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.

Highlights

  • Gram-negative bacteria (GNB) are a significant public health concern due to their nosocomial transmission and high levels of antibiotic resistance, where patients often require admittance to intensive care units (ICU), leading to high morbidity and mortality [1]

  • health care-associated infections (HAIs) associated with antimicrobial-resistant (AMR) and multi-drug-resistant (MDR) bacterial species result in increased morbidity, mortality, and socio-economic impacts on patients

  • E. coli, K. pneumoniae, C. freundii, P. pulmonis, Pseudomonas spp. and Acinetobacter spp. were all identified as ESBL producers, where resistance to penicillins, one or more third-generation cephalosporin and aztreonam was evident

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Summary

Introduction

Gram-negative bacteria (GNB) are a significant public health concern due to their nosocomial transmission and high levels of antibiotic resistance, where patients often require admittance to intensive care units (ICU), leading to high morbidity and mortality [1]. Two major groups, the Enterobacteriaceae and non-fermenters (opportunistic species) are responsible for the majority of HAIs; other clinically important GNBs including Neisseria, Helicobacter pylori, and Psychrobacter must be considered [1]. The three main sites of HAIs are the urinary tract, bloodstream (septicaemia) and respiratory system (pneumonia), with ventilator-associated pneumonia frequently requiring admission to ICU [3]. HAIs associated with antimicrobial-resistant (AMR) and multi-drug-resistant (MDR) bacterial species result in increased morbidity, mortality, and socio-economic impacts on patients

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