Wastewater effluents released in surface water provides suitable nutrient rich environment for the growth and proliferation of antibiotic resistant bacteria (ARB) and genes (ARG). Consequently, bacterial resistance has highly evolved over the recent years and diversified that each antibiotic class is inhibited by a distinct mechanism. In the present study, the prevalence of Multidrug resistant (MDR), extended spectrum β-lactamases (ESBL) and plasmid mediated Amp-C producing strains was analyzed in 28 surface water samples collected near domestic effluent discharge sites in river Ganga located across 11 different geographical indices of Uttar Pradesh, India. A total of 243 bacterial strains with different phenotypes were isolated. Among 243 isolates, 206 (84.77%) exhibited MDR trait displaying maximum resistance towards β-lactams (P = 78.19%; AMX = 72.84%), glycopeptides (VAN = 32.92%; TEI = 79.42%), cephalosporins (CF = 67.90%; CFX = 38.27%), and lincosamides (CD = 78.18%) followed by sulfonamide, macrolide and tetracycline. ESBL production was confirmed in 126 (51.85%) isolates that harbored the genes: blaTEM (95.24%), blaSHV (22.22%), blaOXA (11.90%) and blaCTX-M group (14.28%). The presence of plasmid mediated AmpC was detected only in 6.17% of isolates. The existence of such pathogenic strains in the open environment generates an urgent need for incorporating stringent measures to reduce the antibiotic consumption and hence its release.

Antibiotic resistance surveillance data is lacking in many parts of the world, limiting effective therapy and management of resistance development. Analysis of urban wastewater, which contains bacteria from thousands of individuals, opens up possibilities to generate informative surveillance data in a standardized and resource-efficient way. Here, we evaluate the relationship between antibiotic resistance prevalence in E. coli from wastewater and clinical samples by studying countries with different resistance situations as assessed by traditional clinical surveillance. Composite, influent wastewater samples were collected over 24 h from treatment plants serving major cities in ten European countries. Using a broth screening method, resistance to six antibiotic classes was analyzed for 2507 E. coli isolates (n = 247–252 per country). Resistance prevalence in wastewater E. coli was compared to that in clinical E. coli reported by the European Antibiotic Resistance Surveillance Network. Resistance prevalence was lower in wastewater than clinical E. coli but followed similar geographic trends. Significant relationships were found for resistance to aminopenicillins (R² = 0.72, p = 0.0019) and fluoroquinolones (R² = 0.62, p = 0.0072), but not for aminoglycosides (R² = 0.13, p = 0.31) and third-generation cephalosporins (R² = 0.00, p = 0.99) where regression analyses were based on considerably fewer resistant isolates. When all four antibiotic classes were taken into account, the relationship was strong (R² = 0.85, p < 0.0001). Carbapenem resistance was rare in both wastewater and clinical isolates. Wastewater monitoring shows promise as method for generating surveillance data reflecting the clinical prevalence of antibiotic resistant bacteria. Such data may become especially valuable in regions where clinical surveillance is currently limited.

Discharge of antimicrobial residues and resistant bacteria in hospital effluents is supposed to have strong impacts on the spread of antibiotic resistant bacteria in the environment. This study aimed to characterize the effluents of the Gabriel Montpied teaching hospital, Clermont-Ferrand, France, by simultaneously measuring the concentration of ciprofloxacin and of biological indicators resistant to this molecule in biofilms formed in the hospital effluent and by comparing these data to ciprofloxacin consumption and resistant bacterial isolates of the hospital. Determination of the measured environmental concentration of ciprofloxacin by spot sampling and polar organic chemical integrative (POCIS) sampling over 2 weeks, and comparison with predicted environmental concentrations produced a hazard quotient >1, indicating a potential ecotoxicological risk. A negative impact was also observed with whole hospital effluent samples using the Tetrahymena pyriformis biological model.During the same period, biofilms were formed within the hospital effluent, and analysis of ciprofloxacin-resistant isolates indicated that Gamma-Proteobacteria were numerous, predominantly Aeromonadaceae (69.56%) and Enterobacteriaceae (22.61%). Among the 115 isolates collected, plasmid-mediated fluoroquinolone-resistant genes were detected, with mostly aac(6′)-lb-cr and qnrS. In addition, 60% of the isolates were resistant to up to six antibiotics, including molecules mostly used in the hospital (aminosides and third-generation cephalosporins).In parallel, 1247 bacteria isolated from hospitalized patients and resistant to at least one of the fluoroquinolones were collected. Only 5 of the 14 species identified in the effluent biofilm were also found in the clinical isolates, but PFGE typing of the Gram-negative isolates found in both compartments showed there was no clonality among the strains.Altogether, these data confirm the role of hospital loads as sources of pollution for wastewater and question the role of environmental biofilms communities as efficient shelters for hospital-released resistance genes.

Freshwater mussels are among the most endangered groups of fauna anywhere in world. The indiscriminate use of antibiotics has led to the emergence of resistant strains. These antibiotic-resistant bacteria play a key role in increasing the risk allied with the use of surface water and in spread of resistance genes. Two endangered freshwater mussel species, Margaritifera margaritifera and Potomida littoralis, were sampled at 4 sampling sites along a 50 km stretch of River Tua. Water samples were taken at same sites. Of the total of 135 isolates, 64.44% (39.26% from water and 25.19% from mussels) were coliform bacteria. Site T1, with the lowest concentration of coliform bacteria, and site T2 were the only ones where M. margaritifera was found. No E. coli isolates were found in this species and the pattern between water and mussels was similar. P. littoralis, which was present at T3/T4 sites, is the one that faces the highest concentration of bacterial toxins, which are found in treated wastewater effluents and around population centers. Sites T3/T4 have the isolates (water and mussels) with the highest resistance pattern, mainly to β-lactams. Water and P. littoralis isolates (T3/T4) showed resistance to penicillins and their combination with clavulanic acid, and to cephalosporins, precisely to a fourth generation of cephalosporin antibiotics. The analysis provides important information on the risk to water systems, as well as the need to investigate possible management measures. It is suggested that future studies on the health status of freshwater bivalves should incorporate measures to indicate bacteriological water quality.

Raman spectroscopy was used to investigate sorption mechanisms of cephapirin (CHP), a veterinary antibiotic, onto quartz (SiO₂) and feldspar (KAlSi₃O₈) at different pH. Sorption occurs by electrostatic attraction, monodentate and bidentate complexation. The zwitterion (CHP⁰) adsorbs to a quartz(+) surface by electrostatic attraction of the carboxylate anion group (-COO-) at low pH, but adsorbs to a quartz(-) surface through electrostatic attraction of the pyridinium cation, and possibly COO- bridge complexes, at higher pH. CHP- bonds to quartz(-) surfaces by bidentate complexation between one oxygen of -COO- and oxygen from carbonyl of an acetoxymethyl group. On a feldspar(+/-) surface, CHP⁰ forms monodentate complexes between CO, and possible -COO- bridges and/or electrostatic attachments to localized edge (hydr)oxy-Al surfaces. CHP- adsorbs to feldspar(-) through monodentate CO complexation. Similar mechanisms may operate for other cephalosporins. Results demonstrate, for the first time, that Raman techniques can be effective for evaluating sorption mechanisms of antibiotics. Raman spectroscopy indicates that cephapirin, a veterinary antibiotic, sorbs to quartz and feldspar by electrostatic attraction, and monodentate and bidentate complexation.

β-lactams are large group of antibiotics widely used to suppress the bacterial growth by inhibiting cell wall synthesis. Bacterial resistance against β-lactam antibiotics is primarily mediated through the production of Temoneria (TEM) β-lactamase (BLs), with almost 474 variants identified in Lactamase Engineering Database (LacED). The present study aims to develop a model to track the evolution of TEM BLs and their interactions with β-lactam and BLs inhibitors through data mining and computational approaches. Further, the model will be used to predict the effective combinations of β-lactam and BLs inhibitors to treat the bacterial infection harbouring emerging variants of β-lactamase. The molecular docking study results demonstrated that most TEM mutants recorded the least binding energy to penicillin and cephalosporin (I/II/III/IV/V generations) class of antibiotics. On the contrary, the same mutants recorded higher binding energy to carbapenem and Monobactam class of antibiotics. Among the BLs inhibitors, tazobactam recorded the least binding energy against most of the TEM mutants, indicating that it can lower the catalytic activity of TEM BLs, thereby potentiating antibiotic action. Similarly, data mining work has assisted us in creating a database of TEM mutants that has comprehensive data on mutations, bacterial diversity, Km, MIC, and IRT types. It has been noted that earlier released antibiotics like amoxicillin and ampicillin had lower Km and higher MIC values, which indicates the prevalence of bacterial resistance. By analysing the differential binding energy (ΔBE) of the selected TEM mutants against β-lactam and BLs inhibitors, the most effective combination of β-lactam (carbapenem and monobactam class of antibiotics) and BLs inhibitors (tazobactam) was identified, to cure bacterial diseases/infections and to prevent similar antibiotic resistance outbreaks. Therefore, our study opens a new avenue in developing strategies to manage antibiotic resistance in bacteria.

Due to their widespread occurrence in the aquatic environment, human and veterinary cephalosporin antibiotics have been studied as water pollutants. In order to characterize environmental risks of this compound class, this review evaluates relevant data about physicochemical properties, occurrence, ecotoxicity and degradation of cephalosporins. Although application of cephalosporins is rather low compared to other antibiotics and their environmental life-time is believed to be short (i.e. days), the available data is insufficient to draw conclusions on their environmental relevance. Few studies concerning the fate of cephalosporins in soil are available, while hydrolysis and photo-degradation are suggested as the main attenuation processes in the aquatic environment. Cephalosporins have been detected in different aqueous matrices in concentrations ranging from 0.30 ng L−1 to 0.03 mg L−1, with sewage and wastewater being the main matrices with positive findings. For wastewater treatment purposes, several technologies have been tested for the abatement of cephalosporins, including photolysis and adsorption. In most cases, the technology employed led to complete or significant removal (>95%) of parental drugs but few authors reported on cephalosporins' metabolites and transformation products. Furthermore, the present ecotoxicological data are insufficient for comprehensive ecological risk quotient calculations. Considering the total of 53 cephalosporins, effective values (EC, LC, NOAEC, NOAEL, etc.) are only available for around 30% of parental drugs and are very scarce for cyanobacteria, which is considered to be the most sensitive group of organisms to antibiotics. Furthermore, it has been demonstrated that cephalosporins' transformation products can be more toxic and more persistent than the parental drugs. Few investigations considering this possibility are available. Consequently, more effort on ecotoxicological data generation and verification of biological inactivation of cephalosporins-related products is needed. Likewise, the lack of natural depletion rates and knowledge gaps on mixture effects for cephalosporins’ degradation and toxicity have to be overcome.

Antibiotics have been used as medical remedies for over 50years and have recently emerged as new pollutants in the environment. This review encompasses the fate of several antibiotics in the environment, including sulfonamides, nitrofurans, terfenadines, cephalosporins and cyclosporins. It investigates the cycle of transfer from humans and animals including their metabolic transformation. The results show that antibiotic metabolites are of considerable persistence and are localized to ground-water and drinking water supplies. Furthermore, the results also show that several phases of the cycle of antibiotics in the environment are not well understood, such as how low concentrations of antibiotic metabolites in the diet affect humans and animals. This review also shows that improved wastewater decontamination processes are remediating factors for these emerging pollutants. The results obtained here may help legislators and authorities in understanding the fate and transformation of antibiotics in the environment.

Escherichia coli, as a global source of antimicrobial resistance, is a serious veterinary and public health concern. The transmission of pathogenic multidrug-resistant (MDR) E. coli within diarrheic calves and its correlation with Musca domestica and milk strains have been investigated. In total, 110, 80, and 26 E. coli strains were obtained from 70 rectal swabs from diarrheic calves, 60 milk samples and 20 M. domestica, respectively. Molecular pathotyping of E. coli revealed the presence of pathogenic E. coli with a higher percentage of shigatoxigenic strains within diarrheic calves and M. domestica at 46.4% and 34.6%, respectively. Phenotypic antimicrobial resistance revealed higher β-lactams resistance except for cefquinome that exhibited low resistance in M.domestica and milk strains at 30.8% and 30%, respectively. The extended-spectrum cephalosporin (ESC) resistant strains were detected within fecal, M. domestica, and milk strains at 69.1%, 73.1%, and 71.3%, respectively. All E. coli strains isolated from M. domestica exhibited MDR, while fecal and milk strains were harboring MDR at 99.1% and 85%, respectively. Molecular detection of resistant genes revealed the predominance of the blaTEM gene, while none of these strains harbored the blaOXA gene. The highest percentages for blaCTXM and blaCMYII genes were detected in M. domestica strains at 53.8% and 61.5%, respectively. Regarding colistin resistance, the mcr-1 gene was detected only in fecal and milk strains at 35.5% and 15%, respectively. A high frequency of phylogroup B2 was detected within fecal and M. domestica strains, while milk strains were mainly assigned to the B1 phylogroup. Pathogenic E. coli strains with the same phenotypic and genotypic antimicrobial resistance and phylogroups were identified for both diarrheic calves and M. domestica, suggesting that the possible role of M. domestica in disseminating pathogenic strains and antimicrobial resistance in dairy farms.

Hospital wastewater contains a variety of human antibiotics and pathogens, which makes the treatment of hospital wastewater essential. However, there is a lack of research on these pollutants at hospital wastewater treatment plants. In this study, the characteristics and removal of antibiotics and antibiotic resistance genes (ARGs) in the independent treatment processes of hospitals of different scales (primary hospital, H1; secondary hospital, H2; and tertiary hospital, H3) were investigated. The occurrence of antibiotics and ARGs in wastewater from three hospitals varied greatly. The first-generation cephalosporin cefradine was detected at a concentration of 2.38 μg/L in untreated wastewater from H1, while the fourth-generation cephalosporin cefepime had the highest concentration, 540.39 μg/L, at H3. Ofloxacin was detected at a frequency of 100% and had removal efficiencies of 44.2%, 51.5%, and 81.6% at H1, H2, and H3, respectively. The highest relative abundances of the β-lactam resistance gene blaGES₋₁ (1.77×10⁻³ copies/16S rRNA), the quinolone resistance gene qnrA (8.81×10⁻⁶ copies/16S rRNA), and the integron intI1 (1.86×10⁻⁴ copies/16S rRNA) were detected in the treated wastewater. The concentrations of several ARGs were increased in the treated wastewater (e.g. blaOXA₋₁, blaOXA₋₁₀, and blaTEM₋₁). Several pathogenic or opportunistic bacteria (e.g. Acinetobacter, Klebsiella, Aeromonas, and Pseudomonas) were observed at high relative abundances in the treated wastewater. These results suggested the co-occurrence of antibiotics, ARGs, and antibiotic-resistant pathogens in hospital wastewater, and these factors may spread into the receiving aquatic environment.