title: Potential synergy activity of the novel ceragenin, CSA-13, against carbapenem-resistant Acinetobacter baumannii strains isolated from bacteremia patients.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit, 34116 Istanbul, Turkey.
authors.forename: Cagla
authors.initials: C
authors.lastname: Bozkurt-Guzel
authors.affiliation: Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, Canakkale Onsekiz Mart University, 17100 Canakkale, Turkey.
authors.forename: Alper
authors.initials: A
authors.lastname: Akcali
authors.affiliation: Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit, 34116 Istanbul, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Ozbek-Celik
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000472:pathogenicity; D015780:Carbapenems / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage; D003428:Cross Infection / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015780:Carbapenems; D013256:Steroids; C521528:ceragenin CSA-13; D002939:Ciprofloxacin