Fluoroquinolones

GENERAL PRINCIPLES

• Fluoroquinolones exert their bactericidal effect by inhibiting bacterial enzymes DNA gyrase and topoisomerase IV, which are critical for DNA replication. These antibiotics are well absorbed orally, with serum concentrations that approach those of parenteral administration, making them ideal candidates for switching from IV to PO formulations.

• Concomitant administration with aluminum- or magnesium-containing antacids, sucralfate, bismuth, oral iron, oral calcium, oral zinc, and metallic cation-containing enteral nutrition preparations can markedly impair absorption of oral fluoroquinolones.

TREATMENT

• Ciprofloxacin (250-750 mg PO q12h, 500 mg PO q24h [Cipro XR], or 200-400 mg IV q8-12h) and ofloxacin (200-400 mg IV or PO q12h) are active against gram-negative aerobes including many AmpC-producing pathogens. These agents are commonly used for UTIs, pyelonephritis, infectious diarrhea, prostatitis, and intra-abdominal infections (with metronidazole). Ciprofloxacin has the most reliable activity against P. aeruginosa of all quinolones. However, ciprofloxacin has relatively poor activity against gram-positive pathogens and anaerobes and should not be used as empiric monotherapy for CAP, skin/soft tissue infections, or intra-abdominal infections.

• Levofloxacin (250-750 mg PO/IV q24h), moxifloxacin (400 mg PO/IV q24h daily), and gemifloxacin (320 mg PO q24h daily) have improved coverage of streptococci but generally less gram-negative activity than ciprofloxacin (except levofloxacin, which does cover P. aeruginosa). Moxifloxacin has been used as monotherapy of intra-abdominal infections because of its antianaerobic activity, although resistance among B. fragilis is increasing. Each of these agents is useful for treatment of sinusitis, bronchitis, CAP, and UTIs (except moxifloxacin, which is only minimally eliminated in the urine).

• Delafloxacin (300 mg IV q12h or 450 mg PO q12h) is FDA-approved for acute bacterial skin and skin structure infections and CAP. This agent is active against some MRSA, streptococci, some enterococci, gram-negative bacteria (including Pseudomonas), and anaerobes. Unlike other fluoroquinolones, delafloxacin does not appear to prolong the QTc interval on the electrocardiogram and may be less prone to causing phototoxicity and CNS adverse effects than other fluoroquinolones.

SPECIAL CONSIDERATIONS

• Adverse events include nausea, CNS disturbances (headache, restlessness, and dizziness, especially in the elderly), rash, and phototoxicity. These agents can cause prolongation of the QTc interval (excluding delafloxacin) and should not be used in patients who are receiving class I or class III antiarrhythmics, in patients with known electrolyte or conduction abnormalities, or with other medications that prolong the QTc interval or induce bradycardia. These agents should also be used with caution in the elderly, in whom asymptomatic conduction disturbances are more common. Fluoroquinolones should not be routinely used in patients younger than 18 years or in pregnant or lactating women because of the risk of arthropathy in pediatric patients. They may also cause tendinitis or tendon rupture, especially of the Achilles tendon, particularly in elderly. Peripheral neuropathy, myasthenia gravis exacerbations, and abdominal aortic aneurysms may also rarely occur. An increase in the international normalized ratio may occur when used concurrently with warfarin.

• This class of antimicrobials has major drug interactions. Before initiating use of these agents, it is necessary to review concomitant medications.