Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To create a clinical guideline for the diagnosis and management of urinary tract infections that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In May 2023, new and existing members were solicited for questions on urinary tract infection prevention, diagnosis, and management. For each topic, literature searches were conducted up until early 2024 in any language. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were developed discussing the available literature and associated risks and benefits of various approaches. Findings: A total of 54 members representing 12 countries reviewed 914 articles and submitted information relevant to 5 sections: prophylaxis and prevention (7 questions), diagnosis and diagnostic stewardship (7 questions), empirical treatment (3 questions), definitive treatment and antimicrobial stewardship (10 questions), and special populations and genitourinary syndromes (10 questions). Of 37 unique questions, a clear recommendation could be provided for 6 questions. In 3 of the remaining questions, a clear recommendation could only be provided for certain aspects of the question. Clinical reviews were generated for the remaining questions and aspects of questions not meeting criteria for a clear recommendation. Conclusions and Relevance: In this consensus statement that applied the WikiGuidelines method for clinical guideline development, the majority of topics relating to prevention, diagnosis, and treatment of urinary tract infections lack high-quality prospective data and clear recommendations could not be made. Randomized clinical trials are underway to address some of these gaps; however further research is of utmost importance to inform true evidence-based, rather than eminence-based practice.

The feline coronavirus treatment GS-441524 represents a unique case of translational medicine in reverse: a compound developed for a rare human disease, abandoned in human clinical use, but successfully repurposed to treat a fatal veterinary condition affecting cats. Initially designed as a nucleoside analog for the Ebola virus, GS-441524 underwent preclinical safety testing in animals before being discovered to have unexpected clinical applications in feline infectious peritonitis (FIP), a historically untreatable disease in cats caused by a virulent systemic feline coronavirus (FCoV). This review traces the scientific and regulatory journey of GS-441524 from human antiviral candidate to life-saving feline treatment. We also expand the discussion to include the emerging use of other human antivirals, such as molnupiravir, in veterinary medicine. Ethical and public health tensions created by unregulated, community-driven drug access are examined, alongside the broader One Health implications, including antiviral resistance and the lack of surveillance in non-human hosts. Finally, we explore how lessons from FIP treatment may inform human medicine, particularly in the context of long COVID and future coronavirus pandemics. This translational scenario exemplifies both the potential and the pitfalls of cross-species drug translation, underscoring the need for integrated regulatory and ethical frameworks to support responsible innovation.

Disseminated Mycobacterium tuberculosis (Mtb), where the infection spreads beyond the lungs, is rare in immunocompetent individuals. Disseminated Mtb can affect organs, such as the liver, brain, and bone marrow, and often mimics other diseases, such as fungal infections or cancer. While factors like HIV or immunosuppression increase the risk of Mtb spread, diagnosing disseminated Mtb is challenging because of nonspecific symptoms and limitations in testing. This case study involves a 74-year-old man with no major risk factors for Mtb. He presented with abdominal pain, weight loss, and gastrointestinal issues but later developed lung and neurological symptoms. Initial tests were inconclusive, but Mtb was eventually confirmed after positive quantiferon testing and culture results from ascitic and lung fluid. Despite treatment with RIPE therapy (rifampin, isoniazid, pyrazinamide, ethambutol), the patient died. The case highlights the complexities of diagnosing Mtb, especially when typical tests are inconclusive. Cytokine abnormalities, such as elevated interleukin-2 receptor levels, may be helpful markers for diagnosis and prognosis, particularly in Mtb meningitis (tuberculous meningitis). This discussion emphasizes the importance of considering Mtb in cases of unexplained multiorgan failure and the need for timely Mtb culture and treatment.

BioFire® Blood Culture Identification 2 (BCID2) panel is a rapid multiplex polymerase chain reaction (rm-PCR) testing for 43 organisms associated with bloodstream infections and 10 antimicrobial resistance genes. Previous literature suggested combination of rm-PCR and antibiotic stewardship program (ASP) would improve time to organism identification, optimal therapy, and de-escalation of antibiotics. This study was a retrospective study at Touro Infirmary in New Orleans, Louisiana. All adult patients with positive blood cultures before and after BCID2 implementation in January 2022 (April to September 2021 and April to September 2022 respectively) were included. The outcomes of interest included time to organism identification, time to change of antibiotics (either appropriate escalation or de-escalation), hospital length of stay, 30-day re-admission, and 30-day mortality. A total of 117 patients met the study criteria (refer to Figure 1 and Table 1 for the flowchart of participants and characteristics of participants respectively). Patients with blood cultures that grew one of the organisms of interest were analyzed: methicillin sensitive Staphylococcus aureus (MSSA), coagulase negative Staphylococcus species, extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E), AmpC beta-lactamase-producing Enterobacterales, and Pseudomonas aeruginosa. There was a significant difference in the time to organism identification between pre- and post-BCID groups (45 hours vs. 25.1 hours, p < 0.0001) and there was no discordance between the BCID and blood culture results. In addition, there was a significant decrease in time to antibiotics change between pre- and post-BCID groups (p < 0.01). Notably for patients with MSSA bacteremia, post-BCID group had significantly shorter duration to de-escalate antibiotics than pre-BCID group (43 hours vs. 66.7 hours, p < 0.038). However, there is no statistical difference between pre- and post-BCID groups regarding hospital length of stay, 30-day readmission, and 30-day mortality. Organisms of interest include: methicillin sensitive Staphylococcus aureus, coagulase negative Staphylococcus species, extended-spectrum beta-lactamase producing Enterobacterales, AmpC beta-lactamase producing Enterobacterales, and Pseudomonas aeruginosa. Abbreviations: BCID, blood culture identification panel, BCx, blood cultures. BCID2 significantly reduced the time to organism identification and improved time to effective therapy for MSSA bacteremia. However, significance was limited in other measures due to small sample size. All Authors: No reported disclosures

The principles of evolutionary medicine have significant potential to be useful in a wide variety of clinical situations. Despite this, few demonstrations of clinical applications exist. To address this paucity, a case series applying evolutionary medicine principles to urinary tract infections, a common medical condition is presented. This series demonstrates how applying evolutionary medicine principles can be used to augment clinical decision-making.