Microlevel Study for The Assessment of The Economic Impact of Resistance to Disinfectants Used in The Hospital Environment and Evaluation of New Alternatives

Introduction. The emergence of the antibiotic resistance and multi-resistance to antibiotics drives the acute necessity for the developing of new anti-infective strategies and the permanent changes of the disinfectants used in the hospital environment. The purpose of this study was to investigate by adapted disk diffusion techniques the antimicrobial potential of six (6) newly synthesized chemical compounds (derivatives from phenantroline and cooper complexe combinations with dimethylguanidine), 5 usual disinfectants (Oxigenon, Combi instruments, Virkon, Biguacid, Big spray) and 13 newly synthesized chemical compounds with potential disinfectant activity against 100 enterobacterial strains isolated from different surfaces in the hospital environment grown in planktonic and adherent form, in order to select the most appropriate alternative based on a good cost-effectiveness ratio. Methods: The initial qualitative screening of the antimicrobial activity was performed by disk diffusion and the minimalinhibitory concentration (MIC) of the active chemical compounds was established by Mueller Hinton broth microdillution method using 96-multiwell plates. The microbial strains were tested for their adherence capacity and biofilm developing potential on inert substrata (quantified by a simple method consisting in growing the microbial strains in 60-multiwell plates for 24 hours at 37 C degrees and the biofilms formed on the wall was fixed by methanol and stained by violet crystal and the intensity of color was quantified by measuring the absorbance at 490 nm by an ELISA reader). Results: The 100 enterobacterial strains isolated from surfaces in the hospital environment exhibited high resistance rates to cephuroxime (100%), cephtazidime (100%), ampicillin (98%), cefoxitin (98%), ticarcillin (62%), amoxicillin/ clavulanic acid (53%). 36% of these strains were confirmed for the production of ESBLs and 50% exhibited AMPc inducible beta-lactamases. All tested strains also exhibited high level resistance to tetracyclines (46-53%) and trimetoprim/sulphametoxazole. Concerning their susceptibility to usual disinfectants, the tested strains exhibited high resistance to Oxigenon and to Virkon and were susceptible to Biguacid, Big spray and Combi instruments, the last one being the most effective, active at low concentrations against all tested enterobacterial strains. Concerning the newly synthesized compounds, they exhibited a very low antimicrobial activity. The six derivatives from phenantroline and cooper complexe combinations with dimethylguanidine exhibited antimicrobial activity against the majority of the tested strains with MIC values ranging from 18 to 625 g/ml. The subinhibitory concentrations of the tested chemical compounds slightly inhibited the adherence capacity of the tested strains to the inert substratum. Conclusion. Our results are demonstrating that the increasing rates of resistance to antibiotics in enterobacterial strains are correlated with increasing rates of resistance to the disinfectants used in the hospital environment, as a results of adaptation of an existing resistance mechanism to multiple antimicrobial substrates. The phenantroline derivatives could represent a novel strategy for the antimicrobial treatment, besides the bactericidal effect, the subinhibitory concentrations of newly synthesized chemical compounds impairing the microbial adherence capacity to the inert substratum.