Erythromycin Research Articles

Antimicrobial Resistance Profiles, Virulence Genes, and Genetic Diversity of Thermophilic Campylobacter Species Isolated From a Layer Poultry Farm in Korea.

Thermophilic Campylobacter species are among the major etiologies of bacterial enteritis globally. This study aimed at assessing the antimicrobial resistance (AMR) profiles, virulence genes, and genetic diversity of thermophilic Campylobacter species isolated from a layer poultry farm in South Korea. One hundred fifty-three chicken feces were collected from two layer poultry farms in Gangneung, South Korea. The Campylobacter species were isolated by cultural techniques, while PCR and sequencing were used for species confirmation. Antimicrobial susceptibility testing for six antimicrobials [ciprofloxacin (CIP), nalidixic acid (NAL), sitafloxacin (SIT), erythromycin (ERY), tetracycline (TET), and gentamicin (GEN)] was carried out by broth microdilution. Three AMR and nine virulence genes were screened by PCR. Genotyping was performed by flaA-restriction fragment length polymorphism (RFLP) and multilocus sequence typing (MLST). Of the 153 samples, Campylobacter spp. were detected in 55 (35.9%), with Campylobacter jejuni and Campylobacter coli being 49 (89.1%) and six (10.9%), respectively. High-level resistance was observed for CIP (100%), NAL (100%), and TET (C. jejuni, 93.9%; C. coli: 83.3%). No resistance was observed for SIT. The missense mutation (C257T) in gyrA gene was confirmed by sequencing, while the tet(O) gene was similar to known sequences in GenBank. The rate of multidrug-resistant (MDR) strains was 8.2%, and they all belonged to C. jejuni. All Campylobacter isolates possessed five virulence genes (cdtB, cstII, flaA, cadF, and dnaJ), but none possessed ggt, while the rates for other genes (csrA, ciaB, and pldA) ranged between 33.3 and 95.9%. The flaA-RFLP yielded 26 flaA types (C. jejuni: 21 and C. coli: five), while the MLST showed 10 sequence types (STs) for C. jejuni and three STs for C. coli, with CC-607 (STs 3611) and CC-460 (ST-460) being predominant. Among the 10 STs of C. jejuni, three were newly assigned. The findings of this study highlight the increased resistance to quinolones and TET, the virulence potential, and the diverse genotypes among Campylobacter strains isolated from the layer poultry farm.

CONTROL OF Neospora caninum IN SEMEN OF BULL

O objetivo do presente estudo foi desenvolver um diluente de sêmen de touros eficiente no controle de Neospora caninum. O teste dos antimicrobianos (experimento 1) - trimetoprim isolado (TRI) e associado a sulfadiazina (SDT) e ao sulfametoxazol (SMT), claritromicina (CLA), eritromicina (ERI), azitromicina (AZI) e clindamicina (CLI) - foi realizado utilizando cultivo celular e avaliado quanto à presença de taquizoítas livres e ao efeito citopático na monocamada. Os antimicrobianos que se mostraram eficazes no controle dos taquizoítos in vitro foram utilizados na preparação do diluente para o sêmen. Cada antimicrobiano foi avaliado quanto à toxicidade dos espermatozóides (experimento 2) sendo 8 grupos (7 grupos receberam antibiótico no diluente, exceto 1 grupo- grupo controle). Em relação à análise morfológica, os grupos SMT e AZI apresentaram mais defeitos de acrossoma e de cauda.Os grupos SDT, SMT e AZI apresentaram valores mais baixos da Velocidade de Trajeto. A Velocidade Progressiva foi menor nos grupos SMT e AZI e a Frequência de Batimentos de cauda também foi menor nos grupos CLI e AZI. Os valores de Velocidade Curvilinear dos grupos SDT, SMT e CLA foram menores. Os grupos SMT, ERI e AZI apresentaram valores mais baixos de Motilidade Total e Motilidade Progressiva. Quanto à citometria de fluxo, os grupos SDT, SMT e AZI apresentaram percentagens maiores de reação acrossomal e membrana plasmática lesada. Os antibióticos que podem ser adicionados ao diluente de sêmen bovino foram clindamicina, claritromicina e trimetoprim.

Oxidation of antibiotics by ferrate(VI) in water: Evaluation of their removal efficiency and toxicity changes

Antibiotics in water and wastewater have been determined extensively. The treatment of antibiotics in water needs evaluation of possible harmful effects on aquatic ecosystems and human health. This paper presents the toxicity evaluation of antibiotics after their treatment with ferrate (VI) (FeVIO42−, Fe(VI)) in water. The antibiotics (sulfamethoxazole (SMX), erythromycin (ERY), ofloxacin (OFL), ciprofloxacin (CIP), tetracycline (TET), oxytetracycline (OXY), and trimethoprim (TMP)) were treated at pH 8.0 by applying two concentrations of Fe(VI) to have molar ratios of 5:1 and 10:1 ([Fe(VI)]:[antibiotic]). Under the studied conditions, incomplete removal of antibiotics was observed, suggesting that the treated solutions contained parent antibiotics and their transformation products. The toxicity of antibiotics without Fe(VI) treatment was tested against freshwater green alga Raphidocelis subcapitata and cyanobacterium Synechococcus elongatus, which were determined to be generally sensitive to antibiotics, with EC50 < 1.0 mg/L. The toxicity of Fe(VI) treated solution was tested against R. subcapitata. Results found no toxicity for the treated solutions of OFL, CIP, and OXY. However, SMX, ERY, and TET remained toxic after Fe(VI) treatment (i.e., more than 75% growth inhibition of R. subcapitata). Results demonstrated that R. subcapitata may be applied to test the toxicity of antibiotics after oxidative treatments.

Treatment of pharmaceutical wastewater by ionizing radiation: Removal of antibiotics, antimicrobial resistance genes and antimicrobial activity

In present study, the treatment of real pharmaceutical wastewater from an erythromycin (ERY) production factory by gamma irradiation was investigated. Results showed that a variety of antimicrobial resistance genes (ARGs), involving MLSB, tet, bla, multidrug, sul, MGEs and van genes and plentiful 9 bacterial phyla were identified in the raw wastewater. In addition to ERY, sulfamethoxazole (SMX) and tetracycline (TC) were also identified with the concentration of 3 order of magnitude lower than ERY. Results showed that the abatement of ARGs and antibiotics was much higher than that of antimicrobial activity and COD. With the absorbed dose of 50 kGy, the removal percentage of ARGs, ERY, antimicrobial activity and COD was 96.5–99.8%, 90.0%, 47.8% and 10.3%, respectively. The culturable bacteria were abated fast and completely at 5.0 kGy during gamma irradiation. The genus Pseudomonas was predominant in raw wastewater (56.7%) and its relative abundance decreased after gamma irradiation, to 1.3% at 50 kGy. With addition of peroxymonosulfate (PMS, 50 mM), the antimicrobial activity disappeared completely and ERY removal reached as high as 99.2% at the lower absorbed dose of 25 kGy. Ionizing radiation-coupled technique is a potential option to treat pharmaceutical wastewater for reduction of antibiotics, ARGs and antimicrobial activity.

Effects of Erythromycin on Osteoclasts and Bone Resorption via DEL-1 Induction in Mice.

Macrolides are used to treat various infectious diseases, including periodontitis. Furthermore, macrolides are known to have immunomodulatory effects; however, the underlying mechanism of their action remains unclear. DEL-1 has emerged as an important factor in homeostatic immunity and osteoclastogenesis. Specifically, DEL-1 is downregulated in periodontitis tissues. Therefore, in the present study, we investigated whether the osteoclastogenesis inhibitory effects of erythromycin (ERM) are mediated through upregulation of DEL-1 expression. We used a ligature-induced periodontitis model in C57BL/6Ncrl wild-type or DEL-1-deficient mice and in vitro cell-based mechanistic studies to investigate how ERM inhibits alveolar bone resorption. As a result of measuring alveolar bone resorption and gene expression in the tooth ligation model, ERM treatment reduced bone loss by increasing DEL-1 expression and decreasing the expression of osteoclast-related factors in wild-type mice. In DEL-1-deficient mice, ERM failed to suppress bone loss and gene expression of osteoclast-related factors. In addition, ERM treatment downregulated osteoclast differentiation and calcium resorption in in vitro experiments with mouse bone marrow-derived macrophages. In conclusion, ERM promotes the induction of DEL-1 in periodontal tissue, which may regulate osteoclastogenesis and decrease inflammatory bone resorption. These findings suggest that ERM may exert immunomodulatory effects in a DEL-1-dependent manner.

Protective effects of different anti‑inflammatory drugs ontracheal stenosis following injury and potential mechanisms.

Tracheal stenosis following injury cannot be effectively treated. The current study compared the protective effects of different anti-inflammatory drugs on tracheal stenosis and investigated their possible mechanisms. Rabbit tracheal stenosis models following injury were constructed and confirmed using hematoxylin and eosin (H&E) staining. A total of 30 rabbits were divided into the control (CON), penicillin (PEN), erythromycin (ERY), budesonide (BUD) and PEN + ERY + BUD groups (n=6). Stenotic tracheal tissue, serum and bronchoalveolar lavage fluid (BALF) were collected 10 days after continuous treatment. Pathological changes in the tracheas were observed by H&E staining. Histone deacetylase 2 (HDAC2) expression in tracheal tissues was detected by immunofluorescence. Immunohistochemistry was performed to detect collagen I (Col-I) and collagen III (Col-III) levels in tracheal tissues. Transforming growth factor β1 (TGF-β1), vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) levels in serum and BALF samples were determined using ELISA kits. Western blotting detected HDAC2, IL-8, TGF-β1 and VEGF levels in tracheal tissues. H&E staining demonstrated that tracheal epithelial hyperplasia and fibroblast proliferation in the ERY and PEN + ERY + BUD groups markedly improved compared with the CON group. Furthermore, in tracheal tissues, HDAC2 expression was significantly increased and IL-8, TGF-β1, VEGF, Col-I and Col-III levels were significantly decreased in the ERY and PEN + ERY + BUD groups compared with the CON group. Additionally, the results for the PEN + ERY + BUD were more significant compared with the ERY group. In serum and BALF samples, IL-8, TGF-β1 and VEGF levels in the ERY and PEN + ERY + BUD groups were significantly lower compared with the CON group, with the results of the PEN + ERY + BUD group being more significant compared with the ERY group. There were no significant differences between the PEN, BUD and CON groups. ERY inhibited tracheal granulation tissue proliferation and improved tracheal stenosis following injury and synergistic effects with PEN and BUD further enhanced these protective effects. The mechanism may involve HDAC2 upregulation and inhibition of local airway and systemic inflammatory responses.

Molecular Characteristics of Enterococcus faecalis and Enterococcus faecium from Bulk Tank Milk in Korea.

Simple SummaryEnterococci can be an opportunistic pathogen in milk, which can easily disseminate antimicrobial resistance and virulence genes. The purpose of this study was to characterize and compare the enterococci isolates from samples of bulk tank milk obtained from four dairy companies in Korea to prevent the spread of pathogenic and antimicrobial-resistant enterococci in dairy companies. The results demonstrated various degrees of antimicrobial resistance and virulence-factor distribution in enterococci from bulk tank milk in Korea and support the assessment that pathogens from bulk tank milk can also become a reservoir for dissemination of antimicrobial resistance and virulence factors through cross-contamination processes.Enterococci are considered to be environmental mastitis-causing pathogens that can easily spread antimicrobial resistance or virulence genes via horizontal transfer. In this study, the molecular characteristics of enterococci from bulk tank milk were investigated to assess the importance of dairy herd management. A total of 338 enterococci (305 Enterococcus faecalis and 33 Enterococcus faecium) were isolated from 1584 batches of bulk tank milk samples from 396 farms affiliated with four dairy companies in Korea, and significant differences (40.6–79.7%) (p < 0.05) in the prevalence of enterococci were observed in the samples from different companies. Enterococci showed the highest resistance to tetracycline (TET) (73.4%), followed by doxycycline (DOX) (49.7%) and erythromycin (ERY) (46.2%), while two enterococci isolates showed resistance to vancomycin (VAN). Among 146 tetracycline (TET) and ERY-resistant enterococci, each 50 (19.4%) enterococci carried combination-resistance and transposon gene types erm(B) + tet(M) + IntTn and erm(B) + tet(L) + tet(M) + IntTn, respectively. The virulence genes such as ace (99.0%), efaA (97.7%), cad1 (95.7%), and gelE (85.9%) were highly conserved in E. faecalis and significantly predominated over E. faecium (p < 0.001). Our results indicate that pathogens from bulk tank milk can also become a reservoir for the dissemination of antimicrobial resistance and virulence factors through cross-contamination processes.

Fate of Macrolide Antibiotics with Different Wastewater Treatment Technologies.

Graphical abstractThis comprehensive study addressed the occurrence, seasonal changes, removal efficiencies, and environmental risk assessments of three macrolide antibiotics in five wastewater treatment plants (WWTPs) with conventional and different additional treatment processes. A 1-year monitoring study was conducted, and influents and effluents were collected from Guangzhou (GZ), Shenzhen (SZ), Tai Po (TP), Shatin (ST), and Stonecutters Island (SI) WWTPs. Solid phase extraction and HPLC-MS/MS were used for the pretreatment and determination. The detection limits for azithromycin (AZI), erythromycin (ERY), and roxithromycin (ROX) ranged from 0.80 to 2.13 ng/L for the influent and effluent water samples. AZI was the most abundant antibiotic found in the influents, with average concentrations ranging from 571 ng/L to 1046 ng/L at all the target WWTPs. The seasonal average AZI concentration was the highest in all five WWTPs with the concentration of 984 ng/L in autumn, 849 ng/L in winter, 741 ng/L in summer, and 533 ng/L in spring. The seasonal AZI removal rates in the WWTPs were similar, with an average removal rate above 63.3% from spring to winter. All the treatments in the five WWTPs showed removal abilities for AZI, ERY, and ROX, regardless of the three phase treatments, namely, the UV disinfection process and conventional or chemically enhanced process within the WWTPs. For ERY and ROX, the average total removal rates were significantly decreased in the spring among all five WWTPs, at 53.1% and 57.8%, respectively. The GZ and SZ WWTPs displayed better removal rates than the TP, ST, and SI WWTPs, because the activity underlying the modified A2/O process in the GZ and SZ WWTPs has important effects on the antibiotic removal because the bacteria could produce compact granules and make the antibiotics settle faster in the wastewater. The additional UV disinfection in the SZ WWTP improved the removal efficiencies of the target antibiotics; it enhanced the biodegradability of residual organic pollutants in the WWTP effluent. Moreover, the corresponding environmental risks have been assessed and are viewed as a necessary component of future research. Supplementary InformationThe online version contains supplementary material available at 10.1007/s11270-021-05053-y.

Occurrence and ecological risk assessment of PPCPs in typical inflow rivers of Taihu lake, China

The occurrence and ecological risks of ten typical pharmaceutical and personal care products (PPCPs) at 12 typical inflow rivers of Taihu lake was investigated in this study. Seven out of the ten typical PPCPs targeted were detected in all the water samples and sediment samples tested. The PPCPs concentration detected were 0–94.91 ng/L for water samples and 0–18.27 ng/g for sediment samples. Sulfamethoxazole (SMZ) and erythromycin (ERY) has relatively higher concentration than other PPCPs in surface water samples, ciprofloxacin (CIP) and ofloxacin (OFX) has relatively higher concentration in the sediment samples. Inflow river-Caoqiao river has a relatively highest contamination of TN and TP, the PPCPs concentration in the river channel, estuary, lake-body also shows high value. This occurs in both the surface water and sediment sample, implied a relatively high pollution input from Caoqiao river. SMZ holds high long-term ecological risks in both surface water and sediment of almost all the tested inflow rivers of Taihu lake. Only ERY has medium short-term risks in surface water, other analyzed PPCPs hold low or insignificant short-terms risks for both surface water and sediments. This study fills the gap of PPCPs ecological risk of surface water and sediment of 12 typical inflow rivers of Taihu Lake, and revealed the importance of control sulfanilamide of the economic belt around Taihu Lake. The results of the present study are useful in providing information for PPCPs control and sustainable water management in freshwater lakes.

Attenuation pathways of erythromycin and biochemical responses related to algal growth and lipid synthesis in a microalga-effluent system

Microalgal cultivation in municipal wastewater treatment plants (WWTPs) can realize the coupling of wastewater treatment and microalgae energy utilization, however, the residual antibiotics in effluents from WWTPs affect the growth of microalgae. In this study, green alga (Scenedesmus obliquus) cells were inoculated into the effluents to ascertain the attenuation pathways of erythromycin (ERY) and the biochemical responses of microalga in a microalga-effluent system. Results showed that hydrolysis, photolysis, and biodegradation (including bioadsorption) cause the attenuation of ERY in a microalga-effluent system, and the biodegradation (including bioadsorption) has the greatest removal rate (reaching a maximum of 57.87%), followed by hydrolysis (reaching a maximum of 34.13%), and photolysis (less than 5%) after five days. The photosynthetic pigment contents in cells of microalga decreased the most (by 35.66% for chlorophyll a), and the production of ROS was stimulated (by 33.75%) after five-day exposure to ERY at an initial concentration of 100 μg/L. Meanwhile, the activity of ribulose-1,5-biphosphate carboxylase (RuBPCase) decreased by 55.65%, and the activity of acetyl-CoA carboxylase (ACCase) increased by 55.65%. The ROS level, photosynthetic pigment content, and RuBPCase activity were extremely significantly correlated with each other (P < 0.01), indicating that exposure to ERY changed those biochemical responses related to the rate of photosynthesis of microalga, inhibiting the growth thereof. On the other hand, exposure to ERY increased lipid production by microalga through the induced ACCase activity.

Synthesis and characterization of immobilized titanium-zirconium Sn-doped oxides onto metallic meshes and their photocatalytic activity for erythromycin mineralization

An improvement of the photocatalytic properties of TiO2, by the doping with Sn, a non-critical raw material, was evaluated. A series of Sn-doped titania-zirconia structured photocatalysts were synthesized using the washcoating method on stainless steel meshes. Two methodologies for the Sn incorporation were applied using different Sn sources: oxalate and SnO2 (powder or nanoparticles). Coating properties were characterized by SEM-EDS, XPS and LRS techniques, and their photocatalytic performances were tested for erythromycin (ERY) oxidation. The coating synthesized with the Sn-oxalate suspension presented a more homogeneous distribution of the elements. Surface characterization showed that the Sn-doped catalysts presented a partial reduction of the Ti4+ species to Ti3+ with the presence of some oxygen vacancies, associated to an effective interaction between Ti and Sn (surface Ti1-xSnxO2-like structure). The lowest amount of these vacancies were found when the Sn source was SnO2 (powder or nanoparticles). The formation of a Ti-Sn-O solid solution decreased the recombination of the e-cb/h+vb pair, allowing better performance on the photocatalytic degradation of ERY, with 46% mineralization for the Sn doped photocatalyst and 26% for the Sn-free catalyst. The Sn addition methodology influenced the catalytic activity due to the formation of different oxidizing agents, leading to different carboxylic acids generation. The best photocatalyst presented after more than 400 h of use, a catalytic activity decreases of only 11.3% in mineralization, showing that this photocatalyst has a high catalytic stability. Besides, after a regeneration process, the catalytic activity was almost thoroughly recovered.

Quaternary enteric solid dispersion prepared by hot-melt extrusion to mask the bitter taste and enhance drug stability

To mask the bitterness of drug is profoundly important especially in children’s medication. This study designed and investigated a quaternary enteric solid dispersion (QESD) by secondary hot-melt-extrusion. Erythromycin (EM) was chosen as a model drug. The optimal QESD contained enteric polymer HPMCP-55, plasticizer and water-soluble polymer copovidone VA64. Raman and Atomic force microscope has exploited that majority EM was distributed in VA64 matrix, nanometer-sized EM-VA64 system was entrapped within enteric continuous phase to form a solid emulsion-like structure. For the prepared QESD, EM released concentration was far less than bitterness threshold (7 μg/mL to 20 μg/mL) in artificial saliva within the first 30 s. And dissolution rate was increased by 10% in article intestine fluid, which dominated by water-soluble VA64. Stress testing after two months at high-humidity (75% RH) and high-temperature (60 °C) revealed, compared with traditional enteric SDs, the chemical degradation of EM was slowed down in QESD. Furthermore, hydrogen and salt bonds were respectively formed between EM and VA64 and between leaking EM and HPMCP-55, which increasing the system stability and taste-masking. The effect of masking bitter taste can be satisfied as well as enhance drug dissolution rate in the intestine, and formulation physicochemical stability during storage.

The Computational Intervention of Macrolide Antibiotics in the Treatment of COVID-19.

The spike (S) glycoprotein of SARS corona virus (SARS-CoV-2) and human Angiotensin- converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection. The present work is an effort for computational target to block the spike proteins (S) and ACE2 receptor proteins with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY) along with RNA-dependent RNA polymerase (RdRp). Three-dimensional structure of the SARS-CoV-2RdRp was built by the SWISS-MODEL server, the generated structure showed 96.35% identity to the available structure of SARS-Coronavirus NSP12 (6NUR), for model validity, we utilized the SWISS-model server quality parameters and Ramachandran plots. These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site. Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor. At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2 but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by ERY plays an important role for RdRp inactivation, that can prevent the rise of newly budded progeny virus. These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues (Tyr343, and His235) of Endoribonuclease (NSP15) protein. The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of COVID-19 till some better option available.

Analysis and occurrence of macrolide residues in stream sediments and underlying alluvial aquifer downstream from a pharmaceutical plant.

Macrolide antibiotics azithromycin (AZI), erythromycin (ERY) and clarithromycin (CLA) have been recently included in the EU Watch List of contaminants of emerging concern in the aquatic environment. However, their comprehensive assessment in different environmental compartments, by including synthesis intermediates, by-products and transformation products, is still missing. In this work, a novel method, based on pressurized liquid extraction and liquid chromatography-tandem mass spectrometry, was developed and validated for the determination of such an extended range of macrolide residues in sediment and soil samples at low ng/g levels. The method was applied to determine distribution of 13 macrolides in surface and alluvial aquifer sediments collected in a small stream with a history of chronic exposure to wastewater discharges from AZI production. The total concentrations of the target macrolide compounds in surface sediments were up to 29μg/g and the most prominent individual macrolides were parent AZI, its synthesis intermediate N-demethyl AZI and transformation products decladinosyl AZI and N'-demethyl AZI. Some ERY-related compounds, originating from AZI synthesis, were also frequently detected, though at lower concentration levels (up to 0.31ng/g in total). The distribution of macrolide residues in surface sediments indicated their active longitudinal transport by resuspension and redeposition of the contaminated sediment particles. The vertical concentration profiles in stream sediments and the underlying alluvial aquifer revealed that macrolide residues reached deeper alluvial sediments (up to 5m). Moreover, significant levels of macrolides were found in groundwater samples below the streambed, with the total concentrations reaching up to 1.7μg/L. This study highlights the importance of comprehensive chemical characterization of the macrolide residues, which were shown to persist in surface and alluvial aquifer sediment more than ten years after their discharge into the aquatic environment.

Monitoring and Analysis of Drug Resistance of Yersinia in Fresh Meat

Objective To monitor the drug resistance status of yersinia isolates from fresh meat, grasp the drug resistance spectrum and trend of Yersinia isolates in Our province, and provide important reference data for guiding the rational application of antibiotics in human clinical practice and controlling the spread of drug resistant strains. Methods A total of 600 pieces of fresh pork, beef and chicken were collected from several farmers' markets and supermarkets in Changchun every month for 15 months from August 18th to October 19th. 80 strains of Yersinia strains were detected, and MIC concentrations of drug resistance were detected by microbroth dilution with 15 antibiotic sensitive plates. Results 80 strains of Yersinia strains were counted. The total drug resistance rate of Yersinia pestis was 98.8%, and cefazolin (CFZ) had the highest drug resistance rate of 92.5.% (74/80). Erythromycin (ERY) was followed by 58.8% (47/80). Ampicillin (AMP) 57.5% (46/80); Naproxil acid (NAL) and cefoxitin (CFX) were 28.8 (23/80) and were somewhat resistant to other antibiotics. But all strains were sensitive to imipenem (IMP) and gentamicin (GEN). There were 28 strains with multiple drug resistance, accounting for 35.4% (28/79). Conclusion There are multiple antibiotic resistance in Yersinia strains in this monitoring, and the multiple drug resistance is serious and the resistance spectrum is diverse. In order to ensure food safety and human health, great attention should be paid to and enhanced drug resistance monitoring of Yersinia.

ANALYTICAL SOLUTION FOR SAFE BREASTFEEDING. IMMUNOCHROMATOGRAPHIC ASSAY OF MACROLIDE ANTIBIOTICS IN MOTHER'S MILK

When antibiotics are given to nursing women, clarithromycin (CLA), roxithromycin (ROK), erythromycin (ERI), azithromycin (AZI), dirithromycin (DIR), and oleandomycin (OLE) are excreted in breast milk. A rapid group-specific antibody test for these analytes in breast milk has been developed as a self-monitoring tool for safe feeding in infants.

Clinically Applicable Rapid Susceptibility Testing of Multi-Drug Resistant &lt;i&gt;Staphylococcus Aureus&lt;/i&gt; by Mass Spectrometry and Extreme Gradient Boosting Machine

Multi-drug resistant Staphylococcus aureus is one of the major causes of severe infections. Due to the delays of conventional antibiotic susceptibility test (AST), most cases were prescribed by experience with a lower recovery rate. Linking a 7-year study of over 20,000 Staphylococcus aureus infected patients, we incorporated mass spectrometry and machine learning technology to predict the susceptibilities of patients for 4 different antibiotics that can enable early antibiotic decisions. The predictive models were externally validated in an independent patient cohort, resulting in an area under the receiver operating characteristic curve of 0.94, 0.90, 0.86, 0.91 and an area under the precision-recall curve of 0.93, 0.87, 0.87, 0.81 for oxacillin (OXA), clindamycin (CLI), erythromycin (ERY) and trimethoprim-sulfamethoxazole (SXT), respectively. Moreover, our pipeline provides AST 24–36 h faster than standard workflows, reduction of inappropriate antibiotic usage with preclinical prediction, and demonstrates the potential of combining mass spectrometry with machine learning (ML) to assist early and accurate prescription. Therapies to individual patients could be tailored in the process of precision medicine.

Bioaugmentation with immobilized endophytic Penicillium restrictum to improve quorum quenching activity for biofouling control in an aerobic hollow-fiber membrane bioreactor treating antibiotic-containing wastewater

The effects of bioaugmentation with immobilized Penicillium restrictum on the removal efficiency of sulfamethoxazole (SMX), erythromycin (ERY) and tetracycline (TC) antibiotics as well as membrane biofouling was studied using hollow-fiber membrane bioreactor (HF-MBR). Bioaugmentation with P. restrictum led to a significant change in the antibiotic removal efficiency and relative abundance of aerobic microbial community, most probably as a result of its quorum quenching activity. Furthermore, in addition to its role in the increase of SMX and ERY removal efficiencies and the decrease of their sorption on solid phase, bioaugmentation significantly reduced the transmembrane pressure which in turn reduced membrane clogging. The most abundant phyla in sludge and biofilm samples in the presence of P. restrictum were observed to be Proteobacteria, Bacteroidetes and Firmicutes. Differences in bacterial compositions and their specificity in biodegradation of antibiotics in different reactors showed that bacteria were specifically selected under the pressure of antibiotics and growing fungus.

1463. Activity of Delafloxacin against Multi-Drug-Resistant Fastidious Respiratory Pathogens from European Medical Centers (2014-2019)

BackgroundDelafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019.MethodsA total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC.ResultsThe activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive.ConclusionDLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains.Table 1 DisclosuresJennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)

Development and validation of a stability indicating HPLC method for organic impurities of erythromycin stearate tablets

A rapid, sensitive, and accurate high-performance liquid chromatography (HPLC) method was developed and validated for the separation and analysis of organic impurities in erythromycin stearate tablets. The method separates Erythromycin, Erythromycin B, Erythromycin C and nine impurities (EP Impurity A, B, C, D, E, F, H, I and M). The chromatographic separation was achieved on a Waters XBridge C18 (100 mm × 4.6 mm, 3.5 μm) column. The mobile phase comprised of 0.4 % ammonium hydroxide in water and methanol delivered in a gradient mode. The compounds of interest were monitored at 215 nm. The stability-indicating capability of this method was evaluated by performing stress studies. Erythromycin was found to degrade significantly under acid, base, and oxidative stress conditions and it was only stable under thermal and photolytic degradation conditions. The degradation products were well resolved from the erythromycin peaks. In addition, the major degradants formed under stress conditions were characterized by ultra-high-performance liquid chromatography coupled with Single-Quadrupole Mass Spectrometer (UHPLC-QDa). The method was validated to fulfill International Conference on Harmonization (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, and robustness. The developed method could be incorporated into the USP monograph and applied for routine quality control analysis of erythromycin stearate tablets.