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Contents Clinical and subclinical endometritis are common causes of infertility and subfertility in high producing dairy cattle, delaying the onset of ovarian cyclic activity after parturition, extending luteal phases and reducing conception rates. Escherichia coli and Arcanobacterium pyogenes cause endometrial damage and inflammation. Components of microbes, such as lipopolysaccharide (LPS), are detected by Toll-like receptors on endometrial cells, leading to secretion of cytokines, chemokines and antimicrobial peptides. Long luteal phases associated with endometritis are probably caused by a switch in endometrial prostaglandin production from prostaglandin F2a (PGF) to prostaglandin E2. In addition, LPS impairs the function of the hypothalamus and pituitary, and directly perturbs ovarian granulosa cells steroidogenesis, providing mechanisms to explain the association between uterine disease and anovulatory anoestrus. Cows with uterine disease that ovulate have lower peripheral plasma progesterone concentrations that may further reduce the chance of conception associated with endometritis. [ABSTRACT FROM AUTHOR]

Background: Vancomycin (VAN) protein binding in plasma is influenced by illness and age; hence, doses titrated according to total concentrations are fraught. In this study, model-estimated free VAN concentrations (EFVC) were compared with assumed free VAN concentrations (AFVC) in neonates, children, and adults in the intensive care unit and those on dialysis., Methods: Patient cohorts were identified from the hospital database. Demographics, clinical characteristics, total VAN concentrations, and laboratory variables were obtained from electronic health records. EFVC was derived from 6 models identified in the literature. For all models, total VAN concentration was the most important predictor; other predictors included albumin, total protein, and dialysis status. The AFVC was calculated as 50% of the total concentration (ie, assumption of 50% bound)., Results: Differences between EFVC and AFVC in adults were insignificant; however, differences in pediatric intensive care unit patients, according to 2 different models, were significant: mean ± SD = 4.1 ± 1.58 mg/L and 4.7 ± 2.46 mg/L ( P < 0.001); the percentages within the free VAN trough range = 30.4% versus 55.1% and 30% versus 55.1%; and the supratherapeutic percentages = 65.2% versus 31.9% and 66.7% versus 31.9%, respectively. In neonates, the difference between EFVC and AFVC was mean ± SD = 6.9 ± 1.95 mg/L ( P < 0.001); the percentages within the free VAN trough range for continuous and intermediate dosing were 0% versus 81.3% and 14.3% versus 71.4%, and the supratherapeutic percentages were 100% versus 6.25% and 71.4% versus 0%, respectively., Conclusions: The fraction of free unbound VAN is higher in sick children and neonates than in adults. Therefore, total VAN concentrations do not correlate with the pharmacologically active free VAN concentrations in the same manner as in adults. Adjusting VAN doses in neonates and children to target the same total VAN concentration as the recommended therapeutic range for adults may result in toxicfree concentrations., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Non-tuberculous mycobacteria (NTM) infections predominantly present as pulmonary disease. Although relatively rare, 20-30 % originate from extrapulmonary sites resulting in a wide range of clinical syndromes. Immunocompromised individuals are particularly susceptible. Clinical manifestations include skin and soft-tissue infections, lymphadenitis, musculoskeletal infections and disseminated disease. Diagnosing extrapulmonary NTM is challenging, and management is complex, often involving multiple radiological and microbiological investigations, long courses of combination antibiotic regimens and may require adjuvant surgical interventions. We highlight both the importance of involving NTM experts at an early stage and the role of a multidisciplinary approach in the diagnosis and management of these infections., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Therapeutic drug monitoring of infliximab (IFX) is important to optimise treatment of inflammatory bowel disease (IBD). A recent IBD consensus statement recommends targeting trough serum concentrations of >3 μg/mL, higher than our local recommendation of >1 μg/mL. We therefore investigated the relationship between IFX trough concentrations and C reactive protein (CRP), faecal calprotectin (FCP), clinical outcomes and anti-IFX antibody (AB) development as well as the influence of concomitant thiopurine treatment., Methods: Observational data, prospectively collected in a cohort of adult patients with IBD newly initiated on IFX at a single centre., Results: IFX concentrations >3 μg/mL were associated with a greater reduction in CRP (% change from baseline) and lower FCP; mean (SD) 47 (33.8) % vs 102.3 (136.9) % and 233.9 (505.1) μg/g vs 416.3 (613.5) μg/g, respectively. Lower IFX concentrations were observed in patients who developed AB than those who did not, mean (range) 6.2 (1.1-10) μg/mL vs 0.9 (0.4-4.9) μg/mL, respectively, and also in patients who stopped/switched therapy compared with those who continued, 2.4 (2.9) μg/mL vs 6.5 (2.8) μg/mL; p=0.0002. Patients taking a concomitant thiopurine were found to have higher IFX concentrations; mean (range) 6.4 (0.7-10) μg/mL vs 3.9 (0.4-10) μg/mL., Conclusions: IFX concentrations are correlated with biomarkers, clinical response and AB development in patients with IBD. Concomitant thiopurine therapy appears to be associated with higher IFX concentrations and reduced likelihood of AB development., Competing Interests: Competing interests: HM is a part-time employee of Nova Laboratories Limited. The remaining authors declare no conflicts of interest., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)