Quinolone
Gram-positive: methicillin-susceptible Staphylococcus aureus (MSSA) (lowest quinolone activity vs. MSSA), Streptococcus pneumoniae
Gram-negative: Enterobacteriaceae, H. influenzae, other Haemophilus spp., N. gonorrhoeae, N. meningitides, M. catarrhalis, P. aeruginosa, S. maltophilia
Atypicals: Legionella pneumophilia
Inhibition of topoisomerase (DNA gyrase) enzymes, which inhibits relaxation of supercoiled DNA and promotes breakage of double stranded DNA.
Fluoroquinolones produce both concentration-dependent (peak:MIC), and a combination of concentration and time-dependent killing (AUC:MIC).
Dose of 750mg; Cmax: 3.5mg/ml; Volume of distribution: 3.2 L/kg; Table 2 & Table 3
CNS: headache, insomnia, dizziness; hallucinations, depression, psychotic reactions (rare)
Connective tissue: tendon injury
Renal: interstitial nephritis
Cardiovascular: QTC prolongation, torsades de pointes, arrhythmias
Tablets: 100mg, 250mg, 500mg, 750mg, 500mg extended release tabs, 1000mg extended release tablets
IV: 200mg, 400mg
Suspension: 250mg/5ml and 500mg/5ml (both in 100ml bottles)
Adult patients:
Lower respiratory tract infections: 500-750mg PO q12h / 400mg q8-12h IV x 7-14 days
Acute sinusitis: 500mg PO q12h / 400mg q12h IV x 10 days
Nosocomial pneumonia: 400mg IV q8h x 10-14 days
Uncomplicated UTI: 250mg PO q12h x 3 days
500mg extended release tablets q24h
Complicated UTI/Pyelonephritis: 500mg PO q12h / 400mg IV q12h x 7-14 days
1000mg extended release tablets q24h
Prostatits: 500mg PO q12h / 400mg IV q12h x 28 days
Uncomplicated gonococcal infections: 500mg PO x 1 dose
Chancroid: 500mg PO q12h x 3 doses
Uncomplicated skin/skin structure: 500-750mg PO q12h x 7-14 days / 400mg IV q8-12h
Intra-abdominal infections: 500mg PO q12h x 7-14days / 400mg IV q12h
Infectious diarrhea: 500mg q12h x 3-5 days (current recommendations)
500mg PO q12h x 5-7 days (labeled)
Inhalational anthrax (post-exposure): 500mg PO q12h x 60 days
Febrile neutropenia: 400mg IV q8h
Pediatrics:
Complicated UTI/Pyelonephritis: 6-10mg/kg not to exceed 400mg per dose q8h x 10-21 days
10-20mg/kg not to exceed 750mg per dose q12h x 10-21 days
Inhalational anthrax (post-exposure): 10mg/kg not to exceed 400mg per dose q12h x 60 days
15mg/kg not to exceed 500mg per dose q12h x 60 days
Disease state based dosing:
Renal failure: IV: CrCl 30 mL/min or greater, give usual dose; CrCl 5-29 mL/min, 200-400 mg IV every 18-24 hr
ORAL: CrCl greater than 50 mL/min, give usual dose; CrCl 30-50 mL/min, 250-500 mg every 12 hr; CrCl 5-29 mL/min, 250-500 mg every 18 hr
Hepatic failure: No dosing changes recommended at this time.
Dosing during Continuous Renal Replacement Therapy
CVVH (Continuous venovenous hemofiltration): 200mg IV q12h
CVVHD (Continuous venovenous hemodialysis): 200-40mg IVq12h
CVVHDF (Continuous venovenous hemodiafiltration) 200-400mg g IV q12h
Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.
Contraindications/Warnings/Precautions:
Precautions
Anticoagulants: Warfarin (prolonged warfarin half-life)
Divalent cations: aluminum, magnesium zinc, iron, calcium, antacids, sucralfate – reduced bioavailability of quinolones (potential to cause therapeutic failure)
Theophylline, caffeine, xanthines: clearance of these is inhibited with fluoroquinolones
Pregnancy:
Category C: Risk unknown. Human studies inadequate
Monitoring Requirements:
Therapeutic: Culture and sensitivities, signs and symptoms of infection
Toxic: Urinalysis, BUN, SCr, AST and ALT, physicial examination: encephalopathic changes
Brand names/Manufacturer:
Available by many names and manufacturers (click here)