Fluoroquinolones: Antibiotic Classification
Fluoroquinolones are a class of synthetic broad-spectrum antibacterial agents that inhibit bacterial DNA replication by targeting DNA gyrase (topoisomerase II) and topoisomerase IV enzymes. 1, 2
Mechanism of Action and Chemical Structure
- Fluoroquinolones are chemically distinct from other antibiotic classes, containing a fluorine atom attached to the quinolone nucleus, which differentiates them from the original quinolone prototype nalidixic acid 1
- Their bactericidal action results from inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV, enzymes essential for bacterial DNA replication, transcription, repair, and recombination 2
- This mechanism is fundamentally different from beta-lactams (penicillins, cephalosporins), aminoglycosides, macrolides, and tetracyclines, meaning bacteria resistant to those classes may remain susceptible to fluoroquinolones 2
Generational Classification
Second-Generation Fluoroquinolones
- Include ciprofloxacin, levofloxacin, norfloxacin, and ofloxacin 1
- Provide enhanced Gram-negative spectrum with activity against Pseudomonas aeruginosa 1
- Ciprofloxacin became the first fluoroquinolone approved for pediatric use (ages 1-17 years) in 2004 1
Third-Generation Fluoroquinolones
- Represented by gemifloxacin 1
- Offer substantially increased activity against Streptococcus pneumoniae while retaining Gram-negative coverage 1
- Also effective against atypical pathogens including Mycoplasma pneumoniae and Chlamydophila pneumoniae 1
Fourth-Generation Fluoroquinolones
- Represented by moxifloxacin 1
- Display increased anaerobic activity while maintaining Gram-positive and Gram-negative coverage of third-generation agents 1
- Provide excellent activity against mycobacteria including most U.S. strains of Mycobacterium tuberculosis 1
Antimicrobial Spectrum in UTIs
- Fluoroquinolones demonstrate high in vitro activity against both Gram-negative and Gram-positive uropathogens 1, 3
- Common UTI pathogens covered include Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter species, Pseudomonas aeruginosa, Staphylococcus saprophyticus, and Enterococcus faecalis 2, 4
- Most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile, are resistant to fluoroquinolones 2
Pharmacokinetic Properties Relevant to UTI Treatment
- Fluoroquinolones exhibit concentration-dependent bactericidal activity with high renal excretion 5, 3
- They achieve urinary concentrations several-fold higher than serum concentrations, providing prolonged urinary bactericidal titers 5, 6
- Approximately 20-35% of an oral ciprofloxacin dose is recovered in feces, with only small amounts appearing in bile as unchanged drug 2
Critical Distinction from Other Antibiotic Classes
- There is no known cross-resistance between fluoroquinolones and penicillins, cephalosporins, aminoglycosides, macrolides, or tetracyclines 2
- Resistance to fluoroquinolones develops slowly through multiple-step mutations rather than single-step resistance 2
- The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2, indicating efficient bactericidal activity 2