Advanced carbo-catalytic degradation of antibiotics using conductive polymer-seaweed biochar composite: Exploring N/S functionalization and non-radical dynamics.

Polyaniline (PANI) and Saccharina Japanica seaweed (kelp) biochar (KBC) composites were synthesized in-situ through polymerization. This study presents a novel approach to the degradation of sulfamethoxazole (SMX), a prevalent antibiotic, using a PANI-KBC composite to activate peroxymonosulfate (PMS). Extensive characterizations of the PANI-KBC composite were conducted, resulting in successful synthesis, uniform distribution of PANI on the biochar surface, and the multifunctional role of PANI-KBC in SMX degradation. A removal efficiency of 97.24% for SMX (10 mg L-1) was attained in 60 min with PANI-KBC (0.1 g L-1) and PMS (1.0 mM) at pH 5.2, with PANI-KBC showing effectiveness (>92%) across a pH range of 3.0-9.0. In the degradation of SMX, both radical (SO4•- and •OH) and non-radical (1O2 and electron transfer) pathways are involved. The reaction processes are critically influenced by the roles of SO4•-, 1O2 and electron transfer mechanisms. It was suggested that pyrrolic N, oxidized sulfur (-C-SO2-C-), structural defects, and O-CO were implicated in the production of 1O2 and electron transfer processes, respectively, and a portion of 1O2 originated from the conversion of O2•-. The study evaluated by-product toxicity, composite reusability, and stability, confirming its practical potential for sustainable groundwater remediation.

Tetracycline inhibits the nitrogen fixation ability of soybean (Glycine max (L.) Merr.) nodules in black soil by altering the root and rhizosphere bacterial communities.

Tetracycline is a widely used antibiotic and may thus also be an environmental contaminant with an influence on plant growth. The aim of this study was to investigate the inhibition mechanisms of tetracycline in relation to soybean growth and ecological networks in the roots and rhizosphere. To this end, we conducted a pot experiment in which soybean seedlings were grown in soil treated with 0, 10, or 25 mg/kg tetracycline. The effects of tetracycline pollution on growth, productivity, oxidative stress, and nitrogenase activity were evaluated. We further identified the changes in microbial taxa composition and structure at the genus and species levels by sequencing the 16S rRNA gene region. The results showed that tetracycline activates the antioxidant defense system in soybeans, which reduces the abundance of Bradyrhizobiaceae, inhibits the nitrogen-fixing ability, and decreases the nitrogen content in the root system. Tetracycline was also found to suppress the formation of the rhizospheric environment and decrease the complexity and stability of bacterial networks. Beta diversity analysis showed that the community structure of the root was markedly changed by the addition of tetracycline, which predominantly affected stochastic processes. These findings demonstrate that the influence of tetracycline on soybean roots could be attributed to the decreased stability of the bacterial community structure, which limits the number of rhizobium nodules and inhibits the nitrogen-fixing capacity. This exploration of the inhibitory mechanisms of tetracycline in relation to soybean root development emphasises the potential risks of tetracycline pollution to plant growth in an agricultural setting. Furthermore, this study provides a theoretical foundation from which to improve our understanding of the physiological toxicity of antibiotics in farmland.

Association of Acute Kidney Injury With Antibiotic Loaded Cement Used for Treatment of Periprosthetic Joint Infection.

BACKGROUND: Antibiotic-loaded bone cement (ALBC) is commonly used in the treatment of periprosthetic joint infections (PJIs) to increase the local concentration of antibiotic at the site of infection. Use of ALBC has been associated with rare instances of acute kidney injury (AKI) despite low systemic absorption of the nephrotoxic antibiotics; however, the incidence of AKI is unknown. The purpose of this study was to determine the incidence of and risk factors for AKI associated with ALBC. METHODS: This single-site, retrospective cohort study compared 162 PJI patients who underwent Stage 1 revision to a spacer with ALBC to 115 PJI patients who underwent debridement, antibiotics, and implant retention (DAIR) without the use of ALBC. Both groups received similar systemic antibiotics postoperatively. Descriptive statistics and multivariable logistic regressions were used to analyze risk factors for AKI. RESULTS: There was no statistically significant difference in the rate of AKI: 29 patients (17.9%) in the ALBC group and 17 (14.7%) in DAIR group developed AKI (odds ratio 1.43; 95% CI 0.70 to 2.93). There was a trend toward increased severity of AKI in the ALBC group. Chronic kidney disease, systemic vancomycin, and diuretic use were independent factors associated with the risk of AKI. CONCLUSION: An AKI occurred in 17% of PJI patients receiving either a spacer with ALBC or a DAIR. The use of ALBC was not associated with a significant increased risk of AKI. However, the use of systemic vancomycin and diuretic use were independent predictors of AKI in this patient population.

Kanamycin and Cisplatin Ototoxicity: Differences in Patterns of Oxidative Stress, Antioxidant Enzyme Expression and Hair Cell Loss in the Cochlea.

Kanamycin and cisplatin are ototoxic drugs. The mechanisms are incompletely known. With subcutaneous kanamycin (400 mg/kg, 15 days), auditory threshold shifts were detected at days 12-13 at 16 and 32 kHz, extending to 8 and 4 kHz at days 14-15. The outer hair cell (OHC) loss was concentrated past day 12. The maximum cochlear length showing apoptotic cells, tested with TUNEL, was at day 13. At day 15, 1/5 of the apical cochlea contained preserved OHCs. 3-nitrotyrosine (3-NT) immunolabeling, showing oxidative stress, was found in surviving OHCs and in basal and middle portions of the stria vascularis (SV). The antioxidant Gpx1 gene expression was decreased. The immunocytochemistry showed diminished Gpx1 in OHCs. With intraperitoneal cisplatin (16 mg/kg, single injection), no evoked auditory activity was recorded at the end of treatment, at 72 h. The basal third of the cochlea lacked OHCs. Apoptosis occupied the adjacent 1/3, and the apical third contained preserved OHCs. 3-NT immunolabeling was extensive in OHCs and the SV. Gpx1 and Sod1 gene expression was downregulated. Gpx1 immunostaining diminished in middle and basal SV. More OHCs survived cisplatin than kanamycin towards the apex, despite undetectable evoked activity. Differential regulation of antioxidant enzyme levels suggests differences in the antioxidant response for both drugs.

Sublethal biochemical, histopathological and genotoxicological effects of short-term exposure to ciprofloxacin in catfish Rhamdia quelen.

Ciprofloxacin (Cipro) is commonly detected in water worldwide, however, the ecotoxicological effects to aquatic biota is still not fully understood. In this study, using multiple biomarkers, it was investigated sublethal effects of short-term exposure to Cipro concentrations (1, 10 and 100 µg.L-1) in the Neotropical catfish Rhamdia quelen compared to non-exposure treatment (Control). After 96 h of exposure, the fishes were anesthetized for blood collection to hematological and genotoxicity biomarkers analysis. After euthanasia, the brain and muscle were sampled for biochemical biomarkers analyses. Gills, liver and posterior kidney for genotoxicity, biochemical and histopathological biomarkers analysis and anterior intestine for histopathological biomarkers analysis. Genotoxicity was observed in all tissues, regardless of the Cipro concentrations. Hematological alterations, such as reduction of the number of erythrocytes and leucocytes, as well as in hematocrit concentration and histopathological damages, such as reduction of microridges in gill epithelium and necrosis in liver and posterior kidney, occurred mainly at 100 µg.L-1. In addition, at 100 µg.L-1, Cipro increased antioxidant system activity (Catalase in liver and posterior kidney). These results demonstrated that under short-term exposure, Cipro causes toxic effects in R. quelen that demands attention and surveillance of environmental aquatic concentrations of this antibiotic.

Study of the Mechanisms by Which Aminoglycoside Damage Is Prevented in Chick Embryonic Hair Cells.

A major side effect of aminoglycoside antibiotics is mammalian hair cell death. It is thus intriguing that embryonic chick hair cells treated with aminoglycosides at embryonic day (E) 12 are insensitive to ototoxicity. To exclude some unknown factors in vivo that might be involved in preventing aminoglycoside damage to embryonic hair cells, we first cultured chick embryonic basilar papilla (BP) with an aminoglycoside antibiotic in vitro. The results indicated that the hair cells were almost intact at E12 and E14 and were only moderately damaged in most parts of the BP at E16 and E18. Generally, hair cells residing in the approximate and abneural regions were more susceptible to streptomycin damage. After incubation with gentamicin-conjugated Texas Red (GTTR), which is typically used to trace the entry route of aminoglycosides, GTTR fluorescence was not remarkable in hair cells at E12, was weak at E14, but was relatively strong in the proximal part of BP at E18. This result indicates that the amounts of GTTR that entered the hair cells are related to the degrees of aminoglycoside damage. The study further showed that the fluorescence intensity of GTTR decreased to a low level at E14 to E18 after disruption of mechanotransduction machinery, suggesting that the aminoglycoside entry into hair cells was mainly through mechanotransduction channels. In addition, most of the entered GTTR was not found to be colocalized with mitochondria even at E18. This finding provides another reason to explain why embryonic chick hair cells are insensitive to aminoglycoside damage.

Transcriptomic analysis of chicken cochleae after gentamicin damage and the involvement of four signaling pathways (Notch, FGF, Wnt and BMP) in hair cell regeneration.

Unlike mammalian hair cells, which are essentially unable to regenerate after damage, avian hair cells have a robust capacity for regeneration. The prerequisite for understanding the above difference is knowing the genetic programming of avian hair cell regeneration. Although the major processes have been known, the precise molecular signaling that induces regeneration remains unclear. To address this issue, we performed a high-throughput transcriptomic analysis of gene expression during hair cell regeneration in the chick cochlea after antibiotic injury in vivo. A total of 16,588 genes were found to be expressed in the cochlea, of which about 1000 genes were differentially expressed among the four groups studied, i.e., 2 days (d) or 3 d post-treatment with gentamicin or physiological saline. The differentially expressed genes were distributed across approximately one hundred signaling pathways, including the Notch, MAPK (FGF), Wnt and TGF-ß (BMP) pathways that have been shown to play important roles in embryonic development. Some differentially expressed genes (2-3 in each pathway) were further verified by qRT-PCR. After blocking Notch, FGF or BMP signaling, the number of regenerating hair cells and mitotic supporting cells increased. However, the opposite effect was observed after suppressing the Wnt pathway or enhancing BMP signaling. To our knowledge, the present study provided a relatively complete dataset of candidate genes and signaling pathways most likely involved in hair cell regeneration and should be a useful start in deciphering the genetic circuitry for inducing hair cell regeneration in the chick cochlea.

Growth, microcystin-production and proteomic responses of Microcystis aeruginosa under long-term exposure to amoxicillin.

Ecological risk of antibiotics due to the induction of antibiotic-resistant bacteria has been widely investigated, while studies on the hazard of antibiotic contaminants via the regulation of cyanobacteria were still limited. This study focused on the long-term action effect and mechanism of amoxicillin (a broadly used antibiotic) in Microcystis aeruginosa at environmentally relevant concentrations through 30 days of semi-continuous culture. Amoxicillin stimulated the photosynthesis activity and the production of microcystins, and interaction of differential proteins under amoxicillin exposure further manifested the close correlation between the two processes. D1 protein, ATP synthase subunits alpha and beta, enolase, triosephosphate isomerase and phosphoglycerate kinase were candidate target positions of amoxicillin in M. aeruginosa under long-term exposure. Amoxicillin affected the cellular biosynthesis process and the metabolism of carbohydrate and nucleoside phosphate according to the proteomic responses. Under exposure to amoxicillin, stimulated growth rate at the beginning phase and increased production and release of microcystins during the whole exposure period would lead to a higher contamination of M. aeruginosa cells and microcystins, indicating that amoxicillin was harmful to aquatic environments through the promotion of cyanobacterial bloom.

Microfluidics for Antibiotic Susceptibility and Toxicity Testing.

The recent emergence of antimicrobial resistance has become a major concern for worldwide policy makers as very few new antibiotics have been developed in the last twenty-five years. To prevent the death of millions of people worldwide, there is an urgent need for a cheap, fast and accurate set of tools and techniques that can help to discover and develop new antimicrobial drugs. In the past decade, microfluidic platforms have emerged as potential systems for conducting pharmacological studies. Recent studies have demonstrated that microfluidic platforms can perform rapid antibiotic susceptibility tests to evaluate antimicrobial drugs' efficacy. In addition, the development of cell-on-a-chip and organ-on-a-chip platforms have enabled the early drug testing, providing more accurate insights into conventional cell cultures on the drug pharmacokinetics and toxicity, at the early and cheaper stage of drug development, i.e., prior to animal and human testing. In this review, we focus on the recent developments of microfluidic platforms for rapid antibiotics susceptibility testing, investigating bacterial persistence and non-growing but metabolically active (NGMA) bacteria, evaluating antibiotic effectiveness on biofilms and combinatorial effect of antibiotics, as well as microfluidic platforms that can be used for in vitro antibiotic toxicity testing.

Use of antibiotic-loaded cement in total knee arthroplasty.

Bone cement has the capacity to release antibiotic molecules if any antibiotic is included in it, and these elution properties are improved as cement porosity is increased. In vitro studies have shown high local antibiotic concentration for many hours or few days after its use. Antibiotic loaded bone cement (ALBC) is helpful when treating an infection in total knee arthroplasty (TKA) revision surgery. The purpose of this paper was to review the evidence for the routine use of ALBC in TKA in the literature, its pros and cons. Many authors have recommended the use of ALBC also in primary TKA for infection prophylaxis, but the evidence based on data from National Registries, randomized clinical trials and meta-analysis suggest a protective effect of ALBC against infection when used in hips, but not (or only mild) in knees. A possible explanation to this finding is that the duration and quantity of locally elevated antibiotic levels after surgery are smaller in TKA, due to the smaller amount of cement used for fixation in TKA-only a layer in the bone surface. There are some concerns about the routine use of ALBC in primary TKA as prophylaxis against infection: Firstly, there is a risk of hypersensivity or toxicity even when the chance is highly improbable. Secondly, there is a reduction in the mechanical properties of the cement, but this can be probably neglected if the antibiotic is used in low doses, not more than 1 g per 40 g cement package. Another significant concern is the increased economic cost, which could be overlooked if there were enough savings in treating fewer prosthetic infections. Finally, there is also a risk of selection of antibiotic-resistant strains of bacteria and this could be the main concern. If used, the choice of the antibiotic mixed in ALBC should consider microbiological aspects (broad antimicrobial spectrum and low rate of resistant bacteria), physical and chemical aspects (thermal stability, high water solubility), pharmacological characteristics (low risk to allergic reactions or toxicity) and economic aspects (not too expensive). The most commonly used antibiotics in ALBC are gentamicin, tobramycin and vancomycin. In conclusion, there is a paucity of randomized clinical trials in the use of ALBC in primary TKAs and the actual evidence of the effect of ALBC in reducing the risk of infection is insufficient. This, in addition to concerns about patient safety, risks of increase in the antibiotic resistance of microorganisms and the increase in costs in the procedure, lead us to recommend a cautious use of ALBC, perhaps only in high-risk patients (immunocompromised, morbidly obese, diabetic and patients with previous history of fracture or infection around the knee) unless the benefits of ALBC use were fully proven. Meanwhile, the rigorous use of peri-operative prophylactic systemic antibiotics and adoption of efficient antiseptic procedures and improved surgical techniques must be considered the gold standard in infection prevention in TKA surgery.

Acute toxicity assessment of ANAMMOX substrates and antibiotics by luminescent bacteria test.

Acute toxicities of anaerobic ammonia oxidation (ANAMMOX) substrates and four antibiotics from pharmaceutical wastewaters on ANAMMOX process were reported. Individual and joint acute toxicity assays were performed using 50% inhibitory concentration (IC50). Results showed that IC50 values and their 95% confidence interval of ammonium chloride (A), sodium nitrite (B), penicillin G-Na (C), polymyxin B sulfate (D), chloramphenicol (E) and kanamycin sulfate (F) were 2708.9 (2247.9-3169.9), 1475.4 (1269.9-1680.9), 5114.4 (4946.4-5282.4), 10.2 (1.8-18.6), 409.9 (333.7-486.1) and 5254.1 (3934.4-6573.8) mgL(-1) respectively, suggesting toxicities were in the order of D>E>B>A>C>F. Joint acute toxicities of bicomponent mixtures A and B, C and D, C and F, D and F were independent; D and E, E and F were additive while C and E were synergistic. Joint acute toxicities of multicomponent mixtures were synergistic or additive. Luminescent bacteria test is an easy and robust method for forecasting the feasibility of ANAMMOX process for pharmaceutical wastewater treatment.

Effects of six antibiotics and their binary mixtures on growth of Pseudokirchneriella subcapitata.

The effect of ampicillin (AMP), amoxicillin (AMX), cephalotin (CEP), ciprofloxacin (CPF), gentamycin (GEN), and vancomycin (VAN) have been examined individually and as binary mixtures, on a non-target aquatic organism, the green alga Pseudokichneriella subcapitata. The ß-lactam antibiotics AMP and AMX were not toxic to the alga at concentrations up to 2000 mgl(-1) (less than 10% of algal growth inhibition), whereas the fluoroquinolone CPF, and the aminoglycoside GEN were the most toxic antibiotics, with an EC50=11.3 ± 0.7 mgl(-1) and 19.2 ± 0.5 mgl(-1), respectively. The cephalosporin CEP and the glycopeptide VAN were less toxic than the last two mentioned, showing an EC50>600 mgl(-1) and 724 ± 20 mgl(-1), respectively. The toxicological interactions of binary mixtures were predicted by the two classical models of additivity: concentration addition (CA) and independent action (IA), and compared to the experimentally determined toxicities over a range of concentrations between 1 and 50 mgl(-1). In all cases a clear synergistic effect was observed, showing that single compound toxicity data are not adequate for the prediction of aquatic toxicities of antibiotic mixtures. Risk assessment was performed by calculating the ratio between predicted environmental concentrations (PEC) and the predicted no effect concentration (PNEC). All the antibiotics tested, excepting GEN, have a potential ecological risk, taking into account the PEC of hospital effluents from Buenos Aires, Argentina. These risks increase when antibiotics are present in binary mixtures.