Letters to the Editor
Possible Drug Interactions Among Quinolones
Am Fam Physician. 2004 Feb 1;69(3):489.
to the editor: The article1 on quinolones by Drs. Oliphant and Green was an excellent review of this important, yet often overly prescribed, class of antibiotics. We would like to commend the authors for increasing awareness of the emerging resistance to these agents. However, we would like to further elucidate some of the other issues addressed in the article.
The article1 states that levofloxacin is an effective first-line agent for the treatment of prostatitis, but that “ciprofloxacin should be reserved for use in patients with resistant gram-negative, pseudomonal, and enterococcal prostatitis, because of its superior activity against [Pseudomonas] aeruginosa and enterococci.” The minimum inhibitory concentration (MIC) of levofloxacin (MIC = 4) is usually greater than the activity of ciprofloxacin (MIC = 16). In 2001, we found at our institution that 57 percent of all enterococcal isolates were susceptible to levofloxacin, while only 30 percent were susceptible to ciprofloxacin.
Another issue concerns the penetration of fluoroquinolones into the cerebrospinal fluid (CSF). We agree with the authors' statement that these agents should not be considered as first-line treatment for meningitis. However, CSF concentrations of fluoroquinolones are approximately 20 to 50 percent those of serum in noninflamed meninges.2 In comparison, CSF concentrations of third-generation cephalosporins range from 10 to 40 percent those of serum in inflamed meninges. High-dose ciprofloxacin has been used to treat multidrug-resistant gram-negative meningitis with favorable outcomes.2
Also, the information on the potential interactions between quinolones and other drugs presented in Table 3 of the article1 could possibly be misleading to some readers. Although four case reports have suggested a possible pharmacokinetic or pharmacodynamic drug interaction between cyclosporine and ciprofloxacin, many pharmacokinetic studies have refuted this suspicion.3 Literature discussing the interaction implies that ciprofloxacin has an antagonistic action on the immunosuppressive effect of cyclosporine.4 The significance of this interaction remains controversial. In addition, levofloxacin does not seem to interact pharmacokinetically with cyclosporine.5
Ciprofloxacin may cause an average increase in serum theophylline levels of 50 to 60 percent.2 However, the newer fluoroquinolones (moxifloxacin, gemifloxacin, gatifloxacin, levofloxacin, and trovafloxacin), appear to have no significant effect on theophylline metabolism.2 Ciprofloxacin also has been shown to interact unpredictably with warfarin. Apparently, if warfarin is used concomitantly with one of the newer fluoroquinolones, the combination does not usually result in an increased international normalized ratio (INR).2 Though one pharmacokinetic study states that no interaction exists between levofloxacin and warfarin, three publications describing eight patients (75 percent were elderly with age greater than 70 years and comorbidities) have reported an enhanced anticoagulant effect of warfarin when levofloxacin was added (INR up to 11.5). More research is needed to determine the true nature and significance of the interactions between warfarin and levofloxacin.2,6
1. Oliphant CM, Green GM. Quinolones: a comprehensive review. Am Fam Physician. 2002;65:455–64.
2. Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials. Clin Pharmacokinet. 2001;40:169–87.
3. Hoey LL, Lake KD. Does ciprofloxacin interact with cyclosporine?. Ann Pharmacother. 1994;28:93–6.
4. Wrishko RE, Levine M, Primmett DR, Kim S, Partovi N, Lewis S, et al. Investigation of a possible interaction between ciprofloxacin and cyclosporine in renal transplant patients. Transplantation. 1997;64:996–9.
5. Doose DR, Walker SA, Chien SC, Williams RR, Nayak RK. Levofloxacin does not alter cyclosporine disposition. J Clin Pharmacol. 1998;38:90–3.
6. Jones CB, Fugate SE. Levofloxacin and warfarin interaction. Ann Pharmacother. 2002;36:1554–7.
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