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Intra-arterial and intramammary injection of miconazole for bovine mastitis caused by Aspergillus fumigatus
Br.
vel.
J. (1990). 146,354
INTRA-ARTERIAL AND INTRAMAMMARY INJECTION OF MICONAZOLE FOR BOVINE MASTITIS CAUSED BY ASPERGILLUS FUAfIGATUS
HIRO~1U
KATAMaTO and YASUAKI SHIMADA
Department of Veterinary Surgery, College of Agriculture, University of Osaka Prefecture, 4-804, Mozuume-machi, Sakai, Osaka 591, Japan
SUMMARY
A case of bovine mycotic mastitis was successfully treated by combined intraarterial and intramammary injection on three successive days of the antifungal drug miconazole.
INTRODUCTION
Bovine mycotic mastitis caused by Aspergillus fumigatus does not respond to conventional antibiotic treatment (Thompson et aL, 1978; Schallibaum, Nicolet & Konig, 1980). Miconazole, an imidazole antifungal drug, has recently become available for systemic use. It is effective against the causative organisms in deep mycosis such as Candida, Cryptococcus and Aspergillus (Heel et aL, 1980). Van Damme (1983) reported that miconazole was effective on bovine mastitis caused by yeast but its efficacy in bovine udder aspergillosis has not been evaluated. The present report describes intra-arterial and intramammary administration of miconazole on bovine aspergillosis of the udder.
MATERIALS AND METHODS
A 5-year-old Holstein-Friesian cow became anorectic with ketonuria 1 week after parturition. The right hind quarter of the udder was swollen, fevered and firm. The California mastitis test was positive. Propylene glycol, cobalt sulphate, dexamethasone and succinic acid were administered orally and the right hind quarter was infused twice with antibiotic ointments containing penicillin and kanamycin or oxytetracycline and oleandomycin. The condition of the quarter, however, did not improve and the cow was referred to the University of Osaka Prefecture Veterinary Teaching Hospital on the 15th day after parturition. The cow weighing 630 kg had a rectal temperature of 4t· tOC, heart rate of 96 beats/ min and respiratory rate of 52/min and was depressed and anorectic. The right hind quarter was swollen, hot and with severe induration. Clots were present in the milk, and the reaction of the California mastitis test was scored as +2. Penicillin and streptomycin were infused into the affected quarter, and kanamycin (2' 5 g) was injected into right external pudendal artery.
TREATMENT OF MYCOTIC MASTITIS
355
The next day, rectal temperature was 41 . 2°C and the cow was still depressed and anorectic. Large numbers of fungi were isolated in pure culture from the milk sample. The same mycotic colonies were recovered from the sample 1 week later. The colonies on Sabouraud's agar medium showed a fluffy surface and greyish green pigmentation. Morphologically hyphae were observed by the block-slide culture technique and characteristic conidiophores consistent with the morphology of Aspergillus fumigatus were observed (McGinnis, D' Amato & Land, 1982). As it was considered that the treatment with conventional antibiotics was not effective, miconazole, a specific antibiotic for fungi, was used . Fourteen days after admission, rectal temperature was 38·8°C, and heart rate was 76 beats/min. The cow was anorectic, and the right hind quarter still showed swelling , fever and severe induration. Score of the California mastitis test was +2. Fifty units of oxytocin were administered i.m. to cause milk letdown before the evening milking. After the evening milking, 100 mg of miconazole (to ml) was injected into right external pudendal artery (Fig. 1). The intra-arterial injection was approached from the right lateral deltoid fossa between coxa and femur using a 23 em long needle, being assisted by rectal palpation. Miconazole (100 mg) diluted with 50 ml of saline was also infused into the
Deep r...".al artery
InJectIon stte taternal Pude~l artery
Fig. 1.
Intra-arterial injection site for bovine udder.
affected udder. The same therapy was continued for 3 successive days. Foremilk samples from the quarter were cultured on blood and Sabouraud's agar plates and incubated at 37°C for 48 hours. Somatic cell counts were also made by direct microscopic method (Schalm, Carroll & Jain, 1971) and N-acetyl-p-o-glucosamidase (NAGase) level in milk was measured by the method of Kitchen, Middleton & Salmon (1978) with modifications using fr'nitrophenyl-N-acetyl-p-o-glucosaminide as substrate.
RESULTS AND DISCUSSION The next evening following introduction of therapy , the cow's appetite returned to normal and the fever in the quarter subsided. Before treatment somatic cell counts were 990XtO'/ml and NAGase level was 19·2 nmol/min/m!. Values for both of them
356
BRITISH VETERINARY JOURNAL, 146, 4
decreased during the 3 days of treatment. At 23 days after the initial treatment with miconazole, somatic cell counts and NAGase level decreased to 183Xl()3/ml and 6·7 nmol/min/ml, respectively (Fig. 2). Aspn-gillusfumigatuswas detected for 3 days after the initial treatment but then disappeared. The severe induration in the affected quarter was reduced daily and had completely disappeared at 23 days after the initial treatment. The milk supply was also restored concomitantly.
2. 11 ~
,,-c
... II
14 _ 12
e ~
.
10 ;; ~
~
.
• e: •
to
c
z
o
1
2
)
Days
2)
ar rer
t
nt t ta t
t r es t eent
Fig. 2. Changes of somatic cell counts (e) and N-acetyl-p-u-glucosamidase (NAGase) level (0) in the affected quarter treated with miconazole .
Bovine udder aspergillosis is uncommon in practice and the prognosis is poor (Schallibaum et al., 1980). In human medicine, deep mycosis occurs during antibiotic therapy as an opportunistic infection . However, in cattle the mammary gland is originally a sterile compartment with no relation to opportunistic infection. In this case, fungi might be introduced into the udder at the previous infusions of antibiotic ointment, and the administration of dexamethasone might enhance the proliferation of fungi. The intra-arterial route of administration offers the theoretical advantage of providing high local drug concentration with low total drug infusion (Rettenmaier et al., 1988). In the affected udder, it is difficult to attain effective concentration of the antibiotic in the lesion by intramammary infusion as fungal hyphae are located in the centre of granuloma. The external pudendal artery is the main artery which supplies blood to bovine udder. The present intra-arterial injection could have produced higher levels of the antibiotic in the affected mammary glands than other routes of administration. It is suggested that intra-arterial injection of miconazole combined with intramammary infusion and milk letdown by oxytocin appeared to be effective in the treatment of mycotic infection of the udders in this particular case. Further work is indicated.
ACKNOWLEDGEMENTS
The authors would like to thank Dr T. Baba of this University for identifying the microorganism.
TREATMENT OF MYCOTIC MASTITIS
357
REFERENCES HEEL, R. C., BROGDEN, R. N., PAKES, G. E., SPEIGHT, T. M. & AVERY, G. S. (1980). Drugs 19, 7. KITCHEN, B.]., MIDDLETON, G. & SALMON, M. (1978). Journal of Dairy Research 45,15. MCGI;IINIS, M. R., D'AMATO, R. F. & LAND, G. A. (1982). In Pictorial Handbook of MedicaUy Important Fungi andAerobic Actinomycetes. New York: Praeger Publishers. RETTENMAIER, M. A., MORAN, M. F., RAMSINGHANI, N. F., COLMAN, M., SYED, N. A., PuTHAWALA, A., JANSEN, F. W. & DISAIA, P.]. (1988). CanctT61, 1301. ScHALLIBAUM, M., NICOLET,]. & KONIG, H. (1980). Sabouraudia 18, 33. SCHALM, O. W., CARROLL, E.]. & JAIN, N. C. (1971). In Bovine Mastitis, p. 98. Philadelphia: Lea & Febiger. THOMPSON, K. G., DI MENNA, M. E., CARTER, M. E. & CARMAN, M. G. (1978). New Zealand Veterinary Journal26, 176. VAN DAMME, D. M. (1983). Veterinary MedicinelSmaU AnimalClinician 78, 1425. (Accepted for publication 16August 1989)
vel.
J. (1990). 146,354
INTRA-ARTERIAL AND INTRAMAMMARY INJECTION OF MICONAZOLE FOR BOVINE MASTITIS CAUSED BY ASPERGILLUS FUAfIGATUS
HIRO~1U
KATAMaTO and YASUAKI SHIMADA
Department of Veterinary Surgery, College of Agriculture, University of Osaka Prefecture, 4-804, Mozuume-machi, Sakai, Osaka 591, Japan
SUMMARY
A case of bovine mycotic mastitis was successfully treated by combined intraarterial and intramammary injection on three successive days of the antifungal drug miconazole.
INTRODUCTION
Bovine mycotic mastitis caused by Aspergillus fumigatus does not respond to conventional antibiotic treatment (Thompson et aL, 1978; Schallibaum, Nicolet & Konig, 1980). Miconazole, an imidazole antifungal drug, has recently become available for systemic use. It is effective against the causative organisms in deep mycosis such as Candida, Cryptococcus and Aspergillus (Heel et aL, 1980). Van Damme (1983) reported that miconazole was effective on bovine mastitis caused by yeast but its efficacy in bovine udder aspergillosis has not been evaluated. The present report describes intra-arterial and intramammary administration of miconazole on bovine aspergillosis of the udder.
MATERIALS AND METHODS
A 5-year-old Holstein-Friesian cow became anorectic with ketonuria 1 week after parturition. The right hind quarter of the udder was swollen, fevered and firm. The California mastitis test was positive. Propylene glycol, cobalt sulphate, dexamethasone and succinic acid were administered orally and the right hind quarter was infused twice with antibiotic ointments containing penicillin and kanamycin or oxytetracycline and oleandomycin. The condition of the quarter, however, did not improve and the cow was referred to the University of Osaka Prefecture Veterinary Teaching Hospital on the 15th day after parturition. The cow weighing 630 kg had a rectal temperature of 4t· tOC, heart rate of 96 beats/ min and respiratory rate of 52/min and was depressed and anorectic. The right hind quarter was swollen, hot and with severe induration. Clots were present in the milk, and the reaction of the California mastitis test was scored as +2. Penicillin and streptomycin were infused into the affected quarter, and kanamycin (2' 5 g) was injected into right external pudendal artery.
TREATMENT OF MYCOTIC MASTITIS
355
The next day, rectal temperature was 41 . 2°C and the cow was still depressed and anorectic. Large numbers of fungi were isolated in pure culture from the milk sample. The same mycotic colonies were recovered from the sample 1 week later. The colonies on Sabouraud's agar medium showed a fluffy surface and greyish green pigmentation. Morphologically hyphae were observed by the block-slide culture technique and characteristic conidiophores consistent with the morphology of Aspergillus fumigatus were observed (McGinnis, D' Amato & Land, 1982). As it was considered that the treatment with conventional antibiotics was not effective, miconazole, a specific antibiotic for fungi, was used . Fourteen days after admission, rectal temperature was 38·8°C, and heart rate was 76 beats/min. The cow was anorectic, and the right hind quarter still showed swelling , fever and severe induration. Score of the California mastitis test was +2. Fifty units of oxytocin were administered i.m. to cause milk letdown before the evening milking. After the evening milking, 100 mg of miconazole (to ml) was injected into right external pudendal artery (Fig. 1). The intra-arterial injection was approached from the right lateral deltoid fossa between coxa and femur using a 23 em long needle, being assisted by rectal palpation. Miconazole (100 mg) diluted with 50 ml of saline was also infused into the
Deep r...".al artery
InJectIon stte taternal Pude~l artery
Fig. 1.
Intra-arterial injection site for bovine udder.
affected udder. The same therapy was continued for 3 successive days. Foremilk samples from the quarter were cultured on blood and Sabouraud's agar plates and incubated at 37°C for 48 hours. Somatic cell counts were also made by direct microscopic method (Schalm, Carroll & Jain, 1971) and N-acetyl-p-o-glucosamidase (NAGase) level in milk was measured by the method of Kitchen, Middleton & Salmon (1978) with modifications using fr'nitrophenyl-N-acetyl-p-o-glucosaminide as substrate.
RESULTS AND DISCUSSION The next evening following introduction of therapy , the cow's appetite returned to normal and the fever in the quarter subsided. Before treatment somatic cell counts were 990XtO'/ml and NAGase level was 19·2 nmol/min/m!. Values for both of them
356
BRITISH VETERINARY JOURNAL, 146, 4
decreased during the 3 days of treatment. At 23 days after the initial treatment with miconazole, somatic cell counts and NAGase level decreased to 183Xl()3/ml and 6·7 nmol/min/ml, respectively (Fig. 2). Aspn-gillusfumigatuswas detected for 3 days after the initial treatment but then disappeared. The severe induration in the affected quarter was reduced daily and had completely disappeared at 23 days after the initial treatment. The milk supply was also restored concomitantly.
2. 11 ~
,,-c
... II
14 _ 12
e ~
.
10 ;; ~
~
.
• e: •
to
c
z
o
1
2
)
Days
2)
ar rer
t
nt t ta t
t r es t eent
Fig. 2. Changes of somatic cell counts (e) and N-acetyl-p-u-glucosamidase (NAGase) level (0) in the affected quarter treated with miconazole .
Bovine udder aspergillosis is uncommon in practice and the prognosis is poor (Schallibaum et al., 1980). In human medicine, deep mycosis occurs during antibiotic therapy as an opportunistic infection . However, in cattle the mammary gland is originally a sterile compartment with no relation to opportunistic infection. In this case, fungi might be introduced into the udder at the previous infusions of antibiotic ointment, and the administration of dexamethasone might enhance the proliferation of fungi. The intra-arterial route of administration offers the theoretical advantage of providing high local drug concentration with low total drug infusion (Rettenmaier et al., 1988). In the affected udder, it is difficult to attain effective concentration of the antibiotic in the lesion by intramammary infusion as fungal hyphae are located in the centre of granuloma. The external pudendal artery is the main artery which supplies blood to bovine udder. The present intra-arterial injection could have produced higher levels of the antibiotic in the affected mammary glands than other routes of administration. It is suggested that intra-arterial injection of miconazole combined with intramammary infusion and milk letdown by oxytocin appeared to be effective in the treatment of mycotic infection of the udders in this particular case. Further work is indicated.
ACKNOWLEDGEMENTS
The authors would like to thank Dr T. Baba of this University for identifying the microorganism.
TREATMENT OF MYCOTIC MASTITIS
357
REFERENCES HEEL, R. C., BROGDEN, R. N., PAKES, G. E., SPEIGHT, T. M. & AVERY, G. S. (1980). Drugs 19, 7. KITCHEN, B.]., MIDDLETON, G. & SALMON, M. (1978). Journal of Dairy Research 45,15. MCGI;IINIS, M. R., D'AMATO, R. F. & LAND, G. A. (1982). In Pictorial Handbook of MedicaUy Important Fungi andAerobic Actinomycetes. New York: Praeger Publishers. RETTENMAIER, M. A., MORAN, M. F., RAMSINGHANI, N. F., COLMAN, M., SYED, N. A., PuTHAWALA, A., JANSEN, F. W. & DISAIA, P.]. (1988). CanctT61, 1301. ScHALLIBAUM, M., NICOLET,]. & KONIG, H. (1980). Sabouraudia 18, 33. SCHALM, O. W., CARROLL, E.]. & JAIN, N. C. (1971). In Bovine Mastitis, p. 98. Philadelphia: Lea & Febiger. THOMPSON, K. G., DI MENNA, M. E., CARTER, M. E. & CARMAN, M. G. (1978). New Zealand Veterinary Journal26, 176. VAN DAMME, D. M. (1983). Veterinary MedicinelSmaU AnimalClinician 78, 1425. (Accepted for publication 16August 1989)