Antimicrobial activity of polyhexamethylene guanidine hydrochloride derivatives against multiresistant microbial strains

Abstract

The resistance of bacteria to the disinfectants used is one of the pressing health problems requiring to be addressed in order to prevent formation and spread of resistant strains. Bacterial resistance leads to a sharply decreased effectiveness of anti-epidemic measures and contributes to maintaining a high morbidity level. In the context of the growing HAI incidence rate and related polyetiology, the large adaptive potential of opportunistic microorganisms, and the growing resistance to antimicrobial drugs, it is necessary to search for new or modify the corresponding substances of plant or synthetic origin exerting antimicrobial action used as antimicrobial agents. One of the representatives of this class of compounds are polyguanidines, characterized by high antimicrobial activity and low toxicity. Due to the high reactivity of the guanidine group, as well as ease of synthesis and relative availability of raw materials, N-phenyl- and N-octyl-substituted derivatives of polyhexamethylene guanidine hydrochloride were able to be obtained by melt polycondensation, their molecular weight characteristics were measured as well as the structure investigated by IR spectroscopy. An earlier study on the acute toxicity for polyhexamethylene guanidine hydrochloride derivatives after a single oral drug intake in laboratory animals (white mice) allowed to establish the following LD50 values: polyhexamethylene guanidine hydrochloride — 850.0±112.02 mg/ kg; N-phenyl-substituted polyhexamethylene guanidine hydrochloride — 1399.9±120.51 mg/kg; N-octyl-substituted polyhexamethylene guanidine hydrochloride — 1150.0±137.40 mg/kg. Such values, according to the tabulation of hazard classes, allow the synthesized derivatives to be classified into the fourth hazard class and open up an opportunity for using disinfectants as active components. The evaluation of the antibacterial sample properties was carried out by using serial dilutions in agar on hospital bacterial and fungal strains isolated from the biomaterial of patients at the Republican Clinical Hospital named after V.I. Semashko, according to the clinical guidelines “Laboratory diagnosis of community-acquired pneumonia” 2014, “Bacteriological analysis of urine” 2014, “Determination of the susceptibility of microorganisms to antimicrobial drugs” 2015. It was found that N-substituted derivatives exhibit a greater antimicrobial effect compared with unsubstituted polymer. The most sensitive to all the drugs presented was the yeast-like fungi Candida albicans (No. 2495) (complete suppression), as well as methicillin-resistant S. aureus (no. 2544), and the substituted samples almost completely suppress its growth. The most resistant strains are P. aeruginosa (No. 2281), A. baumannii (No. 2806) and K. pneumoniae (No. 3023), the percentage of reduction of these bacteria under the action of substituted samples does not exceed 41%, which is accounted for by their multi-resistance.

Keywords

• polyguanidines
• polycondensation
• disinfectants
• antimicrobial action
• resistant strains