Search Results (20)

The respiratory epithelium maintains the barrier against inhaled harmful agents. When barrier failure occurs, as in several respiratory diseases, acute or chronic inflammation leading to destructive effects and exacerbations can occur. Macrolides are used to treat a spectrum of infections but are also known for off-label use. Some macrolides, particularly azithromycin (AZM), reduce exacerbations in chronic obstructive pulmonary disease (COPD), whereby its efficacy is thought to be due to its effects on inflammation and oxidative stress. In vitro data indicate that AZM reduces epithelial barrier failure, evidenced by increased transepithelial electrical resistance (TEER). Here, we compared the effects of macrolides on differentiation and barrier integrity in VA10 cells, a bronchial epithelial cell line for 14 and 21 days. Erythromycin, clarithromycin, roxithromycin, AZM, solithromycin, and tobramycin (an aminoglycoside) were analyzed using RNA sequencing, barrier integrity assays, and immunostaining to evaluate effects on the epithelium. All macrolides affected the gene expression of pathways involved in epithelial-to-mesenchymal transition, metabolism, and immunomodulation. Treatment with AZM, clarithromycin, and erythromycin raised TEER and induced phospholipid retention. AZM treatment was distinct in terms of enhancement of the epithelial barrier, retention of phospholipids, vesicle build-up, and its effect on gene sets related to keratinocyte differentiation and establishment of skin barrier. Full article

In contemporary society, the improper use of antibiotics leads to their persistent presence in the ecological environment. Due to the diverse physical and chemical properties of antibiotics, their spatial and temporal distribution in the environment varies. Moreover, antibiotics can stimulate the emergence of antibiotic resistance genes (ARGs), which complicates the monitoring and regulation of antibiotics and poses a significant threat to both aquatic and terrestrial environments. This study investigated the distribution of 15 antibiotics and 11 typical ARGs across four categories at 19 sites of drinking water sources in Wuhan, China. The findings revealed that the concentration of antibiotics during the dry season (nd~61,883 ng/L) was significantly higher compared to both the normal water season (nd~49,883 ng/L) and the wet season (nd~28,686 ng/L). Sulfamethoxazole (SMX), sulfamethoxazole (SMD), sulfadiazine (SD), and roxithromycin (RTM) were the predominant antibiotics in the target water environments. The study indicated that most of the antibiotics analyzed posed little to no risk to aquatic organisms. The primary ARGs detected in the surface water of the study area were sul1, qnrD, and tetO. Furthermore, some ARGs showed a negative correlation with their respective antibiotics. Additional research is necessary to evaluate the impact of these emerging pollutants (antibiotics and ARGs) on the safety of high-quality drinking water for residents in Wuhan City. Full article

In 2023, this study monitored nine types of antibiotics in the influent and effluent of wastewater treatment plants (WWTPs) in the urban and suburban areas of Tangshan. The total antibiotics concentration detected in influent WWTPs was highest in winter, followed by spring, summer, and autumn. The antibiotics concentration in influent and effluent urban WWTPs was higher than that in the suburban WWTPs in spring, summer, and winter, while the trend was reversed in autumn. Roxithromycin and oxytetracycline had a risk quotient (RQ) value of ≥0.1 in the effluent of WWTPs in winter, indicating that they are medium-risk antibiotics that pose a risk to the aquatic ecosystem after discharge. In the study area, the per capita pollution load of antibiotics was highest in spring, summer, and autumn for sulfamethoxazole, while it was highest in winter for ofloxacin. In the urban area, the use of roxithromycin, sulfamethoxazole, sulfamethoxazole, and ofloxacin was highest in spring, summer, autumn, and winter, respectively, while in suburban areas, the use of sulfamethoxazole, norfloxacin, sulfamethoxazole, and ofloxacin was highest during the same period. The use of antibiotics in the urban area was one order of magnitude higher than that in suburban areas, indicating a possible overuse of antibiotics in urban environments. Full article

Background: Prior research has raised concerns regarding the use of macrolides and their association with an increased risk of cardiovascular events. Methods: We conducted a cohort study, where we explored the cardiovascular risks associated with the treatment of COPD patients using macrolide antibiotics–namely azithromycin, clarithromycin, and roxithromycin—with amoxicillin serving as a reference. The study focused on COPD patients in an outpatient setting and included a thorough 3-year follow-up. Patients were categorized into four groups based on their treatment. The primary analysis utilized an adjusted Cox model, supplemented by sensitivity analysis through inverse probability of treatment weighting. Results: No significant differences were found in major adverse cardiovascular events (MACE—stroke, acute myocardial infarction, cardiovascular death) between the macrolide groups, and the amoxicillin/hazard ratios (HR) were azithromycin HR = 1.01, clarithromycin HR = 0.99, and roxithromycin HR = 1.02. Similarly, sensitivity analysis showed no disparities in all-cause mortality and cardiovascular death among the groups. Conclusions: Overall, the study revealed no evidence of increased risk of MACE, all-cause mortality, or cardiovascular death in COPD patients treated with these macrolides compared to amoxicillin over a 3-year period. Full article

The amount of macrolide (MAL) residues in aquatic products, including oleandomycin (OLD), erythromycin (ERM), clarithromycin (CLA), azithromycin (AZI), kitasamycin (KIT), josamycin (JOS), spiramycin (SPI), tilmicosin (TIL), tylosin (TYL), and roxithromycin (ROX), was determined using solid-phase extraction and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). The residues were extracted with 1% ammonia acetonitrile solution and purified by neutral alumina adsorption. Chromatographic separation was completed on an ACQUITY UPLC BEH C₁₈ column with acetonitrile–0.1% formic acid aqueous solution as the mobile phase, and mass spectrometry detection was performed by multiple reaction monitoring scanning with the positive mode in an electrospray ion source (ESI⁺). Five isotopically labeled compounds were used as internal standards for quality control purposes. The findings indicated that across the mass concentration span of 1.0–100 μg/L, there was a strong linear correlation (R² > 0.99) between the concentration and instrumental response for the 10 MALs. The limit of detection of UPLC-MS/MS was 0.25–0.50 μg/kg, and the limit of quantitation was 0.5–1.0 μg/kg. The added recovery of blank matrix samples at standard gradient levels (1.0, 5.0, and 50.0 μg/kg) was 83.1–116.6%, and the intra-day precision and inter-day precisions were 3.7 and 13.8%, respectively. The method is simple and fast, with high accuracy and good repeatability, in line with the requirements for accurate qualitative and quantitative analysis of the residues for 10 MALs in aquatic products. Full article

Background: The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the mainstay of CRS therapies. However, their impact on microbial communities needs to be better understood. This systematic review summarizes the evidence about antibiotics’ and steroids’ impact on the nasal microbiota in patients with CRS. Methods: The search strategy was conducted in accordance with the PRISMA guidelines for systematic reviews. The authors searched all papers in the three major medical databases (PubMed, Scopus, and Cochrane Library) using the PICO tool (population, intervention, comparison, and outcomes). The search was carried out using a combination of the key terms “Microbiota” or “Microbiome” and “Chronic Rhinosinusitis”. Results: Overall, 402 papers were identified, and after duplicate removal (127 papers), excluding papers off-topic (154) and for other structural reasons (110), papers were assessed for eligibility; finally, only 11 papers were included and summarized in the present systematic review. Some authors used only steroids, other researchers used only antibiotics, and others used both antibiotics and steroids. With regard to the use of steroids as exclusive medical treatment, topical mometasone and budesonide were investigated. With regard to the use of antibiotics as exclusive medical treatments, clarithromycin, doxycycline, roxithromycin, and amoxicillin clavulanate were investigated. Regarding the use of both antibiotics and steroids, two associations were investigated: systemic prednisone combined with amoxicillin clavulanate and topical budesonide combined with azithromycin. Conclusions: The impact that therapies can have on the nasal microbiome of CRS patients is very varied. Further studies are needed to understand the role of the nasal microbiome, prevent CRS, and improve therapeutic tools for personalized medicine tailored to the individual patient. Full article

Macrolide antibiotics, which are effective antimicrobial agents, are intensively used in human and veterinary medicine, as well as in agriculture. Consequently, they are found all over the world as environmental pollutants, causing harm to sensitive ecological communities and provoking a selection of resistant forms. A novel azithromycin derivative, which was used as hapten conjugate, ensured the group immunorecognition of six major macrolide representatives (105–41%), namely erythromycin, erythromycin ethylsuccinate, clarithromycin, roxithromycin, azithromycin, and dirithromycin in a competitive immunoassay based on anti-clarithromycin antibodies. The heterologous hapten-based ELISA format resulted in a 5-fold increase in sensitivity, with an IC₅₀ value of 0.04 ng/mL for erythromycin. In this study, we proposed an underexploited strategy in an immunoassay field to significantly improve the detectability of analytes in environmental samples. Unlike most approaches, it does not require special enhancers/amplifiers or additional concentration/extraction procedures; instead, it involves analyzing a larger volume of test samples. A gradual volume increase in the samples (from 0.025 to 10 mL) analyzed using a direct competitive ELISA, immunobeads, and immunofiltration assay formats based on the same reagents resulted in a significant improvement (more than 50-fold) in assay sensitivity and detection limit up to 5 and 1 pg/mL, respectively. The suitability of the test for detecting the macrolide contamination of natural water was confirmed by the recovery of macrolides from spiked blank samples (71.7–141.3%). During 2022–2023, a series of natural water samples from Lake Onega and its influents near Petrozavodsk were analyzed, using both the developed immunoassay and HPLC-MS/MS. The results revealed no contamination of macrolide antibiotic. Full article

A total of 34 antibiotics from five major classes of antibiotics, including macrolides, sulfonamides, quinolones, tetracyclines and chloramphenicol, were considered as contaminants, considering the Yellow River Estuary as the study area. The distribution, sources and ecological risks of typical antibiotics in the Yellow River Estuary were investigated using an optimized solid-phase extraction pre-treatment and an Agilent 6410B tandem triple-quadrupole liquid chromatography–mass spectrometer for antibiotic detection. The results show that antibiotics were widely present in the water bodies of the Yellow River Estuary, with 14 antibiotics detected to varying degrees, including a high detection rate for lincomycin hydrochloride. Farming wastewater and domestic sewage were the primary sources of antibiotics in the Yellow River Estuary. The distribution characteristics of antibiotics in the study area were linked to the development of farming and social activities. The ecological risk evaluation of 14 antibiotics in the Yellow River Estuary watershed showed that clarithromycin and doxycycline hydrochloride were present at medium-risk levels, and lincomycin hydrochloride, sulfamethoxazole, methomyl, oxifloxacin, enrofloxacin, sulfadiazine, roxithromycin, sulfapyridine, sulfadiazine and ciprofloxacin were present at low-risk levels in the samples collected from water bodies of the Yellow River Estuary. This study provides novel, beneficial information for the assessment of the ecological risk presented by antibiotics in the Yellow River Estuary water bodies and provides a scientific basis for future antibiotic pollution control in the Yellow River Basin. Full article

The ability of WWTP outflow bacteria at colonizing rock surfaces and contributing to the formation of river epilithic biofilms was investigated. Bacterial community structures of biofilms (b-) developing on rocks exposed to treated wastewaters (TWW) of a hospital (HTWW) and a domestic (DTWW) clarifier, and to surface waters of the stream located at 10 m, 500 m, and 8 km from the WWTP outlet, were compared. Biofilm bacterial contents were analyzed by cultural approaches and a tpm-based DNA metabarcoding analytical scheme. Co-occurrence distribution pattern analyses between bacterial datasets and eighteen monitored pharmaceuticals were performed. Higher concentrations of iohexol, ranitidine, levofloxacin, and roxithromycin were observed in the b-HTWW while atenolol, diclofenac, propranolol, and trimethoprim were higher in the b-DTWW. MPN growth assays showed recurrent occurrences of Pseudomonas aeruginosa and Aeromonas caviae among these biofilms. An enrichment of multi-resistant P. aeruginosa cells was observed in the hospital sewer line. P. aeruginosa MPN values were negatively correlated to roxithromycin concentrations. The tpm DNA metabarcoding analyses confirmed these trends and allowed an additional tracking of more than 90 species from 24 genera. Among the recorded 3082 tpm ASV (amplicon sequence variants), 41% were allocated to the Pseudomonas. Significant differences through ANOSIM and DESeq2 statistical tests were observed between ASV recovered from b-HTWW, b-DTWW, and epilithic river biofilms. More than 500 ASV were found restricted to a single sewer line such as those allocated to Aeromonas popoffii and Stenotrophomonas humi being strictly found in the b-HTWW file. Several significant correlations between tpm ASV counts per species and pharmaceutical concentrations in biofilms were recorded such as those of Lamprocystis purpurea being positively correlated with trimethoprim concentrations. A tpm source tracking analysis showed the b-DTWW and b-HTWW tpm ASV to have contributed, respectively, at up to 35% and 2.5% of the epilithic river biofilm tpm-taxa recovered downstream from the WWTP outlet. Higher contributions of TWW taxa among epilithic biofilms were recorded closer to the WWTP outlet. These analyses demonstrated a coalescence of WWTP sewer communities with river freshwater taxa among epilithic biofilms developing downstream of a WWTP outlet. Full article

Japanese seabass (Lateolabrax japonicus) is an important species of cultured marine fish with high economic value in China. Nevertheless, from May to November 2019, mass mortality among cultured Japanese seabass occurred in Zhuhai City, Guangdong Province of China. Approximately 0.2–0.5% mortality was recorded daily, and the cumulative mortality was up to 30% during this disease outbreak. In this study, the clinical signs and pathological characteristics of diseased fish were investigated. Furthermore, the pathogenicity and antibiotic sensitivity of identified pathogenic bacteria from diseased fish were analyzed. The infected fish showed clinical signs of uncoordinated swimming; anorexia; pigment changes; and a number of 1–5 mm grayish-white nodules in the liver, spleen, and kidney tissues was also found. A bacterial strain, which was designated as ZHLJ2019, was isolated from the diseased fish. To ensure that ZHLJ2019 isolate was the causative agent, a Koch postulate trial was performed. Healthy Japanese seabass were infected by the intraperitoneal injection of 5 × 10⁴, 5 × 10⁵ and 5 × 10⁶ CFU/fish, and cumulative mortalities within 42 days were 75%, 90%, and 100%, respectively. The bacteria colony had traditional morphological and biochemical characteristics similar to that of Mycobacterium marinum. Phylogenetic molecular analyses of 16S rRNA, rpoB, hsp65, erp, and ITS genes confirmed that the isolated strain ZHLJ2019 was M. marinum. The granulomatous inflammation in internal organs of Japanese seabass naturally and experimentally infected with ZHLJ2019 isolate was consistent with the classic pathological features of mycobacteriosis. Drug susceptibility of ZHLJ2019 isolate to 11 antibiotics was determined by broth dilution method in vitro. The minimum inhibitory concentrations (MICs) of minocycline, rifampicin, ethambutol, isoniazid, streptomycin, doxycycline hydrochloride, kanamycin sulfate, levofloxacin, roxithromycin, and prothionamide against the strain ZHLJ2019 were 4, 2, 8, 4, 16, 8, 8, 8, 4, and 8 μg/mL, respectively. The results of this study suggest that M. marinum is the causal agent responsible for the morbidity and mortality of Japanese seabass cultured in intensive brackish water dirt ponds in southern China. Full article

Mutated channelopathy could play important roles in the pathogenesis of aldosterone-producing adenoma (APA). In this study, we identified a somatic mutation, KCNJ5 157-159delITE, and reported its immunohistological, pathophysiological and pharmacological characteristics. We conducted patch-clamp experiments on HEK293T cells and experiments on expression of aldosterone synthase (CYP11B2) and aldosterone secretion in HAC15 cells to evaluate electrophysiological and functional properties of this mutated KCNJ5. Immunohistochemistry was conducted to identify expressions of several steroidogenic enzymes. Macrolide antibiotics and a calcium channel blocker were administrated to evaluate the functional attenuation of mutated KCNJ5 channel in transfected HAC15 cells. The interaction between macrolides and KCNJ5 protein was evaluated via molecular docking and molecular dynamics simulation analysis. The immunohistochemistry analysis showed strong CYP11B2 immunoreactivity in the APA harboring KCNJ5 157-159delITE mutation. Whole-cell patch-clamp data revealed that mutated KCNJ5 157-159delITE channel exhibited loss of potassium ion selectivity. The mutant-transfected HAC15 cells increased the expression of CYP11B2 and aldosterone secretion, which was partially suppressed by clarithromycin and nifedipine but not roxithromycin treatment. The docking analysis and molecular dynamics simulation disclosed that roxithromycin had strong interaction with KCNJ5 L168R mutant channel but not with this KCNJ5 157-159delITE mutant channel. We showed comprehensive evaluations of the KCNJ5 157-159delITE mutation which revealed that it disrupted potassium channel selectivity and aggravated autonomous aldosterone production. We further demonstrated that macrolide antibiotics, roxithromycin, could not interfere the aberrant electrophysiological properties and gain-of-function aldosterone secretion induced by KCNJ5 157-159delITE mutation. Full article

The phenomenon of drug burst release is the main problem in the field of drug delivery systems, as it means that a good therapeutic effect cannot be acheived. Nanofibers developed by electrospinning technology have large specific surface areas, high porosity, and easily controlled morphology. They are being considered as potential carriers for sustained drug release. In this paper, we obtained polycaprolactone (PCL)/polylactic acid (PLA) core-shell porous drug-carrying nanofibers by using coaxial electrospinning technology and the nonsolvent-induced phase separation method. Roxithromycin (ROX), a kind of antibacterial agent, was encapsulated in the core layer. The morphology, composition, and thermal properties of the resultant nanofibers were characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermogravimetry analysis (TGA). Besides this, the in vitro drug release profile was investigated; it showed that the release rate of the prepared coaxial porous nanofibers with two different pore sizes was 30.10 ± 3.51% and 35.04 ± 1.98% in the first 30 min, and became 92.66 ± 3.13% and 88.94 ± 1.58% after 14 days. Compared with the coaxial nonporous nanofibers and nanofibers prepared by uniaxial electrospinning with or without pores, the prepared coaxial porous nanofibers revealed that the burst release was mitigated and the dissolution rate of the hydrophobic drugs was increased. The further antimicrobial activity demonstrated that the inhibition zone diameter of the coaxial nanofibers with two different pore sizes was 1.70 ± 0.10 cm and 1.73 ± 0.23 cm, exhibiting a good antibacterial effect against Staphylococcus aureus. Therefore, the prepared nanofibers with the coaxial porous structures could serve as promising drug delivery systems. Full article

Cellular senescence is a cellular condition that involves significant changes in gene expression and the arrest of cell proliferation. Recently, it has been suggested in experimental models that the elimination of senescent cells with pharmacological methods delays, prevents, and improves multiple adverse outcomes related to age. In this sense, the so-called senoylitic compounds are a class of drugs that selectively eliminates senescent cells (SCs) and that could be used in order to delay such adverse outcomes. Interestingly, the first senolytic drug (navitoclax) was discovered by using chemoinformatic and network analyses. Thus, in the present study, we searched for novel senolytic compounds through the use of chemoinformatic tools (fingerprinting and network pharmacology) over different chemical databases (InflamNat and BIOFACQUIM) coming from natural products (NPs) that have proven to be quite remarkable for drug development. As a result of screening, we obtained three molecules (hinokitiol, preussomerin C, and tanshinone I) that could be considered senolytic compound candidates since they share similarities in structure with senolytic leads (tunicamycin, ginsenoside Rb1, ABT 737, rapamycin, navitoclax, timosaponin A-III, digoxin, roxithromycin, and azithromycin) and targets involved in senescence pathways with potential use in the treatment of age-related diseases. Full article

Neonatal sepsis caused by resistant bacteria is a worldwide concern due to the associated high mortality and increased hospitals costs. Bacterial pathogens causing neonatal sepsis and their antibiotic resistance patterns vary among hospital settings and at different points in time. This study aimed to determine the antibiotic resistance patterns of pathogens causing neonatal sepsis and to assess trends in antibiotic resistance. The study was conducted among neonates with culture proven sepsis at the University Hospital of Leipzig between November 2012 and September 2020. Blood culture was performed by BacT/ALERT 3D system. Antimicrobial susceptibility testing was done with broth microdilution method based on ISO 20776-1 guideline. Data were analyzed by SPSS version 20 software. From 134 isolates, 99 (74%) were gram positive bacteria. The most common gram positive and gram negative bacteria were S. epidermidis, 51 (38%) and E. coli, 23 (17%), respectively. S. epidermidis showed the highest resistance to penicillin G and roxithromycin (90% each) followed by cefotaxime, cefuroxime, imipenem, oxacillin, and piperacillin-tazobactam (88% each), ampicillin-sulbactam (87%), meropenem (86%), and gentamicin (59%). Moreover, S. epidermidis showed raising levels of resistance to amikacin, gentamicin, ciprofloxacin, levofloxacin, moxifloxacin, and cotrimoxazol. Gram positive bacteria showed less or no resistance to daptomycin, linezolid, teicoplanin, and vancomycin. E. coli showed the highest resistance to ampicillin (74%) followed by ampicillin-sulbactam (52%) and piperacillin (48%). Furthermore, increasing levels in resistance to ampicillin, ampicillin-sulbactam, piperacillin, and cefuroxime were observed over the years. Encouragingly, E. coli showed significantly declining trends of resistance to ciprofloxacin and levofloxacin, and no resistance to amikacin, colistin, fosfomycin, gentamicin, imipenem, piperacillin-tazobactam, and tobramycin. In conclusion, this study demonstrates that gram positive bacteria were the leading causes of neonatal sepsis. Bacterial isolates were highly resistant to first and second-line empiric antibiotics used in this hospital. The high levels of antibiotic resistance patterns highlight the need for modifying empiric treatment regimens considering the most effective antibiotics. Periodic surveillance in hospital settings to monitor changes in pathogens, and antibiotic resistance patterns is crucial in order to implement optimal prevention and treatment strategies. Full article

The gut microbiome is vital to the health and development of an organism, specifically in determining the host response to a chemical (drug) administration. To understand this, we investigated the effects of six antibiotic (AB) treatments (Streptomycin sulfate, Roxithromycin, Sparfloxacin, Vancomycin, Clindamycin and Lincomycin hydrochloride) and diet restriction (–20%) on the gut microbiota in 28-day oral toxicity studies on Wistar rats. The fecal microbiota was determined using 16S rDNA marker gene sequencing. AB-class specific alterations were observed in the bacterial composition, whereas restriction in diet caused no observable difference. These changes associated well with the changes in the LC–MS/MS- and GC–MS-based metabolome profiles, particularly of feces and to a lesser extent of plasma. Particularly strong and AB-specific metabolic alterations were observed for bile acids in both plasma and feces matrices. Although AB-group-specific plasma metabolome changes were observed, weaker associations between fecal and plasma metabolome suggest a profound barrier between them. Numerous correlations between the bacterial families and the fecal metabolites were established, providing a holistic overview of the gut microbial functionality. Strong correlations were observed between microbiota and bile acids, lipids and fatty acids, amino acids and related metabolites. These microbiome–metabolome correlations promote understanding of the functionality of the microbiome for its host. Full article