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

Abstract

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.

Fig 1

Annual percentages of S, I, and R S. maltophilia isolates by MIC. No S. maltophilia isolates were submitted for testing during 2007.

Fig 2

Co-trimoxazole MIC distribution for S. maltophilia.

Fig 3

Interquartile ranges (IQRs) of S. maltophilia susceptibility breakpoint indices for combinations tested ≥10 times. MIN, minocycline; SXT, co-trimoxazole; TZP, piperacillin-tazobactam; CAZ, ceftazidime; LVX, levofloxacin; CHL, chloramphenicol; TIM, ticarcillin/clavulanate; COL, colistin; ATM, aztreonam.

Fig 4

Percent synergistic combinations and median susceptible breakpoint indices for drugs against S. maltophilia.