antibacterials Flashcards
(152 cards)
1
Q
drugs that target cell wall
A
beta-lactams, vancomycin, fosfomycin, bacitracin
2
Q
general properties of B-lactams
A
bactericidal, activity maximal on growing bacteria, G+ and G-, bind PBPs irreversibly, inhibits transpeptidase activity that catalyzes cell wall cross-links (can result in rapid lysis + stx)
3
Q
resistance to B-lactams
A
Beta-lactamase, altered PBPs, intrinsic resistance of some G- due to porins
4
Q
what type of killers are B-lactams?
A
time-dependent: keep drug 4X above MIC for > 50% of total treatment time
have short half life, so more frequent dosing
5
Q
well distributed (low to CSF except during meningitis), some oral, some IV/IM, renal elimination w/ anion transport, short half-lives
A
penicillins
6
Q
types of penicillins
A
amoxicillin, ampicillin, penicillin G, penicillin V, piperacillin, ticarcillin, oxacillin
7
Q
penicillin G & penicillin V
A
V = oral, G = IV/IM
for anaerobes, esp G+ (except B. fragilis)
also for non-B-lactamase-producing G+ (1st line for strep throat), also B. anthracis, s. pneumo, NOT staph or enterococcus
used for syphilis, n. meningitidis
8
Q
penicillin used for B-lactamase-positive staphylococci
A
oxacillin, “methicillin-type drugs”
9
Q
drug used for otitis media in otherwise healthy kids
A
amoxicillin
10
Q
used for B-lactamase-negative G+ bugs (listeria, strep) including enterococcus (UTI)
expanded G- spectrum (includes neisseria, haemophilus, e. coli, salmonella
A
ampicillin, amoxicillin
11
Q
alternate choice for lyme disease, in kids or pregnant/breast-feeding women
A
amoxicillin
12
Q
2 uses of ampicillin not found with amoxicillin
A
meningitis (neisseria, listeria) b/c IV GI infections (shigella) b/c less orally absorbed
13
Q
broad G- with some G+ activity, good for some anaerobes if used with clavulanate, anti-pseudomonal, susceptible to B-lactamases
A
ticarcillin
14
Q
gram-negative spectrum similar to ticarcillin but also with pseudomonas, klebsiella, also ones that are ticarcillin-resistant
often used with B-lactamase inhibitor
A
piperacillin
15
Q
allergic reactions to B-lactams
A
anaphylaxis, serum sickness, dermatitis, maculopapular rash, fever, diarrhea, enterocolitis, elevated liver enzymes, hemolytic anemia, seizures
16
Q
excretion metabolism of penicillins
A
mostly renal (80% anionic excretion/20% glomerular filtration), 30% hepatic metabolism
17
Q
skin test, 90-95% reliable at IDing risk for serious allergic reaction
A
PRE-PEN
18
Q
penicillin administration
A
some only IV/IM, some oral, generally well-distributed, generally short half-lives, CNS distribution poor but increases with inflamed meninges
19
Q
slow-release IM forms of penicillin
A
procaine, benzathine penicillin
20
Q
B-lactamase inhibitors + mechanism
A
clavulanic acid, tazobactam
B-lactam “analogs” that bind irreversibly to B-lactamase
21
Q
B-lactamase inhibitor works with?
A
class A B-lactamases, including plasmid-encoded forms restores utility of some B-lactams (ampicillin, amoxicillin, ticarcillin, piperacillin)
22
Q
B-lactamase inhibitor combination used for MSSA, E. coli, Klebsiella, Haemophilus
A
amoxicillin + clavulanate
23
Q
penicillin-resistant strep pneumo cause?
A
changes in PBPs
24
Q
MRSA resistance cause?
A
acquisition of new PBP2a, encoded by MecA
25
drug class that's well-distributed, injection, same mech as penicillin, resistance mechs similar
cephalosporins
26
1st generation cephalosporins use
gram positive, staph and strep
NOT for enterococcus, listeria, MRSA or meningitis
used for uncomplicated outpatient skin infections & surgical prophylaxis
27
1st generation cephalosporins
cefazolin, cephalexin
28
IV/IM, best G+ activity of 1st generation, longer half life (1-2 hours)
cefazolin
29
oral, used for skin, bone/joint, UTIs, respiratory and otitis media. 50 min half life
cephalexin
30
only 2nd generation that penetrates CSF, best for haemophilus, but not best against enterics. good tolerance to G- beta-lactamases
cefuroxime
31
2nd gen not for CNS, good for some anaerobes including B fragilis, good tolerance to G- beta-lactamases
cefoxitin
32
3rd generation, very good for the 3 meningitis types, 1st choice for honorrhea, long half life (6-9 hrs)
ceftriaxone
33
uses of 3rd generation cephalosporins
gram-negatives: E. coli, klebsiella, enterobacter, proteus... stable against many G- B-lactamases
34
most active of 3rd generation against pseudomonas, bad for G+, shorter half life (90 mins)
ceftazidime
35
good CSF penetrance, similar to ceftazidime but more G- coverage (more resistant to type I beta-lactamases). empirical treatment of serious inpatient infections
cefepime
36
NONE of the cephalosporins are good for
enterococcus, MRSA, listeria, many stomach bugs
37
cephalosporins excretion/metabolism
renal: glomerular filtration, anion secretion
38
cephalosporin side effects
allergic reactions (cross-rxn with penicillins), N/V diarrhea enterocolitis, hepatocellular damage
39
ESBLs
inactivate penicillins, also 3rd generation cephalosporins, monobactams. use carbapenems
40
broad spectrum, aerobes and anaerobes, resistant to many B-lactamases including ESBLs. not for C diff, MRSA, E. faecum
imipenem
41
imipenem uses
mixed infections, ill-defined infections, non-resoponsive or resistant infections. given with cilastatin to extend half-life
42
imipenem side effects
allergic reactions (cross-rxn with penicillins, cephalosporins), seizures/dizziness/confusion, N/V/diarrhea, superinfection
43
no allergic cross-rections with B-lactams, used against G- aerobic rods, resistant to many B-lactamases
aztreonam
44
aztreonam side effects
seizures, anaphylaxis, EKG changes, cramps, N/V, enterocolitis
45
glycopeptide, not a B-lactam, bactericidal, inhibits cell wall synthesis
vancomycin
46
vancomycin mech
binds to D-Ala-D-Ala end of peptide, interferes with crosslinking and elongation of PG chains
47
vancomycin uses
Gram-positives ONLY: staph including MRSA, strep pneumo, enterococcus, C. diff (2nd choice)
48
vancomycin administration
IV for systemic infections, oral for C diff
49
1st line treatment for meningitis in adults in children when you do not yet know the organism causing the infection.
what organisms will this treatment cover?
3rd generation cephalosporin +vancomycin
| this will cover strep pneumo (including cephalosporin-resistant), n. meningitides, and h. influenzae
50
side effects of vancomycin
```
narrow therapeutic window
"red man" or "red neck" syndrome (histamine related)
nephrotoxicity
ototoxicity
phlebitis
```
51
enolpyruvyl transferase inhibitor
fosfomycin
52
uses of fosfomycin
uncomplicated UTIs, caused by E. coli, Enterococcus
53
side effects of fosfomycin
headache, diarrhea, nausea, vaginitis
costly
no cross-resistance with other drugs because of the specific mechanism
54
polypeptide antibiotic, interferes with cell wall synthesis by interfering with carrier that moves early wall components through cell membrane (MurNAc pentapeptide), gram positive spectrum. how is this drug used/administered?
bacitracin
| topical use only
55
side effect of bacitracin?
allergic dermatitis
56
which drugs target the cell membrane?
polymixins (polymixin B) and cyclic lipopeptides (daptomycin)
57
acts as a cationic detergent that binds LPS in the outer membrane of gram-negative bacteria; gram-negative spectrum (including Pseudomonas)
polymixin B
58
side effects of polymixin B
few side effects with topical use besides allergies; for systemic use, potential for serious nephrotoxicity and neurotoxicity
59
antibiotic that binds to bacterial cytoplasmic membrane, causing rapid membrane depolarization; rapidly bactericidal
daptomycin
| depolarization stops essential metabolic and catabolic steps
60
uses for daptomycin?
| which type of bacteria?
gram-positive only!!
used for complicated skin and skin structure infections (staph. aureus-MSSA, MRSA; various step.-pyogenes, agalactiae; enterococcus-vancomycin-susceptible only!)
bacteremia (eg. staph)
NOT for pneumonia
61
side effects of daptomycin
no cross-resistance with other antibacterials
nausea, diarrhea, GI flora alterations
muscle pain and weakness (monitor CPK levels)
62
which antibiotics target nucleic acids?
quinolones (norfloxacin, ciprofloxacin, moxifloxacin), nitrofurantoin, rifampin, metronidazole
63
inhibits alpha (and possibly beta) subunit of DNA gyrase, thereby interfering with control of DNA winding (replication and repair); bactericidal
quinolones
64
how is the bacterial killing of quinolines best predicted?
AUC(24)/MIC; integrated area under curve for 24 hrs
65
what are ways to increase AUC(24)/MIC?
more frequent doses
more drug per dose
longer T1/2 drug
drug with better MICs
66
prototype quinolone for urinary infections, effective agains enterobacteriaceae, some pseudomonas aeruginosa, staphylococcus, enterococcus. What issue caused recommendations against using quinolines for 1st line empiric therapy for routine UTIs?
norfloxacin
| resistance issues
67
this quinolone is useful for infections at many sites; UTIs, infectious diarrhea, bone and joint infections, skin infections
ciprofloxacin
68
is ciprofloxacin the best choice quinolone for gram-positive infections?
no-ciprofloxacin itself is not the best choice for gram-positive infections; other quinolines have better gram-positive and respiratory activity (ex. moxifloxacin)
69
which quinolones are best for gram-positives?
moxifloxacin and levofloxacin
70
uses of ciprofloxacin?
chlamydia; (CDC no longer recommends using ciprofloxacin to treat uncomplicated gonorrhea due to widespread resistance)
71
uses of moxifloxacin
better gram-positive activity than other quinolones;
used for respiratory infections (community-acquired pneumonia; acute exacerbation of bacterial bronchitis; NOT approved for strep. throat)
72
can quinolones be substituted for each other
no-have to pay apptention to approved clinical uses (pathogen, site of infection) local sensitivity patterns, and specific strains.
73
distribution of quinolones
many fluorinated drugs are well-distributed (including the CSF but not indicated for meningitis); some (eg. norfloxacin) and the non fluorinated agents achieve therapeutic concentrations only in the urinary tract
74
administration of quinolones
oral, some also IV
75
side effects of quinolones
nausea, vomiting, abdominal pain, enterocolitis, dizziness, headache, restlessness, depression, rare seizures, rashes (potentially fatal!! STOP drug if rash appears!), EKG irregularities, arrhythmias (prolonged QT interval), peripheral neuropathy, arthropathy, tendon rupture
76
precautions for quinolones
use precaution in patients with seizure disorders, pregnant
| use in children in cautioned (possible cartilage damage)
77
nitroreductase enyme converts these drugs to reactive comounds (including free radicals) which can damage bacterial DNA
nitrofurantoin
78
use for nitrofurantoin
urinary tract infections (lower UTI only, not renal) caused by e. coli, enterococcus, staphylococcus
79
side effects of nitrofurantoin
nausea, vomiting, diarrhea, hypersensitivity, fever, chills, peripheral neuropathy, acute and chronic pulmonary reactions (can cause irreversible pulmonary fibrosis due to oxygen radicals), acute and chronic liver damage, granulocytopenia, leukopenia, megaloblastic anemia, acute hemolytic anemia (in those with glucose-6-P dehydrogenase deficiency)!!
80
antibiotic that binds to and inhibits bacterial RNA polymerase beta; this inhibits RNA synthesis; bactericidal
rifampin
81
uses for rifampin
tuberculosis; meningitis prophylaxis caused by n. meningitides or h. influenza type b
82
side effects of rifampin
```
serious hepatotoxicity (with long-term use)
rifampin strongly induces many enzymes (eg. CYP3A4, 2C9, 2C19, 1A, 2A, 2B) that inactivate other drugs-this can lead to major drug interactions
orange color to urine, saliva, sweat, tears
```
83
non-competitive inhibitor of RNA polymerase; inhibits RNA synthesis
fidaxomicin
84
uses of fidaxomicin and adminitration
c. difficile infection (3rd like to metronidazole, vancomycin)
bactericidal
oral administration, poorly absorbed
85
side effects of fidaxomicin
GI upset, GI bleeding; very expensive!
86
anaerobes reduce the nitro group of metronidazole; the resulting product damages/disrupts DNA; bactericidal
metronidazole
87
uses of metronidazole
anaerobes
1st line for c. difficult enterocolitis
h. pylori combination therapy (metronidazole+tetracycline (or amoxicillin)+bismuth subsalicylate)
gardnerella vaginalis (bacterial vaginosis)
88
side effects of metronidazole
```
nausea, vomiting, anorexia, diarrhea
transient leukopenia, neutropenia
thrombophlebitis after IV infusion
bacterial and fungal super infections (esp. candida)
can cause ethanol intolerance
```
89
c. difficile enterocolitis (causes, considerations, therapy)
can be caused by all antibacterials
consider in all patients with antibacterial drugs in last 2 months
therapy:
metronidazole (1st choice for mild-to-moderate cases)
vancomycin (better for moderate-to-severe cases)
vancomycin + metronidazole (very severe cases)
fidaxomicin
fecal transplant
90
freeze initiation (premature release of ribosome from mRNA)
aminoglycosides
91
prevents tRNA from binding
tetracycline and chloramphenicol
92
blocks peptide bond formation (peptidyl transferase)
chloramphenicol
93
blocks translocation step
erythomycin and clindamycin
94
causes misreading of mRNA
aminoglycosides
95
protein synthesis inhibitors
aminoglycosides (gentamicin, tobramycin, amikacin)
tetracyclines (doxycycline, minocycline)
glycylcycline (tigecycline)
macrolides (erythromycin, clarithromycin, azithromycin)
streptogramins
oxazilidinones (linezolid)
misc. (chloramphenicol, clindamycin)
96
bactericidal, IV/IM/topical; transported into bacterial by energy-requiring aerobic process; bind to several ribosomal sites (30S/50S interface); stops initiation and causes premature release of ribosome from mRNA; causes mRNA misreading
Aminoglycosides
97
use of aminoglycosides
primarily for gram negative "aerobic" bacilli (enterobacteriaceae, Pseudomonas)
often used in combo with cell wall inhibitors or quinolines (synergism)
poor activity against anaerobes
use restricted to serious infection!
narrow therapeutic window
98
how can aminoglycosides be used to treat gram positive infections?
requires drug combinations (staphylococcus, streptococcus, some enterococcus)
use in combo with cell wall inhibitors (B-lactams, vancomycin) to enhance the permeability of aminoglycosides
(but, cannot mix aminoglycosides with B-lactams in vitro; chemical reaction inactivates the aminoglycosides)
99
how to treat Enterococcus bacteremia or endocarditis using aminoglycosides
ampicillin + gentamicin
| vancomycin + gentamicin
100
what is the post-antibiotic effect?
aminoglycosides have a post-antibiotic effect:
sustained activity for several hours after aminoglycoside concentration has dropped below effective levels
less frequent dosing
concentration dependent killing!
101
pharmacokinetics of aminoglycosides and problems related to pharmacokinetics?
concentration-dependent killers; problem=toxicity is dose-related; post-antibiotic effect allows for less frequent dosing
102
aminoglycosides to know...
gentamicin, tobramycin, amikacin
103
choice agent for gentamicin- and tobramycin-resistant strains
amikacin
104
side effects of aminoglycosides
narrow therapeutic window
nephrotoxicity (usually reversible)
ototoxicity (mostly irreversible)
neuromuscular blockade
105
transported into the cells by a protein-carrier system; prevent attachment of aminoacyl-tRNA binding to 30S ribosomal subunits; bacteriostatic
tetracyclines
106
resistance to tetracyclines
drug efflux pump; resistance to one tetracycline often implies resistance to them all (plasmid conferring resistance can easily be transferred
107
uses of tetracyclines
preferred agents for "unusual bugs": rickettsia, Lyme disease (Borrelia), chlamydia, Mycoplasma, Ureaplasma
108
alternative treatment for penicillin G-sensitive syphilis, uncomplicated gonorrhoeae (but, CDC indicates it is not adequate on its own); least affinity for calcium
doxycycline
109
alternative treatment for penicillin G-sensistive syphilis; uncomplicated gonorrhea (CDC indicates it is not adequate on its own-2nd line agent used alongside another 2nd-line agent); more calcium binding than doxycycline
minocycline
110
administration of tetracyclines
oral, parenteral; bind calcium, inhibits tetracycline absorption (so do not take with high calcium foods and antacids, etc!)
111
side effects of tetracyclines
gastrointestinal disturbances, including enterocolitis; Candida superinfection in colon; photosensitization with rash; teeth discoloration
112
contraindications for tetracyclines
avoid use in children, esp. less than 8 years old because of calcium binding and teeth discoloration; contraindicated in pregnancy
113
glycylcycline; works like tetracyclines but also binds additional unique sites in the ribosomes
tigecycline
114
resistance to tigecycine
no cross-resistance with other antibacterials including tetracyclines
115
uses of tigecycline
skin/skin structure infections; complicated intra-abdominal infections; CAP (community-acquired pneumonia)
116
what organisms can tigecycline be used against?
```
gram negatives (e. coli, citrobacter, klebsiella, enterobacter, NOT psuedomonas)
gram positives (staphylococcus-MSSA, MRSA; streptococcus)
anaerobes (bacteroides, clostridium perfringens)
```
117
adverse reactions to tigecycline
nausea, vomiting, enterocolitis
other side effects similar to tetracyclines including calcium binding
-->FDA alert: increased risk of death, especially those with serious infections--considered a last line agent when there are no other good choices
118
interferes with binding of aminoacyl-tRNA to 50S ribosomal subunit and inhibits peptide bond formation; mode of resistance?
chloramphenicol
| resistance: acetylation by CAT
119
chloramphenicol uses and side effects
indiscriminate use in 1950s;
generally bacteriostatic (can be cidal for H. influenza, N. meningitidis, strep. pneumo)
broad spectrum of activity;
very serious side effects (causes irreversible shut-down of bone marrow in some patients)--restrict its use only when no other agents are suitable
120
current indications for chloramphenicol
meningitis (alternative in those with serious cephalosporin allergies)
brain abscesses
121
side effects of chloramphenicol
bone marrow depression--fatal aplastic anemia (1 in 30,000); not necessarily dose-related, can be delayed
grey baby syndrome
optic neuritis and blindness
GI effects including enterocolitis
122
binds to 50S subunit, blocks translocation along ribosomes; bacteriostatic. what drugs are in this class?
macrolides
erythromycin
clarithromycin
azithromycin
123
primarily against gram positive; recommended for strep throat in penicillin-allergic patients; also effective against "unusual" or "atypical" bugs (chlamydia, mycoplasma, legionella, bordetella)
erythromycin
124
side effects of erythromycin
nausea, vomiting (from enhanced GI motility)
inhibits CYP3A metabolism/excretion of many drugs
increases risk of arrythmias and cardiac arrest
125
similar to erythromycin, but better kinetics: less frequent dosing, less GI motility effects, somewhat wider antibacterial spectrum; also has some CV risks (prolongs QT interval)
clarithromycin
126
uses of clarithromycin
```
same as erythromycin (primarily against gram positive; recommended for strep throat in penicillin-allergic patients; also effective against "unusual" or "atypical" bugs (chlamydia, mycoplasma, legionella, bordetella))
plus:
haemophilus influenzae, moraxella
penicillin-resistant strep. pneumoniae
atypical mycobacteria
licensed for helicobacter pylori
```
127
treatment for h. pylori
3-drug combos are becoming the standard:
2 antibacterials: e.g. clarithromycin + amoxicillin
plus and acid blocker
examples:
clarithromycin + amoxacillin + omeprazole
metronidazole + tetracycline + bismuth subsalicylate + PPI
128
very common treatment for outpatient respiratory tract infections; for genital infections (chlamydia)
azithromycin
129
CDC updated gonorrheal recommendations
ceftriaxione + azithromycin or doxycycline
130
adverse reactions to azithromycin?
least GI upset than the other macrocodes; few effects on CYP3A4; cardiac (QT prolongation)
131
binds to 50S ribosomal subunit, blocks translocation along ribosomes; significant cause of c. dif enterocolitis; not a macrolide or ketolide
clindamycin
132
uses for clindamycin
gram positive cocci (e.g. Strep. and MSSA)
suppresses bacterial toxin production of Strep. and Staph.
many anaerobes including Bacteroides fragilis
NOT for C. difficile
133
side effects of clindamycin
GI irritation, diarrhea
antibiotic-associated enterocolitis
hepatotoxicity
134
inhibits protein synthesis; binds to 50S ribosomal subunit, interfering with formation of 70S initiation complex; bacteriostatic for Staph. and Enterococcus
linezolid
135
uses of linezolid
gram positive spectrum
skin/skin structure infections: VRE: vancomycin-resistant Enterococcus faecuim, Staph. aureus, Strep. group A and B
Strep. pneumo (including multi-drug resistant)
Staph.
136
side effects of linezolid
non-selective inhibitor of MAO (many possible drug interactions; avoid foods with tyramine)
diarrhea, superinfection, enterocolitis
headache, nausea/vomiting
bone marrow suppression
137
inhibit folate synthesis
anti-folates
sulfonamides (sulfamethoxazole, sulfadiazine)
trimethoprim
138
bacteriostatic; competitive analogs of p-aminobenzoic acid, a precursor in folate synthesis; inhibit the action of dihydropteroate synthase
sulfonamides
139
uses of sulfonamides
today, most commonly used sulfonamides are combined with other antibacterials
140
used with trimethoprim as part of synergistic combination; best pharmacokinetic match to trimethoprim
sulfamethoxazole
141
used topically for infection prevention in burn patients
silver sulfadiazine
142
side effects of sulfonamides
hypersensitivity (rashes, serum sickness--sunlight (UV) makes rash worse)
GI disturbances
renal damage (crystalluria)
potentiate action of other drugs (inhibit CYP2C9)
143
inhibits folate synthesis in bacteria by competitively inhibiting dihydrofolate reductase; dihydrofolate analog
trimethoprim
144
uses of trimethoprim
usually in combination with sulfamethoxazole: synergistic effect
2 static drugs = 1 cidal drugs
Trimethoprim + Sulfamethoxazole (TMP/SMX)
145
uses of TMP/SMX
first choice empiric therapy for uncomplicated UTIs (cystitis) (enterobacteriaceae, coagulase-negative staph.)
upper respiratory tract, ear infections (h. influenzae, moraxella, strep. pneumoniae)
GI infections (salmonella, shigella)
Pneumocystis jiroveci (1st choice for treatment and prophylaxis)
146
side effects of TMP/SMX
all of the sulfonamide side effects (hypersensitivity (rashes, serum sickness--sunlight (UV) makes rash worse)
GI disturbances
renal damage (crystalluria)
potentiate action of other drugs (inhibit CYP2C9))
Trimethoprim adds:
nausea, vomiting, diarrhea, rashes
bone marrow suppression
(trimethoprim side effects especially pronounced with long-term use, e.g. AIDS patients)
147
what are the four categories of antibacterials used?
prophylactic (e.g. prevent surgical wound infections)
empiric (organism unknown but syndrome known)
pathogen-directed (pathogen known, but susceptibility not yet known)
susceptibility-guided (both pathogen and susceptibility known
148
example of one common use of empiric therapy for uncomplicated cystitis in non pregnant women
1st choice: TMP/SMX
other choices:
nitrofurantoin
fosfomycin
149
what are some reasons for antibacterial failures?
```
drug choice (susceptibility of the pathogen, site of infection--drug penetration, emergence of resistance, superinfection with another organism)
host factors (do abscesses need draining? is host immune response okay? are there foreign bodies, implants, mechanical devices, indwelling lines?)
```
150
what are some other factors to consider with antibacterial choices?
regional and institutional resistance patterns
patient age
renal and liver function
specific disease states
route of administration (site of infection, drug distribution)
151
drugs for hospital-acquired MRSA (HA-MRSA)
vancomycin (IV)
linezolid (HA, oral)
daptomycin (IV)
tigecycine (IV)
152
drugs for community-acquired MRSA (CA-MRSA)
linezolid (oral)
doxycycline, minocycline (oral)
clindamycin (oral)
TMP-SMX (oral)
