Chapter 12: Antimicrobial Agent Mechanisms of Action and Resistance Flashcards
(88 cards)
1
Q
Inhibition of Bacterial Cell Wall Biosynthesis
A
Beta lactam
2
Q
Inhibition of Folate Synthesis
A
Trimethoprim, Sulfamethoxazole
3
Q
Interference with DNA Replication
A
Quinolones
4
Q
Interference with DNA Transcription
A
Rifamycin
5
Q
Interference with DNA Transcription
A
Rifamycin
6
Q
Interference with mRNA Translation
A
Aminoglycoside
7
Q
Antibiotics for Cell Wall Interference
A
Beta-Lactams
Penicillins
Cephalosporins
Vancomycin
8
Q
Antibiotic for PABA -> DHFA Interference
A
Sulfonamides
9
Q
Antibiotic for DHFA -> THFA Interference
A
Trimethoprim
10
Q
Antibiotic for Cell Membrane Interference
A
Polymyxins
11
Q
Antibiotics for DNA Synthesis Interference
A
Nalidixic Acid
Fluoroquinolones
12
Q
Antibiotic for mRNA Interference
A
Rifampin
13
Q
Antibiotic for 30S Inhibition
A
Aminoglycosides
Tetracyclines
Glycylcycline-tigecycline
14
Q
Antibiotic for 50S Inhibition
A
Streptogramine-DQ Oxazolidinone-linezolid Chloramphenicol Clindamycin Erythromycin
15
Q
Steps in Peptidoglycan Biosynthesis
A
- Synthesis of precursors in the cytoplasm
- Transport of lipid-bound precursors across the cytoplasmic membrane
- Insertion of glycan units in the cell wall
- Transpeptidation linking and maturation
16
Q
Beta – Lactam antibiotics such as penems, cephems, carbapenems, and monobactams, act by _______________
A
binding to PBP’s, which are biofunctional transpeptidase-transglycosylase enzymes that mediate peptidoglycan cross-linking
17
Q
Glycopeptides, such as vancomycin, dalbavancin, teicoplanin, and the investigational drugs oritavancin and telavancin act by __________
A
binding to terminal D-Ala-D-Ala of the pentapeptidyl-glycosyl peptidoglycan intermediates. This prevents their incorporation into peptidoglycan chain by blocking the transpeptidation step in cell wall biosynthesis.
18
Q
____________, the clinical spectrum of glycopeptides is limited to gram-positive microorganisms; thus they are mainly used to treat aerobic clinical infections caused by staphylococci, streptococci, and enterococci
A
Because they cannot cross the outer membrane of gram-negative bacteria
19
Q
Antibiotics are also capable of interfering with intracellular anabolic process. The folic acid pathway provides the essential precursor molecules needed in _______
A
DNA biosynthesis
20
Q
The pathway is mediated by two key enzymes, __________, which mediate the formation of ________ from dihydrofolate
A
dihydropteroate synthase and dihydrofolate reductase; tetrahydrofolate (THF)
21
Q
The spectrum of activity of folate pathways inhibitors, especially when provided a combination, __________
A
provides a broad spectrum of activity against the Enterobacteriaceae that cause Urinary Tract Infection
22
Q
Enzyme for Para-aminobenzoic Acid -> Dihydropteroate
A
Dihydropteroate Synthetase
23
Q
Enzyme for Dihydrofolate -> Tetrahydrofolate
A
Dihydrofolate reductase
24
Q
The enzymes necessary for DNA replication are topoisomerases ______
A
I, II, III and IV
25
Antibiotics that affect DNA replication by targeting topoisomerases II (DNA gyrase) and IV, enzymes considered important in controlling DNA replicative cycle
Quinolones
26
The quinolones and fluroquinolones are used to treat ___________
Enterobacteriaceae, pseudomonads and other non-Enterobacteriaceae, staphylococci, enterococci, Neisseria, Streptococcal species than Streptococcus pneumoniae
27
the process whereby a template DNA strand copied into functional RNA sequence, resulting in mature mRNA or structural RNA
DNA Transcription
28
a synthetic derivative of rifamycin B, is used in combination with other antibiotic classes to treat Mycobacterium tuberculosis
Rifampin
29
Aerobic species treated with rifampin include
staphylococci, enterococci, Haemophilus spp. and Streptococcus pneumoniae
30
Rifamycins in combination with ciprofloxacin and clindamycin are reported to be useful for the treatment of ______
bacterial infections relevant to biowarfare or bioterrorism, such as inhalation of anthrax.
31
the cellular machinery of living organisms that decodes mRNA into functional protein
mRNA translation
32
cationic carbohydrate-containing molecules, and their positive charge provides the basis for their interaction with a specific region of the 16S ribosomal subunit.
Aminoglycosides
33
a disaccharide aminocyclitol antibiotic produced by Streptomyces spectabilis active against many gram-negative bacterial species.
Spectinomycin
34
reversibly inhibit protein synthesis
Tetracyclines
35
Examples of Macrolides
erythromycin, clarithromycin, and azithromycin
36
allow initiation and mRNA translation to begin but act by inhibiting peptide elongation
Macrolides and Tetracyclines
37
a new generation of macrolide antibiotics designed to overcome issues with bacterial resistance to macrolides. They are semi-synthetic antibiotics derived from erythromycin (macrolide antibiotic) and the changes give ketolides a broader spectrum of activity.
Ketolides
38
The most recently approved classes of antibiotics targeting protein synthesis are the ________
Oxazolidinones
Streptogramins
Glycylcyclines
39
Represents oxazolidinones
Linezolid
40
Represents Streptogramins
quinopristin-dalfopristin
41
Represents glycylcyclines
tigecycline
42
Resistance to antibiotics is conveniently divided into mechanisms that are _____
instrinsic or acquired resistance.
43
The gene changes or exchanges that result from acquired resistance are usually caused by ___________
genetic mutations, acquisition of genes from other organisms via gene transfer, or combination of mutational and gene transfer events.
44
Resistance genes and transfer mechanisms existed long before the discovery and use of modern therapeutic antimicrobials. If bacterial resistance to antimicrobial agents is not a new phenomenon, where did it originate?
Autotoxicity; It has been postulated that the presence of DNA encoding antimicrobial resistance in antibiotic preparations has been a factor in the rapid development of multiple antibiotic resistance by providing the resistance sequences that can be incorporated by the causative pathogen
45
the innate ability of bacterial species to resist the activity of a particular antimicrobial agent through inherent structural or functional characteristic, allowing tolerance of a particular drug or antimicrobial class
Intrinsic resistance
46
Such natural resistance can be caused by the following:
1. Lack of affinity of drug for bacterial target
2. Inaccessibility of the drug into a bacterial cell
3. Extrusion of the drug by chromosomally encoded efflux pumps.
4. Innate production of enzymes that inactive the drug
47
For antibiotics to affect internal cellular processes, they must penetrate the cell wall of bacteria to reach their target. Influx of antibiotics through the cell wall depends on the chemical nature of the antibiotics and the structural characteristics of the cell wall.
Impermeability
48
Mechanisms of Impermeability for Gram-Negative Bacteria
LPS and OMPs (Outer Membrane Proteins)
49
Naturally serve as outer membrane channels that permit the influx of nutrients and efflux of waste products. They also serve to restrict the influx of antibiotics and maintain low intracellular concentrations
Porins
50
In addition, alterations leading to ________ that reduce their affinity for an antibiotic can alter a resistance phenotype.
decreased porin production or changes in the structure of porins
51
sessile bacterial communities that are irreversibly attached to a solid surface and are embedded in an exopolysaccharide matrix
Biofilms
52
prevalent in the clinical setting, found on numerous environmental surfaces and indwelling medical devices
Bacterial biofilms
53
Genetic Mechanisms of Biofilm antibiotic resistance appear to fall into two general classes
Innate resistance factors and induced resistance factors
54
Intrinsic resistance of bacteria to certain antibiotics is explained by the activity of ____
efflux systems and impermeability
55
found in gram-positive and gram-negative bacteria and function as transporter proteins for the extrusion of toxic substances and antibiotics from the interior of the cell to the external environment
Efflux Pumps
56
Bacterial Efflux Transporters are classified into five (5) major superfamilies
1. MFS
2. RND
3. SMR
4. ABC
5. MATE
57
Bacteria can provide enzymes that destroy the antimicrobial agents before they are able to reach the targets.
Enzymatic Inactivation
58
One of the most commonly acquired and intrinsic resistance mechanism for beta lactam antibiotics.
Enzymatic Inactivation
59
may have acquired new functions in normal housekeeping genes to help detoxify antibiotics.
Organisms that coevolved with antibiotic-producing organisms
60
Thus, the process of natural selection, target organisms may ___________ to survive toxic environments.
acquire, evolve, and disseminate resistance determinants and use multiple combinations of intrinsic and acquired antibiotic resistance strategies
61
Some efflux pumps have translocated to ________ which can be acquired by horizontal gene exchange.
Plasmids
62
In general, multi-drug efflux genes are ______
broadly conserved in bacteria and are chromosome-encoded
63
In general, multi-drug efflux genes are ______
broadly conserved in bacteria and are chromosome-encoded
64
On the other hand, drug specific efflux genes are generally encoded _____
by plasmids, so their acquisition is compounded by their association with MDR
65
Modification of a target can reduce the binding affinity of the antibiotic to the target; occurs primarily by chromosomal mutation, as observed with the quinolone and oxazolidinone antimicrobials, and by enzymatic alteration of macrolide, glycopeptide, and beta lactam antibiotic target sites.
Target site modification
66
Mechanism for Target Site Modification
Chromosomal Mutation
| Enzymatic Target Site Alteration
67
Microorganisms also adapt to become resistant by acquiring cellular targets with reduced affinity for antibiotic
Acquisition of New Targets
68
Inactivating antibiotics directly is one of the first mechanism of resistance identified in bacteria and is a successful strategy used by many organisms to survive the action of many antibiotic classes.
Enzymatic Inactivation of antibiotics
69
Resistance is an evolutionary strategy that allows microorganisms to survive chemically hostile environments, such as those posed by antibiotic exposure. However, the evolution and vertical transfer of these resistance determinants to progeny is only part of the survival strategy used by genetic resources, including resistance genes via (LGT)
Dissemination
70
Mechanisms of Dissemination
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Conjugation
Transformation
Transduction
Transposons
Insertion sequences (ISs)
```
71
Nanotechnology to Deliver Therapeutic Agents
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Nanomedicine
Nanoencapsulation delivery systems
Nanoencapsulation
Encapsulating the drugs
Nanotubes
Nanoshells
Cochleates
```
72
Class: Penems
Subclass: Penicillin
Category: Narrow Spectrum
US Adopted Name: Penicillin g, Penicillin v
73
Class: Penems
Subclass: Penicillin
Category: Penicillinases-sensitive
US Adopted Name: Methicillin, Oxacillin
74
Class: Penems
Subclass: Penicillin
Category: Penicillinases-resistant
US Adopted Name: Amoxicillin, Ampicillin
75
Class: Penems
Subclass: Penicillin
Category: Broad Spectrum
US Adopted Name: Carbenicillin, Ticarcilin
76
Class: Penems
Subclass: Penicillin
Category: Aminopenicillins
US Adopted Name: Piperacillin
77
Class: Penems
Subclass: Penicillin
Category: Antipseudomonals
US Adopted Name: Amoxicillin-clavulanate
78
Class: Penems
Subclass: Penicillin
Category: Extended Spectrum
US Adopted Name: Ampicillin-sulbactam
79
Class: Penems
Subclass: Penicillin
Category: Penem-B-lactamase combinations
US Adopted Name: N/A
80
Class: Cephems
Subclass: Cephalosporin I
Category: Narrow-spectrum, first generation
US Adopted Name: Cephalothin, cefazolin
81
Class: Cephems
Subclass: Cephalosporin II
Category: Expanded spectrum, second generation
US Adopted Name: Cefocinid, Cefuroxime
82
Class: Cephems
Subclass: Cephalosporin III
Category: Broad-Spectrum, Third generation
US Adopted Name: Cefoperazone, ceftazidime
83
Class: Cephems
Subclass: Cephalosporin IV
Category: Extended Spectrum, fourth generation
US Adopted Name: Cefepime
84
Class: Cephems
Subclass: Cephamycin
Category: N/A
US Adopted Name: Cefmetazole, Cefoxitin
85
Class: Cephems
Subclass: Oxacephem
Category: N/A
US Adopted Name: Moxalactam
86
Class: Cephems
Subclass: Carbacephem
Category: N/A
US Adopted Name: Loracarbef
87
Class: Carbapenems
Subclass: N/A
Category: N/A
US Adopted Names: Ertapenem, Imipenem, Meropenem, and Doripenem
88
Class: Monobactams
Subclass: N/A
Category: N/A
US Adopted Name: Aztreonam
