antibiotic agent persist and generally can pass on their resistant genes to other bacteria as well as to subsequent generations.
Plasmid transfer appears to be the major process by which multiple-antibiotic–resistant organisms proliferate, and it facilitates
the transfer of resistance among both Gram-negative and Gram-positive bacteria.7 The plasmid is comprised of double-stranded DNA that is separate from the chromosomal DNA. The plasmid DNA can transfer genetic material horizontally through a process called conjugation; once integrated into the host DNA, the genetic material is present in replicated cells. New genetic material can be shared with incredible speed. Within heterogeneous bacterial populations with appropriate donors, millions of bacteria have been shown to acquire a plasmid within just a few days.8
The alternative mode of resistance transfer is via transposons, which facilitate horizontal DNA transfer, also known as horizontal
gene transfer, or viral transfer of resistance.9
A single bacterium can also develop resistance to a given antibiotic
upon exposure. For example, via the efflux pump, a bacterium can flush out antibiotics before they exert an effect.10
Resistance transfer is of concern not only for the organisms that treatment is targeting, but extends to the possibility of resistance
spreading between organisms; susceptible pathogens can theoretically acquire antimicrobial resistance from other microorganisms. Put another way, we in dermatology need to worry about not only the difficulty of treating resistant P acnes, but also the risk of spreading antibiotic resistance in the treatment
of other infectious diseases.
Resistance in Acne Management
The problem of resistance has been especially well documented
in the management of acne vulgaris and has been linked to
resultant acne treatment failure.2 However, resistance among acne patients is not limited to P acnes; researchers have also identified resistant strains of Staphylococcus epidermidis among acne patients treated with oral erythromycin.11-13 Another
study of acne patients showed that systemic antibiotic therapy was associated with Streptococcus pyogenes colonization
and resistance in the oropharynx. While only 20% of S pyogenes cultures from control subjects not treated with antibiotics
were resistant to at least one tetracycline, 85% of cultures from antibiotic-treated patients demonstrated resistance.13
Against the backdrop of growing antibacterial resistance, guidelines for acne management were published in 2003 that emphasize the use of topical antimicrobials and retinoids as well as shortened courses of systemic antibiotics.14 A 2009 update
of the recommendations further underscores concerns about the risk of resistance, calling for the use of oral or topical antibiotics in combination with BP.15 They also emphasize the critical role of topical retinoids in long-term acne treatment. The guidelines may be influencing practice. Overall, prescribing for topical antibiotic monotherapy for acne actually decreased slightly from 2001 to 2005.16 The use of topical clindamycin/BP combination formulations increased.16
While the use of combination clindamycin/BP formulations is consistent with current guidelines, this approach to acne management
does not fully reflect current knowledge about the prevalence of resistance, the mechanisms of resistance, or our understanding of the pathogenesis of acne vulgaris.
Although the P acnes bacterium is generally considered pathogenic in acne vulgaris, acne is not an infectious process.17 Rather, the findings of recent research and the current treatment guidelines concur that acne is primarily an inflammatory
rather than infectious process. Propionibacterium acnes has been thought to contribute directly to the inflammation
of acne vulgaris by instigating inflammatory cytokine responses via activation of Toll-like receptor 2,18 though even this is now controversial.17 There is clear evidence that acne and associated scarring are associated with a marked increase in inflammatory cytokine gene transcripts in active acne lesions,
including tumor necrosis factor α and interleukin-1β.14 These proinflammatory cytokines amplify nuclear factor kB signaling pathways.18
Presently, the primary oral antibiotics used for acne are the second-generation tetracyclines, minocycline and doxycycline.19,20 Less commonly used alternatives include erythromycin, trimethoprim/sulfamethoxazole, and azithromycin.20 These lipophilic oral antibiotics have all been shown in vivo to reduce P acnes colonization after 6 weeks of therapy.
In an experimental model, the log reduction in P acnes colonization was greatest with minocycline.21