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An unspecific cream vehicle containing 1% erythromycin base was applied once a day for 10 days to one side of the forehead of 16 healthy subjects and the same vehicle without the active agent to the other side. Using the same procedure a solution containing 1.19% clindamycin phosphate (corresponding to 1% clindamycin base) and the corresponding unspecific vehicle was administered to another group of 17 healthy males. Prior to the treatment and after the end bacteria were obtained from the pilosebaceous ducts by means of a special sampling technique. Both ointments containing the antibiotics lead to a significant reduction of the bacterial growth in the pilosebaceous ducts regardless of whether evaluation is made of the total bacterial count or of Propionibacteria. Thus, it could be demonstrated that topical application enables some antibiotics to penetrate into the pilosebaceous duct in an adequate concentration to ensure antibacterial effectiveness if a suitable vehicle is used.

Acne vulgaris is a common skin disorder. Although it is most prevalent in the second decade of life, its beginnings are heralded by increased activity of the sebaceous glands and faulty follicular keratinization, which are already evident in mid to late childhood. The subsequent and increasing proliferation of the follicular anaerobic diphtheroid microflora contribute further as an important pathogenic factor in the generation of inflammatory lesions. Treatments of acne, therefore, are aimed at reducing the follicular anaerobic bacteria, counteracting the follicular hyperkeratosis, and inhibiting the activity of sebaceous glands.

A technique for quantitating bacteria in isolated pilosebaceous follicles is described. This involves microdissection of the follicles from biopsies of skin, using the method of chemical pretreatment of skin to facilitate the separation of the epidermis and epidermal appendages from the dermis. The aerobic cocci and anaerobic diphtheroids in pilosebaceous follicles in 66 biopsies of scalp and 48 biopsies of skin of the upper back were quantitated using this technique. On the back, aerobic staphylococci were very sparse in normal follicles, indicating that their primary habitat on the skin must be on the skin surface rather than within follicles. Of 138 isolated follicles from skin of the upper back, 94 contained no aerobic cocci. Anaerobic organisms were present in high numbers within normal follicles. The geometric mean density of anaerobes in 138 isolated follicles from skin of the upper back was 3.8 X 10(4) diphtheroids per follicle. Eighty-eight follicles contained more than 10(4) anaerobic diphtheroids. Using data from scalp biopsies we found that there was a correlation between the weight of sebaceous glands and the density of anaerobes within the follicles attached to these glands (coefficient of correlation = 0.6).

The structural organization and bacteriological profile of follicular casts and early comedones in prepuberal children were investigated. Follicular casts were present in all samples but were not as abundant as usually seen in older individuals with acne. When examined with the light microscope, all casts and comedones were composed of numerous layers of horny cells and sebum, but were devoid of bacteria. Neither follicular casts nor comedones yielded bacteria when cultured. Electron microscopy of the follicular casts revealed the presence of small round, discrete lipid droplets, and alternating dense and less dense lamellar configurations within the horny cells. Some horny cells closest to the sebum-filled lumen contained large lipid masses, resulting in "balloon-shaped" regions. Prepuberal follicular horny cells contained all of the abnormalities usually seen in follicular casts and biopsy material from acne patients, which suggests that these casts are potential comedones. These aberrations occurred in the complete absence of bacteria indicating that bacteria are not essential to the formation of casts or comedones. Furthermore, our findings indicate that bacteria play little if any role in the initial events of pathological keratinization.

Cholesterol and cholesteryl esters constitute 3 to 5% of the lipids derived from human sebaceous glands. The present study demonstrates that cutaneous bacteria, Staphylococcus epidermidis, and to a lesser extent Propionibacterium acnes, and Propionibacterium granulosum, esterify [4--14C]cholesterol to steryl esters in vitro. The degree of esterification is a characteristic of the strain of organism, ranging from 0 to 32.7% in the organisms tested. Cholesterol esterification in these experiments was dependent on the addition of homogenates of isolated, pooled sebaceous glands to the incubation medium. Indirect evidence suggests that the fatty acids from sebaceous triglycerides are utilized for cholesterol esterification by the bacteria. These results indicate that the proportion of steryl esters in skin surface lipids may be influenced by the density of the microbial population in the skin.

The localization of gram-positive cocci in the normal skin and in the lesions of acne vulgaris was investigated using fluorescein-labeled antiserum raised to gram-positive, coagulase-negative cocci. The cocci were found in 10 of 19 specimens from normal facial skin and in 3 of 11 specimens from the normal skin of the rest of the body. The bacteria were found mostly in the openings of follicles, but in 6 of 10 facial skin specimens, they were also present deeply in the lumina of the dilated sebaceous follicles near the sebaceous glands. Cocci were found in 5 of 6 noninflammatory acne comedones. In inflammatory acne they were demonstrated not only in the follicular canals but also sparsely in the infiltrate surrounding the follicles.

Seventy one papules in the early stages of inflammatory development were isolated from acne vulgaris affected skin and their content of micro-organisms characterized. The progress of lesions prior to excision was monitored by tracing an area of the upper back onto a transparent acetate sheet. This template was used the next day, and in some cases after 3 days, to identify inflamed lesions of less than 1 day and 2-3 days duration. These were biopsied, and pilosebaceous units isolated by micro-dissection, homogenized and microbial populations studied by viable counting and microscopy. Propionibacteria colonised 68% of '1 day' duration lesions and 79% of '3 day' duration lesions; staphylococci colonized 19% and 32% respectively and Pityrosporum spp. (Malassezia furfur) were found in 52% and 68%. Although the prevalence of each microbial group was higher in the more chronic lesions, these differences were not statistically significant. The microbial profile of inflamed lesions was similar both qualitatively and quantitatively to non-inflamed lesions studied previously. These results call into question the role of micro-organisms as the initiators of inflammation in acne vulgaris.

A quantitative study was made of the microflora of 174 acne and 68 non-acne subjects. Two groups of organisms were investigated, the anaerobic diphtheroids and members of the Micrococcaceae. The results showed high numbers of both groups of bacteria in skin bearing blackheads, papules or pustules and in non-acne adolescent skin. There were significantly lower numbers of bacteria in the pilosebaceous ducts of normal looking skin in acne areas and in pre-adolescent skin when compared with non-acne adolescent skin. It is suggested that increased numbers of bacteria alone do not predispose to acne, but that their interaction with the skin, which is a function of the localized skin environment, may be important.

The resident flora of skin surface, sebaceous follicles, and acne comedones: Pityrosporum, micrococci, and corynebacterium (propionibacterium) acnes is described. The nomenclature, topography, incidence, pathogenic role, and especially the ultrastructural morphology of these organisms are presented.

The view is advanced that sebum as originally produced must contain materials, other than lipids, which may serve as a selective substrate for growth of bacteria and yeasts. Growth of large numbers of P. acnes and P. granulosum in some follicles is considered to place those follicles at risk of undergoing pathological changes. Deleterious products of bacterial growth could be not only lipase and free fatty acids, but also other enzymes as well as bacterial antigens and unspecified toxins or irritants. The possibility is suggested that follicles heavily infested with P. acnes and P. granulosum may be identified by their reddish fluorescence under ultraviolet light, thus permitting identification and study of those which are at risk. Antibiotics may be helpful in reducing the formation of harmful bacterial products during continued growth of the organisms. The eventually self-limiting nature of the disease may be due to the immune response to bacterial products, or to an accommodation of the follicular epithelium to the long-continued presence of irritant materials within the follicle.

A method allowing isolation and microbiological analysis of individual pilosebaceous units (follicles) was used to study biopsies of back skin obtained from volunteer acne vulgaris patients. The main microbial groups isolated were members of the genera Propionibacterium, Staphylococcus and Pityrosporum. The incidence (and mean density) of these organisms in 140 normal follicles was 12% (2.6 X 10(5) per follicle), 4% (5.5 X 10(3) per follicle) and 13% (10(2) per follicle) respectively. Colonized follicles were not distributed evenly amongst the subjects studied. The results are analysed and discussed from an ecological standpoint.

Acne is an ubiquitous problem of adolescence. Currently available medications have improved the effectiveness of therapy. Pediatricians should be able to manage most of their patients with acne without referral to dermatologists. The exact pathogenesis of this disorder is not known, but a working hypothesis encompassing the factors involved allows a more rational approach to therapy. Successful treatment not only requires familiarity with the various types of acne lesions and the medications of choice, but an ability to recruit the patient into a partnership of therapy. The more the patient understands about the disorder the better the compliance and chances for success.