principles of infectious disease therapeutics Flashcards
(139 cards)
1
Q
antimicrobial PKPD that is important in combatting superbugs
A
- clinical: focus on the patient
- translational: turning bench research into clinical guidance –> stewardship
- interdisciplinary: pharmacy, medicine, science, pharm sci
- global: bridge collaboration
- trainee focused
2
Q
interdisciplinary aspect of ID
A
- pharmaceutics
- pharmacometrics
- drug delivery and design
- drug discovery and development
- bacterial
- chemotherapy
- gene therapy
- ID
3
Q
most common organism of infection is…
A
the one that lives in that area
4
Q
most common eye infection
A
staph aureus
5
Q
most common gastritis infection (stomach)
A
helicobacter pylori
6
Q
most common food poisoning infection (intestines)
A
Escherichia coli
7
Q
most common urinary tract infection
A
E. coli
8
Q
most common skin infection
A
Staph aureus
9
Q
most common community acquired pneumonia infection (lungs)
A
Strep pneumoniae
10
Q
most common ear infection
A
strep penumoniae
11
Q
most common bacterial meningitis infection (brain)
A
strep penumoniae
12
Q
infectious and parasitic disease is the number __ cause of death globally
A
2
13
Q
post-antibiotic world
A
when superbugs do not respond to the last line antibiotic defense
14
Q
polymyxin mono therapy vs combination therapy for all-cause mortality endpoint
A
for invasive CRE (carbapenem resistant enterobacterales) infections
- combination therapy (second antibiotic causes damage in outer membrane)
for other infections
- no evidence to support combination > monotherapy
- lots of trial issues
15
Q
ID triad
A
- host
- drug
- bacteria
16
Q
ID patient considerations
A
- host
- infection site and severity
- MICs
- treatment regimens
17
Q
vancomycin route of administration
A
IV ONLY!!!
18
Q
if staph aureus, which antibiotics can you NEVER USE alone even if S? why?
A
- ciprofloxacin
- rifampin
***will develop resistance within 24 hours!! (very susceptible to resistance)
(can use in combo therapy tho (?) (only rifampin?))
19
Q
what is the target vanco AUC 24 hr from the guidelines?
A
400 mg*hr/L
20
Q
what is the equation to adjust vanco dosing?
A
D target = D observed (AUC 24 target / AUC 24 obser)
aka
D target AUC 24 target
————- = ————————
D observed AUC 24 observed
21
Q
antibiogram selection considerations
A
- cost
- dosage form (IV vs PO)
- is failure okay or would it be lethal?
- may become resistance once administer it
22
Q
what number on an antibiogram is safe for susceptibility?
A
80
on an exam, highest wins
23
Q
does susceptible mean it will be sucessful?
A
no
24
Q
the primary mechanism of resistance is…
A
the primary mechanism of action of the antibiotic being used
25
mechanism of action for ciprofloxacin --> mechanism of resistance for ciprofloxacin
MoA: fluoroquinolone -> DNA synthesis inhibitor
MoR: mutational event in the DNA replication process
26
mechanism of action for linezolid --> mechanism of resistance for linezolid
MoA: oxazolodonones --> protein synthesis inhibitor
MoR: ribosomal protection (tet protein) --> allows for no inhibition and protein synthesis to continue
27
mechanism of action for vancomycin --> mechanism of resistance for vancomycin
MoA: glycopeptide --> cell wall agent (blocks peptidoglycan synthesis)
MoR: decrease cell wall permeability to vanco --> prevents peptidoglycan synthesis)
28
mechanism of resistance for beta lactamase bacteria enzyme
the beta lactamase enzyme will open the ring of the beta lactam antibiotics, thus inactivating them --> enzymatic inactivation mechanism of resistance
the beta lactamase inhibitor drugs will act as bet lactam decoys and trick the beta lactamase enzymes to break them down instead, thus saving the beta lactam ring and the action of the antibiotics
29
bacteriocidal
99% killing, CFU below 10^4
30
bacteriostatic
inhibitory, CFU above
31
HEM PEK SPACE are all...
gram negative aerobes
32
which HEM PEK SPACE are cocci?
H,M
Haemophilus influenzae
Moraxella catarrhalis
*the rest are bacilli
33
HEM PEK SPACE
H: Haemophilus influenzae
E: Enterobactericiae (group)
M: Moraxella catarrhalis
P: Proteus sp.
E: E. coli
K: Klebsiella sp.
S: Serratia
P: Pseudomonas aeruginosa
A: Acinetobacter
C: Citrobacter
E: Enterobacter sp.
34
what is methicillin?
the first penicillin that caused bacterial resistance, pulled from market for AEs --> use to determine if we can use penicillins or not
35
clindamycin is used for
above diaphragm anaerobes
36
metronidazole is used for
below diaphragm anaerobes
37
staph is
aerobe
gram positive
clusters
38
strep pneumoniae is
aerobe
gram positive
pairs
39
GAS and GBS are
aerobe
gram positive
chains
40
e coli is
aerobe
gram negative
bacilli
41
pseudomonas aeruginosa is
aerobe
gram negative
bacilli
42
staph aureus is
aerobe
gram positive
clusters
coagulase positive
43
staph epidermidis is
aerobe
gram positive
cluster
coagulase negative
44
what is coagulase?
bacterial enzyme that coagulates blood/plasma that is produced by infectious staph
45
is strep pneumoniae typical or atypical bacteria?
typical
46
penicillin MoA
beta lactams --> cell wall active
bind to transpeptidase enzymes (penicillin binding proteins) in the bacterial cell and disrupt cell wall formation
47
penicillins are bacterio...
cidial
48
penicillins are bacterio...
cidia
49
pencillin spectrum
gram positive aerobes
MSSA
some gram negative aerobes
some pseudomonas
50
cephalosporins MoA
beta lactams --> cell wall active
bind to transpeptidase enzymes in bacterial cell wall and disrupt cell wall formation (same as penicillins bc all beta lactams)
51
cephalosporins are bacterio...
cidal
52
cephalosporin spectrum
gram positive aerobes
MSSA
gram negative aerobes
some pseudomonas
53
which cephalosporins cover pseudomonas?
ceftazidime (3rd)
cefepime (4th)
54
which penicillins cover pseudomonas?
piperacillin
piperacillin/tazobactam
ticarcillin
ticarcillin/clavanute
55
which cephalosporins cover MRSA?
ceftaroline (5th)
56
which cephalosporin covers both MRSA and pseudomonas?
none
57
carbapenems MoA
beta lactams --> cell wall active agents
58
carbapenems spectrum
MOST BROAD SPECTRUM SINGLE AGENT!!
gram positive aerobes
MSSA
gram negative aerobes
pseudomonas (NOT ertapenem)
gram negative anaerobes
59
monobactams MoA
beta lactam --> cell wall active agent
60
monobactams spectrum
gram negative aerobes
pseudomonas
61
aminoglycoside MoA
protein synthesis inhibiting agents
bind to 30S ribosomal subunit and inhibit bacterial protein synthesis
62
aminoglycosides are bacterio....
cidal
63
aminoglycoside spectrum
some gram positive aerobes
some MSSA
some MRSA
gram negative aerobes
pseudomonas
64
aminoglycoside rank of activity against pseudomonas
1. amikacin
2. tobramycin
3. gentamicin
65
which amino glycoside covered gram positive aerobes including MSSA and MRSA and infective endocarditis
gentamicin + cell wall active agent
66
aminoglycoside AEs
- nephrotoxicity
- ototoxicity (hearing/balance)
- enhanced neuromuscular blockade
67
which antibiotics cause nephrotoxicity?
- aminoglycosides
- polymyxins
- vancomycin (glycopeptide -- cell wall active)
(- piperacillin/tazobactam (Zosyn))
68
tetracyclines MoA
protein synthesis inhibiting agent
reversibly bind the 30S ribosomal subunit and inhibit bacterial protein synthesis
69
tetracyclines are bacterio...
STATIC!
70
tetracycline counseling
do not take with di and trivalent cations aka milk, antacids, sucralfate --> dec oral absorption
worse with tetracycline than doxycycline
71
tetracycline AEs
- GI intolerance
- phototoxicity (skin or eyes become sensitive to light)
- fanconi syndrome (dec kidney reabsorption)
72
tetracycline spectrum
gram positive aerobes
MSSA
MRSA
gram negative aerobes
atypicals
73
macrolides MoA
protein synthesis inhibitor
reversibly binds to 50S ribosomal subunit and inhibits bacteria protein synthesis
74
macrolides are bacterio...
STATIC
75
macrolide AEs
- GI intolerance (EVEN WITH IV erythromycin)
- IV erythromycin: phlebitis (inflammation that causes blood clot)
76
macrolide spectrum
gram positive aerobes
MSSA
gram negative aerobes
atypical
77
lincosamides MoA
protein synthesis inhibiting agent
reversibly bind 50S ribosomal subunit and inhibit bacteria protein synthesis
78
lincosamides are bacterio...
STATIC
79
lincosamide AEs
- GI
- pseudomembranous colitis (inflammation in colon (large intestine) bc overgrowth of C diff)
80
lincosamide spectrum
gram positive aerobes
MSSA
MRSA
gram negative anaerobes
**excellent bone penetration
81
fluoroquinolone MoA
DNA synthesis inhibitors --> antimetabolite and other
inhibit DNA gyrase which causes breakage of bacterial DNA --> therefore inhibits DNA
82
fluoroquinolones are bacterio...
cidal
83
fluoroquinolone counseling
do not take with di and trivalent cations (milk, antacids, sucralfate) bc dec oral absorption
DDI!!!
84
which two antibiotic classes can you not take with milk, antacids, sucralfate? why?
tetracyclines (doxycycline, tetracycline)
fluoroquinolones (ciprofloxacin, levofloxacin)
dec oral absorption
85
fluoroquinolone AEs
- GI
- HA
- seizures
- dizzy
- QTc prolongation
NOT for children < 18 or pregnant
86
fluoroquinolone spectrum
gram positive aerobes
MSSA
gram negative aerobes
some pseudomonas
atypicals
87
which fluoroquinolones cover pseudomonas?
ciprofloxacin
levofloxacin
88
glycopeptide MoA
cell wall active agent
bind to D-alanyl-D-alanine terminal residue in the growing peptidoglycan chain --> prevents further cell wall formation
89
glycopeptides are bacterio...
cidal
90
glycopeptide AEs
- nephrotoxicity
- ototoxicity
- Red Man's Syndrome (allergic reaction to vanco often after IV infusion, rash on face, neck, torso)
- neutropenia
- rash
91
what is the drug of choice for MRSA?
glycopeptides (vanco)!
92
glycopeptide spectrum
gram positive aerobes
MSSA
MRSA
c. diff
93
lipopeptide MoA
cell membrane active agent
irreversibly binds to bacterial cell membrane and a calcium-dependent molecule insertion occurs --> rapidly depolarize cell membrane --> potassium efflux, ruins ion-concentration gradient --> cell death
94
lipopeptide AE and monitoring
skeletal myopathy (loss of muscle mass)
therefore....all patients monitor for
- muscle pain/weakness, especially in distal extremities
- CPK (creatinine phosphokinase) levels weekly
if elevated CPK levels...
- monitor more frequently
- discontinue treatment for unexplained myopathy s/s + CPK > 1000 (5x ULN)
- discontinue treatment for CPK > 10x ULN
95
lipopeptide spectrum
gram positive aerobes
MSSA
MRSA
96
lipopeptide CI
NOT INDICATED FOR PNEUMONIA!!
- low pulmonary penetration
- microbiological activity inhibited by surfactant
97
which antibiotics cover pseudomonas aeruginosa?
beta lactams
- piperacillin
- ticarcillin
- ceftazidime
- cefepime
- imipenem
- meropenem
- doripenem
(NOT ertapenem)
protein synthesis inhibitors
- gentamicin
- tobramycin
DNA synthesis inhibitors
- ciprofloxacin
- levofloxacin
98
which antibiotics cover MRSA/MRSE?
beta lactams
- ceftarolin
additional cell wall active agents
- vancomycin
cell membrane active agents
- daptomycin
protein synthesis inhibitors
- gentamicin + cell wall active
- tetracycline
- doxycycline
- clindamycin
- linezolid
DNA synthesis inhibitor
- TMP/SMX
99
measures/indicies of drug action
Cmax : MIC
%T > MIC
AUC : MIC
100
which drugs are time dependent minimal/moderate persistent effects?
penicillins
cephalosporins
carbapenems
macrolides
oxazolidiones
101
which drugs are concentration dependent prolonged persistent effects?
aminoglycosides
fluoroquinolones
102
which drugs are time dependent prolonged persistent effects?
vancomycin (glycopeptide)
tetracycline (tetracyclines)
azithromycin (macrolide)
103
are aminoglycosides hydrophilic or lipophilic?
hydrophilic
therefore...
renal CL
tissue distribution limited to extracellular space
104
antibiotics without renal dose adjustment
NOCk a TAD on the DECk MM Lunch
nafcillin
oxacillin
ceftriaxone
tigecycline!!!
azithromycin
doxycycline
dalfopristin/quinupristin
erythromycin
clindamycin
metronidazole
moxifloxacin
linezolid
105
what is the biggest factor controlling PD?
bacteria species!
106
what is the second biggest factor for controlling PD?
MIC
107
which drugs may be S but develop rapid resistance once used --> therefore should be avoided?
rifampin
ciprofloxacin (flourorquinolones)
clindamycin
108
which organisms may appear S at first, but due to inducible AmpC develop rapid resistance --> may need to use less desireable antibiotics?
SPACE-M
Serratia
Pseudomonas aeruginosa
Acinetobacter
Citrobacter
Enterobacter
Moraxella catarrhalis
109
fluoroquinolone optimal target dosing
AUC:MIC ratio between 125 and 250
110
vancomycin optimal target dosing
AUC:MIC ratio above 400 mg*hr/L
111
AUC:MIC is dependent on what factors?
dose 24 (daily dose pt recieves)
patient specific CL
bacterial specific MIC
112
most purulent SSTIs are caused by
staph aureus
most are MSSA
113
signs of systemic infection
fever
leukocytosis
(note that these could also be signs of other causes)
114
which drugs are not reliable for MRSA empirically?
clindamycin
levofloxacin
115
empiric treatment
assume most common situation bc have no labs, start broad bc don't want to miss anything
116
for empiric s. aureus, assume
MRSA
117
defined treatment
once you know organism only target it
118
for defined s. aureus
if MSSA --> deescalate therapy!
119
goal vanco trough for SSTIs
10-15 mcg/mL
120
how is vanco generally doses?
multiple times per day, also monitoring
121
iv vancomycin AEs
nephrotoxicity
infusion AEs
VRE risk (vanco resistant enterococci)
122
daptomycin, ceftaroline, dalbavancin, oritavancin are generally dosed
every 12 hours, once a day, or once a week --> longer, therefore hospitals may want to use
123
how do you Dx SIRS?
systemic inflammatory response syndrome
NEED 2 OR MORE:
temp < 36 Celsius or >38 Celsius
> 24 breaths/min (tachypnea)
> 90 bpm (tachycardia)
WBC < 4000 or > 12000 cells/uL
124
risk factors for non-purulent SSTI
**anything that could allow bacteria to invade deeper tissues
- dry skin
- fragile skin
- obesity
- previous skin trauma
- previous cellulitis
- edema from venous insufficiency
- tinea pedis (athlete's foot)
125
non purulent SSTI cellulitis most caused by
streptococcus (usually group B)
126
duration of purulent SSTI treatment
5-10 days after I and D
127
not reliable for oral streptococcus non purulent SSTI?
doxycycline
SMX/TMP
128
duration of mild cellulitis?
5 days
129
duration of mod-severe cellulitis?
10-14 days, maybe longer
130
what cultures do we need to do in non purulent SSTI?
blood!!
131
necrotizing fascilitis caused by
monomicrobial:
strep pyogenes (GAS) (flesh eating)
s aureus
clostridium
132
which cultures do you need for necrotizing facilitis?
blood
deep tissues
take them from surgery
133
duration of necrotizing facilitis treatment
until..
no longer need debridement
patient clinically improved
afebrile for 48-72 hours
134
which patients do you need bacteriocidal activity in?
CNS infections
immunocompromised
sepsis
135
what inc risk of resistance
previous use of antibiotics long term
hospital exposure
pervious documented resistance
136
linezolid serious AEs
- serotonin syndrome
- thrombocytopenia
137
reasons to assume MRSA in DFI
Hx MRSA infection or colonization
high local prevalence
sereve infection
138
DFI often caused by
gram positive aerobes: strep, staph, MRSA
gram negative aerobes: pseudomonas
anaerobes
polymicrobial
139
reason to assume pseudomonas?
- warm climate
- frequent water exposure
- high prevalence
