1 / 19

Fluoroquinolones

Fluoroquinolones. Mark S. Johnson, Pharm.D ., BCPS Associate Professor and Director of Postgraduate Education. Fluoroquinolones.

rufina
Download Presentation

Fluoroquinolones

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Fluoroquinolones Mark S. Johnson, Pharm.D., BCPS Associate Professor and Director of Postgraduate Education

  2. Fluoroquinolones • Very popular class of antibiotics due to spectrum of coverage (gram positive, gram negative, atypicals), unique mechanism of action resulting in inhibition of bacterial DNA gyrase and topoisomerase IV, excellent PO bioavailability, fairly well tolerated • Has led to overprescribing, resistance • Nalidixic acid was first quinolone (1962) • Had limited antibacterial activity • Associated with rapid development of bacterial resistance • Was only useful for lower UTI’s • Synthesis led to the evolution of the fluoroquinolones.

  3. Fluoroquinolones Increased gram positive coverage with each generation

  4. Nalidixic Acid http://www.rxlist.com/neggram-drug.htm

  5. Fluoroquinolones • Mechanism of action • Block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV • Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for normal transcription and replication • Inhibition of topoisomerase IV interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division • Bactericidal

  6. Quinolones Mechanism of Action

  7. FluoroquinolonesSpectrum of Activity • Gram (–) bacilli – Enterobacteriaceae (E. coli, Salmonella, Shigella, Enterobacter, Klebsiella, Proteus, Serratia); Campylobacter (increasing resistance); Pseudomonas aeruginosa(ciprofloxacin, levofloxacin) • Gram (–) cocci – Neisseriameningitidis • Gram (+) cocci – Staphylococci (MSSA/MRSA) – marginal-to-good activity (resistance can form) • Streptococci (S. pneumoniae) – 3rd generations • Intracellular/atypical bacterial – Chlamydia; Mycoplasma; Legionella; Brucella; Mycobacterium • Anaerobic activity –moxifloxacin

  8. FluoroquinolonesResistance • Resistance mediated by • Mutations in DNA gyrase • Change in outer bacterial membrane permeability • Variant of an aminoglycosideacetyltransferase

  9. FluoroquinolonesPKS • Absorption • Excellent BA (80-95%) • Distribution • Widely distributed in body fluids and tissues • Elimination • Mainly by renal tubular secretion or glomerular filtration • Moxifloxacin—hepatic metabolism, some urinary excretion • Gemifloxacin—both renal and hepatic

  10. FluoroquinolonesSome Clinical Uses • Urinary Tract Infections (not Moxifloxacin) • Respiratory Tract Infections • GI Infections • Soft tissues, bones, joints • Intra-abdominal infections • Anthrax • Others

  11. FluoroquinolonesADR’s • GI—nausea, vomiting, diarrhea • CNS – headache, dizziness, sleep disturbances, and confusion • QT prolongation • sparfloxacin >grepafloxacin > moxifloxacin > gatifloxacin > levofloxacin > ciprofloxacin > ofloxacin • Tendonitis, tendon rupture • Joint cartilage damage/arthropathy--<18yo • Photosensitivity • Hepatotoxity (moxifloxacin) • Hyper/hypoglycemia • Clostridium difficilediarrhea • Skin rash (gemifloxacin)

  12. FluoroquinolonesDrug Interactions • Drug interactions: • Quinolones’ absorption reduced by: di-, tri-valentcations (antacids, Ca supplements, iron, MVI, diary products, etc), sucralfate, ddi • Space out as far apart as can (at least 2h, but more better) • Quinolones can inhibit metabolism of: theophylline, caffeine, warfarin

  13. Fluoroquinolones2ndgeneration • Ciprofloxacin (Cipro, Cipro XR, Proquin XR) • Coverage: pseudomonas coverage, good gram – coverage (E. coli, salmonella, Shigella, Neirsseria, Legionella), some gram + ( no strep pneumo), Atypical coverage • Good for UTIs, pyelonephritis, prostatitis, osteomyelitis, anthrax, infectious diarrhea, travelers diarrhea, typhoid fever, intra-abdominal infections (with metronidazole), possible RTI’s, possible skin • Dosing: • PO 250-500-750mg BID • XR 500-1000mg QD • IV 400mg Q8-12h • Ophthalmic solution 0.3%

  14. Fluoroquinolones2ndgeneration • Ofloxacin (Floxin) • Coverage similar to ciprofloxacin (except Pseudomonas) • Used for: primarily for UTI’s and nongonococcalurethritis and cervicitis • Dosing • 200-400mg PO BID • Ophthalmic Solution 0.3% (Ocuflox)

  15. Fluoroquinolones2ndgeneration • Norfloxacin (Noroxin) • Used for UTI’s, prostatitis • Dosing: • PO 400mg BID

  16. Fluoroquinolones 3rd Generation • Levofloxaxin(Levaquin) • L-isomer of ofloxacin • Improved Gram + coverage and similar Gram –, some Pseudomonas coverage • Used for CAP, COPD exacerbations, sinusitis, skin infections, complicated UTIs • “Respiratory fluoroquinolone” • Dosing: • 250mg-750mg PO/IV Q24h • Ophthalmic solution (Iquix 1.5%, Quixin 0.5%)

  17. Fluoroquinolones 3rd Generation • Moxifloxacin (Avelox) • No renal adjustment, no urinary penetration • Gram negative and positive coverage (high activity for Streptococcus pneumoniae (MDRSP), anaerobes • Uses: pneumonia, AECB, sinusitis, intra-abdominal infections, skin/skin structure • “Respiratory Fluoroquinolone” • Dosing: • 400mg IV/PO Q24h • Ophthalmic 0.5% (Vigamox)

  18. Fluoroquinolones 3rd Generation • Gemifloxacin (Factive) • Similar in coverage to other 3rd generation FQ (not pseudomonas, not anaerobes) • Uses: pneumonia, AECB • “Respiratory fluoroquinolone” • ADR’s: Rash (incidence higher in females, >5d therapy, < 40yo) • Dosing: • 320 PO Q24h

More Related