Micro Chapter 14 - UTA 2460 Dr. Parks

Chemotherapy refers to any use of chemicals or drugs to treat a _____________. It may involve drugs that target _________________ cells or ___________________ drugs that target infectious microorganisms.

disease, cancerous, antimicrobial

Chemical analysis of a skeleton in Nubia (Sudan) show use of ________________, an antimicrobial agent. It was used in _________-making process.

tetracycline, beer

Paul Ehrlich discovered microbes that could kill ____________ without harming the patient. He discovered _______________ ________________, the causative agent of syphilis.

pathogens, treponema pallidum

Josef Klarer, Fritz Mietzsch, & Gerhard Domagk used the synthetic dye _____________ to treat streptococcal and _________________ infections. Sulfanilamide was the first ________________ antimicrobial drug, which was developed from a chemical.

prontosil, synthetic

Alexander Fleming saw that _________ growth inhibited staphylococcal growth. In this, he discovered ___________________, the first __________ antibiotic.

mold, penicillin, natural

Dorothy Hodgkin used ___-_______ for analysis. ___________________ antimicrobial is a chemically modified natural antibiotic. This is done to increase the range of an antibiotic.

x rays, semisynthetic

Selman Waksman studied actinomycetes and found that many were ___________________ in the soil.

antibiotics

If a patient is immunocompromised, a _______________ is required for successful treatment of infections.

bactericide

Broad-spectrum antimicrobial drugs target a wide variety, including gram - _____________ and ______________. They are frequently used for ___________________ infections or as _______________ prevention of infections with surgery/invasive procedures.

positive, negative, polymicrobic, prophylactic

The risk with broad-spectrum antibiotics is a __________________, where a microbe becomes resistant to the antibiotic. Yeast infections (_________________) and C. Diff caused by ______________ ______________.

candidiasis, clostridium difficile

The correct dosage must be given on the basis of adult body _______, how they are ____________ and eliminated from the body, and if there is a history of ___________ or __________ dysfunction.

mass, metabolized, kidney, liver

Route administration is how the drug gets into the body. ____________ is preferred because it is the most convenient. Sometimes intravenous is better because it is ______________ and more direct.

orally, faster

Sometimes, multiple drugs are needed.

________________ and Bactrim together act as a bactericide. This is a _________________ interaction.

trimethoprim, synergistic

Antagonistic drug interactions can cause a ________ in drug activity.

Example: ____________ + birth control

loss, antacids, rifampin

Selective toxicity is when it ________________ kills or inhibits the growth of certain microbes while causing no ___________ to the host.

selectively, harm

Inhibiting Cell Walls for Bacteria - β-lactams

blocks the crosslinking of _______________ chains during the synthesis of new _______________________.

Includes penicillins

Cephalosporins: they are ______________ antibiotics (not man made) and are ______________-spectrum, with increased gram-_______________ spectrum. Provides resistance to enzymatic inactivation by β-______________.

Monobactam: are _________________ antibiotics (somewhat man made). It is a narrow-spectrum that only works on gram - ______________.

Carbapenem: a lot of __________-spectrum drugs.

EXAMPLE:

Vancomycin: from the class of ____________________. It is bactericidal. It creates a structural ____________ in cell walls. It is a _______________ antibiotic with _____________-spectrum against gram-_______________.

Bacitracin: Prevents _______________ of peptidoglycan in cell walls. It is a _____________ antibiotic that is _____________-spectrum.

peptide, peptidoglycan

natural, narrow, negative, lactamases

semisynthetic, negative

broad

glycopeptides, blockage, natural, narrow, positive

incorporation, natural, broad

Types of Penicillins

Penicillin G + V: they are ____________ antibiotics (not man made). They are ______________-spectrum against mostly gram-_______________.

Ampicillin + Amoxicillin: they are _______________ antibiotics (somewhat man made). They are ________________-spectrum against gram-_____________, but with an increased gram-______________ spectrum.

Methicillin: they are _________________ antibiotics (somewhat man made). They are ______________-spectrum against gram-_______________ bacteria only.

natural, narrow, positive

semisynthetic, narrow, positive, negative

semisynthetic, narrow, positive

Inhibiting Protein Synthesis for Bacteria

Bacteria cells are ____S = ______S and _____S subunits

Aminoglycosides: bind to the _______S subunit. It impairs proofreading of the ______________ complex. They are ________-spectrum.

Examples: ___________mycin, __________micin, ______mycin

Tetracyclines: bind to the _____S subunit, they block the association of ________ with the ribosome during __________________.

Macrolides: Bind to the _____S subunit. erythromycin and ______________ inhibit peptide bond formation. They are __________-spectrum.

Lincosamides: particularly active against _________________ and staphylococcal infections. They are ________-spectrum.

Chloramphenicol: Has serious side effects such as ____________ in two different ways. It attacks the __________S ribosome in bacteria and mitochondria. Is a ___________-spectrum antibiotic.

Oxazolidinones: bind to the ______S subunit. Interfere with the initiation process of ______________ and prevent protein translocation.

70, 50, 30

30, ribosomal, broad, strepto, genta, neo

30, tRNA, translation

50, azithromycin, broad

streptococcal

anemia, 70, broad

50, translation

Inhibiting Membrane Function for Bacteria

Polymyxins: have _____________-like properties that interact with the __________________________ component of gram-______________ bacteria.

Daptomycin: is a cyclic __________ that inserts itself into the membrane and specifically targets gram-___________ bacteria.

detergent, lipopolysaccharide, negative

lipopeptide, positive

Inhibiting Nucleic Acid Synthesis for Bacteria

Metronidazole: interferes with DNA _____________. It is ___________-spectrum

Rifampin: blocks RNA _______________, it is ____________-spectrum to mainly gram-_____________.

Both of the above drugs are combined to treat __________________.

Fluoroquinolones: inhibits DNA ________, is ________ spectrum, and has bad side effects.

replication, broad

polymerase,narrow, positive

tuberculosis

gyrase, broad

Inhibiting Metabolic Pathways

Sulfonamides: blocks synthesis of nucleic acids, is ____________________ (inhibits), and is _______-spectrum.

Trimethoprim: inhibits a ____________ step in metabolic pathway. used in combination with a _______ drug to treat UTI, _______ infections, and bronchitis.

Isoniazid: preventing the synthesis of __________ acid and in combo with other drugs, it treats _______________. It is ____________-spectrum.

bacteriostatic, broad

later, sulfa, ear

mycolic, tuberculosis, narrow

Antifungal Drugs

Imidazoles: a fungicide that disrupts _______________ synthesis. Prevents seeds and crops from _____________. Treats fungal _______ infections like ringworm, ______________ foot, and ___________ itch.

Triazole: inhibits _______________ synthesis. treats ____________ infections.

Allylamines: inhibits ____________ synthesis. Terbinafine is used to treat common fungal infections on the ___________, as well as fingernail and toenail.

Polyenes: are naturally produced by an _______________, they create _______ in membranes.

Flucytosine: interferes with DNA ____________

Echinocandins: block synthesis of ___________ and treats ___________ infections

Polyoxins are used for ______________ purposes and Nikkomycin is under development to treat __________ infections

Griseofulvin: interferes with ______________ involved in spindle formation during mitosis

Atovaquone: works on ____________ and ____________.

ergosterol, molding, skin, athlete's, jock

ergosterol, yeast

ergosterol, skin

actinomycete, pores

replication

glucan, yeast

fungi, protozoa

Antiprotozoal Drugs

Proguanil: inhibits __________ acid synthesis, combined with atovaquone it treats _______________

Artemisinin: effective against ____________, produces a reactive ____________ that damages cells.

Metronidazole: introduces DNA strand ________ for Giardia lamblia, _____________ histolytica, and __________________ vaginalis

Pentamidine: treats __________ ___________ sickness, (Trypanosoma brucei) and __________________________ (Leishmania parasite) by binding to DNA or tRNA to prevent ______________ synthesis.

Quinolines: interferes with heme _________________ and is used to treat _______________

folic, malaria

malaria, oxygen

breakage, entamoeba, trichomonas

African sleeping, leishmaniasis, protein

detoxification, malaria

Antihelminthic Drugs

Mebendazole: __________-spectrum, inhibits ________________ formation.

Ivermectin: binds to ___________ channels and blocks neuronal transmission, causing _______________. Used to treat ________________ diseases, as well as parasitic insects.

Niclosamide: treats _________________ infections, inhibits ______ formation in anaerobic conditions

Praziquantel: treats parasitic tapeworms and _________ ___________, as well as schistosomiasis. It causes an influx of ______________ into the worm.

broad, microtubules

chlorine, starvation, roundworms

tapeworm, atp

liver flukes, calcium

Antiviral Drugs

Acyclovir: causes DNA chain ______________, treats _____________ viral infections.

Amantaide & Rimantadine: block escape of a virus from the membrane, treats _______________ A

Oseltamivir: brand name is _______________, it inhibits ___________________ in viruses.

termination, herpes

influenza, Tamiflu, neuraminidase

HIV targets CD___ white blood cells. It is also a ______virus and integrates into genome into the host.

Reverse Transcriptase Inhibitors: blocks the conversion of __________ to _________

Protease Inhibitors: prevents viral _______________

Integrase inhibitors: blocks HIV from ______________ with host genome

Fusion Inhibitors: prevents HIV from _______________ to the host cell

4, retro

RNA, DNA

mutation

genome

binding

Overuse, misuse, inappropriate use, and patient _______________ with antibiotics can all lead to drug ____________.

noncompliance, resistance

Genes responsible for drug resistance are found on ______________ that can be transferred through ___________ gene transfer.

plasmids, horizontal

Drug Modification:

β-lactams: resistance can involve the ____________ of the β-lactam bonds, then it loses its activity

hydrolysis

Prevention of Cellular Uptake:

Changes to the outer membrane __________ composition. Can produce ___________ pumps that pump the drug out of the cell.

lipid, efflux

Target Modification:

__________________ aureus is resistant to ___________________ because it has a new low-affinity PBP.

staphylococcus, methicillin

Overproduction or Enzymatic Bypass:

The microorganism could overproduce a target _____________, so that there is not enough antimicrobial drug to stop it.

May bypass need for specific target.

__________________ resistance in S. aureus uses the ________________ of targets.

enzyme

vancomycin, overproduction

Target Mimicry

_________________ _______________ produces a protein that looks like DNA and prevents the antimicrobial from working.

mycobacterium tuberculosis

Multi-Resistant microbes carry more than ____ resistance mechanisms. Superbugs, known as the ESKAPE pathogens:

E: ______________________ faecium

S: _____________________ aureus

K: ____________________ pneumoniae

A: ________________________ baumannii

P: _______________________ aeruginosa

E: ____________________ spp.

1

enterococcus

staphylococcus

klebsiella

acinetobacter

pseudomonas

enterobacter

The best way to cause a superinfection is to use __________-spectrum antibiotics for a __________ amount of time.

broad, long

Vancomycin resistance is _______________ ______________ involving a structural change in peptidoglycan. Acquired through ______________ gene transfer. _________________ and Staphylococcus ____________________.

target modification, horizontal, enterococci, aureus

Methicillin-resistant (MRSA) _________________ ______________ has a low-affinity PBP; resistance to all β-lactams.

staphylococcus aureus

Extended-spectrum β-lactamases are resistant to all but __________________. Resistance is spread through ______________ gene transfer.

carbapenems, horizontal

Carbapenem-resistant Enterobacteriaceae gain resistance through overproduction of a target _______________ and through ___________ pumps.

enzymes, efflux

MDR-TB strains are resistant to both _______________and isoniazid. XDR-TB strains are additionally resistant to any _____________________.

rifampin, fluoroquinolone

The Kirby-Bauer diffusion test examines how _________________ a microbe is to an antibiotic by looking at the zone of __________________. The larger the ______________ around the disk, the ____________ effective the antibiotic is. It cannot distinguish between _________________ and _____________________.

inhibition, diameter, more, bacteriostatic, bactericide

The minimal inhibitory concentration (MIC), the ______________ concentration of drug that inhibits visible bacterial growth. The minimal bactericidal concentration (MBC) is the lowest drug concentration that ______________ bacteria. Can use test tubes for this and compare _________________, or cloudiness. This is called a _______________ test, and it's needed to distinguish between MIC and MBC.

lowest, kills, turbidity, dilution

Etest places a lawn of bacteria and a strip of ______________________ concentration of a drug, and observes where the drug grows. The intersection of the _________________ zone with the gradient on the strip indicates the ___________(acronym).

increasing, elliptical, MIC

Soils and microbial _____________ are being looked at as antibiotics. Researchers can grow things ____ __________, which means in soil.

Teixobactin targets gram-________________ cell walls.

products, in situ, positive

___________________ chemistry, a process of making many related compounds and testing them for ___________________ activity.

combinatorial, antimicrobial