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56 Cards in this Set
- Front
- Back
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Antimicrobial agent:
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: A general term for drugs, chemicals, or other substances that either kill or slow the growth of microbes.
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Antibiotic:
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A drug used to treat infections caused by bacteria and other microorganisms. Includes synthetically produced drugs. (Old definition only included microbially-produced drugs).
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Selective Toxicity
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inhibition of growth of targeted microbe without damage to the host. Antibiotic treatment is chemotherapy.
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Prodrug:
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a drug that is administered in an inactive form. Activation occurs in vivo upon it being metabolized. (e.g. Isoniazid is activated by Mycobacterium’s catalase enzyme)
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Narrow-spectrum antibiotics
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target only certain classes of bacteria (examples: Gram-negatives, anaerobes, Mycobacterium
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Broad-spectrum antibiotics:
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capable of targeting both Gram-negative and Gram-positive bacteria.
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When is it appropriate to use Broad- or Narrow-spectrum antibiotics?
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Generally, want to use Narrow-spectrum whenever possible. Avoids killing “helpful” natural flora.
Broad-spectrum may be necessary during life-threatening infections due to unknown pathogen. This provides “coverage” against most pathogens, until an appropriate course of treatment is determined Broad-spectrum may be a prophylactic before surgical proceedures. |
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Kirby-Bauer Disc Diffusion
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Qualitative measurement of Minimum Inhibitory Concentration (MIC)
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Determining Quantitative Minimal Inhibitory Concentration (MIC)
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Quantitative analysis for determining antimicrobial suceptibility
typically recorded in mg/ml (micrograms/milliliter) does not determine if bactericidal or bacteristatic . Commercially available strips. Serial dilution of antibiotic across strip. Placed on agar plate containing bacteria. View edge of clearing at lowest concentration of antibiotic. |
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Determining Minimal Bactericidal Concentration (MBC)
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Inoculate from MIC cultures into fresh growth medium lacking antibiotics
MBC will always be greater-than or equal-to MIC |
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All antibiotics work only agaisnt
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growing bacteria
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Be able to recognize betalactam and penicilnn
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beta 4 rings
peniclin 5 |
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Cephalosporins (yes, still b-lactams, still target cell wall)
Benefits over penicillin |
1. more resistant to lactamases
2. R2 group offers more manipulation for changing specificty |
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Cephalosporins 1 Generation
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: target Gram-positives (Strep and Staph)
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Cephalosporins 2 Generation
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broader Gram-negative spectrum; respiratory tract infections, sinusitis and otitis media; urinary tract infections from E. coli, Klebsiella and Proteus
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Cephalosporins 3 Generation
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further increased effectiveness against Gram-negatives, but decreased against many Gram-positives (exception Streptococcus pneumoniae)
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Cephalosporins 4 Generation
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: Broadest coverage against Gram-negatives and positives; best resistance to b-lactamases; some can cross blood-brain barrier (treat meningitis)
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1st generation works best against Gram positive and 2, 3 and 4
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work best gram negative
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Carbapenems (Imipenem)
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Very small b-lactam. Broadest antibacterial coverage. Often given with cilastin (inhibitor of liver enzyme that breaks down this drug). One of few remaining drugs used to treat b-lactam-resistant bacteria.
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Monobactams (Aztreonam)
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Great against Gram-negatives. Broad spectrum when given with vancomycin or clindomycin
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New Superbugs emerging…
Contain gene NDM-1 (New Delhi metallo-beta-lactam-1). Effective against |
carbapenems.
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Mycobacterium Cell wall inhibitors
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mycolic acid biosynthsis inhibition
by interrupting fatty acid biosynthesis Isoniazid, Triclosan, Thiolactomycin |
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Bacterial ribosomes
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70S (50S + 30S)
he put links on slides for videos |
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Inhibitors of 50S
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Macrolides:
Lincosimides: Streptogramins Oxazolidones: Chloramphenicol: |
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Macrolides:
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(Erythromycin, Azithromycin) good against Gram-positives and negatives; low toxicity.
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Streptogramins
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(combination drug quinupristin+dalfopristin); last choice drug due to high occurance of toxicity.
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Oxazolidones
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: Linezolid (zyvox): best against MRSA and VRE. Very expensive. Long-term use has high rates of toxicity.
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Chloramphenicol:
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toxicity is severe (aplastic anemia). Not used in U.S. except topically or eye drops. Thiamphenicol is newer alternative
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30s inhibitors
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Tetracyclines
Aminoglycosides: |
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Tetracyclines
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doxycycline, tigecycline, minocycline); chelates Ca2+; treats Chlamydia, tick-borne diseases, acne; phototoxic
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Aminoglycosides
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Streptomycin, Gentamycin, Tobramycin, Amikacin). Renal and cochlear toxicity at high rates.
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Where do macrolides bind 50s?
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in nacent peptide tunnel
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Erythromycin (macrolide) if added a methyl group becomes
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Zpack and it is more tolerable in the stomach.
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Tetracycline: selectivity is not at the level of ribosome, but
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is taken up by bacteria much more efficiently.
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Aminoglycosides: bind 30S or 50S subunits. Two modes of action:
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inhibits initiation complex and causes misreads of mRNA.
(streptomycin, kanamycin) |
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Rifampin
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inhibits RNA polymerase
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Ciprofloxacin inhibits
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DNA gyrase
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Antibiotics that function as Metabolic Analogs
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Folate metabolism/Thymine biosynthesis
(Sulfa drugs Synergistic TMP+SMX (called Bactrim) ) structural analogs and competitive antagonists to PABA (para-aminobenzoic acid) and Dihydrofolate |
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sulfamethoxazole and trimethoprim (antagonists to PABA are given at the same time because
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otherwise resistance arises more quickly
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Antibiotics that target Membrane, Lipopolysacharide (LPS)
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Polymyxin B, E
forms pores in the membrane by inserting its hydrophobic tail into the membrane |
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look slide 37
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all mechanisms
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Antibiotic use leads to bacterial clearance from the body = killing.
Death is the strongest selective pressure. Any means to survive will emerge (but keep in mind, mutations occur randomly—mutagenesis is NOT |
induced by antimicrobials).
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Alteration of bacterial protein targets.
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if an antibiotic binds and inhibits a protein, then bacteria modify the protein
The ribosome is a common target for modification Cell wall precursors and enzymes |
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Vancomycin-reistance
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change cell-wall component from D-Alanine-D-Alanine to D-Alanine-D-Lactate
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Alteration of bacterial membrane (physical barrier).
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changing permeability of membrane keeps out larger molecules
Gram-negative resistance to b-lactams |
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Enzymatic inhibition of antibiotic
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bacteria produce enzymes that target antibiotics
b-lactamases, aminoglycosidases |
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. Bypass the pathways targeted by antibiotics
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instead of synthesizing metabolite de novo, acquire it from environment
thymidine (nucleic acid for DNA synthesis) gained from host, providing resistance to trimethoprim and sulfamethoxasole |
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. Efflux of antibiotics from bacterial cell.
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pump out toxic compound
tetracycline efflux is common in Staphylococcus and Pseudomonas |
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Means of resistance acquisition
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Single nucleic acid base-pair mutations
Alters protein targets Large DNA rearrangements, deletions Bypass mutations, alters protein targets, membrane permeability 3. Horizontal Gene Transfer Very common mechanism in nosocomial disease Plasmid Conjugation between bacteria Bacteria phage transduction Natural transformation |
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Resistance mechanisms against Penicillins & Cephalosporins
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. Enzymatic cleavage of b-lactams
2. Changing target of penicillins: PBPs penicillin-binding-proteins 3. Decreased permeability to drug (change pore sizes) 4. Tolerance/Persistence: drug inhibits cell wall synthesis, but bacteria do not die. |
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Resistance mechanisms against Vancomycin
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plasmid encoding VanA->changes cell wall cross-linkers
(from D-Ala-D-Ala ->D-ala-D-lactate) |
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Resistance mechanisms against Aminoglycosides and Macrolides
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modification of ribosome
a. acquiring mutation in ribosome b. acquiring modifying enzyme (horizontal gene transfer) 2. decreased permeability to drug |
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Resistance mechanisms against Tetracycline
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reduced permeability
2. molecular efflux pumps |
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Resistance mechanisms against Sulfonamides: (other than bypassing the pathway)
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. efflux pump
2. modification of enzyme target |
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Indiscriminate use of Antibiotics
can lead to |
Toxic effects of antibiotics
Allergic reaction induced in patients Development of drug resistance Alteration of immune response Imbalance of the normal body flora |
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Broad-spectrum antibacterial antibiotic for a prolonged period of time may result in
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oral and vaginal candidiasis by Candida albicans.
GI trouble (pseudomembranous colitis) from Clostridium difficile |
