Eight non-antimicrobial medicaments induce multidrug-resistance in Escherichia coli Ag100 strain

Abstract number: p1243

Tavío  M.M., Aquili  V., Perilli  M., Macià  L., Balagué  C., González-Lama  Z., Amicosante  G.

Objectives: 

Multidrug resistance induced in Escherichia coli by diazepam (a drug used in surgery) was described as equivalent to Mar phenotype resulting from marAB operon activation by salicylate (characterized by OmpF loss and enhanced active efflux). This work studied whether another eight non-antimicrobial medicaments used in surgery could also induce Mar phenotype in the susceptible E. coli Ag100 strain.

Methods: 

The effect of concentrations 1/512, 1/256, 1/128, 1/64, 1/32, 1/16, 1/8, 1/4 MICs of Chlorpromazine, Clonazepam, Dexamethosone, Diclofenac, Haloperidol, Ketoroloac, Methimazol and Propacetamol in Ag100 was evaluated on antibiotic MICs, OmpF expression and norfloxacin intracellular accumulation. Results were compared with those of induction by salicylate. OmpF expression was analysed in SDS-PAGE. Active efflux was evidenced by carbonyl cyanide m-chlorophenylhydrazone (CCCP). Non-induced Ag100 and Ag112 (a marR mutant) were control strains. The inducing concentrations of medicaments were compared with their own levels in plasma in adult humans.

Results: 

Only those concentrations higher than or equal to 1/132 MICs of Clonazepam, Chlorpromazine, Haloperidol, Propacetamol, Ketorolac and Diclofenac, and concentrations higher than or equal to 1/128 MICs of Dexamethasone and Methimazol in the Ag100 strain, induced OmpF loss, increased 2–32 fold cefoxitin, nalidixic acid, norfloxacin, tetracycline and chloramphenicol MICs and decreased norfloxacin uptake in the Ag100 strain. 1/64–1/4 MIC of salicylate in the Ag100 strain led to equivalent results. Norfloxacin accumulation in Ag100 induced by salicylate or any of the eight medicaments was increased 2–4 fold by adding CCCP.

Conclusion: 

i) The tested medicaments like salicylate induced Mar phenotype only with concentration ranges between 1/128–1/4 of their MICs in the Ag100 strain.

ii) Inducing concentrations of Mar phenotype of Clonazepam, Dexamethosone, Diclofenac, Haloperidol, Methimazol and Propacetamol might be found in plasma of patients in the course of treatments with them.