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Flashcards in Combined Test 3 Deck (272):
1

*For what conditions is bactericidal antibiotic therapy required? (4 dz’s)

- Meningitis - Endocarditis - Osteomyelitis - Febrile neutropenia

2

Bactericidal or bacteriostatic? Cell wall formation/synthesis inhibitors are in general _____________. Nucleic acid synthesis inhibitors are ___________. Protein synthesis inhibitors tend to be ____________. Metabolic inhibitors are usually ______________.

Cell wall formation/synthesis inhibitors are in general bacteriocidal. Nucleic acid synthesis inhibitors are bacteriocidal. (exception: aminoglycosides) Protein synthesis inhibitors tend to be bacteriostatic. Metabolic inhibitors are usually bacteriocidal.

3

What are the 3 key concepts to consider regarding infection when considering antibiotic tx?

- Severity - Site - Organism

4

What are the 6 key concepts to consider regarding the host when considering antibiotic tx?

- Allergies - Age - Pregnancy - Renal/hepatic function - Drug interactions (w/theirs) - Underlying disease

5

What are the 7 key concepts to consider regarding the drug when considering antibiotic tx?

- Predicted activity/measured susceptibility - Clinical efficacy - “Drug of choice” - PK and tissue penetration - PD (need cidal?) - Side Effects - Cost

6

What are the 2 groups of natural PCNs?

PCN G and PCN VK (oral)

7

What are the 4 types of penicillinase-resistant penicillins?

Nafcillin, oxacillin, methacillin, dicloxacillin

8

What are the 2 aminopenecillins?

Ampicillin and amoxicillin

9

What is the name of the carboxypenicillin?

Ticarcillin (not avail.)

10

What is the name of the ureidopenicillin?

Piperacillin

11

Name 4 beta-lactamase inhibitor-combo treatments. (just the overall drug names)

- Unasyn - Timentin - Zosyn - Augmentin

12

Are PCNs time- or conc-dependent killing?

- Time-dependent

13

What group does PCNs have synergy w/?

Aminoglycosides (against Enterococcus spp., Staphylococcus spp., viridans strep, and gram-negative bacteria)

14

PCNs distribute throughout body tissues/fluids except for these 3 sites:

Eye, prostate, and uninflammed CSF.

15

*What 5 things are natural PCNs commonly used for treating, besides the organisms previously mentioned? (extra stuff that's on slides but not blue)

- Actinomyces - Bacillus anthracis (anthrax) - Endocarditis prophylaxis - Prevention of rheumatic fever

16

What type of infections (not organisms) are amino-PCNs used to treat?

- Respiratory tract infections - Pharyngitis - Sinusitis - Otitis media - Bronchitis - UTIs

17

Although not clinically available, what types of conditions do ticarcillin and pipercillin typically treat?

Hospital-acquired infections

18

The beta-Lactamase Inhibitor Combination treatment Augmentin is typically used to treat what sx?

Sinusitis, otitis media, upper and lower respiratory tract infections, human or animal bite wounds (similar to amino-PCNs)

19

The beta-Lactamase Inhibitor Combination treatments Unasyn, Zosyn, Timentin are typically used to treat what major types of infections?

- Polymicrobial infections - Empiric therapy for febrile neutropenia or hospital-acquired infections (Zosyn)

20

MoA of all beta-lactams? - Cidal or static?

Inhibit cell wall synthesis by binding and thus inhibiting PBPs. Inhibits final transpeptidation step of peptidoglycan synthesis. - Bactericidal

21

*Most beta-lactams are eliminated by the ___________. *What are the exceptions? (don't forget cephalosporins)

Kidneys - Nafcillin, oxacillin, dicloxacillin (PRPs) - Ceftriaxone (cephalosporin) - Cefoperazone (cephalosporin)

22

What are the beta-lactam mechs of resistance? (Which is most important?)

Beta-lactamase enzymes (most important; cephalosporins are less susceptable), PBP alteration, decreased membrane penetration

23

2 eg's of organisms that inhibit beta-lactams via beta-lactamase are:

- PRSP - MRSA

24

What 2 drugs are contained in Unasyn?

Ampicillin-sulbactam

25

What 2 drugs are contained in Timentin?

Ticarcillin-clavulanate

26

What 2 drugs are contained in Zosyn?

Piperacillin-tazobactam

27

What 2 drugs are contained in Augmentin?

Amoxicillin-clavulanate

28

What is the route of administration of PCN G, aqueous form? Benzathine salt form? Procaine form?

- Aqueous: IV - Benzathine: IM - Procaine: IM

29

What is the route of administration for PCN VK?

PO (acid stable)

30

Which of the 4 penicillinase-resistant penicillins can be given orally?

Dicloxacillin

31

Which of the amino-PCNs have better oral uptake?

Amoxicillin

32

Which of the 4 beta-lactamase inhibitor combo treatment drugs can be given orally?

Augmentin

33

How do drugs like sulbactam, clavulante, and tazobactam block bacteria from attacking PCNs, which are given together with these drugs?

Prevent beta-lactamase enzymes from working

34

With PCNs, do we want more time above MIC, or greater peak:MIC ratio?

More time above MIC (cuz time-dependent killing)

35

ALL penicillins have ________ elimination half-lives, and require (frequent/infrequent) dosing. - What are the 2 exceptions to this?

Short (

36

*Name the main target organisms of natural penicillins.

- Penicillin-susceptible S. pneumoniae - infections due to other streptococci - Neisseria meningitidis - Syphilis - Clostridium perfringens + tetani

37

*Name the main target organism of penicillinase-resistant PCNs (PRPs).

Infections due to MSSA such as skin and soft tissue infections

38

*Name the main target organisms of aminopenicillins.

- Enterococcal infections (often with an aminoglycoside) - Listeria monocytogenes

39

*Name the main target organisms of Carboxypenicillins and Ureidopenicillins.

- Empiric therapy for HA-infections - Infections due to Pseudomonas aeruginosa (esp piperacillin)

40

Adverse effects of PCNs?

- Hypersensitivity rxns (3-10%; cross-reactivity amongst all + some other beta-lactams) - Neurologic (seizures) (- Hematologic) (- GI) (- Interstitial nephritis)

41

What organisms do natural PCNs inhibit?

Gram +: PCN-susc. S. aureus (rare), *PCN-susc. S. pneumoniae, *group streptococci, viridans streptococci, enterococcus spp., bacillus spp. Gram -: *Neisseria spp., Pasteurella multocida. Anaerobes: above the diaphragm, *clostridium spp. Other: treponema pallidus (*syphilis; drug of choice)

42

What organisms do penicillinase-resistant penicillins inhibit?

Gram +: meth.-susc. S. aureus (*MSSA; target), group streptococci, viridans streptococci.

43

What organisms do aminopenicillins inhibit?

Gram +: pen. Susc. S. aureus (rare), pen. Susc. S. pneumoniae, group streptococci, viridans streptococci, *enterococcus spp., *listeria monocytogenes. *Gram -: Proteus mirabilis, some e coli, salmonella, shigella, beta-lactam h. influenzae.

44

What organisms do carboxypenicillins inhibit?

Gram +: "marginal" Gram -: Proteus mirabilis, some e coli, salmonella, shigella, beta-lactam h. influenzae, enterobacter spp., pseudomonas aeruginosa (target)

45

What organisms do ureidopenicillins inhibit? (Lots, maybe just name the 2 targets)

Gram +: Viridans strep, group strep, some enterococcus. Gram -: Proteus mirabilis, some e coli, salmonella, shigella, beta-lactam h. influenzae, enterobacter spp., *pseudomonas aeruginosa (target), serratia marcescens, some klebsiella spp. Anaerobes: faily good activity (target)

46

What organisms do beta-lactamase inhibitor-combos inhibit?

Gram +: S aureus (target; not MRSA). Gram -: H influenzae, e coli, proteus spp., klebsiella spp., Neisseria gonorrhea, moraella catarrhalis. Anaerobes (target): Bacterioids spp.

47

What is FQ's MoA? - Bacteriocidal or bacteriostatic?

Inhibition of DNA gyrase and topoisomerase IV - Bacteriocidal

48

What is FQ's primary mechanism of resistance? - What are some additional MoR's it has?

Chromosomal mutations in DNA gyrase or topoisomerase IV - Also development of efflux pumps, plasmid-mediated resistance, altered cell wall permeability (porins)

49

Which of the FQ's are active against gram-positive aerobes? (Which aren't, then?)

Levofloxacin, moxifloxacin, gemifloxacin (Not ciprofloxacin!)

50

Describe the relative activity of FQs against gram-negative aerobes. What about for pseudomonas?

cipro = levo > moxi cipro > levo, NOT moxi or gemi

51

Which of the FQ's are active against anaerobes?

Only moxifloxacin

52

Which of the FQ's are active against atypical bacteria?

All FQs

53

Which FQ(s) are useful against CA-PNA (CAP)?

Levo, moxi, gemi

54

Which FQ(s) are useful against HA-PNA?

Cipro (+ something for gram-positive coverage), levo

55

Which FQ(s) are useful against sinusitis/bronchitis?

All

56

Which FQ(s) are useful against UTI/prostatitis?

Cipro, levo

57

Besides previously mentioned, what else are FQs useful for? (not sure how to ask this question)

Bone infections, STD’s, TB, intra-abdominal w/ added anaerobe coverage

58

What are the most common adverse affects of FQs? (2) What else can occur?

GI, CNS - Prolonged QTc interval - Tendonitis, tendon rupture - Hepatotoxicity, photosensitivity, hypersensitivity, rash, articular damage

59

What demo should not use FQs? (contraindicated)

Pregnant women and children

60

What drugs do FQs interact w/?

- Divalent, trivalent cations: separate administration to avoid chelation and decreased absorption - Warfarin, cyclosporine, theophylline

61

Methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including PRSP), Viridans streptococci, and Enterococcus spp. are eg's of what class of bacteria?

Gram-positive aerobes

62

Enterobacteriaceae including Citrobacter spp. E. coli, Klebsiella spp, Enterobacter spp, Proteus spp, Salmonella, Shigella, Serratia marcescens, etc; H. influenzae, M. catarrhalis, Neisseria spp., and Pseudomonas aeruginosa are eg's of what class of bacteria?

Gram-negative aerobes

63

Bacteroides spp such as b. fragilis are eg's of what class of bacteria?

Anaerobes

64

Legionella pneumophila, Chlamydophila and Chlamydia spp., Mycoplasma spp. and Ureaplasma urealyticum are eg's of what class of bacteria?

Atypical bacteria

65

All of the FQs are eliminated mostly through the __________ with the exception of __________, which is eliminated through the __________.

- kidney - moxi - liver (therefore can't treat UTI)

66

Metronidazole is mainly used against what class of microbe?

Anaerobes

67

What is the MoA of metronidazole? - What molecule is responsible for this and how? - Bacteriocidal or bacteriostatic?

Inhibits DNA synthesis - Ferredoxins (which nlly make ATP). Metronidazole binds them and creates an e- sink. Drives more drug into cell and reactive species are made. - Bacteriocidal

68

How common is the development of resistance w/metronidazole? What are 2 ways in which bugs acquire resistance to metronidazole?

*Uncommon - Altered growth requirements (e.g. higher local O2 conc.) - Altered ferredoxin levels (lower levels)

69

What 2 types of anaerobic bacteria is metronidazole most active against?

- Bacteroides spp. (all) - Clostridium spp. (all)

70

Metronidazole: - IV/PO or both? - Does it penetrate the CSF? - How is it eliminated?

- Both - Yes - Liver

71

What are the clinical uses of metronidazole? Metronidazole is the drug of choice for _____________.

- Anaerobic Infections (including in the CNS): Intraabdominal, pelvic, (skin/soft tissue), diabetic foot and decubitus ulcer infections; brain abscess, trichomonas MILD to MODERATE c-dif dz

72

What are the most common side effects from metronidazole? What are the most serious side effects?

- GI (stomatitis--metallic taste) - CNS (peripheral neuropathy) - Teratogenic (avoid during pregnancy)

73

What 2 important drugs does metronidazole interact with?

- Warfarin (increased anticoagulant effect) - Alcohol (disulfiram rxn; don't give to alcoholics)

74

FQs are the DOC for what atypical bacterium?

* Legionella

75

What is the target organism for cipro and levo when targeting gram-negative aerobes?

Pseudomonas aeruginosa (NOT moxi)

76

What are the target organisms for levo, moxi, and gemi when targeting gram-positive aerobes?

- Methicillin-susceptible Staphylococcus aureus* - Streptococcus pneumoniae (including PRSP)*

77

Which FQ has good CSF penetration?

Moxifloxacin

78

Trichomonas vaginalis Entamoeba histolytica Giardia lamblia Gardnerella vaginalis are all examples of what class that metronidazole inhibits?

Anaerobic protozoa

79

Bacteroides spp. (ALL)* Fusobacterium Prevotella spp. Clostridium spp. (ALL)* Helicobacter pylori Are all examples of what class of organism that metronidazole inhibits?

Anaerobic bacteria

80

Name the 3 most important AGs. Which is a 4th that is less important?

- Gentamycin (gent) - Tobramycin (tobr) - Amikacin (amik) Streptomycin

81

Which is the most important AG?

Gentamycin

82

What is the general class(es) of organism(s) that gentamycin targets? What are the 3 organisms in this class that it's most effective against? (not sire if I need to be this specific)

Gram-negative *Can also target gram-pos if another drug allows it to get into the cell - E. coli, Klebsiella pneumoniae, Proteus

83

How does the activity of tobramycin differ from gentamycin?

Slightly weaker gram-neg activity but more effective against pseudomonas.

84

What type(s) of pathogen(s) is amikacin effective against?

- Nosocomial gram-negatives (except not as good as tobr for pseudomonas) - Mycobacterial (M. tuberculosis and atypical) - Other: nocardia (rare)

85

What type(s) of pathogen(s) is streptomycin effective against?

- Gram-pos: enterococcus (but gentamycin is preferable) - Mycobacterial (M. tuberculosis, but less effective against atypical vs. amikacin)

86

What type of drugs do AG's have synergy w/?

Cell-wall inhibitors (likely due to enhanced AG uptake)

87

What is unique about the distribution of AGs?

1000-fold higher conc. in urine vs. plasma (good for treating UTIs)

88

Differentiate b/w "traditional" (MDD) and "extended interval" (ODA) dosing.

- Traditional: multiple daily doses (q8-12 hrs) - Extended interval: once daily dosing (no less)

89

With conc-dependent killing, would you aim for higher or lower peak:MIC ratio?

Higher (make sure you understand why)

90

How is the post-antibiotic effect influenced by the peak:MIC ratio?

Bigger peak:MIC ratio = larger dose, and therefore larger PAE w/conc-dependent killing

91

Which is more likely to create resistance: infrequent large doses, or frequent smaller doses? (Why?) - Which leaves the bacterium more susceptible to killing?

Frequent smaller doses (bacteria more likely to survive) - 1 large dose more effective because bacteria more susceptible during drug-free time.

92

Which AGs are effective against gram-neg infections?

- Gentamycin - Tobramycin - Amikacin

93

What type of dosing is preferred when using AGs to fight gram-neg infections?

Extended interval (once daily) dosing

94

Which AGs are effective against gram-pos infections?

- Gentamycin - Strepamycin

95

What type of dosing is preferred when using AGs to fight gram-pos infections?

Traditional dosing * Counter to what has been said, but must be given in combo w/beta-lactam drug to get it into cell. Once in cell, there is synergy w/this other drug, and don't need as high of a dose

96

Which AGs are effective against mycobacterial infections?

- Amikacin - Streptomycin

97

What type of dosing is preferred when using AGs to fight mycobacterial infections?

Extended interval dosing (3 times weekly!) - Amikamycin preferable

98

Explain the reasons why extended-interval dosing is preferable to traditional dosing w/r/t AGs vs. gram-neg bacteria. (6)

- Concentration-dependent bactericidal activity - Post-antibiotic effect (PAE) - Adaptive resistance - *Minimize toxicities - Cost savings - Efficacy

99

What are some factors that influence PAE? (4, not too important)

- Organism - Drug concentration - Duration of drug exposure - Antimicrobial combinations

100

What are the 2 major toxicities related to AGs?

- Nephrotoxicity - Ototoxicity

101

If gram-neg bacteria suspected, AGs can be used for the empiric treatment of __________, especially from a urinary source. What other conditions could they be used for?

Sepsis - Intraabdominal infections - Skin/soft tissue infections

102

If a pt has a h/o CF, which AG would you choose and why?

*Tobramycin (pt is more susceptible to pseudomonas)

103

If treating PNA with AGs, would you use a low, medium, or high dose?

High

104

Recall: when using gentamycin (or sometimes streptomycin) to treat gram positive infections, you would normally combine it with ___________, or sometimes even ___________ for severe infections (e.g. enterococcal or staphylococcal).

- Beta-lactams (ampicillin, nafcillin) - Vancomycin (recall: lower, traditional dosing)

105

What part of the kidney is affected by AG nephrotoxicity?

Proximal tubule (AG uptake is saturable here)

106

How are AG's administered? What are the exceptions?

They are all administered IV and IM (not PO)

107

What are AG's mech of action? (Cidal or static?)

Irreversibly bind to 30S ribosomal subunit to inhibit ptn synth (bacteriocidal).

108

What are AG's mech of resistance?

Synthesis of AG-modifying enzymes (often via plasmid), altered AG uptake (efflux pump of loss of porin channel), change in ribosomal binding site/target modification

109

What organ eliminates AGs?

Kidneys (dose must be adjusted in kidney failure)

110

List the organisms that 1st gen cephalosporins are effective against. Which is target?

Gram-pos: - MSSA (*target) - PCN-susc. Strep pneumo - Group streptococci - Viridians streptococci Grem-neg: (PEK) = - Proteus mirabilis - E. coli - Klebsiella pneumoniae

111

List the organisms that 2nd gen cephalosporins are effective against. *Which group is unique to this gen?

Gram-pos: (slightly less active than 1st gen) - MSSA (*target), PCN-susc. Strep pneumo, Group streptococci, Viridians streptococci. Gram-neg: (HENPEK) = - H. influenzae - Enterobacter spp. - Neisseria spp. - Proteus mirabilis - E. coli - Klebsiella pneumoniae (+ M. catarrhalis). Anaerobes: Bacteroides fragilis /group

112

List the organisms that 3rd gen cephalosporins are effective against. *Which is target?

Gram-neg (HENPECKSSS P) = - H. influenzae - Enterobacter spp. - Neisseria gonorrhoeae - Proteus mirabalis - E. coli - Citrobacter spp. - Klebsiella pneumoniae - Serretia marcescens - Salmonella spp. - Shigella spp.; *Pseudomonas aeruginosa (target) (still have gram-pos activity but less active than earlier gens)

113

Which 3rd gen. cephalosporin does NOT target pseudomonas, unlike the others? Which would you use instead?

Ceftriaxone - Ceftazidime

114

How does the activity of 4th gen cephalosporins change compared to 3rd gen?

Gram-pos: similar to ceftriaxone. Gram-neg: Similar to ceftriaxone but also adds: - Pseudomonas aeruginosa - Beta-lactamse-producing enterobacter spp.

115

List the categories/organisms that 5th gen cephalosporins are effective against. *Which is unique to this gen?

Resp pathogens - H. influenzae - strep. Pneumoniae - Moraxella - Staph aureus. Gram-pos + SSSI: - Strep pneumonia *MRSA*

116

*What important organisms are cephalosporins NOT active against? (6)

SMACLE - Stenotrophomonas maltophilia - MRSA (*except for the 5th gen) - Atypical bacteria (eg Legionella; cuz no cell wall) - C-diff - Listeria - Enterococcus spp.

117

All cephalosporins are eliminated via the ___________ except for ___________ and ___________ (how are each eliminated?)

- Kidney - Ceftriaxone (bile) - Cefoperazone (liver)

118

Which gens of cephalosporins are used for surgical prophylaxis?

1st and 2nd (2nd for more intense surgeries?)

119

What are some of the uses of ceftriaxone? (4 orgs)

- Uncomplicated gonorrhea (single IM dose) - CAP - PRSP - Viridans strep endocarditis

120

What's the most important organisms that 4th gen cephalosporins cover (that ceftriaxone doesn't)?

Pseudomonas

121

What are the major adverse effects of all gen cephalosporins? (2)

1. Hypersensitivity 2. C-diff

122

- Are Carbapenems broad or narrow spectrum? - What major groups are they effective against? - What are their target organisms?

- Most broad-spectrum available - Many gram-pos and gram-neg aerobes, as well as gram-pos/neg anaerobes. - Targets: MSSA, bacteroides.

123

*What organisms are carbapenems NOT effective against? (7)

*NOT effective against: MRSA, PRSP, VRE, coag-neg staph, c-dif, atypical bacteria, S. maltophila

124

-______________, a carbapenem, undergoes hydrolysis by a dihydropeptidase enzyme in the ________________ to a toxic metabolite. - Therefore, it's comarketed with _________, a DHP inhibitor (to prevents this)

- Imipenem - Renal brush border (hepatotoxic) - Cilastatin (not on test, but USMLE)

125

What major drug category do cephalosporins fall under? Carbapenems?

- Beta-lactams - Beta-lactams

126

What are carbapenem's mech of action? - Baciocidal or static? - Time or conc-dependent?

Inhibitors of cell wall synthesis by binding to and inhibiting PBPs; primary target is PBP-2 - Bacteriocidal - Time-dependent

127

Name the major carbapenems. - Which 2 are the "best"?

DIME - Doripenem (best) - Imipenem (best) - Meropenem - Ertapenem

128

What are the mechs of resistance for cephalosporins? (which is most important?)

- Beta-lactamase enzymes (most important) - PBP alteration - Decreased membrane penetration

129

Beta-lactams are all cross-allergenic except for which one?

Aztreonam

130

Are cephalosporins bacteriocidal or bacteriostatic?

Bactericidal

131

Which subset of the cephalosporins are the only ones that have activity against anaerobes? - Which generation is it in?

Cephamycins - 2nd gen

132

*What gen. cephalosporin is used for the treatment of meningitis?

3rd gen

133

When treating meningitis w/3rd gen cephalosporins, if pseudomonas is suspected or present, what specific drug would you use?

Ceftazidime

134

What is the main thing that 5th gen cephalosporins are used for?

Drug-resistant organisms

135

Why were cephalosporins developed?

Beta lactams that are less susceptable to beta-lactamase enzymes.

136

Why were carbapenems developed?

- Extended spectrum of activity - Further beta-lactamase stability

137

What are the clinical uses of carbapenems?

- Empiric therapy for HA-infections - Polymicrobial infections - Infections due to β-lactamase-producing organisms (SPICE, SPACE, others)

138

*If pseudomonas is suspected, which carbapenem would you avoid?

*Avoid ertapenem if pseudomonas suspected

139

What are the main adverse effects of carbapenems?

- CNS (e.g. seizures) - GI - Hypersensitivity

140

Do carbapenems have hypersensitivity/cross-reactivity w/PCNs like cephalosporins do?

Yes

141

What category of drug is a monobactam? - How can it be administered?

Synthetic monocyclic beta-lactam - IV

142

Monobactams are beta-lactams. What specific part of the cell wall do they target? - What is the main class of organisms they target?

PBP-3 - of gram-negative aerobes

143

Recall: what class of organisms do monobactams inhibit? - What's its main target?

Gram-neg aerobes * Pseduomonas

144

Recall: what is the class of drugs that aztreonam is a member of? Since aztreonam is the only beta-lactam that does have cross-allergencitiy, what clinical implications does this have?

- Monobactams - Can be used in PCN-allergic pts

145

What are the major adverse effects of monobactams?

N/D

146

What are the major adverse effects for 2nd gen cephalosporins, besides hypersensitivity and c-diff?

- Hypoprothrombinemia - Ethanol intolerance due to disulfiram-like rxn

147

Which gen's of cephalosporins inhibit pseudomonas?

- 3rd (except ceftriaxone) - 4th

148

Which gen of cephalosporins are effective against anaerobes like bacteroides?

2nd gen only

149

What are the 3 phenotypes of vancomycin resistance?

vanA, vanB, vanC

150

What group of organisms is vancomycin capable of killing? (name the class and the 5 major targets)

Gram-pos ONLY - *MRSA, *MSSA, *coag-negative staph, *PRSP, *c-dif (clostridium spp.) - Also targets other strep pneumoniae, viridians strep, group strep, enterococcus, corynebacterium, bacillus, listeria, actinomyces, clostridium spp., peptococcus, peptostreptococcus.

151

Since vanc is distributed widely in the tissues, you should use ________________ for dosing.

TBW (total body weight?)

152

How long does it take for vanc to distribute into the tissues?

1 hour - Peak should be drawn 1 hr post-infusion

153

For vancomycin, elimination T1/2 depends on _______ function.

renal function

154

Can pts who are allergic to PCNs be given vancomycin?

Yes! (different structure)

155

What's an e.g. of a target of vancomycin that is a multi-drug-resistant bacterium?

PCN-resistant streptococcus pneumoniae (PRSP)

156

Vanc treats ______-______ c-dif colitis.

moderate-severe

157

Recall: what drug is used to treat mild-mod c-diff?

Metronidazole

158

How does Red Man Syndrome occur? - Which drug is it a/w?

Infusion of vancomycin at too high a RATE - Also a/w other glycopeptides

159

In what specific type of infection would you prefer the 2nd gen glycopeptide dalbavancin to vancomycin? - Which genes must be present?

VRE (must have vanB or vanC gene, not vanA.)

160

What is the MoA of vancomycin?

Binds D-ala-D-ala to inhibit cell wall synthesis

161

What is the MoA of linezolid? (is resistance common or uncommon?)

Binds 50S ribosomal binding site (resistance rare)

162

What is the major class that linezolid can inhibit? List the main targets. - What is the other class?

Gram-pos: - *MSSA - *MRSA - *VRSA, - strep-pneumoniae (including *PRSP), - **enterococcus faecium and faecalis (including *VRE) Also: viridian streptococci, group streptococci, coag-neg staph, bacillis, listeria, clostridium spp (except c-diff), peptostreptococcus, c. acnes. Atypical bacteria: mycobacteria

163

What is unique about the pharmacology of linezolid?

100% bioavailable

164

What major category of pathogens is linezolid generally used for? What body area category is it NOT used for?

* Serious/complicated infections caused by resistant gram-positive bacteria: - Not used for UTIs

165

What is linezolid contraindicated with and what condition does it cause?

- SSRIs, MAOIs - Serotonin syndrome

166

What are the major side effects a/w linezolid?

* Thrombocytopenia/anemia - SSRIs/MAOIs: serotonin syndrome. - Lactic acidosis - BM suppression - Neuropathy

167

What category of drugs are linezolid and tedizolid?

Oxazolinidones

168

What's the advantage of tedizolid over linezolid? Why isn't tedizolid prescribed more often?

- Doesn't cause serotonin syndrome - It's even more expensive than linezolid

169

What class of drugs does daptomycin belong in?

Lipopeptide

170

What class of bacteria is daptomycin active against? Name the bacteria. (*or at least the targeted ones).

Gram-pos: *MRSA *MSSA *VRSA coag-neg staph strep pneumoniae (including *PRSP) viridians streptococi group streptococci *Enterococcus faecium and farcalis (including *VRE)

171

*Daptomycin should NOT be used in the treatment of _____________.

*Pneumonia

172

*What is the major adverse effect a/w daptomycin?

Myopathy and CPK elevation (must continually monitor them)

173

Glycopeptides: mech of action (be specific)? - Time or conc-dependent? - Static or cidal?

Inhibits cell wall synth at a site different than beta-lactams, binding to D-alanyl-D-alanine portion of cell wall, preventing cross-linking. - Time-dependent - Bacteriocidal

174

Vancomycin: mech of resistance? - In what 2 organisms, specifically, is this an issue?

Resistant in VRE/VRSA due to change in D-alanyl-D-alanine binding site of PG.

175

Which glycopeptide is more potent than vanc?

Dalbavancin

176

How can linezolid be administered?

PO or IV

177

What class of drug is the quinupristin-dalfopristin combo? - MoA? - Static or cidal?

Synercid - Streptogramins - Protein synthesis inhibitor (50S ribosomal subunits; late stages) - Bacteriostatic, but syngeristic together to be bacteriocidal.

178

What organism class are quinupristin-dalfopristin effective against? - What is the main target organism? What others are its targets?

Gram-positives, namely VRE. Gram-positive organisms (developed for VRE) - Enterococcus faecium (including VRE)* - MSSA, MRSA - Coagulase-negative staphylococci* - PRSP*, and many more. Also coverage vs. gram-neg aerobes and atypical bacteria (in vitro).

179

How is quinupristin-dalfopristin cleared?

Hepatically/biliary

180

What are the glycopeptides we need to know?

VDTO - Vancomycin - Dalbavancin - Telavancin - Oritavancin

181

Name the 3 major side effects a/w vancomycin.

- Red man syndrome - Nephrotoxicity - Ototoxicity

182

Name the major side effects a/w dalbavancin.

GI s/s, skin rxns + flushing - Can also get red man syndrome

183

Name drugs that are highly active/focused towards vs. resistant gram-pos organisms.

Vancomycin Dalbavancin Telavancin Oritavancin Linezolid Tedizolid Daptomycin Quinupristin-dalfopristin

184

Quinupristin-dalfopristin: mech of resistance?

- Alterations in ribosomal binding sites (erm) - Enzymatic inactivation - Active transport out of the cell

185

Via what route is quinupristin-dalfopristin absorbed? - Does it penetrate CSF?

Parenterally - Minimally

186

How is quinupristin-dalfopristin eliminated?

Both via hepatic and biliary

187

What are the main clinical uses for Synercid (quinupristin-dalfopristin)? (2)

- VRE bacteremia - Complicated skin and soft tissue infections due to MSSA or Streptococcus pyogenes

188

Does quinupristin-dalfopristin affect CYP450?

P450 3A4 Inhibitor

189

Adverse effects of quinupristin-dalfopristin?

- Sever GI intolerance (N/V/D) - Venous irritation

190

Although tetracyclines are cross-reactive, ____________ is resistant to this because it is in the tetracyclin derivative category known as ____________.

*Tigecycline - Glycylcylins

191

What classes of microbials can tetracyclines be used against? (list some of the major targets) What 2 general conditions are they commonly used to treat?

- Gram-pos aerobes (*MSSA) - Gram-neg aerobes - Anaerobes - bacteroides spp. - Misc. bacteria. - legionella, chlamydophila, chlamydia, mycoplasma, ureaplasma, rickettsia (sketchy) - Often used for STI infections and dz's caused by tick bites!

192

Does tigecyclin have a more or less broad spectrum of activity vs. tetracyclins? Which organism is tigecyline notably not active against?

- Broader * Pseudomonas

193

Although tetracyclines are cross-reactive, ____________ is resistant to this because it is in the tetracyclin derivative category known as ____________.

*Tigecycline - Glycylcylins

194

What classes of microbials can tetracyclines be used against? (list some of the major targets) What 2 general conditions are they commonly used to treat?

- Gram-pos aerobes (*MSSA) - Gram-neg aerobes - Anaerobes - bacteroides spp. - Misc. bacteria. - legionella, chlamydophila, chlamydia, mycoplasma, ureaplasma, rickettsia (sketchy) - Often used for STI infections and dz's caused by tick bites!

195

Although tetracyclines are cross-reactive, ____________ is resistant to this because it is in the tetracyclin derivative category known as ____________.

*Tigecycline - Glycylcylins

196

What classes of microbials can tetracyclines be used against? (list some of the major targets) What 2 general conditions are they commonly used to treat?

- Gram-pos aerobes (*MSSA) - Gram-neg aerobes - Anaerobes - bacteroides spp. - Misc. bacteria. - legionella, chlamydophila, chlamydia, mycoplasma, ureaplasma, rickettsia (sketchy) - Often used for STI infections and dz's caused by tick bites!

197

Does tigecyclin have a more or less broad spectrum of activity vs. tetracyclins? Which organism is tigecyline notably not active against?

- Broader * Pseudomonas

198

Besides being inactive vs. pseudomonas, what 2 other conditions does tigecycline NOT treat?

*UTIs and *bacteremia

199

*What type of meds are tetracyclines and glycylcyclines contraindicated with?

Di and tri-valent cations (they should even avoid dairy due to Ca2+) - Must separate administration by a few hours

200

What are the major serious side effects a/w tetracyclines/tigecycline?

- Severe N/V - Photosensitivity (should avoid sun)

201

What can occur if expired tetracyclines are prescribed?

Fanconi-like syndrome a/w renal failure

202

What drug acts synergistically w/sulfas?

Trimethoprim (also inhibits folate/purine synth pw but at a different enzyme--dihydrofolate reductase)

203

What is the precursor of purine synthesis? - How is it affected by purine synthesis pw inhibitors?

PABA - Builds up

204

What drugs are in the combination Bactrim?

Trimethoprim-Sulfamethoxazole (TMP-SMX)

205

Explain the target organisms (only) of the broad-spectrum antibiotic TMP-SMX (Bactrim).

gram-pos: *staph aureus (MRSA, CA-MRSA) Gram-neg: - Stenotrophomonas maltophilia. Other: - Pneumocystis carinii. Plus many more (broad spectrum)

206

When giving Bactrim, what lab level should be monitored and why?

CrCl (kidney function; eliminated partially by kidney)

207

*What are the (3) major clinical uses of TMP-SMX?

1. Acute, chronic, or recurrent UTIs 2. Acute or chronic bacterial prostatitis 3. Skin infections due to CA-MRSA

208

What are the major adverse effects a/w TMP-SMX/Bactrim?

- Leukopenia - Thrombocytopenia - Rash/hypersensitvity - Renal impairment (crystaluria)

209

Are dose adjustments required in renal failure when giving chloramphenicol?

No, metabolized by liver

210

*What 2 major adverse effects are the reason that chloramphenicol isn't available in the U.S.?

- Gray Baby Syndrome (resp failure, death) - Aplastic anemia (no RBC production)

211

What are the 2 urinary tract agents that we need to know?

- Nitrofurantoin - Methenamine

212

What is nitrofurantoin used for? What is methenamine used for?

- Nitrofurantoin: used solely for UTIs - Methenamine: used solely as prophylaxis for UTIs if they’ve had recurrent UTIs

213

Which of the enterobacteriacea are lactose fermenters and which are non-lactose fermenters? (All ferment glucose, oxidase negative, reduce nitrate, and use MacConkey)

- Lactose fermenters: E. coli, klebsiella, Enterobacter, Citrobacter, Serratia - Non-lactose fermenters: Salmonella, Shigella, Proteus, Yersinia

214

Distinguish the characteristics of the 5 types of E. coli.

o Enterotoxigenic E. coli (ETEC): Profuse watery diarrhea (Traveler’s diarrhea) o Enteropathogenic E. coli (EPEC): infants; diarrhea w/mucus but no gross blood o Enteroinvasive E. coli (EIEC): blood, mucus, and many leukocytes in stool o Enterohemorrhagic E. coli (EHEC): Bloody diarrhea w/o pyuria. May progress to HUS. ♣ Shiga-toxin producing E. coli (STEC) via E. coli O157:H7 o Enteroaggressive E. coli (EAggEC): Watery diarrhea w/blood and mucus

215

MoA for tetracyclines/glycylcyclines? - Static or cidal?

Reversibly bind 30S ribosomal subunit to inhibit ptn synth. - Bacteriostatic.

216

Mech of resistance for tetracyclines/glycylcyclines? (Which drug is more resistant to these mechs?)

- Efflux pumps - Ribosomal protection proteins - Enzymatic inactivation (Tigecycline more resistant to these mechs)

217

Where's an important body areas that Tetracyclines/Glycylcyclines, distribute to? - What about Bactrim?

Prostate - Same for bactrim

218

What 2 tetracyclines/glycylcyclines are excreted, unchanged, in the urine?

Demeclocycline/tetracycline

219

Do tetra/glycylcyclines have to be modified w/renal disease?

No - Doxycycline, minocycline (metab) and tigecycline (biliary) - excreted mainly by non-renal routes

220

What is tigecycline often used to treat?

Polymicrobial infections

221

Which demo is tetra/tigecycline contraindicated in?

Pregnant (category D) - Affects their children (e.g. teet

222

What's the MoA of sulfonamides? - Static or cidal?

Inhibits dihydropterate reductase (folate/purine synthesis) - Bacteriostatic.

223

What's the MoA of trimethoprim? - Static or cidal, when combined w/sulfas?

Inhibits dihydrofolate reductase - Becomes cidal w/bacteriostatic sulfas

224

What is another name for Trimethoprim-Sulfamethoxazole (TMP-SMX)? - How is the spectrum of activity/resistance affected when the drugs are combined?

Bactrim - Broader spectrum, decreased resistance

225

What organism group does bactrim not have activity against?

Anaerobes

226

What organisms are targeted by chloramphenicol?

- Gram-pos - Gram-neg - Anaerobes (+ and -), etc. (3rd world use only)

227

What is chloramphenicol's MoA? (cidal or static)

Binds 50S ribosomal subunit (bacteriostatic)

228

(MoA). In acidic pH, methenamine is converted to ammonia and ____________.

Formaldehyde

229

What is the MoA for nitrofurantoin?

Not well understood

230

Besides tetracyclines, what other drug class are di-tri-valent cations contraindicated in?

Fluoroquinolones (cipro, levo, moxi, gemi)

231

Clindamycin: mech of resistance?

- Altered target sites – encoded by the erm gene, which alters 50S ribosomal binding site; confers high level resistance to macrolides, clindamycin and Synercid (MLSb resistance) - Active efflux – mef gene encodes for an efflux pump that pumps antibiotic out of the cell - Drug inactivation

232

Describe the spectrum of activity of clindamycin.

Gram positive aerobes: - *MSSA and some CA-MRSA - PSSP: PCN-susc. strep pneumo - Group + viridians strep Anaerobes: * Some bacteriodes spp. - Peptostreptococcus, actinomyces, prevotella spp, propionibacterium, fusobacterium, clostridium spp. (not C. difficile) Other bacteria: - Pneumocystis carinii, Toxoplasmosis gondii, Malaria

233

How is clindamycin administrated? What is the % absorption?

IV, PO (90% absorption, can switch b/w IV and PO)

234

Does clindamycin penetrate the CSF?

Not really

235

Clindamycin primarily metabolized by the ___________. - Does it need adjustments during renal failure? - Is it removed during hemodialysis?

- Liver - Doesn't need adjustments during renal failure - No

236

What are the clinical uses of clindamycin?

- Anaerobic Infections OUTSIDE of the CNS: Pulmonary, intraabdominal, pelvic, diabetic foot and decubitus ulcer infections - Skin & Soft Tissue Infections: Good option for PCN-allergic patients and infections due to CA-MRSA - Alternative therapy: C. perfringens, PCP, Toxoplasmosis, malaria, bacterial vaginosis

237

What are the 2 main side-effects for clindamycin?

- GI - *C-diff colitis (one of the main inducers)

238

What category of drug does clindamycin belong?

Lincosamide

239

What are the 3 macrolides we should know?

- Azithromycin - Clarithromycin - Erythromycin

240

Which 2 macrolides are derivatives of the other?

Azithromycin and clarithromycin derivatives of erythromycin

241

How do azithro and clarithromycin improve upon erythromycin?

- Broader spectrum of activity - Improved PK properties: better bioavailability, better tissue penetration, prolonged half-lives - Improved tolerability

242

Macrolides: MoA? - Cidal or static?

- Reversibly binding to the 50S ribosomal subunit - Static (cidal at high conc)

243

Which of the macrolides and time-dependent, and which are conc.-dependent?

- Erythromycin and clarithromycin are time-dependent - Azithromycin is conc-dependent

244

Macrolides: mech of resistance?

- Active efflux pump (mef gene) - Altered target sites (erm gene)

245

What is the spectrum of activity for macrolides? (groups are targets)

- Gram-pos aerobes (*MSSA) - Gram-neg aerobes - Anaerobes (esp. upper airway) - Atypical bacteria (*Legionella, DOC) - Other bacteria

246

What bacterium do macrolides importantly NOT have activity against?

Enterobacteriacea (gram-neg aerobe class)

247

What are the relative levels of activity for the 3 macrolides against gram-positive aerobes?

CEA Clarithro > Erythro > Azithro (ACE for gram-neg)

248

What are the relative levels of activity for the 3 macrolides against gram-negative aerobes?

ACE Azithro > Clarithro > Erythro (CEA for gram-pos)

249

Discuss the bioavailabilities of each of the of the 3 macrolides. - Which are acid stable?

- Erythromycin: variable absorption (15 to 45%) - Clarithromycin: well-absorbed (55%) - Azithromycin: 37% bioavail. regardless of food Acid stable: Clarithromycin and azithromycin

250

Do macrolides penetrate the CSF?

Not really

251

Describe the elimination routes of each of the 3 macrolides. * Which are metabolized by CYP450 enzymes?

- Erythromycin: excreted in bile, metabolized by *CYP450 - Clarithromycin: also metabolized (*CYP450) and partially eliminated by the kidney - Azithromycin: liver, NO CYP450

252

Name the clinical uses of macrolides.

Respiratory Tract Infections - Pharyngitis/ Tonsillitis: PCN-allergic pts - Sinusitis, COPD exacerbation, OM - CA-PNA: monotherapy in outpatients; with ceftriaxone for inpatients Uncomplicated Skin Infections STDs MAC Alternative for PCN-Allergic pts: - Group A Strep upper respiratory infections - Prophylaxis of bacterial endocarditis - Syphilis and gonorrhea - RF prophylaxis

253

Which macrolide is best when H. influenzae is suspected?

Azithromycin

254

Which macrolide is best for STDs?

Azithromycin

255

How are macrolides used to treat MAC (mycobacterium avium complex)? I hope to god this doesn't come up

- Azithromycin for prophylaxis - Clarithromycin/ Azithromycin for tx

256

What are the adverse effects of macrolides? (there is 1 common group and the others are rare)

- GI (only ones that are common) - Cholestatic hepatitis (rare) - Thrombophlebitis - Prolonged QTc - Ototoxicity (tinnitus/deafness)

257

*Erythromycin and clarithromycin– are inhibitors of cytochrome p450 system in the liver and may increase concentrations of: (just read)

Theophylline Digoxin, Disopyramide Carbamazepine Valproic acid Cyclosporine Terfenadine, Astemizole Phenytoin Cisapride Warfarin Ergot alkaloids

258

Name all of the cell wall inhibitor drug classes we've learned andtheir specific protein targets.

PCN (PBP), cephalosporins (PBP), carbapenems (PBP-2), monobactams (PBP-3), glycopeptides (D-ala-D-ala)

259

Name all of the 30S ribosome inhibitor drug classes we've learned.

AG's, tetracyclins

260

Name all of the 50S ribosome inhibitor drug classes that we've learned.

Oxazolidinones, quinupristin-dalfopristin, chloramphenicol, clindamycin, macrolides

261

Name all of the folate pw inhibitor drug classes that we've learned.

Sulfas, trimethoprim

262

Name all of the DNA gyrase/topoisomerase inhibitor drug classes that we've learned.

FQs

263

Name all of the DNA synthesis inhibitor drug classes that we've learned.

Metronidazole (via ferrodoxins)

264

Causes of meningitis in newborns?

6 months - 6 years?

Adolescents/young adults?

Older adults?

Newborns: Group B Streptococcus, Escherichia coli, Listeria monocytogenes, Elizibethkingia meningoseptica, Citrobacter

6 months - 6 years: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae

Adolescents/young adults: Neisseria meningitidis, Streptococcus pneumoniae

Older adults: Listeria monocytogenes, gram-neg rods (?), *Streptococcus pneumoniae*, Neisseria meningitidis, Haemophilus influenzae type b (Hib), Group B Streptococcus

 

***Strep pneumo is highest overall (doesn't occur in neonates; kids are the reservoir)

265

Define each bioterrorism category, and name the 3 diseases we need to know a/w bioterrorism categories A and B.

  • Category A: easy dissemination, high mortality, public panic, special response
    • Eg’s = Anthrax (bacillus anthraces), Plague (Yersinia pestis), Tularemia (Francisella tularemia)
  • Category B: Mod easy to disseminate, mod morbidity, low mortality, ^ CDC dx and surveillance
    • Eg’s = Brucellosis (Brucella spp.), Food safety threats (salmonella spp., E. coli 0157:H7, Shigella), Melioidosis (Burholderia pseudomallei)
  • Category C: emerging pathogens, could be modified for mass dissemination and fatalities; available

266

What are the 5 organisms a/w neonatal meningitis?

- Which was formerly a cause but eliminated via vaccine?

- Which of the 5 is less common because we test mothers?

- Overall most common cause amongst all age groups?

E coli, GBS, citrobacter, listeria, and elizibethkingia

- Haemofluas influenzae

- GBS (vaginal swag)

- Strep pneumo

267

268

What specific organism do you not use ABX to treat?

STEC (specifically)

269

270

Do beta-lactams (PCNs, cephalosporins, carbapenems, monomactams) generally display time or conc-dependent killing?

*Time-dependent

271

Name the abx eliminated by the kidney. (Good review) Liver?

Kidney: beta-lactams, vancomycin, the aminoglycosides, some FQs, Bactrim, daptomycin, tetracycline (Big, tearful dalmations teased Amy's vag, some F'd).

Liver: Macrolides, Synercid, linezolid, clindamycin, metronidazole, some FQs, Bactrim, doxycycline, tigecycline.

272

What is the DOC for Stenotrophomonoas maltophilia?

Bactrim