Comparison between intrauterine application of an antibiotic and an herbal product to treat clinical endometritis in dairy cattle - A randomized multicentre field study.

Uterine diseases are main indications for antibiotic use in dairy cows. To test a non-antibiotic treatment option, we compared the effect of an intrauterine cephapirin (Metricure®; cefapirin benzathin 500 mg per dosis; CEPH) with an intrauterine applied herbal product (25 ml of EucaComp® PlantaVet containing alcoholic extracts of Calendula officinalis L., Mellissa officinalis L., Origanum majorana L. and Eucalyptus globulus Labill. (EUC)) on the clinical cure of endometritis. Examinations of 816 cows between 21 and 35 days after calving were performed and cases of clinical endometritis (n = 169) were included. Diagnosis based on a scoring system for vaginal discharge. Study animals were randomly assigned to one of two treatment groups and treated immediately. After excluding animals with incomplete datasets, 136 cows (EUC: n = 61; CEPH: n = 75) remained for the final analysis. In total, 64% (EUC: 61%, CEPH: 67%) of analysed endometritis cases were considered as clinically cured 14 ± 2 days after the first treatment, 15% stayed uncured after the application of a maximum of two consecutive treatments, leading to an overall clinical cure rate of 85% (EUC: 82%, CEPH: 88%). No statistically difference in clinical cure rates could be observed between both treatment groups nor 14 ± 2 days after the first treatment (p = 0.956) neither regarding the overall cure rate (p = 0.923). In conclusion, the clinical cure of dairy cows' endometritis after the intrauterine application of the herbal product was non-inferior to the intrauterine application of the antibiotic cephapirin. These results could contribute to reduce the antimicrobial use in the daily veterinary routine treatment of endometritis.

Estimation of epidemiological cut-off values for eight antibiotics used for treatment of bovine mastitis caused by Streptococcus uberis and Streptococcus dysgalactiae subsp. dysgalactiae.

Interpretive criteria for antimicrobial susceptibility testing are lacking for most antimicrobials used for bovine streptococcal mastitis. The objectives of this study were to determine (tentative) epidemiological cut-off ((T)ECOFF) values for clinically relevant antibiotics used for treatment of bovine mastitis, and to estimate the proportion of acquired resistance (non-wild-types) in Streptococcus dysgalactiae subsp. dysgalactiae and Streptococcus uberis. A total of 255 S. uberis and 231 S. dysgalactiae subsp. dysgalactiae isolates were obtained in Denmark and Norway from bovine mastitis. The isolates were tested for susceptibility to 10 antibiotics using broth microdilution. In accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standard operating procedure, additional published MIC distributions were included for the estimation of ECOFFs for cloxacillin, cephapirin, lincomycin and tylosin, and TECOFFs for amoxicillin, benzylpenicillin, cephapirin and oxytetracycline. The proportion of non-wild-type (NWT) isolates for the beta-lactams was significantly higher in the Danish S. uberis (45-55%) compared to the Norwegian isolates (10-13%). For oxytetracycline, the proportion of NWT was significantly higher in the Danish isolates, both for S. uberis (28% vs. 3%) and S. dysgalactiae (22% vs. 0%). A bridging study testing in parallel MICs in a subset of isolates (n = 83) with the CLSI-specified and the EUCAST-specified broths showed excellent correlation between the MICs obtained with the two methods. The new ECOFFs and TECOFFs proposed in this study can be used for surveillance of antimicrobial resistance, and - for antimicrobials licensed for streptococcal bovine mastitis - as surrogate clinical breakpoints for predicting their clinical efficacy for this indication.

In vitro antibiotic susceptibility and biofilm production of Staphylococcus aureus isolates recovered from bovine intramammary infections that persisted or not following extended therapies with cephapirin, pirlimycin or ceftiofur.

Staphylococcus aureus intramammary infections (IMIs) have low cure rates using standard antibiotic treatment and increasing the duration of treatment usually improves therapeutic success. Chronic IMIs are thought to be caused by bacteria presenting a specific virulence phenotype that includes the capacity to produce greater amounts of biofilm. In this study, antibiotic susceptibility and biofilm production by S. aureus isolates recovered from IMIs that were cured or not following an extended therapy with cephapirin, pirlimycin or ceftiofur for 5, 8 and 8 days, respectively, were compared. An isolate was confirmed as from a persistent case (not cured) if the same S. aureus strain was isolated before and after treatment as revealed by the same VNTR profile (variable number of tandem repeats detected by multiplex PCR). The antibiotic minimal inhibitory concentrations (MICs) were determined for these isolates as well as the capacity of the isolates to produce biofilm. Isolates from persistent cases after extended therapy with cephapirin or ceftiofur had higher MICs for these drugs compared to isolates from non-persistent cases (p < 0.05) even though the antibiotic susceptibility breakpoints were not exceeded. Isolates of the ceftiofur study significantly increased their biofilm production in presence of a sub-MIC of ceftiofur (p < 0.05), whereas isolates from the pirlimycin group produced significantly less biofilm in presence of a sub-MIC of pirlimycin (p < 0.001). Relative antibiotic susceptibility of the isolates as well as biofilm production may play a role in the failure of extended therapies. On the other hand, some antibiotics may counteract biofilm formation and improve cure rates.

Relationship between in vitro susceptibility test results and treatment outcomes for gram-positive mastitis pathogens following treatment with cephapirin sodium.

The selection of antimicrobial agents for the treatment of mastitis has often been based on results of in vitro susceptibility testing. However, the results of in vitro susceptibility tests have been shown to be poor predictors of treatment outcomes. The objective of this study was to determine if an association existed between results of antimicrobial susceptibility tests and outcomes of mastitis caused by gram-positive pathogens recovered from quarters that received treatment with cephapirin sodium. Mastitis pathogens were obtained from a multi-site clinical trial that evaluated the benefits of using an on-farm culturing system. Target pathogens (n = 187) comprised coagulase-negative staphylocci (65%), Streptococcus spp. (14%), other pathogens (12%), and Staphylococcus aureus (11%), which were recovered from quarters that received treatment using cephapirin sodium. The antimicrobial susceptibility profile to cephapirin was determined using the broth micro-dilution technique. The overall bacteriological cure rate achieved by cephapirin treatment was 82%. Bacteriological outcomes (cure or treatment failure) were not associated with pathogen type. A recurrent case of mastitis was observed in 10 quarters classified as cures and 3 quarters classified as treatment failures. Recurrence of mastitis was not associated with bacteriological outcomes or susceptibility test results. In vitro susceptibility to cephapirin was exhibited by 94.8 and 91.2% of pathogens recovered from quarters classified as cures and treatment failures, respectively. Bacteriological outcomes of mastitis treated using cephapirin were not associated with in vitro susceptibility test results or in vitro minimum inhibitory concentration values. In this population, there was an 82% probability of treatment success when the isolate was susceptible but only a 27% probability of treatment failure when the isolate was resistant. Based on this research, results of in vitro susceptibility tests should not be used as the primary guide for treatment decisions regarding intramammary cephapirin sodium.

Use of antimicrobial susceptibility testing of bacterial pathogens isolated from the milk of dairy cows with clinical mastitis to predict response to treatment with cephapirin and oxytetracycline.

OBJECTIVE: To determine whether results of antimicrobial susceptibility testing of bacterial pathogens isolated from the milk of dairy cows with clinical mastitis were associated with duration of clinical signs or bacteriologic cure rate following treatment with cephapirin and oxytetracycline. DESIGN: Observational study on a convenience sample. ANIMALS: 58 dairy cows with 121 episodes of clinical mastitis. PROCEDURE: Cows that only had abnormal glandular secretions were treated with cephapirin alone. Cows with an inflamed gland and abnormal glandular secretions were treated with oxytetracycline and cephapirin. Cows with systemic signs of illness, an inflamed gland, and abnormal glandular secretions were treated with oxytetracycline and flunixin meglumine and frequent stripping of the affected glands. The Kirby-Bauer method was used for antimicrobial susceptibility testing, and current guidelines were used to categorize causative bacteria as susceptible or resistant to the treatment regimen. RESULTS: Median durations of episodes of clinical mastitis caused by susceptible (n = 97) and resistant (24) bacteria were not significantly different. Bacteriologic cure rates at 14 and 28 days were similar for episodes caused by susceptible and resistant bacteria; however, for 56 episodes of clinical mastitis caused by gram-positive bacteria and treated with cephapirin alone, bacteriologic cure rate at 28 days was significantly higher for susceptible than for resistant bacteria. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that antimicrobial susceptibility testing was of no value in predicting duration of clinical signs or bacteriologic cure rate in dairy cows with mastitis, except for episodes caused by gram-positive organisms treated with intramammary administration of cephapirin alone.

Comparison of antibiotic administration in conjunction with supportive measures versus supportive measures alone for treatment of dairy cows with clinical mastitis.

OBJECTIVE: To determine whether antibiotic and supportive treatment would improve outcome for dairy cows with naturally developing clinical mastitis, compared with supportive treatment alone. DESIGN: Randomized controlled trial. ANIMALS: 124 cows in one herd with 172 episodes of clinical mastitis. PROCEDURE: Cows were examined at the onset of clinical mastitis, assigned a severity score, and randomly assigned to receive antibiotic (intramammary administration of cephapirin, i.v. administration of oxytetracycline, or both) and supportive treatment (administration of oxytocin, stripping of affected glands, and, in severely affected cows, administration of flunixin meglumine or fluids) or supportive treatment alone. Treatment was continued until 24 hours after signs of clinical mastitis resolved (clinical cure). Milk samples from affected glands were submitted for bacterial culture before initial treatment and every 2 weeks thereafter until the causative organism was no longer isolated (bacteriologic cure). RESULTS: When mastitis was caused by Streptococcus spp or coliform bacteria, clinical cure rate by the tenth milking was significantly higher if antibiotics were used. Bacteriologic cure rate at 14 days was significantly higher when antibiotics were used, particularly if mastitis was caused by Streptococcus spp. Cows receiving antibiotics developed fewer subsequent episodes of clinical mastitis during the 60 days after the initial episode of mastitis and had less severe clinical disease than cows that did not. CLINICAL IMPLICATIONS: Results suggest that, in herds in which mastitis is often caused by environmental bacteria, antibiotic and supportive treatment may result in a better outcome for cows with clinical mastitis than supportive treatment alone.

Efficacy of intramuscular oxytetracycline as a dry cow treatment for Staphylococcus aureus mastitis.

To determine the efficacy of intramuscular oxytetracycline as a supplemental dry cow treatment for Staphylococcus aureus mastitis, 37 Holstein cows were randomly assigned to two treatment groups: intracisternal infusion with a commercial preparation of cephapirin benzathine at drying off (20 cows) and infusion with cephapirin benzathine at drying off and intramuscular oxytetracycline at 11 mg/kg once daily on d 7, 8, 9, and 10 after drying off (17 cows). Milk samples collected 7, 14, 30, and 60 d after calving were plated for bacterial isolation within 24 h after collection and after 24 to 72 h of storage at -20 degrees C. Quarters were defined as infected if S. aureus was isolated from the fresh and frozen cultures from any one sample collected before drying off. An infected quarter was defined as cured if S. aureus was not isolated from the fresh or frozen culture from milk samples obtained following calving. The rate of cure by 30 d after calving for systemic oxytetracycline (in combination with cephapirin treatment) was 29.4% for infected quarters and 29.4% for infected cows, compared with 27.5 and 25.0%, respectively, for the cephapirin treatment only. Results including the culture at 60 d after calving were 21.2 and 22.5%, respectively, for combination therapy and cephapirin therapy only. Systemic oxytetracycline, in combination with intramammary dry cow treatment, did not improve the rate of cure for S. aureus mastitis.

Influence of prepartum antibiotic therapy on intramammary infections in primigravid heifers during early lactation.

Jersey heifers were assigned alternately to three groups: 1) negative control (n = 41), 2) intramammary infusion of 200 mg of sodium cloxacillin (n = 38) at 7 d before expected parturition, and 3) intramammary infusion of 200 mg of cephapirin sodium (n = 36) at 7 d before expected parturition. The percentage of mammary glands infected prior to treatment was 62.2, 50.0, and 70.1 for groups 1, 2, and 3, respectively. The percentage of mammary glands infected during early lactation was 44.5, 8.6, and 2.1 for groups 1, 2, and 3, respectively. Most infections (87.1%) were due to Staphylococcus species other than Staphylococcus aureus. Thirty-six of 460 quarters were infected with major pathogens before treatment, 3 of 22 persisted following antibiotic treatment, and 9 of 14 persisted in the control group. Infusion of sodium cloxacillin resulted in antibiotic residues in 17.4% of samples obtained .5 d postpartum. All samples were negative at 3 and 10 d postpartum. Infusion of cephapirin sodium resulted in antibiotic residues in 84.7, 28.2, and 0% of samples obtained at .5, 3, and 10 d, respectively. Prepartum antibiotic therapy was effective in eliminating many IMI, especially those caused by coagulase-negative staphylococci, but there is the potential for antibiotic residues in milk.

Determination of milk and mammary tissue concentrations of ceftiofur after intramammary and intramuscular therapy.

Twenty-five Staphylococcus aureus strains isolated from bovine mastitis were tested for their susceptibility to ceftiofur. Zone diameter for 30 micrograms disks averaged 39 mm, and minimum inhibitory concentrations ranged from .5 to 1 microgram/ml. Tissue and milk concentrations were determined from biopsy and quarter milk samples collected from eight cows treated with either intramammary infusion of 100 or 200 mg of ceftiofur, one or two intramuscular injections of 500 mg of ceftiofur, or combination therapy of intramammary infusion coupled with intramuscular injection. Three additional cows received two intramammary infusions of 200 mg of cephapirin at 24-h intervals. Intramuscular injections of ceftiofur resulted in tissue and milk concentrations below detectable limits. Staphylococcus aureus was not eliminated from infected mammary glands by infusion of 100 mg of ceftiofur or by injection of 500 mg of ceftiofur by 48 h after treatment. Combination therapy of 100 mg of ceftiofur infused and 500 mg injected reduced S. aureus numbers in milk and tissue markedly, as did infusion of 200 mg of ceftiofur. Cows receiving intramammary infusion of 200 mg of ceftiofur (two doses at 24-h intervals) had highest concentrations in milk (450 micrograms/ml at 4 and 6 h) and in tissue (.08 microgram/mg at 30 h). These concentrations are similar to those obtained with two 200-mg doses of cephapirin at 24-h intervals. Histologic analysis of mammary parenchymal tissues showed that combination therapy resulted in higher percentages of alveolar luminal area and lower percentages of interalveolar stroma compared with infusion or injection alone. Histology of quarters receiving combination therapy was not different from that of quarters receiving cephapirin infusion alone.

Systemic dry cow therapy--a preliminary report.

Efficacy of three different treatment regimens in the elimination and prevention of Staphylococcus aureus intramammary infection was studied in 106 dry cow periods. At drying off, norfloxacin nicotinate was given subcutaneously to 44 cows at 10 mg/kg, oxytetracycline-HCl was administered intramuscularly to 18 cows at 20 mg/kg, 500 mg cephapirin benzathine were infused into each udder quarter of 21 cows, and a group of 23 cows served as an untreated control. Number of existing Staphylococcus aureus intramammary infections was reduced only in the norfloxacin nicotinate treatment group. New infection rate appeared lower in the two systemic treatment groups. The percentage of infected quarters remained the same throughout the dry period in the norfloxacin treatment group but number of infected quarters increased by 33 to 85% (significant in the cephapirin group) in the other groups. Minimal inhibitory concentration of the drugs for 57 S. aureus isolates was determined. Isolates were sensitive to norfloxacin and cephapirin and moderately sensitive to oxytetracycline. Results suggest that systemic dry cow therapy using norfloxacin nicotinate, which possesses large distribution volume, long half-life, and is highly active against the pathogen involved, was more effective than the other treatments.

Effectiveness of two new cephalosporins, cephazolin and cephapirin, administered intermittently in acute and chronic osteomyelitis in children.

Ten patients were treated, most of pre-school age, with acute osteomyelitis, produced by Staphylococcus aureus and Salmonella, having evolved for approximately one week, with sodium cephazolin at doses of 60 mg/kg/day intramuscularly in two daily injections for the first seven days and then in a single dose every twenty-four hours for four to seven weeks. Nine of ten patients were asymptomatic six months after this treatment. The patient who manifested chronic signs at the end of six weeks of therapy continued to be treated with three weekly injections of the same drug at an equal dose until the completion of six months, at the end of which he was asymptomatic. Ten patients with chronic osteomyelitis having evolved for two months to five years, due to penicillin-resistant Staphylococcus aureus, were treated with cephapirin at the dose of 30 mg/kg in one daily injection intramuscularly for three to four weeks and then the same dose on Mondays, Wednesdays and Fridays until the completion of six months. Eight patients who required it were sequestrectomized. Seven of the ten patients improve and remained asymptomatic for the same period of observation. The three patients who did not show marked clinical improvement did exhibit an appreciable radiological recovery. We have presented these regimens of treatment with a view of encouraging research into the intermittent administration of bactericidal antibiotics for pyogenic infections; in spite of the good results, we do not dare to recommend them in daily practice.

Treatment of pneumonia and other serious bacterial infections with cephapirin.

Nineteen patients with pneumonia due to Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, or Escherichia coli were treated with 4 to 18 g of cephapirin daily. There were three treatment failures. One patient each with pneumonia due to E. coli or S. pneumoniae died despite apparent eradication of the pathogen. Lobar pneumonia due to K. pneumoniae progressed during therapy in a third patient to lung gangrene, necessitating pneumonectomy. Five additional patients with pneumococcal pericarditis or septic bursitis, empyema, cannula-associated bacteremia, and thoractomy wound infection due to S. aureus were cured. All isolates of S. aureus, S. pneumoniae, and group A Streptococcus were inhibited by 0.8 mug of cephapirin per ml; minimal inhibitory concentrations of cephalothin were similar. Ninety percent of K. pneumoniae, 85% of Proteus mirabilis, 73% of E. coli, and 30% of Enterobacter were inhibited by 12.5 mug cephapirin per ml. All isolates of Pseudomonas, Serratia and indole-positive Proteus had a cephapirin minimal inhibitory concentration of [Formula: see text] 100 mug/mg. Serum concentrations after intravenous and intramuscular injection were similar to those reported for cephalothin. The intramuscular injections were moderately painful, and intravenous infusions caused phlebitis in three of nine patients treated with doses up to 18 g per day. Cephapirin appears comparable to cephalothin in vitro and is an effective agent in treatment of infection due to S. aureus and S. pneumoniae.