P11 Evaluation of <i>in vitro</i> activity of double β-lactam ‘therapy’ in <i>Escherichia coli</i>: what is the association between ‘synergy’ and <i>in vitro</i> susceptibility?

Abstract Background Emerging antimicrobial resistance is a leading cause of patient morbidity/mortality worldwide. A potential strategy in the treatment resistant infections use combination antibiotics, with hope achieving greater vitro activity, including synergy. It currently assumed that combinations generating greatest synergistic effect will be associated improvement susceptibility (as defined by EUCAST—see Methods). The aim this study was to determine if indeed case. Methods We systematically determined relationship between double β-lactam therapy against 7 Escherichia coli strains variable (4 clinical/3 purchased). This included fully susceptible and low-level isolates (N = 4), extended-spectrum β-lactamase producers (ESBLs) 2) carbapenemase (CPEs) 1). For each 10 MIC individually, subsequently combination, using MTS™ ‘cross’ synergy method (Liofilchem, 2012). fractional inhibitory concentration (FIC) calculated dividing drug alone adding results. See Figure 1. Results were analysed according EUCAST clinical breakpoints correlated potentially improved phenotype. phenotype defined: R/R or R/I I/I monotherapy, improving R/S, I/S S/S (where S susceptible, I intermediate R resistant). Overall, 86/630 (13.7%) showed synergy; 408/630 (64.7%) additive; 136/630 (21.6%) indifferent. No antagonism identified. Synergy most detected ESBL (32% combinations; less frequently CPEs (2% combinations) (4% combinations). 31/630 (5%) mono/combination (according our definitions). Of these 31 combinations, 8 (26%) synergistic, 15 (48%) additive indifferent (by FIC index). 599/630 no susceptibility, 78 (13%) 393 (65.6%) 128 (21.4%) however important note 284/630 (45%), initial monotherapy (i.e. further not possible). more common versus those did not; χ2, P 0.04). Ceftazidime/avibactam + amoxicillin commonly (12/86 Conclusions In tested, effects (78.4%), similar previous work Fosfomycin/β-Lactam (89%), but higher than fosfomycin/non-β-lactam (28%). containing one/two inhibitors. however, rarely leads an criteria highly bug–drug–drug dependent. Further alternative validating methodology required.