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Flashcards in antibacterials Deck (152):
1

drugs that target cell wall

beta-lactams, vancomycin, fosfomycin, bacitracin

2

general properties of B-lactams

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

resistance to B-lactams

Beta-lactamase, altered PBPs, intrinsic resistance of some G- due to porins

4

what type of killers are B-lactams?

time-dependent: keep drug 4X above MIC for > 50% of total treatment time
have short half life, so more frequent dosing

5

well distributed (low to CSF except during meningitis), some oral, some IV/IM, renal elimination w/ anion transport, short half-lives

penicillins

6

types of penicillins

amoxicillin, ampicillin, penicillin G, penicillin V, piperacillin, ticarcillin, oxacillin

7

penicillin G & penicillin V

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

penicillin used for B-lactamase-positive staphylococci

oxacillin, "methicillin-type drugs"

9

drug used for otitis media in otherwise healthy kids

amoxicillin

10

used for B-lactamase-negative G+ bugs (listeria, strep) including enterococcus (UTI)
expanded G- spectrum (includes neisseria, haemophilus, e. coli, salmonella

ampicillin, amoxicillin

11

alternate choice for lyme disease, in kids or pregnant/breast-feeding women

amoxicillin

12

2 uses of ampicillin not found with amoxicillin

meningitis (neisseria, listeria) b/c IV
GI infections (shigella) b/c less orally absorbed

13

broad G- with some G+ activity, good for some anaerobes if used with clavulanate, anti-pseudomonal, susceptible to B-lactamases

ticarcillin

14

gram-negative spectrum similar to ticarcillin but also with pseudomonas, klebsiella, also ones that are ticarcillin-resistant
often used with B-lactamase inhibitor

piperacillin

15

allergic reactions to B-lactams

anaphylaxis, serum sickness, dermatitis, maculopapular rash, fever, diarrhea, enterocolitis, elevated liver enzymes, hemolytic anemia, seizures

16

excretion metabolism of penicillins

mostly renal (80% anionic excretion/20% glomerular filtration), 30% hepatic metabolism

17

skin test, 90-95% reliable at IDing risk for serious allergic reaction

PRE-PEN

18

penicillin administration

some only IV/IM, some oral, generally well-distributed, generally short half-lives, CNS distribution poor but increases with inflamed meninges

19

slow-release IM forms of penicillin

procaine, benzathine penicillin

20

B-lactamase inhibitors + mechanism

clavulanic acid, tazobactam
B-lactam "analogs" that bind irreversibly to B-lactamase

21

B-lactamase inhibitor works with?

class A B-lactamases, including plasmid-encoded forms
restores utility of some B-lactams (ampicillin, amoxicillin, ticarcillin, piperacillin)

22

B-lactamase inhibitor combination used for MSSA, E. coli, Klebsiella, Haemophilus

amoxicillin + clavulanate

23

penicillin-resistant strep pneumo cause?

changes in PBPs

24

MRSA resistance cause?

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)