New options of antibiotic combination therapy for multidrug-resistant Pseudomonas aeruginosa

Several antibiotic combinations have demonstrated increased activity against multidrug-resistant Pseudomonas aeruginosa (MDRP) in vitro compared with a single antibiotic. The aim of this study was to investigate the activity against MDRP of some aminoglycosides in combination with monobactam, piperacillin (PIPC), and carbapenem. Clinical isolates of MDRP were collected between November 2010 and October 2012 from patients in Tokyo Medical University Hospital, Tokyo (1,015 beds). Our new method was designed to evaluate three concentrations around the breakpoint of each drug using the Checkerboard method. The aminoglycosides tested were amikacin (AMK), tobramycin (TOB), and arbekacin (ABK). Ciprofloxacin, PIPC, and biapenem (BIPM), which have been reported to demonstrate combination effects, were also tested. Sixty-six MDRP strains were identified from the 2,417 P. aeruginosa strains. Of the 66, 27 tested positive for metallo-β-lactamase (MBL). Aztreonam (AZT) with AMK or ABK was the most effective against MDRP. PIPC with AMK or ABK were somewhat effective. AZT with AMK or ABK were more effective against MBL-positive strains than MBL-negative strains. However, PIPC with AMK or ABK were more effective against MBL-negative strains than MBL-positive strains. Combination activities showed differences between MBL-positive and MBL-negative strains.