{"title":"利用高浓度和长时间庆大霉素治疗,有效根除带有氨基糖苷修饰酶基因的 MRSA 分离物的生物膜。","authors":"Kohei Ando, Satoshi Miyahara, Shuhei Hanada, Kazumasa Fukuda, Mitsumasa Saito, Akinori Sakai, Akihiro Maruo, Yukichi Zenke","doi":"10.1128/spectrum.00647-24","DOIUrl":null,"url":null,"abstract":"<p><p>Bone and soft tissue infections caused by biofilm-forming bacteria, such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), remain a significant clinical challenge. While the control of local infection is necessary, systemic treatment is also required, and biofilm eradication is a critical target for successful management. Topical antibiotic treatments, such as antibiotic-loaded bone cement (ALBC), have been used for some time, and continuous local antibiotic perfusion therapy, a less invasive method, has been developed by our group. However, the optimal antibiotics and concentrations for biofilms of clinical isolates are still not well understood. We examined the efficacy of high concentrations of gentamicin against MRSA biofilms and the role of gentamicin resistance genes in biofilm eradication. We collected 101 MRSA samples from a hospital in Japan and analyzed their gene properties, including methicillin and gentamicin resistance, and their minimum biofilm eradication concentration (MBEC) values. Our results showed that high concentrations of gentamicin are effective against MRSA biofilms and that even concentrations lower than the MBEC value could eliminate biofilms after prolonged exposure. We also identified three aminoglycoside/gentamicin resistance genes [<i>aac(6')-aph(2″)</i>, <i>aph(3')-III</i>, and <i>ant(4')-IA</i>] and found that the presence or absence of these genes may inform the selection of treatments. It was also found that possession of the <i>aac(6')-aph(2″</i>) gene correlated with the minimum inhibitory concentration/MBEC values of gentamicin. Although this study provides insight into the efficacy of gentamicin against MRSA biofilms and the role of gentamicin resistance genes, careful selection of the optimal treatment strategy is needed for clinical application.</p><p><strong>Importance: </strong>Our analysis of 101 MRSA clinical isolates has provided valuable insights that could enhance treatment selection for biofilm infections in orthopedics. We found that high concentrations of gentamicin were effective against MRSA biofilms, and even prolonged exposure to concentrations lower than the minimum biofilm eradication concentration (MBEC) value could eliminate biofilms. The presence of the <i>aac(6')-aph(2″)</i> gene, an aminoglycoside resistance gene, was found to correlate with the minimum inhibitory concentration (MIC) and MBEC values of gentamicin, providing a potential predictive tool for treatment susceptibility. These results suggest that extended high concentrations of local gentamicin treatment could effectively eliminate MRSA biofilms in orthopedic infections. Furthermore, testing for gentamicin MIC or the possession of the <i>aac(6')-aph(2″)</i> gene could help select treatment, including topical gentamicin administration and surgical debridement.</p>","PeriodicalId":18670,"journal":{"name":"Microbiology spectrum","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effective biofilm eradication in MRSA isolates with aminoglycoside-modifying enzyme genes using high-concentration and prolonged gentamicin treatment.\",\"authors\":\"Kohei Ando, Satoshi Miyahara, Shuhei Hanada, Kazumasa Fukuda, Mitsumasa Saito, Akinori Sakai, Akihiro Maruo, Yukichi Zenke\",\"doi\":\"10.1128/spectrum.00647-24\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Bone and soft tissue infections caused by biofilm-forming bacteria, such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), remain a significant clinical challenge. While the control of local infection is necessary, systemic treatment is also required, and biofilm eradication is a critical target for successful management. Topical antibiotic treatments, such as antibiotic-loaded bone cement (ALBC), have been used for some time, and continuous local antibiotic perfusion therapy, a less invasive method, has been developed by our group. However, the optimal antibiotics and concentrations for biofilms of clinical isolates are still not well understood. We examined the efficacy of high concentrations of gentamicin against MRSA biofilms and the role of gentamicin resistance genes in biofilm eradication. We collected 101 MRSA samples from a hospital in Japan and analyzed their gene properties, including methicillin and gentamicin resistance, and their minimum biofilm eradication concentration (MBEC) values. Our results showed that high concentrations of gentamicin are effective against MRSA biofilms and that even concentrations lower than the MBEC value could eliminate biofilms after prolonged exposure. We also identified three aminoglycoside/gentamicin resistance genes [<i>aac(6')-aph(2″)</i>, <i>aph(3')-III</i>, and <i>ant(4')-IA</i>] and found that the presence or absence of these genes may inform the selection of treatments. It was also found that possession of the <i>aac(6')-aph(2″</i>) gene correlated with the minimum inhibitory concentration/MBEC values of gentamicin. Although this study provides insight into the efficacy of gentamicin against MRSA biofilms and the role of gentamicin resistance genes, careful selection of the optimal treatment strategy is needed for clinical application.</p><p><strong>Importance: </strong>Our analysis of 101 MRSA clinical isolates has provided valuable insights that could enhance treatment selection for biofilm infections in orthopedics. We found that high concentrations of gentamicin were effective against MRSA biofilms, and even prolonged exposure to concentrations lower than the minimum biofilm eradication concentration (MBEC) value could eliminate biofilms. The presence of the <i>aac(6')-aph(2″)</i> gene, an aminoglycoside resistance gene, was found to correlate with the minimum inhibitory concentration (MIC) and MBEC values of gentamicin, providing a potential predictive tool for treatment susceptibility. These results suggest that extended high concentrations of local gentamicin treatment could effectively eliminate MRSA biofilms in orthopedic infections. Furthermore, testing for gentamicin MIC or the possession of the <i>aac(6')-aph(2″)</i> gene could help select treatment, including topical gentamicin administration and surgical debridement.</p>\",\"PeriodicalId\":18670,\"journal\":{\"name\":\"Microbiology spectrum\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-08-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microbiology spectrum\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1128/spectrum.00647-24\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microbiology spectrum","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/spectrum.00647-24","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
Effective biofilm eradication in MRSA isolates with aminoglycoside-modifying enzyme genes using high-concentration and prolonged gentamicin treatment.
Bone and soft tissue infections caused by biofilm-forming bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), remain a significant clinical challenge. While the control of local infection is necessary, systemic treatment is also required, and biofilm eradication is a critical target for successful management. Topical antibiotic treatments, such as antibiotic-loaded bone cement (ALBC), have been used for some time, and continuous local antibiotic perfusion therapy, a less invasive method, has been developed by our group. However, the optimal antibiotics and concentrations for biofilms of clinical isolates are still not well understood. We examined the efficacy of high concentrations of gentamicin against MRSA biofilms and the role of gentamicin resistance genes in biofilm eradication. We collected 101 MRSA samples from a hospital in Japan and analyzed their gene properties, including methicillin and gentamicin resistance, and their minimum biofilm eradication concentration (MBEC) values. Our results showed that high concentrations of gentamicin are effective against MRSA biofilms and that even concentrations lower than the MBEC value could eliminate biofilms after prolonged exposure. We also identified three aminoglycoside/gentamicin resistance genes [aac(6')-aph(2″), aph(3')-III, and ant(4')-IA] and found that the presence or absence of these genes may inform the selection of treatments. It was also found that possession of the aac(6')-aph(2″) gene correlated with the minimum inhibitory concentration/MBEC values of gentamicin. Although this study provides insight into the efficacy of gentamicin against MRSA biofilms and the role of gentamicin resistance genes, careful selection of the optimal treatment strategy is needed for clinical application.
Importance: Our analysis of 101 MRSA clinical isolates has provided valuable insights that could enhance treatment selection for biofilm infections in orthopedics. We found that high concentrations of gentamicin were effective against MRSA biofilms, and even prolonged exposure to concentrations lower than the minimum biofilm eradication concentration (MBEC) value could eliminate biofilms. The presence of the aac(6')-aph(2″) gene, an aminoglycoside resistance gene, was found to correlate with the minimum inhibitory concentration (MIC) and MBEC values of gentamicin, providing a potential predictive tool for treatment susceptibility. These results suggest that extended high concentrations of local gentamicin treatment could effectively eliminate MRSA biofilms in orthopedic infections. Furthermore, testing for gentamicin MIC or the possession of the aac(6')-aph(2″) gene could help select treatment, including topical gentamicin administration and surgical debridement.
期刊介绍:
Microbiology Spectrum publishes commissioned review articles on topics in microbiology representing ten content areas: Archaea; Food Microbiology; Bacterial Genetics, Cell Biology, and Physiology; Clinical Microbiology; Environmental Microbiology and Ecology; Eukaryotic Microbes; Genomics, Computational, and Synthetic Microbiology; Immunology; Pathogenesis; and Virology. Reviews are interrelated, with each review linking to other related content. A large board of Microbiology Spectrum editors aids in the development of topics for potential reviews and in the identification of an editor, or editors, who shepherd each collection.