Cationic compounds with activity against multidrug-resistant bacteria: interest of a new compound compared with two older antiseptics, hexamidine and chlorhexidine

Abstract

Use of antiseptics and disinfectants is essential in infection control practices in hospital and other healthcare settings. In this study, the in vitro activity of a new promising compound, para-guanidinoethylcalix[4]arene (Cx1), has been evaluated in comparison with hexamidine (HX) and chlorhexidine (CHX), two older cationic antiseptics. The MICs for 69 clinical isolates comprising methicillin-resistant Staphylococcus aureus, methicillin-sensitive S. aureus, coagulase-negative staphylococci (CoNS) (with or without mecA), vancomycin-resistant enterococci, Enterobacteriaceae producing various beta-lactamases and non-fermenting bacilli (Pseudomonas aeruginosa, Acinetobacter baumanii, Stenotrophomonas maltophilia) were determined. Cx1 showed similar activity against S. aureus, CoNS and Enterococcus spp., irrespective of the presence of mecA or van genes, or associated resistance genes, with very good activity against CoNS (MIC <1 mg/L). Variable activities were observed against Enterobacteriaceae; the MICs determined seemed to be dependent both on the genus (MICs of 2, 8 and 64 mg/L for Escherichia coli, Klebsiella pneumoniae and Yersinia enterocolitica, respectively) and on the resistance phenotype production of [Extended Spectrum beta-Lactase (ESBLs) or other beta-lactamases; overproduction of AmpC]. Poor activity was found against non-fermenting bacilli, irrespective of the resistance phenotype. CHX appeared to be the most active compound against all strains, with broad-spectrum and conserved activity against multidrug-resistant strains. HX showed a lower activity, essentially against Gram-positive strains. Consequently, the differences observed with respect to Cx1 suggest that they are certainly not the consequence of antibiotic resistance phenotypes, but rather the result of membrane composition modifications (e.g. of lipopolysaccharide), or of the presence of (activated) efflux-pumps. These results raise the possibility that Cx1 may be a potent new antibacterial agent of somewhat lower activity but significantly lower toxicity than CHX.

Stenotrophomonas maltophilia: an Emerging Global Opportunistic Pathogen

“…Cationic compounds act by binding to the negatively charged surfaces of the bacterial cell wall and membranes. The results of that study showed that two strains of MDR S. maltophilia demonstrated susceptibility to CHX (MIC Ͻ 1 to 32 mg/ liter), some susceptibility to HX (MIC ϭ 32 to 256 mg/liter), and resistance to CxI (MIC ϭ 256 mg/liter) (132).…”

“…The antibacterial activities of new cationic compounds (e.g., hexamidine diisethionate [HX], chlorhexidine digluconate [CHX], and para-guanidinoethylcalix [4]arene [CxI]) have been assessed (132). Cationic compounds act by binding to the negatively charged surfaces of the bacterial cell wall and membranes.…”

Non-leaching antimicrobial biodegradable PBAT films through a facile and novel approach

“…More importantly, it has been noted that guanidine-based polymers can overcome bacterial resistance [27,28]. Polyhexamethylene guanidine hydrochloride (PHGH) has been known to exhibit antimicrobial property for years.…”

Polymorphic Variation in Susceptibility and Metabolism of Triclosan-Resistant Mutants of Escherichia coli and Klebsiella pneumoniae Clinical Strains Obtained after Exposure to Biocides and Antibiotics

“…However, only a few studies with limited data have been performed with either E. coli or K. pneumoniae, and less is known in the case of clinical isolates (19,(22)(23)(24)(25)(26)(27). The aim of this study was to determine the effect of preexposure to the more commonly used biocides in hospitals and domestic settings (TRI, CHX, benzalkonium chloride [BKC], and sodium hypochlorite [SHC]), or to antibiotics of wide consumption (ampicillin [AMP] and ciprofloxacin [CIP]) on the selection of biocide-resistant variants and to explore the associated changes in metabolism and bacterial growth rate.…”