levofloxacin

Levofloxacin is the L-isomer of ofloxacin and belongs to the fluoroquinolone class of antibiotics. Mechanism: inhibits DNA gyrase (topoisomerase II) predominantly in gram-negative bacteria and topoisomerase IV predominantly in gram-positive bacteria, blocking bacterial DNA replication, transcription, and repair, leading to bactericidal effect. Spectrum: excellent gram-negative coverage (E. coli, Klebsiella, Pseudomonas aeruginosa at higher doses), atypical organisms (Legionella, Mycoplasma, Chlamydia), and improved gram-positive coverage including Streptococcus pneumoniae (hence classified as a 'respiratory fluoroquinolone' along with moxifloxacin). Clinical uses: community-acquired pneumonia, hospital-acquired pneumonia, complicated UTIs/pyelonephritis, prostatitis, sinusitis, skin/soft tissue infections, and as part of multidrug regimens for tuberculosis (second-line). Pharmacokinetics: excellent oral bioavailability (~99%), allowing IV-to-PO conversion; renally excreted, requiring dose adjustment in renal impairment. Adverse effects (boards-relevant, black box warnings): tendinopathy/tendon rupture (especially Achilles, increased risk in elderly, corticosteroid use, transplant patients), QT prolongation (avoid with other QT-prolonging drugs), CNS effects (dizziness, hallucinations, seizures - lowers seizure threshold), peripheral neuropathy, aortic aneurysm/dissection risk, hypoglycemia/hyperglycemia (especially in diabetics), and photosensitivity. Contraindicated in pregnancy and children (cartilage damage in animal studies) except in specific situations where benefits outweigh risks. Drug interactions: chelation with divalent/trivalent cations (antacids, calcium, iron, zinc) reduces absorption; separate administration by several hours. Resistance mechanisms include mutations in gyrA/parC genes and efflux pumps.