Effective Antimicrobial Solutions for Eradicating Multi-Resistant and β-Lactamase-Producing Nosocomial Gram-Negative Pathogens

Abstract

Antimicrobial resistance (AMR) remains one of the greatest public health-perturbing crises of the 21st century, where species have evolved a myriad of defence strategies to resist conventional therapy. The production of extended-spectrum β-lactamase (ESBL), AmpC and carbapenemases in Gram-negative bacteria (GNB) is one such mechanism that currently poses a significant threat to the continuity of first-line and last-line β-lactam agents, where multi-drug-resistant GNB currently warrant a pandemic on their own merit. The World Health Organisation (WHO) has long recognised the need for an improved and coordinated global effort to contain these pathogens, where two factors in particular, international travel and exposure to antimicrobials, play an important role in the emergence and dissemination of antibiotic-resistant genes. Studies described herein assess the resistance patterns of isolated nosocomial pathogens, where levels of resistance were detected using recognised in vitro methods. Additionally, studies conducted extensively investigated alternative biocide (namely peracetic acid, triameen and benzalkonium chloride) and therapeutic options (specifically 1,10-phenanthroline-5,6-dione), where the levels of induced endotoxin from E. coli were also studied for the latter. Antibiotic susceptibility testing revealed there was a significant association between multi-drug resistance and ESBL production, where the WHO critical-priority pathogens, namely E. coli, K. pneumoniae, A. baumannii and P. aeruginosa, exhibited among the greatest levels of multi-drug resistance. Novel compound 1,10-phenanthroline-5,6-dione (phendione) shows promising antimicrobial activity, with MICs determined for all bacterial species, where levels of induced endotoxin varied depending on the concentration used. Tested biocide agents show potential to act as intermediate-level disinfectants in hospital settings, where all tested clinical isolates were susceptible to treatment.

Keywords: 1,10-phenanthroline-5,6-dione; intermediate-level disinfectants; multi-drug resistant; nosocomial pathogens.

Figure 1

Effects of ceftazidime and phendione at 2× and 10× MIC on (a) growth and (b) release of endotoxin from ESBL E. coli, where drugs were added at time 0. Control cultures contained sterile media only.

Figure 2

Log₁₀ reduction in viable cfu/ml of test species as determined by BSEN 1276 following 5 min exposure to 0.01%, 0.1% and 1% (a) peracetic acid (b) triameen and (c) BAC in high interfering solution 10 g/L BSA and yeast extract (+/− Standard deviation). A, B, C, D, E, F and G denote a significant difference between the strains, where groups displaying the same letter are statistically similar whilst those denoted by a different letter are statistically different.

Figure 2

Log₁₀ reduction in viable cfu/ml of test species as determined by BSEN 1276 following 5 min exposure to 0.01%, 0.1% and 1% (a) peracetic acid (b) triameen and (c) BAC in high interfering solution 10 g/L BSA and yeast extract (+/− Standard deviation). A, B, C, D, E, F and G denote a significant difference between the strains, where groups displaying the same letter are statistically similar whilst those denoted by a different letter are statistically different.