Chapter 35  ·  Module 5  ·  Antibacterial Agents
Fluoroquinolones
Mechanism, generations, adverse effects, and resistance at a glance
Abbreviations: DNA = deoxyribonucleic acid  ·  AUC/MIC = area under curve / minimum inhibitory concentration  ·  QTc = corrected QT interval  ·  CAP = community-acquired pneumonia  ·  UTI = urinary tract infection  ·  QRDR = quinolone resistance-determining region  ·  ESBL = extended-spectrum beta-lactamase  ·  FDA = US Food and Drug Administration
Fluoroquinolone Generations
GenKey AgentsGram-PositiveGram-NegativeAtypicalsKey Use
1st Nalidixic acid Minimal Enterobacteriaceae only No Historical; uncomplicated UTI only
2nd Ciprofloxacin, Ofloxacin MSSA (not pneumococcus) Broad; Pseudomonas Yes Pseudomonas; UTI; pyelonephritis; anthrax
3rd Levofloxacin + Streptococcus pneumoniae (penicillin-resistant) Broad; less Pseudomonas than ciprofloxacin Yes CAP; respiratory infections; tuberculosis regimens
4th Moxifloxacin Best gram-positive Good; NO reliable Pseudomonas Yes + anaerobes CAP; aspiration pneumonia; NOT for Pseudomonas
Black Box Warnings & Key Adverse Effects
Musculoskeletal
Tendinopathy & Rupture
  • Achilles tendon most affected
  • Risk: age > 60, corticosteroids, transplant
  • Stop drug if tendon pain develops
  • Rupture can occur months after therapy
Neurological
Neuropathy & CNS Effects
  • Peripheral neuropathy — can be irreversible
  • Seizures, psychosis, psychiatric effects (2016 warning)
  • Contraindicated in myasthenia gravis
  • Stop immediately if neuropathy develops
Cardiac / Metabolic / Vascular
QTc, Dysglycemia, Aorta
  • QTc prolongation: moxifloxacin > levofloxacin > ciprofloxacin
  • Hypoglycemia risk with sulfonylureas/insulin
  • Aortic aneurysm/dissection risk (2018 warning)
  • Avoid in known aortic aneurysm
Resistance Mechanisms
MechanismHow It WorksClinical Implication
QRDR mutations (gyrA, parC) Sequential mutations in primary then secondary topoisomerase target Stepwise resistance; dual-target agents (moxifloxacin) suppress emergence better
Efflux pump overexpression AcrAB-TolC (Enterobacteriaceae), MexAB-OprM (Pseudomonas) extrude drug Often multidrug resistance; synergizes with porin loss
Plasmid-mediated (qnr genes) Protect topoisomerases from fluoroquinolone binding; low-level resistance Stepping stone to high-level resistance; co-located with ESBL genes — resistance near-universal in ESBL organisms
Key Rules

Moxifloxacin has no reliable Pseudomonas activity — do not use when Pseudomonas coverage is needed. Take oral fluoroquinolones at least 2 hours before or 4-6 hours after antacids, calcium, iron, or zinc. Ciprofloxacin inhibits CYP1A2 — reduce theophylline dose; tizanidine combination contraindicated.

FDA 2016: Reserve for serious infections. Do not use for uncomplicated UTI, bronchitis, or sinusitis when safer alternatives exist.