Antibiotic Concentrations Research Articles

Insights into interspecies protein binding variability using clindamycin as an example

Abstract Background In the preclinical development of new drugs, animal models are often employed to predict their efficacy in humans, relying on translational pharmacokinetic/pharmacodynamic (PK/PD) studies. We performed in vitro experiments focusing on the comparison of plasma protein binding (PPB) and bacterial growth dynamics of clindamycin, a commonly used antimicrobial agent, across a range of drug concentrations and plasma environments. Methods Human, bovine and rat plasma were used for determining PPB of clindamycin at various antibiotic concentrations in buffer and media containing 20% to 70% plasma or pure plasma using ultrafiltration (UF) and equilibrium dialysis (ED). Also bacterial growth and time–kill assays were performed in Mueller–Hinton broth (MHB) containing various percentages of plasma. Results Protein binding of clindamycin correlated well between UF and ED. Notably, clindamycin exhibited substantially lower protein binding to rat plasma compared with human and bovine plasma. Staphylococcus aureus growth was significantly reduced in 70% human, bovine, and rat plasma after 4, 8 and 24 h compared with standard MHB. Time–kill data demonstrated that bacterial counts at both 20% and 70% plasmas were less when compared with MHB at drug concentrations lower than MIC after 4 and 8 h of incubation. For rat plasma, the difference was maintained over 24 h of incubation. Furthermore, a complete bacterial killing at 16 mg/L was observed after 24 h in 20% and 70% human and bovine plasma, but not for rat plasma. Conclusions Recognizing interspecies differences in PB might be essential for optimizing the translational relevance of preclinical studies.

The role of antibiotic-derived mycobacterial vesicles in tuberculosis pathogenesis.

Pulmonary tuberculosis (TB) causes progressive and irreversible damage to lung tissue, a damage that may not fully resolve after treatment. Mycobacterial vesicles (MVs), which are poorly understood, may contribute to TB pathology. This study investigated the effects of stress, such as treatment with conventional TB antibiotics rifampicin, isoniazid, ethambutol, or treatment with an antimycobacterial peptide (NZX), on mycobacterial vesiculation. Stress from minimal inhibitory concentrations of antibiotics, or peptide all increased MV formation. Electron microscopy and lipid profiling revealed that these vesicles, about 40nm in size, were released from the bacterial inner membrane and consisted of apolar lipids. Using mass spectrometry, the study identified key differences in MVs protein cargo dependent on the antibiotic used, especially with ethambutol-induced MVs that contained proteins from several mycobacterial pathways. Additionally, toxicology analysis using different concentrations of MVs on primary human macrophages and the monocytic cells indicated that MVs from the different treatments were not toxic to human cells, however induced specific inflammatory profiles. In conclusion, this study identified mycobacterial vesicles to be a potential contributor to tuberculosis pathology.

In Vivo Efficacy of a Nanoconjugated Glycopeptide Antibiotic in Silkworm Larvae Infected by Staphylococcus aureus

To contrast the rapid spread of antibiotic resistance in bacteria, new alternative therapeutic options are urgently needed. The use of nanoparticles as carriers for clinically relevant antibiotics represents a promising solution to potentiate their efficacy. In this study, we used Bombyx mori larvae for the first time as an animal model for testing a nanoconjugated glycopeptide antibiotic (teicoplanin) against Staphylococcus aureus infection. B. mori larvae might thus replace the use of mammalian models for preclinical tests, in agreement with the European Parliament Directive 2010/63/EU. The curative effect of teicoplanin (a last resort antibiotic against Gram-positive bacterial pathogens) conjugated to iron oxide nanoparticles was assessed by monitoring the survival rate of the larvae and some immunological markers (i.e., hemocyte viability, phenoloxidase system activation, and lysozyme activity). Human physiological conditions of infection were reproduced by performing the experiments at 37 °C. In this condition, nanoconjugated teicoplanin cured the bacterial infection at the same antibiotic concentration of the free counterpart, blocking the insect immune response without causing mortality of silkworm larvae. These results demonstrate the value and robustness of the silkworm as an infection model for testing the in vivo efficacy of nanoconjugated antimicrobial molecules.

Optical Properties and Antimicrobial Activity of Si/PVP Hybrid Material Combined with Antibiotics

Silica–poly (vinylpyrrolidone) hybrid material was prepared using the sol–gel method. Tetramethyl ortosilane (TMOS) was used as a silica precursor. XRD analysis established that the as-prepared material is amorphous. The morphological structure of the final product was determined by the incorporated PVP. The UV–Vis analysis showed that the obtained hybrid exhibited absorption in the ultraviolet range. The antimicrobial activity of the SiO2/15PVP hybrid material was tested on Staphylococcus epidermidis ATCC 14990, Salmonella typhimurium ATCC BAA-2162, Candida albicans, and Saccharomyces cerevisiae in combination with the following antibiotics: Vancomycin for Gram-positive bacteria, Ciprofloxacin for Gram-negative bacteria, and Nystatin for yeast. The results confirmed a concentration-dependent synergistic effect of the antibiotic in combination with the TM15/PVP hybrid particles, especially at their highest concentration of 100 mg/mL on Gram-positive bacteria and for the Gram-negative Salmonella. On Candida albicans ATCC 18804 and Saccharomyces cerevisiae CCY 21-6-3, the effect was synergistic again, and a fungicidal effect was observed at 6.25 and 1.50 mg/mL for the antibiotic concentration and concentrations of hybrid material at 100 mg/mL. The toxicity on Daphnia magna was also tested. The registered prooxidant activity of SiO2/15PVP shows possible applications at very low concentrations. The obtained results demonstrate the possibility of clinical implementations of the newly synthesized hybrid material.

Occurrence, spatiotemporal distribution, and health risk of antibiotics in the Wuhan section of the Yangtze River, China.

The occurrence, spatiotemporal changes, and health hazard of antibiotics in source water and finished water in the Wuhan section of the Yangtze River are not well understood. In this study, 43 source water and finished water samples were collected from 11 water plants in Wuhan in August 2021 and May 2022. Fifty-one antibiotics from eight categories were measured. A total of 41 antibiotics were detected in the source water samples, and 24 in the finished water samples. The total antibiotic concentration in source water ranged from 1.68 to 437.18 ng/L, which is significantly higher than that in finished water (2.04-87.25 ng/L). Sulfonamides and lincosamides were predominant, accounting for nearly 80% of the total antibiotic concentration. Lincomycin constituted nearly 30% of the total antibiotic concentration in the source water. In August 2021, the average total antibiotic concentration in source water was 107.12 ng/L, higher than in May 2022 (63.13 ng/L). Spatially, the total antibiotic concentrations in samples collected from the Han River, a tributary of the Yangtze River, were higher than those in the main stream of the Yangtze River. Ecological risk assessment indicated that the hazard posed by most antibiotics were negligible. Lincomycin potentially posed a high health hazard, and clarithromycin and roxithromycin posed a moderate hazard to infants.

Safety, tolerability and pharmacokinetics of subcutaneous meropenem as an alternative to intravenous administration.

Subcutaneous delivery of antibiotics is a practical alternative to IV administration. Meropenem is commonly used to treat infections caused by resistant Gram-negative organisms. This was a prospective, crossover self-controlled study in 11 stable inpatients established on meropenem. Participants received a single dose of subcutaneous meropenem, in 50 mL normal saline via gravity feed. Venous blood sampling was performed at baseline, 0.5, 1, 2, 4 and 8 h following the subcutaneous and IV doses. Antibiotic concentrations were measured using UPLC-MS/MS. Pharmacokinetic data were analysed using a non-linear mixed-effects modelling approach. Pain scores and infusion site reactions (oedema/erythema) were assessed. Subcutaneous meropenem was well tolerated. The bioavailability of subcutaneous administration was 81.5% (95% CI 71.6%-93.2%). Increasing BMI was associated with slower absorption from subcutaneous tissue. Compared with IV, subcutaneous administration resulted in lower peak and higher trough concentrations. Despite the lower bioavailability observed, the PTA for free drug concentrations greater than the MIC for more than 40% of the time between doses was higher for subcutaneous than IV administration at MIC values between 0.03 and 8 mg/L. Simulated subcutaneous doses of 1.5 g twice daily, or 3 g continuous 24 h infusion had improved PTA relative to standard IV dosing of 1 g three times daily. Subcutaneous meropenem appears to be well tolerated and has a favourable pharmacokinetic profile. Either 1.5 g twice daily or 3 g as a 24 h subcutaneous infusion could be considered for future evaluation.

Coexistence of the blaZ gene and selected virulence determinants in multidrug-resistant Staphylococcus aureus: insights from three Nigerian tertiary hospitals.

Infections caused by β-lactamase-producing strains of Staphylococcus aureus have become increasingly difficult to treat due to the expression of multiple virulence factors. This has heightened concerns about managing S. aureus-related infections. This study was conducted to characterize the blaZ gene and selected virulence determinants in β-lactam resistant S. aureus from human sources in three Nigerian tertiary hospitals. Three hundred and sixty samples were collected for the study. S. aureus was isolated and characterized following standard microbiological protocols and nuc gene amplification. Antibiotic susceptibility and minimum inhibitory concentration tests were performed using the disk diffusion method and E-tests, respectively. Biofilm formation and β-lactamase production were assessed using Congo red agar and nitrocefin kits, while the blaZ gene was examined using conventional PCR. Capsular polysaccharide genotyping, accessory gene regulator (agr) detection, Panton-valentine leucocidin (PVL), and PVL proteins were performed using PCR and Western blotting. S. aureus was recovered from 145 samples, 50 (34.5%) of these isolates exhibited multidrug resistance, with MICs ranging from 0.125 to 1.00µg/mL, and showed significant resistance to aminoglycosides, fluoroquinolones, and β-lactams. Of these, 31 strains produced β-lactamases, 30 of which carried the blaZ gene in combination with cap8 (80%) or cap5 (20%). Biofilm formation and PVL gene were observed in 85% of the 20 randomly selected blaZ-positive multidrug-resistant (MDR) strains. The agr2 allele was predominant, found in 70% of the selected MDR strains. No significant difference in the occurrence of the blaZ gene was found among the three clinical sources (p ≤ α0.05). The co-occurrence of the blaZ gene with PVL, capsular polysaccharide genes, and agr alleles is associated with biofilm formation, indicating a high risk of β-lactam-resistant S. aureus infections. Our findings highlight the need for continuous molecular surveillance to enhance infection management, treatment options, and patient outcomes in the study locality. A limitation of this study is the random selection of MDR isolates, which may affect the comprehensiveness of the analyses.

Fe/Co-modified Enteromorpha bio-hydrochar enhanced anaerobic digestion of chicken manure with sulfadimethazine: focusing on synergistic mechanism and microbial community succession

Abstract Residual antibiotics in chicken manure may interfere with the stability of anaerobic digestion (AD) and inhibit resource utilization efficiency. In this study, we aimed to enhance chicken manure bio-methanation in AD with high-concentration of sulfamethazine (SMZ) by adding metal (Fe, Co)-modified Enteromorpha-based hydrochar (Co-HC, Fe-HC). The results showed that Fe-HC and Co-HC increased the degree of acidogenesis by 1.25 times and 1.58 times, respectively. The maximum protein concentration in EPS was increased by 47.64% and 72.5% after adding Fe-HC and Co-HC. However, only Co-HC demonstrated notable improvements in both methane production and SMZ removal efficiency. Electrochemical analysis showed that Co-HC possessed a richer variety of oxygen and nitrogen functional groups, along with superior electron exchange capabilities compared to Fe-HC. Furthermore, microbiological assessments revealed that Co-HC enriched syntrophic bacteria (such as Syntrophomonas and Mesotoga), facilitating direct interspecies electron transfer (DIET) and subsequently enhancing biomethane production. The abundance of genes involved in electron transfer increased significantly with Co-HC, with a maximum increase of 75.86% in Co1.5-HC treatment. Additionally, the elimination of antibiotic resistance genes (sul1, sul2) increased by 65.66% in the Co1.5-HC treatment. This study offers a theoretical foundation and empirical support for the synergistic improvement of livestock and poultry manure containing high antibiotic concentrations, thereby helping to overcome challenges posed by recalcitrant substances. Graphical Abstract

Antibiotic exposure and risk of overweight/obesity in children: a biomonitoring-based study from eastern Jiangsu, China

ObjectiveTo describe antibiotic exposure in children and explore its association with overweight/obesity.MethodsIn June 2022, 328 kindergarten and primary school children were selected from Nantong city in Jiangsu Province. Questionnaires were distributed, and morning urine samples were obtained. Total urinary concentrations of 41 antibiotics were measured using ultra-performance liquid chromatography and tandem mass spectrometry. The rates of antibiotic exposure were expressed as percentages (%), specific percentiles (P95 and P99), and the maximum values were used to describe the concentration of antibiotics. The association between urinary antibiotic creatinine-adjusted and overweight/obesity was analyzed using logistic regression.ResultsA total of 328 children were initially recruited, of which 295 aged 3–8 years met the inclusion criteria and were finally included in the study. The biomonitoring results revealed that 35 antibiotics were detected, with a total detection frequency of 98.31%. Among the included children, 24.75% were classified as overweight/obesity. Multinomial logistic regression analyses revealed significant associations between overweight/obese and exposure to veterinary antibiotics (VAs) and preferred veterinary antibiotics (PVAs). After adjusting for various overweight/obesity-relevant variables, higher exposure to sulfamethoxazole [OR = 2.35, 95% confidence interval (CI):1.17–4.70], norfloxacin (OR = 2.66, 95% CI: 1.01–7.08), and fluoroquinolones (OR = 1.97, 95% CI: 1.02–3.78) were significantly associated with overweight/obesity (p < 0.05). In addition, after stratification by sex and adjustment for confounding variables, sex-specific differences were observed in the association between antibiotic exposure and overweight/obesity. Notably, these associations were predominantly observed among boys.ConclusionChildren were extensively exposed to antibiotics. Exposure to certain types of veterinary antibiotics and preferred veterinary antibiotic exposure, mainly through food or drinking water, are associated with an increased risk of overweight/obesity in children.

Antibiotic concentrations induce morphological changes and increase biofilm formation in multi-antibiotic and heavy metal resistant Kluyvera cryocrescens and Serratia fonticola

Water pollution is the biggest challenge that has rendered existing water resources unusable due to contamination with antibiotics and heavy metals. Antibiotics are often used to treat bacterial diseases. Heavy metals, on the other hand, are micro-pollutants that pose a threat to aquatic systems, especially when they accumulate in nature. Increasing pollution and the uncontrolled use of antibiotics have exposed bacteria to non-lethal concentrations (sub-MIC), potentially leading to resistance. In this study, Kluyvera cryocrescens and Serratia fonticola were isolated from a freshwater source and characterised. The resistance profiles of the isolates to 16 antibiotics and 8 heavy metals were determined, revealing that they are multidrug-resistant. The effects of sub-MICs (MIC/2 and MIC/4) of antibiotics on biofilm formation, siderophore production, and cell morphology of bacteria were analysed. It was found that at some sub-MIC values of kanamycin, tetracycline, meropenem, erythromycin, and clarithromycin, biofilm formation by K. cryocrescens increased. An increase in biofilm production was also observed in S. fonticola at sub-MIC values of imipenem, meropenem, ceftazidime, ciprofloxacin, and clarithromycin. Moreover, significant morphological changes were observed in both isolates following treatment with meropenem, ciprofloxacin, and ceftazidime. After treatment with meropenem, the typical rod-shaped (bacillary) morphology of the isolates shifted to a round (coccoid) form. In contrast, the bacteria developed into long filaments after treatment with ciprofloxacin and ceftazidime. These changes in the bacteria may favour the development of resistance and pose challenges for the prevention and treatment of diseases. Therefore, it is crucial to understand how sub-MIC levels of antimicrobial agents alter the virulence properties of bacteria.

Emergence of Antibiotic Residues and Antibiotic-Resistant Bacteria in Hospital Wastewater: A Potential Route of Spread to African Streams and Rivers, a Review

Medicinal activities carried out within hospitals lead to high consumption of antibiotics and subsequently result in a high excretion rate of antibiotic residues. When consumed by humans, these antibiotics are not fully absorbed by the body and are often discharged into the environment along with biological waste from infected human patients. The significant water consumption in hospitals and the pharmaceutical impact on wastewater from healthcare facilities facilitate the emergence and spread of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in the environment. Hospital effluents could be doubly involved in the dissemination of antibiotic molecules and multidrug-resistant bacteria in various ecosystems. The aim of this review is to characterize hospital effluents by assessing antibiotic concentrations and the diversity of antibiotic-resistant bacteria in these hospital wastewaters within the environment (aquatic environments; rivers) as well as to inventory the bacteria present and those carrying antibiotic resistance in both hospital wastewater and the environment.

Antibiotic contaminants and their impact in Gingee River, Puducherry: insights from SPE-UPLC-MS/MS and zebrafish study.

The accumulation of antibiotic residues in ecosystems is intricately tied to the proliferation of bacterial resistance to antibiotics, with far-reaching consequences for the health and welfare of both humans and animal well-being. The analytical approach integrates solid phase extraction (SPE) with ultra performance liquid chromatography-mass spectrometry (UPLC-MS/MS) for quantification of multiclass antibiotic residues. Upon applying the aforementioned method to analyse water samples collected from the Gingee River, revealed the existence of five distinct antibiotics. This is the first study reporting antibiotic concentration in the Gingee River, Puducherry. The concentrations of nalidixic acid, sulfamethoxazole, and tetracycline were determined to be 8.5, 6.9, and 4.8μg/L, respectively. Metronidazole and trimethoprim were detected at concentrations below the quantifiable limit. The microbial study of water samples also indicated that Shigella sp. and Acinetobacter sp. were the most predominant bacterial species present. Our preliminary observation underscores the importance of comprehending the intricate relationship between the presence of antibiotics in water and the concurrent proliferation of antibiotic-resistant bacteria within bacterial populations in the Gingee River. Further, we evaluated the developmental toxicity of environmentally relevant concentrations of antibiotics in zebrafish. The zebrafish model confirms that these antibiotics are sublethally hazardous to human health at environmentally relevant concentrations. This integrated approach allows unique views on the environmental impact of antibiotic residues, their role in the evolution of antibiotic resistance, and their impact on human health.

The effect of clinically relevant antibiotics on bacterial extracellular vesicle release from E. coli.

Sepsis, a leading cause of death in hospitals, can be defined as a dysregulated host inflammatory response to infection, which can lead to tissue damage, organ failure, and cardiovascular complications. Although there is no cure for sepsis, the condition is typically managed with broad-spectrum antibiotics to eliminate any potential bacterial source of infection. However, a potential side-effect of antibiotic treatment is the enhanced release of bacterial extracellular vesicles (BEVs), membrane-bound nanoparticles containing proteins and other biological molecules from their parent bacterium. Some of the Gram-negative EV cargo, including Peptidoglycan associated lipoprotein (Pal) and Outer membrane protein A (OmpA), have been shown to induce both acute and chronic inflammation in host tissue. We hypothesize that antibiotic concentration and its mechanism of action can have an effect on the amount of released BEVs, which could potentially exacerbate the host inflammatory response. In this study, we evaluated nine clinically relevant antibiotics for their effect on EV release from Escherichia coli. Several beta-lactam antibiotics caused significantly more EV release, while quinolone and aminoglycosides caused relatively less vesiculation. Further study is warranted to corroborate the correlation between an antibiotic's mechanism of action and its effect on EV release, but these results underline the importance of antibiotic choice when treating sepsis patients.

Efflux-mediated Multidrug Resistance in Critical Gram-negative Bacteria and Natural Efflux Pump Inhibitors.

Multidrug Resistance mechanisms in microorganisms confer the slackness of the existing drugs, leading to added difficulty in treating infections. As a consequence, efficient novel drugs and innovative therapies to treat MDR infections are necessarily required. One of the primary contributors to the emergence of multidrug resistance in gram-negative bacteria has been identified as the efflux pumps. These transporter efflux pumps reduce the intracellular concentration of antibiotics and aid bacterial survival in suboptimal low antibiotic concentration environments that may cause treatment failure. The reversal of this resistance via inhibition of the efflux mechanism is a promising method for increasing the effectiveness of antibiotics against multidrug-resistant pathogens. Such EPI, in combination with antibiotics, can make it easier to reintroduce traditional antibiotics into clinical practice. This review mostly examines efflux-mediated multidrug resistance in critical gram-negative bacterial pathogens and EPI of plant origin that have been reported over previous decades.

Degradation of oxytetracycline in soil by a Pseudomonas strain

Oxytetracycline (OTC) is used extensively in animal husbandry and enters the soil in different forms, causing severe environmental pollution. Previous studies have shown that the genus Pseudomonas can potentially degrade antibiotics in the soil environment. Environmental conditions, such as the initial concentration of antibiotics, incubation temperature and others, have significant impacts on the activity of antibiotic-degrading bacteria. However, few reports have clarified the environmental impacts on the effectiveness of Pseudomonas spp. In the present study, we investigated the effects of different initial concentrations of OTC and incubation temperatures, as well as soil sterilization, on OTC degradation by Pseudomonas <pg=>strain T4. We also focused on the microbial degradation pathways of OTC, and variations in both antibiotic resistance genes (ARGs) and microbial communities with T4 functioning under optimal conditions. The results showed that the most effective degradation occurred under an initial OTC concentration of 2.5 mg kg-1 at 30°C in unsterilized soil spiked with T4. These conditions yielded an OTC degradation rate of 69.53% within 63 days. The putative degradation pathways of OTC in the presence of T4 included dehydration, demethylation, deamination, hydroxylation, oxidation and ring opening. Bacteroidetes, Proteobacteria and Acidobacteria played key roles in the biodegradation of OTC with T4 in the soil. The results also showed that tet(G) was the most frequently detected among the 13 common tetracycline ARGs that were investigated. The bacterial community shift observed in this study may provide new insights into the microbial degradation of OTC in soil.

Temporal dynamic of soil microbial communities and antibiotic resistance markers exposed to increasing concentrations of sulfamethoxazole

The reuse of treated wastewater (TWW) for irrigation is widely applied to alleviate pressure on freshwater resources. However, TWW contains antibiotics that once in soils, can exert selective pressure, promoting the emergence and spread of antimicrobial resistance (AMR) in the environment. Current environmental risk assessments for antibiotic residues rely on indicators such as Predicted No Effect Concentrations (PNECs), usually determined in liquid media. These PNECs aim to predict antibiotic concentrations that may promote resistance in the environment. Given the complexity of soil matrices, few studies have established PNEC values for soil, which likely differ significantly from aquatic environments.To address this gap, we developed a simplified experimental model using soil microcosms irrigated with TWW and the antibiotic sulfamethoxazole (SMX) to estimate threshold concentrations favouring resistance transfer or/and emergence within the soil microbiome. We identified SMX concentrations between 0.01 and 0.1 mg/kgdry soil that likely increased the abundance of sulfonamide resistance genes in soil. A time window of 1 to 7 days post-exposure showed a temporary rise in sul1 and intl1 gene abundance (over 1 log/soil 16S rDNA), the appearance of SMX transformation products, and an increase in some Rhodocyclaceae. After 1.5 months of incubation and complete SMX transformation, the relative abundance of sul1 and intl1 remained about 0.5 log higher than in SMX-free controls and soils with SMX levels below 0.1 mg/kg dry soil. A persistent transformation product, 4-N-glucuronide-SMX, was also observed.Here, the estimated PNEC for SMX in soil, between 0.01 and 0.1 mg/kg, exceeds typical SMX concentrations found in soils exposed to TWW. This may suggest low impact on resistance selection for this compound in the context of TWW exposure. However further studies on other soils, water, and antibiotics need to be conducted to expand our knowledge on soil PNECs.

Combined toxicity of microplastics and antibiotics towards aquatic ecosystems: A case study in Beiluo River, China

Microplastics (MPs) can adsorb antibiotics to form complex pollutants that seriously threaten the health of freshwater ecosystems. However, few studies have examined the combined ecotoxicity of MPs and multiple antibiotics in natural aquatic environments. In this study, we examined the effects of combined exposure to antibiotics and MPs on aquatic community structure in natural settings in the Beiluo River using eDNA analysis. The results revealed that antibiotic pollution in the Beiluo River mainly originates from animal husbandry and agriculture, whereas MPs mainly originate from agriculture and urban sewage. The community structure of aquatic organisms was significantly correlated with the concentrations of antibiotics and MPs and that the combined effects of antibiotics and MPs were highly interpretable for cyanobacteria and phytoplankton. The effect of MPs on antibiotic toxicity is highly dependent on the antibiotic type and MP particle size. These insights highlight that co-exposure to MPs and antibiotics in the natural environment is a common phenomenon and that co-exposure to MPs can alter the toxicological profile of antibiotics. The results enhance our comprehensive understanding of the complex combined effects of MPs and antibiotics on aquatic organisms, emphasising the necessity of informed scientific management of these emerging contaminants.

The adsorption of drugs on nanoplastics has severe biological impact

Micro- and nanoplastics can interact with various biologically active compounds forming aggregates of which the effects have yet to be understood. To this end, it is vital to characterize these aggregates of key compounds and micro- and nanoplastics. In this study, we examined the adsorption of the antibiotic tetracycline on four different nanoplastics, made of polyethylene (PE), polypropylene (PP), polystyrene (PS), and nylon 6,6 (N66) through chemical computation. Two separate approaches were employed to generate relevant conformations of the tetracycline-plastic complexes. In the first approach, we folded the plastic particle from individual polymer chains in the presence of the drug through multiple separate simulated annealing setups. In the second, more biased, approach, the neat plastic was pre-folded through simulated annealing, and the drug was placed at its surface in multiple orientations. The former approach was clearly superior to the other, obtaining lower energy conformations even with the antibiotic buried inside the plastic particle. Quantum chemical calculations on the structures revealed that the adsorption energies show a trend of decreasing affinity to the drug in the order of N66> PS> PP> PE. In vitro experiments on tetracycline-sensitive cell lines demonstrated that, in qualitative agreement with the calculations, the biological activity of tetracycline drops significantly in the presence of PS particles. Preliminary molecular dynamics simulations on two selected aggregates with each plastic served as first stability test of the aggregates under influence of temperature and in water. We found that all the selected cases persisted in water indicating that the aggregates may be stable also in more realistic environments. In summary, our data show that the interaction of micro- and nanoplastics with drugs can alter drug absorption, facilitate drug transport to new locations, and increase local antibiotic concentrations, potentially attenuating antibiotic effect and at the same time promoting antibiotic resistance.

Differential frequency of persister cells in clinically derived isolates of Pseudomonas aeruginosa after exposure to cefiderocol and ceftolozane/tazobactam.

Bacterial persistence is a phenomenon whereby a subpopulation of bacteria survive high concentrations of an active antibiotic in the absence of phenotypic alterations. Persisters are associated with chronic and recurrent infections for pathogens including Pseudomonas aeruginosa. Understanding persister profiles of newer antibiotics such as cefiderocol and ceftolozane/tazobactam against P. aeruginosa is warranted as these agents generally target difficult-to-treat infections. Persister formation was assessed using in vitro assays against nine clinical P. aeruginosa isolates exposed to cefiderocol or ceftolozane/tazobactam. Quantitative persister assays were performed using a stationary phase of bacteria challenged with 10-fold MIC drug concentrations. Persisters were quantitated as the percent persisters at 24 h and the log ratio (LR) difference in AUC for cfu for each antibiotic alone compared with growth control. The tolerance disc test (TDtest) was used to qualitatively detect persisters. Percent persisters at 24 h was lower with cefiderocol compared with ceftolozane/tazobactam for six of the nine tested isolates. Eight of the nine isolates had higher reduction in LR for cefiderocol groups, suggesting an overall higher and more rapid bacterial reduction in cefiderocol groups. For cefiderocol, five of the nine tested isolates lacked regrowth after replacement with glucose disc, suggesting no persistence via the TDtest. For ceftolozane/tazobactam, three isolates lacked persister formation. Cefiderocol resulted in less bacterial persistence relative to ceftolozane/tazobactam against nine clinical P. aeruginosa isolates. Cefiderocol's siderophore mechanism may be advantageous over ceftolozane/tazobactam through enhanced anti-persister effects. Clinical correlation of these findings is warranted as persisters can lead to antibiotic resistance and treatment failure.

Formulation and Evaluation of Novel Chondroitin Sulphate Based Hydrogel Containing Green- Synthesised Magnesium Oxide Nanoparticles for Treatment of Osteomyelitis- An in Vitro Study

Musculoskeletal infections, particularly osteomyelitis (OM), pose a significant challenge for patients, healthcare providers, and the healthcare system overall. Osteomyelitis of the jaw is characterized by exposed bone in the mouth that does not heal despite adequate treatment. It involves inflammation of the bone cortex and marrow, typically arising in the jaw following a chronic infection. Given the persistent nature of osteomyelitis (OM), along with its expensive and prolonged treatment process and high rates of disability, there is an urgent need for better treatment approaches. While some therapies, including vaccines and monoclonal antibodies (mAbs) have been explored, the standard treatment for OM continues to rely on identifying bacterial species, using appropriate antibiotics, removing implants, performing extensive debridement, and administering systemic antibiotics for 4 to 6 weeks. However, issues like inadequate local antibiotic concentrations due to local blood supply and various bacterial resistance mechanisms often limit the effectiveness of systemic treatments. This approach allows for higher concentrations of drugs to be delivered directly to the affected area while minimizing side effects. To lower the reinfection rate in chronic osteomyelitis treatment, the drug delivery system should be biodegradable, eliminating the need for material removal after therapy. Hence the aim of this study was to formulate and evaluate a novel chondroitin sulphate based hydrogel containing magnesium oxide nanoparticles for treatment of osteomyelitis