ANTIMICROBIAL RESISTANCE IS A MAJOR PUBLIC HEALTH CONCERN, AND ITS DEVELOPMENT AND SPREAD IS PARTIALLY BLAMED ON THE USE OF ANTIMICROBIAL DRUGS IN FOOD ANIMALS. METRITIS IS A UTERINE DISEASE OF DAIRY COWS THAT IS CAUSED BY MIXED BACTERIAL INFECTION THAT OCCURS WITHIN THE FIRST COUPLE OF WEEKS AFTER PARTURITION. METRITIS AFFECTS ABOUT 10-20% OF POSTPARTUM COWS, AND THEREFORE ITS TREATMENT REPRESENTS A MAJOR DRIVER OF ANTIMICROBIAL DRUGS USAGE IN THE DAIRY INDUSTRY. CURRENTLY, SUBCUTANEOUS INJECTION OF CEFTIOFUR IS RECOMMENDED FOR METRITIS TREATMENT. ALTHOUGH THIS THERAPY HAS BEEN REPORTED TO INCREASE METRITIS CURE FROM 55-62% IN UNTREATED COWS TO 74-77% IN TREATED ONES, IT IS IMPORTANT TO HIGHLIGHT THAT MORE THAN HALF OF THE ANIMALS UNDERGO SPONTANEOUS CURE (ANIMALS THAT WERE CURED FROM METRITIS WITHOUT THE USE OF ANTIMICROBIALS). ADDITIONALLY, TREATMENT FAILURE (CASES OF METRITIS THAT DID NOT CURE AFTER ANTIMICROBIAL THERAPY) OCCURS IN IN 23-26%. HENCE, WE CAN CONCLUDE THAT CEFTIOFURTHERAPY ONLY CHANGES THE METRITIS CURE OUTCOMES IN 1 OUT OF 5 COWS. HOWEVER, WE STILL CANNOT PREDICT WHO THOSE COWS ARE. THEREFORE, MORE RESEARCH IS NEEDED TO IDENTIFY FACTORS THAT CAN BE USED TO TARGET METRITIS CASES THAT WILL BENEFIT FROM ANTIMICROBIAL THERAPY. THE SUCCESSFUL IMPLEMENTATION OF SELECTIVE THERAPY STRATEGIES FOR METRITIS WILL DEPEND ON HOW USING CEFTIOFUR FOR METRITIS THERAPY AFFECTS ECONOMIC OUTPUTS (MILK PRODUCTION AND FERTILITY) AND ANTIMICROBIAL RESISTANCE DEVELOPMENT. THE GOALS OF THIS STUDY ARE TO IDENTIFY COW-RELATED FACTORS THAT COULD BE USED TO PREDICT METRITIC COWS THAT WILL LIKELY BENEFIT FROM ANTIMICROBIAL TREATMENT, AND TO EVALUATE THE BENEFITS AND DRAWBACKS OF USING ANTIBIOTICS TO TREAT METRITIS, CONSIDERING PRODUCTIVITY AND ANTIMICROBIAL RESISTANCE DEVELOPMENT. THIS WILL CONTRIBUTE FOR THE JUDICIOUS USE OF ANTIBIOTICS IN THE DAIRY INDUSTRY, CONSIDERING THE PUBLIC HEALTH CONCERNS ABOUT ANTIMICROBIAL USE AND ENSURING ANIMAL HEALTH, AND PRODUCER PROFITABILITY.FOUR HUNDRED COWS AFFECTED WITH METRITIS WILL BE ENROLLED IN THIS STUDY. ANIMALS WILL BE ENROLLED FROM FARMS LOCATED AT TX, NM, IL, AND FL. AT ENROLLMENT, HALF OF COWS WILL RECEIVE SYSTEMIC CEFTIOFUR THERAPY, WHILE THE OTHER HALF WILL REMAIN UNTREATED. TWO WEEKS LATER, COWS WILL BE RE-EVALUATED FOR METRITIS CURE (ABSENCE OF CLINICAL SIGNS THAT ARE CHARACTERISTIC OF METRITIS). AT THE TIME OF ENROLLMENT, BLOOD SAMPLES WILL BE COLLECTED FOR THE ASSESSMENT OF SEVERAL IMMUNOLOGIC, INFLAMMATORY, AND METABOLIC BIOMARKERS. THE ACCURACY OF THESE MARKERS AND OTHER COW-RELATED FACTORS (E. G., AGE, DYSTOCIA) ON PREDICTING SPONTANEOUS CURE AND TREATMENT FAILURE WILL BE ASSESSED USING SEVERAL STATISTICAL MODELS. USING DATA COLLECTED ON MILK PRODUCTION, FERTILITY, AND SURVIVABILITY, WE WILL ALSO DETERMINE THE IMPACT OF SYSTEMIC CEFTIOFUR THERAPY OF METRITIS ON ECONOMICALLY IMPORTANT OUTCOMES. ADDITIONALLY, WE WILL EVALUATE THE IMPACT OF CEFTIOFUR TREATMENT OF METRITIS ON THE DEVELOPMENT OF ANTIMICROBIAL RESISTANCE FROM FECAL BACTERIA. FOR A SUBSET OF ANIMALS, FECAL SAMPLES WILL BE COLLECTED AT ENROLLMENT, AND AT FIVE AND FOURTEEN DAYS AFTER ENROLLMENT. THOSE SAMPLES WILL BE SUBMITTED TO A SERIES OF ANALYSIS WHICH WILL QUANTIFY, THROUGH SEQUENCING OF THE DNA OF EXISTING BACTERIA, THE ABUNDANCE OF ANTIMICROBIAL RESISTANCE GENES IN TREATED AND UNTREATED COWS. HENCE, WE WILL DETERMINE THE ANTIMICROBIAL RESISTANCE BURDEN OF USING ANTIBIOTICS FOR THE TREATMENT OF METRITIS IN DAIRY COWS. UPON COMPLETION OF THIS STUDY, WE WILL HAVE GENERATED CRUCIAL KNOWLEDGE FOR DEVELOPMENT OF SELECTIVE THERAPY OF METRITIS IN DAIRY COWS THAT WILL NOT COMPROMISE ANIMAL HEALTH AND PRODUCTIVITY. WE WILL ALSO HAVE ASSESSED HOW THE USE OF CEFTIOFUR FOR THE TREATMENT OF METRITIS IMPACTS PROFITABILITY AND THE DEVELOPMENT AND SPREAD OF ANTIMICROBIAL RESISTANCE. WE ANTICIPATE THAT THIS KNOWLEDGE WILL BE INSTRUMENTAL FOR EVIDENCE-BASED DECISIONS FOR STAKEHOLDERS AND WILL BE USED BY LAWMAKERS TO IMPLEMENT NEW POLICIES ENDORSING JUDICIOUS USE OF ANTIMICROBIALS IN DAIRY FARMING.