List of Fluoroquinolones
The fluoroquinolones include ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, gemifloxacin, ofloxacin, norfloxacin, and delafloxacin, which are categorized into different generations based on their antimicrobial spectrum and development timeline. 1
Classification by Generation
First Generation
- Nalidixic acid (prototype quinolone, approved by FDA in 1964)
Second Generation
- Ciprofloxacin
- Levofloxacin
- Ofloxacin
- Norfloxacin
Third Generation
- Gemifloxacin (increased activity against Streptococcus pneumoniae while maintaining activity against many Gram-negative pathogens)
Fourth Generation
- Moxifloxacin (increased activity against anaerobes while maintaining Gram-positive and Gram-negative activity)
- Gatifloxacin
- Delafloxacin
Antimicrobial Spectrum
- Second-generation agents have greater Gram-negative spectrum with activity against Pseudomonas aeruginosa 1
- Third-generation agents provide substantially increased activity against Streptococcus pneumoniae, Mycoplasma pneumoniae, and Chlamydophila pneumoniae 1
- Fourth-generation agents display increased activity against anaerobes while maintaining the Gram-positive and Gram-negative activity 1
Clinical Applications
Fluoroquinolones are used for various infections including:
- Urinary tract infections (UTIs) caused by E. coli, Pseudomonas aeruginosa, Enterobacter species, Citrobacter species, and Serratia species 1
- Respiratory infections (pneumonia, acute otitis media, sinusitis) 1
- Gastrointestinal infections (Salmonella, Shigella) 1
- Tuberculosis (levofloxacin, moxifloxacin, gatifloxacin) 2
- Plague (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) 3
Important Safety Considerations
- Fluoroquinolones can cause QT interval prolongation and should be avoided in patients with known QT prolongation, uncorrected electrolyte abnormalities, or those receiving Class IA or III antiarrhythmic agents 4
- Tendinitis and tendon ruptures can occur during treatment or months after treatment, particularly in patients >60 years, those with chronic renal disease, or those using corticosteroids 4
- CNS effects including dizziness, insomnia, tremulousness, and headache may occur and require careful monitoring, especially in elderly patients 4
- Contraindicated in children, adolescents, and pregnant women due to potential effects on cartilage development 5
- Several fluoroquinolones have been withdrawn from the market due to serious adverse effects:
- Clinafloxacin (phototoxicity and hypoglycemia)
- Grepafloxacin (QTc prolongation and torsades de pointes)
- Sparfloxacin (phototoxicity)
- Trovafloxacin (hepatotoxicity) 6
Clinical Pearls
- Ciprofloxacin maintains the best in vitro activity against Pseudomonas aeruginosa among the fluoroquinolones 6
- Absorption can be impaired by aluminum- or magnesium-containing antacids and by zinc, iron, or calcium supplements 5
- Increasing bacterial resistance to fluoroquinolones is a concern, particularly with increased use 1
- Use should be restricted to situations where there is no safe and effective alternative to treat multidrug-resistant bacteria or when parenteral therapy is not feasible 7
The appropriate selection of a fluoroquinolone should be based on the specific pathogen, site of infection, patient factors, and local resistance patterns to optimize outcomes in terms of morbidity and mortality.