COMPARATIVE SURVEY OF THREE TREATMENT PROCEDURE OF POST PARTURIENT METRITIS IN HOLSTEIN COWS

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1 : ISSN: COMPARATIVE SURVEY OF THREE TREATMENT PROCEDURE OF POST PARTURIENT METRITIS IN HOLSTEIN COWS SHAHRAD GHRAYELI MOGHADAM 1, AFSHIN DAVASAZ TABRIZI 2* 1: Student Of Veterinary Medicine, College Of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran 2: Department Of Clinical Science, College Of Veterinary Medicine, Tabriz Branch, Islamic Azad University, Tabriz, Iran *Corresponding Author's Postpartum uterine diseases of dairy cows compromise animal welfare and may result in early removal from the herd or impaired reproductive performance.the aim of present study was to comparative survey of three treatment procedure of post parturient metritis in Holstein cows. 24 cows for selected and divided into 3 groups of 8 in each by chance. Group 1 received only penicillin at a dose of IU per KgBW for 4 days. Group 2 received penicillin plus Ketoprofen at a dose of 3 ml per 100 KgBW for 4 days. Group 3 received penicillin plus flunixinmeglumine at a dose of 2.2 mg per KgBW for 4 days. For comparison of 3 different therapeutic methods, uterine clearance test was done 30, 45 and 60 days after parturition and quality of treatments were assayed. It shown that there is no statistical difference among groups.in conclusion it can be mentioned that selection a strategy for treatment of postpartum metritis should be chosen by considering the economic situations. Results of our and recently studies indicate that administration of NSAIDs like ketoprofen and flunixinmeglumine cause no significant treatment in metritis so we advise to remove these protocols from treatment of filed cases. Also, this protocol may decrease the costs of treatment. Keywords: Penicillin, Ketoprofen, Flunixinmeglumine, Metritis, Cow INTRODUCTION Postpartum uterine diseases of dairy cows reproductive performance. Metritisis compromise animal welfare and may result defined by an abnormally enlarged uterus in early removal from the herd or impaired and a fetid, watery, red-brown uterine 1166

2 discharge associated with signs of systemic illness (decreased milk yield, dullness, or other signs of toxemia) and temperature >39.5 C within 21 d after parturition. Endometritis refers to inflammation of the uterus without systemic illness, happening later than 21 d postpartum (Sheldon et al., 2006). In North America, metritis affects 10% to 20% of cows (LeBlanc et al., 2011), whereas the incidence of endometritis is approximately 28%, ranging from 5.3% to 52.6% (Cheong et al., 2012; Dubuc et al., 2010). Puerperal metritis is commonly treated with antibiotics like penicillin or third-generation cephalosporins. However, antibiotic resistance worldwide is recognized already as a top public health challenge facing the 21st century, and thus there is growing concern regarding the potential impact of extensive use of antibiotics in food animals, including latergeneration cephalosporins (Aust et al., 2012; Dolejska et al., 2011). Overton and Fetrow (2008) reported the cost of each case of metritis to be approximately US$ , due to antibiotic treatment and the detrimental effects of metritis on reproductive performance, milk production, and survivability. An efficacious vaccine against uterine diseases will have a significant positive impact on the dairy industry, limiting the use of antibiotics, and decreasing economic losses due to these disorders. Owing to the multifactorial nature of puerperal metritis and endometritis, a vaccine should likely be multivalent, including antigens from the most important etiological agents of uterine infections. Escherichia coli, Trueperellapyogenes and Fusobacteriu mnecrophorum are the primary bacterial causes of uterine diseases (Miller et al., 2007; Santos et al., 2011; Bicalho et al., 2010). In the first days postpartum, E. coli is the predominant bacteria in the infected uterus, and is highly associated with uterine inflammation and impaired reproductive performance (Machado et al., 2012; Bicalho et al., 2012; Bondurant, 1999). This early uterine contamination with E. coli leads to subsequent infection by F. necrophorum and T. pyogenes at 7 and >25 days postpartum, respectively (Bicalho et al., 2012; Dohmen et al., 2000), which are associated with both metritis and endometritis (Machado et al., 2012; Williams et al., 2005). The aim of present study was to comparative survey of three treatment procedure of post parturient metritis in Holstein cows. MATERIALS AND METHODS For this study, we referred to Tabriz husbandry farms and detected cows with post-partum metritis. 24 cows for selected 1167

3 and divided into 3 groups of 8 in each by chance. Group 1 received only penicillin at a dose of IU per KgBW for 4 days. Group 2 received penicillin plus Ketoprofen at a dose of 3 ml per 100 KgBW for 4 days. Group 3 received penicillin plus flunixinm eglumine at a dose of 2.2 mg per KgBW for 4 days. For comparison of 3 different therapeutic methods, uterine clearance test was done 30 days after parturition and quality of treatments were assayed. This method was repeated again on days 45 and 60 postpartum. RESULTS Data related to the 3 different therapeutic methods in cows of different groups after parturition are given in Table 1. As can be seen in table it shown that there is no statistical difference among groups. Table 1: parameters related to treated cows with 3 different therapeutic methods Group Uterine involution 30 Daysafter parturition Uterine involution 45 Daysafter parturition Uterine involution 60 Daysafter parturition 1 (penicillin) 2 cows (25%) a 5 cows (62.5%) b 8 cows (100%) c 2 (penicillin+ketoprofen) 3 cows (37.5%) a 5 cows (62.5%) b 8 cows (100%) c 3 (penicillin+ flunixinmeglumine) 3 cows (37.5%) a 6 cows (75%) b 8 cows (100%) c Dissimilar letters in each column show statistical difference. DISCUSSION AND CONCLUSION Metritisis characterized by inflammation of the entire thickness of the uterine walls, and is associated with signs of systemic illness such as dullness, decreased milk yield and fever. The signs of metritis (presence of fetid, watery, red-brown uterine discharge and rectal temperature greater than 39.5 C) used for the diagnosis of metritis in this study is widely used by researchers and veterinarians. In a recent study, it was reported that there is a considerable inconsistency between observers to classify animals as healthy or metritic based on the assessment of vaginal discharge odor, suggesting that the classification of disease based on the signs used is prone to errors. There are extensive arguments concerning the treatment of specific forms of postpartummetritis with antimicrobial agents. Antimicrobial agents may be needed to control infectioncaused by bacteria and prevent the progression of disease (Ball et al., 1984; Olson et al., 1985). Compounds from numerousantimicrobial families (e.g., sulfonamides, tetracyclines, ß-lactams, aminoglycosides,cephalosporins) have been used singularly or in combination for treating postpartum metritis. The use of antibiotics in dairy cattle could result in a milk-residue violation, a human healthrisk, and/or bacterial resistance. A major consideration when using antibiotics in dairy cattle isdrug residues. Currently, oxytetracycline is the only antimicrobial 1168

4 agent approved by the FDAfor use in lactating cows and thus labeled for the treatment of postpartum metritis (Arrioja, 2001). Oxytetracycline is specifically labeled for acute or toxic puerperal metritis caused by strains ofstaphylococci and streptococci (Arrioja, 2001). All other antimicrobial agents are not labeled for treating anyform of postpartum metritis. Because of potential drug residues from extralabel drug use, theus Dairy Quality Assurance Program was developed to ensure food safety. When treatingpostpartum metritis, various treatment routes, such as local (i.e., intrauterine) or systemic (i.e., IV, IM, SC), are available. Many antimicrobial agents are readily absorbed systemically from the uterus, includingsulfonamides, tetracyclines, penicillins, nitrofurazone, aminoglycosides, andchloramphenicol (Gilbert and Schwark, 1992). However, it is important to understand that intrauterine use of all theseantibiotics is off label. Days postpartum, uterine condition, uterine tissueabsorptive capabilities, and drug distributionare the major factors affecting the efficacy of most drugs infused into the postpartumuterus (Righter et al., 1975; Masera et al., 1980). The molecular structure of the antimicrobial agent and the vehicle used to deliverthe drug influence its absorption into the uterine tissue after local uterine infusion (Gustafsson, 1984). Thecompletely involuted uterus has better absorptive capabilities than the immediate postpartumuterus. Endometritis also results in poor concentration of drugs within the uterine tissue afterintrauterine treatment (Masera et al., 1980; Bretzlaff et al., 1983). The result of poor local uterine absorption is a high concentrationof drug on the endometrium but an inadequate concentration in the subendometrial tissues,vagina, cervix, ovaries, and oviducts (Gustafsson, 1984). Also, the high concentration of drug on the endometriummay result in local irritation of the uterine lining (Paisley et al., 1986). The environment of the postpartum uterus diminishes the efficacy of many drugs. Such factorsas low oxygen tension, antibioticdegrading enzymes, mucopurulent discharge, and organicdebris could lead to poor efficacy of certain antimicrobial agents infused into the postpartumuterus (Whitacre, 1992). In addition, infusion of antimicrobial agents has been shown to adversely affectleukocyte function and cause contamination of meat and milk products (Paisley et al., 1986). A mild case of endometritis may be the only form of postpartum metritis in which intrauterinetreatment is justified (Gustafsson, 1984). However, diagnosing 1169

5 mild endometritis is difficult in clinical practice.more severe pathologic changes, such as those seen in cows with postpuerperal metritis, toxicpuerperal metritis, and pyometra, may not respond to treatment by intrauterine infusion. Onereason could be that these disease conditions greatly reduce uterine tissue uptake of theantimicrobial agent (Bretzlaff et al., 1983; Gustafsson and Ott, 1981). Because of the many acknowledged shortcomings of intrauterineantibiotics, it is believed that intrauterine infusion alone often fails as a therapy forpostpartummetritis (Gustafsson, 1984). Amiridis et al., 2001 showed that Flunixinmeglumine accelerates uterine involution and shortens the calving-to-firstoestrus interval in cows with puerperal metritis. In a study by Drillich et al., 2001 on a financial analysis with 87 different cost scenarios demonstrated that a systemic treatment of toxic puerperal metr itis in cattle with ceftiofur is an effective alternative to the combination of local and systemic treatments. In another study by Drillich et al., 2007 reported that a single administration of 2.2 mg/kg of BW of FM in addition to a systemic antibiotic treatment of cows having APM did not result in beneficial effects on clinical cure, milk yield within 6 d after the first treatment, or reproductive performance. In conclusion it can be mentioned that selection a strategy for treatment of postpartum metritis should be chosen by considering the economic situations. Results of our and recently studies indicate that administration of NSAIDs like ketoprofen and flunixinmeglumine cause no significant treatment in metritis so we advise to remove these protocols from treatment of filed cases. Also, this protocol may decrease the costs of treatment. REFERENCES [1] Amiridis GS, Leontides L, Tassos E, Kostoulas P, Fthenakis GC.Flunixinmeglumine accelerates uterine involution and shortens the calving-to-first-oestrus interval in cows with puerperal metritis.j Vet PharmacolTher 2001;24(5): [2] Arrioja A: Product monographs, in Arrioja A (ed): Compendium of Veterinary Products, ed 6.Port Huron, MI, Adrian J. Bayley, [3] Aust V1, Knappstein K, Kunz HJ, Kaspar H, Wallmann J, Kaske M. Feeding untreated and pasteurized waste milk and bulk milk to calves: effects on calf performance, health status and antibiotic resistance of faecal bacteria. J 1170

6 AnimPhysiolAnimNutr (Berl). 2013; 97(6): [4] Ball L, Olson JD, Mortimer RG: Bacteriology of the postpartum uterus. ProcSocTherio: , [5] Bicalho ML, Machado VS, Oikonomou G, Gilbert RO, Bicalho RC (2012) Association between virulence factors of escherichia coli, fusobacteriumnecrophorum, and arcanobacteriumpyogenes and uterine diseases of dairy cows. Vet Microbiol 157: [6] Bicalho RC, Machado VS, Bicalho ML, Gilbert RO, Teixeira AG, et al. (2010) Molecular and epidemiological characterization of bovine intrauterine escherichia coli. J Dairy Sci 93: [7] Bondurant RH (1999) Inflammation in the bovine female reproductive tract. J AnimSci 77 Suppl 2: [8] Bretzlaff KN, Ott RS, Koritz GD, et al: Distribution of oxytetracycline in genital tract tissues of postpartum cows given the drug by intravenous and intrauterine routes. Am J Vet Res 44: , [9] Cheong SH, Nydam DV, Galvao KN, Crosier BM, Ricci A, et al. (2012) Use of reagent test strips for diagnosis of endometritis in dairy cows. Theriogenology 77: [10] Dohmen MJ, Joop K, Sturk A, Bols PE, Lohuis JA (2000) Relationship between intra-uterine bacterial contamination, endotoxin levels and the development of endometritis in postpartum cows with dystocia or retained placenta. Theriogenology 54: [11] Dolejska M, Jurcickova Z, Literak I, Pokludova L, Bures J, et al. (2011) IncN plasmids carrying bla CTX-M-1 in escherichia coli isolates on a dairy farm. Vet Microbiol 149: [12] Drillich M, Beetz O, Pfützner A, Sabin M, Sabin HJ, Kutzer P, Nattermann H, Heuwieser W.Evaluation of a systemic antibiotic treatment of toxic puerperal metritis in dairy cows.j Dairy Sci. 2001;84(9): [13] Drillich M1, Voigt D, Forderung D, Heuwieser W.Treatment of acute puerperal metritis with flunixinmeglumine in addition to antibiotic treatment.j Dairy Sci. 2007;90(8): [14] Dubuc J, Duffield TF, Leslie KE, Walton JS, LeBlanc SJ (2010) Definitions and diagnosis of 1171

7 postpartum endometritis in dairy cows. J Dairy Sci 93: [15] Gilbert RO, Schwark WS: Pharmacologic considerations in the management of peripartum conditions in the cow. Vet Clin North Am Food AnimPract 8:29 56, [16] Gustafsson BK, Ott RS: Current trends in the treatment of genital infections in large animals.compendcontineducpract Vet 3:S147 S151, [17] Gustafsson BK: Therapeutic strategies involving antimicrobial treatment of the uterus in large animals. JAVMA 185: , [18] LeBlanc SJ, Osawa T, Dubuc J (2011) Reproductive tract defense and disease in postpartum dairy cows.theriogenology 76: [19] Machado VS, Bicalho ML, Pereira RV, Caixeta LS, Bittar JH, et al. (2012) The effect of intrauterine administration of mannose or bacteriophage on uterine health and fertility of dairy cows with special focus on escherichia coli and arcanobacteriumpyogenes. J Dairy Sci 95: [20] Machado VS, Oikonomou G, Bicalho ML, Knauer WA, Gilbert R, et al. (2012) Investigation of postpartum dairy cows' uterine microbial diversity using metagenomic pyrosequencing of the 16S rrna gene. Vet Microbiol159: [21] Masera J, Gustafsson BK, Afiefy MM, et al: Disposition of oxytetracycline in the bovine genital tract: Systemic vs intrauterine administration. JAVMA 176: , [22] Miller AN, Williams EJ, Sibley K, Herath S, Lane EA, et al. (2007) The effects of arcanobacteriumpyogenes on endometrial function in vitro, and on uterine and ovarian function in vivo. Theriogenology 68: [23] Olson JD, Ball L, Mortimer RG: Therapy of postpartum uterine infections. Bovine Pract 17: , [24] Overton M, Fetrow J (2008) Economics of postpartum uterine health. Proc Dairy Cattle Reproduction Council [25] Paisley LG, Mickelsen WD, Anderson PB: Mechanisms and therapy for retained fetal membranes and uterine infections 1172

8 of cows: A review. Theriogenology 25: , [26] Righter HF, Mercer HD, Kline DA, et al: Absorption of antibacterial agents by the bovine involuting uterus. Can Vet J 16:10 15, [27] Santos TM, Gilbert RO, Bicalho RC (2011) Metagenomic analysis of the uterine bacterial microbiota in healthy and metritic postpartum dairy cows. J Dairy Sci 94: [28] Sheldon IM, Lewis GS, LeBlanc S, Gilbert RO (2006) Defining postpartum uterine disease in cattle.theriogenology 65: [29] Whitacre MD: Intrauterine infusion in the postpartum dairy cow. Vet Med 87: , [30] Williams EJ, Fischer DP, Pfeiffer DU, England GC, Noakes DE, et al. (2005) Clinical evaluation of postpartum vaginal mucus reflects uterine bacterial infection and the immune response in cattle. Theriogenology 63:

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