Sawicki- Antimicrobials Flashcards
1
Q
greatest cause of morbidity and mortality worldwide
A
infections from parasitic organisms
2
Q
therapeutic index (ratio)
A
amount that causes therapeutic effect vs toxic.. LD50/ED50
3
Q
empirical therapy
A
used when not possible to obtain specimen (broader than therapy based on susceptibility testing or directed at a certain pathogen)
4
Q
antibiogram
A
result of lab testing for the sensitivity of an isolated bacterial strain to different antibiotics (in vitro sensitivity)- directed therapy
5
Q
bacteriocidal
A
killed
6
Q
bacteriostatic
A
prevented from growing
7
Q
sulfonamides (static or cidal?)
A
static
8
Q
trimetoprim (static or cidal?)
A
s
9
Q
chloramphenicol (static or cidal?)
A
s
10
Q
tetracycline (static or cidal?)
A
s
11
Q
erythromycin (static or cidal?)
A
s
12
Q
quinolones (static or cidal?)
A
c
13
Q
penicillins (static or cidal?)
A
c
14
Q
cephalosporins (static or cidal?)
A
c
15
Q
aminoglycosides (static or cidal?)
A
most c
16
Q
aminoglycosides (static or cidal?)
A
most c
17
Q
MIC
A
minimum inhibitory concentration: lowest concentration of antimicrobial agent that prevents visible growth after 18-24 hr incubation
18
Q
MBC
A
minimal bactericidal concentration= minimal concentration of antimicrobial agent that kills 99.9% cells
19
Q
treatment for areas protected from host immune response, or neutropenic individuals
A
cidal
20
Q
treatment for uncomplicated infections
A
static
21
Q
drugs exhibiting concentration dependent kiling
A
kills bacteria faster at higher concentrations: fluoroquinolones and aminoglycosides. Also have a post antibiotic effect (inhibit for several hours after drug concentration falls below MIC in serum. 2 properties= administered less frequently than predicted by half life. Most beta lactams DO NOT have either of these
22
Q
site of infection influences
A
dose, route, duration and type of antibiotic. Peak concentration at infection site should be at least 4x MIC
23
Q
route required to treat pleural and pericardial infections
A
parenteral
24
Q
nephro and otto toxicity
A
aminoglycosides (beta lactams and fluroquinolones are better choice)
25
allergies common with
beta lactams (penicilins) and sulfonamides
26
tetracyclines and children
no- bind to developing teeth and bone
27
sulfonamides in newborns
displace bilirubin from albumin and cause nervous system disorders
28
age dependent infection
bacterial meninjitis
29
antimicrobial combination: indifferent effect
combined effect equals sum of seperate
30
antimicrobial combination: synergism
combined effect is greater than sum of independent activities
31
antimicrobial combination: antagonistic
combination effect is less than could be achieved by using seperately
32
3 combinations with synergistic effects
1) penicillin/ampicillin (inh cell wall synthesis)-allow gent to enter- and gentamycin (aminogycoside that inh protein synthesis) *enterococcal endocarditis
2) act on sequential steps in metabolic pathway (trimethoprim and sulfamethoxazole)
3) claculanate (beta lactamase inh) inh the enzyme that inactivates amoxicillin
33
intrinsic antibiotic resistance vs acquired
acquired: mutation of existing genetic info, acquisition of new genes, exchange of genetic material among bacteria
34
mechanisms of genetic exchange
1) conjugation (physically attach and exhange plasmid DNA)
2) transduction: happens with a virus (bacteriophage) carrying resistance to target bacteria
3) transformation: certain bacteria pick up free DNA from environment
35
mechanisms of genetic exchange
1) conjugation (physically attach and exhange plasmid DNA)
2) transduction: happens with a virus (bacteriophage) carrying resistance to target bacteria
3) transformation: certain bacteria pick up free DNA from environment
36
4 mechanisms of resistance
1) develop altered receptors or targets so drug can't bind
2) decrease rate of entry or rate of removal (reduce concentration of drug that reaches receptors)
3) enhance destruction or inactivation of drug
4) create resistant metabolic pathways
37
act by inhibiting cell wall
-beta lactams
includes penicillins, beta lactamase inhibitors, cephalosporins,carbapenams, monobactams
-glycopeptides
includes bacitracin and vancomycin
-maximal activity against rapidly dividing bacteria
38
beta lactams (static or cidal)
c
39
penicillans
- gram positive
| - distribute to eye, brain, CSF and prostate low
40
penicillans
- gram positive
| - distribute to eye, brain, CSF and prostate low
41
cephalosporins
- few enter CSF in sufficient concentration
- Generations:
1) don't enter CSF
2) better gram neg, retain some gram pos. more resistant to beta lactamase
3) further increased gram neg, broad spectrum. Decreased gram pos. Enter CSF
4) extended spectrum, similar gram positive as 1st gen, greater resistance to beta lactamase than 3rd. Many cross BBB and effective in meningitis
42
cephalosporins
- few enter CSF in sufficient concentration
- Generations:
1) don't enter CSF
2) better gram neg, retain some gram pos. more resistant to beta lactamase
3) further increased gram neg, broad spectrum. Decreased gram pos. Enter CSF
4) extended spectrum, similar gram positive as 1st gen, greater resistance to beta lactamase than 3rd. Many cross BBB and effective in meningitis
43
carbapenams
-highly resistant to beta lactamase
44
impenem is given with
cilastatin; b/c im is hydrolyzed in mammalian kidney by a dehydropeptidase enzyme, so give dehydropeptidase inh. Im is a carbapenam
45
beta lactam where ring is alone and not fused
monobactam (only one available is aztreonam)
46
beta lactam where ring is alone and not fused
monobactam (only one available is aztreonam-activity against gram negative, synergistic with aminoglycosides)
47
vancomycin
glycopeptide antibiotic
- IV or oral
- cell wall inh that doesn't contain beta lactam nucleus
- gram positive
- high resistance therefore *last resort
48
bacitracin
glycopeptide antibiotic
- topical (due to SEs)
- cell wall inh that doesn't contain beta lactam nucleus
- gram positive and some gram neg
49
3 mechanisms of resistance to beta lactams
1) destruction by beta lactamase enzymes
2) failure to reach target penicillin binding proteins
3) failure to bind target penicillin binding proteins
50
Ma's special ox clint-tetra chloroformed a muppet with strep
Bind to bacterial ribosomes and interfere with protein synthesis
- Macrolides
- spectinomycin
- oxazolidinones
- clindamycin
- tetracyclines
- chloramphenicol
- mupirocin
- streptogramins
51
Ma's special ox clint-tetra chloroformed a muppet with strep
Bind to bacterial ribosomes and interfere with protein synthesis
- Macrolides
- spectinomycin
- oxazolidinones
- clindamycin
- aminoglycosides (cidal)
- tetracyclines
- chloramphenicol
- mupirocin (cidal)
- streptogramins
52
tetracyclines entering cytoplasm
- gram positive (energy dependent)
| - gram negative (diffusion through porins)
53
tetracyclines entering cytoplasm
- gram positive (energy dependent)
| - gram negative (diffusion through porins)
54
macrolides and statins
myopathy
55
aminoglycosides ineffective against
anaerobic
56
aminoglycosides administered
IV and IM
57
chloramphenicol
- static
| - low income countries, rare serious side effect aplastic anemia
58
chloramphenicol
- static
| - low income countries, rare serious side effect aplastic anemia
59
3 resistance mechanism to aminoglycosides
1) altered ribosomes, relatively uncommon, but in enterococci sometimes
2) inadequate transport across cytoplasmic membrane seen in strict anaerobes, but uncommon in aerobic or facultative
3) enzymatic modification of drug is most common, through phosphorylation/adenylation/acetylation
60
3 resistance mechanisms to tetracyclines
1) drug efflux (from a new protein)
2) alteration of outer membrane proteins (mutation in chromosomal genes)
3) ribosomal binding site protected (by plasmid generated protein)
61
3 resistance mechanisms to tetracyclines
1) drug efflux (from a new protein)
2) alteration of outer membrane proteins (mutation in chromosomal genes)
3) ribosomal binding site protected (by plasmid generated protein)
62
tetrahydrofolic acid
form of folic acid fully reduced, carries 1 C groups
| -bacteria synthesize folic acid, humans get from diet
63
sulfonamids and trimethoprim
folate antagonists
64
sulfonamides MOA
stucutral analogues of PABA and competitively inhibit dihydropteroate s*ynthase and block folate synthesis
-mainly for UTIs (AEs= GI
65
trimethoprim MOA
blocks tetrahydrofolate from dihydrofolate by reversible inh of dihydrofolate reductase
-mainly for UTIs (AEs=GI, allergic skin
66
trimethoprim and sulfamethoxazole combo
synergistic and gives bactericidal activity (static on own)
67
resistance to sulfonamides
- inhibition by sulfonamides can be reversed by addition of purines, thymidine, methionine and serine
- widespread
1) reduced cellular uptake
2) altered dihydropteroate synthase
3) production of increased PABA
4) altered enzyme (can develop during therapy)
68
inhibit or damage bacterial DNA
fluoroquinolones (floxacins)
| nitrofurans (nitrofurantoine)
69
nitrofurans were widely used but now
are banned in canada (mutagenicity and carcinogenicity concern) for treatment of animal from food chain
- UTIs
- reduced form highly reactive so resistance based on inhibition of its reductase
70
nitrofurans (static or cidal)
cidal
71
do not use in patients with creatinine clearance of 60ml/min or less
nitrofurantoin (nitrofuran)
72
fluoroquinolones MOA
-bind to enzyme DNA complex and trap DNA synthesis, eventually lethal (possibly by releasing lethal double stand DNA breaks from complex)
73
fluroquinolones resistance
1) mutations in DNA topoisomerase (most of them this*)
2) decreased permeability
3) active efflux
4) plasmid mediated resistance
74
fluroquinolones resistance
1) mutations in DNA topoisomerase (most of them this*)
2) decreased permeability
3) active efflux
4) plasmid mediated resistance
75
2 drugs used to inhibit synthesis or damage cytoplasmic membrane
-polymixin E (colistin) and B
76
polymixins indication
IM for pseudomonas aeruginosa and acinetobacter baumannii
- not well absorbed from GI therefore occasionally for diarrhea
- use abandoned except in cystic fibrosis because of toxicity (affect human cell membranes too= kidney and neuro tox)
- cyclic decapeptides
77
polymixins (static or cidal)
cidal
78
resistance to polymixins
1) cell walls restrict transport
| 2) elevated concentrations of Ca or Mg reduce activity
79
resistance to polymixins
1) cell walls restrict transport
| 2) elevated concentrations of Ca or Mg reduce activity
80
cause of TB and leprosy
actinobacteria (mycobacterium)
| -gram pos, aerobic
81
second leading cause of death worldwide
TB
- more than 8 million new cases and 2 million deaths per year
- can be latent or active pulmonary or extrapulmonary disease
- long term treatment needed
- resistance= concern therefore need drug combo
82
therapy for TB
direct observed, combo drugs
83
caused by mycobacterium leprae
- leprosy (hansen's disease)
- aerobic
- grows 2-4 years (slow)
- clinical manifestations depend on immune response
84
therapy for leprosy
long term multi drug therapy
85
therapy for TB
direct observed, combo/multi drugs (never single due to resistance)
86
therapy for leprosy
long term multi drug therapy
- can give thalidominde--> birth defects
- WHO gives free treatment for ppl worldwide
87
TB drugs MOA
- classified 1st or 2nd line
1) inhibit DNA dependent RNA polymerase
2) inh protein synthesis
3) inhibit mycolic acid synthesis
4) affect THF synthesis
5) disrupt plasma membrane
88
TB drugs MOA
- classified 1st or 2nd line
1) inhibit DNA dependent RNA polymerase
2) inh protein synthesis
3) inhibit mycolic acid synthesis
4) affect THF synthesis
5) disrupt plasma membrane
89
isoniazid MOA
- anti TB first line
- enters by passive diffusion, activated by catalase, attacks multiple targets
- unique susceptibility of m tuberculosis to it can be from deficient efflux and insufficient metabolism of isoniazid derived radicals (active form)
90
pyrazinamide MOA
- first line anti TB
- fatty acid synthase and mycobacterial membranes are targets
- selective defect in POA efflux in M TB gives selectivity to kill M TB not other mycobacteria
91
anti leprosy drugs
1) rifampin
2) dapsone
3) clofazimine
92
anti leprosy MOA
rifampin- inhibit DNA dependent RNA polumerase
| dapsone- inhibit dihydropteroate synthase (like sulfonamides)
93
fungi unique properties
different ribosomes, cell wall different components, discrete nuclear membrane
94
capsofungin
antifungal
| targets cell wall 1-3 beta d glucan
95
target ergosterol (antifungals) (cell membranes)
ketoconazole, amphotericin (polyenes), triazoles, terbinafine
96
capsofungin
antifungal
targets cell wall 1-3 beta d glucan
IV
97
target ergosterol (antifungals) (cell membranes)
ketoconazole, amphotericin (polyenes), triazoles, terbinafine (allylamines)
98
target nuclear division (antifungal)
griseofulvin- inhibit mitosis by binding tubulin
99
target nucleic acid synthesis (antifungal)
flucytosine- inh DNA synthase
100
antifungal that may intensify or induce subacute cutaneous lupus erythematosus
terbinafine
101
most widely used antifungal
amphotericin B
- binds to sterols (ergosterol-which has a higher affinity for polyenes than cholesterol), form channels in membrane, K and Mg leak out
- polyenes show greater activity against fungal cells than mammalian
102
fungi without ergosterol are not susceptible to
amphotericin B or polyenes
103
amphotericin B SEs
- fever as high as 40=initial reaction
| - anemia with hematocrit of 22-35% develops with normal use
104
nystatin
polyene, minimal SEs, not allergic on skin
