NEWS CLOXACILLIN AND VETERINARY MEDICINE* The use of cloxacillin in veterinary medicine has been considered by a Working Party of the National Health and Medical Research Council which is investigating the use of antibiotics in human and veterinary medicine. The Association was asked t o give its views and this request was subsequently referred t o us, as members of the Sub-committee on Bovine Mastitis. through the Standing Committee on Disease and its Control. Some medical authorities have argued that resistant sgrains of Staphylococcus aureus may develop in cattle, that these strains may infect man and that resistance could then be spread to human pathogens. While there can be no simple reply to such a proposal, it is considered that the use of cloxacillin in veterinary medicine, in particular with reference to therapy of mastitis in cattle, does not constitute a risk to human health. This conclusion is based on the following evidence. Use of Methicillin in Man Methicillin and cloxacillin are similar semisynthetic penicillins, and for the purposes of this discussion can be considered synonymous. Methicillin was first reported in 1960 (Rollinson et al 1960) and resistant strains in man were discovered soon after this (Jevons 1961). Since then resistant strains have been reported from many countries, particularly from Europe. However, the nature of this resistance is ill-understood. Though transfer can be achieved under highly specific and artificial conditions, for epidemiologic purposes it can be considered nontransferable. There is some evidence that resistant Strains arose from a single clone and that the widespread use of methicillin has allowed it to spread. There is also some doubt as to the clinical significance of such resistance (see review by Lacey 1975). These resistant strains are curious in that they do not appear to maintain themselves indefinitely in the hospital environment as do penicillin resistant strains. Recognition of the clinical importance of such an antibiotic and the possibility of further spread of resistance has prompted a responsible and careful approach to the use of the drug in man which should now prolong its effective use. Use of Cloxacillin in Cattle Methicillin and cloxacillin were both used in initial trials and cloxacillin was preferred for use in mastitis therapy (Wilson et a1 1962). Since then cloxacillin has been widely used in most dairying countries of the world. It was developed as a drug of choice in the method of mastitis control which evolved from the National Institute for Research in Dairying, Reading (Dodd and Neave 1970) and the efficacy of the formulations of cloxacillin is better documented than is any other intramammary drug. In almost every trial it has performed better than other preparations and though this performance was sometimes marginal, it can be considered the drug of choice for dry-cow therapy. It should be stressed that the control system developed at Reading has been the most important advance in mastitis control since penicillin was first introduced. An essential part of the program is the use *This statement was prepared by the A V A Subcommitt&pm Mastitis (R. J. T. Hoare. Convener),
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of dry-cow therapy which in the long term results in an overall reduction in the use of antibiotics. As far as we are aware, the only known resistant strains in cattle were reported from Belgium, and it was shown subsequently that they were of human origin, of the type referred to above. Otherwise, millions of doses have been used without evidence of the emergence of resietant strains. It is clear then ‘ore that the use of cloxacillin in cattle has not pose& ‘ny threat to human health, though the possibility of oi,.:r developments must be considered. Other Forms of Resistance It may be argued that another form of resistance to the semisynthetic penicillin may appear, analogous to that of resistance to many other antibiotics. In particular it could be plasmid-controlled and able to be transferred. Should such a strain develop in animal staphylococci there is the possibility of transfer to human pathogens. This possibility would seem remote for the following reasons. The manner in which cloxacillin is used The formulation for dry-cow therapy allows high dose, prolonged effect of the drug which should minimise the opportunity for selection. The selection pressure supplied by such antibiotic therapy is not great as it is not continuous either in the one animal or in the herd. Cases in which infection persists are those with severe udder fibrosis which prevent antibiotic diffusion. Such cases are eventually culled and rarely are sold to other farms. The opportunity for spread of a resistant strain is therefore not great, as the dairy herd is not the equivalent of the medical hospital in terms of a focus for the development, maintenance and spread of antibiotic resistant organisms. This is substantiated by evidence from diagnostic and research laboratories, which indicates that while resistance to antibiotics may appear -in an occasional herd (e.g. to streptomycin, neomycin, erythromycin, spiramycin) , it does not appear to spread to other herds and the overall level of resistance, apart from that to penicillin, is low. The evidence suggests that the strains of staphylococci harboured by the different animal species form different populations from an ecological point of view. Phage patterns shown by staphylococci from different animal species usually differ, and though some overlap undoubtedly occurs, cross infections are not common and usually do not persist. Pasteurisation of milk means the number of people exposed to this chance of cross-infection is very low, further reducing the potential significance of this means of transfer. A s long as methicillin continues to be used in man, the possibility remains of selection favouring such resistance should it occur, and evidence from using other antibiotics in man suggests this to be a most potent form of selection pressure. A range of antibiotics, including semisynthetic penicillins, is used in small-animal medicine. These are rarely used for prolonged therapy, and expense rules out all but the most common antibiotics. It is considered that usage of antibiotics such as cloxa245
cillin in this way to be insignificant in terms of risk to the human health. If antibiotics are to maintain their role in both human and veterinary medicine, they must be used carefully and responsibly. This has been argued strongly others and we support this and the principles of the Swam and other similar reuorts. We consider that the therapeutic use in animak of drugs such as cloxacillinpconforms to these principles and presents no significant risk to human health.
References Dodd, F. H., and Neave, F. K. (1970)-Bien Rev. Nat. Znst. Dair.. u. ~21. Jevons, M. p. (1961)-Br. med. J . 1: 124. Lacey, R. (1975)-Bact. Rev. 39: Rowlinson, G . N.,Stevens, S., Batchelor, F. R., Wood, J. c., and Chain, E. B. ( 1 9 6 O ) - h c e t i: 564. Wilson, C. D., Coates, W. A., and Brander, G. C. (1962)--'Vet. Rec. 74: 1120. I
LETTERS TO THE EDITOR SALVAGE OF A VALUABLE BULL AFFECTED WITH UNILATERAL BRUCELLA ABORTUS ORCHITIS Galloway ( 1974) considered that partial castration cision was left open to drain. The bull was then placed of valuable bulls affected with unilateral orchitis caused on a 2 week course of chloramphenicol succinate Of by Bruceffa abortus may allow their continued use. rolitetracyclinet at the rate of 4g intra-muscularly every 36 hours. This communication details one successful attempt. The removed testicle on dissection contained a cystA 3-year-old purebred Brahman bull was grazed with 19 breeding cows on a farm in the Alice Springs like cavity 7 cm in diameter, filled with fluid and District. It had been vaccinated with Br. abortus inspissated purulent material. This material yielded a heavy growth of Br. abortus biotype I. 45/20* vaccine at 2 years of age. Histopathological examination of formalin fixed Serum of the bull reacted positively to the Rose testis showed a thick fibrous capsule surrounding areas Bengal test (RBT) and the complement fixation test of lymphocytes, plasma cells, foamy macrophages, (CFT) for brucellosis with a titre of 128. It was multinvcleate giant cells and inspissated serum. The noticed to be walking awkwardly on the day it was central areas were necrotic. bled and closer examination revealed a unilateral right At 3, 4 and 5 months after castration, semen was testicular swelling twice the diameter of the adjoining collected from the bull by electroejawlation and testicle. It was extremely tense. and hot to feel. Deep inoculated directly onto Brucella Agar plates and also palpation revealed a central area (about 7 cm) of injected into guinea pigs. No brucellas were recovered putty-like consistency. The left testicle was dislocated from direct culture or from the guinea pig spleens, and dorsally into the neck of the scrotum by the enlarged the guinea pigs failed to develop serological reactions right testicle and was flaccid in tone suggesting de- to the RBT and CFT for brucellosis. At the third generation associated with local hyperthermia. Its size ejaculation, 5 months after castration, the bull was was normal. Palpation of the internal genitalia re- bled and its serum reacted positively to the RBT and vealed no abnormalities. CFT although the CFT titre had fallen to 64. The The bull was kept in isolation for 6 months, during semen was assessed as satisfactory on the basis of which time he was subjected to the following treatment good density and wave pattern. Palpation of the reregime. Initially, he was spelled for 3 weeks to allow maining testicle revealed no abnormalities. Tonus was acute inflammation to regress. No antibiotics were normal. All other reproductive organs were normal. administered during this period as it was intended to A decision was made to release the bull because of culture the testicle. A right unilateral open castration the absence of brucellas in his semen, there was dewas performed. Much dissection was necessary due to cline in the CFT titre, and there were no palpable extensive adhesions between the testicle and epididymis abnormalities in the remainder of the reproductive and the tunica vaginalis and the subcutaneous scrota1 tract. It was then joined with 39 cows for 5 months. fascia. The haemorrhage was much more severe than All cows had been vaccinated with Br. abortus 45/20 that associated with removal of a normal mature tes- vaccine and the serum of all cows was negative to the ticle. The adhesions were confined to the ventral half CFT for brucellosis in the 3 months prior to joining. of the scrotum. There was no inflammation of the The bull was removed from the herd after 4 months vas deferens or the dorsal portion of the tunica vagin- and slaughtered and bled. The remaining testicle, the alis. The pampiniform plexus was grossly enlarged. other genital glands, and the internal and external iliac Consequently the spermatic vessels were ligated and superficial inguinal lymph nodes were examined separately with No. 3 chromic catgut. The skin int Protercicline V-2OoO Proter, S.p.a., Agents V.S. Supplies, *Duphavac N. A.
- Philips-Duphar, Sydney,
New South Wales
Australian Veterinary Journal, Vol. 53, May, 1977