Clinical Usefulness Of Quinolones
Ciprofloxacin, a second-generation quinolone, remains the most potent antipseudomonal quinolone in terms of in vitro activity. For instance, ciprofloxacin is consistently two to four times more active in vitro compared with trovafloxacin. Pharma-codynamically, ciprofloxacin's AUC:MIC ratio against P. aeruginosa is superior to any other available quinolone. Although this advantage is not clinically relevant in the therapy of cystitis because high urinary tract concentrations are achieved with almost all quinolones with antipseudomonal activity, it may have importance in respiratory tract infections that involve this organism.
One must consider, however, that ciprofloxacin's strength against P. aeruginosa is counterbalanced by poor in vitro activity against many gram-positive microorganisms. For instance, ciprofloxacin is at least two to four times less active against Staphylococcus aureus and S. pneumoniae compared with gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin. Moreover, ciprofloxacin is pharmacodynamically inferior to any of these third- and fourth-generation agents in this regard.
Therefore, ciprofloxacin's place in the therapy of respiratory tract infections should be limited to those that are likely or known to involve P. aeruginosa. Moreover, the use of ciprofloxacin should be avoided in the therapy of community-acquired respiratory tract infections, such as pneumonia, acute bacterial exacerbation of chronic bronchitis, and sinusitis for the aforementioned pharmacodynamic reasons.
The third-generation quinolones have perhaps the broadest potential for use of all agents in this class. Because of optimal pharmacodynamic profiles, these agents are useful in a variety of community-acquired infections, such as pneumonia, acute exacerbation of chronic bronchitis, sinusitis, cystitis, gonorrhea, and skin and soft tissue infections.
However, there are significant differences between these agents in terms of toxicity and safety. For instance, because of phototoxicity sparfloxacin has not gained significant usage. Moreover, grepafloxacin use has been hampered by taste perversion similar to claritromycin, in addition to having the potential to generate arrhythmia (QTc prolongation). These agents are also only available as oral formulations.
On the other hand, levofloxacin is well-tolerated, with an overall adverse event rate of less than 3%. Similarly, gatifloxacin also appears to be exceptionally well-tolerated and like levofloxacin will be available in intravenous and oral formulations. Gatifloxacin is twofold more active in vitro than levofloxacin against the pneumococci and generally has greater AUC:MIC ratios against gram-positive organisms. However, it is unclear if this will translate to a greater probability for clinical success in community-acquired respiratory tract infections.
The fourth-generation agents (e.g., trovafloxacin, clinafloxacin, and moxifloxacin) have expanded the spectrum of activity of the third-generation quinolones to include anaerobes. However, this breadth of spectrum can be viewed as an advantage and a disadvantage. Although these agents have a clear use in mixed aerobic and anaerobic infection, such as intra-abdominal infection and diabetic foot infection, their spectrum is too broad for most community- acquired infection, in which the causative pathogen is rarely anaerobic.
Additionally, these agents also have significant toxicity issues. Trovafloxacin usage is associated with severe dizziness, which generally resolves after the third day of dosing, and hepatotoxicity. In fact, trovafloxacin FDA labeling has already been changed to highlight hepatotoxicity, which can occur during both short- and long-duration therapy. Clinafloxacin, as mentioned earlier, has significant phototoxic potential. Clinically, in the critical care unit (CCU), clinafloxacin toxicity should be bal-anced against its impressive pharmacodynamic profile against multidrug resistant bacteria. Clinafloxacin is highly active against P. aeruginosa, Xanthamonas maltophilia, and other difficult to treat pseudomonads.
Semin Respir Crit Care Med. 2000;21(1) © 2000 Thieme Medical Publishers
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