由生物膜形成细菌引起的骨和软组织感染,例如耐甲氧西林金黄色葡萄球菌(MRSA),仍然是一个重大的临床挑战。虽然控制局部感染是必要的,还需要全身治疗,和生物膜根除是成功管理的关键目标。局部抗生素治疗,如负载抗生素的骨水泥(ALBC),已经使用了一段时间,和持续的局部抗生素灌注治疗,一种侵入性较小的方法,是我们集团开发的。然而,临床分离株生物膜的最佳抗生素和浓度仍不清楚.我们研究了高浓度庆大霉素对MRSA生物膜的功效以及庆大霉素抗性基因在生物膜根除中的作用。我们从日本一家医院收集了101份MRSA样本,并分析了它们的基因特性,包括耐甲氧西林和庆大霉素,和它们的最小生物膜根除浓度(MBEC)值。我们的结果表明,高浓度的庆大霉素对MRSA生物膜有效,即使浓度低于MBEC值也可以在长时间暴露后消除生物膜。我们还确定了三个氨基糖苷/庆大霉素抗性基因[aac(6')-aph(2”),aph(3')-III,和ant(4')-IA],并发现这些基因的存在或不存在可以告知治疗的选择。还发现,aac(6')-aph(2”)基因的拥有与庆大霉素的最低抑制浓度/MBEC值相关。尽管这项研究提供了有关庆大霉素对MRSA生物膜的功效以及庆大霉素抗性基因的作用的见解,临床应用需要仔细选择最佳治疗策略。
目的:我们对101株MRSA临床分离株的分析提供了有价值的见解,可以增强骨科生物膜感染的治疗选择。我们发现高浓度的庆大霉素对MRSA生物膜有效,甚至长时间暴露于低于最小生物膜根除浓度(MBEC)值的浓度可以消除生物膜。aac(6')-aph(2″)基因的存在,氨基糖苷抗性基因,发现与庆大霉素的最小抑制浓度(MIC)和MBEC值相关,为治疗敏感性提供潜在的预测工具。这些结果表明,延长高浓度的局部庆大霉素治疗可以有效消除骨科感染中的MRSA生物膜。此外,测试庆大霉素MIC或拥有aac(6\')-aph(2”)基因可以帮助选择治疗,包括局部庆大霉素给药和手术清创术。
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.
OBJECTIVE: 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.