UNASSIGNED: Outbreaks of fowl adenovirus (FAdV) infection in chicken flocks in Poland threaten birds\' health and lives and are rising in frequency. The risk of these infections in immunocompromised poultry flocks with developed clinical symptoms was analysed through virus detection in broiler chicks and correlation of cases with the birds\' immune strength.
UNASSIGNED: Samples were analysed from four broiler farms with chicks from the same hatchery in Silesia, Poland where feeding regimes were different. A normal diet was provided to birds on the control farm; a normal diet and probiotic, prebiotic, vitamin and microelement supplementation was supplied on another farm; a normal diet and antibiotics on the third; and a normal diet and both forms of supplementation were given on the fourth farm. Amplification of the virus DNA in a PCR with hexon gene L1 loop hypervariable region 1-4 primers determined the molecular characteristics of isolates of adenovirus strains obtained from necropsy tissue samples. The amplicon sequences were analysed, the pair-wise distances were determined, the maximum likelihood estimate for the gamma parameter for site rates was produced, Tajima\'s D neutrality test was run and the relative synonymous codon usage and transition/transversion bias were calculated.
UNASSIGNED: Two species and two serotypes of fowl adenovirus - MW353018-FAdV-1/A-L-liver and MW353019-FAdV-5/B-I-intestine - were isolated in three-week-old broiler chicks on the control farm.
UNASSIGNED: Supplementation of broiler chicken flocks with probiotics, prebiotics, vitamins and microelements may have a significant beneficial effect on immunity and can prevent virus infection. The studies provided new information on the molecular characteristics of adenovirus strains isolated from chicks with a low level of immunity.

UNASSIGNED: This study aimed to explore the anti-oxidative and anti-inflammatory properties of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) and investigate its effects on the intestinal barrier, cranial nerve, and motor function in mice treated with antibiotics.
UNASSIGNED: Mice were administered an antibiotic mixture (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole file 5 mg/mL, and lipopolysaccharide 1.5 μg/mL) intraperitoneally, and oxidative stress and inflammatory markers in the serum and brain tissues, and liver index were measured. H&E staining was performed to detect pathological alterations in brain tissues. The expression of intestinal-barrier-related genes and that of genes involved in inflammatory pathways in the brain were detected using polymerase chain reaction (PCR).
UNASSIGNED: LLSLHFY14 administration extended the weight-loaded swimming and running times of mice and decreased the liver index. Moreover, the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the serum and brain tissue were reduced, whereas those of superoxide dismutase (SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated. Elevated brain expression of the protein kinase B (AKT)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase 1 (ERK1) pathway, decreased brain expression of the IL-6 gene, and elevated cecum expression of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes were noted. LLSLHFY14 supplementation significantly increased Bacteroidetes expression but decreased Firmicutes expression, thus increasing the Bacteroidetes/Firmicutes ratio.
UNASSIGNED: Overall, LLSLHFY14 supplementation ameliorated antibiotic-induced oxidative stress and inflammation in the mouse central nervous system, intestinal barrier dysfunction, and increased motor function, thus confirming its potential application as probiotics.

Heavy metal ions and antibiotic contamination have become a major environmental concern worldwide. The development of efficient recognition strategies of these pollutants at ultra-low concentrations in aqueous solutions as well as the elucidation of the intrinsic sensing mechanism are challenging tasks. In this work, unique luminescent Ln-MOF materials (NIIC-3-Ln) were assembled by rational ligand design. Among them, NIIC-3-Tb demonstrated highly selective luminescence quenching response toward Hg2+ and sulfadiazine (SDI) at subnanomolar concentrations in less than 7 s. In addition, a Hg2+ sensing mechanism through chelation was proposed on the basis of single-crystal X-ray diffraction analysis and Hg2+ adsorption study. The interaction mechanism of NIIC-3-Tb with SDI was revealed using a newly developed approach involving a (TD-)DFT based quantification of the charge transfer of a MOF-analyte supramolecular complex model in the ground and excited states. Effect of ultrasonic treatment on the surface morphology important for MOF sensing performance was revealed by gas adsorption experiments. The presented results indicate that NIIC-3-Ln is not only an advanced sensing material for the efficient detection of Hg2+ and SDI at ultra-low concentrations, but also opens up a new approach to study the sensing mechanism at the molecular level at ultra-low concentrations.

BACKGROUND: Hospitalised neonates are vulnerable to infection and have high rates of antibiotic utilisation.
METHODS: Fourteen South African neonatal units (seven public, seven private sector) assembled multidisciplinary teams involving neonatologists, microbiologists, pharmacists, and nurses to implement prospective audit and feedback neonatal antimicrobial stewardship (NeoAMS) interventions. The teams attended seven online training sessions. Pharmacists conducted weekday antibiotic prescription reviews in the neonatal intensive care unit and/or neonatal wards providing feedback to the clinical teams. Anonymised demographic and NeoAMS interventions data were aggregated for descriptive purposes and statistical analysis.
RESULTS: During the 20-week NeoAMS intervention in 2022, 565 neonates were enrolled. Pharmacists evaluated seven hundred antibiotic prescription episodes; rule-out sepsis (180; 26%) and culture-negative sepsis (138; 20%) were the most frequent indications for antibiotic prescription. For infection episodes with an identified pathogen, only 51% (116/229) of empiric treatments provided adequate antimicrobial coverage. Pharmacists recommended 437 NeoAMS interventions (0·6 per antibiotic prescription episode), with antibiotic discontinuation (42%), therapeutic drug monitoring (17%), and dosing (15%) recommendations most frequent. Neonatal clinicians\' acceptance rates for AMS recommendations were high (338; 77%). Mean antibiotic length of therapy decreased by 24% from 9·1 to 6·9 days (0·1 day decrease per intervention week; p=0·001), with the greatest decline in length of therapy for culture-negative sepsis (8·2 days (95%CI 5·7-11·7) to 5·9 days (95% CI 4·6-7·5); p=0·032).
CONCLUSIONS: This neonatal AMS programme was successfully implemented in heterogenous and resource-limited settings. Pharmacist-recommended AMS interventions had high rates of clinician acceptance. The NeoAMS intervention significantly reduced neonatal antibiotic use, particularly for culture-negative sepsis.
BACKGROUND: A grant from Merck provided partial support.

Antimicrobial resistance (AMR) stands as an escalating public health crisis fueled by antimicrobial residues in the environment, particularly in soil, which acts as a reservoir for antimicrobial resistance genes (ARGs). Merely quantifying the total extractable concentration of antimicrobials, instead of bioavailable fractions, may substantially underestimate their minimal selection concentration for propagating ARGs. To shed light on the role of bioavailability in ARG abundance within soil, a systematic bioavailability assessment method was established for accurately quantifying the partitioning of multi-class antimicrobials in representative Chinese soils. Microcosm studies unveiled that antimicrobials persisting in the bioavailable fraction could potentially prolong their selection pressure duration to trigger AMR. Notably, the co-occurrence of pesticide or steroid hormone influenced the development trends of ARG subtypes, with fluoroquinolone resistance genes (RGs) being particularly susceptible. Partial least squares path model (PLS-PM) analysis uncovered potentially distinct induction mechanisms of antimicrobials: observable results suggested that extractable residual concentration may exert a direct selection pressure on the development of ARGs, while bioavailable concentration could potentially play a stepwise role in affecting the abundance of mobile genetic elements and initiating ARG dissemination. Such unprecedented scrutinization of the interplay between bioavailable antimicrobials in soils and ARG abundance provides valuable insights into strategizing regulatory policy or guidelines for soil remediation.

The long-term stability of antibiotics in culture media remains underexplored in scientific literature. This study evaluated the stability of eight distinct antibiotic stock solutions-amoxicillin, cefotaxime, neomycin, oxytetracycline, florfenicol, enrofloxacin, colistin, and potentiated sulfonamide-and their 10-fold dilution series in tryptone soy broth (TSB) at 37 °C, over 12 days. Samples were collected immediately after preparation and on days 1, 2, 5, 7, 9, and 12, with active substance concentrations measured using ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry. The results indicated that among the ultrapure water stock solutions, neomycin, florfenicol, and potentiated sulfonamide maintained stability (>95%). Within the culture medium, florfenicol showed consistent stability (100%) throughout the study, potentiated sulfonamide experienced minor degradation (>85%), and neomycin underwent significant degradation. Amoxicillin, oxytetracycline, and colistin displayed considerable degradation in both solution types but were more stable in ultrapure water solutions. The stability of cefotaxime and enrofloxacin in ultrapure water solutions and in the medium was very similar when compared; however, 3.6% of the former and 88.7% of the latter remained detectable by day 12. These findings are crucial for minimum inhibitory concentration (MIC) assessments, especially in minimum bactericidal concentration (MBC) studies, and in experiments concerning long-term evolution and co-selection. This study underscores the necessity of stability assessments in culture media to validate future experimental outcomes.

Infections caused by KPC-producing K. pneumoniae continue to pose a significant clinical challenge due to their emerging resistance to new antimicrobials. We investigated the association between two drugs whose roles have been repurposed against multidrug-resistant bacteria: fosfomycin and temocillin. Temocillin exhibits unusual stability against KPC enzymes, while fosfomycin acts as a potent \"synergizer\". We conducted in vitro antimicrobial activity studies on 100 clinical isolates of KPC-producing K. pneumoniae using a combination of fosfomycin and temocillin. The results demonstrated synergistic activity in 91% of the isolates. Subsequently, we assessed the effect on Galleria mellonella larvae using five genetically different KPC-Kp isolates. The addition of fosfomycin to temocillin increased larvae survival from 73 to 97% (+Δ 32%; isolate 1), from 93 to 100% (+Δ 7%; isolate 2), from 63 to 86% (+Δ 36%; isolate 3), from 63 to 90% (+Δ 42%; isolate 4), and from 93 to 97% (+Δ 4%; isolate 10). Among the temocillin-resistant KPC-producing K. pneumoniae isolates (24 isolates), the addition of fosfomycin reduced temocillin MIC values below the resistance breakpoint in all isolates except one. Temocillin combined with fosfomycin emerges as a promising combination against KPC-producing K. pneumoniae, warranting further clinical evaluation.

Interactions between drugs are a common problem in Intensive Care Unit patients, as they mainly have a critical condition that often demands the administration of multiple drugs simultaneously. Antibiotics are among the most frequently used medications, as infectious diseases are often observed in ICU patients. In this review, the most important antibiotic-drug interactions, based on the pharmacokinetic and pharmacodynamic mechanisms, were gathered together and described. In particular, some of the most important interactions with main groups of antibacterial drugs were observed in patients simultaneously prescribed oral anticoagulants, NSAIDs, loop diuretics, and valproic acid. As a result, the activity of drugs can be increased or decreased, as dosage modification might be necessary. It should be noted that these crucial interactions can help predict and avoid negative consequences, leading to better patient recovery. Moreover, since there are other factors, such as fluid therapy or albumins, which may also modify the effectiveness of antibacterial therapy, it is important for anaesthesiologists to be aware of them.

Despite the beneficial effects of antibiotics such as chloramphenicol (CAP), they exert some destructive impacts on human health. We designed an electrochemical sensor based on reduced graphene oxide (rGO)/Au/Co2CuS4 nanohybrid for determination of CAP in food and biological samples. The Co2CuS4 was synthesized from binuclear metal-organic framework (CoCu-BDC) through a two-step process. Nanohybrid was characterized by X-ray photoelectron spectroscopy and transmission electron microscopy. The rGO/Au/Co2CuS4 provides more active sites and good electrical conductivity to reduce charge transfer resistance and improve the electrocatalytic activity for determination of CAP. The prepared sensor has a wide linear range from 7 to 141 nM with a limit of detection of 2.5 nM and a limit of quantification of 21.92 nM. It also provided high selectivity and repeatability with a relative standard deviation of 2.6%. Stability studies showed that the electrode has acceptable performance with efficiency of 95% after 33 days.

BACKGROUND:  \"Direct-to-consumer (DTC) telemedicine\" is increasing worldwide and changing the map of primary health care (PHC). Virtual care has increased in the last decade and with the ongoing COVID-19 pandemic, patients\' use of online care has increased even further. In Sweden, online consultations are a part of government-supported health care today, and there are several digital care providers on the Swedish market, which makes it possible to get in touch with a doctor within a few minutes. The fast expansion of this market has raised questions about the quality of primary care provided only in an online setting without any physical appointments. Antibiotic prescribing is a common treatment in PHC.
OBJECTIVE:  This study aimed to compare antibiotic prescribing between digital PHC providers (internet-PHC) and traditional physical PHC providers (physical-PHC) and to determine whether prescriptions for specific diagnoses differed between internet-PHC and physical-PHC appointments, adjusted for the effects of attained age at the time of appointment, gender, and time relative to the COVID-19 pandemic.
METHODS:  Antibiotic prescribing data based on Anatomical Therapeutic Chemical (ATC) codes were obtained for Region Sörmland residents from January 2020 until March 2021 from the Regional Administrative Office. In total, 160,238 appointments for 68,332 Sörmland residents were included (124,398 physical-PHC and 35,840 internet-PHC appointments). Prescriptions issued by internet-PHC or physical-PHC physicians were considered. Information on the appointment date, staff category serving the patient, ICD-10 (International Statistical Classification of Diseases, Tenth Revision) diagnosis codes, ATC codes of prescribed medicines, and patient-attained age and gender were used.
RESULTS:  A total of 160,238 health care appointments were registered, of which 18,433 led to an infection diagnosis. There were large differences in gender and attained age distributions among physical-PHC and internet-PHC appointments. Physical-PHC appointments peaked among patients aged 60-80 years while internet-PHC appointments peaked at 20-30 years of age for both genders. Antibiotics with the ATC codes J01A-J01X were prescribed in 9.3% (11,609/124,398) of physical-PHC appointments as compared with 6.1% (2201/35,840) of internet-PHC appointments. In addition, 61.3% (6412/10,454) of physical-PHC infection appointments resulted in antibiotic prescriptions, as compared with only 25.8% (2057/7979) of internet-PHC appointments. Analyses of the prescribed antibiotics showed that internet-PHC followed regional recommendations for all diagnoses. Physical-PHC also followed the recommendations but used a wider spectrum of antibiotics. The odds ratio of receiving an antibiotic prescription (after adjustments for attained age at the time of appointment, patient gender, and whether the prescription was issued before or during the COVID-19 pandemic) during an internet-PHC appointment was 0.23-0.39 as compared with a physical-PHC appointment.
CONCLUSIONS:  Internet-PHC appointments resulted in a significantly lower number of antibiotics prescriptions than physical-PHC appointments, adjusted for the large differences in the characteristics of patients who consult internet-PHC and physical-PHC. Internet-PHC prescribers showed appropriate prescribing according to guidelines.