title: Demonstration of non-inferiority of a novel combination intramammary antimicrobial in the treatment of clinical mastitis.
abstract: OBJECTIVE
  To test the non-inferiority of a novel combination intramammary product containing penicillin and cloxacillin to a reference intramammary product containing oxytetracycline, oleandomycin, neomycin and prednisolone with regard to bacteriological cure and clinical cure.
  
  
  METHODS
  Clinical cases of mastitis were sourced from 30 spring-calving dairy farms in the Southland region of New Zealand. Affected quarters were infused three times at 24 hourly intervals with either the novel combination product containing 1 g penicillin and 200 mg cloxacillin, or a reference product containing 200 mg oxytetracycline, 100 mg oleandomycin, 100 mg neomycin and 5 mg prednisolone. Cows were enrolled when a farmer detected a case of clinical mastitis. Milk samples were collected for microbiological culture immediately before treatment (Day 0) and on Days 9, 16 and 23. Bacteriological cure was compared for 187 and 178 quarters treated with the reference and novel product, respectively, and clinical cure was compared for 235 and 223 quarters, respectively. Non-inferiority was assessed by calculating the difference in cure rates between the two products and constructing a 95% CI around the difference, using the variance inflation factor to account for herd level clustering. The non-inferiority margin was 20% for both bacteriological and clinical cure. Generalising estimating equation models were used to determine predictor variables.
  
  
  RESULTS
  The bacteriological cure percentage, adjusted to account for herd-level clustering, was 8.5 (95% CI=-1.7-21.8)% higher for quarters treated with the novel than the reference product. The adjusted clinical cure percentage was 0.3 (95% CI=-11.2-12.0)% higher for clinical quarters treated with the novel than the reference product. Bacterial species was the only covariate for bacteriological cure (p=0.003), and quarter score at enrolment (indicating udder inflammation) was the only covariate for clinical cure (p=0.032) in the multivariable models.
  
  
  CONCLUSIONS
  The novel combination product was demonstrated to be non-inferior to the reference product with regards to both bacteriological cure and clinical cure.
  
  
  CONCLUSIONS
  Clinicians treating mastitis now have access to this novel combination intramammary product, and demonstration of its non-inferiority compared to the existing reference product will provide options for treatment approaches. The novel product contains fewer antimicrobials; which are of a narrower spectrum of activity.
authors.affiliation: a Vetsouth Ltd , PO Box 12, Winton , 9741 , New Zealand.
authors.forename: M A
authors.initials: MA
authors.lastname: Bryan
authors.affiliation: a Vetsouth Ltd , PO Box 12, Winton , 9741 , New Zealand.
authors.forename: S Y
authors.initials: SY
authors.lastname: Hea
authors.affiliation: b Estendart Ltd , PO Box 45, Palmerston North , New Zealand.
authors.forename: S A
authors.initials: SA
authors.lastname: Mannering
authors.affiliation: c Stockguard Laboratories (NZ) Ltd , PO Box 10305, Hamilton , 3241 , New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Booker
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002417:Cattle; D003023:Cloxacillin / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000662:veterinary; D005260:Female; D007267:Injections / Q000662:veterinary; D008321:Mammary Glands, Animal; D008414:Mastitis, Bovine / Q000188:drug therapy*; D009355:Neomycin / Q000008:administration & dosage / Q000627:therapeutic use; D009827:Oleandomycin / Q000008:administration & dosage / Q000627:therapeutic use; D010118:Oxytetracycline / Q000008:administration & dosage / Q000627:therapeutic use; D010406:Penicillins / Q000008:administration & dosage / Q000627:therapeutic use; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D010406:Penicillins; D011239:Prednisolone; D009355:Neomycin; D003023:Cloxacillin; D009827:Oleandomycin; D010118:Oxytetracycline
keywords: Penicillin; bacteriological cure; clinical cure; clinical mastitis; cloxacillin; non-inferiority