Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne

BACKGROUND: Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. OBJECTIVE: To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. METHODS: Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. RESULTS: After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. CONCLUSIONS: Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.     

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

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. OBJECTIVES: To monitor the prevalence of skin colonization by antibiotic-resistant propionibacteria in acne patients attending the dermatology out-patient clinic at Leeds General Infirmary over a 10-year period beginning in 1991, and to examine the distribution of resistant strains on acne-prone skin and in the nares. METHODS: Propionibacterial samples were obtained from the skin surface of the worst affected site (usually the face) of 4274 acne patients using a moistened swab. The swab was used to inoculate agar plates with and without selective antibiotics. After anaerobic incubation at 37 degrees C for 7 days, the amount of growth in the presence of each antibiotic was scored on a scale from 0 to 5+. A small number of patients (72) were selected for more detailed quantitative sampling at six different sites to examine the distribution of resistant propionibacteria on acne-prone skin and in the anterior nares. RESULTS: The proportion of patients carrying strains resistant to one or more commonly used antiacne antibiotics rose steadily from 34.5% in 1991 to a peak of 64% in 1997. The prevalence dropped to 50.5% during 1999 and then rose again to 55.5% in 2000. Resistance to erythromycin was the most common and the majority of erythromycin-resistant strains were cross-resistant to clindamycin. Resistance to tetracyclines was less common in all years and with little increase over time. The more detailed quantitative study in 72 patients showed that population densities of resistant propionibacteria varied considerably between sites and between individuals. Almost invariably, patients were colonized with resistant strains at multiple sites, including the nares. CONCLUSIONS: Skin colonization with antibiotic-resistant propionibacteria is much more common now than a decade ago. Resistant propionibacteria are widely distributed on acne-prone skin and in the nares. This suggests that they will be very difficult to eradicate using existing therapeutic regimens, especially from the nasal reservoir.     

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 subjects (P less than 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 greater than P greater than 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 less than 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.     

Treatment of acne with topical antibiotics: lessons from clinical studies

BACKGROUND: Over the past 20 years, major concerns have been repeatedly expressed over antibiotic-resistant acne in Europe and in the U.S.A. However, the clinical significance of these resistance patterns is poorly defined so that topical antibiotics remain one of the cornerstones of acne management. OBJECTIVES: To determine whether we are facing decreased efficacy of topical formulations of erythromycin and clindamycin in clinical trials of therapeutic interventions for acne. METHODS: To review systematically the results of the clinical trials investigating topical formulations of erythromycin and clindamycin for the treatment of inflammatory acne and to establish whether or not there is a decrease in the efficacy of these topical antibiotic formulations since their widespread introduction in the mid 1970s. RESULTS: Of the 50 eligible controlled trials identified using a systematic electronic database search strategy, 45 (90%) incorporated a lesion count, making comparison across trials possible. Analysis of clinical studies investigating the effect of topical erythromycin in acne patients indicates a significant decrease in the effect of this antibiotic on inflammatory and noninflammatory lesion count over time (r = -2.140, P = 0.001 and r = -2.032, P = 0.001, respectively). Efficacy of topical clindamycin remained stable during the study period. CONCLUSIONS: There is a gradual decrease in the efficacy of topical erythromycin in clinical trials of therapeutic intervention for acne, which is probably related to the development of antibiotic-resistant propionibacteria.     

Antimicrobial susceptibility of Propionibacterium acnes isolates from acne patients in Colombia

Background The increasing prevalence of antimicrobial resistance in Propionibacterium acnes poses a significant challenge to successful treatment outcomes in acne patients. Although P. acnes resistance has been demonstrated throughout the world, no previous data regarding the antimicrobial susceptibility of P. acnes in Colombia are available. Objectives The aim of this study was to determine the antimicrobial susceptibility of P.  acnes to common antibiotics used in the treatment of acne in a Colombian population. Methods Samples were collected from facial acne lesions of 100 dermatology patients. All samples were cultured in anaerobic conditions, and final identification of isolates was performed. Isolates of P. acnes were then subjected to antimicrobial susceptibility tests using erythromycin, clindamycin, tetracycline, doxycycline, and minocycline. Results Propionibacterium acnes isolates resistant to erythromycin (35%), clindamycin (15%), doxycycline (9%), tetracycline (8%), and minocycline (1%) were observed. Isolates with cross‐resistance were also observed (to erythromycin and clindamycin [12%] and to doxycycline and tetracycline [6%]). Overall, 46% of isolates taken from patients with a history of antibiotic use demonstrated resistance, whereas 29% of isolates taken from patients who had never used antibiotics demonstrated resistance. Conclusions Antimicrobial resistance in P. acnes in this Colombian population has a lower prevalence than those reported in Europe and follows a similar pattern to findings elsewhere in Latin America. Resistance is demonstrated even in isolates from patients with no previous history of antibiotic use. Resistance to erythromycin is most commonly observed. Minocycline emerges as the most effective antibiotic.     

Antibiotic resistance of microbial strains isolated from Korean acne patients

Over several decades, topical and systemic antibiotics have been the mainstay of treatment for acne vulgaris. The widespread and long‐term use of antibiotics in the treatment of acne has resulted in the spread of resistant bacterial strains and treatment failure. We aimed to examine the bacteriology of acne vulgaris and to evaluate its susceptibility to the antibiotics widely used for acne in Korea. We examined the species of bacteria aerobically and anaerobically isolated from 100 Korean acne patients. Among the bacteria isolated, Staphylococcus epidermidis (36 patients) was the most common, followed by Propionibacterium acnes (30 patients). Eleven strains of P. acnes (36.7%) and 25 strains of S. epidermidis (69.4%) were resistant to one or other of the antibiotics tested. A higher proportion of P. acnes isolates were resistant to clindamycin (30%) and erythromycin (26.7%), than to any other antibiotics tested (P = 0.0003). Some S. epidermidis isolates were resistant to tetracycline and doxycycline in addition to clindamycin and erythromycin. In the previous studies, few strains of P. acnes were found to be resistant to any of the antibiotics, but this study shows that antibiotic‐resistant strains have been increasing in Korea acne patients.     

Phenotypic and genotypic characterization of antibiotic-resistant Propionibacterium acnes isolated from acne patients attending dermatology clinics in Europe, the U.S.A., Japan and Australia

BACKGROUND: Propionibacterium acnes is the target of antimicrobial treatments for acne vulgaris. Acquired resistance to erythromycin, clindamycin and tetracyclines has been reported in strains from diverse geographical loci, but the molecular basis of resistance, via mutations in genes encoding 23S and 16S rRNA, respectively, has so far only been elucidated for isolates from the U.K. OBJECTIVES: To determine whether similar or different resistance mechanisms occur in resistant P. acnes isolates from outside the U.K. METHODS: The phenotypes and genotypes of 73 antibiotic-resistant strains of P. acnes obtained from the skin of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were compared. Antibiotic susceptibilities were determined by minimum inhibitory concentration (MIC) measurements, and polymerase chain reaction and DNA sequencing were used to identify mutations in genes encoding rRNA. RESULTS: Most erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross-resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(-1)). As in the U.K., resistance to erythromycin was associated with point mutations in 23S rRNA in 49 of 58 strains. An A-->G transition at Escherichia coli equivalent base 2058 was present in 24 strains. This gave a unique cross-resistance phenotype against a panel of macrolide, lincosamide and type B streptogramin antibiotics. Two further point mutations (at E. coli equivalent bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and these were also associated with specific cross-resistance patterns originally identified in isolates from the U.K. However, nine of 10 erythromycin resistant-strains from Germany did not exhibit any of the three base mutations identified and, in six cases, cross-resistance patterns were atypical. Consistent with previous U.K. data, 34 of 38 tetracycline-resistant strains carried a base mutation at E. coli 16S rRNA equivalent base 1058. Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline, but isolates from the U.S.A. had higher MICs for minocycline (4--16 microg mL(-1)) than isolates from other countries and, in particular, Australia. All the P. acnes isolates resistant to one or more of the commonly used antiacne antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the fluoroquinolone, nadifloxacin. All but one isolate (from the U.K.) were sensitive to trimethoprim. CONCLUSIONS: This study shows that 23S and 16S mutations identified in the U.K. conferring antibiotic resistance in P. acnes are distributed widely. However, resistant strains were isolated in which mutations could not be identified, suggesting that as yet uncharacterized resistance mechanisms have evolved. This is the first report of high-level resistance to minocycline and is of concern as these strains are predicted to be clinically resistant and are unlikely to remain confined to the U.S.A. Epidemiological studies are urgently required to monitor how resistant strains are selected, how they spread and to ascertain whether the prevalence of resistance correlates with antibiotic usage patterns in the different countries.     

Is Antibiotic Resistance in Cutaneous Propionibacteria Clinically Relevant?

It is well recognized that some patients with acne do not respond adequately to antibiotic therapy. It is important to distinguish antibiotic recalcitrant acne which we would suggest represents acne that shows a diminished response to treatment irrespective of the cause as opposed to 'antibiotic-resistant acne' which is acne that is less responsive to treatment as a direct consequence of skin colonization with resistant propionibacteria. Here we show that antibiotic-resistant acne is not just a theoretical possibility but a real phenomenon that could have important consequences for patients and prescribers. The relationship between skin colonization by antibiotic-resistant propionibacteria and treatment outcomes is a complex one that is explained at the follicular level by physiological differences affecting local drug concentrations. A systematic review of the literature on antibiotic-resistant propionibacteria revealed methodological shortcomings in studies of their prevalence and a paucity of evidence on their clinical significance. Despite the elucidation of resistance mechanisms in cutaneous propionibacteria, our continuing inability to distinguish between strains of Propionibacterium acnes means that we still do not fully understand how resistance spreads, although person-to-person transfer is most likely. Finally, we present a decision tree for acne management in an era of prudent antimicrobial prescribing that provides an alternative to existing treatment algorithms by placing topical retinoids and not antibiotics at the cornerstone of acne management.     

Antimicrobial susceptibility and genetic characteristics of Propionibacterium acnes isolated from patients with acne

Background Propionibacterium acnes is an important target in acne management. Antibiotic resistance has increased, reducing its clinical efficiency. Objective To study the prevalence, antimicrobial susceptibility patterns, and resistance mechanisms of P. acnes isolated from patients with acne. Methods Skin swabs were collected from 83 patients. Agar dilution determined the minimum inhibitory concentrations of five antibiotics. Polymerase chain reaction and DNA sequencing were used to identify mutations. Results P. acnes was isolated in 80 of 83 patients (96%), and 27 patients had resistance to antibiotics (33.7%). The mean age was older in the antibiotic‐resistant group (20.8 ± 5.8 vs. 18.3 ± 3.7, P = 0.02). Resistance to trimethoprim–sulfamethoxazole was 26.3%, erythromycin 12.5%, and clindamycin 7.5%. All clindamycin‐resistant strains had cross‐resistance to erythromycin, and 40% erythromycin‐resistant strains had cross‐resistance to trimethoprim–sulfamethoxazole. All strains were sensitive to tetracycline and doxycycline. The use of topical erythromycin or clindamycin was a risk factor to carry resistant strains (P = 0.02, P = 0.04, respectively). Resistance to trimethoprim–sulfamethoxazole was associated with acne severity (P = 0.02). Six of the 10 erythromycin‐resistant strains had a mutation in the peptidyl transferase region of the 23S rRNA gene: one A2058G and five A2059G. No strain carrying mutation G2057A was found. Conclusions Resistance to trimethoprim–sulfamethoxazole was the most common pattern found, and further studies are required to clarify its resistance mechanism. A certain tetracycline resistance was expected, but interestingly all strains remained sensitive. Resistance to erythromycin and clindamycin were influenced using topical formulations. Mutation A2059G was related to high resistance to erythromycin. Antibiotic resistance is increasing, and new strategies are needed.     

Antibiotic susceptibility of Propionibacterium acnes isolated from acne vulgaris in Korea

Propionibacterium acnes plays an important role in the development of acne, and inflammatory lesions are improved by antibiotics. Long-term use of antibiotics may result in development of resistant strains and treatment failure. The aim of the present study was to investigate the isolation rate of P. acnes and to evaluate its antibiotic susceptibility to widely used antibiotics in acne in Korea. Among 46 patients, 31 P. acnes strains were cultured. Isolated P. acnes was measured for minimum inhibitory concentration (MIC) of tetracycline, doxycycline, minocycline, erythromycin and clindamycin using an Epsilometer test. Age, disease duration and previous history of antibiotic therapy for acne were compared in relation to the MIC. The mean MIC of tetracycline, minocyclines, doxycycline, clindamycin and erythromycin were all below the breakpoint of antibiotic resistance. The patients with acne vulgaris with disease duration of more than 2 years documented higher MIC values in doxycycline, erythromycin, and clindamycin than those of less than 2 years. The patients who were previously treated with topical or systemic antibiotics showed higher MIC in doxycycline. Antibiotic resistance of P. acnes is still low in Korea, but at this point, there is an increasing trend of MIC. Caution and acknowledgement of increased risk of antibiotic resistant P. acnes should be advised in acne antibiotic treatment to minimize and avoid the emergence of the resistant strain.     

In vitro antimicrobial susceptibility of Propionibacterium acnes isolated from acne patients in northern Mexico

Background Antimicrobials are essential in acne therapy. In the last decades, Propionibacterium acnes has become resistant to different antibiotics. Objective To determine antimicrobial susceptibility patterns of P. acnes to frequently used drugs. Materials and methods Cutaneous lesion samples were obtained from 50 patients with acne vulgaris, which were cultured in anaerobic media to demonstrate the presence of P. acnes. After that, antimicrobial susceptibility tests to tetracycline, minocycline, doxycycline, erythromycin, azithromycin, clindamycin, trimethoprim/sulfamethoxazole (SXT) and levofloxacin were performed. Results In the general study group, resistance to azithromycin was 82%, the most prevalent one (P < 0.05), followed by trimethoprim/sulfamethoxazole (68%) and erythromycin (46%). On the other hand, all strains isolated were susceptible to minocycline. Resistance bias were similar when subgroups with and without the previous antimicrobial therapy were performed, finding a low prevalence of resistance to tetracyclines and levofloxacin in both groups. Conclusions In our region, P. acnes is highly resistant to azithromycin, SXT, erythromycin and clindamycin; and being very susceptible to minocycline, levofloxacin and tetracycline, in vitro in both groups: with and without the previous antibiotic use. To our knowledge, high resistance prevalence to azithromycin and SXT has never been reported.     

The bacteriology of acne vulgaris and antimicrobial susceptibility of Propionibacterium acnes and Staphylococcus epidermidis isolated from acne lesions

We examined the species of bacteria aerobically and anaerobically isolated from 30 acne lesions and determined antimicrobial susceptibilities of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) using nine antimicrobial agents. Among the bacteria isolated, S. epidermidis was most dominant. Both P. acnes and S. epidermidis were isolated from half of the acne lesions. The MIC of seven antimicrobials (ampicillin, erythromycin, roxithromycin, clindamycin, tetracycline, minocycline, nadifloxacin) against P. acnes was under 3.13 micrograms/ml. There were very few resistant strains of P. acnes, but many of S. epidermidis. More than 30% of the S. epidermidis isolates were resistant to erythromycin, roxithromycin, and clindamycin. After long-term systemic antibiotic therapy, the resistant strains of S. epidermidis increased, but P. acnes resistance was still limited. When we use antimicrobial agents for the treatment of acne, it should be noticed that not only P. acnes but also S. epidermidis in the acne lesions may acquire resistance to antimicrobials.     

Antibiotic‐resistant Propionibacterium acnes among acne patients in a regional skin centre in Hong Kong

Background There has been no study on antibiotic‐resistant Propionibacterium acnes in Hong Kong. Objective We investigated the prevalence and pattern of antibiotic‐resistant P. acnes and to identify any associated factors for harbouring the resistant strains. Methods Culture and sensitivity testing of P. acnes to commonly used antibiotics were performed. Resistance to tetracycline was defined at a minimal inhibitory concentration (MIC) of 2 μg/mL or more; erythromycin at an MIC of 0.5 μg/mL or more; clindamycin at an MIC of 0.25 μg/mL or more according to EUCAST. For breakpoints of doxycycline and minocycline, those with an MIC of 1 μg/mL or more were defined as resistant strains. Results Among the 111 specimens collected from 111 patients, 86 strains of P. acnes were recovered, one from each specimen. Twenty‐five specimens had no growth. Forty‐seven (54.8%) strains were found to be resistant to one or more antibiotics. Forty‐six (53.5%), 18 (20.9%), 14 (16.3%), 14(16.3%) and 14 (16.3%) strains were resistant to clindamycin (CL), erythromycin (EM), tetracycline (TET), doxycycline (DOX) and minocycline (MR) respectively. Ten strains (11.6%) had cross resistance between the MLS antibiotics (erythromycin or clindamycin), one strain (1.2%) had cross resistance among the cyclines and 14 strains (16.4%) had cross resistance between the MLS and cycline antibiotics. Binary logistic regression showed an association between MLS antibiotic resistance with an increased age whereas cycline resistance was associated with the duration of treatment. Conclusions Antibiotic‐resistant P. acnes is prevalent in Hong Kong. Dermatologists should be more vigilant in prescribing antibiotics for acne patients.     

Bacterial resistance in French acne patients

Background The percentage of strains of Propionibacterium acnes resistant to antibiotics in acne is increasing in many countries, raising the question of the risks associated with bacterial resistance. Numerous series of cases have been published on European populations of acne patients, but at the moment we still have very few data regarding France. Objectives The aim of this study was to evaluate the prevalence of P. acnes resistant strains to erythromycin, tetracycline, and doxycycline in a population of French acne patients. Methods Specimens were collected from 273 patients in 43 centers located throughout France (12 hospitals and 31 private office practices). Results 75.1% of the patients were carriers of P. acnes strains resistant to erythromycin and 9.5% to tetracycline. One hundred percent of strains resistant to tetracycline were also resistant to doxycycline. There was no significant difference among the regions and between patients followed in hospital or private office. Conclusions It clearly appears that the percentage of patients with P. acnes strains resistant to erythromycin is similar to that in other countries, but lower for tetracycline or doxycycline in comparison to other European countries.     

Inhibition of erythromycin-resistant propionibacteria on the skin of acne patients by topical erythromycin with and without zinc

Summary Propionibacteria resistant to high concentrations of erythromycin [minimal inhibitory concentration (MIC)≥0·5 mg/ml) are now commonly isolated from the skin of antibiotic-treated acne patients. This double-blind study was carried out to assess the ability of 4% w·v erythromycin with and without 1–2% w/v nine acetate to reduce the numbers of erythromycin-resistant propionibacteria in vivo, and also to monitor the acquisition of resistant strains de novo during therapy. Under laboratory conditions, erythromycin-resistant propionibacteria were shown to be as sensitive to zinc acetate as fully sensitive strains. In vivo, the erythromycin/zinc complex and erythromycin alone produced highly significant reductions in total propionibacteria (P<0·01) and in the number of erythromycin-resistant strains (P<0·01 at 8 weeks). After 12 weeks, resistant propionibacteria were re-acquired, or acquired de novo. by three patients treated with erythromycin alone and four patients treated with the erythromycin/zinc complex. In contrast, changes in numbers of Micrococcaceae were slight and. after 12 weeks, erythromycin-resistant strains were predominant in both treatment groups. In vitro MIC determinations suggested that this finding might be explained by the exceptionally high degree of erythromycin resistance displayed by some staphylococcal strains (MIC>4 mg/ml) and by the relative insensitivity of all staphylococcal strains to zinc acetate. Krythromycin with and without zinc was clinically effective, and both preparations produced significant reductions in acne grade, and inflamed and non-inflamed lesion counts (F<0·001). In particular, 11 of 12 patients who harboured >10³ c.f.u. erythromycin-resistant propionibacteria/cm² skin pretreatment (seven on the erythromycin/zinc complex and five on erythromycin alone) showed clinical improvement, with a>50% reduction in acne grade and/or lesion count. These results show that topical 4% w/v erythromycin with and without zinc eradicates erythromycin-resistant propionibac-teria in vivo, and is thus therapeutlcally effective in patients who harbour such strains.     

Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide, and combination therapy

Antibiotic resistance of the resident cutaneous bacterial flora is a well recognized consequence of systemic antibiotic therapy. In this study, we followed the development of antibiotic resistance of coagulase-negative staphylococci (CNS), the most numerous aerobic bacteria found on the skin surface, during treatment with three topical antimicrobial agents used to treat acne vulgaris. Groups of 20 subjects received either topical erythromycin, benzoyl peroxide or a combination of the two for 16 weeks. After 12 weeks of treatment with erythromycin, the aerobic flora was dominated by S. epidermidis which was completely resistant to erythromycin. In addition there was an increase in resistance to clindamycin and tetracycline. Treatment with benzoyl peroxide and the combination of erythromycin and benzoyl peroxide resulted in a significant reduction in the number of aerobic bacteria without any change in the resistance pattern to erythromycin or other antibiotics.     

武汉市丙酸杆菌对红霉素耐药与23S rRNA点突变和携带erm基因相关

目的 探讨武汉市耐红霉素丙酸杆菌23S rRNA 有无点突变以及携带ermX基因的Tn5432转座子是否转入了丙酸杆菌。 方法 从痤疮患者皮损中分离丙酸杆菌,E-test法检测分离株对红霉素和克林霉素的MIC值。PCR扩增耐药株23S rRNA、ermX、ermX（cj）、IS1249a、IS1249b并测序,并在基因库中比较。 结果 19株痤疮丙酸杆菌（P.acnes）和10株卵白丙酸杆菌（P.avidum）对红霉素均表现为高度耐药（MIC均 > 256 μg/ml）。19株P.acnes中,16株对克林霉素高度耐药（MIC > 256 μg/ml）,3株敏感;10株P.avidum对克林霉素高度耐药（MIC > 256 μg/ml）。19株P.acnes耐药株中,7株在相当于E.coli 23S rRNA 2058位点发现由A→G点突变,均对红霉素和克林霉素高度耐药;4株在相当于E.coli 23S rRNA 2059位点发现由A→G点突变,其中1株对克林霉素耐药,3株敏感;另外8株P.acnes扩增ermX阳性,其序列与基因库中P.acnes ermX基因100%同源。10株P.avidum中,2株ermX扩增阳性,其序列与P.acnes ermX基因100%同源;另外8株扩增ermX（cj）得到预期片段PCR产物,与基因库中Corynebacterium jeikeium ermX（cj）序列99%同源,而与P.acnes ermX基因仅有94%的同源性。10株扩增ermX基因阳性的菌株扩增IS1249a和IS1249b均阳性,而其余菌株均阴性。 结论 武汉市耐红霉素丙酸杆菌分别由相当于E.coli 23S rRNA 2058、2059由A→G点突变、携带ermX的Tn5432传入以及ermX（cj）传入丙酸杆菌引起。     

Superior antibacterial action and reduced incidence of bacterial resistance in minocycline compared to tetracycline-treated acne patients

Twenty-five previously untreated acne patients were monitored throughout a 6-month course of therapy with either tetracycline or minocycline for changes in the numbers of staphylococci, propionibacteria and yeasts of the genus Malessezia on the skin surface. Antibiotic resistant staphylococci and propionibacteria were also counted. Minocycline (50 mg b.d.) produced a 10-fold greater reduction in propionibacterial numbers compared to tetracycline (500 mg b.d.) after 12 (P less than 0.02, t-test) and 24 weeks (P less than 0.05) of therapy. As treatment progressed, propionibacteria were replaced by yeasts, numbers of which were significantly increased by week 12 (P less than 0.02) in tetracycline-treated patients and by week 24 (P less than 0.01) in minocycline-treated patients. This suggests that yeasts have no role in the pathogenesis of acne but may compete with propionibacteria for the same niche. Overgrowth of antibiotic resistant staphylococci prevented any decrease in staphylococcal numbers in tetracycline-treated patients, but minocycline produced a significant and sustained reduction in staphylococcal numbers after 1 week of therapy (P less than 0.001). An increase in the number of multiply resistant (greater than or equal to 3 resistances) staphylococci occurred in 67% of tetracycline-treated and 33% of minocycline-treated patients by the end of the treatment period. There was no evidence of propionibacterial resistance in either treatment group. This study shows that minocycline has much greater antibacterial activity in vivo against both staphylococci and propionibacteria and produces less staphylococcal antibiotic resistance than tetracycline.     

Antimicrobial susceptibility and phylogenetic analysis of Propionibacterium acnes isolated from acne patients in Japan between 2013 and 2015

The prevalence of antimicrobial‐resistant Propionibacterium acnes strains isolated from acne patients has been increasing in Japan. Here, to estimate the current resistance rate, we tested antimicrobial susceptibility among P. acnes from acne patients having visited a specialized dermatology clinic between 2013 and 2015. Rates of resistance to macrolides and clindamycin were 44.3 (31/70) and 38.6% (27/70), respectively. erm(X), which confers high‐level clindamycin resistance (minimum inhibitory concentration ≥256 μg/mL), was detected in six isolates, whereas no resistance determinants were identified in eight strains showing high‐level resistance to clindamycin. Using single‐locus sequence typing, the P. acnes isolates were classified into five clades (A, E, F, H and K), with all high‐level clindamycin‐resistant strains lacking known clindamycin resistance determinants being grouped together (in clade F). P. acnes isolates from patients previously treated with macrolides and clindamycin showed a macrolide resistance rate (55.3%) significantly higher than that of those from patients not having received these treatments (21.7%, P < 0.05). Furthermore, strains of clade F, which were very rarely isolated from healthy individuals, were more frequently recovered from patients with severe acne (40.0%) than those with mild acne (23.3%). Our data showed an increase in macrolide‐resistant P. acnes prevalence in Japan due to the use of antimicrobial agents for acne treatment. Furthermore, we identified strains of specific phylogenetic groups frequently associated with severe acne patients.     

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.