Concern has been raised about widespread empiric use of fluoroquinolones because evidence in human medicine suggests that they concentrate in gut and nasal mucosa, and their use is a risk factor for selection of resistant gram-negative bacterial populations in the gastrointestinal tract and infections by Peptoclostridium difficile (formerly Clostridium difficile; ulcerative colitis).¹ However, a goal is to emphasize rational use of antibiotics such as fluoroquinolones, because they are critical and effective drugs for treatment of many susceptible and serious bacterial infections, such as pyelonephritis, prostatitis, and pneumonia, and for initial treatment of sepsis when the causative agent is not known.

Most veterinary fluoroquinolones (enrofloxacin, marbofloxacin, orbifloxacin) have activity primarily against gram-negative bacteria by acting on DNA gyrase, inhibiting supercoiling of DNA. Some activity exists against gram-positive bacteria as a result of their action on topoisomerase IV. Fluoroquinolones are concentration-dependent antimicrobial drugs, which means they are most effective when used at higher doses once a day. In general, twice-daily therapy with fluoroquinolones is not necessary and should be avoided.

Pradofloxacin is a third-generation fluoroquinolone that has potential value for the treatment of gram-positive and gram-negative infections in cats. Pradofloxacin was released in 2011 in Europe for treatment of bacterial infections in dogs and cats, and in 2013 in the United States for treatment of bacterial infections in cats. Pradofloxacin is an 8-cyanofluoroquinolone that has greater in vitro activity against gram-positive aerobic bacteria and anaerobes in vitro than other veterinary fluoroquinolones.² It also has enhanced in vitro activity against some other bacterial species, including Bartonella henselae, Bordetella bronchiseptica, extra­intestinal Escherichia coli, and some mycobacterial species. Pradofloxacin inhibits both DNA gyrase and topoisomerase IV in gram-positive bacteria, leading to improved in vitro activity against gram-positive and anaerobic bacterial pathogens. Because of these two mechanisms of action, there is the potential for reduced likelihood of selection of drug-resistant mutants when compared with other veterinary fluoroquinolones. Pradofloxacin also lacks retinal toxicity in cats, unlike enrofloxacin.

Situations in which fluoroquinolones should be considered as first-line treatments for empiric therapy include:

1.  Pyelonephritis should be considered in dogs and cats with clinicopathologic evidence of acute or progressive renal insufficiency and bacteriuria, especially if accompanied by fever and leukocytosis. Fluoroquinolones generally have excellent tissue penetration. Penicillins alone may not achieve adequate concentrations in infected kidney tissue, and there may be concerns about treatment with trimethoprim-sulfamethoxazole because of the greater risk of adverse effects with long treatment durations. Whenever feasible, culture and susceptibility (C&S) testing of the urine should be performed in dogs and cats suspected to have pyelonephritis before initiation of antimicrobial treatment, because resistant infections are widespread and the implications of inappropriate treatment on renal function may be profound. Treatment of pyelonephritis should then be commenced, before the results of C&S testing are available. Once the results of C&S testing are available, treatment should be narrowed to only the drugs necessary if combination therapy was used initially. Currently, veterinary guidelines recommend treatment of pyelonephritis for 4 to 6 weeks, but shorter durations of therapy (10–14 days) may be adequate. In cats that can tolerate oral medications, a fluoroquinolone that is not associated with retinal toxicity, such as marbofloxacin or pradofloxacin, should be used because renal insufficiency may impair fluoroquinolone metabolism and excretion, leading to toxic plasma concentrations.

2.  Antimicrobial drugs that penetrate the prostate are limited to fluoroquinolones, trimethoprim-sulfamethoxazole, and chloramphenicol. Because of potential adverse effects of trimethoprim-sulfamethoxazole and chloramphenicol, fluoroquinolones are usually the drugs of choice. As with the treatment of bacterial pyelonephritis, C&S testing should be performed when possible, but treatment should be initiated before receiving C&S results.

3.  In this case, parenteral administration of a fluoroquinolone is indicated together with a drug that has activity against gram-positive and anaerobic bacteria (e.g., ampicillin or clindamycin) until the results of C&S testing are available. Most veterinary textbooks recommend treatment of bacterial pneumonia and pyothorax for 4 to 6 weeks, but shorter courses of treatment, such as those used to treat pneumonia in humans, might be effective in some cases. In patients with pyothorax, antibiotics are usually only effective following the removal of the septic exudate by surgery and/or chest tubes. Animals with pneumonia or pyothorax should be re-evaluated 10 to 14 days after starting treatment, and a decision made as to whether to extend therapy.

4.  In one study, pradofloxacin was superior to doxycycline for treatment of cats with feline infectious anemia.³

5.  These are situations in which the use of high concentrations of an active fluoroquinolone can overwhelm bacterial resistance mechanisms and be effective when other therapies fail.

6.  Treatment of rapidly-growing mycobacterial infections. Fluoroquinolones concentrate intracellularly within infected leukocytes and may be effective alone or in combination with other drugs for refractory mycobacterial infections.

References

1.  Werner NL, Hecker MT, Sethi AK, et al. Unnecessary use of fluoroquinolone antibiotics in hospitalized patients. BMC Infect Dis. 2011;11:187.

2.  Sykes JE, Blondeau JM. Pradofloxacin: a novel veterinary fluoroquinolone for treatment of bacterial infections in cats. Vet J. 2014;201:207–214.

3.  Dowers KL, Tasker S, Radecki SV, et al. Use of pradofloxacin to treat experimentally induced Mycoplasma haemofelis infection in cats. Am J Vet Res. 2009;70:105–111.

4.  Vishkautsan P, Reagan KL, Keel MK, Sykes JE. Mycobacterial panniculitis caused by Mycobacterium thermoresistibile in a cat. J Feline Med Surg. 2016;2(2):2055116916672786.