Microbiology Ch. 12 - Control of Microorganisms (Antimicrobials)

Exam 1

salvarsan

magic bullet

discovered by ehrlich and sahachiro hata

effective against syphilis spirochete

selective toxicity

means that a drug should harm the pathogen but not the host

toxic dose: concentration causing harm to the host

therapeutic host: concentration eliminating pathogens in the host

formulates the chemotherapeutic index

prontosil

red dye found to inhibit some gram-positive bacterial species

penicillin

alexander fleming’s discovery ushered in the era of antibiotics

penicillium mold produces a substance that kills gram-positive bacteria and some gram-negative bacteria

beta-lactam group because they include a beta-lactam ring with a variable side group

interfere with cell wall synthesis in rapidly growing cells, causing the cell to burst

synthetic agents

made in pharmaceutical lab

antibiotics

products of or derived from living microorganisms

semisynthetic drugs

include synthetic and antibiotic elements

broad spectrum drugs

affect many taxonomic groups

narrow spectrum drugs

affect only a few pathogens

antibiotics for inhibition of translation

aminoglycosides, chloramphenicol, tetracyclines, macrolides, clindamycin, streptogramins, oxazolidinones

antibiotics for inhibition of nucleic acid synthesis

DNA replication quinolones, RNA transcription rifampin

antibiotics for block cell wall synthesis

penicillins, cephalosporins, vancomycin, bacitracin, carbapenems

antibiotics for DNA precursor synthesis

sulfonamides

antibiotics for membrane injury

polymyxin b

sulfanilamide

target specific metabolic reactions

compete essential folic acid components for binding sites in a bacterial enzyme

prevent nucleic acid synthesis and DNA replication

isoniazid

interferes with cell wall synthesis in species of mycobacterium

enzymes involved in cell wall synthesis

aminopeptidases and carboxypeptidase

beta-lactam antibiotics target…

bacterial cell wall synthesis

natural penicillins include…

penicillin g and penicillin v

semisynthetic penicillins include…

ampicillin and amoxicillin (broader-spectrum)

MRSA

methicillin-resistant staphylococcus aureus

resistant to semisynthetic penicillin and natural penicillin

co-drugs

beta-lactamase inhibitors that have been developed to work synergistically with penicillin

cephalosporins

beta-lactam antibiotic for inhibiting cell wall synthesis

used in cases of penicillin resistance by the pathogen or penicillin allergy by the patient

newest ones are better against gram-negative bacteria than gram-positve bacteria

carbapenems

beta-lactam antibiotic for inhibiting cell wall synthesis

highly resistant to beta-lactamase enzymes

used as last resort

prescribed in combination to prevent premature degradation by the kidneys

monobactams

beta-lactam antibiotic for inhibiting cell wall synthesis

effective only against aerobic gram-positive bacteria like neisseria, pseudomonas, etc.

currently the only commercially available monobactam is aztreonam

side effects like skin rash and abnormal liver functions

no cross-hypersensitivity reactions with penicillin, but like other penicillins, can trigger seizures in patients with a history of seizures

glycopeptide antibiotics

inhibit bacterial cell wall synthesis

vancomycin

effective against gram-positive bacteria such as staphylococci

side effects like damage to the ears and kidneys

used a last resort

treats MRSA

polypeptide antibiotics affect…

cell membrane

have an unacceptable therapeutic window for internal use because they cause renal failure and respiratory paralysis

used topically

bacitracin

interferes with the transport of cell wall precursors through the membrane

used topically

polymyxins

increases membrane permeability of gram-negative rods

polymyxin e is used against many superbugs

polymyxin b and bacitracin are combined to make polysporin

daptomycin

bactericidal against gram-positive bacteria only

proven in vitro membrane disruption activity against enterococci, staphylococci, streptococci, and corynebacterial

antibiotics that affect protein synthesis

aminoglycosides, tetracyclines, glycylcyline, chloramphenicol, macrolides, lincosamides, streptogramins, and oxazolidinones

aminoglycosides

attach to bacterial 30S ribosomes, blocking transcription

streptomycin

generally prescribed as a co-drug for treatment of antibiotic-susceptible cases of tuberculosis

gentamicin, tobramycin, and amikacin

used against gram-negative infections in the urinary tract

neomycin

used for intestinal infections and as an ointment

kanamycin

used against gram-negative bacteria in wound tissue

tetracyclines

broad-spectrum antibiotic that targets the attachment of tRNA to the 30S subunit

have benzene ring formation

can destroy intestinal microbiota and cause staining of teeth and stunted bones

doxycycline is used for infections of gram-negative bacteria, including syphilis, gonorrhea, and pneumococcal pneumonia

glycylcycline

tigecycline is a broad-spectrum drug similar to tetracycline administered intravenously

macrolides

bind to the 50S subunit and inhibit elongation of polypeptides

antibiotic macrolides include erythromycin (used against gram-positive bacteria), azithromycin, clarithromycin, dirithromycin, roxithromycin, telithromycin

chloramphenicol

used against wide variety of bacteria, and some rickettsiea and fungi

reserved for serious infections like meningitis, cholera, typhoid and typhus fevers, and rocky mountain spotted fever

side effects include aplastic anemia (bone marrow doesn’t produce enough new cells), gray syndrome (found in babies, limpness, cyanosis, low bp, low body temperature, etc.)

lincosamides

block tRNA binding to the 50S subunit

clindamycin is a semisynthetic drug used against penicillin-resistant bacteria

pseudomembranous colitis can occur is microbiota are killed, allowing cdif to flourish

streptogramins

cyclic peptide that interferes with translation on the 50S subunit

broadly effective against gram-positive bacteria

oxazolidinones

prevents peptide bond formation

effective against gram-positive bacteria, including MRSA\

used as last resort

rifamin

interferes with RNA synthesis by binding to the bacterial RNA polymerase

effective against tb, leprosy, and meningitis

can cause liver damage

quinolones

block DNA synthesis in bacteria

include ciprofloxacin, ophthalmic, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, sparfloxacin, trovafloxacin, gatifloxacin, cinoxacin, nalidixic acid

tube dilution method

uses a series of tubes with different concentrations of an antibiotic to determine the lowest concentration of the antibiotic that is effective (MIC, minimum inhibitory concentration)

etest

determines MIC using an antibiotic-infused strip placed on an agar plate

measure zone of inhbition

disk diffusion method (kirby-bauer)

involved different antibiotics diffusing from paper disks on a bacterial confluent growth

measure zone of inhbition

antibiograms

used by clinicians to assess local susceptibility rates as an aid in selecting empiric antibiotic therapy and in monitoring resistance trends

antivirals

interfere with viral replication

virus attachment and penetration used to fight HIV and viruses cannot infect if they cannot invade cells

genome replication

used to fight HIV and herpes

prematurely terminates DNA synthesis or inhibits viral DNA polymerase

assembly and release

used to fight HIV and the flu

protease inhibitors inhibit viral assembly, and neuraminidase inhibitors prevent release

antifungals

cause membrane damage

because fungal pathogen metabolism is similar to the metabolic activity of human cells, drugs affecting fungal cells also have mild to severe toxic affects on the patient

antiparasitic

goal is to eradicate the parasite

aminoquinolines

antimalarial drugs that accumulate in parasitized red blood cells to interfere with the parasite’s ability to break down and digest hemoglobin

artemisin

destroys malarial parasites by releasing free radicals in red blood cells

anthelminthic agents

target nondividing helminths

praziquantel

changes membrane permeability

uses contraction and paralysis in the parasite

used for flukes and tapeworms

mebendazole

inhibits nutrient uptake in worms in the host intestine

prevents ATP synthesis

used for larval and adult nematodes and cestodes invading the intestine

avermectins

affects the nervous system

causes paralysis

used against a wide variety of roundworms

antibiotic drug resistance

mutations: spontaneous changes in genetic material

horizontal gene transfer: from donor cells, including transformation, transduction, conjugation

antibiotic resistance protection stages

antibiotic hydrolysis, antibiotic modification, membrane modification, target modification, and metabolic pathway alteration

antibiotic resistance is caused by…

improper or excessive use of antibiotics, like prescription abuse, misuse, misuse by healthcare organizations, and antibiotics in animal feed