Gatifloxacin

Antibiotic Class:

Quinolone

Antimicrobial Spectrum:

Gram-positive:  methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Listeria monocytogenes

Gram-negative:  Enterobacteriaceae, H. influenzae, other Haemophilus spp., N. gonorrhoeae, N. meningitides, M. catarrhalis, Stenotrophomonas maltophilia, S. maltophilia

Mycobacteria:  Mycobacterium tuberculosis, M. fortuitum

Atypicals:  Legionella pneumophilia, Chlamydia pneumonia, Mycoplasma pneumoniae

Mechanism of Action:

Inhibition of topoisomerase (DNA gyrase) enzymes, which inhibits relaxation of supercoiled DNA and promotes breakage of double stranded DNA.

Pharmacodynamics:

Fluoroquinolones produce both concentration-dependent (peak:MIC), and a combination of concentration and time-dependent killing (AUC:MIC).

Pharmacokinetics:

400mg dose; Cmax: 3.4mg/L; Volume of distribution: 1.7 L/kg; Table 2  & Table 3

Adverse Effects:

Divalent cations:  aluminum, magnesium zinc, iron, calcium, antacids, sucralfate – reduced bioavailability of quinolones (can cause therapeutic failure)

Dosage:

Tablets: 200mg, 400mg tablets

IV: 2mg/ml for IV administration

Opthalmic: 0.3% solution

Adult:

Community acquired pneumonia: 400mg IV/PO x 7-14 days

Acute sinusitis: 400mg IV/PO x 10 days

Conjunctivitis: 1 drop into affected eye q2h while awake up to 8 times per day x 2 days, then 1 drop up to 4 times/day for 4 more days.

Acute exacerbation of chronic bronchitis: 400mg IV/PO x 5 days

Uncomplicated UTI: 400mg IV/PO x 1 dose / 200mg IV/PO q24h x 3 days

Complicated UTI/Pyelonephritis: 400mg IV/PO x 7-10 days

Uncomplicated gonococcal infections: 400mg IV/PO x 1 dose

Uncomplicated skin/skin structure: 400mg IV/PO x 7-10 days

Pediatric:

Conjunctivitis: 1 drop into affected eye q2h while awake up to 8 times per day x 2 days, then 1 drop up to 4 times/day for 4 more days.

Table 4

Disease state based dosing:

Renal failure: CrCl < 40 mL/min:  400mg x 1, then 200mg q 24 hours

Hemodialysis: 400mg x 1, then 200mg q 24 hours after dialysis

Peritoneal dialysis: 400mg x 1, then 200mg q 24 hours

Hepatic failure:  No dosing changes recommended at this time.

Contraindications/Warnings/Precautions:

Precautions: 

• Prolongation of QT interval; avoid concurrent use with other drugs that prolong QT interval and in patients with risk factors for torsades de pointes (hypokalemia, significant bradycardia, cardiomyopathy)
• Central nervous system disorders (eg, epilepsy and cerebrovascular disease)
• Patients with glucose 6-phosphate dehydrogenase deficiency
• Diabetes mellitus; disturbances of blood glucose have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent or with insulin

Drug Interactions:

Anticoagulants:  Warfarin (prolonged warfarin half-life)

Divalent cations:  aluminum, magnesium zinc, iron, calcium, antacids, sucralfate – reduced bioavailability of quinolones (can 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:

• BONOQ (Grunenthal - GERMANY)
• GATIFLO (Kyorin - JAPAN)
• STAROX (Grunenthal - CHILE)
• TEQUIN (Bristol-Myers, USA, AUSTRALIA, MEXICO, BRAZIL, CANADA, THAILAND, SINGAPORE, SOUTH AFRICA, MALAYSIA, CANADA)
• ZYMAR (Opthalmic solution - Allergan - USA)