Quinolones Quinolones - Are chemically related compounds of Nalidixic acid which was the first class of antimicrobial agents

use for the treatment of UTI. Nalidixic acid  Suboptimal pharmacokinetic profile  Narrow spectrum  Microbial resistance problem Floroquinolones - Differ from older compounds in that they a fluorine at the position C6, and a piperazinyl moiety at C7 position of the quinolone nucleus.

11. Pasteurella multocida 12. Aeromonas hydrophila 13. Salmonella 14. Shigella 15. Campylobacter jejuni 16. Yersinia enterocolitica 17. Vibrio 18. P. acroginosa 19. H. influenza 20. H. ducreyi 21. Neisseria meningitis 22. N. gonorrhoea 23. Branhamella catathalic

1. M. Tuberculosis 2. M. Kankasii 3. M. fortuitum

Activity against anaerobic baderia is poor

Poor activity against Anerobic bacteria (except Tosufloxacin) Members: 1. Ciprofloxacin Sesquihydrate 2. Norfloxacin 3. Pefloxacin 4. Ofloxacin Tosufloxacin 5. Levofloxacin Sparfloxacin 6. Moxifloxacin Grepafloxacin 7. Lumifloxacin Pharmacokinetics Bioavailability after oral adm – 95-100% Elimination is through renal excretion via active tubular secretion. Pefloxacin is metabolize by the liver (non- renal excretion). Moxifloxacin, sparfloxacin, and trovafloxacin are eliminated partly by hepatic and biliary excretion. 8. Enoxacin 9. Rosoxacin 10. Fleroxacin 11. 12. 13.

Mechanism of Action They interfere with bacterial DNA synthesis by inhibiting topoisomerase II (DNA gyrase) and topoisomerase IV. Antimicrobial Activity - Bactericidal Antimicrobial Spectrum - broad Gm (-) bacteria 1. 2. 3. 4. E. coli Klebsiella Enterobacter Serratia marcescens 5. Proteus 6. Morganella 7. Providenica 8. Citrobacter 9. Acidetobacter 10. Eikenella corrodens Gm (+) Orgs 1. Methicillin susceptible and resistant strain of a. S. Auerus b. S. Epidermidis c. Other coagulase (-) staph

Drug Interaction: 1. Al(OH)3 + Mg(OH)3 (Antacid) GI absorption 2. Sucralfate 3. Inhibits theophylline met. serum level of theophyllin

2. Streptococcus pneumonia (same as M3) 3. Strep A, B, C, D and G – are only marginally susceptible Other Organism

(Drug) Adverse Effects – Infrequent 1. GIT dist 2. CNS dist (headache, restlessness, dizziness tremors, rarely seizure) 3. Skin reaction, photosensitization 4. serum transaminases, LOH, alk PO4 5. Cartilage erosion in children Summary of appropriate indication for fluoroquinolones: Indications Preferred fluoroquinolones

M. Tuberculosis, M. avium

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Ciprofloxacin

When fluroquinolones are Not indicated: 1. Uncomplicated UTI that can be treated with cheaper or alteration agents 2. Bacteriuria or UTI assoc with foreign bodies (e.g. foley catheter, renal calculi) in which prolonged therapy will just select out resistant bacteria. 3. P.I.D due to syphilis 4. S. aureus osteomylitis 5. Community acquired pneumonia due to S. pneumonia, mycoplasma 6. Aspiration pneumonia (due to anaerobic organisms) 7. Strep grp A or S. aureus skin infections 8. Otitis media / sinusitis 9. Anaerobic infections 10. Children, pregnant women and nursing mothers. Specific Clinical Uses of some fluroquinolones Levofloxacin – good activity against organisms assoc with community – acquired pneumonia. Including atypical pneumonia. Sparfloxacin activity against gm (+) organisms including penicillin – resistant pneumococci. Contraindicated in patients taking drugs that prolong the QT interval. (e.g. antiarrhythmic agents) Moxifloxacin & trovafloxacin – have the widest spectrum including gm (-) and anaerobic bacteria Grepfloxacin – can cause serious cardiotoxicity

1. Complicated UTI in which - All fluoroquinolone will orgs resistant to usual oral work antibiotics exist 2. Chronic bacterial prostatis when THR-SMZ cannot be use or has failed 3. Osteomylitis due to susceptible gm (-) bacilli but not due to S. aureus 4. Invasive (malignant) external otitis due to P. aeroginosa 5. Gm (-) nosocomial pneumonia 6. Shigella infections 7. traveler’s diarrhea 8. Several bacterial gm (-) infections bacteria gastroenteritis/salmonella Gm (-) soft tissue infections - 1st choice – Ofloxacin, but any will work - Ciprofloxacin

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Ciprofloxacin

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Ciprofloxacin Any will work

a. Norfloxacin b. Ciprofloxacin Ciprofloxacin is the 1st choice

9. Uncomplicated Gonorrhea -

Any will work Single dose a. Ciprofloxacin 500mg b. Ofloxacin 400mg c. Norfloxacin 800mg d. Enoxacin 400mg Ofloxacin 300mg P.O bid for 7 days

10. Chlamydia trachomatis 11. Chancroid due to H. ducreyi 12. Mycobacterium infections:

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- Ciprofloxacin 500mg x 3 days (resistant cases only) Ciprofloxacin ofloxacin