10 Fluoroquinolones Cupo Flashcards by Chris Clark

What are the mechanisms of FQ resistance?

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

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What are the characteristics of Plasmid Mediated resistance?

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

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Which bacteria is plasmid mediated resistance seen in?

Kleb pneum, E. coli, Enterobacter cloacae

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What is the 1st generation FQ?

Norfloxacin

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What is the spectrum of activity for Norfloxacin?

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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What is the 2nd generation FQ used?

Ciprofloxacin (sometimes Ofloxacin)

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What is the spectrum of activity for Ciprofloxacin, Ofloxacin?

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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Which bacteria does Ciprofloxacin, Ofloxacin have excellent activity against?

Gram (-) aerobes

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Which FQ is most potent against P. aeruginosa?

Ciprofloxacin

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What are the 3rd generation FQs used?

Levofloxacin, Moxifloxacin, Gatifloxacin (not used anymore)

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What is the spectrum of activity for Levofloxacin, Moxifloxacin?

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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Which bacteria do Levofloxacin, Moxifloxacin have excellent activity against?

Gram (-) aerobes. Atypicals

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Which FQ has a better MIC for S. pneumoniae?

Moxifloxacin

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Which FQ has a better MIC for E. coli?

Moxifloxacin

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

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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What are the pharmacodynamic features of quinolones?

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

Which FQ has the best BA?

Levo > Moxi > Cipro

Which FQ has the most protein binding?

Moxi > Levo ~ Cipro

Which FQ has no CSF distribution?

Moxi

Which FQ has the longest t 1/2?

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

Which FQ has the least renal clearance?

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

Which FQ is primarily renally cleared?

Levofloxacin, Ofloxacin

Which FQ is mixed clearance?

Ciprofloxacin

Which FQ is primarily non-renally cleared?

Moxi

What are the class adverse effects for FQs?

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

What are some common ADRs associated with FQs?

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

What is cartilage toxicity life for FQs?

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

Which patients have higher incidence of Gemifloxacin Rash?

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

What is phototoxicity like for FQs?

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

What are the characteristics of FQ tendinopathy?

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

What is the BBW associated with FQs?

Tendon-Related ADRs

What are some rare ADRs associated with FQs?

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

What are the Drug-Drug interactions like for FQs?

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

What is the FQ multivalent cation interaction management?

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)

What is the QT interval prolongation like for FQs?

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

What are the glucose hemostasis disturbances like for FQs?

Hypo and hyperglycemia. Glyburide + gatifloxacin or ciprofloxacin (gati >> cipro)

What is patient education for FQs?

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

When should patients on FQs STOP taking the medication?

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

What are FQs role in therapy?

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