247. Activities of Doripenem and Comparators with Important Gram-negative Pathogens in an In vitro MBEC™ Biofilm Model
Session: Poster Abstract Session: Antimicrobial Susceptibility and Resistance
Friday, October 21, 2011
Room: Poster Hall B1
Background: Biofilms are an important component of many persistent microbial diseases, including foreign body infections.  In these studies, the efficacy of doripenem (DOR) was compared to meropenem (MEM), imipenem (IPM), ceftazidime (CAZ), colistin (COL) and tobramycin (TOB) in killing bacteria within vitro biofilms formed by Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli

Methods: Biofilms were formed on MBEC™ microtiter lid pegs in cation-adjusted Mueller Hinton broth (CAMHB) for 1 day (D) (37°C, 120 rpm ) and treated with antibiotics at clinical free-drug (f) Cmax or ¼ Cmax concentrations for 1 day (1D/1D), or formed in CAMHB for 4 days and treated with antibiotics (¼ fCmax or fCmax) for 3 or 7 days (4D/3D or 4D/7D).  Following antibiotic exposure, viable cells in biofilms were quantitated by determining colony forming units (CFUs) recovered from pegs following release by sonication (30 min).  Antibiotic resistance was determined in parallel by plating on agar with the respective test agent at 8X the MIC.

Results: Against two P. aeruginosa isolates, DOR and MEM (fCmax) decreased CFUs of 1D/1D biofilms by ≥3 log10, and decreased CFUs of 4D/3D or 4D/7D biofilms by ~2 log10 and ~3 log10, respectively.  IPM appeared less effective vs P. aeruginosa, with CFU reductions that were generally ≥0.5 log10 smaller (fCmax) than those of DOR and MEM.  These trends with DOR and MEM vs IPM were similar at ¼ Cmax.  CFU reductions with A. baumannii (N = 1), K. pneumoniae (N = 1) and E. coli (N = 1) biofilms were similar for all carbapenems. Results for CAZ were generally similar to the carbapenems for all isolates.  COL had limited or no effect on P. aeruginosa, K. pneumoniae or E. coli biofilms, but decreased CFUs of A. baumannii by >2 log10 after 7 D treatment (fCmax).  TOB was generally effective, reducing biofilm CFUs by as much as 5.5 log10 against the isolates tested. 

Conclusion: Against P. aeruginosa biofilms, DOR and MEM yielded CFU reductions that were consistently larger than those observed with IPM.  Against the other gram-negative isolates tested, CFU reductions by the three carbapenems were similar.  CAZ and TOB were effective in this model, while COL generally had little impact on CFUs with species other than A. baumannii.


Subject Category: A. Antimicrobial agents and Resistance

Darren Abbanat, PhD, Wenchi Shang, MS, Karen Amsler, MS and A. Simon Lynch, PhD, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Raritan, NJ

Disclosures:

D. Abbanat, Johnson & Johnson: Employee, Salary

W. Shang, Johnson & Johnson: Employee, Salary

K. Amsler, Johnson & Johnson: Employee, Salary

A. S. Lynch, Johnson & Johnson: Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.