Antibiotic resistance in acne: Avoid monotherapy

The most striking finding from a recent review about the impact of acne-related antibiotic use on microbial resistance is a lack of high-quality studies upon which to base recommendations. However, authors conclude, the few studies available sound sufficient alarm to renew major dermatologic societies' calls to limit antibiotic use wherever possible.

The issue of antibiotic resistance is pertinent not only to dermatologists, but also to general, medical and family practitioners who treat acne, said co-author Brandon L. Adler, M.D. He is a second-year dermatology resident (PGY-3) at the University of Southern California Keck School of Medicine.

"Studies can be meaningful in 2 directions: positive findings, or an absence of findings. The latter is more relevant to what we found." Dating back to 1987, researchers examined 5 clinical trials (none randomized) that reported patient-level data.

"Essentially, we don't know as much as we should about problems relating to antibiotic resistance in acne because of a lack of good, high-quality studies. The little that we do know is troubling enough" that possible changes to prescribing habits must continue to be discussed.

AAD AND EADV RECOMMENDATIONS

Both the American Academy of Dermatology (AAD) and the European Academy of Dermatology and Venereology (EADV) discourage topical or oral antibiotic monotherapy.^1,2 "The official stance of major Academies of dermatology in the United States and Europe is that monotherapy with either topical or oral antibiotics is strongly discouraged because the available evidence shows that there's a trend toward resistance among Propionibacterium acnes and possibly off-target effects" such as increased antibiotic resistance among Staphylococcus aureus associated with topical antibiotics,³ said Dr. Adler.

"Often," he said, "our solution for avoiding monotherapy is having patients use over-the-counter products like benzoyl peroxide (BP) – which they're not always purchasing. This can lead to a kind of functional monotherapy. So even though we may be recommending the use of benzoyl peroxide, that's not always being adhered to on the patient end. That's why patient education becomes such a major focus."

As dermatology residents, "We've been very well exposed to the idea of combination therapy for acne. There are excellent combination products available that incorporate a topical antibiotic with benzoyl peroxide. This makes it much easier for both the practitioner and patient" to use more than one topical agent simultaneously.

Dermatologists typically have very busy clinics, he said, "And it can be tough sitting down with patients to try and educate them as fully as possible. But we need to explain to them that not only will their acne get better, but on a personal and population level as well, using multiple therapeutic modalities is geared toward stemming the tide of rising antimicrobial resistance, which carries possible serious implications going forward."

While the AAD and EADV agree that dermatologists should limit courses of oral antibiotics to 3 to 4 months wherever possible, the Academies differ regarding the specific role of BP in combination therapies. For mild-to-moderate acne, the AAD recommends BP, topical retinoids or combination therapy, which may include a topical antibiotic and any of the foregoing medications, as first-line treatment. Conversely, EADV guidelines for mild-to-moderate acne allow fixed-dose antibiotic/retinoid combinations without BP.

For first-line treatment of moderate-to-severe acne, the AAD recommends oral antibiotics (specifically doxycycline and minocycline, which have antimicrobial and anti-inflammatory effects) combined with BP and a topical retinoid. Topical antibiotics are also permissible, provided practitioners prescribe BP concomitantly. To facilitate limiting oral antibiotic courses to 3 or 4 months, patients should continue BP and topical retinoids as maintenance therapy after stopping oral antibiotics.

The EADV recommends combining oral antibiotics with topical retinoids, fixed-dose topical retinoid/BP or azelaic acid for moderate-to-severe acne. But while the strength of evidence for these combinations is medium, says the EADV, it assigns only a low strength of recommendation to the combination of oral antibiotics plus BP.

Dr. Adler said, "The differences highlight the fact that the data are limited. All the guidelines are based as much as possible on available evidence. The AAD recommends using benzoyl peroxide topically whenever oral antibiotics are being used for acne. The EADV still recommends that, but they make a point of saying that the evidence to support it is low. That makes sense because if someone's taking an oral antibiotic – getting systemic distribution of the drug throughout the body – there's not great evidence that using benzoyl peroxide topically on the face, chest or back will appreciably alter the resistance load among their bacteria."

Both groups' recommendations for BP are reasonable based on available evidence, he said. "Adding benzoyl peroxide is a low-cost intervention with very minimal opportunity for harm – and a potentially fair to very good opportunity for limiting resistance," depending on the antibiotic and acne location. Regarding research gaps, Dr. Adler and colleagues call for additional studies to help quantify reductions in bacterial resistance achieved by combining BP with both oral and fixed-dose topical formulations.

REFERENCES

1. Zaenglein AL, Pathy AL, Schlosser BJ, et al. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016;74(5):945-73.e33.

2. Nast A, Dréno B, Bettoli V, et al. European evidence-based (S3) guideline for the treatment of acne – updated 2016 – short version. J Eur Acad Dermatol Venereol. 2016;30(8):1261-1268.

3. Fanelli M, Kupperman E, Lautenbach E, Edelstein PH, Margolis DJ. Antibiotics, acne, and Staphylococcus aureus colonization. Arch Dermatol. 2011;147(8):917-21.