Kurakado Sanae, Yasuda Kakeru, Matsumoto Yasuhiko, Sugita Takashi
Department of Microbiology, Meiji Pharmaceutical University, Tokyo, Japan.
J Med Microbiol. 2025 Sep;74(9). doi: 10.1099/jmm.0.002061.
Biofilms are a primary form of device-associated infections and typically exhibit high tolerance to antimicrobial agents. In biofilms formed by multiple microbial species, microorganisms may show even greater tolerance, complicating treatment. There is evidence that meropenem (MEPM) tolerance in is increased in dual-species biofilms with , and effective treatments have not been established. If the presence of viable increases the MEPM tolerance of in mature biofilms, then the killing of will attenuate the MEPM tolerance of . We evaluated the effectiveness of various antifungal combination treatments against dual-species biofilms of and and . The reduction in the number of viable cells in dual-species mature biofilms formed by and was evaluated after treatment with a combination of antifungal drugs (fluconazole, amphotericin B and micafungin) and MEPM. In addition, the effects of combination therapy were assessed using a silkworm biofilm infection model. The combination of amphotericin B and MEPM reduced the viable cell counts of both and within dual-species biofilms. In contrast, the combination of fluconazole and MEPM did not reduce the viable cell count of either species, whereas the combination of micafungin and MEPM reduced only. The reduction in viable counts by micafungin was less than that by amphotericin B, suggesting that micafungin did not affect the tolerance of . The combination of amphotericin B and MEPM also reduced the viable cell counts of both and in the model. These findings suggest that the combination of amphotericin B and antibacterial agents is a potential treatment option to reduce the -induced bacterial tolerance for catheter-related infections involving co-infection.
生物膜是与器械相关感染的主要形式，通常对抗菌剂表现出高度耐受性。在由多种微生物形成的生物膜中，微生物可能表现出更高的耐受性，使治疗变得复杂。有证据表明，在与[具体微生物名称1]形成的双物种生物膜中，美罗培南（MEPM）耐受性增加，且尚未确立有效的治疗方法。如果活的[具体微生物名称2]的存在增加了成熟生物膜中[具体微生物名称1]对MEPM的耐受性，那么杀灭[具体微生物名称2]将减弱[具体微生物名称1]对MEPM的耐受性。我们评估了各种抗真菌联合治疗对[具体微生物名称1]与[具体微生物名称2]以及[具体微生物名称3]的双物种生物膜的有效性。在用抗真菌药物（氟康唑、两性霉素B和米卡芬净）与MEPM联合治疗后，评估了由[具体微生物名称1]和[具体微生物名称2]形成的双物种成熟生物膜中活细胞数量的减少情况。此外，使用家蚕生物膜感染模型评估了联合治疗的效果。两性霉素B和MEPM的联合使用减少了双物种生物膜中[具体微生物名称1]和[具体微生物名称2]的活细胞数量。相比之下，氟康唑和MEPM的联合使用并未减少任何一种物种的活细胞数量，而米卡芬净和MEPM的联合使用仅减少了[具体微生物名称1]。米卡芬净对[具体微生物名称1]活细胞数量的减少少于两性霉素B，表明米卡芬净不影响[具体微生物名称2]的耐受性。两性霉素B和MEPM的联合使用在[家蚕生物膜感染]模型中也减少了[具体微生物名称1]和[具体微生物名称2]的活细胞数量。这些发现表明，两性霉素B与抗菌剂的联合使用是一种潜在的治疗选择，可降低[具体微生物名称2]诱导的与导管相关感染（涉及[具体微生物名称2]共感染）的细菌耐受性。
