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Thursday, October 3, 2013

Aglepristone treatment for pyometra


Keywords: aglepristone, canine, bitch, pyometra, ultrasound

Note that all of the images in this entry enlarge to a resolution of 72 ppi; standard for web use. They are too small for print use. The images relate to a five year old pit bull female with a history of three successful whelpings.


A purulent vaginal discharge containing numerous PMNs started about 14 days after the last breeding (for the intended fourth litter).  At that time, the CBC was normal and the bitch was bright alert and had a normal appetite. The rDVM started ampicillin Rx and referred the case to us
approximately 22 days post breeding.

Several days after the ampicillin treatment was started the vaginal discharge diminished and was non-existent at the time that the bitch underwent ultrasonography at the AVC. The images below show the transabdominal ultrasonographs.



At this time the bitch was still bright, alert and responsive, its feces and appetite normal. Interestingly a tentative diagnosis of hydrometra was made by a radiologist, based on the well-being of the bitch, the absence of a purulent discharge and the appearance of the contents of the uterus i.e. the fluid content was non-echogenic. However, because of the rarity of hydrometra in bitches and the fact that pus can often appear non-echogenic, the author queried this diagnosis.
 
The vaginal cytology in this case (seen below) also suggested the absence of pyometra, with a virtual absence of neutrophils and very few bacteria.


Therefore the true nature of this fluid was not obvious. Pyometra is usually classified as "open" or "closed" depending on evidence of an overt purulent discharge from the vulva lips. However, vaginal cytology in all cases reveals that very few are actually "closed". If this was indeed a case of closed pyometra it appeared important to verify that diagnosis before the systemic symptoms of pyometra began to develop. For that reason, an ultrasound guided aspiration of the uterine contents was conducted. This showed hemorrhagic pus:


As shown below, this pus contained many degenerated neutrophils and large numbers of streptococcal and rod-like bacteria. 



Gram staining demonstrated the two distinct populations of bacteria seen below i.e. Gram positive cocci (dark bluish-purple) and the red to pink Gram negative rods (red arrows). These were probably Streptoccus spp and E.coli respectively.

 
Based on the presence of E.coli, a bacterium usually resistant to ampicillin, antibiotic treatment was changed from ampicillin to clavumox. Also, treatment with the progesterone receptor site antagonist, aglepristone (Alizin 30mg/ml Virbac) was started at a dose of 12mg/kg sq, once.


Note: Aglepristone is widely available outside North America but in Canada and the United States, it is only available through emergency drug release programs or by special arrangement. 

Aglepristone treatment was repeated 24 hours later.

The only side effect of aglepristone treatment in this case was mild gagging, about three hours after the onset of treatment but this was not observed after the second treatment. Therefore its significance with regard to treatment was questionable. Although signs of local swelling have occasionally been reported after aglepristone use, no swellings were seen in this case.
 
Culture and sensitivity of the uterine aspirate at 24 hours post sampling showed that the cocci seen on the smear were Streptoccus canis (Group G), susceptible to beta lactams. This culture is shown below, illustrating the beta hemolysis that typically occurs around the colonies of Streptoccus canis.




In the image below, the blood culture (top) is the same Streptoccus canis (Group G) culture seen in the image above but as expected, the culture also contained E.Coli. That isolate (seen below on a MacConkeys agar plate at 18hrs) was resistant to Clavumox and other beta lactams but sensitive to enrofloxacin.


Both bacteria were sensitive to fluoroquinolones therefore the antibiotic treatment was changed from clavumox to enrofloxacin @ 2.5mg/kg bid for 10 days.

As shown in the image below, a copious discharge of pus was seen at 24 hours, at the time of the second treatment of aglepristone.


Objective studies have shown 24 hours to be the mean interval to cervical opening after the first treatment with aglepristone. Obviously therefore, the canine cervix is acutely sensitive to progesterone and is under rapid dynamic control of progesterone as well. This raises the question: Are PGE1 and/or PG2 obligatory intermediaries in cervical relaxation in bitches as they appear to be in farm animals?
 
Ten days after the second treatment with aglepristone (approximately 32 days post breeding) the bitch was re-examined by ultrasound to assess the effect of treatment. At this examination, it was noted that a small volume of pus was still present at the base of the left uterine horn. It is likely that a small amount of pus also remained in the right uterine horn. The ultrasonographs with these findings are shown below.


Two additional treatments of aglepristone were given at this time i.e. 10 and 12 days after the onset of treatment. Again, no side effects were seen..

On day 12 (the day of the fourth treatment with aglepristone) the bitch was also treated with cloprostenol at a dose of 1microgram/kg. This was because it has been shown that treatment with cloprostenol as well as aglepristone was advantageous in cases of pyometra (Fieni, F, 2006. Theriogenology 66: 1550–155). This bitch's cervix had been open for some time, therefore treatment with an ecbolic such as cloprostenol was deemed safe.

It has to be acknowledged that part of any beneficial effect of cloprostenol treatment in this case may have been due to its luteolytic as well as its ecbolic effects. Indeed, the corpora lutea in this bitch would have probably been susceptible to cloprostenol induced luteoly1600at that time; about 35 days post breeding. Bitches frequently vomit or defecate after cloprostenol treatment but this did not occur here.


As seen above, vaginal cytology on day 12 after the first aglepristone treatment showed active phagocytosis of E.coli in neutrophils. No Streptoccal spp.bacteria were seen. Image size: 3000 x 1118 px

Note: Owner compliance with regard to the use of antibiotics was poor. Being under the impression that the ampicillin and clavumox should not be wasted (!) the owner had continued with these previous treatments for several days after being informed that enrofloxacin should be used instead.
 
On day 14 after the onset of treatment i.e. two days after the end of the last aglepristone and cloprostenol treatments,  the owner reported that the bitch was bright, alert and responsive and its feces and appetite were normal.

Only three months after treatment ended, this bitch showed estrus and was bred. An early return to estrus was not entirely unexpected because some data suggest that early expression of estrus is common  after aglepristone treatment. The bitch was bred naturally at that time and three puppies were delivered by cesarean section after an apparently normal pregnancy. Adhesions were noted between the uterus and body wall at the time of the cesarean section. These were ascribed to serosal inflammation that may have occurred while the bitch had experienced pyometra.