Antimicrobial Agents Flashcards
1
Q
Bacteriostatic
A
prevents bacterial growth/division
2
Q
Bactericide
A
kills bacteria
3
Q
Selective toxicity
A
Efficient against the bacteria, but low toxicity for the
patient
4
Q
Mechanisms of resistance
A
- Target modification
- Reduced permeability
- Reduced access to target
- Active efflux
- Enzymatic inactivation or modification
- Alternative pathways
5
Q
Penicillin
A
- Inhibits bacterial cell wall synthesis
- Very efficient against Gram-positive bacteria
- Low production cost
- Low toxicity for humans
6
Q
Penicillin resistance
A
b-lactamases
7
Q
b-lactamases
A
- Secreted in Gram+
- Periplasm in Gram-
- inhibited by: Clavulanic acid, Sulbactam, Tazobactam
- new are not bound by inhibitors
8
Q
Methicillin
A
- New penicillin derivative
- Resistant to the new b-lactamases
- New PBP
9
Q
β-lactam resistance – Gram+
A
- Target modification
- Enzymatic inactivation or modification
10
Q
β-lactam resistance – Gram-
A
- Target modification
- Enzymatic inactivation or modification
- Reduced permeability
- Reduced access to target
- Active efflux
11
Q
β-lactams
A
- Penicillins
- Cephalosporins
- Monobactams
- Cephamycins
- Carbapenems
12
Q
Cephalosporins
A
- 1st generation: narrow spectrum
- 2nd generation: expanded spectrum
- 3rd generation: broad spectrum
- 4th generation: extended spectrum
- 5th generation: activity against MRSA
13
Q
MRSA
A
Methicillin-resistant Staphylococcus aureus
14
Q
Glycopeptides
A
- Parenteric
- Large molecules – unable to enter Gram-
- Prevent peptidoglycan synthesis by interacting with D-Ala-D-Ala termini, inhibiting PBP activity.
- Intrinsic resistance in species with D-Ala-D-Lac or D-Ala-D-Ser termini
- Acquired resistance by modification of the D-Ala-D-Ala terminal – van genes located in plasmids and transposons (Enterococcus) – detected in MRSA!
15
Q
Glycopeptide resistance
A
Alternative pathways
16
Q
Other inhibitors of cell wall synthesis
A
- Bacitracin: membrane carrier molecules that transport the building-blocks of the peptidoglycan bacterial cell wall
- Fosfomycin: inactivating the enzyme UDP-N acetylglucosamine-3 enolpyruvyltransferase, also known as MurA
17
Q
Inhibition of protein synthesis
A
Ribossomes:
- Prokaryotes 70S (50S + 30S)
- Eukaryotes 80S (60S + 40S)
18
Q
Aminoglycosides
A
- Irreversibly bind to the 30S sub-unit
- Streptomycin, gentamicin, amikacin, tobramycin
- Bactericidal
- Serious infections caused by Gram- rods and some Gram+
- Frequently administered in association with inhibitor of cell wall synthesis
19
Q
Aminoglycosides resistance
A
- Resistance in anaerobes or aerobes in anerobic environment
- Resistance in streptococci and enterococci
- Enzymatic inactivation or modification
20
Q
Tetracyclines
A
- Tetracycline, doxycycline, minocycline
- Reversibly bind to the 30S sub-unit (bacteriostatic)
- Blocks docking site of tRNA, preventing peptide chain
elongation
21
Q
Tetracyclines resistance
A
Active efflux
22
Q
Chloramphenicol
A
- Reversibly binds to the peptidyltransferase component of the 50S sub-unit (bacteriostatic)
- Prevents peptide chain elongation
- Limited use because it disrupts protein synthesis in human bone marrow cells - blood dyscrasias
23
Q
Chloramphenicol resistance
A
Enzymatic inactivation or modification
24
Q
Macrolides and lincosamides
A
- Most Gram- bacteria are resistant to macrolides
- Clindamycin is active against anaerobic Gram- rods
25
Macrolide resistance
- Active efflux
| - Target modification
26
M phenotype
- Resistance to 14- and 15-member macrolides mef genes (efflux pumps)
- Active efflux
27
cMLSB phenotype
- Resistance to all macrolides, lincosamides and streptogramin B
- erm genes
- rRNA methylation
28
iMLSB phenotype
- rRNA methylation
- Resistance to all macrolides, lincosamides and streptogramin B in presence of macrolides
- erm genes
29
Quinolones
- Inhibition of nucleic acid synthesis
- preventing bacterial DNA from unwinding and duplicating
- inhibit the ligase activity
30
Quinolone resistance
- Target modification
- Reduced access to target
- Reduced permeability
- Active efflux
31
Antimetabolites
- Sulfonamides
- Trimethoprim
- affect purine and pyrimidine formation
- Synergistic effect
32
Antimetabolites resistance
- Intrinsic resistance in bacteria that use exogenous thymidine (e.g., enterococci)
- Acquired resistance to trimethoprim due to production of alternative dihydrofolate reductase with low afinity for
trimethoprim
33
Rifampin (=Rifampicin)
- Binds DNA-dependent RNA polymerase and inhibits the
initiation of RNA synthesis
- Active against aerobic Gram+ cocci and Mycobacterium
- Instrinsic resistance in Gram- due to decreased uptake
- Acquired resistance due to mutations in the gene encoding the beta subunit of RNA polymerase
34
Antimycobacterial agents
- Isoniazid: Inhibition of mycolic acids synthesis
- Ethambutol: Inhibition of arabinogalactan synthesis
- Pyrazinamide: Unknown mechanism of action
35
Antimicrobial associations
- Synergistic effect
- Prevent treatment failures due to resistance emergence
- Treatment of polymicrobial infections
- Treatment of severe infections before pathogen identification
36
Antifungal agents
- Polyenes
- Azoles
- Echinocandins
37
Polyenes
- Amphotericin B:
Binds ergosterol, forming pores in the membrane
Binds cholesterol - toxicity in humans
- Nystatin (Topical agent)
38
Azoles
- Inhibit ergosterol synthesis
| - Clotrimazole, Ketoconazole, Fluconazole, Voriconazole, Posaconazole
39
Echinocandins
- Inhibit glucan synthesis
- Specific toxicity against fungi with 1,3-β-glucan as the main glucan
- Caspofungin, Micafungin
40
Flucytosine
- Antimetabolite (nucleotide analogous): interferes with the synthesis of DNA, RNA, and proteins
- Combination with amphotericin B or fluconazole due to the propensity for resistance emergence
41
Griseofulvin
Interacts with microtubules -Inhibition of mitosis
42
Terbinafine
- Allylamine: inhibits ergosterol synthesis
| - Oral and topical
43
Antifungal resistance
- Antifungal inactivation is not observed
- Resistance genes are not transmissible from cell to cell
- Resistance develops slowly
- Emergence of intrinsically resistant species or gradual,
stepwise alteration of cellular structures or functions
following exposure to the antifungal agent
44
Nitroimimidazoles
- Metronidazole
- Anaerobic bacteria and protozoa
- Reduction of the antibiotic (anaerobic metabolism) produces cytotoxic compounds that disrupt the host DNA
- Resistance due to reduced uptake or elimination of the
cytotoxic compounds
45
Polymyxins
- Cyclic polypeptides
- Insert into bacterial membranes, by interacting with lipopolysaccharides and phospholipids in the outer membrane
- Nephrotoxicity
- Gram-: Multidrug resistant Klebsiella, Acinetobacter, Pseudomonas
46
Lipopeptides
- Daptomycin
| - Tigecycline (Glycylcycline)
47
Daptomycin
- Binds cytoplasmic membrane - Depolarization; disruption of ionic gradients
- Gram+: Multidrug resistant Staphylococci, Streptococci,
Enterococci (including vancomycin-resistant)
48
Tigecycline (Glycylcycline)
- Derivative of minocycline
- Higher binding affinity for the ribosome
- Less affected by efflux or enzymatic modification
