Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin.

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.

Roxithromycin exposure induces motoneuron malformation and behavioral deficits of zebrafish by interfering with the differentiation of motor neuron progenitor cells.

Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development. Early exposure to ROX induces marked developmental toxicity in zebrafish embryos, significantly reducing hatching rates (n=100), body lengths (n=100), and increased malformation rates (n=100). The zebrafish embryos treated with a corresponding volume of DMSO (0.1%, v/v) served as vehicle controls (veh). Moreover, ROX exposure adversely affected the locomotive capacity of zebrafish embryos, and observations in transgenic zebrafish Tg(hb9:eGFP) revealed axonal loss in motor neurons, evident through reduced or irregular axonal lengths (n=80). Concurrently, abnormal apoptosis in ROX-exposed zebrafish embryos intensified alongside the upregulation of apoptosis-related genes (bax, bcl2, caspase-3a). Single-cell sequencing further disclosed substantial effects of ROX on genes involved in the differentiation of motor neuron progenitor cells (ngn1, olig2), axon development (cd82a, mbpa, plp1b, sema5a), and neuroimmunity (aplnrb, aplnra) in zebrafish larvae (n=30). Furthermore, the CaP motor neuron defects and behavioral deficits induced by ROX can be rescued by administering ngn1 agonist (n=80). In summary, ROX exposure leads to early-life abnormalities in zebrafish motor neurons and locomotor behavior by hindering the differentiation of motor neuron progenitor cells and inducing abnormal apoptosis.

A systematic review and meta-analysis of macrolides in the management of adult patients with asthma.

BACKGROUND: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma. METHODS: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides. RESULTS: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo. CONCLUSIONS: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma.

Evaluation of Roxithromycin as a Treatment Option for Small Abdominal Aortic Aneurysms: An Integrated Study of Meta-analysis and Network Pharmacology.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a segmental, progressive, and fatal vascular disorder, and the current strategy for small AAAs is close observation alone.The purpose of this study is to summarize the available evidence to assess the effects of antibiotics on small abdominal aortic aneurysms (AAA). METHODS: We searched PubMed, EMBASE, Web of Science, and Scopus from inception to September 29, 2023, and included randomized controlled trials (RCTs) that evaluated the effects of antibiotics on small AAAs in humans. We first performed a meta-analysis to assess the effects of antibiotics on small AAAs. Afterward, network pharmacology analysis was applied to investigate the optimal drug generated from the meta-analysis results. We searched Pharmmapper and GeneCards to obtain the common potential targets of the selected drug and AAA-related targets. The protein-protein interaction network and functional enrichment analysis were performed by the STRING database, Cytoscape 3.7.2 software, and R, respectively. Docking studies were carried out for validation. RESULTS: We incorporated data from six RCTs involving a total of 997 patients. The results of this meta-analysis revealed that roxithromycin exhibited a modest yet statistically significant protective effect in terms of slowing down the AAA expansion rate. Furthermore, our subsequent bioinformatics analysis pinpointed MMP-2, MMP-9, ALB, MMP-3, and CCL-5 as potential therapeutic targets that could be explored for the treatment of AAA using roxithromycin. CONCLUSION: In conclusion, the study indicates roxithromycin is a promising drug for treating small AAAs and supports its underlying clinical use in small AAAs.

Roxithromycin and rhEGF Co-loaded Reactive Oxygen Species Responsive Nanoparticles for Accelerating Wound Healing.

BACKGROUND: Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation. OBJECTIVE: Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat Staphylococcus aureus-infected wounds. METHODS: By using our previously prepared reactive oxygen species-responsive material (Oxi-αCD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-αCD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-αCD NPs) were successfully fabricated. The in vivo efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds. RESULTS: ROX/Oxi-αCD NPs and rhEGF/ROX/Oxi-αCD NPs had a spherical structure and their particle sizes were 164 ± 5 nm and 190 ± 8 nm, respectively. The in vitro antibacterial experiments showed that ROX/Oxi-αCD NPs had a lower minimum inhibitory concentration than ROX. The in vivo animal experiments demonstrated that rhEGF/ROX/Oxi-αCD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-αCD NPs (P < 0.05). CONCLUSION: ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.

Competitive adsorption and bioaccumulation of sulfamethoxazole and roxithromycin by sediment and zebrafish (Danio rerio) during individual and combined exposure in water.

Antibiotics are extensively used for health protection and food production, causing antibiotic pollution in the aquatic environment. This study aims to determine the bioavailability and bioaccumulation of typical antibiotics sulfamethoxazole (SMX) and roxithromycin (RTM) in zebrafish under environmentally realistic conditions. Four different microcosms, i.e. water, water-sediment, water-zebrafish, and water-sediment-zebrafish were constructed, with three replicates in parallel. The concentrations of SMX and RTM in water, sediment and zebrafish were extracted and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) to assess their kinetic behavior and bioavailability. In the water-sediment system, the dissolved concentration of both SMX and RTM decreased with time following the first-order kinetic while their adsorption by sediment increased with time. In the water-zebrafish system, SMX and RTM bioaccumulation was increasing with time following the pseudo second-order kinetics. RTM bioaccumulation in zebrafish (up to 16.4 ng/g) was an order of magnitude higher than SMX (up to 5.2 ng/g), likely due to RTM being more hydrophobic than SMX. In addition, the bioaccumulation factor (BAF) value of SMX in zebrafish was greater than its sediment partition coefficient, while the opposite trend was observed for RTM, demonstrating the importance of antibiotics properties in affecting their bioavailability. Furthermore, increasing dissolved organic carbon concentration in water reduced SMX bioaccumulation, but increased RTM bioaccumulation at the same time. The findings are important in future studies of environmental fate and bioavailability of toxic chemicals with different pollution sources and physicochemical properties.

Effects of ammonia and roxithromycin exposure on skin mucus microbiota composition and immune response of juvenile yellow catfish Pelteobagrus fulvidraco.

As an inevitable factor in aquaculture, ammonia plays a critical role in macrolide antibiotic resistance, leading to accumulating of antibiotic-resistant bacteria in fish skin mucus. In this study, four experimental groups were implemented to test the effects of ammonia alone or in combination with roxithromycin for 28 days on skin mucus microbial composition and the immune response of yellow catfish: CON (control), AN (50.00 mg L-1 total ammonia nitrogen, TA-N), ROX (100 µg L-1 roxithromycin), and HR (50.00 mg L-1 TA-N, 100 µg L-1 ROX). This study demonstrated that ammonia or roxithromycin exposure resulted in increased plasma ammonia content and decreased total antioxidant capacity. Compared with AN group, the combined exposure of ammonia and roxithromycin inhibited the skin mucus immune response. Microbial composition analysis showed that combined exposure of ammonia and roxithromycin had no significant effect on skin mucus α-diversity as compared with CON group. The abundance of Cetobacterium, Rhizobiales_Incertae_Sedis_uncultured and Acinetobacter was increased significantly with the combined effect of ammonia and roxithromycin, these bacteria may be potentially antibiotic-resistant. As compared with CON group, the combined exposure of ammonia and roxithromycin did not affect skin goblet cell counts. This study suggests that combined exposure to ammonia and ROX increases the risk of the emergence of antibiotic-resistant bacteria.

Treatment of aseptic facial granuloma as a manifestation of pediatric rosacea with oral macrolides.

Aseptic facial granuloma is a rare pediatric disease, presenting with asymptomatic facial nodules on the cheeks or the eyelids and may represent a form of granulomatous rosacea in children. In this retrospective case series, 12 children with aseptic facial granuloma were treated with oral macrolides (erythromycin or roxithromycin) resulting in a healing of the lesions within a mean treatment time of 5.25 months with no recurrences. The treatment was mainly well tolerated. Oral macrolides may be effective in the treatment of patients with aseptic facial granuloma.

Childhood granulomatous periorificial dermatitis in 31 Chinese children successfully treated with oral roxithromycin.

Data regarding the treatment of childhood granulomatous periorificial dermatitis (CGPD) using oral therapies are limited. This study included 31 Chinese children with CGPD treated with oral roxithromycin. After 12 weeks of treatment, 90.3% of the patients recovered, and there were no severe adverse effects. Our results suggest that oral roxithromycin is an effective and safe treatment for CGPD.

Seasonal facial erythema in a patient with allergic rhinitis treated using a combination of tranilast and roxithromycin.

OBJECTIVE: A competitive effect with suppression of Th2 immune responses of the tranilast and roxithromycin combination is examined in an allergic rhinitis patient. PATIENT AND METHODS: A 42-year-old female patient with allergic rhinitis caused by cedar pollen, which is one of the most common allergies during the spring, exhibited facial erythema with itching, particularly on both cheeks, and rhinitis symptoms, such as nasal discharge, and 200 mg/day of tranilast (original) and 300 mg/day of roxithromycin were administered. RESULTS: After 2 weeks, the patient's skin lesions were mostly eliminated, with the skin appearing almost normal; itching was nearly absent; and rhinitis symptoms disappeared. CONCLUSION: This combination may be a promising new therapeutic strategy for allergic rhinitis.

Pregnancy outcomes following maternal macrolide use: A systematic review and meta-analysis.

To determine whether gestational use of all or specific macrolides (azithromycin, clarithromycin, roxithromycin or erythromycin) lead to an increase in rates of overall major congenital malformations, organ-specific malformations, and other adverse pregnancy outcomes in infants. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox® databases were searched. Dichotomous outcomes or calculated log odds ratios and standard errors from observational studies are combined using the random-effects method in Review Manager 5.3. No significant increased risks for major congenital malformation (OR 1.06 [95% CI 0.99, 1.13]) and congenital heart defect (OR 1.05 [95% CI 0.92, 1.19]) following all macrolides use during the first trimester were detected. Prenatal azithromycin use was associated with a significantly increased risk of major congenital malformations in the analysis of cohort studies (OR 1.21 [95% CI 1.08-1.36]). This significance was also present in the sensitivity analysis. There were no statistically significant associations between the risk of organ specific malformations and all or specific macrolide exposures except for the decreased risk in hypospadias following erythromycin use in the meta-analysis of case-control studies (OR 0.38 [95% CI 0.18, 0.81]. Also, a significant 1.5-fold increased risk for spontaneous abortion following macrolide use was detected. A slight yet significantly increased rate of major congenital malformation with azithromycin exposure during pregnancy may be associated with maternal confounders. Nevertheless, level II ultrasound can be suggested following maternal azithromycin use during the first trimester. Future studies should take into account the inclusion of a disease-matched control group and accurate classification of the malformations.

Transformation of macrolide antibiotics during chlorination process: Kinetics, degradation products, and comprehensive toxicity evaluation.

Antibiotics are ubiquitous in wastewater and surface water and their presence is of grave concern. Chlorination, an important disinfection process used in wastewater treatment plants and waterworks, causes antibiotics to be degraded. However, interactions of antibiotics with chlorine result in the generation of multiple transformation products (TPs). TPs may be more toxic than the parent compounds, but their structures, yields and ecotoxicity remain to be ascertained in most cases. This study examined the degradation by chlorine of two typical macrolide (MLs) antibiotics, erythromycin (ERY) and roxithromycin (ROX), and identified the TPs formed as a result of ERY and ROX chlorination. The ecotoxicity of ERY, ROX and their TPs was evaluated using a combination of bioassay and ECOSAR prediction. The degradation of ERY and ROX followed pseudo-first-order kinetic at the molar ratio of FAC to MLs of 10:1, and the degradation kinetic rate depends on pH values. Six TPs of ERY including three chlorinated TPs, and six TPs of ROX including two chlorinated TPs were identified. The tertiary N of the desosamine moiety of ERY and ROX was determined to be the main reactive site. Demethylation and chlorine substitution at the reactive site are the main degradation pathways of ERY and ROX. ECOSAR results showed that the chlorinated byproducts of ERY TP578, TP542 and TP528, and the reduced hydroxylation products of ROX TP851 exhibited higher ecotoxicity than their parent compounds. However, algae growth inhibition assays indicated that the overall ecotoxicity of the chlorinated ERY or ROX mixture was lower than that of ERY or ROX prior to chlorination. This may be attributed to the removal of the parent compound and lower yields of toxic substances. While the yields of the toxic TPs may be low, their accumulation and combined effects of the TPs and other co-occurring pollutants should be examined further.

Application of moving bed biofilm reactor - nanofiltration - membrane bioreactor with loose nanofiltration hollow fiber membranes for synthetic roxithromycin-containing wastewater treatment: Long-term performance, membrane fouling and microbial community.

The present study operated the novel moving bed biofilm reactor-nanofiltration-membrane bioreactor (MBBR-NF-MBR) with loose polyamide NF membranes for the first time to treat roxithromycin (ROX) wastewater. Results showed that both MBBR-NF-MBRs achieved superior COD removal of 98.4% and 97.2% and excellent removal of ROX at 74.1% and 65.5%, respectively. The main membrane fouling mechanism was reversible fouling caused by the combination of abundant polysaccharides, proteins and Ca-P precipitates, which could be effectively removed by acidic cleaning. Sorption and biodegradation were the main removal routes of ROX in MBBR. Partial retention of loose NF membrane contributed to microbial metabolism and increased microbial diversity, especially the genera Hyphomicrobium in attached biofilm, which was reasonable for ROX removal. The cleavage of cladinose, demethylation, phosphorylation and ß-oxidation in macrolactone ring were the main biotransformation reactions of ROX. This study provides novel insights for micropollutants wastewater treatment by using loose NF membrane in MBR.

Lichen Planopilaris Arising between Two Linear Surgical Scars.

Lichen planopilaris (LPP) is a type of lymphocytic cicatricial alopecia, which can occur at unusual sites. It can be difficult to diagnose at an early stage and may be misdiagnosed as seborrheic dermatitis or psoriasis in early stages before alopecia occurs. We report a rare case in which alopecia occurred between two long surgical scars on the scalp several years after surgery. Dermoscopy and biopsy led to a diagnosis of LPP. The localization of the lesions in our case suggests that oxidative stress from the failure of lymph flow might have induced LPP. Oral roxithromycin, a macrolide antibiotic, with anti-oxidative and anti-inflammatory was effective at stopping its progression.

Intergenerational and biological effects of roxithromycin and polystyrene microplastics to Daphnia magna.

The influence of microplastics (MPs) on transgenerational effects of pharmaceuticals are drawing growing attention, however, whether aged process will alter the carrier effects of MPs were unknown. In this study, the intergenerational toxicity of single and combined exposure of polystyrene microplastics (PS-MPs) and roxithromycin (ROX) were investigated at the environmentally related concentrations, using Daphina magna as test organism. In the presence of UV-aged PS-MPs, the survival of D. magna for maternal generation (F0) at ROX concentration of 0.1 and 10 µg/L were increased by 20% and 40%, respectively. Meanwhile, the inhibition effects of ROX on the number of offspring and intrinsic rate of natural increase were obviously moderated. All these reproductive toxicity of ROX and PS-MPs in the first offspring (F1) were further aggravated both for the single and combined exposure. And the adverse effects disappeared much easier for the single exposure compared to the co-exposure through subsequent recovery. The combined exposure resulted in the change of inhibition of ROX on the swimming velocity and acceleration of D. magna into induction, while the feeding behavior kept inhibited. The AChE activity was distinctly increased by 1.61-3.25 times for the single and combined treatments, and the induction level of UV-aged MPs was higher than that of original MPs. Oxidative stress of the single exposure of ROX and original PS-MPs was observed with obvious induction of T-AOC and SOD activity, while the significant increase of MDA content was observed for the co-exposure. Among all indicators, the biochemical biomarkers and time of first brood were attributed to a class among all indicators, indicating that the time of first brood might be the most sensitive reproductive toxicity index. These results illustrated that both maternal impacts and offspring quality need to be considered for assessment of interaction of emerging contaminants.

The Effect of Macrolides on Mortality in Bacteremic Pneumococcal Pneumonia: A Retrospective, Nationwide Cohort Study, Israel, 2009-2017.

BACKGROUND: Previous cohort studies of pneumonia patients reported lower mortality with advanced macrolides. Our aim was to characterize antibiotic treatment patterns and assess the role of quinolones or macrolides in empirical therapy. MATERIALS: An historical cohort, 1 July 2009 to 30 June 2017, included, through active surveillance, all culture-confirmed bacteremic pneumococcal pneumonia (BPP) among adults in Israel. Cases without information on antibiotic treatment were excluded. Logistic regression analysis was used to assess independent predictors of in-hospital mortality. RESULTS: A total of 2016 patients with BPP were identified. The median age was 67.2 years (interquartile range [IQR] 53.2-80.6); 55.1% were men. Lobar pneumonia was present in 1440 (71.4%), multi-lobar in 576 (28.6%). Median length of stay was 6 days (IQR 4-11). A total of 1921 cases (95.3%) received empiric antibiotics with anti-pneumococcal coverage: ceftriaxone, in 1267 (62.8%). Coverage for atypical bacteria was given to 1159 (57.5%), 64% of these, with macrolides. A total of 372 (18.5%) required mechanical ventilation, and 397 (19.7%) died. Independent predictors of mortality were age (odds ratio [OR] 1.051, 95% confidence interval [CI] 1.039, 1.063), being at high-risk for pneumococcal disease (OR 2.040, 95% CI 1.351, 3.083), multi-lobar pneumonia (OR 2.356, 95% CI 1.741, 3.189). Female sex and macrolide therapy were predictors of survival: (OR 0.702, 95% CI .516, .955; and OR 0.554, 95% CI .394, .779, respectively). Either azithromycin or roxithromycin treatment for as short as two days was predictor of survival. Quinolone therapy had no effect. CONCLUSIONS: Empirical therapy with macrolides reduced odds for mortality by 45%. This effect was evident with azithromycin and with roxithromycin. The effect did not require a full course of therapy.

Migration of antibiotic resistance genes and evolution of flora structure in the Xenopus tropicalis intestinal tract with combined exposure to roxithromycin and oxytetracycline.

The intestinal flora is one of the most important environments for antibiotic resistance development, owing to its diverse mix of bacteria. An excellent medicine model organism, Xenopus tropicalis, was selected to investigate the spread of antibiotic resistance genes (ARGs) in the intestinal bacterial community with single or combined exposure to roxithromycin (ROX) and oxytetracycline (OTC). Seventeen resistance genes (tetA, tetB, tetE, tetM, tetO, tetS, tetX, ermF, msrA, mefA, ereA, ereB, mphA, mphB, intI1, intI2, intI3) were detected in the intestines of Xenopus tropicalis living in three testing tanks (ROX tanks, OTC tanks, ROX + OTC tanks) and a blank tank for 20 days. The results showed that the relative abundance of total ARGs increased obviously in the tank with single stress but decreased in the tank with combined stress, and the genes encoding the macrolide antibiotic efflux pump (msrA), phosphatase (mphB) and integron (intI2, intI3) were the most sensitive. With the aid of AFM scanning, DNA was found to be scattered short chain in the blank, became extended or curled and then compacted with the stress from a single antibiotic, and was compacted and then fragmented with combined stress, which might be the reason for the variation of the abundance of ARGs with stress. The ratio of Firmicutes/Bacteroides related to diseases was increased by ROX and OTC. The very significant correlation between intI2 and intI3 with tetS (p ≤ 0.001) hinted at a high risk of ARG transmission in the intestines. Collectively, our results suggested that the relative abundance of intestinal ARGs could be changed depending on the intestinal microbiome and DNA structures upon exposure to antibiotics at environmental concentrations.

Physiological, biochemical and transcriptional responses of cyanobacteria to environmentally relevant concentrations of a typical antibiotic-roxithromycin.

The frequent occurrence of antibiotics in source waters may affect the formation of harmful algal blooms (HABs) dominated by the cyanobacterium Microcystis aeruginosa. However, it remains poorly understood whether dissolved algal organic matters (AOM) can be altered by the introduction of antibiotics in source waters. To resolve these discrepancies, this study investigated the physiological, biochemical, and transcriptional responses of a toxigenic strain of M. aeruginosa to the commonly-detected antibiotic roxithromycin (ROX) at environmentally relevant concentrations ranging from 30 to 8000 ng L-1. The growth and microcystin (MC) production of M. aeruginosa was significantly stimulated by 300 and 1000 ng L-1 ROX, whereas inhibited by 5000 and 8000 ng L-1 ROX. This may be owing to the regulation of genes related to photosynthesis and MCs. Although the membrane of cyanobacterial cells remained intact, the release of MCs was increased significantly with the growing ROX dosages, which may cause additional challenges in drinking water treatment. The amounts of AOM were enhanced by 300 and 1000 ng L-1 ROX, while decreased by 5000 and 8000 ng L-1 ROX. It may be attributed to the changes of cyanobacterial cell growth and the gene expression related to carbon fixation, carbohydrate metabolism and nitrogen metabolism. To further understand the regulation of related genes in M. aeruginosa exposed to ROX, trend analysis of differentially expressed genes was performed. The results indicated that the regulation of metabolism-related genes (e.g., lipopolysaccharide biosynthesis) may be also responsible for the changes of cyanobacterial cell densities. Generally, low levels of ROX (300 and 1000 ng L-1) could stimulated the cyanobacterial growth, MC synthesis and AOM production, which may promote the formation of HABs and reduce the source water quality. Although higher levels of ROX (5000 and 8000 ng L-1) inhibited the formation of HABs, the threat of increasing extracellular MCs should be considered.

Fast dissolving nanofiber mat for the local antimicrobial application of roxithromycin in oral cavity.

Fast disintegrating and dissolving nanofiber (NF) mat was devised to deliver roxithromycin for the treatment of the respiratory tract infection. NF membrane was made by an electrospinning process with poly(vinyl alcohol) (PVA), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and d-α-tocopheryl polyethylene glycol succinate (TPGS) for local application of roxithromycin. Roxithromycin has a poor water solubility thus HP-ß-CD is introduced for enhancing drug solubility by forming an inclusion complex in this study. The addition of TPGS provided multiple roles such as accelerating wetting, disintegration, and dissolution speed and overcoming bacterial resistance. Roxithromycin was successfully entrapped in NF structure and drug amorphization occurred during the electrospinning process. PVA/HP-ß-CD/TPGS/roxithromycin (PHTR) NF exhibited faster wetting, disintegration, and dissolution speed rather than the other NF mats. PHTR NF displayed higher antibacterial potentials in Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) compared to other NF mat formulations. The administration of PHTR NF to oral cavity in pneumococcal disease mouse model provided the most efficient therapeutic potentials in lung tissue. Designed multiple phase-based NF mat may be one of powerful local drug delivery systems for the therapy of respiratory tract infection.