Prevalence of antimicrobial-resistant Cutibacterium isolates and development of multiplex PCR method for Cutibacterium species identification.

INTRODUCTION: Cutibacterium species such as C. acnes, C. avidum, and C. granulosum are known anaerobic skin inhabitants and often cause surgical site infections. These species are genetically similar and are difficult to identify rapidly. In addition, their pathogenicity and antimicrobial resistance remain unknown. In this study, antimicrobial resistance in Cutibacterium isolates was studied and a multiplex PCR method for their identification was developed. METHODS: A total of 497 C. acnes, 71 C. avidum, and 25 C. granulosum strains which were isolated from the acne pustule and infectious regions, were used. RESULTS: The antimicrobial resistance rates of C. acnes, C. avidum, and C. granulosum strains isolated from patients with acne vulgaris were higher than those of strains isolated from patients with infectious diseases. In particular, macrolide-clindamycin-resistant strains were isolated most frequently from all species. Among the resistant strains, strains with 23S rRNA mutations were the most common in C. acnes (24.3%, 71/292), whereas C. avidum and C. granulosum strains were most frequently found with erm(X). For the first time, a C. granulosum strain carrying pTZC1, which codes erm(50) and tet(W), was isolated from patients with acne vulgaris. Regarding the rapid identification of causative pathogens from infectious regions, three Cutibacterium species were identified with 100% sensitivity and specificity using multiplex PCR method. CONCLUSIONS: Our data showed that antimicrobial resistance differed among Cutibacterium species. The multiplex PCR method may contribute to the rapid detection of Cutibacterium species and selection of appropriate antimicrobial agents.

Cutibacterium acnes phylogenetic type IC and II isolated from patients with non-acne diseases exhibit high-level biofilm formation.

Cutibacterium (formerly Propionibacterium) acnes is an important for not only exacerbating factor of acne vulgaris but also pathogen of surgical site infections (SSIs) in orthopedics and plastic surgery. Although biofilm-forming (BF) C. acnes are associated with intractable SSI, characteristics of these strains were still unknown. Here, we explored detailed molecular epidemiological features of BF C. acnes isolated as causative pathogen of infectious diseases. Phylogenetic types of 205 C. acnes strains isolated between 2013 and 2018 from 18 clinical departments of a university hospital in Japan were determined by single-locus sequence type (SLST). Clade H (traditional type IC) and K (type II) which are less relevant with healthy skin and acne vulgaris, were detected in 26.8% (55/205) and 16.1% (33/205) of the strains, respectively. The incidence of them was significantly higher than that of acne patients (H and K, each 2.9%, P < 0.05). In addition, SLST distribution of C. acnes strains differed by each department and isolation site. When biofilm formation was quantified, 51 strains (24.9%) were defined as high-BF strains. Notably, most high-BF strains were classified into the strains of clade H (56.4%, 31/55) and clade K (54.4%, 18/33), and these strains were frequently found in the strains isolated from patients of medical emergency center and plastic surgery. Similarly, high-BF strains were frequently found among the isolates from blood (35.7%) and catheters (30.0%), with a high proportion belonging to clades H and K. Compared to C. acnes strains isolated from acne patients, antimicrobial-resistant strains were less identified in non-acne patients. Our findings showed that pathogenicity of C. acnes strains differs by their phylogenetic types. Furthermore, we showed clade H and K have the ability of high biofilm formation and suggest that these strains have potential to become a risk factor for SSI.

Antimicrobial activity and additive effect of the modified Gingyo-san with antimicrobials against Helicobacter pylori.

INTRODUCTION: Helicobacter pylori is an important factor in the development of gastroduodenal ulcers and gastric cancer. Although H. pylori eradication therapy has been employed, the eradication rate has decreased in recent years owing to an increase in clarithromycin-resistant strains. We previously reported the anti-infective effect of herbal medicines against several bacterial species. Here, we evaluated the growth inhibitory activity of herbal medicines alone and in combination with antimicrobials against H. pylori. METHODS AND RESULTS: Nine of 37 herbal medicines inhibited the growth of H. pylori ATCC700392. In particular, modified Gingyo-san showed the strongest growth inhibitory activity with a minimum inhibitory concentration (MIC) of 512 µg/ml for not only ATCC700392 but also clarithromycin-resistant strains having a 23 S rRNA mutation. Results of Time-Kill Kinetics Assay showed that 1 mg/mL modified Gingyo-san treatment for one hour killed 50% of the H. pylori population. Furthermore, modified Gingyo-san showed additive effects with clarithromycin, amoxicillin, and metronidazole against H. pylori ATCC700392 and clarithromycin-resistant strains. CONCLUSIONS: Our findings showed that modified Gingyo-san inhibits the growth of H. pylori and improves antimicrobial susceptibility when used in combination. Therefore, modified Gingyo-san has the potential to enhance the eradication rate of clarithromycin-resistant H. pylori.

Transferable Multidrug-Resistance Plasmid Carrying a Novel Macrolide-Clindamycin Resistance Gene, erm(50), in Cutibacterium acnes.

Antimicrobial-resistant Cutibacterium acnes strains have emerged and disseminated throughout the world. The 23S rRNA mutation and erm(X) gene are known as the major resistance determinants of macrolides and clindamycin in C. acnes We isolated eight high-level macrolide-clindamycin-resistant C. acnes strains with no known resistance determinants, such as 23S rRNA mutation and erm(X), from different acne patients in 2008 between 2013 and 2015. The aim of this study was to identify the novel mechanisms of resistance in C. acnes Whole-genome sequencing revealed the existence of a plasmid DNA, denoted pTZC1 (length, 31,440 bp), carrying the novel macrolide-clindamycin resistance gene erm(50) and tetracycline resistance gene tet(W). pTZC1 was detected in all C. acnes isolates (eight strains) exhibiting high-level macrolide-clindamycin resistance, with no known resistance determinants (MIC of clarithromycin, ≥256 µg/ml; clindamycin, ≥256 µg/ml). Transconjugation experiments demonstrated that the pTZC1 was horizontally transferred among C. acnes strains and conferred resistance to macrolides, clindamycin, and tetracyclines. Our data showed, for the first time, the existence of a transferable multidrug-resistant plasmid in C. acnes Increased prevalence of this plasmid will be a great threat to antimicrobial therapy for acne vulgaris.

Evaluation of in Vitro Bactericidal Activity of 1.5% Olanexidine Gluconate, a Novel Biguanide Antiseptic Agent.

Recently, 1.5% olanexidine gluconate, a biguanide compounds, was launched as a new antiseptic agent in Japan. However, the comprehensive bactericidal spectrum of olanexidine gluconate is still unknown. In this study, we evaluated in vitro bactericidal activity of olanexidine gluconate using time-kill assay against various bacteria, mycobacteria, and fungi. With the exception of Burkholderia cepacia and Mycobacterium spp., 1.5% olanexidine gluconate exhibited fast-acting (≤60 s) bactericidal activity against all tested Gram-positive and Gram-negative bacteria, including vancomycin-resistant Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, extended spectrum ß-lactamase producing Klebsiella pneumoniae, and multidrug-resistant Pseudomonas aeruginosa. Furthermore, 1.5% olanexidine gluconate eradicated Candida albicans, Microsporum canis, and Malassezia furfur within 3 min. Our findings indicate that olanexidine gluconate has broad spectrum bactericidal activity; therefore, it may be useful for the prevention of a wide range of infectious diseases.

Exogenous gene transfer of Rab38 small GTPase ameliorates aberrant lung surfactant homeostasis in Ruby rats.

BACKGROUND: Rab38 small GTPase regulates intracellular transport in melanocytes and alveolar type II epithelial cells. Ruby rats carrying Rab38 and other gene mutations exhibit oculocutaneous albinism, bleeding diathesis, and hence, are a rat model of human Hermansky-Pudlak syndrome (HPS). We previously showed that Long Evans Cinnamon (LEC) rats, one strain of the Ruby rats, developed aberrant lung surfactant homeostasis with remarkably enlarged lamellar bodies in alveolar type II cells. METHODS: A replication-deficient recombinant adenovirus expressing rat Rab38 (Ad-Rab38) was constructed. Alveolar type II cells were isolated from the LEC rats and tested for lung surfactant phosphatidylcholine secretion. The rats were also examined whether exogenous expression of Ad- Rab38 could rescue the altered lung surfactant homeostasis in the lungs. RESULTS: Isolated type II cells infected with Ad-Rab38 exhibited improved secretion patterns of [3H]phosphatidylcholine, i.e. increased basal hyposecretion and decreased agonist-induced hypersecretion. Endobronchial administration of Ad-Rab38 improved the morphology of type II cells and lamellar bodies, reducing their sizes close to those of wild-type rats. The increased amounts of phosphatidylcholine and surfactant protein B in the lamellar body fractions were decreased in the Ad-Rab38 infected lungs. CONCLUSIONS: These results provide strong evidence that the aberrant lung surfactant homeostasis in the LEC rats is caused by Rab38 deficit, and suggest that endobronchial delivery of the responsive transgene could be an effective method to ameliorate the abnormal lung phenotype in the animal model of HPS.

Determination of the Mutant Prevention Concentration and the Mutant Selection Window of Topical Antimicrobial Agents against Propionibacterium acnes.

Determination of the mutant prevention concentration (MPC) and the mutant selection window (MSW) of antimicrobial agents used to treat pathogenic bacteria is important in order to apply effective antimicrobial therapies. Here, we determined the MPCs of the major topical antimicrobial agents against Propionibacterium acnes and Staphylococcus aureus which cause skin infections and compared their MSWs. Among the MPCs of nadifloxacin and clindamycin, the clindamycin MPC was determined to be the lowest against P. acnes. In contrast, the nadifloxacin MPC was the lowest against S. aureus. Calculations based on the minimum inhibitory concentrations and MPCs showed that clindamycin has the lowest MSW against both P. acnes and S. aureus. Nadifloxacin MSWs were 4-fold higher against P. acnes than against S. aureus. It is more likely for P. acnes to acquire resistance to fluoroquinolones than S. aureus. Therefore, topical application of clindamycin contributes very little to the emergence of resistant P. acnes and S. aureus strains.

Methicillin-Resistant Staphylococcus epidermidis Is Part of the Skin Flora on the Hands of Both Healthy Individuals and Hospital Workers.

Staphylococcus epidermidis, a major skin flora on hands, acts as a reservoir of various antimicrobial resistance determinants including staphylococcal cassette chromosome mec (SCCmec) and contributes to multidrug resistance for S. aureus. The aim of this study was understanding the characteristics of commensal S. epidermidis on the hands of hospital workers and healthy individuals. A total of 23 hospital workers (physicians, nurses, and hospital pharmacists), 13 community pharmacists, and 24 healthy individuals (students) were studied. Commensal bacteria on hands were recovered using a glove-juice method. For methicillin-resistant S. epidermidis (MRSE), we performed SCCmec typing, pulsed-field gel electrophoresis (PFGE), and determined the antimicrobial susceptibility. The detection rates of MRSE in community pharmacists (92.3%) and students (87.5%) were higher than those in hospital workers (66.7 to 81.8%). SCCmec type IV strains were predominant in both hospital workers and students. PFGE analysis strongly suggested that the MRSE of hospital workers and students were normal inhabitants of each subject. The antimicrobial resistance rates and levels in MRSE of hospital workers were higher than those of students. Our findings showed that MRSE was frequently colonized on the hands of healthy individuals as well as hospital workers.

Emergence of fluoroquinolone-resistant Propionibacterium acnes caused by amino acid substitutions of DNA gyrase but not DNA topoisomerase IV.

With the aim of elucidating the mechanisms of fluoroquinolones resistance in Propionibacterium acnes, we determined the susceptibility of fluoroquinolones in 211 isolates from patients with acne vulgaris. We identified five isolates (2.4%) with reduced susceptibility to nadifloxacin (minimum inhibitory concentration ≥ 4 µg/ml). Determination of the sequences of the DNA gyrase (gyrA and gyrB) and DNA topoisomerase (parC and parE) genes showed the amino acid substitutions Ser101Leu and Asp105Gly of GyrA in four and one of the isolates, respectively. In vitro mutation experiments showed that low-level fluoroquinolone-resistant mutants with the Ser101Leu or Asp105Gly substitution in GyrA could be obtained from selection with ciprofloxacin and levofloxacin. The pattern of substitution (Ser101Trp in GyrA) caused by nadifloxacin selection was different from that induced by the other fluoroquinolones. In the isolation of further high-level resistant mutants, acquisition of another amino acid substitution of GyrB in addition to those of GyrA was detected, but there were no substitutions of ParC and ParE. In addition, the mutant prevention concentration and mutation frequency of nadifloxacin were lowest among the tested fluoroquinolones. The growth of the Ser101Trp mutant was lower than that of the other mutants. Our findings suggest that the Ser101Trp mutant of P. acnes emerges rarely and disappears immediately, and the risk for the prevalence of fluoroquinolones-resistant P. acnes differs according to the GyrA mutation type. To our knowledge, this study is the first to demonstrate the mechanisms of resistance to fluoroquinolones in P. acnes.

Emergence of Cutibacterium avidum with erm(X) on a Mobile Genetic Element Identical to That of Cutibacterium acnes.

We determined that the Cutibacterium avidum isolate TP-CV302, from a patient with acne vulgaris in Japan, had the macrolide-clindamycin resistance factor erm(X) located on Tn5432. Although this mobile genetic element (MGE) is well recognized in Cutibacterium acnes, it has not been found in Cutibacterium avidum.

Avidumicin, a novel cyclic bacteriocin, produced by Cutibacterium avidum shows anti-Cutibacterium acnes activity.

The prevalence of antimicrobial-resistant Cutibacterium acnes in acne patients has increased owing to inappropriate antimicrobial use. Commensal skin bacteria may play an important role in maintaining the balance of the skin microbiome by producing antimicrobial substances. Inhibition of Cu. acnes overgrowth can prevent the development and exacerbation of acne vulgaris. Here, we evaluated skin bacteria with anti-Cu. acnes activity. Growth inhibition activity against Cu. acnes was tested using 122 strains isolated from the skin of healthy volunteers and acne patients. Comparative genomic analysis of the bacterium with or without anti-Cu. acnes activity was conducted. The anti-Cu. acnes activity was confirmed by cloning an identified gene cluster and chemically synthesized peptides. Cu. avidum ATCC25577 and 89.7% of the Cu. avidum clinical isolates (26/29 strains) inhibited Cu. acnes growth. The growth inhibition activity was also found against other Cutibacterium, Lactiplantibacillus, and Corynebacterium species, but not against Staphylococcus species. The genome sequence of Cu. avidum showed a gene cluster encoding a novel bacteriocin named avidumicin. The precursor protein encoded by avdA undergoes post-translational modifications, supposedly becoming a circular bacteriocin. The anti-Cu. acnes activity of avidumicin was confirmed by Lactococcus lactis MG1363 carrying avdA. The C-terminal region of the avidumicin may be essential for anti-Cu. acnes activity. A commensal skin bacterium, Cu. avidum, producing avidumicin has anti-Cu. acnes activity. Therefore, avidumicin is a novel cyclic bacteriocin with a narrow antimicrobial spectrum. These findings suggest that Cu. avidum and avidumicin represent potential alternative agents in antimicrobial therapy for acne vulgaris.

Multidrug Resistance Plasmid pTZC1 Could Be Pooled among Cutibacterium Strains on the Skin Surface.

Acne vulgaris is a chronic inflammatory skin disease that is exacerbated by Cutibacterium acnes. Although antimicrobials such as macrolides, clindamycin, and tetracyclines are used to treat acne caused by C. acnes, the increasing prevalence of antimicrobial-resistant C. acnes strains has become a global concern. In this study, we investigated the mechanism by which interspecies transfer of multidrug-resistant genes can lead to antimicrobial resistance. Specifically, the transfer of pTZC1 between C. acnes and C. granulosum isolated from specimens of patients with acne was investigated. Among the C. acnes and C. granulosum isolated from 10 patients with acne vulgaris, 60.0% and 70.0% of the isolates showed resistance to macrolides and clindamycin, respectively. The multidrug resistance plasmid pTZC1, which codes for macrolide-clindamycin resistance gene erm(50) and tetracycline resistance gene tet(W), was identified in both C. acnes and C. granulosum isolated from the same patient. In addition, whole-genome sequencing revealed that the pTZC1 sequences of C. acnes and C. granulosum showed 100% identity using comparative whole-genome sequencing analysis. Therefore, we hypothesize that the horizontal transfer of pTZC1 between C. acnes and C. granulosum strains may occur on the skin surface. The plasmid transfer test revealed a bidirectional transfer of pTZC1 between C. acnes and C. granulosum, and transconjugants that obtained pTZC1 exhibited multidrug resistance. In conclusion, our results revealed that the multidrug resistance plasmid pTZC1 could be transferred between C. acnes and C. granulosum. Furthermore, since pTZC1 transfer among different species may aid in the prevalence of multidrug resistant strains, antimicrobial resistance genes may have been pooled on the skin surface. IMPORTANCE The emergence of antimicrobial resistance not only in Cutibacterium acnes strain but also other skin bacteria such as Staphylococcus epidermidis is a big concern due to antimicrobial use for the treatment of acne vulgaris. Increased prevalence of macrolides-clindamycin resistant C. acnes relates to the acquisition of exogenous antimicrobial resistance genes. erm(50) is harbored by the multidrug resistance plasmid pTZC1, which has been found in C. acnes and C. granulosum strains isolated from patients with acne vulgaris. In this study, C. acnes and C. granulosum with pTZC1 were found in the same patient, and plasmid transfer between C. acnes and C. granulosum was proved by transconjugation assay. This study showed plasmid transfer between other species and the possibility of further prevalence antimicrobial resistance between Cutibacterium species.

A case of severe pneumonia caused by Legionella longbeachae with positive results by a Legionella urinary antigen detection kit.

Legionella longbeachae is a Legionella bacteria often detected in soil, and is known as a rare cause of Legionella infections in Japan. In addition, detection of this Legionella species is often overlooked due to negative results from Legionella urinary antigen tests, which could lead to errors in the therapeutic approach. An 80-year-old woman was admitted to our hospital because of fever and dyspnea. Her blood tests showed elevated white blood cells, increased C-reactive protein and transaminases, and hyponatremia. Chest computed tomography showed dense consolidation in the right lung. We diagnosed Legionella pneumonia because the Legionella urinary antigen test was positive on the day after her admission. The patient was intubated and mechanically ventilated on the third day of hospitalization, because of respiratory failure. However, her condition did not improve and she died on the 10th day after admission. After her death, L. longbeachae was detected from sputum culture from her tracheal tube, and was diagnosed as the causative organism of her pneumonia. L. longbeachae infection reportedly rarely produces positive urinary antigen test results. Our experience suggests that the urinary antigen test using Ribotest Legionella might be able to detect Legionella spp. other than L. pneumophila.

Increased frequency of clindamycin-resistant Cutibacterium acnes strains isolated from Japanese patients with acne vulgaris caused by the prevalence of exogenous resistance genes.

Cutibacterium acnes, a resident bacterium of the skin, is a target for antimicrobial treatment of acne vulgaris, because it exacerbates inflammation. Recently, antimicrobial-resistant C. acnes strains have been isolated worldwide, and their prevalence has led to failure of antimicrobial treatment. This study aimed to analyze the antimicrobial resistance of C. acnes strains isolated from Japanese patients with acne vulgaris who visited the hospital and dermatological clinics between 2019 and 2020. Resistance rates to roxithromycin and clindamycin increased during 2019 to 2020 compared with those during 2013 to 2018. Additionally, the proportion of doxycycline-resistant and low-susceptibility strains (minimum inhibitory concentration [MIC] ≥8 µg/mL) increased. No difference in clindamycin resistance rates between patients with and without a history of antimicrobial use was observed during 2019 to 2020, which were significantly higher for patients with a history than for patients without a history during 2016 to 2018. The proportion of high-level clindamycin-resistant strains (MIC ≥256 µg/mL) gradually increased; particularly, the resistance rate was 2.5 times higher in 2020 than that in 2013. The proportion of strains showing high-level clindamycin resistance that also have the exogenous resistance genes erm(X) or erm(50), which confer high resistance, showed a strong positive correlation (r = 0.82). Strains with the multidrug resistance plasmid pTZC1 encoding erm(50) and tet(W) genes were frequent in clinic patients. Notably, most strains with erm(X) or erm(50) were classified as single-locus sequence types A and F (traditional types IA1 and IA2). Our data show that the prevalence of antimicrobial-resistant C. acnes is increasing in patients with acne vulgaris attributable to acquisition of exogenous genes in specific strains. To control the increasing prevalence of antimicrobial-resistant strains, it is important to select the appropriate antimicrobials while taking into consideration the latest information on resistant strains.

Differential response in patients with large cell neuroendocrine carcinoma of the lung to initial therapy: A case series.

BACKGROUND: Large cell neuroendocrine tumors of the lung (LCNEC) are rare. Chemotherapy with the small cell lung carcinoma (SCLC) regimen is the most appropriate treatment for LCNEC. However, there is evidence that the non-small cell lung cancer regimen is also effective in some reported cases. Due to the differences in response to LCNEC treatment, a standard of care for LCNEC has not been established. CASES: The clinical records of nine patients with LCNEC who were treated with anticancer drugs based on an SCLC regimen from March 2016 to March 2022 were retrospectively reviewed. The patients who responded to treatment after one cycle of systemic chemotherapy were compared to those who did not respond. All patients in the responder group had a performance status (PS) of 0 or 1. However, 5 of the 6 patients in the non-responder group had a PS of 2 or 3, indicating that many patients were in poor general condition. Although patients with multiple metastases to more than one organ prior to treatment were not identified in the responder group, five of these patients were in the non-responder group. In the non-responder group, all patients discontinued treatment due to deterioration of general condition during first-line treatment. Thus, none of them were able to start the second-line treatment. CONCLUSION: The results of this study may suggest that early diagnosis and initiation of treatment before multiple organ metastasis development and PS decline may have clinical implications that could lead to improved treatment response in patients with LCNEC.

Influencing factors of efficacy and long-term use of amrubicin in patients with small cell lung cancer.

BACKGROUND: Amrubicin (AMR) has become the standard of care for post-relapse small cell lung cancer (SCLC). It has also been reported to achieve long-term disease control in patients with good treatment response. However, the optimal patient population for whom AMR is effective and the factors associated with long-term disease control are yet to be identified. The aim of the study was to identify the clinical characteristics and factors associated with long-term disease control in patients with recurrent SCLC who would benefit from AMR therapy. METHODS: The clinical records of 33 patients diagnosed with recurrent SCLC and treated with AMR were retrospectively reviewed. Clinical information was compared between patients who achieved disease control (effective group) and who developed disease progression (noneffective group) on the first efficacy assessment after AMR and between patients who continued AMR for more than seven cycles (maintenance group) and those who terminated treatment after 1-6 cycles (discontinuation group). RESULTS: The noneffective group included significantly more patients with AMR dose reductions after the second cycle (p = 0.006). AMR dose reduction was an independent risk factor for disease progression. The maintenance group had significantly lower pretreatment lactate dehydrogenase (LDH) levels than the discontinuation group (p = 0.046). A high LDH level was an independent risk factor for short AMR discontinuation. Overall survival was significantly longer in the effective group than in the noneffective group (p < 0.001). CONCLUSIONS: In AMR therapy for patients with relapsed SCLC, continuation of AMR without dose reduction after the second cycle may contribute to disease control and prolonged survival.

Identification of a Transferable Linear Plasmid Carrying the Macrolide-Clindamycin Resistance Gene erm(X) in a Cutibacterium acnes Isolate from a Patient with Acne Vulgaris in Japan.

Cutibacterium acnes, one of the common skin bacteria, is known to exacerbate acne vulgaris. Macrolide-clindamycin-resistant C. acnes strains have been reported worldwide. In this study, we found a transferable linear plasmid carrying the macrolide-clindamycin resistance gene erm(X) in a C. acnes strain isolated from a patient with acne vulgaris.

Development of skin sebum medium and inhibition of lipase activity in Cutibacterium acnes by oleic acid.

Cutibacterium acnes is associated with the exacerbated inflammation of acne vulgaris, which occurs through the immune induction and pathogenicity factor production. Sebum, which is not present in the growth medium currently used to study acne, is present in acne pustules in differing concentrations among the pathological stages, such as the initial formation and inflammatory phase. To evaluate the effect of C. acnes on inflammation exacerbation in acne pustules in vitro, we developed an skin sebum medium containing artificial sebum and studied the growth and pathogenicity factor production of C. acnes in the skin sebum medium. The growth and lipase activity of C. acnes ATCC11828 were tested using skin sebum medium containing different sebum concentrations. Only lipase activity decreased in the skin sebum medium culture containing 0.5 % sebum when compared with that without sebum, while both growth and lipase activity decreased in cultures with 1.0 % sebum. Therefore, the growth and lipase activity of C. acnes changed in the presence of sebum. Furthermore, when the growth and lipase activity of C. acnes were tested in skin sebum medium containing sebum components, unsaturated fatty acids, such as oleic acid and triolein, led to a decrease in lipase activity without inducing a change in growth. In the presence of oleic acid, C. acnes lipase activity decreased noncompetitively in a concentration-dependent manner. Our data showed that C. acnes growth and lipase activity changed upon sebum addition to the skin sebum medium, and acne inflammation caused by C. acnes needs to be studied under conditions similar to those in acne pustules.

Increased Prevalence of Minocycline-Resistant Staphylococcus epidermidis with tet(M) by Tetracycline Use for Acne Treatment.

Staphylococcus epidermidis, a major skin bacterium, can cause opportunistic infections. Use of antimicrobial agents against Cutibacterium acnes for acne treatment becomes a risk factor for emergence of antimicrobial-resistant skin bacteria. In this study, the impact of antimicrobial treatment of acne vulgaris on S. epidermidis antimicrobial resistance was assessed. A total of 344 S. epidermidis strains isolated from patients with acne vulgaris who visited hospital (165 strains) and dermatological clinics (179 strains), respectively, were analyzed. Except for doxycycline, the resistance rates were higher in strains isolated from patients who had used antimicrobials for acne treatment than in those isolated from patients who had not used antimicrobials. The prevalence rates of strains with erm(C) from patients who used macrolides and clindamycin (hospital, 78.0%; clinics, 61.3%) and those of strains with tet(M) from patients who used tetracyclines (hospital, 27.5%; clinics, 42.4%) were significantly higher than those of strains from patients who did not use antimicrobials (p < 0.05). All strains with erm(A) (8/8) and 91.7% strains with erm(C) (156/170) showed high-level resistance to macrolides and clindamycin (MIC ≥256 µg/mL). Furthermore, almost all strains with tet(M) showed resistance to minocycline. Our results showed that the use of antimicrobials for acne treatment may lead to an increased prevalence of antimicrobial-resistant S. epidermidis. In particular, the emergence of minocycline-resistant strains with tet(M) owing to the use of tetracyclines (doxycycline and minocycline) is a critical issue. Appropriate antimicrobial use for acne treatment may be an important strategy to prevent the emergence of antimicrobial-resistant skin bacteria.

Acquired pulmonary arteriovenous malformation associated with bronchiectasis: a case report.

BACKGROUND: Pulmonary arteriovenous malformations are mostly caused by congenitally abnormal shunts between pulmonary arteries and pulmonary veins. CASE PRESENTATION: A 74-year-old Japanese woman with a history of bronchiectasis was admitted to our hospital because of dyspnea on exertion. Pulmonary angiography and reconstructed three-dimensional contrast-enhanced computed tomography images showed shunts between pulmonary arteries and pulmonary veins, indicating a diagnosis of pulmonary arteriovenous malformations. Coil embolization of the shunts was successful. CONCLUSIONS: Our findings imply that bronchiectasis can cause pulmonary arteriovenous malformations, and thus patients who present with hypoxemia with bronchiectasis should be carefully evaluated.