Use of newest fluoroquinolones varies among practitioners

A: For all infectious conditions

Ernie Bowling

Ernie Bowling, OD, MS, FAAO, Dipl: I use new-generation fluoroquinolones for anything and everything infectious. The second-generation fluoroquinolones changed the way we treated ocular infections in a primary care practice, and the fourth-generation fluoroquinolones are a continuation and improvement upon that paradigm.

An overwhelming majority of red eyes seen in optometric settings are caused by conjunctivitis, yet the clinical variation in a patient with presumed bacterial conjunctivitis may range from a simple, straightforward presentation to a complex and sight-threatening clinical finding. A prompt diagnosis and intervention with an effective, fast-acting drug is ideal for the patient.

Bacterial conjunctivitis is by and large a self-limiting infection lasting approximately 1 week. Proactive treatment, however, will speed recovery, decrease the chance of secondary sequelae, reduce the possible spread of infection and allow your patients to return to their normal daily routines more rapidly, making for a happy patient. Happy patients equal successful doctors.

Gram-positive organisms are the most common cause of bacterial conjunctivitis and are also the most common cause of ocular infection (Limberg M, Buggé C. Cornea. 1994;13:496-499). The ideal antibiotic for ocular infections should be a broad-spectrum agent with excellent gram-positive coverage and potency that is effective against key pathogens, such as Staphylococcus and Streptococcus species.

The fourth-generation fluoroquinolones — moxifloxacin and gatifloxacin — have excellent effectiveness against gram-positive bacteria. In a recent study, moxifloxacin demonstrated high susceptibility (100%) for S. pneumoniae and H. influenzae and the highest susceptibility (82%) among the tested fluoroquinolones for S. aureus (Kowalski RP, et al. In vitro comparison of antibiotic resistance from 1996 to 2004 for antibiotics used for conjunctivitis therapy. Invest Ophthalmol Vis Sci. 2005;46:E-Abstract 2780). The greater level of potency exhibited by moxifloxacin will allow pathogens to be eradicated more quickly and effectively than any other fluoroquinolone.

Emerging drug resistance is of growing concern in antibiotic use. Pathogens such as coagulase-negative Staphylococcus and Staphylococcus aureus have developed resistance to the second- and third-generation fluoroquinolones, while the fourth-generations are still efficacious against these tough organisms (Mather R, Karenchak LM, Romanowski EG, et al. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002;133:463-466).

And of course, we all want to use medications that are safe. No one wishes to put their patients at risk. In clinical trials, no serious ophthalmic or systemic adverse reactions related to the use of moxifloxacin ophthalmic solution 0.5% or gatifloxacin ophthalmic solution 0.3% were reported. Across all clinical trials, moxifloxacin and gatifloxacin were found to be safe and well-tolerated in pediatric and adult patients with bacterial conjunctivitis.

In short, fourth-generation fluoroquinolones are safe, effective and well-tolerated, and they possess less risk for bacterial resistance.

As for dosing, I tend to follow the Wills Eye Manual guidelines (Lippincott Williams & Wilkins, 2004). For suspected bacterial conjunctivitis the usual dose is one drop four times daily. Suspected bacterial keratitis presenting as a small, non-staining peripheral inflitrate is dosed at every 2 hours. Larger peripheral inflitrates and any inflitrates with an overlying epithelial defect are dosed every hour for the first 24 hours, and I follow them daily. The fluoroquinolone is gradually tapered according to the clinical presentation. The “vision threatening” bacterial keratitis is out of my personal comfort zone. These patients are going to the corneal specialist for diagnostic scrapings and cultures.

• Ernie Bowling, OD, MS, FAAO, Dipl, is in private practice in Summerville and Lafayette, Ga. He can be reached at 76 Georgia Ave., Summerville, GA 30747; (706) 857-4015; fax: (706) 857-7782; e-mail: bowling@roman.net. Dr. Bowling has no direct financial interest in the products he mentions. He is on the speaker’s bureau for both Alcon and Allergan.

A: When treating a sight-threatening bacterial condition

Nicky R. Holdeman

Nicky R. Holdeman, OD, MD: I appreciate the use of the term “new-generation” vs. fourth-generation fluoroquinolones. Depending on one’s perspective and background, most medical specialists would contend, based on the history of systemic fluoroquinolones, that levofloxacin, gatifloxacin and moxifloxacin are actually all third-generation antibiotics. I mention this classification scheme only to point out the fact that the systemic forms of each of these antibiotics have been available since the late 1990s; the topical forms took an additional 40+ months to receive Food and Drug Administration approval.

It is also well known that drug-resistant bacteria continue to pose a major public health threat and that there are very few new antibiotics now in development to combat these deadly pathogens. Since 1998, only 10 new antibiotics have been approved, and only two are novel agents that have a new target of action. Pharmaceutical companies have less incentive to develop new antibiotics because they are not as profitable as other drugs that patients take for life, such as insulin and statins.

While eye doctors probably contribute little to bacterial resistance when compared to other specialties, I personally try to assess the severity of the condition when selecting a topical (or oral) antibiotic. When treating a self-limiting condition, such as an acute, community-acquired bacterial conjunctivitis, I am more likely to prescribe something like Polytrim (trimethoprim sulfate, polymyxin B sulfate, Allergan) or Ocuflox (ofloxacin, Allergan) four times daily in an attempt to accelerate resolution and reduce the risk of transmission. It should also be mentioned that if topical antibiotics are dosed as intended, most resistance problems are minimized, because dead organisms cannot mutate. Tapering below the recommended dosing regimen gives bacteria a better chance to develop resistance.

When confronted with a potentially sight-threatening condition, such as a bacterial keratitis, I carefully culture the cornea before beginning therapy. Not only do I want to identify the offending pathogen(s), but I also want to ensure that my initial selection of antibiotics is truly efficacious.

• Nicky R. Holdeman, OD, MD, is associate dean for clinical education and executive director, University Eye Institute, chief of medical services, University of Houston, 505 J. Davis Armistead Bldg., Houston, TX 77204-2020; (713) 743-1886; fax: (713) 743-0965; e-mail: nrholdeman@uh.edu. Dr. Holdeman has no direct financial interest in the products he mentions, nor is he a paid consultant for any of the companies.