New options: Levofloxacin and trovafloxacin

Despite some concerns that the introduction of breakthrough antibiotics may be over, antibiotic class variations continue to come to market.

Two new fluoroquinolones — levofloxacin and trovafloxacin — merit consideration both for the antibiotic formulary and how they may fit into anti-resistance strategies.

As potential second-generation fluoroquino-lones, both drugs are getting high marks for their efficacy against gram-positive bacteria and for simply outshining other drugs in their class. Both drugs are praised for their single-daily dosage capabilities, overall tolerability, and decreased potential for phototoxicity when compared with other quinolones.

The drug interaction pharmacokinetics are quite similar to other quinolones. And in terms of anti-resistance capabilities, there are positive early signs, but the paucity of studies leads researchers to believe that overall resistance would mirror other quinolones.

One in vitro anti-resistance study of levoflox-acin does note that based on repeated exposure to coagulase-negative staphylococci, resistance developed more slowly to levofloxacin than to cipro-floxacin, while trovafloxacin has shown efficacy against penicillin-resistant pneumonia strains in animal models.

Both drugs ‘potentially valuable’

These points are detailed in a 13-page review buoyed by 110 clinical study references in the American Journal of Health-System Pharmacists.1 In it, the authors note that both drugs have proven more potent than the drugs in their class against a host of common gram-negative quinolones, while stressing that the flexibility of the drugs and their effects on gram-positive bacteria make them "potentially valuable additions" to antibiotic formularies.

Marketed as Levaquin by Ortho-McNeil, levofloxacin has received FDA approval for adult use against pneumonia, sinusitis, bronchitis, and skin and urinary tract infections. The drug has a half-life of about eight hours and comes in both oral and IV solutions, recommended for a once-daily 500 mg dose for mild or moderate infections, twice a day for more serious cases. (Dosages of 250 mg are recommended for genitourinary infections.)

Compared with three other quinolones, levofloxacin is cheaper than ofloxacin, ciprofloxacin and sparfloxacin, averaging $350 for 50 500 mg tabs and $39.60 for a 500 mg vial (a little more than $10 cheaper than an equivalent vial of ciproflox-acin). In daily oral doses, levofloxacin costs $7, compared with $8.28 for ofloxacin, $11.58 for ciprofloxacin, and $7.36 for sparfloxacin.

Phase III trials for trovafloxin, developed by Pfizer (CP-99, 219), include pneumonia, bronchitis, urinary tract infections, uncomplicated gonorrhea, and h. pylori. The drug also is being evaluated for skin or soft tissue infections, intra-abdominal infections, and, most notably, for pediatric meningitis.

Current dosage levels are 100 mg daily, up to 200 to 300 mg for more severe infections. The drug carries a half-life of 12 hours.

The authors note that, like levofloxacin, trovafloxacin is proving more potent than other quinolones against common bacterial enemies, but they are most impressed by the drug’s activity — moreso than shown by levofloxacin — against "problematic gram-positive pathogens such as enterococci, streptococci and staphylococci."

[For more information, contact Marianne Billeter, PharmD, Shenandoah University School of Pharmacy, 1460 University Drive, Winchester, VA 22601. Telephone: (540) 678-4395. Victor Lampasona, PharmD, Director of Clinical Pharmaceutical Research, Emory University Medical Center, 13805 Oxford Road, Atlanta, GA 30322. Telephone: (404) 727-5983. Robert Gaynes, MD, Chief of Surveillance Activity, Hospital Infections, CDC, 1600 Clifton Road, Atlanta, GA 30333. Telephone: (404) 639-6436. Michael Ernst, PharmD, Specialty Resident, University of Iowa College of Pharmacy, S428 Pharmacy Bldg., Iowa City, Iowa 52242. Telephone: (319) 335-3500.]

Reference

1. Ernst, M. et al. Levofloxacin and trovafloxacin: The next generation of fluoroquinolones? Am J Health-Syst Pharm 1997; 54:2,569-2,584.