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Antibiotic Exit Strategy Can Reduce Resistance


 

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 (MRSA), 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 "utilize 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.

Even though it is bactericidal, no resistance develops in response to benzoyl peroxide, she said.

"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 arrived in 2003 with a disturbing 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).

Another study looked retrospectively at the charts of 118,496 patients, finding 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, since 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.)

"Do we overprescribe antibiotics? Of course we do," Dr. Baldwin said. Dermatologists write 8–9 million prescriptions a year for antibiotics and 40%–50% of all prescriptions for tetracyclines.

The reasons are many: not wanting to miss infections, avoiding medicolegal problems, and basically just wanting a quick response to inflammatory conditions such as acne and rosacea. "Sometimes patients just wear us the heck down," she admitted.

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.

'The message is getting out … that antibiotic resistance is here, it's now, and we have to worry about it.' DR. BALDWIN

Antibiotic Choices for MRSA Reviewed

Currently Available Antibiotics

Tetracyclines: Cover 80% of MRSA.

Penicillins/cephalosporins: Ineffective against MRSA.

Trimethoprim-sulfamethoxazole: Reasonable, cheap; sufficient to cover most MRSA but not Streptococcus.

Fluoroquinolones (ciprofloxacin, levofloxacin, etc.): Promote emergence of MRSA.

Lincosamides (clindamycin): Resistance is growing. Covers some MRSA, but resistance to erythromycin may signal resistance to clindamycin as well, even if culture suggests sensitivity.

Glycopeptides (vancomycin): 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 (linezolid, etc.): Oral, but very expensive, with significant adverse effects. Resistance is developing.

Daptomycin: Intravenous only, but very 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: The application of this injectable has been delayed indefinitely by the Food and Drug Administration.

Ceftobiprole: The application of this new cephalosporin has been delayed indefinitely by the FDA.

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