Abdul-Mutakabbir Jacinda C, Yim Juwon, Nguyen Logan, Maassen Philip T, Stamper Kyle, Shiekh Zain, Kebriaei Razieh, Shields Ryan K, Castanheira Mariana, Kaye Keith S, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA.
Division of Infectious Diseases, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA.
Antibiotics (Basel). 2021 Jul 20;10(7):880. doi: 10.3390/antibiotics10070880.
is currently classified as one of six pathogens that contribute to increased patient mortality. Thus, exploratory studies navigating alternative treatment strategies are of supreme interest. Herein, we completed minimum inhibitory concentration (MIC) testing, and time-kill analyses (TKA) on 50 carbapenem-resistant isolates including 28 colistin-resistant isolates. Upon testing of MEM or TGC in the presence of sub-inhibitory COL against the 50 isolates, there was a median 2-fold reduction in MEM and TGC MICs. In the TKAs, the COL+MEM combination was synergistic in 45 (90%) isolates and bactericidal in 43 (86%) isolates at 24 hours, whereas the COL+TGC combination TKAs demonstrated synergy in 32 (64%) isolates and bactericidal activity was shown in 28 (56%) isolates. Additionally, sulbactam (SUL) and TGC were added to the COL+MEM dual therapy regimen to assess the possible utility of a triple therapy regimen against five non-responsive isolates. The COL+MEM+SUL and COL+MEM+TGC regimens effectively restored synergy in (5/5) 100% of the isolates. The results of this study demonstrate the potential utility of COL combinations in the treatment of carbapenem-resistant isolates.
目前被归类为导致患者死亡率增加的六种病原体之一。因此，探索替代治疗策略的研究极具意义。在此，我们对50株耐碳青霉烯类菌株（包括28株耐黏菌素菌株）进行了最低抑菌浓度（MIC）测试和时间杀菌分析（TKA）。在用亚抑菌浓度的黏菌素（COL）存在的情况下对50株菌株测试美罗培南（MEM）或替加环素（TGC）时，MEM和TGC的MIC中位数降低了2倍。在TKA中，COL+MEM组合在45株（90%）菌株中具有协同作用，在24小时时对43株（86%）菌株具有杀菌作用，而COL+TGC组合的TKA在32株（64%）菌株中显示出协同作用，在28株（56%）菌株中显示出杀菌活性。此外，将舒巴坦（SUL）和TGC添加到COL+MEM联合治疗方案中，以评估三联治疗方案对五株无反应菌株的可能效用。COL+MEM+SUL和COL+MEM+TGC方案在100%（5/5）的菌株中有效恢复了协同作用。本研究结果证明了COL联合用药在治疗耐碳青霉烯类菌株方面的潜在效用。
