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  1. 1. Ariana Hurtado Garcia Medico Interno
  2. 2. <ul><li>Quinolones were first developed in the 1960s and can be classified into generations based on antimicrobial activity. </li></ul><ul><li>First Nalidixic acid in 1962. </li></ul>
  3. 3. <ul><li>Quinolones </li></ul>
  4. 4. <ul><li>First Generation </li></ul><ul><li>Gram-negative, but Pseudomonas spp. </li></ul><ul><li>Second Generation </li></ul><ul><ul><li>Gram-negative, some gram-positive and mycobacteria. </li></ul></ul><ul><li>Third and Fourth Generation </li></ul><ul><li>Have increased activity against gram-positive pathogens including S. pneumoniae. They are also active against many agents causing zoonotic infection and against mycobacteria. </li></ul>
  5. 5. <ul><li>First Generation </li></ul><ul><ul><li>Cinoxacin </li></ul></ul><ul><ul><li>Nalidixic Acid </li></ul></ul><ul><ul><li>Oxolinic acid </li></ul></ul><ul><li>Second Generation </li></ul><ul><ul><li>Ciprofloxacin </li></ul></ul><ul><ul><li>Enoxacin </li></ul></ul><ul><ul><li>Fleroxacin </li></ul></ul><ul><ul><li>Lomefloxacin </li></ul></ul><ul><ul><li>Levofloxacin </li></ul></ul><ul><ul><li>Norfloxacin </li></ul></ul><ul><ul><li>Ofloxacin </li></ul></ul><ul><ul><li>rulfloxacin </li></ul></ul><ul><li>Third Generation </li></ul><ul><ul><li>Gatifloxacin </li></ul></ul><ul><ul><li>Grepafloxacin </li></ul></ul><ul><ul><li>Pazufloxacin </li></ul></ul><ul><ul><li>Sparfloxacin </li></ul></ul><ul><ul><li>Tosufloxacin </li></ul></ul><ul><li>Fourth Generation </li></ul><ul><ul><li>Clinafloxacin </li></ul></ul><ul><ul><li>Gemifloxacin </li></ul></ul><ul><ul><li>Moxifloxacin </li></ul></ul><ul><ul><li>Trovafloxacin </li></ul></ul>
  6. 6. <ul><li>Quinolones </li></ul>
  7. 7. The fluoroquinolones act by inhibiting type 2 bacterial DNA topoisomerases, DNA gyrase and topoisomerase IV. They bind to and trapp the enzyme-DNA complex. This blocks DNA synthesis and cell growth and ultimately has a lethal effect on the cell.
  8. 8. <ul><li>Quinolones </li></ul>
  9. 9. <ul><li>The fluoroquinolones are potent bactericidal agents against: </li></ul><ul><li>E. coli and various species of Salmonella, Shigella, Enterobacter, Campylobacter, and Neisseria </li></ul><ul><li>Ciprofloxacin is more active than norfioxacin against P. aeruginosa </li></ul><ul><li>Fluoroquinolones also have good activity against staphylococci, including methicillin­resistant strains </li></ul><ul><li>Several intracellular bacteria are inhibited by </li></ul><ul><li>fluoroquinolones these include species of Chlamydia, </li></ul><ul><li>Mycoplasma, Legionella, Brucella, and </li></ul><ul><li>Mycobacterium (including Mycobacterium tuberculosis) </li></ul>
  10. 10. <ul><li>Quinolones </li></ul>
  11. 11. <ul><li>Resistance to quinolones may develop during therapy via mutations in the bacterial chromosomal genes encoding DNA gyrase or topoisomerase IV, or by active transport of the drug out of the bacteria. </li></ul>
  12. 13. <ul><li>Quinolones </li></ul>
  13. 14. M, Metabolized; R, renal excretion as unchanged drug. Agent Administration Absorption Half-Life (hrs) Disposition Norfloxacin Oral 50% 4 (8 in anuria) M (20%)         R (27%) Ciprofloxacin Oral, IV 75% 4 (10 in anuria) R (50%) M Levofloxacin Oral, IV 98% 7 R (80%) Gatifloxacin Oral, IV 96% 7-8 R (70%) Moxifloxacin Oral, IV 89% 10-14 R (20%)         M (25%) (in liver) Nitrofurantoin Oral Adequate 0.6-1.2 R, M (in tissue) Polymyxin B Topical, oral, IV Not absorbed in adults; absorbed in children 6 by IV R
  14. 15. <ul><li>Quinolones </li></ul>
  15. 16. Disease Recommendations RESPIRATORY TRACT INFECTIONS Pharyngitis, otitis media Not appropriate Necrotizing otitis Ciprofloxacin for Pseudomonas aeruginosa Sinusitis Third-generation fluoroquinolone Community-acquired pneumonia Third-generation fluoroquinolone Hospital-acquired pneumonia Ciprofloxacin, for susceptible gram-negative pathogens URINARY TRACT INFECTIONS Cystitis, uncomplicated All effective (second generation most appropriate) Pyelonephritis All effective (second generation most appropriate) Prostatitis All effective SKIN STRUCTURE INFECTIONS Primary cellulitis Not appropriate as first line therapy Anaerobic soft-tissue infections Not appropriate
  16. 17. Disease Recommendations OSTEOMYELITIS Gram-negative bacterial infections Ciprofloxacin BACTERIAL DIARRHEAL DISEASES Ciprofloxacin used most commonly; all considered likely to be effective SEXUALLY TRANSMITTED DISEASES Gonorrhea Resistance testing required Chlamydia Ofloxacin, levofloxacin Chancroid All likely to be effective Mycoplasma Ofloxacin, levofloxacin Syphilis Not appropriate MYCOBACTERIAL DISEASES Disseminated M. avium complex Ciprofloxacin, ofloxacin as fourth agent if needed M. tuberculosis Ofloxacin, levofloxacin for drug-resistance or intolerance to first-line agents
  17. 18. <ul><li>Quinolones </li></ul>
  18. 19. <ul><li>Gastrointestinal effects </li></ul><ul><li>Central nervous system agitation (rarely seizures) </li></ul><ul><li>Damage to growing cartilage (not recommended for use in children) </li></ul><ul><li>Theophylline interaction (with ciprofloxacin) </li></ul>
  19. 21. <ul><li>Quinolones </li></ul>
  20. 22. Quinolonas disponibles en nuestro medio : - Acido nalidíxico: tabletas de 500 mg y susp. 250mg/5ml. 1gr c/6h VO (Acido Nalidixico y Wintomylon) - Acido pipemídico: comprimidos de 200 y 400 mg -Ciprofloxacino: comprimidos de 250, 500, 750 mg. ampollas de uso i.v de 100, 200 y 400 mg. 500-750mg c/12h VO 200-400mg c/12h IV (Cilaxon, Cigram,Cifloxin, Cipro, Cipro XR, Ciprofloxacina, Quinoprón)
  21. 23. -Levofloxacino: comprimidos de 250, 500 mg y frasco-ampollas de uso i.v de 500 mg. 500mg VO o IV c/24h (Levaquin, Levovax, Respilox, Tavanic) - Norfloxacino: comprimidos de 400 mg. 400mg c/12h VO (Ambigram, Nefrixine, Noprose, Norfloxacino, Senro, Urigen, Zoronix) - Pefloxacino: comprimidos y ampollas de uso IV 400 mg. -Moxifloxacino: comprimidos de 400 mg
  22. 24. <ul><li>Grazie… </li></ul>