Antimicrobial pharmaceuticals are classified as emergent micropollutants of concern, implying that even at low concentrations, long-term exposure to the environment can have significant eco-toxicological effects. There is a lack of a standardized regulatory framework governing the permissible antibiotic content for monitoring environmental water quality standards. Therefore, indiscriminate discharge of antimicrobials at potentially active concentrations into urban wastewater treatment facilities is rampant. Antimicrobials may exert selective pressure on bacteria, leading to resistance development and eventual health consequences. The emergence of clinically important multiple antibiotic-resistant bacteria in untreated hospital effluents and wastewater treatment plants (WWTPs) has been linked to the continuous exposure of bacteria to antimicrobials. The levels of environmental exposure to antibiotics and their correlation to the evolution and spread of resistant bacteria need to be elucidated to help in the formulation of mitigation measures. This review explores frequently detected antimicrobials in wastewater and gives a comprehensive coverage of bacterial resistance mechanisms to different antibiotic classes through the expression of a wide variety of antibiotic resistance genes either inherent and/or exchanged among bacteria or acquired from the reservoir of antibiotic resistance genes (ARGs) in wastewater systems. To complement the removal of antibiotics and ARGs from WWTPs, upscaling the implementation of prospective interventions such as vaccines, phage therapy, and natural compounds as alternatives to widespread antibiotic use provides a multifaceted approach to minimize the spread of antimicrobial resistance.

Antimicrobials in wastewater promote the emergence of antibiotic resistance, facilitated by selective pressure and transfer of resistant genes. Enteric bacteria belonging to Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Citrobacter species (n = 126) from hospital effluents and proximate wastewater treatment plant were assayed for susceptibility to four antimicrobial classes. The β-lactamase encoding genes harbored in plasmids were genotyped and the plasmids were sequenced. A multidrug resistance phenotype was found in 72% (n = 58) of E. coli isolates, 70% (n = 43) of Klebsiella species isolates, and 40% (n = 25) of Enterobacter and Citrobacter species. Moreover, 86% (n = 50) of E. coli, 77% (n = 33) of Klebsiella species, and 25% (n = 4) of Citrobacter species isolates phenotypically expressed extended spectrum β-lactamase. Regarding ESBL genes, blaCTX-M-27 and blaTEM-1 were found in E. coli, while Klebsiella species harbored blaCTX-M-15, blaCTX-M-30, or blaSHV-12. Genes coding for aminoglycoside modifying enzymes, adenylyltransferases (aadA1, aadA5), phosphotransferases (aph(6)-1d, aph(3″)-Ib), acetyltransferases (aac(3)-IIa), (aac(6)-Ib), sulfonamide/trimethoprim resistant dihydropteroate synthase (sul), dihydrofolate reductase (dfrA), and quinolone resistance protein (qnrB1) were also identified. Monitoring wastewater from human sources for acquired resistance in clinically important bacteria may provide a cheaper alternative in regions facing challenges that limit clinical surveillance.

Antimicrobial pharmaceuticals are classified as emergent micropollutants of concern, implying that even at low concentrations long-term exposure to the environment can have significant eco-toxicological effects. There is a lack of a standardized regulatory framework governing the permissible antibiotic content for monitoring environmental water quality standards. Therefore, indiscriminate discharge of antimicrobials at potentially active concentrations into urban wastewater treatment facilities is rampant. Antimicrobials may exert selective pressure on bacteria, leading to resistance development and eventual health consequences. The emergence of clinically Prime Archives in Immunology: 2 nd Edition 3 www.videleaf.com important multiple antibiotic-resistant bacteria (ARB) in untreated hospital effluents and wastewater treatment plants (WWTPs) has been linked to the continuous exposure of bacteria to antimicrobials. The levels of environmental exposure to antibiotics and their correlation to the evolution and spread of resistant bacteria need to be elucidated to help in the formulation of mitigation measures. This review explores frequently detected antimicrobials in wastewater and gives a comprehensive coverage of bacterial resistance mechanisms to different antibiotic classes through the expression of a wide variety of antibiotic resistance genes either inherent and/or exchanged among bacteria or acquired from the reservoir of antibiotic resistance genes (ARGs) in wastewater systems. To complement the removal of antibiotics and ARGs from WWTPs, upscaling the implementation of prospective interventions such as vaccines, phage therapy, and natural compounds as alternatives to widespread antibiotic use provides a multifaceted approach to minimize the spread of antimicrobial resistance.

No abstract

The order Enterobacterales contains a large number of genera which are mainly gut microbiota bearing similar biochemical and genetic characteristics. They are ubiquitous and the members include several that are among important opportunistic human pathogens, which cause infections including urinary tract, bloodstream, respiratory tract, (hospital and health care associated pneumonia), as well as intestinal and intra-abdominal infections. Klebsiella pneumoniae, Escherichia coli, Proteus, Citrobacter, Enterobacter, Hafnia, Morganella, Providencia, and Serratia are some of the genera that cause opportunistic infections. Other members are primary pathogens such as Salmonella, Shigella, and Yersinia. β-lactam antibiotics, which include penicillins, cephalosporins, and carbapenems, are among the most commonly prescribed antibiotics and preferred therapeutic options for infections caused by Enterobacterales. Resistance to these antibiotics is due to inaccessibility of the antibiotics to their target enzymes, modification of target enzymes, and direct deactivation of the antibiotics by β-lactamases. This review explores the common Extended Spectrum β-Lactamase (ESBL) and carbapenemase gene families, which are commonly involved in resistance to the β-lactams in Enterobacterales.