Activity of colistin in combination with tigecycline or rifampicin against multidrug-resistant Stenotrophomonas maltophilia.
The antimicrobial treatment of Stenotrophomonas maltophilia infections is complicated by intrinsic multidrug resistance and a lack of reliable susceptibility data. We assessed the activity of colistin (COL), rifampicin (RIF) and tigecycline (TGC) alone and in combination using a range of in vitro susceptibility testing methodologies and a simple invertebrate model of S. maltophilia infection (Galleria mellonella). Synergy [fractional inhibitory concentration indices (FICIs) ≤0.5] between COL and either RIF or TGC was observed against 92 % and 88 % of 25 S. maltophilia isolates, respectively, despite resistance to one or another of the single agents alone. In time-kill assays, COL combined with either RIF or TGC was superior to single agents, but only the COL/RIF regimen was reliably bactericidal. The in vitro findings correlated with treatment outcomes in G. mellonella, with heightened survival observed for larvae treated with COL/RIF or COL/TGC compared with COL, RIF or TGC alone. COL combined with RIF was the most effective combination overall in both in vitro and in vivo (p < 0.05) assays. Given the difficulty in selecting appropriate therapy for S. maltophilia infections, regimens consisting of COL combined with RIF or TGC could be considered for clinical use.
Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Queen Mary, University of London, Blizard Building, 4 Newark Street, Whitechapel, London, E1 2AT, UK.
J W
JW
Betts
L M
LM
Phee
N
N
Woodford
D W
DW
Wareham
D000818:Animals; D003091:Colistin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination / Q000379:methods; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D007915:Lepidoptera; D050296:Microbial Viability / Q000187:drug effects; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use*; D020615:Stenotrophomonas maltophilia / Q000187:drug effects*; D016019:Survival Analysis; D000078304:Tigecycline; D016896:Treatment Outcome
D000078304:Tigecycline; D008911:Minocycline; D012293:Rifampin; D003091:Colistin