De Oliveira David M P, Walker Mark J
The University of Queensland, School of Chemistry and Molecular Biosciences, Australian Infectious Diseases Research Centre, Brisbane, QLD, Australia.
Microb Cell. 2022 Feb 15;9(3):69-71. doi: 10.15698/mic2022.03.772. eCollection 2022 Mar 7.
Within intensive care units, multi-drug resistant outbreaks are a frequent cause of ventilator-associated pneumonia. During the on-going COVID-19 pandemic, patients who receive ventilator support experience a 2-fold increased risk of mortality when they contract a secondary pulmonary infection. In our recent paper (De Oliveira (2022), Mbio, doi: 10.1128/mbio.03517-21), we demonstrate that the 8-hydroxquinoline ionophore, PBT2 breaks the resistance of to tetracycline class antibiotics. , the combination of PBT2 and zinc with either tetracycline, doxycycline, or tigecycline was shown to be bactericidal against multi-drug-resistant , and any resistance that did arise imposed a fitness cost. Using a murine model of pulmonary infection, treatment with PBT2 in combination with tetracycline or tigecycline proved efficacious against multidrug-resistant . These findings suggest that PBT2 may find utility as a resistance breaker to rescue the efficacy of tetracycline-class antibiotics commonly employed to treat multi-drug resistant infections.
在重症监护病房中，多重耐药性爆发是呼吸机相关性肺炎的常见原因。在持续的COVID-19大流行期间，接受呼吸机支持的患者在感染继发性肺部感染时死亡风险增加两倍。在我们最近的论文（De Oliveira （2022年），《微生物学》，doi: 10.1128/mbio.03517-21）中，我们证明8-羟基喹啉离子载体PBT2可打破对四环素类抗生素的耐药性。此外，PBT2与锌与四环素、强力霉素或替加环素的组合对多重耐药菌具有杀菌作用，并且出现的任何耐药性都会带来适应性代价。使用肺部感染小鼠模型，PBT2与四环素或替加环素联合治疗对多重耐药菌有效。这些发现表明，PBT2可能作为一种耐药性突破剂，用于恢复通常用于治疗多重耐药菌感染的四环素类抗生素的疗效。
