Cystitis in the dog and cat

The term “cystitis” indicates an inflammatory process of the bladder; it is one of the manifestations of urinary tract infections (UTI) and may be acute or chronic and caused by bacteria, parasites, fungi, trauma or cancer or may be idiopathic. The following discussion is focused on bacterial cystitis, while brief comments are made on cystitis caused by moulds, yeasts, cyclophosphamide, polyps and parasites.

BACTERIAL CYSTITIS

Bacterial cystitis develops as a consequence of a loss of the normal balance existing between host defences (Tab. 1) and bacterial virulence (Tab. 2).

Tab. 1. Host defence mechanisms.

Tab. 2. Bacterial virulence factors.

The ascending route, through the urethra, is the most common pathway of infection; furthermore, the inflammatory process can extend upwards from the bladder to the kidneys through the ureters. Iatrogenic procedures (e.g. catheterisation) are another important source of infections, while blood-borne infections, although possible, do not seem to be a relevant cause of cystitis in dogs or cats.

The micro-organisms responsible for cystitis are usually of faecal origin and have various virulence factors: for example, some bacteria, such as E. coli^1,2,3, are endowed with fimbriae and adhesins, proteins that enable the bacteria to bind to specific sites on the endothelium of the urogenital tract; others are able to produce endotoxins and exotoxins which can indirectly cause destruction of the urothelial glycosaminoglycans and thus facilitate bacterial colonisation.

Cystitis, which is one of the types of UTIs, is classified as “complicated” or “uncomplicated” depending on whether or not there are structural or functional abnormalities present as predisposing factors. In fact, if the defence mechanisms are normal, only a heavy infective load or particularly virulent strains of bacteria can cause infection; in contrast, in the presence of anatomical defects, changes in micturition, urothelial impairment, alterations in the composition of the urine (e.g., glycosuria) or compromised immune system function (e.g., Cushing’s disease) any micro-organism will be able to cause an infection, independently of its  load or virulence factors. This difference is of fundamental importance with regards to treatment.

The most commonly reported clinical signs are dysuria, pollakiuria, stranguria, haematuria and/or periuria; however, in animals with Cushing’s disease or receiving corticosteroid therapy, cystitis may be completely asymptomatic and be found incidentally. In both cases, the owners may report that the urine appears turbid, has an unpleasant smell and/or contains blood.

Clinically the patient is otherwise normal, although there may be inflammation of the penile mucosa and of the abdominal skin, in some cases associated with alopecia, particularly in cats. This loss of hair is secondary to the continuous licking with which the animal tries to soothe the irritation present. Fever is common when there is a concomitant bacterial prostatitis. Transabdominal palpation of the bladder causes pain/annoyance and can identify masses or urinary tract stones or thickening of the bladder wall (Fig. 1). The bladder of a patient with cystitis is almost always empty.

In order to make a diagnosis of bacterial cystitis it is essential to have a sample of urine obtained by cystocentesis for the physico-chemical, microbiological and sediment studies. The finding of phagocytosed bacteria in granulocytes in the sediment (Figs. 2 and 3) suggests the presence of infection of the urinary tract, but does not demonstrate the site of the infection: the examination of the urinary sediment must be meticulous in order to detect any casts with granulocyte inclusions or cells of the upper urinary tract (Fig. 4) which could indicate that the kidneys (although not necessarily only the kidneys) are involved. 

The urine pH should be interpreted with care because it can be altered by many factors (e.g. the diet) and only some bacteria are able to produce ureases (Proteus spp., Ureaplasma spp.). Proteinuria is not a constant finding, but when present is compatible with the suspected diagnosis of cystitis.

Urine cultures are essential because their diagnostic sensitivity is greater than that of sediment studies (cocci and rods are difficult to show in the urine if the bacterial load is below 100,000/ml and 10,000/ml, respectively) and an antibiogram is always recommended.

Two different methods are currently used to evaluate sensitivity to antibiotics:

1)  the agar-diffusion (or disk-diffusion or Kirby-Bauer) method: in this test a standardised suspension of a single uropathogen is inoculated on an agar plate; wafers impregnated with various antibiotics are then placed on the plate which is incubated at 37°C for 18 hours before  sensitivity to the different antibiotics is estimated from measuring the zone of bacterial growth inhibition around each disk; the areas of inhibition are interpreted and classified, in comparison with pre-determined standards, as indicating resistance, sensitivity or an intermediate result. Since the concentration of the antibiotic (with the exception of nitrofurantoin⁴) in the disk is comparable to that of the concentration of the antibiotic in the serum, and not that in the urine, the in vitro and in vivo efficacy may not be the same; in fact many antibiotics that are ineffective in the agar-diffusion test can be therapeutically effective if excreted in high concentrations in the urine (ampicillin, cephalexin, chloramphenicol, enrofloxacin, penicillin G and trimethoprim).

2)  the broth dilution test for antibiotic sensitivity: this test determines the minimum inhibitory concentration (MIC) of a given drug; after inoculation and incubation of the uropathogens in wells containing series of doubling dilutions of the antibiotic, at concentrations that can be reached in tissue and urine of patients treated with usual doses, the MIC is defined as the minimum concentration of antibiotic that prevents appreciable growth of bacteria. The MIC is many dilutions lower than the minimum bactericidal concentration (MBC) of the drug. In general, an antibiotic is effective if a concentration 4-fold higher than the MIC can be reached: this observation is particularly important given that many antibiotics excreted through the kidneys reach concentrations 10- to 100-fold higher in the urine than in the serum.

Despite the validity of sensitivity tests, the definitive parameter for evaluating therapeutic success is the combination of clinical and laboratory responses to the antibiotic: the in vivo efficacy of a drug can be influenced by factors other than the in vitro sensitivity and the role of the host’s natural defence mechanisms must also be considered.

Cystitis is always considered uncomplicated at its first presentation and in this case the duration of the treatment depends on the sex of the animal: 10-14 days of antibiotic treatment are sufficient for females and castrated males, while uncastrated males must be treated for 1 month, preferably with an antibiotic that is able to concentrate in the prostate. The treatment is suspended only when the clinical signs have disappeared, even though this in itself is not a guarantee that the animal has been cured.

Recurrences usually occur within a few weeks of suspending treatment and are due to the same micro-organism. There is a broad range of possible causes: administration of the wrong antibiotics, mixed infections, inadequate dose/interval of administration, lack of compliance by the animal’s owner, development of antibiotic resistance_⁵ or the presence of foci of infection outside the urinary tract (e.g. prostate). If the recurrence is manifested within 10 days of suspension of therapy or if the course of treatment was too short, the same antibiotic can be used; otherwise (previous treatment correct and/or recurrence more than 10 days after suspension of treatment) a new urine culture with antibiogram must be performed and then repeated 7-10 days after starting the new therapeutic protocol in order to determine whether the samples have become negative (if so, the treatment should be continued for 6-8 weeks in the male and at least 4 weeks in the female) or remain positive. In the case of persistent positivity, the microbiological examination must be repeated before interrupting treatment and, if still positive, the antibiotic should be changed. Re-infection is a new infection caused by different micro-organisms more than 4 weeks after conclusion of the preceding treatment: in this case the urine culture and antibiogram must be repeated and treatment prolonged for 6-8 weeks.

In order to identify cases of complicated cystitis it is worth remembering that if the same patient has more than three episodes of cystitis in a year, the animal may well have predisposing factors.

If, despite thorough investigations, a cause of the recurrent infections cannot be found, it is important to try to increase the periods that the urine is sterile in order to prevent the infection from extending to the renal parenchyma. This can be achieved by using a prophylactic regimen, administering one-third of the dose of antibiotic in the evening after the last time the patient has emptied its bladder, and monitoring the patient monthly. Once six urine cultures have been negative, the preventive treatment can be interrupted.

When a sensitivity test shows the presence of multiresistant bacteria, antibiotic therapy is not useful. In this case it can be helpful to re-evaluate the patient after a few weeks; in the meantime, palliative treatment can be prescribed aimed at decreasing the irritation/pain associated with the cystitis (non-steroidal anti-inflammatory drugs) and at re-establishing the patient’s normal defence mechanisms (cranberries, supplements with glycosaminoglycans and probiotics) although their efficacy in veterinary medicine has not yet been demonstrated.

Instillation of tris-EDTA_^6,7,8 directly into the bladder, through a catheter inserted for cystotomy, can help to reduce the incidence of bacterial cystitis.

Some studies have demonstrated the efficacy of vaccines based on the fimbriae of E. coli in the prevention of pyelonephritis in rats and monkeys; as of present, no comparable studies have been published regarding dogs and cats.

EMPHYSEMATOUS CYSTITIS

Emphysematous cystitis is a particular type of bacterial cystitis characterized by the production of gas in the layers of the bladder wall; in most cases it is due to bacterial fermentation of glucose_^9-12 in dogs with UTI and glycosuria (diabetic or non-diabetic), but may occasionally occur in patients without glycosuria_^13,14. The diagnosis is made on the basis of results of instrumental investigations such as ultrasound_^14,15  and X-rays of the abdomen_¹⁵.  The treatment is the same as that for bacterial cystitis; however, if glycosuria is present, it is essential that this is controlled.

CYCLOPHOSPHAMIDE-INDUCED CYSTITIS

This is a sterile, haemorrhagic cystitis caused by the excretion of a toxic metabolite of cyclophosphamide in the urine_^16-18. Prophylactic administration of furosemide, together with the cyclophosphamide, reduces the risk of developing this condition. In no circumstances should thiazide diuretics be administered during the treatment of this pathology since they potentiate the myelotoxic effects of cyclophosphamide_¹⁶.

CYSTITIS DUE TO MOULDS AND YEASTS

Fungal infections are rare in dogs and cats and usually caused by Candida spp._^19,20. Cystitis due to Aspergillus spp. has also been reported in the cat_²¹.

In most patients with candida cystitis predisposing conditions or factors can be found, such as glycosuria (diabetic_²² or non-diabetic), Cushing’s disease, chemotherapy in patients with cancer_²³ or chronic administration of antibiotics or corticosteroids_²⁴: indeed, all subjects with compromised local or systemic immunity are candidates for developing this mycosis_^25-27, although the infection can also occur, albeit rarely, in otherwise healthy subjects_²⁸. The clinical signs are usually dysuria, haematuria, pollakiuria, anorexia, depression and fever.

The management is multifaceted: first of all any predisposing condition present must be treated; it can also be useful to administer alkalinising diets or agents (an alkaline pH inhibits fungal growth). In acute cases it is essential to give an anti-fungal drug that is excreted through the kidneys. Amphotericin B has this property but, given its nephrotoxicity and the fact that it must be administered parenterally, is rarely used for this purpose. The drugs used are fluconazole and itraconazole which can both be administered orally: the efficacy of itraconazole has not, however, been demonstrated.

PARASITIC CYSTITIS

Bladder worms (Capillaria plica) are very small parasites, difficult to see by the naked eye, which are an aetiological cause of parasitic cystitis in dogs and cats_^29,30. They are thin nematodes and are between 1-5 cm long; the eggs are similar to those of whipworms (Trichuris) in that they have two polar opercula, but they are colourless, rounded and measure 63-68 µm by 24-27 µm.

The definitive host is infected by eating the intermediate host, an earthworm containing first stage larvae within its tissues. The eggs appear for the first time in the urine of the definitive host about 2 months after ingestion of the infesting larvae. With the anterior part of the body, the adult parasite penetrates into the mucosa of the bladder and sometimes of the ureters and renal pelvis; however, in most cases dogs and cats do not have any evident clinical signs and the diagnosis is usually made incidentally following routine examinations of the patient and the identification of the parasite’s eggs in the urinary sediment. The infestation tends to be self-limiting (in about 90 days) in the absence of re-infestation. Levamisole, ivermectin_³¹ as well as prolonged treatment with albendazole are effective treatments.

POLYPOID CYSTITIS

Polypoid cystitis can occur in animals with chronic cystitis. It is a benign condition that must be differentiated from a neoplasm_³². The polyps are an inflammatory response to an underlying condition (chronic bacterial UTI, urolithiasis). They can be completely asymptomatic or cause haematuria, dysuria and pollakiuria.

There is usually a history of the typical clinical signs of UTI, while the examination is normal. Urinalysis may show haematuria, pyuria and bacteriuria and urine culture is often positive. Although these benign polyps are usually pedunculated, they cannot be differentiated from malignant ones by ultrasonography_³³, since they can have different shapes and sizes. They are typically found in the cranio-ventral part of the bladder, but can also occur in the cranio-dorsal part and for this reason it is essential to take a biopsy, via cystoscopy, for histological studies.

There are various components of the treatment: it is essential to control the UTI, although this can be difficult to treat effectively until the polyps are removed. In this case surgical excision of persistent polyps is indicated, either by partial cystectomy or removal of the submucosa and mucosa of the bladder.

Suggested readings

1. Ettinger SJ, Feldman EC: “Textbook of Veterinary Internal Medicine, 6^th edn”. Elsevier-Saunders, St. Louis 2005.
2. Couto CG, Nelson WR: “Medicina interna del cane e del gatto”Elservier-Masson, 2010.
3. BSAVA Manual of Canine and Feline Nephrology and Urology Second edition, Edited by Johnathan Elliot and Gregory F. Grauer, 2007.
4. EvansHE: “Miller’s Anatomy of the dog, 3rd ed.” WB Saunders, Toronto, 1993.
5. OsborneCA, Finco DR: Canine and feline nephrology and urology. Williams & Wilkins, Philadelphia, 1995.

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