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Flashcards in Test 3 SHUFFLED Deck (275):
1

Name the 3 major side effects a/w vancomycin.

- Red man syndrome - Nephrotoxicity - Ototoxicity

2

Metronidazole is mainly used against what class of microbe?

Anaerobes

3

What is the name of the carboxypenicillin?

Ticarcillin (not avail.)

4

Which AGs are effective against mycobacterial infections?

- Amikacin - Streptomycin

5

What is unique about the pharmacology of linezolid?

100% bioavailable

6

Which gens of cephalosporins are used for surgical prophylaxis?

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

7

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

8

How is clindamycin administrated? What is the % absorption?

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

9

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

10

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

Pseudomonas aeruginosa (NOT moxi)

11

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

12

*Name the main target organisms of natural penicillins.

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

13

Which FQ has good CSF penetration?

Moxifloxacin

14

How does the activity of tobramycin differ from gentamycin?

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

15

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)

16

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

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

17

What bacterium do macrolides importantly NOT have activity against?

Enterobacteriacea (gram-neg aerobe class)

18

What are the 3 macrolides we should know?

- Azithromycin - Clarithromycin - Erythromycin

19

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.

20

What 2 drugs are contained in Timentin?

Ticarcillin-clavulanate

21

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

All

22

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

Dicloxacillin

23

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

- Severity - Site - Organism

24

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

- Broader * Pseudomonas

25

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

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

26

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

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

27

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

Myopathy and CPK elevation (must continually monitor them)

28

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

29

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

*Tigecycline - Glycylcylins

30

Does clindamycin penetrate the CSF?

Not really

31

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

All FQs

32

Which demo is tetra/tigecycline contraindicated in?

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

33

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

Metronidazole

34

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

Synthetic monocyclic beta-lactam - IV

35

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)

36

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

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

37

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.

38

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)

39

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

- Unasyn - Timentin - Zosyn - Augmentin

40

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

41

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

Higher (make sure you understand why)

42

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

Levo, moxi, gemi

43

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

44

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.

45

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

- Broader * Pseudomonas

46

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

47

What 2 important drugs does metronidazole interact with?

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

48

Are dose adjustments required in renal failure when giving chloramphenicol?

No, metabolized by liver

49

*Name the main target organisms of aminopenicillins.

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

50

51

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

Short (

52

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

FQs

53

*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

54

What are the 2 groups of natural PCNs?

PCN G and PCN VK (oral)

55

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

Anaerobes

56

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

Hospital-acquired infections

57

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

Metronidazole (via ferrodoxins)

58

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

59

What drugs do FQs interact w/?

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

60

MoA for tetracyclines/glycylcyclines? - Static or cidal?

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

61

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).

62

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

PCN-resistant streptococcus pneumoniae (PRSP)

63

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

64

What part of the kidney is affected by AG nephrotoxicity?

Proximal tubule (AG uptake is saturable here)

65

What class of drugs does daptomycin belong in?

Lipopeptide

66

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

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

67

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

*Pneumonia

68

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

Extended interval (once daily) dosing

69

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

70

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)

71

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

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

72

How is quinupristin-dalfopristin cleared?

Hepatically/biliary

73

Which AGs are effective against gram-pos infections?

- Gentamycin - Strepamycin

74

FQs are the DOC for what atypical bacterium?

* Legionella

75

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

Oxazolidinones, quinupristin-dalfopristin, chloramphenicol, clindamycin, macrolides

76

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

- Both - Yes - Liver

77

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

Vancomycin Dalbavancin Telavancin Oritavancin Linezolid Tedizolid Daptomycin Quinupristin-dalfopristin

78

Name the major side effects a/w dalbavancin.

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

79

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

- PRSP - MRSA

80

*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

81

What is the name of the ureidopenicillin?

Piperacillin

82

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

Ceftazidime

83

What 2 drugs are contained in Zosyn?

Piperacillin-tazobactam

84

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.

85

What is the route of administration for PCN VK?

PO (acid stable)

86

What are the 4 types of penicillinase-resistant penicillins?

Nafcillin, oxacillin, methacillin, dicloxacillin

87

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

Inhibition of DNA gyrase and topoisomerase IV - Bacteriocidal

88

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

89

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)

90

What is unique about the distribution of AGs?

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

91

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

1. Hypersensitivity 2. C-diff

92

What organisms are targeted by chloramphenicol?

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

93

What are the clinical uses of carbapenems?

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

94

Are PCNs time- or conc-dependent killing?

- Time-dependent

95

Which gen's of cephalosporins inhibit pseudomonas?

- 3rd (except ceftriaxone) - 4th

96

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)

97

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!

98

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

PABA - Builds up

99

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

- Meningitis - Endocarditis - Osteomyelitis - Febrile neutropenia

100

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

TBW (total body weight?)

101

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)

102

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

Anaerobic bacteria

103

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

Formaldehyde

104

Are cephalosporins bacteriocidal or bacteriostatic?

Bactericidal

105

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

High

106

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

Infections due to MSSA such as skin and soft tissue infections

107

What are the 2 main side-effects for clindamycin?

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

108

*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)

109

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.

110

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

Demeclocycline/tetracycline

111

What organisms do penicillinase-resistant penicillins inhibit?

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

112

What are the 2 major toxicities related to AGs?

- Nephrotoxicity - Ototoxicity

113

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!

114

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

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

115

What are the 3 phenotypes of vancomycin resistance?

vanA, vanB, vanC

116

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

Sulfas, trimethoprim

117

Adverse effects of quinupristin-dalfopristin?

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

118

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

Fluoroquinolones (cipro, levo, moxi, gemi)

119

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

120

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

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

121

*Name the main target organisms of Carboxypenicillins and Ureidopenicillins.

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

122

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

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

123

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

124

Why were carbapenems developed?

- Extended spectrum of activity - Further beta-lactamase stability

125

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)

126

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

*Tigecycline - Glycylcylins

127

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

128

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

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

129

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

CrCl (kidney function; eliminated partially by kidney)

130

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

Binds 50S ribosomal subunit (bacteriostatic)

131

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

132

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)

133

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

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

134

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)

135

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)

136

What drug acts synergistically w/sulfas?

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

137

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

Yes

138

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

Aztreonam

139

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

140

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

*Tobramycin (pt is more susceptible to pseudomonas)

141

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

Gram-positive aerobes

142

143

What are the 2 aminopenecillins?

Ampicillin and amoxicillin

144

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

- Hypoprothrombinemia - Ethanol intolerance due to disulfiram-like rxn

145

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

More time above MIC (cuz time-dependent killing)

146

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

Binds 50S ribosomal binding site (resistance rare)

147

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

*Time-dependent

148

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

149

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

150

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

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

151

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

152

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

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

153

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

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

154

*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.

155

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

156

What is the DOC for Stenotrophomonoas maltophilia?

Bactrim

157

Adverse effects of PCNs?

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

158

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

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

159

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

160

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

161

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

162

What are the glycopeptides we need to know?

VDTO - Vancomycin - Dalbavancin - Telavancin - Oritavancin

163

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

164

What category of drugs are linezolid and tedizolid?

Oxazolinidones

165

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

166

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

*Avoid ertapenem if pseudomonas suspected

167

What is the MoA of vancomycin?

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

168

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

Anaerobic protozoa

169

Which macrolide is best when H. influenzae is suspected?

Azithromycin

170

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

171

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

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

172

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)

173

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

Gram-neg aerobes * Pseduomonas

174

Can pts who are allergic to PCNs be given vancomycin?

Yes! (different structure)

175

How can linezolid be administered?

PO or IV

176

What category of drug does clindamycin belong?

Lincosamide

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

Drug-resistant organisms

179

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

Prostate - Same for bactrim

180

What major drug category do cephalosporins fall under? Carbapenems?

- Beta-lactams - Beta-lactams

181

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

*UTIs and *bacteremia

182

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

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

183

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

Cephamycins - 2nd gen

184

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

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

185

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

186

How is quinupristin-dalfopristin eliminated?

Both via hepatic and biliary

187

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

188

Which 2 macrolides are derivatives of the other?

Azithromycin and clarithromycin derivatives of erythromycin

189

Which of the amino-PCNs have better oral uptake?

Amoxicillin

190

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

*Tigecycline - Glycylcylins

191

- 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.

192

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.

193

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

194

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

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

195

Macrolides: mech of resistance?

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

196

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

Parenterally - Minimally

197

Which is the most important AG?

Gentamycin

198

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)

199

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.

200

What can occur if expired tetracyclines are prescribed?

Fanconi-like syndrome a/w renal failure

201

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

- SSRIs, MAOIs - Serotonin syndrome

202

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

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

203

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*

204

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

205

What 2 drugs are contained in Unasyn?

Ampicillin-sulbactam

206

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

207

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

208

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

209

What organism group does bactrim not have activity against?

Anaerobes

210

What are the major side effects a/w linezolid?

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

211

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.)

212

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

Atypical bacteria

213

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

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

214

What is the MoA for nitrofurantoin?

Not well understood

215

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

renal function

216

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

217

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.

218

Which of the FQ's are active against anaerobes?

Only moxifloxacin

219

Why were cephalosporins developed?

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

220

*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

221

Do macrolides penetrate the CSF?

Not really

222

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

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

223

Which glycopeptide is more potent than vanc?

Dalbavancin

224

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

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

225

Vanc treats ______-______ c-dif colitis.

moderate-severe

226

What demo should not use FQs? (contraindicated)

Pregnant women and children

227

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)

228

Which macrolide is best for STDs?

Azithromycin

229

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

230

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

AG's, tetracyclins

231

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

232

What 2 drugs are contained in Augmentin?

Amoxicillin-clavulanate

233

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

They are all administered IV and IM (not PO)

234

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

Ceftriaxone - Ceftazidime

235

Quinupristin-dalfopristin: mech of resistance?

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

236

What specific organism do you not use ABX to treat?

STEC (specifically)

237

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

238

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

239

Macrolides: MoA? - Cidal or static?

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

240

Does quinupristin-dalfopristin affect CYP450?

P450 3A4 Inhibitor

241

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

242

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

Eye, prostate, and uninflammed CSF.

243

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

244

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

245

What is tigecycline often used to treat?

Polymicrobial infections

246

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

247

What organisms do carboxypenicillins inhibit?

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

248

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)

249

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)

250

-______________, 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)

251

What are the major adverse effects of monobactams?

N/D

252

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

Levofloxacin, moxifloxacin, gemifloxacin (Not ciprofloxacin!)

253

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

Pseudomonas

254

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

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

255

What drugs are in the combination Bactrim?

Trimethoprim-Sulfamethoxazole (TMP-SMX)

256

What group does PCNs have synergy w/?

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

257

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

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

258

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

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

259

*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

260

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!

261

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

Augmentin

262

Which AGs are effective against gram-neg infections?

- Gentamycin - Tobramycin - Amikacin

263

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

264

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

Cipro, levo

265

Which gen of cephalosporins are effective against anaerobes like bacteroides?

2nd gen only

266

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

- Nitrofurantoin - Methenamine

267

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)

268

What organ eliminates AGs?

Kidneys (dose must be adjusted in kidney failure)

269

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

Inhibits dihydrofolate reductase - Becomes cidal w/bacteriostatic sulfas

270

What are the main adverse effects of carbapenems?

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

271

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

3rd gen

272

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)

273

How can ceftriaxone be administered?

IV (not effective orally)

274

Which drugs cause a disulfuram-like rxn after drinking etoh?

2nd + 3rd gen cephalosporins, carbapenems, metronidazole

275

What 2 drug classes did we learn that could potentially lead to prolonged QT syndrome?

Macrolides, FQs