UNASSIGNED: Antibiotics frequently induce abnormal liver function. Omadacycline is a novel aminomethylcycline antibiotic, which shows potent activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical (including Legionella pneumophila) bacteria. Of note, omadacycline is tolerable in most patients with liver impairment. However, evidence regarding the application of omadacycline in patients with Legionella pneumophila pneumonia after experiencing liver dysfunction is scarce.
UNASSIGNED: The current study reported 6 cases of patients with Legionella pneumophila pneumonia receiving omadacycline as subsequent antibiotics after experiencing liver dysfunction.
UNASSIGNED: These 6 cases were admitted to the hospital for pneumonia and received antibiotic therapy, including piperacillin-tazobactam, imipenem, meropenem, and moxifloxacin. After receiving these antibiotics, increased liver enzymes were noted. Although hepatoprotective therapy (such as magnesium isoglycyrrhizinate and glutathione) was given, the liver function was still abnormal. According to metagenomic next-generation sequencing, these patients were diagnosed with Legionella pneumophila pneumonia. Considering the abnormal liver function, the antibiotic therapy was switched to omadacycline-containing antibiotic therapy. After that, liver function was improved, and the infection was ameliorated. Ultimately, all patients discharged from the hospital, including 2 patients who achieved complete clinical symptomatic improvement and 4 patients who achieved partial clinical symptomatic improvement.
UNASSIGNED: This study emphasizes the successful treatment of switching to omadacycline after experiencing abnormal liver function in patients with Legionella pneumophila pneumonia. This study suggests that omadacycline may serve as an optional antibiotic for patients with Legionella pneumophila pneumonia, especially when occurring liver dysfunction. However, more clinical studies are required to validate our findings.

暂无摘要。

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.

Omadacycline is an FDA-approved agent for community-acquired bacterial pneumonia (CABP). The purpose of this study is to evaluate the effectiveness of omadacycline for treating CABP patients infected with Staphylococcus aureus, including Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA), using pharmacokinetic/pharmacodynamic (PK/PD) analysis. Monte Carlo simulations (MCSs) were performed by utilizing omadacycline pharmacokinetic (PK) parameters, minimum inhibitory concentration (MIC) data, and in vivo PK/PD targets to calculate the probability of target attainment (PTA) and cumulative fraction of response (CFR) values for different dose regimens against MRSA and MSSA in CABP patients. A dosage regimen with a PTA or CFR expectation value greater than 90% was considered optimal. For all recommended dose regimens, PTA values for MRSA MIC ≤1 and MSSA MIC ≤4 on days 1, 4, and 7 were greater than 90%. Based on the MIC distribution of Staphylococcus aureus, all dose regimens had CFR values greater than 90% for both MRSA and MSSA. CFR values for different bacterial strains were still greater than 90% within the range of PK/PD target values less than 40, although they gradually decreased with increasing PK/PD target values. PK/PD modeling demonstrated that all recommended dose regimens of omadacycline are highly effective against CABP patients infected with MRSA and MSSA. The study provides theoretical support for the efficacy of omadacycline in different dose regimens.

Background Stress affects mental health significantly and is a ubiquitous feature of contemporary living. Among the possible antibiotics are omadacycline and vancomycin, whose anti-inflammatory properties have also been thoroughly documented in recent research. The goal of the current study was to examine their complex involvement in the brain\'s stress response circuits and how they modulate stress. An established model organism that provides a useful platform for examining stress-induced behaviors and possible therapeutic approaches is the zebrafish. To investigate how dopamine affects the stress response, we used a zebrafish model that was exposed to stress. Methodology For three minutes, zebrafish were continually subjected to chasing stress. They were then given antibiotic combinations of 50 µg/mL each of vancomycin and omadacycline at various ratios of 1:1, 3:1, and 3:1. Behavior alterations, including freezing bouts, top-bottom ratios, and latency periods, were analyzed and contrasted with control groups. ImageJ software was utilized to analyze the video footage of the fish. Results The study showed that the combination of omadacycline and vancomycin greatly reduced the behaviors in zebrafish caused by stress. They chose their concentration (50 µg/mL) according to the lethal concentration 50% result. By shortening the latency time and increasing the intensity of breezing sessions, these chemicals restored almost normal activity. There was statistical significance in the outcomes. The results show that the combination of vancomycin and omadacycline may have an anti-psychotic impact on zebrafish behaviors brought on by stress. Their control of stress reactions is consistent with their known roles in the reward and stress circuits of the brain. These results emphasize the complex interactions between neurotransmitter systems and the control of stress, highlighting the therapeutic potential of dopamine in the treatment of stress-related mental illnesses. Conclusions The combination of vancomycin and omadacycline has been shown to have anti-psychotic effects, which presents potential opportunities for the development of new treatment strategies for mental diseases associated with stress. To fully understand the specific processes underpinning their involvement in stress management and how they relate to mental illnesses in humans, more investigation is necessary.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia, tetracycline-resistant Streptococcus pneumonia, MRSA and β-lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

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.

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.

The crystal structure of the title compound {systematic name: (4S,4aS,5aR,12aR)-4,7-bis-(di-methyl-amino)-9-[(2,2-di-methyl-propyl-amino)-meth-yl]-1,10,11,12a-tetra-hydroxy-3,12-dioxo-4a,5,5a,6-tetra-hydro-4H-tetra-cene-2-carb-oxamide dihydrate, C29H40N4O7·2H2O} has been solved and refined using synchrotron X-ray powder diffraction data: it crystallizes in space group R3 with a = 24.34430 (7), c = 14.55212 (4) Å, V = 7468.81 (2) Å3 and Z = 9. Most of the hydrogen bonds are intra-molecular, but two classical N-H⋯O inter-molecular hydrogen bonds (along with probable weak C-H⋯O and C-H⋯N hydrogen bonds) link the mol-ecules into a three-dimensional framework. The framework contains voids, which contain disordered water mol-ecules. Keto-enol tautomerism is apparently important in this mol-ecule, and the exact mol-ecular structure is ambiguous.

This study developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify omadacycline and its epimerization in stool to facilitate microbiome studies. Omadacycline was extracted in a methanol-water-ethylenediaminetetraacetic acid (ETDA) solvent containing deuterated omadacycline as internal standard, followed by dilution. In an optimal gradient elution mode, omadacycline and its C4 epimer were separated within 5 min on reversed-phase C18 column. The method showed a broad working range of 0.1-200 ng/ml with a limitation of detection (LOD) of 0.03 ng/ml, little fecal matrix effect, good intra-day and inter-day accuracy (90-101 %), precision (2-15 %), and recovery rate (99-105 %). The method was sufficiently sensitive to quantify omadacycline in human fecal samples (n = 82) collected during a 10-day therapy course and at follow-up (day 13 and day 30) that ranged from 1 to 4785 µg/g. Further analysis revealed that ∼9 % of omadacycline was epimerized in fecal matrix control while, on average, 37.4 % was epimerized in human fecal samples. This study developed and validated a novel, simple, sensitive, and accurate method utilizing LC-MS/MS to quantify omadacycline its epimerization in the human gut. This has important implications for future studies of omadacycline and other tetracycline-class antibiotics as part of gut microbiome studies.