It is crucial to discover novel antimicrobial drugs to combat resistance. This study investigated the antibacterial properties of halicin (SU3327), an AI-identified anti-diabetic drug, against 13 kinds of common clinical pathogens of animal origin, including multidrug-resistant strains. Employing minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assessments, halicin demonstrated a broad-spectrum antibacterial effect. Time-killing assays revealed its concentration-dependent bactericidal activity against Escherichia coli ATCC 25922 (E. coli ATCC 25922), Staphylococcus aureus ATCC 29213 (S. aureus ATCC 29213), and Actinobacillus pleuropneumoniae S6 (APP S6) after 4 h of treatment at concentrations above the MIC. Halicin exhibited longer post-antibiotic effects (PAEs) and sub-MIC effects (PA-SMEs) for E. coli 25922, S. aureus 29213, and APP S6 compared to ceftiofur and ciprofloxacin, the commonly used veterinary antimicrobial agents, indicating sustained antibacterial action. Additionally, the results of consecutive passaging experiments over 40 d at sub-inhibitory concentrations showed that bacteria exhibited difficulty in developing resistance to halicin. Toxicology studies confirmed that halicin exhibited low acute toxicity, being non-mutagenic, non-reproductive-toxic, and non-genotoxic. Blood biochemical results suggested that halicin has no significant impact on hematological parameters, liver function, and kidney function. Furthermore, halicin effectively treated respiratory A. pleuropneumoniae infections in murine models. These results underscore the potential of halicin as a new antibacterial agent with applications against clinically relevant pathogens in veterinary medicine.

OBJECTIVE: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant P. multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis.
RESULTS: Danofloxacin at seven dosing regimens and five days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h danofloxacin area under the concentration-time curve to MIC ratios (AUC24h/MIC) associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/MPC (mutant prevention concentration)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of 3 times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants.
CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

OBJECTIVE: To systematically review evidence on and devise treatment recommendations for patient monitoring before, during, and following CPR in dogs and cats, and to identify critical knowledge gaps.
METHODS: Standardized, systematic evaluation of literature pertinent to peri-CPR monitoring following Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Prioritized questions were each reviewed by Evidence Evaluators, and findings were reconciled by Monitoring Domain Chairs and Reassessment Campaign on Veterinary Resuscitation (RECOVER) Co-Chairs to arrive at treatment recommendations commensurate to quality of evidence, risk:benefit relationship, and clinical feasibility. This process was implemented using an Evidence Profile Worksheet for each question that included an introduction, consensus on science, treatment recommendations, justification for these recommendations, and important knowledge gaps. A draft of these worksheets was distributed to veterinary professionals for comment for 4 weeks prior to finalization.
METHODS: Transdisciplinary, international collaboration in university, specialty, and emergency practice.
RESULTS: Thirteen questions pertaining to hemodynamic, respiratory, and metabolic monitoring practices for identification of cardiopulmonary arrest, quality of CPR, and postcardiac arrest care were examined, and 24 treatment recommendations were formulated. Of these, 5 recommendations pertained to aspects of end-tidal CO2 (ETco2) measurement. The recommendations were founded predominantly on very low quality of evidence, with some based on expert opinion.
CONCLUSIONS: The Monitoring Domain authors continue to support initiation of chest compressions without pulse palpation. We recommend multimodal monitoring of patients at risk of cardiopulmonary arrest, at risk of re-arrest, or under general anesthesia. This report highlights the utility of ETco2 monitoring to verify correct intubation, identify return of spontaneous circulation, evaluate quality of CPR, and guide basic life support measures. Treatment recommendations further suggest intra-arrest evaluation of electrolytes (ie, potassium and calcium), as these may inform outcome-relevant interventions.

OBJECTIVE: To describe the methodology used by the Reassessment Campaign on Veterinary Resuscitation (RECOVER) to re-evaluate the scientific evidence relevant to CPR in small and large animals, to newborn resuscitation, and to first aid and to formulate the respective consensus-based clinical guidelines.
METHODS: This report describes the evidence-to-guidelines process employed by RECOVER that is based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and includes Information Specialist-driven systematic literature search, evidence evaluation conducted by more than 200 veterinary professionals, and provision of clinical guidelines in the domains of Preparedness and Prevention, Basic Life Support, Advanced Life Support, Post-cardiac Arrest Care, Newborn Resuscitation, First Aid, and Large Animal CPR.
METHODS: Transdisciplinary, international collaboration in academia, referral practice, and general practice.
RESULTS: For this update to the RECOVER 2012 CPR guidelines, we answered 135 Population, Intervention, Comparator, and Outcome (PICO) questions with the help of a team of Domain Chairs, Information Specialists, and more than 200 Evidence Evaluators. Most primary contributors were veterinary specialists or veterinary technician specialists. The RECOVER 2024 Guidelines represent the first veterinary application of the GRADE approach to clinical guideline development. We employed an iterative process that follows a predefined sequence of steps designed to reduce bias of Evidence Evaluators and to increase the repeatability of the quality of evidence assessments and ultimately the treatment recommendations. The process also allowed numerous important knowledge gaps to emerge that form the foundation for prioritizing research efforts in veterinary resuscitation science.
CONCLUSIONS: Large collaborative, volunteer-based development of evidence- and consensus-based clinical guidelines is challenging and complex but feasible. The experience gained will help refine the process for future veterinary guidelines initiatives.

OBJECTIVE: To systematically review the evidence and devise clinical recommendations on advanced life support (ALS) in dogs and cats and to identify critical knowledge gaps.
METHODS: Standardized, systematic evaluation of literature pertinent to ALS following Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Prioritized questions were each reviewed by Evidence Evaluators, and findings were reconciled by ALS Domain Chairs and Reassessment Campaign on Veterinary Resuscitation (RECOVER) Co-Chairs to arrive at treatment recommendations commensurate to quality of evidence, risk:benefit relationship, and clinical feasibility. This process was implemented using an Evidence Profile Worksheet for each question that included an introduction, consensus on science, treatment recommendations, justification for these recommendations, and important knowledge gaps. A draft of these worksheets was distributed to veterinary professionals for comment for 4 weeks prior to finalization.
METHODS: Transdisciplinary, international collaboration in university, specialty, and emergency practice.
RESULTS: Seventeen questions pertaining to vascular access, vasopressors in shockable and nonshockable rhythms, anticholinergics, defibrillation, antiarrhythmics, and adjunct drug therapy as well as open-chest CPR were reviewed. Of the 33 treatment recommendations formulated, 6 recommendations addressed the management of patients with nonshockable arrest rhythms, 10 addressed shockable rhythms, and 6 provided guidance on open-chest CPR. We recommend against high-dose epinephrine even after prolonged CPR and suggest that atropine, when indicated, is used only once. In animals with a shockable rhythm in which initial defibrillation was unsuccessful, we recommend doubling the defibrillator dose once and suggest vasopressin (or epinephrine if vasopressin is not available), esmolol, lidocaine in dogs, and/or amiodarone in cats.
CONCLUSIONS: These updated RECOVER ALS guidelines clarify the approach to refractory shockable rhythms and prolonged CPR. Very low quality of evidence due to absence of clinical data in dogs and cats continues to compromise the certainty with which recommendations can be made.

OBJECTIVE: To systematically review evidence and devise treatment recommendations for basic life support (BLS) in dogs and cats and to identify critical knowledge gaps.
METHODS: Standardized, systematic evaluation of literature pertinent to BLS following Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Prioritized questions were each reviewed by 2 Evidence Evaluators, and findings were reconciled by BLS Domain Chairs and Reassessment Campaign on Veterinary Resuscitation (RECOVER) Co-Chairs to arrive at treatment recommendations commensurate to quality of evidence, risk to benefit relationship, and clinical feasibility. This process was implemented using an Evidence Profile Worksheet for each question that included an introduction, consensus on science, treatment recommendations, justification for these recommendations, and important knowledge gaps. A draft of these worksheets was distributed to veterinary professionals for comment for 4 weeks prior to finalization.
METHODS: Transdisciplinary, international collaboration in university, specialty, and emergency practice.
RESULTS: Twenty questions regarding animal position, chest compression point and technique, ventilation strategies, as well as the duration of CPR cycles and chest compression pauses were examined, and 32 treatment recommendations were formulated. Out of these, 25 addressed chest compressions and 7 informed ventilation during CPR. The recommendations were founded predominantly on very low quality of evidence and expert opinion. These new treatment recommendations continue to emphasize the critical importance of high-quality, uninterrupted chest compressions, with a modification suggested for the chest compression technique in wide-chested dogs. When intubation is not possible, bag-mask ventilation using a tight-fitting facemask with oxygen supplementation is recommended rather than mouth-to-nose ventilation.
CONCLUSIONS: These updated RECOVER BLS treatment recommendations emphasize continuous chest compressions, conformation-specific chest compression techniques, and ventilation for all animals. Very low quality of evidence due to absence of clinical data in dogs and cats consistently compromised the certainty of recommendations, emphasizing the need for more veterinary research in this area.

Ischemic teat necrosis (ITN) is a growing problem in the dairy industry characterized by teat lesions, necrosis, pruritus and automutilation. Despite the economic and welfare consequences, there is no treatment, and the etiology of the disease remains poorly understood. The aim of this study was to investigate ITN by analyzing its clinical presentation, potential risk factors and microbial involvement. Methods included collection of milk and swab samples from affected cows over a period of one-and-a-half years and completion of questionnaires by veterinarians and farmers. Microbial testing included PCR testing for Treponema spp. and cultural testing by anaerobic and aerobic incubation on blood agar. The results showed a high and significant prevalence of Treponema spp. and Staphylococcus aureus in affected teats compared to non-ITN-affected control teats, indicating their potential role in the development of ITN. Other factors such as edema and milking practices also appear to contribute to the tissue damage. First-lactation and early-lactation heifers are particularly at risk. In conclusion, ITN appears to have a multifactorial etiology with both infectious and non-infectious factors playing a role. Further research is needed to better understand the complex interplay of these factors and to develop effective prevention and management strategies.

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