SANTA BARBARA, CALIF. — Tetracyclines may wind up being the safest, cheapest, easiest to tolerate nonintravenous drugs available to treat future cases of methicillin-resistant Staphylococcus aureus, and that should be reason enough to get on the bandwagon to preserve tetracycline's potency through wise use, according to one dermatologist.
“I view the tetracyclines as the drugs I would like to save … for the future,” Dr. Hilary Baldwin said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery.
Dermatologic prescribing of antibiotics for acne and rosacea, as well as for skin infections, may be driving resistance in unexpected ways, suggested Dr. Baldwin of the State University of New York, Brooklyn.
“The message is getting out to dermatologists and nondermatologists that antibiotic resistance is here, it's now, and we have to worry about it,” she said.
Her strategy has been to use antibiotics “when necessary, but devise an exit strategy on day 1.”
For example, she may prescribe a topical retinoid, hormonal therapy, or an androgen receptor blocker alongside an antibiotic, so that the time clock will begin ticking right away for nonantibiotic workhorses that don't necessary act quickly. By the time a topical retinoid really is beginning to take hold—at about 12 weeks—the antibiotic will have produced quick, patient-pleasing results and can be discontinued.
“On the day you stop topical or oral antibiotics [while continuing the alternative medication], also start benzoyl peroxide,” she advised, adding that even though it is bactericidal, no resistance develops in response to benzoyl peroxide.
“What I don't think people worry about are topical antibiotics,” she said, noting that the timing of serious resistance problems coincides with the introduction of topical erythromycin and clindamycin.
More specific evidence emerged in 2003 with a study showing tetracycline-resistant Streptococcus pyogenes in the throats of 85% of long-term users of topical or oral antibiotics, compared with 20% of controls (Arch. Dermatol. 2003;139:467–71).
A retrospective study looked at the charts of 118,496 patients, and found that patients who had received 6 weeks or more of topical or systemic antibiotics were at more than a twofold risk of upper respiratory infections (Arch. Dermatol. 2005;141:1132–6).
“The issue is bigger than [Propionibacterium] acnes resistance or upper respiratory infections,” Dr. Baldwin said. “The whole thing ends up being a story of more severe organisms and MRSA.”
Community-acquired MRSA is increasingly familiar to dermatologists, because it presents as skin and soft-tissue infections in 85% of cases. Abscesses often occur below the waist, and pain is more severe than the clinical appearance of lesions might suggest.
“The treatment is drainage, drainage, drainage,” she said, adding that it most often works in the sentinel patient. Contacts at home, especially siblings, may develop severe necrotizing pneumonia and death.
When MRSA does get nasty, “tetracyclines are probably the easiest drugs that we have to treat it,” she said. (See box.)
Dr. Baldwin disclosed ties with Allergan Inc., Coria Laboratories, Galderma S.A., GlaxoSmithKline, OrthoNeutrogena, Medicis Pharmaceutical Corp., Ranbaxy Pharmaceuticals Inc., Sanofi-Aventis, SkinMedica Inc., and Stiefel Laboratories Inc.
Agents in Hand and on the Horizon
Currently Available Antibiotics
Tetracyclines: Cover 80% of MRSA.
Penicillins/cephalosporins: Ineffective.
Trimethoprim-sulfamethoxazole: Reasonable, cheap; sufficient to cover most MRSA but not Streptococcus.
Fluoroquinolones: Promote emergence of MRSA.
Lincosamides (clindamycin): Resistance is growing. Covers some MRSA, but resistance to erythromycin may also signal resistance to clindamycin.
Glycopeptides: Resistance is increasing. Requires intravenous dosing. Not effective for many serious infections.
Streptogramins: Effective, but require intravenous dosing. They are very expensive and have major adverse effects.
Oxazolidinones: Oral, but very expensive, with significant adverse effects. Resistance is developing.
Daptomycin: Intravenous only, but effective for skin/soft tissue infections.
Tigecycline: The newest antibiotic is intravenous only, but very effective.
Drugs on the Horizon
Dalbavancin: Pfizer withdrew the application of this once-weekly injectable pending further study.
Telavancin: FDAhas indefinitely delayed the application of this injectable.
Ceftobiprole: The application of this new cephalosporin has been also been delayed indefinitely by the FDA.
Oral antibiotics: none.
Sources: Dr. Baldwin, Dr. Paul Holtom