Retrospective study and outcome of 307 cats with feline infectious peritonitis treated with legally sourced veterinary compounded preparations of remdesivir and GS-441524 (2020-2022).

OBJECTIVES: Feline infectious peritonitis (FIP) is a serious disease that arises due to feline coronavirus infection. The nucleoside analogues remdesivir and GS-441524 can be effective in its treatment, but most studies have used unregulated products of unknown composition. The aim of the present study was to describe the treatment of FIP using legally sourced veterinary-prescribed regulated veterinary compounded products containing known amounts of remdesivir (injectable) or GS-441524 (oral tablets). METHODS: Cats were recruited via email advice services, product sales contacts and study publicity. Cats were excluded if they were deemed unlikely to have FIP, were not treated exclusively with the veterinary compounded products, or if there was a lack of cat and/or treatment (including response) data. Extensive cat and treatment data were collected. RESULTS: Among the 307 cats recruited, the predominant type of FIP was most commonly abdominal effusive (49.5%) and then neurological (14.3%). Three treatment protocols were used; remdesivir alone (33.9%), remdesivir followed by GS-441524 (55.7%) and GS-441524 alone (10.4%). The median (range) initial treatment period duration and longest follow-up time point after starting treatment were 84 (1-330) days and 248 (1-814) days, respectively. The most common side effect was injection pain (in 47.8% of those given subcutaneous remdesivir). Of the 307 cats, 33 (10.8%) relapsed, 15 (45.5%) during and 18 (54.5%) after the initial treatment period. At the longest follow-up time point after completion of the initial treatment period, 84.4% of cats were alive. The cats achieving a complete response within 30 days of starting treatment were significantly more likely to be alive at the end of the initial treatment period than those cats that did not. CONCLUSIONS AND RELEVANCE: Legally sourced remdesivir and GS-441524 products, either alone or used sequentially, were very effective in the treatment of FIP in this group of cats. Variable protocols precluded statistical comparison of treatment regimens.

Chronic Enteropathy in Dogs-Epidemiologic Aspects and Clinical Characteristics of Dogs Presenting at Two Swedish Animal Hospitals.

Information about prevalence and breed predisposition of canine chronic enteropathy (CE) is limited. The aim of this retrospective study was to investigate period prevalence, breed disposition, clinical features, diagnostic results, and treatment response of CE in dogs presenting at two Swedish animal hospitals during 2013−2018. A medical record search was performed to identify CE dogs including those with ≥3 visits because of gastrointestinal disease and/or that had undergone gastroduodenoscopy/colonoscopy during 2013−2018. Dog characteristics, case history, physical examination, laboratory variables, therapeutic protocol, and treatment response were recorded. Inclusion criteria for CE were met by 814 dogs. Period prevalence of CE was 1.1% of total number of dogs. Breeds with the highest relative risk included Norwegian Lundehund, West Highland White Terrier, and Miniature Poodle. Median age at presentation was 3.8 (IQR 1.8−6.8) years. French Bulldogs and Miniature Schnauzers presented at a younger age (<2.5 years) compared to other breeds (p < 0.05). In a subset of dogs, serum hypoalbuminemia (116/662, 17.5%), hypocobalaminemia (98/647, 15.1%), and increased C-reactive protein (CRP) concentrations (145/267, 54.3%) were diagnosed. Treatment outcome was classified in 72.9% of dogs and characterized as immunosuppressant-responsive (55.2%), food-responsive (11.4%), non-responsive (5.2%), and antibiotic-responsive (1.1%). Non-responsive dogs were more likely to present with anemia hypoproteinemia/albuminemia, increased CRP, and ascites (p < 0.05). In conclusion, the prevalence of dogs with CE at Swedish hospitals agreed with earlier reports, but risk breeds differed slightly and, compared to other breeds, a younger age of CE onset was found in two breeds. The largest proportion of dogs was immunosuppressant-responsive and the smallest antibiotic-responsive.

Regulatory role of proteins binding to the spa (protein A) and sarS (staphylococcal accessory regulator) promoter regions in Staphylococcus aureus NTCC 8325-4.

Production of protein A (SpA) in Staphylococcus aureus is controlled by several global regulators including agr (RNAIII), sarA, sarS, sarT, rot and mgrA, which appear to form a regulatory network. SarS, which is an activator of spa, seems to be a key regulator in this network. Previous studies have shown that expression of sarS is upregulated in agr, sarA and mgrA mutants, resulting in increased spa expression. In an agr mutant, upregulation of sarS and spa required rot and sarT. In this study regulatory proteins binding to spa and sarS promoter fragments coupled to magnetic beads were identified by MALDI-TOF-MS. Expression of sarS and spa in mutants deficient for one, two or three of the identified regulators and in mutants over-expressing selected regulators was analyzed by Northern and Western blotting. Binding and transcription analysis indicated that SarA represses sarS by direct binding to the promoter, and that stimulation of sarS by sarT was rot-dependent. We also found that MgrA bound to the sarS promoter and was required for expression of both sarS and spa in an agr mutant. However, mgrA and rot were not required for stimulation of sarS in the absence of SarA, suggesting that these regulators, together with SarT, counteract the repressive activity of SarA. Our data indicate that SarS competes with SarA for binding to the spa promoter. This is consistent with the requirement for sarS in spa transcription even in the absence of the repressor, SarA. We also demonstrated binding of MgrA and Rot to the spa promoter, and that rot could stimulate spa transcription even in a sarS mutant. A provisional model for spa regulation involving agr, sarA, sarS, sarT, rot and mgrA is presented.