A Promising Future
The new fluoroquinolone moxifloxacin holds hope for future treatment.
By Hans M. Kell, O.D., F.A.A.O., Louisville, Colo.

As you may know, fluoroquinolones are potent topical, oral and intravenous broad-spectrum antimicrobial agents that are used to treat infectious diseases. Ophthalmic fluoroquinolones have become commonplace in treating bacterial conjunctivitis and bacterial keratitis and for post-surgical use as well.

Pharmacologically, fluoro-quinolone medications target the activity of two bacterial enzymes required for DNA replication: topoisomerase IV (Gram-positive bacteria) and DNA gyrase (Gram-negative bacteria).

In the early days

The early fluoroquinolones demonstrated broad Gram-negative coverage with variable Gram-positive coverage. One of the first generation agents, ciprofloxacin, has an excellent safety profile and is many doctors' standard optimal therapeutic choices for treatment of many Gram-negative organisms.

Systemic fluoroquinolone research

Fluoroquinolones constitute the mainstay of antibiotic research development today. Today's research challenge is to improve Gram-positive and Gram-negative coverage, as well as to eradicate those organisms that are resistant to other antimicrobial medications.

The new systemic fluoroquin-olones (clinafloxacin, gatifloxacin, gemifloxacin, grepaflox-acin, levofloxacin, moxiflox-acin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g., against S. pneumoniae and S. aureus) over ciprofloxacin.

However, ciprofloxacin continues to maintain the best in vitro activity against Pseudomonas aeruginosa.

Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g., Bacteroides fragilis) when compared to ciprofloxacin. They also demonstrate improved bioavailability and longer serum half-lives, which allow for once-daily dose administration.

Nevertheless, despite their promise, several of these new fluoroquinolone compounds have been withdrawn from the market. Others have had their use severely restricted because of adverse effects (hepatotoxicity [trovaflox-acin], cardiotoxicity [grepafloxacin], phototoxicity and hypoglycemia [clinafloxacin], phototoxicity [sparfloxacin]). Still others have been discontinued during developmental phases.

The remaining fluoroquinolones, including gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin, have adverse effect profiles similar to that of ciprofloxacin.

On trial

Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated their good efficacy in various community-acquired respiratory infections (e.g., pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis).

Gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin offer several advantages over ciprofloxacin and are promising as important therapeutic agents in treating community-acquired respiratory infections.

Moxifloxacin and gatiflox-acin are more highly potent against penicillin-susceptible and multi-drug-resistant S. pneumoniae, while retaining activity against enterobacteria.

Clinical Phase III development of these antibiotics has shown them to produce satisfactory clinical and bacteriologic responses in respiratory infections and to be remarkably free of clinically significant adverse effects.

Their broad spectrum of activity, which includes penicillin- and macrolide-resistant S. pneumoniae, favorable pharmacokinetic parameters, good bacteriological and clinical efficacy, will lead to their growing use to treat community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis. At the same time, they might save costs when they can be used orally in place of intravenous antibacterials.

Ophthalmic moxifloxacin

Although it's still undergoing clinical trial investigation, moxifloxacin shows great potential against ophthalmic infectious disease. While data are limited, early research suggests that this new fluoroquinolone may be equally or more potent than competitive quinolone agents in treating Gram-negative organisms, and more potent in treating Gram-positive organisms.

It demonstrates the highest efficacy in treating fluoroquin-olone-resistant S. aureus and coagulase negative Staphylococcus.

Supportive evidence

In an in vitro study, Mather, et al demonstrated the following:

• Generally, the order of significant susceptibility for Gram-negative bacteria was: moxifloxacin = gatifloxacin = ciprofloxacin = levofloxacin > ofloxacin.
• Generally, the order of significant susceptibility for Gram-positive bacteria was: moxifloxacin > gatifloxacin > ciprofloxacin = levofloxacin > ofloxacin.
• The order of significant susceptibility for second-generation (ciprofloxacin and ofloxacin) fluoroquinolone-resistant S. aureus was: moxifloxacin > gatifloxacin > levofloxacin > ciprofloxacin = ofloxacin.
• The order of significant susceptibility for second-generation (ciprofloxacin and ofloxacin) fluoroquinolone-resistant coagulase negative Staphylococcus was: moxifloxacin = gatifloxacin > levofloxacin = ciprofloxacin = ofloxacin.
• second, unrelated study also found that moxifloxacin was highly effective in treating both quinolone-sensitive and quinolone-resistant experimental S. aureus isolates.

Bright days ahead

Overall, moxifloxacin shows great promise as a possible first choice topical anti-microbial medication for treating bacterial conjunctivitis, bacterial keratitis, endophthalmitis, and for post-surgical management.

Its extensive Gram-negative coverage, respectable Gram-positive coverage and reported safety profile makes it a highly promising ophthalmic medication. Once the FDA approves this drug, we'll have yet another great option to choose from when treating bacterial conjunctivitis and bacterial keratitis in our patients.

Dr. Kell is a frequent national lecturer speaking on various topics within the field of optometric care and has been published in ophthalmic literature as well. Dr. Kell is also a fellow of the American Academy of Optometry.

Dr. Christensen has a partnership practice in Midwest City, Okla. He's a diplomate in the Cornea and Contact Lens Section of the American Academy of Optometry. He's also a member of National Academies of Practice.