This article is more than 5 years old. Information may no longer be current.
Next-generation fluoroquinolones offer broader spectrum of activity
Click Here to Manage Email Alerts
The advent of next-generation fluoroquinolones promises to make treatment for ocular infections more effective than ever. Significantly greater gram-positive coverage has the potential to further subdue organisms such as methicillin-resistant Staphylococcus aureus and resistant Streptococcus.
“There has been a fall-off in gram-positive activity for some of the current drugs such as ciprofloxacin, as shown in several in vitro studies,” said Bruce E. Onofrey, OD, RPh, a practitioner based in Albuquerque and a Primary Care Optometry News Editorial Board member. “The third- and fourth-generation fluoroquinolones have improved gram-positive activity as well as good gram-negative activity against gram-negative organisms such as Pseudomonas.”
Increasing resistance
According to Regis Kowalski, MS, a researcher based in Pittsburgh, Pa., susceptibility testing in his laboratory has evaluated S. aureus for its resistance. “S. aureus is showing an increase in resistance, and that is to the second and third generations of fluoroquinolones,” he said.
Mr. Kowalski also discussed resistant forms of pseudomonal infection. “We really don’t have much experience with that in Pittsburgh,” he said. “But in places like New York City, Miami and India, they have been seeing increased resistance to ciprofloxacin. At the same time, there’s no sure treatment yet.”
If asked what treatment he would recommend, Mr. Kowalski said he would suggest tobramycin for fluoroquinolone-resistant Pseudomonas aeruginosa. “Our model has shown a decrease in bacteria with tobramycin, although not as much as we would like. So that’s the way they’re going – tobramycin and a prayer,” he said.
According to Michael E. Zegans, MD, assistant professor of surgery at Dartmouth University, practitioners should stay informed about increases in pseudomonal resistance. “Those who treat with fluoroquinolones should be aware that pseudomonal resistance is possible and that they should obtain cultures,” he said. “They should also be aware that other non-pseudomonal organisms such as Streptococcus, which can cause bacterial keratitis, have much higher rates of resistance already.”
Gatifloxacin, moxifloxacin
Two fourth-generation fluoroquinolones receiving much attention are gatifloxacin and moxifloxacin, both of which have demonstrated greater gram-positive coverage than their predecessors.
“My general assessment of this process is that these drugs will become more specifically directed toward treating severe disease or significant bacterial keratitis,” Dr. Onofrey said. “I think Ocuflox (0.3% ofloxacin, Allergan), Ciloxan (0.3% ciprofloxacin, Alcon) and Quixin (0.5% levofloxacin, Santen) will be directed toward the more day-to-day use of anti-infectives. The drugs that are really going to end up leaving the field of play are the aminoglycosides.”
Studies conducted at the Charles T. Campbell Laboratory in Pittsburgh by R. Mather, L.M. Karenchak, E.G. Romanowski and Mr. Kowalski supported the gram-positive efficacy of fourth-generation quinolones.
One in vitro study concluded that fourth-generation fluoroquinolones are more potent than the second- and third-generation fluoroquinolones for gram-positive bacteria and are equally potent for gram-negative bacteria.
“Phase 3 clinical trials show that fourth-generation fluoroquinolones are 16 times more effective than third-generation fluoroquinolones against gram-positive organisms,” said J. James Thimons, OD, a practitioner based in Fairfield, Conn., and a Primary Care Optometry News Editorial Board member. “Also, they have an equal activity level on DNA gyrase as topo-4, which is the same as the older fluoroquinolones.”
Moxifloxacin study
A study conducted at Creighton University School of Medicine in Omaha by A. Pong, K.S. Thomson, S.A. Chartrand and C.C. Sanders analyzed moxifloxacin’s activity against pathogens with increased susceptibility to ciprofloxacin. In the study, a panel of 279 clinical isolates of gram-positive cocci and gram-negative bacilli with varying levels of resistance to ciprofloxacin were analyzed for susceptibility to moxifloxacin, ciprofloxacin, ofloxacin and nalidixic acid.
Moxifloxacin was eight to 32 times more potent than ciprofloxacin and ofloxacin against staphylococci and Streptococcus pneumoniae and eight times more potent against enterococci.
The study indicated that moxifloxacin is more potent than ciprofloxacin and ofloxacin against gram-positive pathogens, may be comparable in activity against less quinolone-susceptible gram-negative isolates and is less affected than ciprofloxacin by mechanisms responsible for increasing quinolone resistance in staphylococci.
Gatifloxacin findings
Other studies have yielded similar results on gatifloxacin. Pre-clinical studies conducted by A. Okumura and H. Naka in Japan have concluded that gatifloxacin has a broader antibacterial spectrum against gram-positive and gram-negative organisms, with particularly more potent gram-positive activity.
The study found that gatifloxacin has strong microbial activity compared to ofloxacin to induce bacterial resistance less frequently. Furthermore, gatifloxacin was found to have good water-solubility, stable metabolism, low phototoxicity, good tissue penetration and a low degree of interaction with nonsteroidal anti-inflammatory agents.
Indications for Quixin
Quixin, the newest available fluoroquinolone, is a third-generation fluoroquinolone that is active against a broad spectrum of gram-positive and gram-negative pathogens. It demonstrated significant efficacy in randomized, double-masked, multicenter controlled trials. Patients were dosed for 5 days, and clinical cures were confirmed in 79% of patients treated for bacterial conjunctivitis. Microbial outcomes for the same clinical trials demonstrated an eradication rate of 90% for presumed pathogens.
Richard L. Lindstrom, MD, a practitioner based in Minneapolis and a Primary Care Optometry News Editorial Board member, uses Quixin for several purposes. “I use it for presumed or culture-positive bacterial conjunctivitis and keratitis. Occasionally, I use it for dacryocystitis and staph blepharitis.”
Paul M. Karpecki, OD, a practitioner based in Overland Park, Kan., and a Primary Care Optometry News Editorial Board member, said, “Quixin is a next-generation fluoroquinolone, as it is the L-isomer, or a modification of an already-effective first-generation fluoroquinolone, ofloxacin. This modification has resulted in a neutral pH of the medication, greater solubility and a concentration of 0.5% rather than 0.3%.
“The next version is likely to be a 1.5% concentration,” he continued. “In clinical trials, the concentration was so high that there was no need for a preservative. This will result in further concentration of drug in the aqueous or corneal stroma, with the same solubility but even less toxicity, as it will be preservative-free.”
Shifting roles
Dr. Thimons said the third-generation fluoroquinolones will most likely assume a more “everyday” role in treatment. “The third generations will become the probable inheritors of the more common therapeutic interventions,” he said. “And the fourth generations will be more directed toward specific therapeutic interventions.”
Dr. Onofrey added that a new generation of fluoroquinolones is needed to combat decreases in efficacy shown by the second generation. “Gram-positive activity is the number one cause of bacterial infection in adults,” he said. “Ocular infection is caused by organisms like staph and strep. That’s where we need a new generation, to make up for the fall in efficacy. Levofloxacin is the best of the available fluoroquinolones and has the highest activity against gram-positive pathogens such as staph and strep.”
For Your Information:
- Bruce E. Onofrey, OD, RPh, can be reached at 5150 Journal Center Boulevard, Albuquerque, NM 87109; (505) 275-4226; fax: (505) 275-4203. Dr. Onofrey has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Regis Kowalski, MS, can be reached at 203 Lothrop Street, Pittsburgh, PA 15213; (412) 647-7211; fax: (412) 647-5331. Mr. Kowalski has no direct financial interest in the products mentioned in this article. He is a paid consultant for Alcon.
- Michael E. Zegans, MD, can be reached at Dartmouth-Hitchcock Medical Center, Section of Ophthalmology, One Medical Center Dr., Lebanon, NH 03756-0001; (603) 605-8755; fax: (603) 650-1318. Dr. Zegans has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- J. James Thimons, OD, can be reached at 75 Kings Highway Cutoff, Fairfield, CT 06430; (203) 334-2020; fax: (203) 334-2401. Dr. Thimons has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Richard L. Lindstrom, MD, can be reached at 710 East 24th Street, Minneapolis, MN 55404; (612) 813-3633; fax: (612) 813-3660. Dr. Lindstrom has no direct financial interest in the products mentioned in this article. He is a paid consultant for Santen and Allergan.
- Paul M. Karpecki, OD, can be reached at 1115 West 109th St., Overland Park, KS 66210; (913) 906-9329; fax: (913) 906-0729. Dr. Karpecki is a consultant for Santen.