliding motility and specialized filamentous tips end =burrow between cilia within the respiratoryepithelium• leads to sloughing of the respiratory epithelial cells

walking pneumonia epidemiology

frequent cause of community-acquired respiratory infections in adults and children, 5-20 yrs old, epidemics of mycoplasmal pneumonia tend to occur every 3-7 years in the general population, closed populations, military and institutional, late summer and fall

walking pneumonia tx and prevention

erythromycin, tetracycline, tx for several weeks to prevent relapse, good hand hygiene, covering coughs and avoiding those who have the disease (no vaccine)

drugs that act on dna and rna

fluoroquinolones: work by binding to dna gyrase and to poisomerase IV, broad spectrum effectiveness, careful monitoring of their use to prevent ciprofloxacin-resistant bacteria

tetracycline antibiotics

broad-spectrum, block protein synthesis by binding ribosomes, tx for std, lyme disease, generic tetracycline is low in cost but limited by its side effects

antifungal drugs

hard bc most are eukaryotic cells so we have to make them target only the pathogen not our cells, main groups of drugs that have been developed to specifically treat fungal infections are macrolide polyene antibiotics, griseofulvin, synthetic azoles, flucytosine, echinocandins, fungerps

antiparasitic chemotherapy

antimalarial drugs - quinine, chloroquine

antiprotozoan drugs - metronidazole (Flagyl), etracyclines

antihelminthic drugs

antiviral chemotheraputic agents

hard to completely kill a virus, most designed to block a step in viral process

1) block penetration into host cell

2) block replication, transcription, or translation of genetic material

3) prevent maturation of viral particles

interferon (ifn)

human-based glycoprotein produced primarily by fibroblasts and leukocytes, reducing healing time and some complications of infections, preventing or reducing symptoms of cold and papilloma virus, slowing the progress of certain cancers, leukemias, and lymphomas, tx of hepatitis C, genital warts, Kaposi's sarcoma in AIDS patients

drug resistance

an adaptive response in which microorganisms begin to tolerate an amount of drug that would ordinarily be inhibitory, result of genetic versatility and adaptability of microbial populations, can be intrinsic and acquired, acquisition of resistance is the main problem for microbial chemotherapy

how does drug resistance develop?

spontaneous mutations in critical chromosomal genes, acquisition of new genes or sets of genes via transfer from another species, through intermicrobial transfer: transfer of plasmids encoded with drug resistance, transposons duplicated and inserted from one plasmid to another or from a plasmid to the chromosome

mechanisms of acquired drug resistance

1) drug inactivation: inactivation of a drug like penicillin by penicillinase, an enzyme that cleaves a portion of the molecule and renders it inactive

2) decreased permeability: receptor that transports the drug is altered, so that the drug cannot enter the cell

3) activation of drug pumps: specialized membrane proteins are activated and continually pump the drug out of the cell

4) change in drug binding site

5) use of alternate metabolic pathway: drug has blocked the usual metabolic pathway so the microbe circumvents it by using an alternate, unblocked pathway that achieves the required outcome

drug toxicity

adverse effects of an antibiotic, major side effects: direct damage to tissue due to toxicity of drug, allergic reactions, disruption of the body's microbiota

selecting an antibiotic

degree of microbe's susceptibiltiy to drug, overall medical condition of pt, nature of the microorganism causing the infection: specimens should be taken before antimicrobials are initiated, direct examination of body fluids, sputum, or stool provides rapid detection of bacteria and fungi, molecular diagnosis has improved diagnosis

test to determine which antibiotic

Kirby-bauer: grows a known quantity of bacteria on agar plates in the presence of thin wafers containing antibiotics

tube dilution: used to determined the minimum inhibitory concentration (MIC), smallest concentration of drug in series that visibly inhibits microbial growth

ETest

minimum inhibitory concentration

in vitro activity of a drug is not always correlated with in vivo effect, if therapy fails, a different drug, combination of drugs, or different administration must be considered, best to chose a drug with highest level of selectivity but lowest level toxicity (measured by theraputic index): ratio of the dose of the drug that is toxic to humans as compared to its minimum effective dose, high index is desirable