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NAPLEX Review > Infectious Disease I - Abx Classes > Flashcards

Infectious Disease I - Abx Classes Flashcards

1
Q

Which antibiotic classes target ribosomes? Which ribosomal subunit do they bind to?

A

30s - aminoglycosides (irreversible), tetracyclines

50s - macrolides, quinupristin/dalfopristin, oxazolidinones, clindamycin

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2
Q

Which classes of antibiotics inhibit cell wall formation?

A

vanc, lipoglycopeptides, beta-lactams

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3
Q

MOA of fluoroquinolones

A

inhibition of bacterial topoisomerase and gyrase

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4
Q

MOA of metronidazole

A

molecule is reduced intracellularly only in anaerobic environments (oxygen competes for electrons in aerobes) - reduced metronidazole interacts with DNA to cause strand breakage

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5
Q

MOA of rifampin

A

binds to and inhibits bacterial RNA polymerase

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6
Q

Which antibiotics inhibit folic acid synthesis?

A

sulfonamides, trimethoprim, dapsone

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7
Q

What general PK principles can be predicted based on the hydrophilicity/lipophilicity of an antibiotic?

A

1) Vd (larger for more lipophilic drugs)
2) route of elimination (likely renal for water soluble, hepatic for fat soluble)
3) tissue penetration (lipophilic drugs have better tissue penetration
4) intracellular concentrations (higher for lipophilic agents, predicts potential activity against atypicals)
5) bioavailability (higher for lipophilic)
6) alteration of activity in sepsis (Vd becomes higher for hydrophilic drugs, necessitating higher doses)

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8
Q

Which antibiotic classes are hydrophilic?

A

beta-lactams, aminoglycosides, dapto, polymyxins, glycopeptides

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9
Q

Which antibiotic classes are lipophilic?

A

quinolones, macrolides, tetracyclines, linezolid, rifampin

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10
Q

Which beta-lactams do not require renal adjustment?

A

nafcillin, oxacillin, ceftriaxone

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11
Q

Which group of penicillins has the narrowest spectrum of activity? Which organisms do they cover?

A

the natural penicillins (PenVK, benzathine) cover strep and enterococci (NOT staph) with negligible gram negative activity

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12
Q

Name the penicillins in the “antistaphylococcal” group.

A

(di)cloxacillin, nafcillin, oxacillin

best drugs for MSSA

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13
Q

Which penicillins are “aminopenicillins”? How does their spectrum of activity differ from that of other penicillins?

A

ampicillin, amoxicillin

Aminos are better suited for gram (-) bugs, but still have a narrower spectrum of activity than extended-spectrum.

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14
Q

HNPEK

A

haemophilus, neisseria, proteus, e. coli, klebsiella

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15
Q

CAPES

A

citrobacter, acinetobacter, providencia, enterobacter, serratia

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16
Q

What is the spectrum of activity of aminopenicillins?

A

HNPEK, salmonella-shigella, slightly less G+ activity than natural penicillins, listeria (DOC in meningitis)

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17
Q

What is the spectrum of activity of extended-spectrum penicillins, like pip/tazo?

A

HNPEK, CAPES, Pseudomonas, MSSA

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18
Q

A patient with a PMH of afib, HTN, cholestasis, cirrhosis (Child-Pugh B), and HLD is being discharged home on an oral regimen for Haemophilus pneumonia. Which agents, per their PMH, would you avoid, and why?

A

Augmentin and Unasyn due to h/o cholestasis and liver dysfunction

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19
Q

Which antibiotics can be diluted in NS only?

A

anything containing ampicillin, ertapenem, daptomycin (Cubicin RF)

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20
Q

Which penicillins contain an appreciable amount of sodium?

A

nafcillin, zosyn, sodium penG

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21
Q

What is a key drug interaction with carbapenems?

A

Carbapenems can decrease the concentration of valproic acid. The risk of seizures is further elevated with drug accumulation and concomitant use of other drugs that decrease the seizure threshold (tramadol, bupropion)

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22
Q

Which penicillin is a vesicant?

A

nafcillin - extravasation managed with hyaluronidase, cold packs

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23
Q

What are the 3 most relevant penicillin drug interactions?

A

warfarin - may increase INR
mycophenolate - decreases concentration due to inhibition of enterohepatic recycling
methotrexate - increases concentration

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24
Q

No cephalosporins have activity against this species of G(+) bug:

A

enterococcus

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25
Q

What are examples of first generation cephalosporins?

A

cephalexin, cefazolin, cefadroxil

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26
Q

With each successive generation of cephalosporins, what happens to the spectrum of activity?

A

Later generations have increasing amounts of G(-) activity and similar/slightly increasing G(+) activity.

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27
Q

Which two 2nd gen cephalosporins have anaerobic activity?

A

cefotetan and cefoxitin

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28
Q

The third generation of cephalosporins is divided into two groups based on what key characteristic? Which agents have this property?

A

pseudomonas coverage: ceftazidime has it

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29
Q

What are the key second gen cephalosporins?

A

cefotetan, cefuroxime

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30
Q

What are the most common third gen cephalosporins?

A

cefdinir (PO), ceftriaxone, ceftazidime, cefpodoxime, cefotaxime

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31
Q

What are one key drug interaction with cephalosporins?

A

1) agents that reduce stomach acid can reduce F of cefuroxime, cefpodoxime, cefdinir, and cefditoren

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32
Q

Which two cephalosporins come in a beta-lactamase inhibitor combination that can be used for multidrug resistant organisms, such as CRE?

A

ceftazidime/avibactam (Avycaz)

ceftolozane/tazobactam (Zerbaxa)

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33
Q

What are the side effects of beta-lactams?

A

similar to penicillins: rash (may be SJS/TEN), diarrhea/GI upset, seizures (if accumulation)

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34
Q

What is a key structural element of cefotetan that has potential clinical effects?

A

the NMTT side chain increases bleeding risk and causes a disulfiram-like reaction if alcohol is consumed

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35
Q

Which cephalosporin is dangerous if used in neonates? Why?

A

ceftriaxone - can cause biliary sludging and kernicterus

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36
Q

Carbapenems are very broad agents, but lack activity against what 4 key pathogens?

A

C. diff, VRE, MRSA, and atypicals

37
Q

Ertapenem lacks coverage of what two key organisms?

A

pseudomonas and enterococcus

38
Q

What purpose does cilastatin serve for imipenem?

A

Cilastatin prevents degradation of imipenem by renal tubular dihydropeptidases.

39
Q

Describe the place in therapy of aminoglycosides.

A

Primarily for synergy in G(-) infections. Rarely used as montherapy. Good for complicated UTI, endocarditis, more severe cases of pneumonia (VAP).

40
Q

What are the most common toxicities of aminoglycosides?

A

They are nephro- and ototoxic. This is partially overcome by extended interval dosing, which takes advantage of PK properties of AGs (concentration-dependent killing, PAE) to allow clinical efficacy and enough time for kidneys to recover between doses.

41
Q

For the following weight groups, describe how you would initially dose an AG:
underweight
overweight
appropriate weight

A 
If underweight (eg. less than IBW) - use TBW
If appropriate weight - use IBW
If obese (BMI >30) - use AdjBW
42
Q

How are AG levels monitored and used?

A

Depends on the dosing regimen. In traditional dosing, peaks and troughs are used at steady state (after 4-5 doses) to calculate the rate of clearance, and the dose is adjusted from there to maintain trough levels <2 mcg/mL. For synergy, the goal peaks and troughs are lower.

In traditional dosing, random levels are used and a dosing frequency is established using the Hartford nomogram. Level should be 6-14 hours after the end of the infusion.

43
Q

How does ototoxicity manifest in patients receiving AGs?

A

Hearing loss will start with high-pitched sounds. There may be some vestibular toxicity that will show as loss of balance or difficulty walking if the patient is ambulatory.

44
Q

What is the most common dose of gent/tob selected for extended interval dosing?

A

7 mg/kg (make sure to use appropriate weight)

45
Q

Which AG has higher peak and trough targets?

A

amikacin (peak 20-30, trough <5)

46
Q

Which FQs are considered “respiratory” FQs? Why?

A

gemi, levo, and moxi due to their increase activity against S. pneumo and atypicals

47
Q

Which two FQs have pseudomonas coverage?

A

levo and cipro

48
Q

Which FQ has MRSA coverage?

A

dela

49
Q

One FQ that cannot be used for UTI

A

moxi

50
Q

Which FQ has the best G(+) activity?

A

moxi

51
Q

Are FQs time or concentration dependent?

A

concentration (PAE of 1-2 hours)

52
Q

What are the unique properties of moxifloxacin compared to other FQs?

A

1) no renal adjustment required, as it is not removed primarily by the kidneys
2) subsequently, not effective for UTIs
3) enhanced gram positive and anaerobic activity

53
Q

What are the boxed warnings of FQ as a class?

A

1) tendon rupture
2) seizures and other CNS effects
3) peripheral neuropathy
4) exacerbation of myasthenia gravis

54
Q

Which two FQs have a 1:1 IV/PO conversion?

A

levo and moxi

55
Q

What are some adverse effects associated with FQs (other than their boxed warnings)?

A

1) QTc prolongation
2) photosensitivity
3) hyper/hypoglycemia - increase monitoring in diabetics
4) psychiatric disturbances
5) musculoskeletal toxicity in children and pregnancy
6) N/D, HA
7) serious skin reactions

56
Q

Describe the tendon rupture associated with FQ use. When can it occur? What other risk factor increase the likelihood of the AE?

A

Tendon rupture can occur in patients within hours or days of starting, or up to months after discontinuation. Systemic corticosteroids increases the risk, as well as age >60 and having received an organ transplant.

57
Q

Name the substances that can chelate with FQ with concomitant oral administration. How should these agents be separated?

A

Antacids and other polyvalent cations, multivitamins, sucralfate, and bile acid resins (eg. colesevelam) can decrease absorption of FQs. Administer FQ either 1 hour before or 4 hours after these drugs.

58
Q

What are the effects of lanthanum and sevelamer on FQ absorption?

A

They decrease absorption - give FQ 2 hours before or 2-4 hours after lanthanum or 6 hours after sevelamer.

59
Q

What elements of a PMH and lab values would you want to be aware of during FQ treatment based on their propensity to prolong the QT interval?

A

preexisting CVD, K, Mg

60
Q

Name the group of organisms that macrolides are best known for their coverage of.

A

atypicals

61
Q

What kinds of infections are macrolides most commonly used for?

A

pneumonia, STDs (chlamydia, gono)

62
Q

Name the two macrolides associated with CYP interactions and some of the drugs to avoid concomitant administration of.

A

clarithromycin (Biaxin) and erythromycin (Erythrocin)

simvastatin, lovastatin, DOACs, warfarin, pimozide

These two macrolides are potent CYP3A4 inhibitors and can increase concentrations/toxicities of these drugs.

63
Q

What are some monitoring parameters for macrolides related to their potential toxicities?

A

QT interval, LFTs, s/sx of severe skin reactions

64
Q

Which macrolide is associated with the fewest drug interactions?

A

azith

65
Q

What are the common uses for tetracyclines?

A

CAP, tick-borne diseases, anything caused by other unique pathogens, skin infections, CA-MRSA

doxycycline can be used for VRE UTIs only

66
Q

What is the IV:PO ratio for doxy and mino?

A

1:1

67
Q

What is a unique toxicity of minocycline?

A

drug-induced lupus

68
Q

What are two groups of people in whom tetracyclines are contraindicated?

A

children under 8 due to permanent teeth discoloration and disruption of skeletal development

pregnancy/breastfeeding

69
Q

What are side effects of tetracyclines?

A

photosensitivity, N/V/D, rash, increase LFTs

70
Q

Which tetracycline has no renal adjustment?

A

doxy

71
Q

What are some notable tetracycline drug interactions?

A

1) cations - separate administration 1 hour before or 4 hours after
2) warfarin - increases INR
3) lanthanum

Note that these are similar to the DDIs of FQs.

72
Q

Which antibiotic class can be associated with hemolytic anemia? Which lab test confirms this?

A

sulfonamides - Coombs test

73
Q

Which genetic abnormality is associated with an elevated risk of hemolytic anemia with sulfonamide use?

A

G6PD deficiency

74
Q

What are some warnings with sulfonamide use?

A

SJS/TEN, TTP, G6PD deficiency

75
Q

What are the 3 most common side effects with Bactrim use?

A

1) photosensitivity
2) hyperkalemia
3) crystalluria

76
Q

Name the most common clinical uses of Bactrim.

A

1) PCP ppx/tx

2) uncomplicated UTI

77
Q

Why is a CBC part of the monitoring recommendations for Bactrim?

A

can cause various blood dyscrasias including agranulocytosis, aplastic anemia, and TTP

78
Q

notable drug interactions with SMX/TMP

A

1) warfarin - SMX/TMP potent inhibitor of 2C9
2) potent inducers of 2C9 decrease SMX/TMP concentrations
3) leucovorin
4) other drugs that increase K

79
Q

What is an infusion-related reaction to vancomycin? How is it prevented?

A

Red-man syndrome (trunk rash, pruritis, dizziness, agitation, hypotension/angioedema in severe cases) occurs when vancomycin is infused too fast. Though it is managed with IV diphenhydramine, it is generally prevented by not infusing more than 1g per hour.

80
Q

How do lipoglycopeptides (LGPs) inhibit bacterial cell wall synthesis?

A

1) inhibiting D-ala:D-ala binding in PG formation

2) inserting depolarizing tails into membrane

81
Q

What boxed warning comes with telavancin? What is one important consideration prior to starting this agent knowing this?

A

demonstrated fetal risk - should have a negative pregnancy test to initiate

also for nephrotoxicity that caused worse outcomes in patients w pre-existing renal disease compared to vanc

82
Q

What LGPs can be given in a single-dose regimen?

A

orita and dalba (extremely long half-lives, hundreds of hours)

83
Q

What is an adverse effect unique to telavancin in the LGP class?

A

QT prolongation (TELAvancin = TELEmetry)

84
Q

What is a warning/contraindication among all agents in the LGP class? How is this navigated in clinical practice?

A

ability to falsely elevate PT/aPTT/INR without increasing bleeding risk

The management is different, though, between agents. Telavancin has by far the shortest half-life, so concomitant administration is not indicated, but IVUFH could be started sooner after. Oritavancin has a 240 hour half life, and IVUFH cannot be administered within 120 hours of the last infusion.

85
Q

What’s the deal with oritavancin and osteomyelitis?

A

Osteomyelitis was observed in more patients treated with oritavancin than other drugs. Monitor for s/sx of osteo and select a different antibiotic if it appears.

86
Q

What is a side effect unique to dalbavancin?

A

increased ALT

87
Q

Which species of VRE does daptomycin have coverage for?

A

both (faecium and faecalis)

88
Q

What are 3 warnings associated with daptomycin?

A

1) eosinophilic pneumonia that can develop 2-4 weeks after initiation
2) myopathy/rhabdo - monitor CPK during treatment
3) falsely elevates PT/INR without increasing bleeding risk

89
Q

One important consideration for the reconstitution of daptomycin is:

A

no formulation is compatible with dextrose (use NS - check PI for dilution instructions)

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