Combination antimicrobial susceptibility testing of multidrug-resistant Stenotrophomonas maltophilia from cystic fibrosis patients.

Stenotrophomonas maltophilia is increasingly being isolated from the respiratory tract of individuals with cystic fibrosis, and, because of its multidrug-resistant nature, the selection of suitable treatment regimens can be problematical. Etest methodology was used to facilitate MIC and antimicrobial combination testing on 80 isolates of S. maltophilia cultured from the respiratory tract of Scottish individuals with cystic fibrosis between 2001 and 2010. The overall rate of susceptibility for the 1,410 MIC tests was 23.1%, and resistance was 68.9%. The most active antimicrobials were minocycline, co-trimoxazole, and doxycycline, with 92.4%, 87.3%, and 58.8% of isolates being susceptible, respectively. Of the 517 combinations, 13.2% were synergistic, with the most synergistic being ticarcillin/clavulanate plus aztreonam (91.7% synergistic), ticarcillin/clavulanate plus colistin (40%), and ticarcillin/clavulanate plus levofloxacin (19.4%). Colistin plus tobramycin was the only antagonistic combination (0.2%). By the median susceptible breakpoint index, the most active combinations were minocycline plus co-trimoxazole (median index, 20), minocycline plus piperacillin-tazobactam (median, 20), and co-trimoxazole plus ceftazidime (median, 16.5). The increasing problem of multidrug resistance in organisms recovered from the respiratory tracts of individuals with cystic fibrosis is not going to go away. Current susceptibility testing methods do not address the slow-growing organisms associated with chronic infection, and interpretive standards are based on achievable blood levels of antimicrobials. Addressing these issues specifically for organisms recovered from the respiratory tracts of individuals with cystic fibrosis should lead to better therapeutic outcomes and improved wellbeing of individuals with cystic fibrosis.

Combination testing of multidrug-resistant cystic fibrosis isolates of Pseudomonas aeruginosa: use of a new parameter, the susceptible breakpoint index.

OBJECTIVES: The microbiology laboratory at Aberdeen Royal Infirmary operates an extended susceptibility testing service for multidrug-resistant Gram-negative non-fermenting isolates from the sputum of Scottish cystic fibrosis patients. The service aims to provide clinicians with useful treatment options and developed the use of a novel parameter-the susceptible breakpoint index (SBPI), which allows easy ranking of the antimicrobial combinations in order of their possible in vivo effectiveness. METHODS: Three hundred and fifteen isolates of Pseudomonas aeruginosa were submitted for testing. MICs of 14 antimicrobials were determined using the Etest and the results categorized using CLSI guidelines. Usually, six antimicrobial pairs were tested in combination also using the Etest. The results were assessed using the fractional inhibitory concentration index (FICI) and also by a novel parameter, the SBPI. RESULTS: Some 4173 MICs and 1663 combination pairs were performed. The most active individual antimicrobials were colistin, tobramycin and amikacin, with 84%, 69% and 32% of isolates susceptible, respectively. Twenty-eight of 44 antimicrobial combinations were tested >10 times. Of the combinations, 3.6% were synergistic (FICI < or = 0.5) and 0.1% were antagonistic (FICI > 4.0). Amikacin + ceftazidime (17%), ciprofloxacin + ceftazidime (12.9%) and ciprofloxacin + piperacillin/tazobactam (12%) were the most synergistic combinations. By median SBPI, the most effective combinations in vitro were colistin + ticarcillin/clavulanate, colistin + piperacillin/tazobactam and colistin + meropenem. CONCLUSIONS: The Etest is a useful tool for determining MICs and testing antimicrobial combinations. The SBPI is more discriminatory than the FICI, allowing easy ranking of the combinations, and is likely to have clinical relevance.