Antimicrobials Flashcards
(89 cards)
1
Q
minimum inhibitory concentration
A
- lowest concentration of drug that can inhibit growth of a particular bacterial species
2
Q
minimum bactericidal concentration
A
- smallest concentration of a drug to kill 50% of the bacterial population
3
Q
if you have bacteriostatic
A
- MBC»_space;> MIC
4
Q
If you have bactericidal
A
- MBC = MIC
5
Q
culture based methods to determine microbial susceptibly/resistance
A
- disk diffusion
- E-test
6
Q
molecular detection of resistance mutations
A
- PCR
- sequencing
7
Q
antibiograms
A
- summaries of antibiotic susceptibilities of local isolates
- sent to clinical micro lab
- aid in selecting empiric therapy
8
Q
efficacy of antimicrobial drugs limited by
A
- mechanism of action
- susceptibility of the target organism
- side effects on the host
- pharmacodynamics
- cost
- patient compliance
9
Q
efficacy of antimicrobial drugs mechanism of action
A
- has to be able to get to the site of infection
10
Q
efficacy of antimicrobial drugs cost
A
- if the prescription is more than your patient can afford
- they won’t take it
- won’t be efficacious
11
Q
efficacy of antimicrobial drugs patient compliance
A
- will the patient actually take it
12
Q
Cmax
A
- max concentration you can get from a dose
13
Q
area under curve
A
- total concentration of drug that has accumulated in the patient during that dosing interval
14
Q
time dependent killing
A
- maximize time above MIC
15
Q
drugs that use TDK
A
Wall inhibitors - penicillins - cephalosporins Protein inhibitors - macrolides - clindamycin
16
Q
concentration dependent killing
A
- maximize Cmax and therefore AUC
17
Q
drugs that use CDK
A
DNA inhibitors
- fluoroquinolones
Protein inhibitors
- Aminoglycosides
18
Q
post antibiotic effect
A
- the time it takes bacteria to return to log-phase growth following removal of antibiotic
19
Q
post antibiotic effect TDK
A
- minimal because we have extended amount of time where the drug is above MIC
20
Q
post antibiotic effect CDK
A
- quite long to extend amount of time before next drug needs to be administered
21
Q
importance of long PAEs
A
- reduce required frequency of dosing
- reduce toxicities and cost
22
Q
cefriaxone
A
- subclass: cephalosporin
- class: beta lactam
23
Q
bacterial cell envelope includes
A
- cell membrane
- peptidoglycan layer
- outer membrane
24
Q
bacterial cell envelope doesn’t include
A
- intracellular structures
- extracellular polysaccharide capsules
- secreted molecules
25
classes of agents that interfere with bacterial cell envelope
- beta lactamase
- glycopeptides
- isoniazid
- ethambutol
- bacitracin
- phosphomycin
- cycloserine
- lipopeptides
- polymyxins
26
beta lactam examples
- penicillins
- cephalosporins
- carbapenems
- monobactams
27
gram negative cell envelope
- small peptidoglycan layer
- lipopolysaccharide layer (important for gram negatives)
- Lipid A
28
LPS layer
- outer membrane of gram negative cell envelope
29
lipid A
- endotoxin
| - toxic molecule of LPS
30
gram positive cell envelope
- lots of peptidoglycan
| - lipotechoic acid unique to gram positives
31
peptidoglycan
- alternating units of NAG and NAM
32
what do beta lactams inhibit?
- transpeptidation
33
peptidoglycan amino acids
- D-Ala-D-Ala
| - this what penicillin targets
34
penicillin binding proteins
- have the transpeptidase activity
| - may also have the transglycosylation activity to put sugar backbone together
35
structural basis of beta lactams
- they look a lot like D-Ala-D-Ala
- drug named for beta lactam ring
- inhibits activity of enzyme that looks for D-Ala-D-Ala
36
Classes of B lactams
- penicillin
| - cephalosporins
37
antibiotic resistance mechanisms
- enzymatically inactivate drug
- alter drug target
- alter drug exposure
38
enzymatically inactivate drug
- beta lactamases
| - often on mobile genetic elements
39
alter drug target
- mutation
| - can occur via horizontal exchange
40
alter drug exposure
- decreased uptake (gram negatives)
| - increased efflux
41
how do gram negatives have decreased uptake?
- they can change the size of their pores to allow nutrients to get in
- exclude drugs because they are bigger
42
beta lactamases
- break bond in beta lactam ring of penicillin
| - disables molecule
43
types of beta lactamases
- ESBL
| - metal dependent (NDM-1)
44
ESBL
- mostly derived from active site mutations in TEM/SHV
| - results in activity against extended spectrum cephalosporins
45
clavulanic acid
- resistance to cleavage by beta lactamases
| - will deactivate beta lactamase
46
alternative penicillin resistant PBP
- have low affinity for B-lactams but retain transpeptidase activity
- can arise through mutation (gonorrhea)
- can be acquired horizontally (MRSA)
47
fitness cost of antibiotic resistance
- it costs the bacteria something to become resistance to antibiotic
- won't grow as well as the susceptible drug
48
rationale for understanding mechanisms of resistance
- choose antibiotics with higher fitness cost for resistance
49
altered penicillin transport
- decreased membrane permeability
| - increased efflux
50
altered penicillin transport decreased membrane permeability
- only relevant for gram negatives
| - can arise via spontaneous mutations in porin genes
51
altered penicillin transport increased efflux
- horizontal acquisition of new pump
| - mutation that alters specificity or expression
52
multiple mechanisms of resistance
- higher levels of resistance
53
multiple mechanisms of resistance examples
- alterations in porin (gram -)
- alternations in PBPs
- production of beta lactamases
- over expression of efflux pump
54
glycopeptide example
- vancomycin
| - for gram positives
55
what do glycopeptides do?
- inhibit transglycosylation of peptidoglycan
| - binds to D-ala-D-ala and blocks incorporation
56
vancomycin resistance mechanisms
- synthesis of D-ala-D-lac precursors that cannot bind vancomycin
57
bacitracin
- inhibits regeneration of PG lipid carrier
58
phosphomycin
- prevents attachment of NAG to NAM
59
cycloserine
- prevents attachment of peptide to NAM
60
mycobacterium species
- have mycolic acid
- and arabinogalactan
- acid fast stain
61
agents that work on mycobacterial species
- isoniazid
| - ethambutol
62
isoniazid
- inhibits mycolic acid synthesis
63
ethambutol
- inhibits arabinotransferases
64
lipopeptides MOA
- form pores in cytoplasmic membrane of gram positive cell
- bind to phosphatidylglycerol which is abundant in bacterial cell membranes
- rare in eukaryotic cell membranes
65
lipopeptides example
- daptomycin
66
why don't we use lipopeptides to treat pneumonia
- surfactant is coated in phosphatidylglycerol
| - not good because lipopeptides break holes in this
67
bacterial folate synthesis inhibitors
- sulfonamides
- trimethoprim
- humans don't synthesize their own folate.
- bacteria do
68
sulfonamides
- bacteriostatic on their own
- generally included trimethoprim
- sulfamethoxazole
69
resistance to sulfonamides altered drug target
- spontaneous mutation of dhps
| - horizontal acquisition of alternate DHPS
70
resistance to sulfonamides swamp the system
- increased production of folate precursor PABA
71
resistance to sulfonamides altered drug exposure
- decreased uptake
72
combinatorial synergy
- lower amount of each drug we need to use and get same outcome
- each drug works better in presence of the other drug
73
trimethoprim
- bactericidal
| - inhibits dihydrofolate reductase
74
Tmp/Smx
- synergistic combination
| - smx becomes bactericidal with combined with tmp
75
quinolones/fluoroquinolones
- inhibit DNA gyrase (topo II and topo IV)
- bactericidal
- work best against gram negatives
76
quinolones/fluoroquinolones example
- ciprofloxacin
77
role of topoisomerase IV
- separates newly replicated chromosomes into daughter cells
78
problem with cipro
- may rupture tendons
79
resistance of quinolones altered drug target
- chromosomal mutation in gyrase and topoisomerase genes
80
resistance of quinolones altered drug exposure
- decreased uptake via mutations in gram negative porin proteins
- increased efflux due to mutations in efflux pump activity
- cross-resistance leading to multi drug resistance
81
rifamycins
- inhibit DNA synthesis
| - can be bactericidal or static dependent on concentration
82
rifamycins MOA
- bind to bacterial DdRp with higher affinity than for human enzyme
83
rifamycins example
- rifampin
| - mostly used for mycobacterium or meningococcal
84
resistance to monotherapy
- spontaneous mutations in RNA pol gene
| - rarely used as mono therapy
85
nitroimidazole use
- bactericidal
| - anaerobic microbes
86
nitroimidazole type of drug
- pro-drug - must be converted by microbial enzyme to active form
87
nitroimidazole MOA
- active drug forms toxic free radicals that damage DNA
88
nitroimidazole example
- metronidazole
89
resistance to nitroimidazole
- failture to enzymatically activate drug
| - mutations in enzymes that convert the prodrug to the active compound.
