Bozkurt-Guzel Cagla, Savage Paul B, Akcali Alper, Ozbek-Celik Berna
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit, 34116 Istanbul, Turkey.
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
Biomed Res Int. 2014;2014:710273. doi: 10.1155/2014/710273. Epub 2014 Mar 24.
Carbapenem-resistant Acinetobacter baumannii is an important cause of nosocomial infections, particularly in patients in the intensive care units. As chronic infections are difficult to treat, attempts have been made to discover new antimicrobials. Ceragenins, designed to mimic the activities of antimicrobial peptides, are a new class of antimicrobial agents. In this study, the in vitro activities of CSA-13 either alone or in combination with colistin (sulphate), tobramycin, and ciprofloxacin were investigated using 60 carbapenem-resistant A. baumannii strains isolated from bacteremia patients blood specimens. MICs and MBCs were determined by microbroth dilution technique. Combinations were assessed by using checkerboard technique. The MIC50 values (mg/L) of CSA-13, colistin, tobramycin, and ciprofloxacin were 2, 1, 1.25, and 80, respectively. The MIC90 (mg/L) of CSA-13 and colistin were 8 and 4. The MBCs were equal to or twice greater than those of the MICs. Synergistic interactions were mostly seen with CSA-13-colistin (55%), whereas the least synergistic interactions were observed in the CSA-13-tobramycin (35%) combination. No antagonism was observed. CSA-13 appears to be a good candidate for further investigations in the treatment of A. baumannii infections. However, future studies should be performed to correlate the safety, efficacy, and pharmacokinetic parameters of this molecule.
耐碳青霉烯类鲍曼不动杆菌是医院感染的重要原因,尤其是在重症监护病房的患者中。由于慢性感染难以治疗,人们一直在尝试发现新的抗菌药物。设计用于模拟抗菌肽活性的杀菌肽是一类新型抗菌剂。在本研究中,使用从菌血症患者血液标本中分离出的60株耐碳青霉烯类鲍曼不动杆菌菌株,研究了CSA - 13单独使用或与黏菌素(硫酸盐)、妥布霉素和环丙沙星联合使用时的体外活性。通过微量肉汤稀释技术测定最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。采用棋盘法评估联合用药情况。CSA - 13、黏菌素、妥布霉素和环丙沙星的MIC50值(mg/L)分别为2、1、1.25和80。CSA - 13和黏菌素的MIC90(mg/L)分别为8和4。MBC等于或比MIC大两倍。协同相互作用大多见于CSA - 13 - 黏菌素组合(55%),而在CSA - 13 - 妥布霉素组合(35%)中观察到的协同相互作用最少。未观察到拮抗作用。CSA - 13似乎是进一步研究治疗鲍曼不动杆菌感染的良好候选药物。然而,未来应进行研究以关联该分子的安全性、有效性和药代动力学参数。