W.J. Cunliffe

Erythromycin resistant propionibacteria in antibiotic treated acne patients: association with therapeutic failure

Erythromycin resistant (EmR propionibacteria were isolated from the skin surface of 51% of patients treated with oral erythromycin and 42% of patients treated with topical clindamycin compared with 3% of untreated control subject (P < 0.001). Amongst the topical clindamycin‐treated patients, there was a higher incidence of EmR propionibacterial carriage in those patients who had previously been treated with oral erythromycin (64%) than in patients with no known previous exposure to erythromycin (20%; 0.01 > P > 0.001). Patients responding to oral erythromycin treatment carried EmR propionibacteria less frequently (24%) than patients who were not responding or who had relapsed (70%; P < 0.001). These observations suggest that the use of oral erythromycin and/or topical clindamycin encourages the development of resistant propionibacteria and that the emergence of resistant strains is associated with therapeutic failure in erythromycin‐treated patients. In total 63 resistant isolates were obtained from 52 subjects. There were 42 strains of Propionibacterium acnes, 16 strains of Propionibacterium granulosum and five strains of Propionibacterium avidum. The majority of isolates were inducibly or constitutively resistant to macrolide (e.g. erythromycin), lincosamide (e.g. clindamycin) and streptogramin B type antibiotics. Therefore, the isolates are phenotypically indistinguishable from the majority of EmR bacteria in which resistance is due to methylation of 23S ribosomal RNA.

Topical aminolaevulinic acid‐photodynamic therapy for the treatment of acne vulgaris: a study of clinical efficacy and mechanism of action

Background   Acne affects 83–95% of 16‐year‐olds of both sexes, and many seek help from a clinician. Emerging problems with conventional acne treatments, specifically antibiotic resistance of Propionibacterium acnes and fears over the safety and tolerance of oral isotretinoin, create a demand for novel treatment modalities in acne.

A clinical evaluation of acne scarring and its incidence

Despite scarring being a recognized sequel of acne, the actual extent and incidence of residual scarring remains unknown. One hundred and eighty‐five acne patients were included in this study (101 females, 84 males). Patients were selected from acne clinics and their acne scarring was examined. The scarring was quantified according to a lesion count and allocated a score. The type and extent of scarring was correlated to the age and sex of the patient, the site of the acne, the previous acne grade according to the Leeds Technique,1 acne type (noted in clinic at the original referral time) and duration of acne, before adequate therapeutic measures had been instituted. Results indicate that facial scarring affects both sexes equally and occurs to some degree in 95% of cases. Total scarring on the trunk was significantly greater in males, as was hypertrophic and keloid scarring in these sites (P <0.05). There were significant correlations between the initial acne grade and the overall severity of scarring in all sites and in both sexes (P<0.01). Superficial inflamed papular acne lesions as well as nodular lesions were capable of producing scars, A time delay up to 3 years between acne onset and adequate treatment related to the ultimate degree of scarring in both sexes and in all three sites. This emphasizes the need for earlier adequate therapy in an attempt to minimize the subsequent scarring caused by acne.

Prevalence of antibiotic‐resistant propionibacteria on the skin of acne patients: 10‐year surveillance data and snapshot distribution study

Summary Background Cutaneous propionibacteria are implicated in acne pathogenesis, although their exact role in the genesis of inflammation is still poorly understood. Agents, including antibiotics, that reduce the numbers of propionibacteria on skin are therapeutic. Resistance in the target organism is a well‐recognized consequence of antibiotic therapy for acne but formal prevalence and distribution data are lacking.

Comedogenesis: some new aetiological, clinical and therapeutic strategies.

Hypercornification is an early feature of acne and precedes inflammation. It is associated with ductal hyperproliferation and there are many controlling factors such as androgens, retinoids and cytokines. Cycling of normal follicles and of comedones may explain the natural resolution of comedones and, in the longer term, resolution of the disease itself. There is a need to tailor treatment according to comedonal type. Suboptimal therapy can often result from inappropriate assessments of comedones, especially microcomedones, missed comedones, sandpaper comedones, submarine comedones and macrocomedones. Macrocomedones can produce devastating acne flares, particularly if patients are inappropriately prescribed oral isotretinoin. Gentle cautery under topical local anaesthesia is a useful therapy in the treatment of such lesions. The newer retinoids and new formulations of all‐trans‐retinoic acid show a better benefit/risk ratio. Evidence‐based studies are required to allow adequate comparisons.

EFFECTS OF BENZOYL PEROXIDE AND ERYTHROMYCIN ALONE AND IN COMBINATION AGAINST ANTIBIOTIC-SENSITIVE AND -RESISTANT SKIN BACTERIA FROM ACNE PATIENTS

Topical formulations of erythromycin and benzoyl peroxide are popular and effective treatments for mild to moderate acne vulgaris. Use of the former is associated with resistance gain in both skin propionibacteria and coagulase‐negative staphylococci, whereas use of the latter is not. We evaluated the efficacy of a combination of erythromycin and benzoyl peroxide against a total of 40 erythromycin‐sensitive and ‐resistant strains of Staphylococcus epidermidis and skin propioni‐ bacteria in vitro. Using the checkerboard technique, five erythromycin resistant strains of Propionibacterium acnes were inhibited synergistically or additively by the combination. Complete mutual indifference was exhibited between the drugs against the remaining 35 strains. However, erythromycin resistant staphylococci and propionibacteria were inhibited by the same concentration of benzoyl peroxide as erythromycin‐sensitive strains. These results suggest that, although the combination of erythromycin and benzoyl peroxide is not synergistic against the majority of erythromycin‐resistant staphylococci and propionibacteria, the concomitant therapeutic use of both drugs should counteract the selection of erythromycin‐resistant variants and reduce the number of pre‐existing resistant organisms on the skin of acne patients.

The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin resistant propionibacteria

Summary Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of crythromycin‐resistant coagulase‐negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre‐existing erythromycin‐resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double‐blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P < 0.001, Wilcoxons matched pairs) and also significantly reduced the number of erythromycin‐resistant propionibacteria (P < 0.05). In contrast, erythromycin alone reduced the total propionibacterial count by < 1.5 log10 c.f.u./cm2 after 6 weeks (P < 0.05) and did not affect the number of erythromycin‐resistant strains. The combined formulation was significantly more effective at reducing total propionibacterial numbers at 6 (P < 0.01, Mann‐Whitney) and 12 weeks (P < 0.05) than erythromycin alone, although, after 12 weeks, the anti‐propionibacterial efficacy of both preparations was less marked. Five patients on combination therapy, and five treated with erythromycin alone, acquired erythromycin‐resistant strains de novo at week 6 or week 12. In an open study in 21 acne patients, who each carried > 103 c.f.u. erythromycin‐resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of erythromycin‐resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo antipropionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin‐resistant propionibacterial strains pretreatment.

Endocrine factors in pre- and postmenopausal women with hidradenitis suppurativa

The relationship between hidradenitis suppurativa (HS) and hyperandrogenism is largely based on the finding of an increased free androgen index due to a low sex hormone binding globulin (SHBG). As SHBG is now believed to be regulated by factors that influence body weight, and previous studies were not controlled for body weight, we have re‐evaluated the androgen status of female patients with HS. We have studied the endocrine status of 66 women with HS. Twenty‐three had acne, and 23 were significantly obese (body mass index: BMI >30). There was no relationship between obesity and disease duration. Nineteen of 56 women were hirsute. A premenstrual flare in disease activity was reported by 32 women, but this was not related to menstrual disturbances. No consistent relationship was reported with pregnancy. Eight women with HS were menopausal at presentation, and one developed her disease 6 years after the menopause. Plasma androgens in women with HS were compared with controls matched for BMI and hirsuties. There was no difference between HS and controls. Testosterone and dehydroepiandrosterone sulphate were normal in all subjects with HS. In obese subjects, SHBG was reduced, consistent with BMI‐matched controls. We have found no supporting evidence for biochemical hyperandrogenism in women with HS when compared with age‐, weight‐ and hirsuties‐matched controls. We report the continuation and primary development of HS in postmenopausal women.

Isotretinoin for the treatment of acne vulgaris: which factors may predict the need for more than one course?

We investigated 299 patients treated 5‐10 years ago with isotretinoin, and followed them for 5 years post‐treatment. Of the 299 patients 22·7% required repeat courses of treatment; 17% had two courses, 5% had three courses and 1% had 4‐5 courses. Response to further treatment was predictably successful, was not associated with any additional adverse reactions, and produced no persistent side‐effects.

A clinical and therapeutic study of 29 patients with infantile acne

Background  Infantile acne is a relatively uncommon condition; there are few data in the literature on the optimum treatment for this disorder.