A Controversial Proposal

No More Antibiotics for Acne!

Muneeza Muhammad, BA; Ted Rosen, MD

Disclosures

Skin Therapy Letter. 2013;18(5) 

In This Article

Rationale for Eliminating Antibiotic Use for Acne

Success against antimicrobial resistance requires a comprehensive and multifaceted approach, including increased microbial surveillance; more judicious use of antimicrobials in human medicine, agriculture, and animal husbandry; increased research on the biology of microbes and mechanisms of resistance; development of novel antibiotics and vaccines as well as rapid, point-of-care diagnostics; and, most importantly pertinent to this manuscript, alteration of old prescribing habits.[12] For the dermatologist, the latter point particularly means eliminating the use of antibiotics to treat acne (and rosacea). This statement might appear to be hyperbolic and extreme in scope. But, at the very least, dermatologists should consider carefully each and every prescription for antibiotics dispensed for acne (or rosacea) in light of the apocalyptic threat posed by the mounting crescendo of antimicrobial resistance. Let us also note additional points relevant to the consideration of eliminating antibiotics in the management of acne.

Antibiotics and Side Effects

Antibiotics have serious side effects, and even brief treatment can have long-lasting effects. Pseudomembranous colitis, infamously associated with antibiotic use, alters the colonic flora and enables Clostridium difficile (C. difficile) to proliferate and produce toxins with cytopathic effects on the colonic mucosa; acute peritonitis, toxic megacolon, and colonic perforation may ensue.[13] However, these changes in bowel flora are neither temporary nor limited to the treated patient. Evidence suggests that even a 7-day course of clindamycin shows resistance patterns in gut flora up to 2 years after therapy has been discontinued.[11] Studies have also shown that changes in bowel flora after tetracycline use are not limited to the patient, but can also lead to resistance patterns in the gastrointestinal flora of close personal contacts.[1]

Overgrowth of gram-negative microbes on the skin such as Escherichia coli (E. coli), Klebsiella, Proteus, or Enterobacter, is another potential side effect of long-term antibacterial treatment.[14] A rather dramatic gram-negative folliculitis, replete with painful, boggy nodules, may result.[14] Side effects including hypersensitivity reactions like urticaria and DRESS (drug rash with eosinophilia and systemic symptoms) syndrome; dyschromia of skin, teeth, gums, palate, conjunctiva, or sclera from tetracyclines;[15–18] pseudotumor cerebri; and adverse hepatic, renal and hematological effects may also occur. Although controversial, literature exists to suggest that antibiotic use may be associated with development of inflammatory bowel disease, particularly among those with a familial predisposition.[19–21] Does the risk-benefit ratio really warrant the routine use of antibiotics, especially in light of alternate therapies which offer similar outcomes without this litany of potential adverse events?

Prevalence of Propionibacterium Acnes Resistance

In the last few decades Propionibacterium acnes (P. acnes) has become resistant to many different antibiotics, making them less efficacious in treating acne.[1,22] In a topical benzoyl peroxide study, 100% of patients had pre-treatment high-level erythromycinresistant organisms and intermediate- to high-level resistance to tetracycline, doxycycline, minocycline, and clindamycin.[22]

Moreover, the prevalence of P. acnes resistance worldwide highlights the near futility of oral antibiotic treatment. In countries like Mexico,[23] Sweden,[24] France,[25] Japan,[26] and Singapore[27] there is already a high level of resistance to antibiotics like azithromycin, trimethoprim/sulfamethoxazole, erythromycin, and clindamycin. Additionally, patients who harbor resistant P. acnes may be clinically more treatment refractory due to higher bacterial counts; the limited, direct experimental evidence for this assertion is nicely summarized in a recent manuscript by Patel and co-authors.[1]

Worsening of the Overall Resistance Problem

Antibiotic use for acne can worsen the already serious overall antimicrobial resistance dilemma. Studies have shown that Streptococcus pyogenes colonization and resistance in the oropharynx is associated with antibiotic therapy in patients with acne.[28] Moreover, the problem of resistant bacteria is not limited to patients receiving therapy. Contacts of acne patients being treated with antibiotics demonstrate significant increased prevalence and density of resistant strains of coagulase-negative Staphylococcus (CNS) compared to those with no contact with acne patients.[29] CNS can horizontally transfer resistance genes to coagulasepositive staphylococci such as S. aureus, further emphasizing the concern that dermatologists might induce resistance against the arsenal for MRSA. This puts not only patients, but potentially the whole community at risk; the longer the resistant CNS colonizes the skin, the greater the opportunity it has to spread resistant genes to other bacteria.[1]

BPO Monotherapy Non-inferior to Antibiotics

Benzoyl peroxide (BPO) has been used since the 1930s due to its antibacterial, keratolytic, and comedolytic properties.[30] Studies done on patients with mild to moderate acne have shown no statistically significant difference between 5% topical BPO twice daily and oral doxycycline 100 mg 4 times daily, or to other tetracyclines like oxytetracycline and minocycline.[30,31] In fact, BPO was actually shown to be the most cost-effective treatment in these investigations.[31] In the study done by Leyden et al., 6% BPO cleanser effectively reduced tetracycline-resistant P. acnes populations 1 week after treatment—reductions were >1 log after 2 weeks and ≥2 log after 3 weeks.[22] With the anticipated decreased efficacy of tetracyclines due to pre-existing P. acnes resistance, an aggressive BPO regimen may prove to be useful therapy for controlling both acne and antibiotic resistance prevalent in P. acnes at baseline.[22,31]

Alternatives to Antibiotic Treatment

There are many alternate therapies available that are convenient and effective in treating acne aside from topical monotherapy with BPO, including physical therapeutic modalities such as high intensity light,[32] photodynamic therapy,[33] and thermotherapy;[34] hormonal therapy with oral contraceptive pills[35] or spironolactone;[36] subantimicrobial doses of doxycycline which exploit the non-antimicrobial, anti-inflammatory properties of the antibiotic;[37] dapsone;[38] isotretinoin; zinc plus or minus nicotinamide;[39] and topical bleach. These modalities have varying mechanisms of action but have been shown to significantly reduce both inflammatory and/or non-inflammatory acne lesions. Although more experimental and clinical evidence is needed, creative application of these alternative modalities may allow many, if not most, patients to be well managed without ever receiving an antibiotic.

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