Classes Of Antibiotics Research Articles

Occurrence, Source Apportionment, and Risk Assessment of Antibiotics in Mangrove Sediments from the Lianzhou Bay, China.

In recent years, the widespread application of antibiotics has raised global concerns, posing a severe threat to ecological health. In this study, the occurrence, source, and ecological risks of 39 antibiotics belonging to 5 classes in mangrove sediments from Lianzhou Bay, China, were assessed. The total concentrations of the antibiotics (∑39 antibiotics) ranged from 65.45 to 202.24 ng/g dry weight (dw), with an average of 142.73 ± 36.76 ng/g dw. The concentrations of these five classes of antibiotics were as follows: Sulfonamides (SAs) > Tetracyclines (TCs) > Fluoroquinolones (QUs) > Penicillin (PCs) > Macrolides (MLs). The spatial distribution of antibiotics varied as high tidal zone > middle tidal zone > low tidal zone. The total organic carbon (TOC), pH, nitrate (NO3--N), and nitrite (NO2--N) of the sediment significantly influenced the distribution of antibiotics (p < 0.05). A source analysis identified untreated sewage from aquaculture as the primary source of antibiotics in the local mangrove. A risk assessment revealed that ciprofloxacin, norfloxacin, ofloxacin of QUs, and tetracycline of TCs exhibited medium risks to algae in certain sampling sites, while other antibiotics exhibited low or no risks to all organisms. Nevertheless, the total risk of all the detected antibiotics to algae was medium in 95% of the sites. The overall ecological risk level of antibiotics in the middle tidal zone was slightly lower than in the high tidal zone and the lowest in the low tidal zone. In summary, the experimental results provided insights into the fate and transport behaviors of antibiotics in mangrove sediments from Lianzhou Bay.

Regulation of trehalose metabolism mediated by validamycin on chitin synthesis in Spodoptera frugiperda

AbstractTrehalase (TRE) is a key enzyme for degrading trehalose, which plays a vital role in the growth and development of insects. Although validamycin, a compound belonging to a class of efficient antibiotics and fungicides, can control pests by suppressing TRE activities, it remains unknown whether it acts on both trehalose and chitin metabolism in Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), a major pest of maize (Zea mays L., Poaceae). This study investigated the changes in trehalose metabolism after validamycin treatment in S. frugiperda and its effects on the downstream chitin synthesis pathway. Compared with the control, S. frugiperda exhibited varying degrees of mortality after treatment with four concentrations of validamycin, showing a dose‐dependent increase in mortality rate. The mortality rates 24 and 48 h after treatment with 0.07 mg μL−1 validamycin were 35.6% and 42.2%, respectively, indicating the effective lethal concentration. Treatment with 0.07 mg μL−1 validamycin led to developmental delay, abnormal molting, and death in S. frugiperda, but it exerted no lasting effects on the survival rate, pupal weight, and phenotype during its subsequent developmental stages. At 24 h after validamycin treatment, TRE1 and TRE2 activities and glucose content decreased significantly, whereas the trehalose content increased significantly. Treatment with validamycin significantly upregulated TRE1 and TRE2 expression after 24 and 48 h and downregulated the mRNA expression of chitin synthase A and B genes. However, after 72 h, chitin content was not significantly affected. Hence, validamycin can destroy the dynamic transformation balance of trehalose and glucose by inhibiting the activities of the two TREs, and further affect the expression of downstream chitin synthase genes. These findings provide a theoretical basis for using TRE inhibitors to control S. frugiperda.

Full green assay of parenteral dosage forms of polymyxins utilizing xanthene dye: application to content uniformity testing

Due to the lack of other treatment options, a rebirth of polymyxins is urgently required. Colistin (also called polymyxin E) and polymyxin B are the only two examples of this antibiotic class that were effectively employed in such critical situations. In the present work, both of the two studied medications were quantified via a simple, green, and non-extracting spectrophotometric approach based on the formation of ion-pair complexes with Erythrosine B. Without using any organic solvents, the pink color of the created complexes was detected at wavelength = 558 nm. To achieve the highest intensity of absorbance, optimum conditions were established by the screening of many experimental factors such as pH, buffer volume, the volume of Erythrosine B, and the time consumed to undergo the reaction. For Colistin and Polymyxin B respectively, Beer-Lambert’s law was observed at the concentration ranges of 1–6, 1–9 µg mL− 1. The technique was approved and validated following ICH recommendations. Lastly, the suggested approach has been successfully implemented to quantify the cited medications colorimetrically, for the first time, in their parenteral dosage forms with excellent recoveries. Also, Content uniformity testing was implemented.

Contrasting methods to operationalize antibiotic exposure in clinical research: a real-world application on healthcare-associated Clostridioides difficile infection.

The goal of this article is to summarize common methods of antibiotic operationalization used in clinical research and demonstrate methods for exposure variable selection. We demonstrate three methods for modeling exposure, using data from a case-control study on Clostridioides difficile infection in hospitalized patients: 1) factor analysis, 2) logistic regression models, and 3) Least Absolute Shrinkage and Selection Operator (LASSO) regression. The factor analysis identified 8 variables contributing the most variation in the dataset: any antibiotic exposure; number of antibiotic classes; number of antibiotic courses; dose; and specific classes monobactam, 𝛽-lactam 𝛽-lactamase inhibitors, rifamycin, and cephalosporin. The logistic regression models resulting in the best model fit used predictors representing any antibiotic exposure and the proportion of a patient's hospitalization on antibiotics. The LASSO model selected 22 variables for inclusion in the predictive model, of which 10 were antibiotic exposure variables, including: any antibiotic exposure; classes 𝛽-lactam 𝛽-lactamase inhibitors, carbapenem, cephalosporin, fluoroquinolone, monobactam, rifamycin, sulfonamides, and miscellaneous; and proportion of hospitalization on antibiotics. Investigators studying antibiotic use should consider multiple characteristics of exposure informed by their research question and the theory on how antibiotics may impact the distribution of the outcome in their target population.

Multidrug Resistance of Escherichia coli in cats and the Level of Understanding of Cat Owners on Antimicrobial Resistance

Multidrug resistance poses a global health risk to humans, animals, and the environment.The impact of this issue is so great that it has gained international attention, ranging from the rising morbidity to the mortality rate of infectious diseases in humans and animals. Because of their peculiar eliminative behavior habit of burying their waste in the ground, cats may contribute to the spread of microorganisms resistant to antibiotics. The purpose of this study was to map the prevalence of antibiotic-resistant E. coli bacteria in cats and to determine the degree of cat owners' comprehension as a risk factor for the development of antimicrobial resistance. In this investigation, 353 cat anal swab samples were found to contain E. coli. The study was carried out in 2023 between March and May. The Mueller Hilton Agar medium was used to test for multidrug resistance to beta-lactam, aminoglycoside, and tetracycline class antibiotics using the diffusion method. Using a questionnaire, the degree of knowledge on antibiotic resistance among 373 cat owners was assessed. Respondent variables include identification, knowledge, demeanor, attitude, and cat care. After that, data were descriptively examined. E. coli was detected in 87.82% (310/353) of the cat anal swab samples (n = 353) in this investigation. Additionally, multidrug resistance was shown in 7.4% (23/310) of the isolates; this frequency was higher in stray cats (8.75%) than in domestic cats (6%). For ampicillin, tetracycline, and streptomycin, the rates of antimicrobial resistance were 28.39% (88/310), 15.81% (49/310), and 14.84% (46/310), in that order. According to an analysis of the questionnaires used to gauge cat owners' comprehension of antimicrobial-resistant events, 64.3% (240/373) of the owners did not know what antimicrobial resistance was. In addition, 72.7% (271/373) of the cat owners were aware of the medications their cats were given, and 66% (246/373) of them knew how to give antibiotics to their pets. These findings are consistent with the findings of another survey that showed 70% (261/373) of cat owners took their sick cats to the veterinarian. Compared to domestic cats, stray cats in this study had a higher rate of multidrug resistance.This is consistent with the relatively positive findings of a survey on cat owners' comprehension of cat maintenance and care; yet, the poor awareness of antimicrobial resistance among cat owners may contribute to its emergence. To raise awareness regarding antimicrobial resistance in cats, cat owners need to get education.

Assessment of the presence of multidrug-resistant Escherichiacoli, Salmonella and Staphylococcus in chicken meat, eggs and faeces in Mymensingh division of Bangladesh

The emergence of bacteria that is resistant to several drugs of clinical importance poses a threat to successful treatment, a phenomenon known as multidrug resistance that affects diverse classes of antibiotics. The purpose of this study was to evaluate the prevalence of multidrug-resistant Escherichiacoli, Salmonella spp. and Staphylococcusaureus in chicken egg, meat and faeces from four districts of Bangladesh. A total of 120 chicken samples were collected from different poultry farms. Conventional culture and molecular detection methods were used for identification of bacterial isolates from the collected samples followed by antibiotic susceptibility test through the disc diffusion method, finally antibiotic resistant genes were detected by PCR. E. coli, Salmonella spp. and Staphylococcusaureus were detected in meat, egg and faecal samples. Antimicrobial susceptibility results revealed isolates from faeces were 100 % resistant to amoxicillin, while all S.aureus and Salmonella sp. from faeces were resistant to doxycycline, tetracycline and erythromycin. Salmonella spp. isolates from eggs indicated 100 % resistance to erythromycin, amoxycillin, while E.coli were 100 % resistant to erythromycin. E.coli and S.aureus from meat were 100 % resistant to amoxicillin and erythromycin. However, Salmonella spp. from eggs were 100 % susceptible to doxycycline, gentamicin, levofloxacin and tetracycline. The mecA and aac(3)-IV genes were only found in S.aureus and E.coli, respectively. The Sul1,tetB, and aadA1 were highest in Salmonella spp. and S.aureus, while the sul1,tetA and blaSHV were higher in E.coli. Isolates from all samples were multidrug resistant. These findings indicate a high risk of transmission of resistance genes from microbial contamination to food of animal origin. The study emphasizes the need for effective biosecurity measures, responsible antibiotic use, and strict regulations in poultry production to prevent the spread of antibiotic resistance.

Tackling Microbial Resistance and Emerging Pathogens with Next-Generation Antibiotics

In the 19th century, the discovery of penicillin revolutionized medicine, saving millions from infectious diseases. People believed that they had won the war against infections. However, the misuse and abuse of antimicrobial agents are accompanied by major ramifications like antimicrobial resistance, creating drug-resistant superbugs. This issue is concerning worldwide, as dwindling effective antibiotics lead to rising healthcare costs, re-hospitalization, and disease severity. Consequently, multiple initiatives have been undertaken to address these phenomena, including the development of antimicrobials with novel modes of action. Without novel discoveries of newer antimicrobial agents, we may face the risk of entering a post-antibiotic era where uncomplicated infections become untreatable. Ultimately, the morbidity and mortality rate would rise higher than in the pre-antibiotic era. This study highlights the recent developments in antimicrobials over the past five years and explores the strategies employed by the new generation of drugs to act against resistance. For example, we discuss the treatment of Carbapenem-resistant Enterobacteriaceae, such as Klebsiella pneumoniae Carbapenamase-producing Gram-negative bacteria, by using meropenem-vaborbactam. Plazomicin, lacking a hydroxyl group, effectively combats metallo-beta-lactamase, which meropenem-vaborbactam is unable to address. It is also preferred over tobramycin and gentamicin due to its hydroxyethyl group. Furthermore, we explore the conjugation of nanoparticles with antibiotics, which demonstrated synergistic effects and positive outcomes on different bacterial resistance. Mechanisms include increased drug adhesion to bacterial cell walls, generating oxidative stress, and causing mistranslation by detaching ribosomes from tRNA. Additionally, the IspH inhibitors like 4’-flurouridine targeting the MEP pathway which is also included in the discussion. This report thoroughly examines newer generations and classes of antibiotics, highlighting the improvements made by scientists to combat bacterial resistance effectively.

Antimicrobial Susceptibility of Methicillin-resistant Staphylococcus Aureus and Methicillin-sensitive Staphylococcus Aureus in a Pediatric Tertiary Care Hospital in Southern India

Objectives: To determine the current antimicrobial sensitivity profile of MRSA and compare it with the antimicrobial sensitivity of MSSA (Methicillin Sensitive Staphylococcus aureus) Material and Methods: Antimicrobial resistance in Staphylococcus aureus is a global public health concern. Methicillin-resistant Staphylococcus aureus (MRSA) is often resistant to the many classes of antibiotics compared to the methicillin-sensitive Staphylococcus aureus (MSSA). Five hundred and fifty S. aureus isolates obtained from clinical samples of pediatric patients were studied to determine the difference in the antimicrobial susceptibility between MRSA and MSSA. Results: Out of 550 S. aureus isolates, 59.3% were MSSA, and 40.7% were MRSA. The antimicrobial sensitivity to ciprofloxacin, gentamicin, clindamycin, erythomycin, tetracycline of MSSA was 26.4% , 93.6%, 81.5%, 61.2%, 95.4% respectively, and that of MRSA was 4.9%, 56.2%, 58%, 31%, 89.8% respectively. Conclusion: Antimicrobial sensitivity to ciprofloxacin, gentamicin, clindamycin, erythromycin, and tetracycline were significantly higher in MSSA than in MRSA.

Solid waste dumpsite leachate and contiguous surface water contain multidrug-resistant ESBL-producing Escherichia coli carrying Extended Spectrum β-Lactamase (ESBL) genes

Dumpsites generate leachates containing bacteria that may carry antibiotic resistance genes, such as extended spectrum β-lactamase (ESBL). However, the contribution of dumpsite leachates in the environmental spread of ESBL genes has not been investigated in greater detail. This study aimed to quantify the impact of Ajakanga dumpsite leachate on the spread of ESBL genes through surface water. The susceptibility of Escherichia coli isolated from dumpsite leachate and the accompanying surface water to selected antibiotics was assessed by the standardized disc diffusion method. The isolates were evaluated for phenotypic ESBL production using the double disc synergy test (DDST). The detection of ESBL genes in the isolates was carried out using a primer-specific polymerase chain reaction (PCR). Escherichia coli isolates from leachate (n = 26/32) and surface water (n = 9/12) expressed ESBL phenotype. The ESBL-producing isolates showed the highest level of resistance to the 3rd generation cephalosporin antibiotics: cefotaxime (100%), cefpodoxime (97%), ceftazidime (97%), with low resistance observed to imipenem (6%) and azithromycin (3%). All the isolates were multidrug-resistant, showing resistance to three or more classes of antibiotics. All the ESBL-producing E. coli obtained carried blaCTX−M, 21/35 (60%) carried blaTEM while none of the isolates bore blaSHV. This study found that ESBL-producing Escherichia coli from dumpsite leachate and nearby surface water had identical resistance signatures indicating the relatedness of the isolates, and that dumpsite leachate could contribute to the transfer of ESBL-producing bacteria and their genes to receiving surface water. This study has necessitated the need for a review of the guidelines and operational procedures of dumpsites to forestall a potential public health challenge.

Bacterial keratitis : Clinical aspects, pathogens and treatment

Bacterial infections are by far the most frequent cause of infectious keratitis in high-income countries. The clinical appearance can vary widely depending on the type and species of bacteria, ranging from small superficial infiltrates to necrotizing forms. The numerous classes of available antibiotics render the treatment scope diverse and complex, especially before the pathogen has been specified and the sensitivity to antibiotics has been tested. New therapeutic approaches to reduce bacterial virulence are in development. This CME article focuses on the clinical, diagnostic and therapeutic approaches to recognize and treat bacterial keratitis.

Insights into macrolide resistance in Arcobacter butzleri: potential resistance mechanisms and impact on bacterial fitness and virulence.

Macrolides are recommended for treating the emerging enteropathogen Arcobacter butzleri; nonetheless, this bacterium often exhibits highly variable resistance rates, and the mechanisms behind this resistance phenotype remain largely unexplored. To understand the phenotypic and genotypic consequences associated with the acquisition of erythromycin resistance in A. butzleri, as well as the effects on the fitness of this species. Resistant strains resulting from spontaneous mutations and adaptive laboratory evolution under increasing erythromycin concentrations were examined regarding their cross-resistance and collateral susceptibility profiles. Genetic causes of phenotypic antibiotic resistance were analysed by sequencing and bioinformatics, with functional correlation through ethidium bromide accumulation assays. Growth profiles in the presence and absence of erythromycin, motility and biofilm formation abilities were assessed to detect potential changes in fitness and virulence. Clones from spontaneous mutation rate evolution demonstrated decreased susceptibility to erythromycin and other classes of antibiotics, associated with mutations in the transcriptional repressor areR, causing overexpression of the AreABC efflux pump. In turn, WGS analysis of the evolved strain showed additional mutations in the ribosomal proteins L4 and L22 and in the areR gene. Furthermore, the acquisition of macrolide resistance altered A. butzleri virulence and entailed a high biological cost. The findings of this study have proved that efflux activity contributes synergistically with mutations in the ribosomal proteins L4 and L22 to A. butzleri's high-level macrolide resistance. The results further suggest an impact on the bacterial physiology and virulence, with the increased fitness cost justifying the low worldwide prevalence of high-level resistant circulating strains.

Review on antibiotic pollution dynamics: insights to occurrence, environmental behaviour, ecotoxicity, and management strategies.

Antibiotic contamination poses a significant global concern due to its far-reaching impact on public health and the environment. This comprehensive review delves into the prevalence of various antibiotic classes in environmental pollution and their interactions with natural ecosystems. Fluoroquinolones, macrolides, tetracyclines, and sulphonamides have emerged as prevalent contaminants in environmental matrices worldwide. The concentrations of these antibiotics vary across diverse environments, influenced by production practices, consumer behaviours, and socio-economic factors. Low- and low-middle-income countries face unique challenges in managing antibiotic contamination, with dominant mechanisms like hydrolysis, sorption, and biodegradation leading to the formation of toxic byproducts. Ecotoxicity reports reveal the detrimental effects of these byproducts on aquatic and terrestrial ecosystems, further emphasizing the gravity of the issue. Notably, monitoring the antibiotic parent compound alone may be inadequate for framing effective control and management strategies for antibiotic pollution. This review underscores the imperative of a comprehensive, multi-sectoral approach to address environmental antibiotic contamination and combat antimicrobial resistance. It also advocates for the development and implementation of tailored national action plans that consider specific environmental conditions and factors. Thus, an approach is crucial for safeguarding both public health and the delicate balance of our natural ecosystems.

Average Nucleotide Identity and Digital DNA-DNA Hybridization Analysis Following PromethION Nanopore-Based Whole Genome Sequencing Allows for Accurate Prokaryotic Typing.

Whole-genome sequencing (WGS) is revolutionizing clinical bacteriology. However, bacterial typing remains investigated by reference techniques with inherent limitations. This stresses the need for alternative methods providing robust and accurate sequence type (ST) classification. This study optimized and evaluated a GridION nanopore sequencing protocol, adapted for the PromethION platform. Forty-eight Escherichia coli clinical isolates with diverse STs were sequenced to assess two alternative typing methods and resistance profiling applications. Multi-locus sequence typing (MLST) was used as the reference typing method. Genomic relatedness was assessed using Average Nucleotide Identity (ANI) and digital DNA-DNA Hybridization (DDH), and cut-offs for discriminative strain resolution were evaluated. WGS-based antibiotic resistance prediction was compared to reference Minimum Inhibitory Concentration (MIC) assays. We found ANI and DDH cut-offs of 99.3% and 94.1%, respectively, which correlated well with MLST classifications and demonstrated potentially higher discriminative resolution than MLST. WGS-based antibiotic resistance prediction showed categorical agreements of ≥ 93% with MIC assays for amoxicillin, ceftazidime, amikacin, tobramycin, and trimethoprim-sulfamethoxazole. Performance was suboptimal (68.8-81.3%) for amoxicillin-clavulanic acid, cefepime, aztreonam, and ciprofloxacin. A minimal sequencing coverage of 12× was required to maintain essential genomic features and typing accuracy. Our protocol allows the integration of PromethION technology in clinical laboratories, with ANI and DDH proving to be accurate and robust alternative typing methods, potentially offering superior resolution. WGS-based antibiotic resistance prediction holds promise for specific antibiotic classes.

Metagenomics uncovers microbiome and resistome in soil and reindeer faeces from Ny-Ålesund (Svalbard, High Arctic)

Research on the microbiome and resistome in polar environments, such as the Arctic, is crucial for understanding the emergence and spread of antibiotic resistance genes (ARGs) in the environment. In this study, soil and reindeer faeces samples collected from Ny-Ålesund (Svalbard, High Arctic) were examined to analyze the microbiome, ARGs, and biocide/metal resistance genes (BMRGs). The dominant phyla in both soil and faeces were Pseudomonadota, Actinomycetota, and Bacteroidota. A total of 2618 predicted Open Reading Frames (ORFs) containing antibiotic resistance genes (ARGs) were detected. These ARGs belong to 162 different genes across 17 antibiotic classes, with rifamycin and multidrug resistance genes being the most prevalent. We focused on investigating antibiotic resistance mechanisms in the Ny-Ålesund environment by analyzing the resistance genes and their biological pathways. Procrustes analysis demonstrated a significant correlation between bacterial communities and ARG/BMRG profiles in soil and faeces samples. Correlation analysis revealed that Pseudomonadota contributed most to multidrug and triclosan resistance, while Actinomycetota were predominant contributors to rifamycin and aminoglycoside resistance. The geochemical factors, SiO42− and NH4+, were found to significantly influence the microbial composition and ARG distribution in the soil samples. Analysis of ARGs, BMRGs, virulence factors (VFs), and pathogens identified potential health risks associated with certain bacteria, such as Cryobacterium and Pseudomonas, due to the presence of different genetic elements. This study provided valuable insights into the molecular mechanisms and geochemical factors contributing to antibiotic resistance and enhanced our understanding of the evolution of antibiotic resistance genes in the environment.

Development of a Sensitive Monoclonal Antibody-Based Colloidal Gold Immunochromatographic Strip for Lomefloxacin Detection in Meat Products.

Lomefloxacin (LOM), an antibiotic crucial for preventing various animal diseases in animal husbandry, can pose serious health risks when found in excessive amounts in meat products. The development of highly specific and sensitive colloidal gold immunochromatographic test strips is essential for the accurate detection of this class of antibiotics. Our study utilized a monoclonal antibody (mAb) assay and immunochromatographic strips to detect lomefloxacin residues in meat products. The results showed minimal cross-reactivity with other structural analogs, with a maximum half inhibitory concentration (IC50) of 0.93 ng/mL and a linear range of 0.38 to 2.3 ng/mL for the indirect competitive enzyme-linked immunosorbent assay (ic-ELISA). The recovery of LOM was 80% to 120%, with an average coefficient of variation below 5%. The immunochromatographic strip test results showed a visual detection limit of 2.5 ng/g, meeting the market requirements for the test. This study highlights the significance of specific and sensitive testing methods for detecting lomefloxacin, ensuring consumers' safety and health.

Antibiotic use and risk of Clostridioides difficile infection in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI) compared with those without IBD, which is worsened with antibiotic usage. While prior studies have shown a correlation between CDI development and certain classes of antibiotics, the IBD population has not been well represented. This study evaluates the rates of CDI with outpatient antibiotic use in patients with IBD. We conducted a retrospective cohort study composed of patients with IBD and compared the incidence of CDI in patients who received an outpatient prescription for antibiotics (6694 patients) against those without prescriptions (6025 patients) from 2014 to 2020 at our institution. We compared CDI rates based on nine antibiotic classes: penicillins, cephalosporins, sulfonamides, tetracyclines, macrolides, quinolones, clindamycin, metronidazole, and nitrofurantoin. The risk of CDI was low (0.7%) but significantly higher for those with antibiotic exposure (0.9% vs 0.5%, P=0.005) and had a positive correlation with a smoking history. The increased risk of CDI in the IBD population was attributable to the clindamycin and metronidazole classes (odds ratio=4.7, 95% confidence interval: 1.9-11.9, P=0.001; odds ratio=3.6, 95% confidence interval: 2.1-6.2, P<0.0001, respectively). The use of clindamycin or metronidazole prescribed in an outpatient setting was associated with a statistically significant increased risk of CDI in patients with IBD. Although the association between clindamycin and CDI is a well-established and common finding, the association between metronidazole and CDI is unique in this study.

Fluorescence array sensor based on lanthanide complex for pattern recognition detection of fluoroquinolone antibiotics

Fluoroquinolone antibiotics, a class of animal and human useful antibiotics, are widely utilized in numerous fields including biomedical science, animal husbandry, and aquatic finfish farming. Its high demand and wide application have directly or indirectly led to substantial consumption and discharge of antibiotics, affecting not only the environment but also endangering human health through bioaccumulation. Hence, rapid and precise detection of trace antibiotics in water, food, and biological samples is critically important. This research synthesized Tb3+/Eu3+ complexes with dual emission centers, and a fluorescence sensor array was constructed with the fluorescence intensity ratio F1/F2 of the two emission centers as a signal. Different sensitization effect of fluoroquinolone antibiotics towards lanthanide complexes aided in differentiating five fluoroquinolone antibiotics from two others. Additionally, the sensor array can effectively detect fluoroquinolone antibiotics in real samples, suggesting its reliability and practicality of complex sample analysis. The excellent qualitative and quantitative analysis ability of this strategy for fluoroquinolone antibiotics offers a novel perspective for antibiotic residue detection, showcasing a new opportunity for lanthanide complex application in sensor arrays.

Synergism of colistin and globular endolysins against multidrug-resistant gram-negative bacteria

Endolysins (lysins), a novel class of antibacterial agents derived from bacteriophages, efficiently lyse bacteria by degrading the peptidoglycan layer within the bacterial wall. Colistin, a classic peptide antibiotic with the ability to permeabilize the outer membrane, has recently shown great promise in synergizing with lysins against gram-negative bacteria. However, the exact mechanisms responsible for their synergy remain unclear. Here, we first demonstrated the synergistic bacterial killing of various lysin and colistin combinations. With a model lysin, LysAB2, we then confirmed that there is a threshold concentration of colistin causing sufficient permeabilization of the outer membrane for lysin to access the peptidoglycan layer and subsequently exert its lytic ability. The threshold colistin concentrations were found to range 0.2−0.8 μM for the tested bacteria, with the exact value largely depending on the density of lipopolysaccharides on the outer membrane. Beyond the threshold colistin level, LysAB2 could synergize with colistin at a concentration as low as 0.31 μM. Next, we proved for the first time that lysin-induced degradation of the peptidoglycan layer facilitated the disruption of cytoplasmic membrane by colistin, elevated the level of reactive oxygen species in bacterial cells, and boosted the killing effect of colistin. Additionally, the colistin-lysin combination could effectively eliminate established biofilms due to the biofilm dispersal ability of lysin. The in-vivo efficacy was preliminary confirmed in a Galleria mellonella infection model for combination with colistin doses (≥ 1.8 μg/larvae), which could reach beyond the threshold concentration, and a fixed LysAB2 dose (10 μg/larvae). In summary, our study provided the first experimental evidence unravelling the mechanisms behind the synergy of colistin and lysins. All these findings provided important insights in guiding the dosing strategy for applying this combination in future development.

Exposure to doxycycline increases risk of carrying a broad range of enteric antimicrobial resistance determinants in an elderly cohort

High rates of antibiotic prescription in residential aged care are likely to promote enteric carriage of antibiotic-resistant pathogens and increase the risk of antibiotic treatment failure. Despite their importance, relationships between antibiotic exposures and patterns of enteric resistance carriage in this population remain poorly understood. We conducted a cross-sectional metagenomic cohort analysis of stool samples from residents of five long-term aged-care facilities in South Australia. Taxonomic composition was determined, and enteric carriage of antibiotic resistance genes (ARGs) was identified and quantified against the Comprehensive Antibiotic Resistance Database. Both the detection and abundance of stool taxa and ARGs were related to antibiotic exposures up to 12 months prior. Factors associated with the abundance of ARGs of high clinical concern were identified. Stool samples were provided by 164 participants (median age: 88 years, IQR 81-93; 72% female). Sixty-one percent (n=100) of participants were prescribed antibiotics at least once in the prior 12 months (median prescriptions: 4, range: 1-52), most commonly a penicillin (n=55, 33.5%), cephalosporin (n=53, 32.3%), diaminopyrimidine (trimethoprim) (n=36, 22%), or tetracycline (doxycycline) (n=21, 12.8%). More than 1100 unique ARGs, conferring resistance to 38 antibiotic classes, were identified, including 20 ARGs of high clinical concern. Multivariate logistic regression showed doxycycline exposure to be the greatest risk factor for high ARG abundance (adjusted odds ratio [aOR]=14.8, q<0.001) and a significant contributor to inter-class selection, particularly for ARGs relating to penicillins (aOR=3.1, q=0.0004) and cephalosporins (aOR=3.4, q=0.003). High enteric ARG abundance was associated with the number of separate antibiotic exposures (aOR: 6.4, q<0.001), exposures within the prior 30 days (aOR: 4.6, q=0.008) and prior 30-100 days (aOR: 2.6, q=0.008), high duration of antibiotic exposure (aOR: 7.9, q<0.001), and exposure to 3 or more antibiotic classes (aOR: 7.4, q<0.001). Carriage of one or more ARGs of high clinical concern was identified in 99% of participants (n=162, median: 3, IQR: 2-4), involving 11 ARGs conferring resistance to aminoglycosides, four to beta-lactams, one to glycopeptides, three to fluoroquinolones, and one to oxazolidinones. Carriage of ARGs of high clinical concern was positively associated with exposure to doxycycline (aminoglycoside, fluoroquinolone, and oxazolidinone ARGs) and trimethoprim (fluoroquinolone and beta-lactam ARGs). Analysis of doxycycline impact on microbiota composition suggested that observed resistome changes arose principally through direct ARG selection, rather than through the antibiotic depletion of sensitive bacterial populations. The gut microbiome of aged care residents is a major reservoir of antibiotic resistance. As a critical antibiotic in medical practice, a comprehensive understanding of the impact of doxycycline exposure on the gut resistome is paramount for informed antibiotic use, particularly in an evolving landscape of prophylactic applications. Near-universal asymptomatic carriage of clinically critical resistance determinants is highly concerning and reinforces the urgent need for improved management of antibiotic use in long-term aged care.

Phenotypic and molecular characterization of multidrug-resistant Enterobacterales isolated from clinical samples in Palestine: a focus on extended-spectrum β-lactamase- and carbapenemase-producing isolates

BackgroundInfections resulting from multidrug-resistant Enterobacterales (MDR-E) pose a growing global threat, presenting challenges in treatment and contributing significantly to morbidity and mortality rates. The main objective of this study was to characterize phenotypically and genetically extended-spectrum β-lactamase- and carbapenemase- producing Enterobacterales (ESBLE and CPE respectively) isolated from clinical samples in the West Bank, Palestine.MethodsA cross sectional study was conducted in October 2023 on clinical bacterial isolates collected from five governmental hospitals in the West Bank, Palestine. The isolates obtained from the microbiology laboratories of the participating hospitals, underwent identification and antibiotic susceptibility testing (AST) using the VITEK® 2 Compact system. ESBL production was determined by the Vitek2 Compact system. A modified carbapenem inactivation method (mCIM) was employed to identify carbapenemase-producing Enterobacterales (CPE). Resistance genes were detected by real-time PCR.ResultsOut of the total 1380 collected isolates, we randomly selected 600 isolates for analysis. Our analysis indicated that 287 (47.83%) were extended-spectrum beta-lactamase producers (ESBLE), and 102 (17%) as carbapenem-resistant Enterobacterales (CRE) isolates. A total of 424 isolates (70.67%) were identified as multidrug-resistant Enterobacterales (MDRE). The most prevalent ESBL species were K. pneumoniae (n = 124; 43.2%), E. coli (n = 119; 41.5%) and E. cloacae (n = 31; 10.8%). Among the CRE isolates, 85 (83.33%) were carbapenemase-producing Enterobacterales (CPE). The most frequent CRE species were K. pneumoniae (n = 63; 61.7%), E. coli (n = 25; 24.5%) and E. cloacae (n = 13; 12.8%). Additionally, 47 (7.83%) isolates exhibited resistance to colistin (CT), with 38 (37.62%) being CT-resistant CRE and 9 (3.14%) being CT-resistant ESBLE while sensitive to carbapenems. We noticed that 11 isolates (6 Klebsiella pneumoniae and 5 Enterobacter cloacae complex) demonstrated sensitivity to carbapenems by phenotype but carried silent CPE genes (1 blaOXA48, and 6 blaNDM, 4 blaOXA48, blaNDM). ESBL-producing Enterobacterales strains exhibited varied resistance patterns across different antibiotic classes. E. coli isolates showed notable 48% resistance to trimethoprim/sulfamethoxazole. K. pneumoniae isolates displayed a significant resistance to trimethoprim/sulfamethoxazole, nitrofurantoin, and fosfomycin (54%, 90%, and 70% respectively). E. cloacae isolates showed complete resistance to nitrofurantoin and fosfomycin. P. mirabilis isolates exhibited high resistance against fluoroquinolones (83%), and complete resistance to trimethoprim/sulfamethoxazole, nitrofurantoin and fosfomycin.ConclusionThis study showed the high burden of the ESBLE and CRE among the samples collected from the participating hospitals. The most common species were K. pneumoniae and E. coli. There was a high prevalence of blaCTXm. Adopting both conventional and molecular techniques is essential for better surveillance of the emergence and spread of antimicrobial-resistant Enterobacterales infections in Palestine.