title: Individual or Combined Effects of Meropenem, Imipenem, Sulbactam, Colistin, and Tigecycline on Biofilm-Embedded Acinetobacter baumannii and Biofilm Architecture.
abstract: Acinetobacter baumannii biofilms are difficult to eradicate. We investigated the effects of meropenem (2 mg/liter), imipenem (2 mg/liter), sulbactam (4 mg/liter), colistin (2 mg/liter), and tigecycline (2 mg/liter), alone or in combination, on biofilm-embedded carbapenem-resistant and carbapenem-susceptible A. baumannii (CRAb and CSAb, respectively) cells, as well as on the architecture of the biofilms. A. baumannii ATCC 15151 (Ab15151) and its OXA-82-overproducing transformant, along with two clinical CSAb and two clinical CRAb isolates of differing clonalities, were used. The minimal bactericidal concentrations for biofilm-embedded cells of the six tested isolates were >50-fold those of their planktonic cells. When used individually, meropenem exhibited a higher killing effect than the other four antimicrobials on biofilm-embedded CSAb cells in the colony biofilm assay. For two clinical CRAb isolates, meropenem plus sulbactam or sulbactam plus tigecycline showed >100-fold the bactericidal effect exhibited by these agents used alone after 48 h of treatment. The effect of antimicrobials on the architecture of Ab15151 biofilm emitting green fluorescence was determined by confocal laser scanning microscopy using COMSTAT software. Significant decreases in the maximum biofilm thickness were observed after exposure to meropenem and imipenem. Meropenem plus sulbactam significantly decreased the biomass and mean thickness and increased the roughness coefficient of biofilms, but sulbactam plus tigecycline only decreased the maximum and mean biofilm thickness compared to any of these agents used alone. Meropenem was active against biofilm-embedded CSAb, whereas meropenem plus sulbactam exhibited synergism against biofilm-embedded CRAb and caused significantly more damage to the biofilm architecture than did any of the agents used alone.
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yung-Chih
authors.initials: YC
authors.lastname: Wang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Kuo
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ya-Sung
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Emergency Department, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yi-Tzu
authors.initials: YT
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Chiu
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Ming-Fen
authors.initials: MF
authors.lastname: Chuang
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jung-Chung
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Feng-Yee
authors.initials: FY
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan tecklayyy@gmail.com.
authors.forename: Te-Li
authors.initials: TL
authors.lastname: Chen
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D015780:Carbapenems / Q000494:pharmacology; D003091:Colistin / Q000494:pharmacology*; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D006801:Humans; D015378:Imipenem / Q000494:pharmacology*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests / Q000379:methods; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013407:Sulbactam / Q000494:pharmacology*; D013845:Thienamycins / Q000494:pharmacology*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004338:Drug Combinations; D013845:Thienamycins; D000078304:Tigecycline; D015378:Imipenem; D000077731:Meropenem; D008911:Minocycline; D013407:Sulbactam; D003091:Colistin