UNASSIGNED: Young farm animals are susceptible to opportunistic infections which may cause economic losses due to mortality and poor weight gain. The development of antimicrobial resistance and the desire to improve therapy efficacy and safety are the reasons to seek for new antibacterial drugs ensuring rapid recovery with minimum adverse events.
UNASSIGNED: To estimate the efficacy of DOKSI AVZ 500 in respiratory pathologies in young pigs.
UNASSIGNED: The study was conducted in 65-70-day-old Yorkshire piglets with signs of bacterial respiratory pathologies. The animals were treated with the test drug for 3 or 5 days. The reference group received TETRAMAX 500 which is similar to the test drug in terms of chemical structure, mechanism of action, and activity spectrum. The animal\'s status was assessed using clinical examination, clinical blood count, and bacteriological tests.
UNASSIGNED: Both test and reference drugs were well tolerated and ensured the animal recovery within about 4 days. The recovery was accompanied by normalization of hematological parameters and flora composition. The bacterium associated with the disease development, Streptococcus suis, was virtually completely eliminated in all groups. No adverse events were noted. After the treatment, all the animals readily gained weight and live market quality.
UNASSIGNED: DOKSI AVZ 500 was a highly efficient therapy for respiratory pathologies caused by the resident opportunistic flora in piglets. It has also shown noninferiority vs. TETRAMAX 500 in terms of all the health-related parameters and thus can be recommended for introduction in veterinary practice in pig farms.

The abuse and irrational use of tetracyclines (TCs) in human medicine and animal husbandry has become a serious concern, affecting the ecological environment and human health. The aim of this study was to develop a sensitive and selective method using fully automatic solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of twelve TCs in water. Four isotope-labeled internal standards for TCs were used to correct matrix effects. Several parameters affecting extraction efficiency were systematically optimized, and the optimum experimental conditions found were 1.0 L water sample with 0.5 g/L Na2EDTA (pH 3.0) extracted and enriched by CNW HLB cartridge and eluted by 4 mL of acetone:methanol (v/v, 1:1). The enrichment factors were up to 798-1059 but only requiring about 60 min per six samples. Under the optimized conditions, the linearity of the method ranged from 0.2 to 100 μg/L for 12 TCs, the detection limits were as low as 0.01-0.15 ng/L, and the recoveries were in the range of 70%-118%, with relative standard deviations less than 15%. The developed method can be successfully utilized for the determination of 12 TCs in pure water, tap water, river water, and mariculture seawater. In summary, three and six TCs were detected in river water and mariculture seawater, respectively, with total concentrations of 0.074-0.520 ng/L (mean 0.248 ng/L) and 0.792-58.369 ng/L (12.629 ng/L), respectively. Tetracycline (TC) and oxytetracycline (OTC) were the dominant TCs in river water, while doxytetracycline (DXC) and OTC were dominant in mariculture seawater.

Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical application of antibiotics could potentially facilitate the selection of antibiotic resistance in bacteria, yet no studies have investigated antibiotic use in the retail ornamental fish sector and its impact on microbial communities. The present study analyzed the concentrations of twenty antibiotics in the carriage water (which also originates from fish tanks in retail shops) collected monthly from ten local ornamental fish shops over a duration of three months. The antibiotic concentrations were correlated with the sequenced microbial community composition, and the risk of resistance selection in bacteria was assessed. Results revealed that the detected concentrations of tetracyclines were the highest among samples, followed by fluoroquinolones and macrolides. The concentrations of oxytetracycline (44.3 to 2,262,064.2 ng L-1) detected across three months demonstrated a high risk for resistance selection at most of the sampled shops. Zoonotic pathogens (species of Rhodococcus, Legionella, and Citrobacter) were positively correlated with the concentrations of oxytetracycline, tetracycline, chlortetracycline, and enrofloxacin. This suggests that antibiotic use in retail shops may increase the likelihood of selecting for zoonotic pathogens. These findings shed light on the potential for ornamental fish retail shops to create a favorable environment for the selection of pathogens with antibiotics, thereby highlighting the urgent need for enhanced antibiotic stewardship within the industry.

UNASSIGNED: Periorificial dermatitis (POD) is a common, chronic, inflammatory facial skin rash that presents as tiny papules and papulopustules with underlying eczematous-like patches, typically confined to the perioral, perinasal, and periorbital areas. There is currently no Food and Drug Administration (FDA)-indicated treatment for POD; however, broad-spectrum antibiotics are efficacious as a treatment option. Broad-spectrum antibiotics negatively impact gut flora and lead to antibiotic resistance. Narrow-spectrum tetracyclines, such as sarecycline, have a low potential for promoting bacterial resistance and gastrointestinal issues.
UNASSIGNED: We conducted a retrospective chart review in order to evaluate the efficacy of sarecycline in a cohort of patients diagnosed with POD that were treated with sarecycline.
UNASSIGNED: A review of medical records was completed using an electronic medical record. Inclusion criteria included males and females aged 18 to 95 with a diagnosis of POD, treated with sarecycline with a documented follow-up.
UNASSIGNED: Six patients met inclusion criteria, all of which had shown improvement with no reported side effects. Of the six patients, four were female and two were male and the patient ages ranged from 26 to 58 years old (mean=41 years). The course of therapy ranged from 30 to180 days (median=90 days).
UNASSIGNED: Based on the outcomes, there are many potential benefits to treatment of POD with sarecycline over the alternative tetracycline-class antibiotics. There is a need for more large-scale clinical studies evaluating treatment options for POD. Based on the efficacy and tolerability of sarecycline in large- scale acne studies, sarecycline may be an appropriate novel treatment option for POD and should be explored further.

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.

Prosthetic joint infections are often managed with debridement and implant retention (DAIR) or resection arthroplasty with destination spacer placement. Both surgical approaches require long courses of postoperative antibiotics, for which tetracycline antibiotics have not been well-studied. In this retrospective case series, we included patients at our institution treated for staphylococcal prosthetic joint infection managed with DAIR or destination spacer placement who were switched from IV antibiotics to oral tetracycline within 12 weeks of surgery. Our primary outcome of interest was treatment failure within one year of initial surgery. Among the patients in our series, 88.2% (n = 15) of patients who underwent DAIR and 100% (n = 7) of patients who underwent resection arthroplasty with destination spacer remained event-free for one year. These results demonstrated that the use of oral tetracyclines as long-term therapy in the treatment of these infections was effective and well-tolerated.

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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.
CONCLUSIONS: 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.

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.

UNASSIGNED: The escalating resistance of Mycoplasma pneumoniae to macrolides has become a significant global health concern, particularly in low-income and middle-income countries (LMICs). Although tetracyclines and quinolones have been proposed as alternative therapeutic options, concerns regarding age-specific safety issues and the lack of consensus in recommendations across various national guidelines prevail. Thus, the primary objective of this study is to ascertain the most efficacious interventions for second-line treatment of M. pneumoniae infection while considering the age-specific safety issues associated with these interventions.
UNASSIGNED: In this systematic review and network meta-analysis we searched PubMed, Embase, CNKI, and WanFang Data, from inception up to November 11th, 2023. Studies of quinolones or tetracyclines for the treatment of people with M. pneumoniae infection were collected and screened by reading published reports, with any type of study included, and no individual patient-level data requested. A systematic review and direct meta-analysis compared the efficacy of tetracyclines and quinolones regarding time to defervescence (TTD) and the rates of fever disappearance within 24 h and 48 h of antibiotic administration, for managing M. pneumoniae infection. Bayesian network meta-analysis (NMA) was employed to indirectly assess the relative effectiveness of different interventions in people with M. pneumoniae infection and the safety profile of medication in paediatric patients. This study is registered with PROSPERO, CRD42023478383.
UNASSIGNED: The systematic review and direct meta-analysis included a total of 4 articles involving 246 patients, while the NMA encompassed 85 articles involving a substantial cohort of 7095 patients. The NMA measured the effectiveness across all ages and included 7043 patients, with a mean age of 37.80 ± 3.91 years. Of the 85 included studies, 14 (16.5%) were at low risk of bias, 71 (83.5%) were at moderate risk, and no studies were rated as having a high risk of bias. In the direct meta-analysis, no statistically significant differences were found between tetracyclines and quinolones concerning TTD (mean difference: -0.40, 95% CI: -1.43 to 0.63; I2 = 0%), fever disappearance rate within 24 h of antibiotic administration (OR: 0.37, 95% CI: 0.08-1.79; I2 = 58%), and fever disappearance rate within 48 h of antibiotic administration (OR: 1.10, 95% CI: 0.30-3.98; I2 = 59%). However, the comprehensive NMA analysis of clinical response (in 70 studies; n = 6143 patients), shortening of TTD (in 52 studies; n = 4363 patients), shortening length of cough relief or disappearance (in 39 studies; n = 3235 patients), fever disappearance rate at 48 h (in four studies; n = 418 patients) revealed that minocycline exhibited the most favourable outcomes across these various parameters, and the analysis of fever disappearance rate at 24 h (in three studies; n = 145 patients) revealed that levofloxacin may be the most effective, as indicated by the rank probabilities and surface under the cumulative ranking area (SUCRA) value. Moxifloxacin ranked second in clinical response and in shortening the length of cough relief or disappearance, and third in shortening TTD. Notably, when evaluating the occurrence of adverse reactions in paediatric patients (in four studies; n = 239 children), levofloxacin was associated with the highest SUCRA value rankings for the rate of adverse events.
UNASSIGNED: Our findings suggest that tetracyclines and quinolones may be equally effective. Based on the age of participants in the included studies, minocycline may be the most effective intervention for children over eight years of age when all preventive measures are considered, whereas moxifloxacin may benefit people under eight years of age. However, these results should be interpreted with caution, given the limited number of studies and patients included, and the heterogeneity between included studies. Based on a limited number of studies in children, levofloxacin is likely to have one of the highest rates of adverse reactions. The majority of the studies included in the NMA were from the Asian region, and more randomised controlled trials comparing different therapeutic strategies in patients with M. pneumoniae are warranted. This comparative study provides clinical pharmacists and clinicians with important information to enable them to make informed decisions about treatment options, considering drug efficacy and safety.
UNASSIGNED: The Natural Science Foundation of Fujian Province, China.