Erythromycin Treatment Research Articles

Erythromycin disrupts Acinetobacter baumannii biofilms through destruction of the quorum sensing system.

This study was conducted to explore the effects of erythromycin on biofilms comprising Acinetobacter baumannii (A baumannii). To clarify the effect of erythromycin on the biofilms of A baumannii, we collected pure Ab strains isolated and identified from a variety of sample types extracted from patients in the microbiological laboratory of our hospital from April to August 2023, and divided them into an experimental group (treated with erythromycin) and a control group (without erythromycin). The morphology and quantity of A baumannii biofilm were observed at 24h, 48h, 72h, and 5d post-treatment, respectively, and the expression of quorum sensing (QS) system gene (abaI, abaR) mRNA was detected by fluorescence quantitative PCR. The results showed that A baumanniis are prone to form multiple drug-resistant (MDR) bacteria, against which the most commonly used clinical antibiotics are ineffective. Overall, we found that the number of bacteria, the number of bacteria in the biofilm, and the number of biofilms formed gradually increased over time, with a statistical difference (P < .05). After the addition of erythromycin, significant improvements in biofilm formation were achieved, indicating that erythromycin can destroy A baumannii biofilms, inhibiting bacterial growth to a certain extent. The expression levels of abaI and abaR gradually increased over time, indicating that the role of the QS system became more apparent over time. Biofilm formation is related to the QS system of A baumanniis. After erythromycin treatment, abaI and abaR mRNA expression was downregulated in the experimental group. Erythromycin disrupts A baumannii biofilms by destroying the quorum sensing system.

Efficacy of Low-Level Laser Versus Topical Erythromycin 2% in the Treatment of Inflammatory Acne Vulgaris.

Acne vulgaris is a skin problem affecting many people of different ages. Despite many options that are available for treatment of acne vulgaris, many patients still respond inadequately to treatment. Phototherapy is one of the best acne treatment options. It was to compare the efficacy of low-level laser therapy in treatment of inflammatory acne versus topical erythromycin 2% cream. This study included 40 patients (18 males, 22 females) with different clinical severities of acne vulgaris. All the participants underwent split-face treatment: one side with 8 treatments (twice per week) of a low-level continuous infrared diode laser (808 nm) wavelength and (500 Hz) frequency and the other side with topical erythromycin 2% twice daily (aknemycin cream 2%). Evaluation was done at start of sessions, 2 weeks after the end of sessions and 3 months after stoppage of treatment depending on: photographs, global evaluation of acne scale, and Indian acne association grading. There was improvement of acne lesions on laser side and antibiotic side (assessed as non-inflammatory and inflammatory lesion counts). Laser side showed better results than antibiotic side. Patients were more satisfied with laser treatment due to minimal side effects and less relapse. A series of 8 treatments using low level continuous infrared diode laser represents a cheap, safe and effective non-invasive therapeutic option for acne vulgaris.

Long-Term Erythromycin Treatment Alters the Airway and Gut Microbiota: Data from Chronic Obstructive Pulmonary Disease Patients and Mice with Emphysema

Introduction: Although long-term macrolide antibiotics could reduce the recurrent exacerbation of chronic obstructive pulmonary disease (COPD), the side effect of bacterial resistance and the impact on the microbiota remain concerning. We investigated the influence of long-term erythromycin treatment on the airway and gut microbiota in mice with emphysema and patients with COPD. Methods: We conducted 16S rRNA gene sequencing to explore the effect of erythromycin treatment on the lung and gut microbiota in mice with emphysema. Liquid chromatography-mass spectrometry was used for lung metabolomics. A randomized controlled trial was performed to investigate the effect of 48-week erythromycin treatment on the airway and gut microbiota in COPD patients. Results: The mouse lung and gut microbiota were disrupted after cigarette smoke exposure. Erythromycin treatment depleted harmful bacteria and altered lung metabolism. Erythromycin treatment did not alter airway or gut microbial diversity in COPD patients. It reduced the abundance of pathogens, such as Burkholderia, in the airway of COPD patients and increased levels of symbiotic bacteria, such as Prevotella and Veillonella. The proportions of Blautia, Ruminococcus, and Lachnospiraceae in the gut were increased in COPD patients after erythromycin treatment. The time to the first exacerbation following treatment was significantly longer in the erythromycin treatment group than in the COPD group. Conclusion: Long-term erythromycin treatment reduces airway and gut microbe abundance in COPD patients but does not affect microbial diversity and restores microbiota balance in COPD patients by reducing the abundance of pathogenic bacteria.

Erythromycin mediates co-flocculation between cyanobacterium Synechocystis sp. PCC 6803 and filamentous fungi in liquid cultivation without organic compounds

Photoautotrophic cyanobacteria assimilate the greenhouse gas carbon dioxide as their sole carbon source for producing useful bioproducts. However, harvesting the cells from their liquid media is a major bottleneck in the process. Thus, an easy-to-harvest method, such as auto-flocculation, is desirable. Here, we found that cyanobacterium Synechocystis sp. PCC 6803 co-flocculated with a natural fungal contamination in the presence of the antibiotic erythromycin (EM) but not without EM. The fungi in the co-flocculated biomass were isolated and found to consist of five species with the filamentous Purpureocillium lilacinum and Aspergillus protuberus making up 71% of the overall fungal population. The optimal co-cultivation for flocculation was an initial 5 mg (fresh weight) of fungi, an initial cell density of Synechocystis of 0.2 OD730, 10 µM EM, and 14 days of cultivation in 100 mL of BG11 medium with no organic compound. This yielded 248 ± 28 mg/L of the Synechocystis-fungi flocculated biomass from 560 ± 35 mg/L of total biomass, a 44 ± 2% biomass flocculation efficiency. Furthermore, the EM treated Synechocystis cells in the Synechocystis-fungi flocculate had a normal cell color and morphology, while those in the axenic suspension exhibited strong chlorosis. Thus, the occurrence of the Synechocystis-fungi flocculation was mediated by EM, and the co-flocculation with the fungi protected Synechocystis against the development of chlorosis. Transcriptomic analysis suggested that the EM-mediated co-flocculation was a result of down-regulation of the minor pilin genes and up-regulation of several genes including the chaperone gene for pilin regulation, the S-layer protein genes, the exopolysaccharide-polymerization gene, and the genes for signaling proteins involved in cell attachment and abiotic-stress responses. The CuSO4 stress can also mediate Synechocystis-fungi flocculation but at a lower flocculation efficiency than that caused by EM. The EM treatment may be applied in the co-culture between other cyanobacteria and fungi to mediate cell bio-flocculation.

Metabolomic Response of Thalassiosira weissflogii to Erythromycin Stress: Detoxification Systems, Steroidal Metabolites, and Energy Metabolism

Erythromycin, a macrolide antibiotic, is a prioritized pollutant that poses a high risk to environmental health. It has been detected in different environmental matrices and can cause undesired effects in aquatic organisms, particularly freshwater algae, which are primary producers. However, the impact of erythromycin on marine algae remains largely unexplored. Erythromycin has been reported to induce hormetic effects in the marine diatom Thalassiosira weissflogii (T. weissflogii). These effects are associated with the molecular pathways and biological processes of ribosome assembly, protein translation, photosynthesis, and oxidative stress. However, the alterations in the global gene expression have yet to be validated at the metabolic level. The present study used non-targeted metabolomic analysis to reveal the altered metabolic profiles of T. weissflogii under erythromycin stress. The results showed that the increased cell density was possibly attributed to the accumulation of steroidal compounds with potential hormonic action at the metabolic level. Additionally, slight increases in the mitochondrial membrane potential (MMP) and viable cells were observed in the treatment of 0.001 mg/L of erythromycin (an environmentally realistic level). Contrarily, the 0.75 and 2.5 mg/L erythromycin treatments (corresponding to EC20 and EC50, respectively) showed decreases in the MMP, cell density, and viable algal cells, which were associated with modified metabolic pathways involving ATP-binding cassette (ABC) transporters, the metabolism of hydrocarbons and lipids, thiamine metabolism, and the metabolism of porphyrin and chlorophyll. These findings suggest that metabolomic analysis, as a complement to the measurement of apical endpoints, could provide novel insights into the molecular mechanisms of hormesis induced by antibiotic agents in algae.

Add-on Erythromycin and Tacrolimus Treatment for Primary Sjogren’s Syndrome-Related Immune Thrombocytopenia: A Case Report

Add-on Erythromycin and Tacrolimus Treatment for Primary Sjogren’s Syndrome-Related Immune Thrombocytopenia: A Case Report

Erythromycin treatment under a specific nitrogen supply affects carbon metabolism and increases poly(3-hydroxybutyrate) and glycogen accumulation in cyanobacterium Synechocystis sp. PCC 6803

Under an adequate nitrate supply (BG11), cyanobacterium Synechocystis sp. PCC 6803 has high protein content but a low storage of glycogen and poly(3-hydroxybutyrate) (PHB). In contrast, when deprived of nitrogen (N), protein synthesis was repressed and the accumulation of glycogen and PHB was remarkably increased. The repressed protein synthesis caused by sulfur deprivation or treatment with chloramphenicol was also found to slightly enhance PHB accumulation in Synechocystis. Thus, the repressed protein synthesis is associated with the increased PHB and glycogen storage. Here, we examined two other antibiotics that inhibit protein synthesis, erythromycin (EM) and streptomycin (SM) for their effect on the accumulation of PHB and glycogen in Synechocystis. Under N cultivation, 10 μM EM treatment significantly increased the PHB level to 18 % (w/w cell dry weight [DW]) compared to 3 % (w/w DW) in the untreated cells; however, SM treatment did not increase the PHB level. Under BG11 cultivation, exposure to 0.7 μM SM and 5 μM EM enhanced glycogen accumulation up to 15 % and 41 % (w/w DW) respectively, compared to only 7 % (w/w DW) in the untreated cells. The EM treatment also remarkably reduced the total protein and phycobiliprotein contents. Results from metabolomic analysis suggested that EM treatment caused protein degradation into amino acids, some of which were metabolized into substrates that can be used for PHB and glycogen synthesis. This was substantiated by the result showing that EM treated cells had significantly increased levels of both the PHB-synthesizing substrates (acetyl-CoA, acetoacetyl-CoA, and 3-hydroxybutyryl-CoA) when cultured under N, and the glycogen-synthesizing substrates (fructose-1,6-BP, fructose-6-P, glucose-6-P, glucose-1-P, and ADP-glucose) when cultured in BG11. Therefore, EM treatment might be applicable for enhancing the accumulation of these two biopolymers in other cyanobacteria.

On the use of antibiotics in plasticity research: Gastropod shells unveil a tale of caution.

Through phenotypic plasticity, individual genotypes can produce multiple phenotypes dependent on the environment. In the modern world, anthropogenic influences such as man-made pharmaceuticals are increasingly prevalent. They might alter observable patterns of plasticity and distort our conclusions regarding the adaptive potential of natural populations. Antibiotics are nowadays nearly ubiquitous in aquatic environments and prophylactic antibiotic use is also becoming more common to optimize animal survival and reproductive output in artificial settings. In the well-studied plasticity model system Physella acuta, prophylactic erythromycin treatment acts against gram-positive bacteria and thereby reduces mortality. Here, we study its consequences for inducible defence formation in the same species. In a 2 × 2 split-clutch design, we reared 635 P. acuta in either the presence or absence of this antibiotic, followed by 28-day exposure to either high or low predation risk as perceived through conspecific alarm cues. Under antibiotic treatment, risk-induced increases in shell thickness, a well-known plastic response in this model system, were larger and consistently detectable. Antibiotic treatment reduced shell thickness in low-risk individuals, suggesting that in controls, undiscovered pathogen infection increased shell thickness under low risk. Family variation in risk-induced plasticity was low, but the large variation in responses to antibiotics among families suggests different pathogen susceptibility between genotypes. Lastly, individuals that developed thicker shells had reduced total mass, which highlights resource trade-offs. Antibiotics thus have the potential to uncover a larger extent of plasticity, but might counterintuitively distort plasticity estimates for natural populations where pathogens are a part of natural ecology.

Transcriptomic analysis of Staphylococcus equorum KM1031 from the high-salt fermented seafood jeotgal under chloramphenicol, erythromycin and lincomycin stresses

Staphylococcus equorum strain KM1031 is resistant to chloramphenicol, erythromycin and lincomycin. To shed light on the genetic factors underlying these antibiotic resistances, we determined the global gene expression profile of S. equorum KM1031 using RNA sequencing. During chloramphenicol, erythromycin and lincomycin treatment, 8.3% (183/2,336), 16.0% (354/2,336), and 2.9% (63/2,336) of S. equorum KM1031 genes exhibited significant differences in expression, respectively. These three antibiotics upregulated genes related to efflux and downregulated genes related to transporters. Antibiotic treatment also upregulated osmoprotectant-related genes involved in salt tolerance. To identify specific genes functionally related to antibiotic resistance, we compared the genome of strain KM1031 with those of three S. equorum strains that are sensitive to these three antibiotics. We identified three genes of particular interest: an antibiotic biosynthesis monooxygenase gene (abm, AWC34_RS01805) related to chloramphenicol resistance, an antibiotic ABC transporter ATP-binding protein gene (msr, AWC34_RS11115) related to erythromycin resistance, and a lincosamide nucleotydyltransferase gene (lnuA, AWC34_RS13300) related to lincomycin resistance. These genes were upregulated in response to the corresponding antibiotic; in particular, msr was upregulated more than fourfold by erythromycin treatment. Finally, the results of RNA sequencing were validated by quantitative real-time PCR. This transcriptomic analysis provides genetic evidence regarding antibiotic stress responses of S. equorum strain KM1031.

Development of Fluoroquinolone Resistance through Antibiotic Tolerance in Campylobacter jejuni.

ABSTRACTAntibiotic tolerance not only enables bacteria to survive acute antibiotic exposures but also provides bacteria with a window of time in which to develop antibiotic resistance. The increasing prevalence of Campylobacter jejuni isolates resistant to clinically important antibiotics, particularly fluoroquinolones (FQs), is a global public health concern. Currently, little is known about antibiotic tolerance and its effects on resistance development in C. jejuni. Here, we show that exposure to ciprofloxacin or tetracycline at concentrations 10 and 100 times higher than the MIC induces antibiotic tolerance in C. jejuni, whereas gentamicin or erythromycin treatment causes cell death. Interestingly, FQ resistance rapidly develops in C. jejuni after tolerance induction by ciprofloxacin and tetracycline. Furthermore, after tolerance is induced, alkyl hydroperoxide reductase (AhpC) plays a critical role in reducing FQ resistance development by alleviating oxidative stress. Together, these results demonstrate that exposure of C. jejuni to antibiotics can induce antibiotic tolerance and that FQ-resistant (FQR) C. jejuni clones rapidly emerge after tolerance induction. This study elucidates the mechanisms underlying the high prevalence of FQR C. jejuni and provides insights into the effects of antibiotic tolerance on resistance development.IMPORTANCE Antibiotic tolerance compromises the efficacy of antibiotic treatment by extending bacterial survival and facilitating the development of mutations associated with antibiotic resistance. Despite growing public health concerns about antibiotic resistance in C. jejuni, antibiotic tolerance has not yet been investigated in this important zoonotic pathogen. Here, our results show that exposure of C. jejuni to ciprofloxacin or tetracycline leads to antibiotic tolerance development, which subsequently facilitates the emergence of FQR C. jejuni. Importantly, these antibiotics are commonly used in animal agriculture. Moreover, our study suggests that the use of non-FQ drugs in animal agriculture promotes FQ resistance development, which is crucial because antibiotic-resistant C. jejuni is primarily transmitted from animals to humans. Overall, these findings increase our understanding of the mechanisms of resistance development through the induction of antibiotic tolerance.

Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation

BackgroundImmunomodulatory therapies that improve the outcome of sepsis are not available. We sought to determine whether treatment of critically ill patients with sepsis with low-dose erythromycin—a macrolide antibiotic with broad immunomodulatory effects—decreased mortality and ameliorated underlying disease pathophysiology.MethodsWe conducted a target trial emulation, comparing patients with sepsis admitted to two intensive care units (ICU) in the Netherlands for at least 72 h, who were either exposed or not exposed during this period to treatment with low-dose erythromycin (up to 600 mg per day, administered as a prokinetic agent) but no other macrolides. We used two common propensity score methods (matching and inverse probability of treatment weighting) to deal with confounding by indication and subsequently used Cox regression models to estimate the treatment effect on the primary outcome of mortality rate up to day 90. Secondary clinical outcomes included change in SOFA, duration of mechanical ventilation and the incidence of ICU-acquired infections. We used linear mixed models to assess differences in 15 host response biomarkers reflective of key pathophysiological processes from admission to day 4.ResultsIn total, 235 patients started low-dose erythromycin treatment, 470 patients served as controls. Treatment started at a median of 38 [IQR 25–52] hours after ICU admission for a median of 5 [IQR 3–8] total doses in the first course. Matching and weighting resulted in populations well balanced for proposed confounders. We found no differences between patients treated with low-dose erythromycin and control subjects in mortality rate up to day 90: matching HR 0.89 (95% CI 0.64–1.24), weighting HR 0.95 (95% CI 0.66–1.36). There were no differences in secondary clinical outcomes. The change in host response biomarker levels from admission to day 4 was similar between erythromycin-treated and control subjects.ConclusionIn this target trial emulation in critically ill patients with sepsis, we could not demonstrate an effect of treatment with low-dose erythromycin on mortality, secondary clinical outcomes or host response biomarkers.

Metabolomic profiles in a green alga (Raphidocelis subcapitata) following erythromycin treatment: ABC transporters and energy metabolism

A recent study showed that erythromycin (ERY) exposure caused hormesis in a model alga (Raphidocelis subcapitata) where the growth was promoted at an environmentally realistic concentration (4 µg/L) but inhibited at two higher concentrations (80 and 120 µg/L), associated with opposite actions of certain signaling pathways (e.g., xenobiotic metabolism, DNA replication). However, these transcriptional alterations remain to be investigated and verified at the metabolomic level. This study uncovered metabolomic profiles and detailed toxic mechanisms of ERY in R. subcapitata using untargeted metabolomics. The metabolomic analysis showed that metabolomic pathways including ABC transporters, fatty acid biosynthesis and purine metabolism were associated with growth promotion in algae treated with 4 µg/L ERY. An overcompensation was possibly activated by the low level of ERY in algae where more resources were reallocated to efficiently restore the temporary impairments, ultimately leading to the outperformance of growth. By contrast, algal growth inhibition in the 80 and 120 µg/L ERY treatments was likely attributed to the dysfunction of metabolomic pathways related to ABC transporters, energy metabolism and metabolism of nucleosides. Apart from binding of ERY to the 50S subunit of ribosomes to inhibit protein translation as in bacteria, the data presented here indicate that inhibition of protein translation and growth performance of algae by ERY may also result from the suppression of amino acid biosynthesis and aminoacyl-tRNA biosynthesis. This study provides novel insights into the dose-dependent toxicity of ERY on R. subcapitata.

Trends of drug resistance to the commonly used antibiotics to combat the COVID-19 pandemic: Experience from a super-speciality institute of Northern India.

Coronavirus disease 2019 (COVID-19) is purely a viral illness which is not affected by the usage of antibiotics, but the risk of development of secondary bacterial infections during the course of respiratory illness or hospitalisation has led to a surge of antibiotic use. Anti-microbial resistance has taken an upward trend to some of the commonly used or over-used antibiotics. The present study was planned to focus on the trends of resistance rates noticed for the common antibiotics, namely, doxycycline, azithromycin, and so on, before and after the advent of this pandemic. The study was conducted at a tertiary care hospital of North India with 2000 samples, 1000 samples between March 2019 and March 2020 before the COVID pandemic and 1000 samples between April 2020 and April 2021 after the advent of the pandemic. Identification and zones for doxycycline and erythromycin were interpreted as per Clinical and Laboratory Standards Institute guidelines. Among the various samples, pus/aspirated fluids were in majority (47%), followed by blood (29%), respiratory specimens (18%), and urine (6%). On stratifying the various pathogens associated with the treatment of doxycycline and erythromycin, Staphylococcus species were the predominant ones in almost 82% of the cases, followed by Enterococcus (12%) and Streptococcus (6%) species. For doxycycline, the overall sensitivity was noted to be 46% in the year 2019-20 and 31% in the year 2020-21, whereas for erythromycin, the sensitivity was seen as 39% in 2019-20 and dropped down to 26% in 2020-21. The authors noted a dip in the overall sensitivity towards doxycycline and azithromycin. This finding clearly indicates the increasing rates of antibiotic resistance in a developing country such as India during these COVID times. A proper anti-microbial stewardship programme during these times will help to de-escalate the increasing resistance rates and will prove to be of great help to the primary care physicians.

AcrB-TolC efflux system is essential for macrolide resistance in Helicobacter pylori

The prevalence of Helicobacter pylori strains resistant to macrolide is increasing worldwide. Macrolide molecules can be generally extruded by the AcrB-TolC system in bacteria. The H. pylori 26695 genome was assessed for putative translocases and the outer membrane efflux of AcrB (HP607) and TolC (HP605) proteins. We investigated the role of the AcrB-TolC efflux system in macrolide resistant (M-R) H. pylori. Both acrB- and tolC-mutant M-R strains were constructed from M-R strains by insertional inactivation of the acrB and tolC genes. The minimal inhibition concentrations (MICs) of erythromycin (EM) and clarithromycin (CLR) were determined by an agar dilution assay. To investigate the efflux ability of macrolides, intracellular accumulation of radiolabeled EM in the H. pylori 26695 strain, M-R strain, and acrB- and tolC-mutant M-R strains was measured by a liquid scintillation counter. For Post antibiotic effect (PAE), EM-treated H. pylori was diluted 1000-fold to remove antimicrobial activity. After additional 24 hours incubation, the CFU was measured. The decrease in the levels of resistance to EM and CLR was 32-fold higher for the acrB- and tolC-mutant M-R strains than the M-R strains. The intracellular EM concentration significantly increased in the acrB- and tolC-mutant M-R strains than the H. pylori 26695 and M-R strains. Diluted acrB, and tolC M-R mutant H. pylori after EM treatment was markedly reduced compared to M-R H. pylori. Our result showed that the M-R mechanism of H. pylori is significantly associated with AcrB-TolC efflux system.

Effect of erythromycin on abomasal emptying in suckling lambs with experimental endotoxemia

Abomasal hypomotility and consequently a decrease in abomasal emptying rate is one of the most important factors in ruminant abomasal disorders. Endotoxemia is clinically recognized by abnormalities in cardiovascular function, renal failure, decreased gastrointestinal motility and shock. This can lead to bloating and sudden death in lambs that have not received enough colostrum. The aim of the study was to investigate the effect of erythromycin treatment on abomasal emptying rate in endotoxemic lambs. Fifteen suckling lambs arranged in 3 groups (n = 5) were studied in this study. Endotoxemia was induced in two groups (Positive control and Erythromycin) at 0.1 μg/kg body weight LPS in 10 mL normal saline over 5 min IV and erythromycin was injected to erythromycin group at 8.8 mg/kg BW IM. Negative control received 2 mL normal saline IM. Abomasal emptying rate was assessed by acetaminophen absorption test, which was fed with milk at 50 mg/kg BW, 30 min after each treatment. Samples were collected at 15 min intervals up to 240 min and abomasal emptying rate was assessed for each group. Results showed there were significant differences in Cmax, Tmax and AUC among groups (endotoxemia groups and control group) (P < 0.05), confirming a decrease in abomasal emptying rate in lambs with endotoxemia. The results also indicated that compared to affected lambs not treated with erythromycin, abomasal emptying rate was significantly higher in lambs treated with erythromycin that means erythromycin increased abomasal emptying rate (P < 0.05).

Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.

Unravelling the collateral damage of antibiotics on gut bacteria.

Antibiotics are used to fight pathogens but also target commensal bacteria, disturbing the composition of gut microbiota and causing dysbiosis and disease1. Despite this well-known collateral damage, the activity spectrum of different antibiotic classes on gut bacteria remains poorly characterized. Here we characterize further 144 antibiotics from a previous screen of more than 1,000 drugs on 38 representative human gut microbiome species2. Antibiotic classes exhibited distinct inhibition spectra, including generation dependence for quinolones and phylogeny independence for β-lactams. Macrolides and tetracyclines, both prototypic bacteriostatic protein synthesis inhibitors, inhibited nearly all commensals tested but also killed several species. Killed bacteria were more readily eliminated from in vitro communities than those inhibited. This species-specific killing activity challenges the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provides a possible explanation for the strong effect of macrolides on animal3-5 and human6,7 gut microbiomes. To mitigate this collateral damage of macrolides and tetracyclines, we screened for drugs that specifically antagonized the antibiotic activity against abundant Bacteroides species but not against relevant pathogens. Such antidotes selectively protected Bacteroides species from erythromycin treatment in human-stool-derived communities and gnotobiotic mice. These findings illluminate the activity spectra of antibiotics in commensal bacteria and suggest strategies to circumvent their adverse effects on the gut microbiota.

Comparative Effectiveness of Intravenous Azithromycin Versus Erythromycin Stimulating Antroduodenal Motility in Children.

Azithromycin has been shown to improve gastrointestinal motility in adults and may have fewer drug interactions and reduced arrhythmogenic effects than erythromycin. We hypothesized that azithromycin is comparable to erythromycin in eliciting pharmacodynamic outcomes for antral and small bowel motility. To compare the pharmacodynamic effectiveness of azithromycin and erythromycin for eliciting antral and duodenal motility in pediatric patients who underwent antroduodenal manometry for different indications. We conducted a retrospective comparison of clinic data and manometric pharmacodynamics outcomes in patients who underwent antroduodenal manometry between 2013 and 2017. Fifty-one patients mean age (± standard deviation) 9.7 (5.4) years, received either azithromycin 3 mg/kg (n = 20) or erythromycin 2 mg/kg (n = 31) during antroduodenal manometry. For patients receiving erythromycin, mean area under the curve (AUC) across all eight pressure ports increased from median [95% confidence interval] 2256 [1585, 2602] to 8742 [5876, 11761] mmHg × s (P < 0.001) and mean motility index increased from 8.63 [7.87, 9.42] to 11.98 [11.20, 12.21] (P < 0.001). For patients receiving azithromycin, mean AUC increased from 2255 [1585, 2602] to 8254 [5649, 10470] mmHg × s (P < 0.001) and motility index increased from 8.63 [7.87,9.42] to 11.79 [11.03, 12.21] (P < 0.001). Neither mean stimulated AUC nor mean motility index was significantly different between azithromycin and erythromycin treatments. There was no significant difference in side effects between groups. Azithromycin and erythromycin have similar pharmacodynamic effects on antral and small bowel contractility in children. Azithromycin should be considered an acceptable alternative to erythromycin as an upper gastrointestinal tract prokinetic for children and has historically had fewer side effects than erythromycin.

Using bacterial whole genome sequencing to identify toxin genes associated with disease outbreaks in black tiger shrimp (Penaeus monodon) aquaculture production

Vibrio-related diseases cause significant economic impact on global shrimp production. Although toxin expression is a well-established mechanism of Vibrio-related disease in humans, the role of toxin expression in Vibrio disease in aquaculture generally is not well defined. The current study investigated a sustained, rapid onset, mass mortality at a commercial tiger prawn, Penaeus monodon, hatchery. Affected shrimp were between mysis-2 and post-larvae-15. Disease outbreaks were prevented through prophylactic treatment with oxytetracycline, suggesting a bacterial-related causative agent. Conversely, mortality was not reduced with erythromycin treatment. Whole genome sequencing (WGS) using the Illumina Nextera XT protocol performed on mixed microbial cultures from erythromycin and non-erythromycin infused thiosulphate-citrate-bile salts-sucrose (TCBS) TCBS agar on a MiSeq, and postlarval samples on a HiSeq. The WGS revealed several Vibrio-related sequences dominated by reads with highest homology to Vibrio harveyi and Vibrio alginolyticus. In addition, a range of putative virulence genes encoding for antibiotic resistance and toxin production were identified. Taqman qPCR assays were designed to specifically quantify four of the putative toxin-genes found, namely the Zonula occludens toxin (ZOT), hemolysin d toxin (HylD), YaFO toxin-antitoxin and Repeats–in-Toxin (RTX) genes. The qPCR assays confirmed the presence of the toxin target genes with low cycle threshold value (Ct) in the bacterial cultures and postlarval samples. Specifically, the ZOT and HylD genes were detected in high copy number in the non-erythromycin and erythromycin-treated cultures. Although the detection of toxin-genes does not demonstrate causation of mortality, the application of WGS combined with qPCR analysis has revealed the presence of a range of virulence factors within the hatchery system and allowed a rapid implementation of management protocols to prevent entry of genetically toxin-armed Vibrio spp. until more conclusive studies into disease mechanisms could be conducted.

Growth Inhibition and Oxidative Stress in Two Green Algal Species Exposed to Erythromycin

AbstractChlorella vulgaris (C. vulgaris) and Raphidocelis subcapitata (R. subcapitata) are two model algal species applied for the testing of chemicals, whereas a considerable variation in their sensitivity to antibiotics has been reported. The difference in species sensitivity may be attributed to the xenobiotic‐induced oxidative stress in algal cells. Thus, this study compared the responses of these two model green algae toward the exposure of erythromycin (ERY), a macrolide antibiotic, at the concentration levels of 0, 20, 40, 60 μg/L, and elucidated the toxic mechanism of action from the point of oxidative damage and antioxidant defense. To achieve this, effects on the endpoints of algal growth, malondialdehyde (MDA), antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GP], glutathione, and glutathione S‐transferase), and photosynthetic pigment contents were evaluated. After exposing for seven days, the growth of R. subcapitata was significantly stimulated at ERY 20 μg/L but inhibited at the higher exposure level of 60 μg/L. Contrarily, hormesis in C. vulgaris exposed to all ERY treatments was detected. With the increase in ERY exposure, MDA content, and the antioxidant activity of SOD, CAT, GP in R. subcapitata were gradually enhanced. In C. vulgaris, a declining trend in the MDA content and the activity of SOD, CAT, and GP was detected. These results provide insights into the ERY‐altered production of reactive oxygen species and the antioxidant responses in two algae.