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?
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?
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.
- Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med 2002;113:5S-13S.
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
- Ciprofloxacin (Cipro®) product package insert. Bayer Healthcare Pharmaceuticals Inc. Wayne, NJ. April 2009.
- Levofloxacin (Levaquin®) product package insert. Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ. December 2008.
- Gemifloxacin (Factive®) product package insert. Oscient Pharmaceuticals Corporation. Waltham, MA. October 2008.
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