Efficacy of omadacycline in the treatment of Legionella pneumonia: a case report.

Legionella, one of the main pathogens that causes community-acquired pneumonia, can lead to Legionella pneumonia, a condition characterized predominantly by severe pneumonia. This disease, caused by the bacterium Legionella pneumophila, can quickly progress to critical pneumonia and is often associated with damage to multiple organs. As a result, it requires close attention in terms of clinical diagnosis and treatment. Omadacycline, a new type of tetracycline derivative belonging to the aminomethylcycline class of antibiotics, is a semi-synthetic compound derived from minocycline. Its key structural feature, the aminomethyl modification, allows omadacycline to overcome bacterial resistance and broadens its range of effectiveness against bacteria. Clinical studies have demonstrated that omadacycline is not metabolized in the body, and patients with hepatic and renal dysfunction do not need to adjust their dosage. This paper reports a case of successful treatment of Legionella pneumonia with omadacycline in a patient who initially did not respond to empirical treatment with moxifloxacin. The patient also experienced electrolyte disturbance, as well as dysfunction in the liver and kidneys, delirium, and other related psychiatric symptoms.

Development, synthesis, and application of magnetic layered double hydroxides (Fe3O4@SiO-LDH/DS-) as an efficient adsorbent for the removal of tetracyclines from milk samples.

This work presents the development, synthesis, and application of a layered double hydroxide (LDH) coupled to magnetic particles for the removal of antibiotics as tetracyclines (TC´s): tetracycline (TC), chlortetracycline (CT), oxytetracycline (OT), and doxycycline (DT) from milk samples. The LDH synthesis conditions, reaction time (30-90 min), molar ratios Mg2+/Al3+ (7:1-1:7), interlayer anion (NO3-, Cl-, CO32-, and dodecyl sulphate (DS-)) were evaluated. Under synthesis conditions (reaction time of 30 min, Mg2+/Al3+ molar ratio of 7:1, and DS- as interlayer anion), the LDH was coupled in a magnetic solid phase microextraction (MSPµE) methodology. At the optimal extraction conditions (pH 6, 5 min of contact time, 10 mg of adsorbent), a removal percentage of 99.0 % was obtained for each tetracycline. FTIR, TGA, SEM, and adsorption isotherms were employed to characterize the optimal adsorbent. Each experiment was corroborated by large-volume sample stacking capillary electrophoresis (LVSS-CE). The adsorbent was applied directly to positive milk samples (previously tested) for TC´s removal.

Integrated assessment of the spatial distribution, sources, degradation, and human risk of tetracyclines in honey in China.

Tetracyclines are widely used in Chinese apiculture. However, limited information is available on the presence of tetracycline residues in honey and the sources, degradation patterns, and associated health risks of these compounds. In this study, the presence of tetracyclines in honey samples across China was investigated over a four-year period. Additionally, the risks of dietary intake, as well as the sources and degradation patterns of tetracyclines in honey, were assessed. The three-dimensional spatial distributions (floral region, geographical region and entomological origin) of tetracyclines contamination varied significantly. Tetracycline residues in honey posed a moderate risk to children aged 3-10 years in Northwest China. Source analysis indicated that colony migration serves as the primary source of tetracyclines in honey. Based on the degradation patterns of tetracyclines in honey within colonies and during storage, oxytetracycline is more readily degraded than other tetracyclines. The main degradation products of tetracyclines are epimers and dehydration products, and the effects of these products on human health and the environment should be further evaluated in future studies. This comprehensive investigation provides valuable insights into the safe use and regulation of tetracyclines in Chinese apiculture.

Magnetic solid-phase extraction of tetracyclines from milk using metal-organic framework MIL-101(Cr)-NH2 functionalised hydrophilic magnetic nanoparticles.

Novel metal-organic framework MIL-101(Cr)-NH2 functionalised hydrophilic polydopamine-modified Fe3O4 magnetic nanoparticles (Fe3O4@PDA@MIL-101(Cr)-NH2) were synthesised and used as magnetic solid-phase extraction (MSPE) adsorbents for extracting tetracyclines (TCs) from milk samples. The integrated Fe3O4@PDA@MIL-101(Cr)-NH2 exhibited convenient magnetic separation and exceptional multi-target binding capabilities. Furthermore, the PDA coating significantly enhanced the hydrophilicity and extraction efficiency of the material, thereby facilitating the extraction of trace TCs. Various factors affecting MSPE, such as adsorbent dosage, extraction time, pH value, and desorption conditions, were optimised. The developed MSPE method coupled with high-performance liquid chromatography demonstrated good linearity (R2 ≥ 0.9989), acceptable accuracy (82.2%-106.1%), good repeatability (intra-day precision of 0.8%-4.7% and inter-day precision of 1.1%-4.5%), low limits of detection (2.18-6.25 µg L-1), and low limits of quantification (6.54-18.75 µg L-1) in TCs detection. The approach was successfully used for the quantification of trace TCs in real milk samples.

Eravacycline: a comprehensive review of in vitro activity, clinical efficacy, and real-world applications.

INTRODUCTION: The escalating threat of multidrug-resistant organisms necessitates constant exploration for novel antimicrobial agents. Eravacycline has emerged as a promising solution due to its unique chemical structure, which enhances potency and expands its spectrum of activity. AREA COVERED: This review provides a thorough examination of eravacycline, encompassing its in vitro activity against Gram-positive and Gram-negative aerobes, carbapenem-non-susceptible organisms, anaerobes, and other bacterial strains. Additionally, it evaluates evidence from clinical studies to establish its clinical effect and safety. EXPERT OPINION: Eravacycline, a synthetic fluorocycline, belongs to the tetracyclines class. Similar to other tetracycline, eravacycline exerts its antibacterial action by reversibly binding to the bacterial ribosomal 30S subunit. Eravacycline demonstrates potent in vitro activity against many Gram-positive and Gram-negative aerobes, anaerobes, and multidrug-resistant organisms. Randomized controlled trials and its associated meta-analysis affirm eravacycline's efficacy in treating complicated intra-abdominal infections. Moreover, real-world studies showcase eravacycline's adaptability and effectiveness in diverse clinical conditions, emphasizing its utility beyond labeled indications. Despite common gastrointestinal adverse events, eravacycline maintains an overall favorable safety profile, reinforcing its status as a tolerable antibiotic. However, ongoing research is essential for refining eravacycline's role, exploring combination therapy, and assessing its performance against biofilms, in combating challenging bacterial infections.

A novel fluorescence platform for specific detection of tetracycline antibiotics based on [MQDA-Eu3+] system.

Tetracycline antibiotics (TCs) are extensively used in clinical medicine, animal husbandry, and aquaculture because of their cost-effectiveness and high antibacterial efficacy. However, the presence of TCs residues in the environment poses risks to humans. In this study, an inner filter effect (IFE) fluorescent probe, 2,2'-(ethane-1,2-diylbis((2-((2-methylquinolin-8-yl)amino)-2-oxoethyl)azanediyl))diacetic acid (MQDA), was developed for the rapid detection of Eu3+ within 30 s. And its complex [MQDA-Eu3+] was successfully used for the detection of TCs. Upon coordination of a carboxyl of MQDA with Eu3+ to form a [MQDA-Eu3+] complex, the carboxyl served as an antenna ligand for the effective detection of Eu3+ to intensify the emission intensity of MQDA via "antenna effect", the process was the energy absorbed by TCs via UV excitation was effectively transferred to Eu3+. Fluorescence quenching of the [MQDA-Eu3+] complex was caused by the IFE in multicolor fluorescence systems. The limits of detection of [MQDA-Eu3+] for oxytetracycline, chlorotetracycline hydrochloride, and tetracycline were 0.80, 0.93, and 1.7 µM in DMSO/HEPES (7:3, v/v, pH = 7.0), respectively. [MQDA-Eu3+] demonstrated sensitive detection of TCs in environmental and food samples with satisfactory recoveries and exhibited excellent imaging capabilities for TCs in living cells and zebrafish with low cytotoxicity. The proposed approach demonstrated considerable potential for the quantitative detection of TCs.

Omadacycline drug susceptibility testing for non-tuberculous mycobacteria using oxyrase to overcome challenges with drug degradation.

BACKGROUND: Drug susceptibility testing (DST) protocol of omadacycline against non-tuberculous mycobacteria has not yet been established. We developed a method to accurately determine MIC omadacycline MIC against Mycobacterium abscessus (Mab), Mycobacterium avium-complex (MAC), and Mycobacterium kansasii (Mkn). METHODS: First, we identified the oxyrase concentration not affecting Mab, MAC, and Mkn growth followed by omadacycline MIC experiments with and without oxyrase using reference and clinical strains. RESULTS: Oxyrase 0.5 % (v/v) stabilized omadacycline in the culture medium. The median omadacycline MIC was 1 mg/L for Mab and 8 mg/L for Mkn. For MAC, the median omadacycline MIC was 2 mg/L for M. avium, 256 mg/L for M. intracellulare, and 4 mg/L for M. chimaera (p < 0.0001). Wilcoxon matched-pairs signed rank test revealed statistically lower MICs with oxyrase for all MAC subspecies (p < 0.0001), all Mab subspecies (p < 0.0001), and Mkn (p = 0.0002). The decrease in MICs with oxyrase was 17/18 of Mab, 14/19 of Mkn, 8/8 of M. avium, 4/5 M. chimera, but only 11/18 of M. intracellulare (p < 0.013). CONCLUSION: Use of 0.5 % oxyrase could be a potential solution to reliable and reproducible omadacycline MIC of Mab. However, oxyrase demonstrated a variable effect in reducing MICs against MAC and Mkn.

Low concentration of peroxymonosulfate coupled with visible light triggers oxygen reactive species generation over constructed Bi25FeO40/BiOCl Z-scheme heterojunction for various tetracycline antibiotics removal.

Photocatalytic peroxymonosulfate (PMS) oxidation systems demonstrate significant potential and promising prospects through the interconnection of photocatalytic and PMS oxidation for simultaneously achieving efficient pollutant removal and reduction of PMS dosage, which prevents resource wastage and secondary pollution. In this study, a Z-scheme Bi25FeO40/BiOCl (BOFC) heterojunction was constructed to carry out the photocatalytic PMS oxidation process for tetracyclines (TCs) pollutants at low PMS concentrations (0.08 mM). The photocatalytic PMS oxidation rate of Bi25FeO40/BiOCl composites for tetracycline hydrochloride (TCH), chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DXC) reaches 86.6%, 83.6%, 86.7%, and 88.0% within 120 min. Simultaneously, the BOFC/PMS system under visible light (Vis) equally displayed the practical application prospects for the solo and mixed simulated TCs antibiotics wastewater. Based on the electron spin resonance (ESR) and X-ray photoelectron spectroscopy (XPS) valence band spectrum, a Z-scheme electron migration pathway was proposed to elucidate the mechanism underlying the performance enhancement of BOFC composites. Bi25FeO40 in BOFC composites can serve as active site for activating PMS by the formation of Fe3+/Fe2+ cycle. Toxicity estimation software tool (T.E.S.T.) and mung beans planting experiment demonstrates that BOFC/PMS/Vis system can reduce toxicity of TCs wastewater. Therefore, BOFC/PMS/Vis system achieves efficient examination in different water environments and efficient utilization of PMS, which displays a scientific reference for achieving environmentally-friendly and resource-saving handling processes.

Evaluation of the synergistic effect of eravacycline and tigecycline against carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a substantial healthcare challenge. This study assessed the in vitro efficacy of selected antibiotic combinations against CRKP infections. METHODS: Our research involved the evaluation of 40 clinical isolates of CRKP, with half expressing Klebsiella pneumoniae carbapenemase (KPC) and half producing Metallo-ß-lactamase (MBL), two key enzymes contributing to carbapenem resistance. We determined the minimum inhibitory concentrations (MICs) of four antibiotics: eravacycline, tigecycline, polymyxin-B, and ceftazidime/avibactam. Synergistic interactions between these antibiotic combinations were examined using checkerboard and time-kill analyses. RESULTS: We noted significant differences in the MICs of ceftazidime/avibactam between KPC and MBL isolates. Checkerboard analysis revealed appreciable synergy between combinations of tigecycline (35%) or eravacycline (40%) with polymyxin-B. The synergy rates for the combination of tigecycline or eravacycline with polymyxin-B were similar among the KPC and MBL isolates. These combinations maintained a synergy rate of 70.6% even against polymyxin-B resistant isolates. In contrast, combinations of tigecycline (5%) or eravacycline (10%) with ceftazidime/avibactam showed significantly lower synergy than combinations with polymyxin-B (P < 0.001 and P = 0.002, respectively). Among the MBL CRKP isolates, only one exhibited synergy with eravacycline or tigecycline and ceftazidime/avibactam combinations, and no synergistic activity was identified in the time-kill analysis for these combinations. The combination of eravacycline and polymyxin-B demonstrated the most promising synergy in the time-kill analysis. CONCLUSION: This study provides substantial evidence of a significant synergy when combining tigecycline or eravacycline with polymyxin-B against CRKP strains, including those producing MBL. These results highlight potential therapeutic strategies against CRKP infections.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Eravacycline, an antibacterial drug, repurposed for pancreatic cancer therapy: insights from a molecular-based deep learning model.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a serious threat to health, with limited effective therapeutic options, especially due to advanced stage at diagnosis and its inherent resistance to chemotherapy, making it one of the leading causes of cancer-related deaths worldwide. The lack of clear treatment directions underscores the urgent need for innovative approaches to address and manage this deadly condition. In this research, we repurpose drugs with potential anti-cancer activity using machine learning (ML). METHODS: We tackle the problem by using a neural network trained on drug-target interaction information enriched with drug-drug interaction information, which has not been used for anti-cancer drug repurposing before. We focus on eravacycline, an antibacterial drug, which was selected and evaluated to assess its anti-cancer effects. RESULTS: Eravacycline significantly inhibited the proliferation and migration of BxPC-3 cells and induced apoptosis. CONCLUSION: Our study highlights the potential of drug repurposing for cancer treatment using ML. Eravacycline showed promising results in inhibiting cancer cell proliferation, migration and inducing apoptosis in PDAC. These findings demonstrate that our developed ML drug repurposing models can be applied to a wide range of new oncology therapeutics, to identify potential anti-cancer agents. This highlights the potential and presents a promising approach for identifying new therapeutic options.

45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis.

There is considerable interest in the use of doxycycline post exposure prophylaxis (PEP) to reduce the incidence of bacterial sexually transmitted infections (STIs). An important concern is that this could select for tetracycline resistance in these STIs and other species. We searched PubMed and Google Scholar, (1948-2023) for randomized controlled trials comparing tetracycline PEP with non-tetracycline controls. The primary outcome was antimicrobial resistance (AMR) to tetracyclines in all bacterial species with available data. Our search yielded 140 studies, of which three met the inclusion criteria. Tetracycline PEP was associated with an increasedprevalence of tetracycline resistance in Neisseria gonorrhoeae, but this effect was not statistically significant (Pooled OR 2.3, 95% CI 0.9-3.4). PEP had a marked effect on the N. gonorrhoeae tetracycline MIC distribution in the one study where this was assessed. Prophylactic efficacy was 100% at low MICs and 0% at high MICs. In the one study where this was assessed, PEP resulted in a significant increase in tetracycline resistance in commensal Neisseria species compared to the control group (OR 2.9, 95% CI 1.5-5.5) but no significant effect on the prevalence of tetracycline resistance in Staphylococcus aureus. The available evidence suggests that PEP with tetracyclines could be associated with selecting tetracycline resistance in N. gonorrhoeae and commensal Neisseria species.

Covalent organic framework aerogel for high-performance solid-phase extraction of tetracycline antibiotics: Experiment and simulated calculation on adsorption behavior.

Three-dimensional sponge-architecture covalent organic frameworks (COFs)-aerogel was successfully designed and synthesized via a freeze-drying template approach, and utilized as an efficient sorbent in solid-phase extraction (SPE). A method for selective enrichment of pharmaceutical contaminants including tetracycline, chlortetracycline, methacycline and oxytetracycline in the environment and food samples was proposed by combining with high performance liquid chromatography (HPLC). To understand the adsorption mechanism, selectivity test and molecular dynamics (MD) simulated calculation were both carried out. The experimental and in-silico results demonstrated that the COFs-aerogel possessed high selectivity for contaminants with H bond acceptors/donors and good efficiency with maximum adsorption capacity up to 294.1 mg/g. The SPE-based HPLC method worked well in the range of 8-1000 ng/mL, with the need of little dose of adsorbent and sample volume while no need of spectrometer, outgoing the reported adsorbents. Under the optimized conditions, the intra-day and inter-day relative standard deviations (RSD) of repeatability were within 2.78-6.29 % and 2.44-8.42 % (n = 5). The results meet the current detection requirement for practical applications, and could be extended for further design of promising adsorbents.

Quantitative determination of tetracyclines in medicated feed for food-producing animals by HPLC-DAD.

Tetracyclines are a group of antibiotic substances largely administered through medicated feed to control diseases in food-producing animals. Fine dosing of antibiotics contained in medicated feed is crucial for the success of the treatment as well as minimising potential threats such as the spread of antimicrobial resistance and the transfer of antibiotic residues in food. A rapid analytical method based on HPLC with diode array detection (HPLC-DAD) was developed to quantify oxytetracycline, chlortetracycline and doxycycline in medicated feed. The reported method underwent in-house validation and was found to be suitable for the quantification of three target tetracyclines within the concentration range of 40-1000 mg kg-1 in official routine analysis. The method was applied to 103 official samples in the framework of the Italian National Plan on animal feed during the years 2021-2023 and nine non-compliant concentrations were identified in swine and fish feed samples.

Development, validation, and clinical application of a UPLC-MS/MS method for omadacycline determination in human serum.

BACKGROUND: Omadacycline is the first aminomethyl-tetracycline variety to successfully enter clinical applications. To support regular therapeutic drug monitoring (TDM) in clinical practice, an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed that would allow omadacycline quantification in human serum. METHODS: Proteins were precipitated from serum samples using methanol. Tigecycline was used as the internal standard. Mobile phase A was formic acid in water (0.1% v/v) and mobile phase B was methanol. UPLC-MS/MS was performed for analyte separation using a gradient elution program at a flow rate of 0.3 mL/min and a total run time of 5 min. The chromatography column was a ZORBAX PRHD SB-Aq (3 × 50 mm, 1.8 µm, Agilent, USA). The multiple reaction monitoring transitions at m/z = 557.4/470.3 and 586.5/513.3 were selected for omadacycline and tigecycline in the positive mode, respectively. RESULTS: The validated curve ranges were 0.5-25.0 µg/mL. This method exhibited acceptable selectivity, matrix effects, and recovery. The inter- and intra-run accuracies ranged from 93.5% to 114.8%, and the inter- and intra-run precisions were between 1.29% and 5.55%. CONCLUSIONS: The LC-MS/MS method provided a simple, specific, and rapid quantification of omadacycline in the serum of patients with pulmonary infection.

Assessing Clinician Utilization of Next-Generation Antibiotics Against Resistant Gram-Negative Infections in U.S. Hospitals : A Retrospective Cohort Study.

BACKGROUND: The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. OBJECTIVE: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics). DESIGN: Retrospective cohort. SETTING: 619 U.S. hospitals. PARTICIPANTS: Adult inpatients. MEASUREMENTS: Quarterly percentage change in antibiotic use was calculated using weighted linear regression. Machine learning selected candidate variables, and mixed models identified factors associated with new (vs. traditional) antibiotic use in DTR infections. RESULTS: Between quarter 1 of 2016 and quarter 2 of 2021, ceftolozane-tazobactam (approved 2014) and ceftazidime-avibactam (2015) predominated new antibiotic usage whereas subsequently approved gram-negative antibiotics saw relatively sluggish uptake. Among gram-negative infection hospitalizations, 0.7% (2551 [2631 episodes] of 362 142) displayed DTR pathogens. Patients were treated exclusively using traditional agents in 1091 of 2631 DTR episodes (41.5%), including "reserve" antibiotics such as polymyxins, aminoglycosides, and tigecycline in 865 of 1091 episodes (79.3%). Patients with bacteremia and chronic diseases had greater adjusted probabilities and those with do-not-resuscitate status, acute liver failure, and Acinetobacter baumannii complex and other nonpseudomonal nonfermenter pathogens had lower adjusted probabilities of receiving newer (vs. traditional) antibiotics for DTR infections, respectively. Availability of susceptibility testing for new antibiotics increased probability of usage. LIMITATION: Residual confounding. CONCLUSION: Despite FDA approval of 7 next-generation gram-negative antibiotics between 2014 and 2019, clinicians still frequently treat resistant gram-negative infections with older, generic antibiotics with suboptimal safety-efficacy profiles. Future antibiotics with innovative mechanisms targeting untapped pathogen niches, widely available susceptibility testing, and evidence demonstrating improved outcomes in resistant infections might enhance utilization. PRIMARY FUNDING SOURCE: U.S. Food and Drug Administration; NIH Intramural Research Program.

Novel insights into the co-selection of metal-driven antibiotic resistance in bacteria: a study of arsenic and antibiotic co-exposure.

The simultaneous development of antibiotic resistance in bacteria due to metal exposure poses a significant threat to the environment and human health. This study explored how exposure to both arsenic and antibiotics affects the ability of an arsenite oxidizer, Achromobacter xylosoxidans CAW4, to transform arsenite and its antibiotic resistance patterns. The bacterium was isolated from arsenic-contaminated groundwater in the Chandpur district of Bangladesh. We determined the minimum inhibitory concentration (MIC) of arsenite, cefotaxime, and tetracycline for A. xylosoxidans CAW4, demonstrating a multidrug resistance (MDR) trait. Following this determination, we aimed to mimic an environment where A. xylosoxidans CAW4 was exposed to both arsenite and antibiotics. We enabled the strain to grow in sub-MIC concentrations of 1 mM arsenite, 40 µg/mL cefotaxime, and 20 µg/mL tetracycline. The expression dynamics of the arsenite oxidase (aioA) gene in the presence or absence of antibiotics were analyzed. The findings indicated that simultaneous exposure to arsenite and antibiotics adversely affected the bacteria's capacity to metabolize arsenic. However, when arsenite was present in antibiotics-containing media, it promoted bacterial growth. The study observed a global downregulation of the aioA gene in arsenic-antibiotic conditions, indicating the possibility of increased susceptibility through co-resistance across the entire bacterial population of the environment. This study interprets that bacterial arsenic-metabolizing ability can rescue the bacteria from antibiotic stress, further disseminating environmental cross-resistance. Therefore, the co-selection of metal-driven antibiotic resistance in bacteria highlights the need for effective measures to address this emerging threat to human health and the environment.

An expanded transcriptome atlas for Bacteroides thetaiotaomicron reveals a small RNA that modulates tetracycline sensitivity.

Plasticity in gene expression allows bacteria to adapt to diverse environments. This is particularly relevant in the dynamic niche of the human intestinal tract; however, transcriptional networks remain largely unknown for gut-resident bacteria. Here we apply differential RNA sequencing (RNA-seq) and conventional RNA-seq to the model gut bacterium Bacteroides thetaiotaomicron to map transcriptional units and profile their expression levels across 15 in vivo-relevant growth conditions. We infer stress- and carbon source-specific transcriptional regulons and expand the annotation of small RNAs (sRNAs). Integrating this expression atlas with published transposon mutant fitness data, we predict conditionally important sRNAs. These include MasB, which downregulates tetracycline tolerance. Using MS2 affinity purification and RNA-seq, we identify a putative MasB target and assess its role in the context of the MasB-associated phenotype. These data-publicly available through the Theta-Base web browser ( http://micromix.helmholtz-hiri.de/bacteroides/ )-constitute a valuable resource for the microbiome community.

In vitro activity of omadacycline against clinical isolates of Nocardia.

Nocardiosis typically requires a prolonged treatment duration of ≥6 months and initial combination therapy with 2-3 antibiotics. First-line regimens for nocardiosis are associated with considerable toxicity; therefore, alternative therapies are needed. Omadacycline is an aminomethylcycline with broad antimicrobial activity whose in vitro activity against Nocardia species has not been formally assessed. The in vitro potency of omadacycline was evaluated against 300 Nocardia clinical isolates by broth microdilution. The most common Nocardia species tested were N. cyriacigeorgica (21%), N. nova (20%), and N. farcinica (12%). The most common specimens were respiratory (178 isolates, 59%) and wound (57 isolates, 19%). Omadacycline minimum inhibitory concentrations (MICs) across all Nocardia species ranged from 0.06 µg/mL to 8 µg/mL, with an MIC50 of 2 µg/mL and MIC90 of 4 µg/mL. The lowest MICs were found among N. paucivorans (MIC50 = 0.25 µg/mL, MIC90 = 0.25 µg/mL), N. asiatica (MIC50 = 0.25 µg/mL, MIC90 = 1 µg/mL), N. abscessus complex (MIC50 = 0.5 µg/mL, MIC90 = 1 µg/mL), N. beijingensis (MIC50 = 0.5 µg/mL, MIC90 = 2 µg/mL), and N. otitidiscaviarum (MIC50 = 1 µg/mL, MIC90 = 2 µg/mL). The highest MICs were found among N. farcinica (MIC50 = 4 µg/mL, MIC90 = 8 µg/mL). In vitro potency differed by species among Nocardia clinical isolates. Further studies are warranted to evaluate the potential clinical utility of omadacycline for nocardiosis.

Comprehensive Assessment of Environmental Emissions, Fate, and Risks of Veterinary Antibiotics in China: An Environmental Fate Modeling Approach.

China is one of the major global consumers of veterinary antibiotics. Insufficient recognition of emissions and environmental contamination hamper global efforts to prevent antibiotic resistance development. This pioneering study combined empirical data and modeling approaches to predict total 2010-2020 emissions of 80 veterinary antibiotics ranging from 23,110 to 40,850 tonnes/year, after 36-50% antibiotic removal by manure treatment. Following an initial increase of 10% from 2010 to 2015, emissions declined thereafter by 43%. While 85% of emissions discharged into soils, approximately 56%, 23%, and 18% of environmental residue were ultimately distributed in soils, freshwaters, and seawaters under steady-state conditions. In 2020, 657 (319-1470) tonnes entered the ocean from inland freshwaters. Median ∑antibiotics concentrations were estimated at 4.7 × 103 ng/L in freshwaters and 2.9 ng/g in soils, with tetracyclines and sulfonamides as the predominant components. We identified 44 veterinary antibiotics potentially posing high risks of resistance development in freshwaters, with seven exhibiting high risks in >10% of Chinese freshwater areas. Tetracyclines were the category with the most antibiotics exhibiting elevated risks; however, sulfamethylthiazole demonstrated the highest individual compound risk. The Haihe River Basin displayed the highest susceptibility overall. The findings offer valuable support for control of veterinary antibiotic contamination in China.