Fluoroquinolones

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, delafloxacin) are bactericidal synthetic agents with excellent oral bioavailability and broad activity against Gram-negative bacilli, atypical organisms, and (levofloxacin, moxifloxacin) pneumococci and mycobacteria. Their value is offset by disabling and sometimes permanent adverse effects, so their use is restricted to infections where alternatives are unsuitable.

Mechanism. Inhibition of DNA gyrase (Gram-negatives) and topoisomerase IV (Gram-positives), causing lethal DNA breaks. Concentration-dependent killing; efficacy follows AUC to MIC.

Pharmacokinetics. Bioavailability 70 to 99 percent; wide tissue penetration including prostate, bone, lung and CSF (variable); large volume of distribution. Ciprofloxacin and ofloxacin are renally cleared; moxifloxacin is hepatically cleared and does not reach adequate urinary concentrations. Absorption is cut by divalent cations.

Resistance. Mutations in gyrA and parC; plasmid-mediated qnr and aac(6’)-Ib-cr; efflux. Salmonella Typhi and E. coli resistance is common.

Adult regimens (normal renal function).

• Ciprofloxacin 500 to 750 mg orally every 12 hours; IV 400 mg every 8 to 12 hours. Cystitis (3 days); pyelonephritis 7 days; prostatitis 4 weeks; cholera 1 g once; typhoid and invasive Salmonella 7 to 14 days where susceptible.
• Levofloxacin 500 mg to 750 mg daily. Community pneumonia (alternative agent): 750 mg daily for 5 days or 500 mg daily for 7 to 10 days.
• Moxifloxacin 400 mg orally or IV daily.
• Tuberculosis (MDR regimens): levofloxacin 750 to 1000 mg daily or moxifloxacin 400 mg daily, as part of multidrug therapy.
• Febrile neutropenia prophylaxis in selected high-risk patients: levofloxacin 500 mg daily.
• Children: used only for MDR tuberculosis, anthrax, plague, resistant complicated urinary infection and similar serious indications (ciprofloxacin 10 to 15 mg/kg every 12 hours).

Selection. Reserve for infections without safer options: Pseudomonas oral therapy, complicated urinary infection and prostatitis when susceptible, enteric infection, legionellosis, and drug-resistant tuberculosis. Avoid for uncomplicated cystitis, sinusitis, bronchitis and sore throat. Avoid empirical use in patients with possible tuberculosis, since partial treatment delays diagnosis and selects resistance.

Contraindications. Prior tendon disorder with a fluoroquinolone; myasthenia gravis; known aortic aneurysm or risk factors where alternatives exist; pregnancy and breastfeeding unless essential; children except for MDR tuberculosis, anthrax, plague and resistant complicated urinary infection; concurrent tizanidine with ciprofloxacin.

Serious effects. Tendinitis and tendon rupture (risk up with age over 60, corticosteroids, renal impairment); peripheral neuropathy; CNS effects (seizures, psychosis, delirium); myasthenia gravis exacerbation; aortic aneurysm and dissection; QT prolongation (moxifloxacin highest); dysglycaemia, especially hypoglycaemia in older diabetic patients on insulin or sulphonylureas; C. difficile infection; photosensitivity; hepatotoxicity.

Interactions. Antacids, iron, zinc, calcium, sucralfate (take fluoroquinolone 2 hours before or 6 hours after); theophylline and caffeine (ciprofloxacin); warfarin; NSAIDs (seizures); QT-prolonging drugs; corticosteroids.

Monitoring. Counsel to stop at the first tendon pain, paraesthesia or confusion; glucose in diabetics; ECG where QT risk exists; renal function.

Special groups.

• Renal impairment: ciprofloxacin 250 to 500 mg every 18 to 24 hours at creatinine clearance 5 to 29 mL/min; levofloxacin 750 mg regimen every 48 hours at clearance 20 to 49 mL/min, and 750 mg then 500 mg every 48 hours at 10 to 19 mL/min; moxifloxacin needs no adjustment.
• Older adults: higher risk of tendon, CNS and glucose effects; avoid where alternatives exist.
• Pregnancy: avoided.