Infection
Update

 

Levofloxacin: First-Line Therapy in Pyelonephritis,Complicated and Nosocomial Urinary Tract Infections,and Bacterial Prostatitis

 

There are numerous reports supporting the use of fluoroquinolones in urological infections with Prof. Naber noting that levofloxacin is particularly useful due to its broad-spectrum antimicrobial coverage, urinary excretion and advantageous pharmacokinetic and pharmacodynamic (PK/PD) profile. He also noted that urinary excretion rates differ widely among the fluoroquinolones with levofloxacin possessing a high urinary excretion (84%), compared with an intermediate rate for ciprofloxacin (43%), and a low rate for moxifloxacin (20%) (1).

Levofloxacin is even more beneficial in that it can be given as a high-dose (750 mg) regimen, which reaches almost twice the peak plasma concentration levels compared with the 500 mg dose. As a concentration-dependent antimicrobial, the higher levofloxacin dose achieves higher area under the curve (AUC) or peak level to minimal inhibitory concentration (MIC) ratios, which is associated with rapid and more effective bacterial killing. These features enable the levofloxacin 750 mg once-daily regimen to be successfully administered as a 5-day treatment, while maintaining efficacy compared with longer durations of therapy.

Prof. Naber emphasized the efficacy of the shorter levofloxacin regimen by reporting results from a trial comparing 5 days of 750 mg IV/oral levofloxacin once daily with 10 days of 400 mg IV/500 mg orally twice daily ciprofloxacin in patients with complicated urinary tract infections (UTIs) and acute pyelonephritis. The bacterial eradication rates for levofloxacin (86.0%) and ciprofloxacin (89.2%) were in general comparable (2) but, in the subgroup of catheterized patients, high-dose levofloxacin was shown to achieve even higher bacterial eradication rates compared with the ciprofloxacin 10-day regimen (78.9% vs. 53.3%) (3), a feature which Prof. Naber described as being particularly useful in managing biofilm infections. In addition, he noted that the 750 mg, 5-day levofloxacin regimen has been shown to be as safe and well tolerated as the 500 mg, 10-day schedule. The levofloxacin 750 mg regimen is also less likely to result in resistance, particularly compared with lower dose ciprofloxacin as levofloxacin is not affected by any of the 3 efflux pumps affecting other fluoroquinolones (4).

Prof. Naber then turned his attention to complicated and nosocomial UTIs noting that the 2013 European Association of Urology (EAU) guidelines (5) recommend treating these infections with a fluoroquinolone. He stressed that levofloxacin is especially indicated in these often difficult to treat UTIs.

The empiric treatment of acute bacterial prostatitis should also start with fluoroquinolones and/or β-lactams, and then be adjusted if necessary depending on susceptibility results. Fluoroquinolones are the drugs of choice for chronic bacterial prostatitis due to their excellent penetration into prostatic tissue with levofloxacin achieving high tissue and fluid concentrations for this chronic infection. In fact, 250 mg levofloxacin achieves a 0.89 mg/L concentration in prostatic fluid compared with only 0.16 mg/L for 250 mg ciprofloxacin, a 5.5 times higher concentration (6).

Prof. Naber concluded that levofloxacin demonstrates good results in UTIs, especially pyelonephritis, complicated and nosocomial UTIs, and bacterial prostatitis. While optimal dosage and treatment durations need to be reassessed, the high-dose, short-term levofloxacin regimen is a useful option.

References
(1) Naber KG. Int J Antimicrob Agents 2001; 17: 331-41.
(2) LEVAQUIN® (levofloxacin) Prescribing Information. Raritan, NJ: Ortho-McNeil-Janssen Pharmaceuticals, Inc. March 2009.
(3) Peterson J, et al. Urology 2008; 71: 17-22.
(4) Yang S, et al. J Antimicrob Chemother 2003; 51: 545-56.
(5) Grabe M, et al. Guidelines on Urological Infections. European Association of Urology, 2013.
(6) Bulitta JB, et al. Chemotherapy 2011; 57: 402-16.



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