title: Rifaximin combined with polymyxins: A potential regimen for selective decontamination of multidrug-resistant bacteria in the digestive tract?
abstract: Selective decontamination of the digestive tract (SDD) using combinations of oral non-absorbable antibiotics has been proposed as a means of preventing multidrug-resistant (MDR) infections. The minimum inhibitory concentrations (MICs) of rifaximin (RIFAX) were determined against 262 Gram-negative and Gram-positive bacterial isolates by broth microtitre assay. Rifampicin (RIF) was used as a comparator in the analysis. Synergistic interactions between RIFAX and polymyxin B (PMB) were assessed by using the chequerboard method and calculating the fractional inhibitory concentration index (FICI). The antimicrobial activities of both RIFAX and RIF were similar with little variation in the overall MIC distributions for Gram-negative non-fermenters and Gram-positive bacteria. However, against Enterobacteriaceae higher MICs (>16mg/L) were observed for RIFAX than for RIF (50% vs 27%). Amongst the 262 isolates tested, 100 could be considered resistant to RIFAX. Overall, the combination of RIFAX and PMB was more active against all of the isolates tested compared with either drug alone, with reductions of 2-11 doubling dilutions in individual MICs. Potent synergy was observed with the RIFAX+PMB combination using FICI criteria (FICI range 0.02-0.5). The data presented here suggest that combination therapy may be significantly more effective against isolates with RIFAX and/or PMB resistance and could be considered as part of a SDD regimen aimed at reducing enteric carriage of MDR pathogens in colonised and infected patients.
authors.affiliation: Queen Mary University London, Antimicrobial Research Group, Blizard Institute, Barts & The London School of Medicine and Dentistry, London, UK. Electronic address: Jono.betts@btinternet.com.
authors.forename: J W
authors.initials: JW
authors.lastname: Betts
authors.affiliation: Queen Mary University London, Antimicrobial Research Group, Blizard Institute, Barts & The London School of Medicine and Dentistry, London, UK; Division of Infection, Barts Health NHS Trust, London, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Phee
authors.affiliation: Queen Mary University London, Antimicrobial Research Group, Blizard Institute, Barts & The London School of Medicine and Dentistry, London, UK; Division of Infection, Barts Health NHS Trust, London, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Wareham
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003666:Decontamination; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D011113:Polymyxins / Q000627:therapeutic use*; D012294:Rifamycins / Q000627:therapeutic use*; D000078262:Rifaximin
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; D012294:Rifamycins; D000078262:Rifaximin
keywords: Antimicrobial synergy; Gut decontamination; Polymyxins; Rifamycins; Rifaximin