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Antibiotic therapy directed against Propionibacterium acnes has been a mainstay of treatment for more than 40 years. Despite years of widespread use of systemic tetracyclines and erythromycin, change in P. acnes sensitivity to antibiotics was not seen until the early 1980s. The first clinically relevant changes in P. acnes antibiotic sensitivity were found in the USA shortly after the introduction of topical formulations of erythromycin and clindamycin. By the late 1980s, P. acnes strains with very high MIC levels for erythromycin and elevated MICs for tetracycline were increasingly found in the UK and the USA. Mutations in the genes encoding the 23S and 16S subunits of ribosomal RNA were first identified in the UK and also seen in a recent survey from clinics in Europe, Japan, Australia and the USA. In addition, strains were found in which these known mutations could not be identified, indicating that as yet unidentified resistance mechanisms have evolved. These findings indicate the need to develop strategies to minimize the use of antibiotics in acne therapy., (Copyright 2003 S. Karger AG, Basel)

Background and Objective: Erythromycin-sensitive and/or clindamycin-sensitive strains of Propionibacterium acnes show a reduced lipase production at levels below the minimal growth-inhibitory concentration (MIC). The objective of this study was to determine whether erythromycin and clindamycin concentrations far below the MIC inhibit lipase production in P. acnes strains resistant to these antibiotics., Methods: Of 42 P. acnes strains, 10 showed an MIC >256 micro g/ml for erythromycin. Two strains showed MICs of 0.19 and 0.25 micro g/ml, while the MIC of the remaining strains was 256 micro g/ml were also tested for lipase inhibition by clindamycin. While this method fails to differentiate between inhibition of lipase production and inhibition of lipase activity, the absence of inhibition of lipase activity rules out inhibition of lipase production., Results: Inhibition of lipolysis by sub-MIC concentrations was demonstrated only for clindamycin in 3 P. acnes strains. However, lipase inhibition was seen only at the dilution level immediately below the MIC., Conclusions: Resistant P. acnes strains with high erythromycin and/or clindamycin MICs can be ruled out to show in vitro inhibition of lipase production at antibiotic concentrations far below the MIC., (Copyright 2002 S. Karger AG, Basel)

Some studies have been published about the in vitro activity of zinc acetate (ZA), erythromycin (E) and their combination (ZA/E) against Propionibacterium spp., especially erythromycin resistant strains. The efficacy of topical ZA/E combination has been reported as well, but a comparison to ZA monotherapy is missing. Therefore, the MIC values of ZA, E and the ZA/E combination were determined for 15 erythromycin-resistant and 12 erythromycin-sensitive Propionibacterium strains using the agar dilution method and the checkerboard technique. Furthermore, the antimicrobial efficacy of ZA (1.2%) vs. the ZA/E (1.2%/4%) combination in an alcoholic solution was tested in a 7-day treatment administered to 32 acne patients. The MIC 100 for ZA was 1024 micrograms ZA/ml for both, erythromycin resistant and erythromycin sensitive Propionibacterium strains. The ZA, as well as the ZA/E solution showed efficacy reducing both the Propionibacterium spp., and the Micrococcaceae in the sebaceous gland infundibula of acne patients. There was no significant difference between the two treatments. As the MIC 100 of ZA/E was equal to the MIC 100 of ZA, the decrease of the erythromycin MIC of the ZA/E combination in erythromycin-resistant strains may be partly attributed to the addition of ZA to E. The in vivo antibacterial efficacy on 32 acne patients supports the hypothesis that the antibacterial effect of ZA/E in short-term treatment can be mostly attributed to ZA.

In the present study, MIC values of 6 antibiotics were determined for 70 Propionibacterium acnes and 13 P.granulosum strains from 71 untreated acne patients using the agar dilution method. The interpretation of in vitro results is difficult because there are only poor data about the concentrations of antibiotics achievable in the sebaceous gland infundibulum. Based on breakpoint concentrations according to DIN 58,944, no resistance was found against chlortetracycline, doxycycline, minocycline, and chloramphenicol. In contrast, 11% of the P.acnes and 31% of the P.granulosum strains were not susceptible in vitro to erythromycin at a breakpoint concentration of 4 micrograms/ml. The present study shows that these strains are not suppressed even at higher erythromycin concentrations up to 256 micrograms/ml. Data from the literature reporting ineffective treatment of patients carrying erythromycin-resistant P.acnes strains may be explained by our study. Concerning clindamycin, resistance was found in only 6.8% of P.acnes and in 0% of the P.granulosum strains. Since sensitivity was seen in 100% of the strains already at a concentration of 16 micrograms/ml, a therapeutic effect may be possible.

In a 3-armed, multicentre, randomized, double-blind, vehicle-controlled study involving 91 patients with acne papulopustulosa, Plewig's grade II-III, evidence could be provided of a significant reduction of the propionibacteria as well as a subosuppressive effect (squalene reduction) under a combination of 1% chloramphenicol (CAS 56-75-7) and 0.5% pale sulfonated shale oil versus the alcoholic vehicle (1-2 ml twice daily). Likewise, monotherapy with chloramphenicol resulted in a significant reduction in bacteria compared to the vehicle. The combination therapy was superior to the monotherapy with regard to the sebosuppressive effects. Based on a kinetics test carried out for a total of 2 h, a clinically relevant percutaneous absorption of chloramphenicol was ruled out. The chloramphenicol serum level was between < 5.0 microgram/l to 180 microgram/l (average 25 micogram/l). This is important because with systemic application (peroral, i.v.), the therapeutic chloramphenicol level is > 25 mg/l (25,000 microgram 1). None of the blood count and serum parameters were pathologically changed in a clinically relevant way before and after the therapy. An induction of resistance against chloramphenicol in the propionibacteria could be excluded. No adverse events and side effects occurred. The topical therapy of acne papulopustulosa with chloramphenicol as a monosubstance or in combination with pale sulfonated shale oil represents an effective and safe local antibiotic treatment possibility.

Acne vulgaris is one of the most widespread of all diseases and is frequently the object of treatment in general and specialist medical practice. New insights into the pathophysiology of acne show that the most important therapeutic principle is suppression of the propionibacteria in the pilosebaceous duct since these bacteria have a key role in the genesis of the comedo and of inflammatory acne efflorescences. Experimental findings are shown which prove the value of a local treatment with antibiotics and ethanol-containing masks. The second therapeutic principle is "keratolytic" therapy. Retinoic acid, benzoyl peroxide and salicylic acid are in the forefront here. The third therapeutic principle is the reduction of seborrhea. Benzoyl peroxide is especially suitable for local treatment. Differential diagnosis of acne vulgaris and additional possibilities of treatment in problem cases are dealt with.

Investigations are reported which attempt to contribute towards an understanding of those cases in which topical treatment with erythromycin is unsuccessful. In 13 acne patients no resistance of P. acnes was observed after seven weeks of topical treatment with erythromycin. This demonstrates that the 20% frequency of resistance induction reported in the literature is too high. In the 13 treated patients there was no essential reduction in the number of inflammatory lesions although a decrease in the number of Propionibacteria in the pilosebaceous ducts occurred. This result is perhaps connected with a concurrent increase in Micrococcaceae, which could suggest that not only Propionibacteria, but also Micrococcaceae play a role in the pathogenesis of acne.

In 24 persons with a severe inflammatory acne and 48 control subjects, bacteria were sampled from the sebaceous gland exretory ducts with the glass sampling head method according to Holland et al. After anaerobic culture bacterial counts were performed. The total numbers of P. acnes and the frequency of detection of P. granulosum were determined. The bacterial counts of P. acnes were almost idendical in the two collectives. P. granulosum was detected at a significantly higher frequence in the acne patients than in the control subjects. It can be assumed on the basis of the results that an increase in the bacterial counts of P. acnes is not to be regarded as a pathogenetic factor in the inflammatory acne of older patients. On the other hand, they suggest that P. granulosum may have an appreciable role in acne.

Among cutaneous propionibacteria, synthesis of neuraminidase is highest in strains of the species P, acnes. In the present study, neuraminidase activity was discovered in 90.0% of P. acnes strains isolated from acne lesions compared with 72.7% of strains from normal human skin. Neuraminidase-positive strains from acne lesions, moreover, produced statistically significant higher amounts of the enzyme (X = 727 microunits/ml bacterial suspension) than isolates from normal skin (X - 392 microunits/ml). Whereas the moderate production of neuraminidase by strains from patients with seborrheic eczema is probably of no causative importance, the enzyme has to be discussed a potential etiologic factor in acne vulgaris.

Determinations of the minimum inhibitory concentrations for various antimicrobial surfactants with reference to the bacteria P. acnes, P. granulosum, and St. epidermidis are reported. The results show that quaternary ammonium compounds can display minimum inhibitory concentrations corresponding to those of relevant antibiotics. With the especially effective substance fractionated dimethylcocobenzalkoniumchloride )ARQUAD DMMCD-B), it could be further shown that with in vivo application in 70% isopropanol or in an ethanol-containing film mask ointment suppression can be obtained of P. acnes, all propionibacteria added, and all pilosebaceous duct bacteria which can be cultured under anaerobic conditions. The studies may point out a way of replacing antibiotics in the antimicrobial therapy of acne by quaternary ammonium compounds.

A questionnaire was presented to 2009 18--19 year old recruitment candidates. The questionnaire enabled appraisal of antipathy towards patients with severe acne vulgaris and the occupational inpediment of severe acne. It was shown in comparison of patients with clinically relevant acne and healthy subjects or patients with a minor variant of acne that acne patients are more prepared to tolerate other acne patients than are healthy subjects. A questionnaire which enabled appraisal of attitudes to therapy was presented in addition to 351 patients with clinically relevant acne in this collective. The schools attended were also recorded in these patients. It was shown that the motivation to undergo treatment can be assumed in only half of the acne patients; this motivation is less the more radical the therapy. However, the motivation is greater the higher the educational level of the person questioned.

In 29 healthy male subjects aged between 20 to 25 years a powder face mask, consisting of 1.19% clindamycin phosphate (= 1% clindamycin base) in 70% ethanol was applied to the right side of the forehead once daily over a period of 5 days. At the same time half of the test subjects were treated in the same way on the left side of the forehead with a solution consisting of 1.19% clindamycin phosphate in 70% ethanol, and the other half with the same powder mask as on the right side but without clindamycin phosphate. The face mask containing clindamycin phosphate leads to a greater reduction of P. acnes. the total propionibacteria and the total bacterial counts (anaerobic culture) in the pilosebaceous duct than both other preparations. Compared with the initial values these do, however, reduce the bacterial count. The use of face masks containing antibiotics seems to offer a successful way of topical antibiotic treatment of acne.

A total of 375 anaerobic and microaerophilic coryneform rods, isolated from the pilosebaceous ducts of 26 healthy persons (71 strains) and from comedones (93 strains), pustules (107 strains), and the unaffected skin (104 strains) of 36 acne patients were classified according to the species key in Bergey's manual, the biotyping scheme of Pulverer and ko, the serotyping schedule of Höffer et al., and the phage typing schedule of Jong et al. The statistical evaluation demonstrated certain differences in the frequencies of the Propionibacterium species and types between the different groups tested. Thus, the species P. granulosum was isolated only from acne patients (50.0% of patients examined) and was found more frequently in comedones and pustules than in unaffected follicles in acne patients. The majority of P. granulosum strains belonged to serotype II (95). Biotype A propionibacteria were more frequently found in strains from healthy controls (52.1% of strains) than in strains from healthy controls (52.1% of strains) than in strains from comedones (17.2%), pustules (27.1%) and unaffected skin (38.5%) of the acne patients. The results of phage-typing showed that the P. acnes lysotype I was more frequent in acne patients (total: 73.2% of strains), especially in the inflamed pustules (88.5%), than in healthy controls (55.1%).

16 healthy persons were treated for 7 weeks with a 1% erythromycin containing ointment. Another 25 persons (among them 10 acne patients) were treated during the same period of time with a combination therapy consisting of erythromycin (1% in an unspecific ointment base) and benzoylperoxide (5% in a gel base). The combined therapy reduces the micrococcaceae in the pilosebaceous ducts significantly. On the other side the therapy consisting only of erythromycin causes only initially a decrease and then an increase in the number of micrococcaceae. Induction of resistance to erythromycin is in both cases considerable. In both cases a reduction of propionibacteria which are most important for the pathogenesis of acne must be assumed. Because of the probable pathogenetic role of staphylococci in acne vulgaris an additional improvement of the therapeutical results can be expected in the case of combination therapy. In vitro experiments demonstrate further that an erythromycin treatment leads to considerable resistance induction in S. aureus, regardless of whether it is applied alone or in combination with benzoyl peroxide.

Two groups of 27 and 23 patients with acne vulgaris were first treated for a period of one week with 1 g oxytetracycline a day p.o. In a second treatment period of 6 weeks the first group received 100 mg oxytetracycline a day p.o. and the second group a combination of 100 mg oxytetracycline and 1.2 g sodiumbituminosulfonates a day p.o. In the third treatment period, similarly continued for 6 weeks, the method was reversed. Gastric juice-insoluble preparations were used for the investigation. All criteria for a double-blind study were considered. Amount and composition of the skin surface lipids were analysed before beginning the treatment, at the end of the 2nd and at the end of the 3rd treatment period. The combination of both agents in gastric juice-insoluble preparations suppresses to a great extent the known effects brought about by the substances separately, namely the reduction in free fatty acids and the decrease in the skin surface lipids. The findings also show that the reduction of the free fatty acids was in a limited time observed only in patients treated with 100 mg oxytetracycline a day p.o. if they had been treated in the beginning of this therapy with a higher dosage of tetracycline.

375 strains of propionibacteria isolated from pustules, comedones, and from normal skin of patients with acne vulgaris and from healthy persons have been examined for their enzymatic activity. In contrast to healthy individuals, protease and caseinase production of strains from acne patients was significantly lower. On the other hand, DNA'ase production of strains from acne lesions was increased, and lecithinase could be demonstrated in strains from acne patients only.

Thin-layer chromatographic investigations of the skin surface lipids have been performed on 10 healthy subjects before and after treatment with film masks containing 1% ethyl lactate and 50% ehtanol. From the results obtained it can be assumed that there is a reduction in the fraction of free fatty acids on the skin surface. Clinical studies with the same mask on 23 patients with acne vulgaris over a period of 3 weeks proved that this treatment led to a significant reduction in comedones and inflammatory acne efflorescences. No side effects whatsoever were obtained. This therapy, therefore presents a valuable element in the treatment of acne vulgaris. These investigations show also that a decrease in the free fatty acids of the skin surface lipids points to a favourable therapeutical effect on inflamed and not-inflamed efflorescens of acne vulgaris when testing antimicrobial agents.

A questionnaire was presented to 2009 18--19 year old military recruitment candidates which enabled assessment of antipathy towards patients with severe acne vulgaris, the occupational handicap associated with severe acne and subjective inhibitions in acne patients. In addition, these persons were examined clinically with regard to presence of acne vulgaris. Finally, the level of education of the persons questioned was determined. The investigations show that severe acne has an appreciable disease rating. This results from antipathy of other people, the occupational inpediment and the psychological inhibitions of the acne patient. This disease rating appears to be objectively greater the lower the level of education of the acne patient. The disease rating does not appear to be entirely clear to the acne patient with a low level of education.

Ozone therapy using the Vapozone 9, an instrument in normal commercial usage, has been carried out on the forehead of 16 male test persons on 7 consecutive days. Before the treatment began and at the end of the treatment period the skin surface lipids on the unchanged skin (casual level) and two hours after defatting the skin (replacement sum) were taken by direct extraction and analysed by means of thin layer chromatography. The results of these investigations rule out a decrease in the free fatty acids by this therapy. As a result of this finding it may assumed that no desinfecting effect on the corynebacterium acnes and other lipasereleasing microorganisms can be attributed to ozone therapy.

Stickl's method of oral treatment of acne vulgaris with antigens has been carried out on 26 test persons. During the treatment the number of comedones increased significantly and the number of papules decreased significantly. Biochemically, a significant increase of the free fatty acids and a significant decrease of the triglycerides could be demonstrated in the skin surface lipids, the total amount remaining unchanged. The following important conclusions for the pathogenesis of acne may be drawn: 1. The living conditions for Corynebacterium acnes on the surface of the skin or in the ducts of sebaceous glands respectively are influenced by the immunological system of the host. 2. The free fatty acids have a comedogenic effect in vivo. 3. The free fatty acids are not responsible for the development of inflammatory acne efflorescences.