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Thera VII > 10 Fluoroquinolones Cupo > Flashcards

10 Fluoroquinolones Cupo Flashcards

1
Q

What are the mechanisms of FQ resistance?

A

1) Target site mutation. 2) Decreased uptake, increased drug efflux (multidrug efflux pumps in P. aeruginosa). Plasmid mediated

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2
Q

What are the characteristics of Plasmid Mediated resistance?

A

gnr gene. Protects FQ targets from inhibition. Confers low-level resistance. Plasmids also carry Extended Spectrum Beta-Lactamase (ESBL)

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3
Q

Which bacteria is plasmid mediated resistance seen in?

A

Kleb pneum, E. coli, Enterobacter cloacae

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4
Q

What is the 1st generation FQ?

A

Norfloxacin

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5
Q

What is the spectrum of activity for Norfloxacin?

A

Gram (-) Aerobes: Enteric pathogens (Proteus, E. coli, Klebsiella, Shigella, C. jejuni, Salmonella), Nosocomial pathogens (Citrobacter, Acinetobacter, P. aeruginosa, Enterobacter, Serratia marcescens)

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6
Q

What is the 2nd generation FQ used?

A

Ciprofloxacin (sometimes Ofloxacin)

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7
Q

What is the spectrum of activity for Ciprofloxacin, Ofloxacin?

A

Gram (-) aerobes (excellent activity). Same as 1st gen, but also: H. influenza, M. catarrhalis, Legionella. Gram (+) aerobes (poor to moderate activity): S. aureus, S. epidermidis, Enterococcus (poor, sufficient for urine only), S. pneumoniae (poor)

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8
Q

Which bacteria does Ciprofloxacin, Ofloxacin have excellent activity against?

A

Gram (-) aerobes

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9
Q

Which FQ is most potent against P. aeruginosa?

A

Ciprofloxacin

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10
Q

What are the 3rd generation FQs used?

A

Levofloxacin, Moxifloxacin, Gatifloxacin (not used anymore)

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11
Q

What is the spectrum of activity for Levofloxacin, Moxifloxacin?

A

Gram (-) aerobes (excellent activity): same as 2nd gen (less potent than cipro vs. P. aeruginosa). Gram (+) aerobes: same as 2nd gen but also S. pneumoniae (variable, but better than cipro). Atypicals (excellent activity): Chlamydia pneumoniae, Mycoplasma pneumoniea, Mycobacterium

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12
Q

Which bacteria do Levofloxacin, Moxifloxacin have excellent activity against?

A

Gram (-) aerobes. Atypicals

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13
Q

Which FQ has a better MIC for S. pneumoniae?

A

Moxifloxacin

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14
Q

Which FQ has a better MIC for E. coli?

A

Moxifloxacin

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15
Q

What is a quick summary for the spectrum of activity for 1-3rd gen FQs?

A

1st Gen: Gram (-) aerobes (urine). 2nd Gen: Gram (-) aerobes + Gram (+) aerobes (mod-poor). 3rd Gen: Gram (-) aerobes + Gram (+) aerobes (mod) + Atypicals

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16
Q

What are the pharmacodynamic features of quinolones?

A

Concentration-dependent. Bactericidal. Moderate-prolonged persistent effects (S. aureus ~1-3 hrs, Enterobacteriaceae ~1-6 hrs, P. aeruginosa ~1-6 hrs)

17
Q

Which FQ has the best BA?

A

Levo > Moxi > Cipro

18
Q

Which FQ has the most protein binding?

A

Moxi > Levo ~ Cipro

19
Q

Which FQ has no CSF distribution?

A

Moxi

20
Q

Which FQ has the longest t 1/2?

A

Moxi (12h) > Levo (6-8h) > Cipro (3-4h)

21
Q

Which FQ has the least renal clearance?

A

Moxi (20%) < Cipro (50%) < Levo (85%)

22
Q

Which FQ is primarily renally cleared?

A

Levofloxacin, Ofloxacin

23
Q

Which FQ is mixed clearance?

A

Ciprofloxacin

24
Q

Which FQ is primarily non-renally cleared?

A

Moxi

25
Q

What are the class adverse effects for FQs?

A

Joint cartilage erosions. Severe tendinitis/rupture. Phototoxicity. CNS disorders

26
Q

What are some common ADRs associated with FQs?

A

GI (N/V/D). CNS (stimulation, HA, Dizziness). Dermatologic

27
Q

What is cartilage toxicity life for FQs?

A

Tendonitis/Tendon rupture, now with BBW. Contraindicated in children < 16. Pregnancy Category C

28
Q

Which patients have higher incidence of Gemifloxacin Rash?

A

Female < 40 or postmenopausal taking HRT. Longer treatment duration (> 7 days). Incidence not related to “idiosyncratic” rash and systemic exposure (Cmax or AUC)

29
Q

What is phototoxicity like for FQs?

A

Moxi and Gati have 0% d/t no fluorine group. Low in Levofloxacin < Ofloxacin ~ Ciprofloxacin

30
Q

What are the characteristics of FQ tendinopathy?

A

Achilles tendon most often (risk factor > 60, steroid use). Mechanism unknown (possible oxidative stress). Pefloxacin > Ofloxacin > Norfloxacin > Ciprofloxacin)

31
Q

What is the BBW associated with FQs?

A

Tendon-Related ADRs

32
Q

What are some rare ADRs associated with FQs?

A

Seizures. Hepatic. Hematologic. Renal. Cardiac (QT prolongation)

33
Q

What are the Drug-Drug interactions like for FQs?

A

ALL FQ agents interact with multivalent cations (Mg, Al, Fe, Ca, Zn): chelation reaction resulting in formation of insoluble, inactive complex. Significant reduction (~90%) in BA when administered concomitantly with: antacids, iron preparations, zinc, sucralfate (contains Al), enteral feedings

34
Q

What is the FQ multivalent cation interaction management?

A

Change to alternative antibiotic. DC cation for duration of quinolone tx. Change antacid/sucralfate to H2-RA or PPI. Recommend appropriate dosing interval (administer quinolone at least 4 hrs BEFORE multivalent cation)

35
Q

What is the QT interval prolongation like for FQs?

A

Levo, Gati, Moxi: should be avoided in patients receiving therapy agents (i.e. erythromycin, antipsychotics, tricyclic antidepressants) known to produce an increase in the QTc interval minimize the risk of life-threatening cardiac arrhythmias, including torsades de pointes

36
Q

What are the glucose hemostasis disturbances like for FQs?

A

Hypo and hyperglycemia. Glyburide + gatifloxacin or ciprofloxacin (gati&raquo_space; cipro)

37
Q

What is patient education for FQs?

A

May get drowsy or dizzy. Avoid/minimize caffeine intake. Antacids, Ca, iron, multivitamins, and Zn can stop the drug from working (take at least 4 hrs before/after antibiotic). Keep out of sun, wear protective clothing. Do not use sun lamps or sun tanning beds or booths. Pregnancy Category C

38
Q

When should patients on FQs STOP taking the medication?

A

Pain, swelling, or rupture of a tendon. Abnormal heartburn or fainting spells (QT)

39
Q

What are FQs role in therapy?

A

Rarely used as 1st line therapy (collateral damage (gm (-), gm (+), C. diff risk)). Reserve for management of documented or suspected infections caused by multi-drug resistant pathogens. Patients intolerant of alternative agents d/t: allergy or toxicity risk

Thera VII (37 decks)

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