Urinary tract infections (UTI) have been reported to result in nearly 7 million office visits, 1 million emergency department visits, and up to 100,000 hospitalizations annually with an annual cost of $1.6 billion.1 Most of these cases occur in women with nearly 1 in 3 women having at least 1 UTI prior to the age of 24 years.  For men, the risk increases after the age of 65 years.1  Other risk factors that predispose patients to UTIs include being an infant, pregnancy, diabetes, indwelling urinary catheters, spinal cord injuries, immunodeficiencies, and underlying urologic abnormalities.1  Regardless of whether the patient is experiencing a complicated or uncomplicated UTI, a 3 to 7 day course of many fluoroquinolone antibiotics has resulted in eradication rates greater than 90%.2  However, this data does not apply to all fluoroquinolones currently available on the market (ciprofloxacin (Cipro), gemifloxacin (Factive), levofloxacin (Levaquin), moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin)). Which fluoroquinolones can be used for the treatment of UTIs?

Of the fluoroquinolones available, only ciprofloxacin, levofloxacin, norfloxacin, and ofloxacin are approved for the treatment of UTI.2-4  As the previous list suggests, gemifloxacin and moxifloxacin are the only two that do not have Food and Drug Administration (FDA) approval for treatment of UTI.5,6  Interestingly, gemifloxacin has demonstrated superior in-vitro activity against many bacteria that are known to cause UTIs (with the exception of Proteus mirabilis) when compared to ofloxacin.7  In-vitro data for moxifloxacin also shows good antimicrobial activity against similar bacteria.5  Why then are these fluoroquinolones not effective in-vivo during the actual treatment of a UTI caused by these same organisms?  

In short, a medication is only effective if it reaches the desired site of action.  The process of sensitivity testing allows for the antibiotic to be placed directly in the presence of the bacteria in question.  The pharmacokinetics of a medication does not usually allow for such easy delivery of drug to the tissue(s) being targeted.  Thus, efficacy observed in the laboratory does not always translate into clinical efficacy.  Gemifloxacin and moxifloxacin are not effective for the treatment of UTIs because they do not achieve adequate concentrations in the urine.5-7  The fluoroquinolones indicated for UTI are excreted in the urine as greater than 40% unchanged drug while gemifloxacin is less than 35% and moxifloxacin is only 20%.5-7  Therefore, gemifloxacin and moxifloxacin do not reach the site of action in concentrations sufficient to result in eradication rates comparable to many other treatment options.  As such, they should not be used or relied upon for this indication.  

This is an important observation for clinicians to make in order to avoid inappropriately extrapolating data from one fluoroquinolone to another when treating a specific condition.  Other examples include activity against Pseudomonas aeruginosa or the treatment of community acquired pneumonia (CAP) with fluoroquinolone antibiotics; not all fluoroquinolones are effective in these situations.2-6  Failure of clinicians to recognize such differences within a drug class may result in ineffective treatment of the patient and may put the healthcare provider at risk for medical/legal action.

References:

1. Foxman B.  Epidemiology of urinary tract infections: incidence, morbidity, and economic costs.  Am J Med  2002;113:5S-13S.  
2. Warren JW, Abrutyn E, Hebel JR et al.  Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women.  Infectious Diseases Society of America (IDSA).  Clin Infect Dis  1999;29:745-58.  
3. Ciprofloxacin (Cipro®) product package insert.  Bayer Healthcare Pharmaceuticals Inc.  Wayne, NJ.  April 2009.
4. Levofloxacin (Levaquin®) product package insert.  Ortho-McNeil-Janssen Pharmaceuticals, Inc.  Raritan, NJ.  December 2008.
5. Gemifloxacin (Factive®) product package insert.  Oscient Pharmaceuticals Corporation.  Waltham, MA.  October 2008.
6. Naber CK, Hammer M, Kinzig-Schippers M et al.  Urinary excretion and bactericidal activities of gemifloxacin and ofloxacin after a single oral dose in healthy volunteers.  Antimicrob Agents Chemother  2001;45:3524-30.