Lower urinary tract obstruction secondary to Corynebacterium urealyticum -associated struvite urolithiasis in a female cat

Abstract

Case summary

A 10-year-old female neutered domestic shorthair cat presented with stranguria. The cat was bradycardic and had a firm urinary bladder on physical examination. On initial laboratory testing, the cat had severe azotemia with a creatinine of 15.8 mg/dl (reference interval [RI] 1.1–2.2), blood urea nitrogen of 217 mg/dl (RI 18–33) and potassium of 8.9 mmol/l (RI 3.5–5.0). Abdominal radiography revealed three cystoliths, with one cystolith suspected of being lodged within the trigone. Ultrasound of the abdomen showed marked suspended echogenic debris within the urinary bladder. Corynebacterium urealyticum was isolated from aerobic bacterial urine culture. A cystotomy was performed, and crystallographic analysis of the removed cystoliths showed they were composed of 94% struvite and 6% calcium phosphate. The cat recovered well and was discharged 2 days postoperatively. Three weeks postoperatively, the cat showed resolution of all clinical signs and azotemia.

Relevance and novel information

Urethral obstruction is common in male cats because of the narrow diameter of their urethra. In contrast, it is rare for female cats to experience lower urinary tract obstruction (LUTO). Identifying the underlying cause of LUTO is crucial for providing appropriate and targeted treatment. This case report describes a unique cause of LUTO resulting from C urealyticum associated with struvite urolithiasis in a female cat.

Introduction

Lower urinary tract obstruction (LUTO) can be a life-threatening condition in cats. It is estimated that 5.73–6.08% of cats presenting to an emergency service have LUTO, ¹ with the majority of affected cats being male, ² owing to their narrower urethral lumen. Urethral plugs are the most common cause of LUTO in cats, ³ often forming in individuals with obstructive feline idiopathic cystitis (FIC).^4,5 Other causes of LUTO include urethroliths, ⁴ neoplasia, ⁶ strictures, ⁶ pseudomembranous cystitis, ⁷ foreign bodies ⁸ and extraluminal compression of the urethra. ⁴ Although LUTO is extremely rare in female cats, it is most often documented in conjunction with malignant neoplasia ⁹ or neurologic disease.^10,11

Corynebacterium urealyticum is a gram-positive, lipophilic, slow-growing bacillus bacteria ¹² with urease-producing ability.^12,13 It is uncommonly isolated from the urinary tract of cats, comprising approximately 0.2% of all urinary bacterial isolates from cats. ¹⁴ C urealyticum can cause encrusting cystitis in cats^15,16 and dogs ¹⁶ ; however, urethral obstruction secondary to infection associated with solid struvite urolithiasis has not been reported in cats.

Case description

A 10-year-old female spayed domestic shorthair cat presented with a 24-h history of lethargy, hyporexia and stranguria, but without urine production. Upon exam-ination, the cat was overweight (5.5 kg) with a body condition score (BCS) of 7/9. Hypothermia (99.2°F, 37.3°C) and bradycardia (140 beats/min) were noted, and abdominal palpation revealed a firm, moderately sized non-expressible bladder.

Venous blood gas analysis (ABL 800; Radiometer Medical A/S) revealed marked hyperkalemia at 8.9 mmol/l (reference interval [RI] 3.5–5.0 [3.5–5.0 mEq/l]) and mild ionized hypocalcemia at 1.04 mmol/l (RI 1.20–1.45 [4.8–5.8 mg/dl]). A cephalic intravenous (IV) catheter was inserted and 1 ml/kg of 10% calcium gluconate (Fresenius Kabi) was administered slowly via IV infusion. Given the hyperkalemia, 1 IU of regular insulin (0.18 IU/kg) (Novalin R; Novo Nordisk) and 50% dextrose (2 g IV) were also administered.

On abdominal radiography, the bladder was moderately distended (4.5 cm × 4.8 cm) and contained two uroliths in the urinary bladder lumen, with an additional urolith lodged in the caudal trigone (Figure 1). The cat was sedated with midazolam (0.2 mg/kg IV) and hydromorphone (0.1 mg/kg). Alfaxalone (Alfaxan; Zoetis) was then titrated to provide adequate chemical restraint.

Figure 1

Cystolithiasis (arrows) with the one cystolith suspected to be lodged at the level of the trigone

After several unsuccessful attempts to relieve the LUTO using a 3.5 F × 14 cm urinary catheter (Slippery Sam; Smiths Medical), a hydrophilic-coated guidewire (0.018 inch × 150 cm) (Weasel Wire; Infiniti Medical) was successfully passed in a retrograde fashion into the urethra and confirmed to be in the urinary bladder via ultrasonography. A 3.5 F × 14 cm urinary catheter (Slippery Sam; Smiths Medical) was then passed over the guidewire. Once the guidewire was removed, the catheter was sutured in place using 3-0 monofilament nylon. Urine was collected from the urinary catheter and submitted for urinalysis and aerobic bacterial culture. The urine specimen was highly viscous, hindering a complete urinalysis assessment. Microscopic examination of a direct urine smear revealed dense pink mucus, amorphous refractile material, scattered struvite crystals and numerous extracellular bacteria. C urealyticum was cultured after 48 h of incubation. Susceptibility results are shown in Table 1.

Table 1

Results of antimicrobial susceptibility tests for Corynebacterium urealyticum determined by broth microdilution

Antimicrobial	Broth microdilution (µg/ml)	Interpretation
Amikacin	⩽16	NI
Amoxicillin/clavulanic acid	⩽0.25	NI
Ampicillin	⩽0.25	NI
Cefazolin	⩽2	NI
Chloramphenicol	⩽8	NI
Clindamycin	>4	R
Doxycycline	⩽0.12	S
Enrofloxacin	⩽0.25	NI
Erythromycin	4	R
Gentamicin	⩽4	S
Marbofloxacin	⩽1	NI
Penicillin	0.25	I
Rifampin	⩽1	S
Tetracycline	⩽0.25	S
Trimethoprim/sulfamethoxazole	⩽2	S
Vancomycin	⩽1	S

I = intermediate; NI = no Clinical and Laboratory Standards Institute interpretative guidelines for this antibiotic/organism combination ¹⁷ ; R = resistant; S = susceptible

The cat was hospitalized, treated with IV fluids (lactated Ringer’s solution, 15 ml/h), buprenorphine (13 µg/kg IV q8h) and a constant rate infusion of regular insulin at 0.1 IU/kg/h to manage persistent hyperkalemia. In addition, 25% dextrose was supplemented intravenously at 5 ml/h via a central line. Pending the results of the initial urine culture and sensitivity tests, the cat was treated with ampicillin-sulbactam (50 mg/kg IV q8h, Unasyn; Pfizer) and enrofloxacin (5 mg/kg IV q24h).

At 12 h after admission, a complete blood count was performed, revealing a non-regenerative anemia with a hematocrit of 24.5% (RI 30–50). A serum biochemistry panel indicated marked azotemia, with a creatinine of 15.8 mg/dl (RI 1.1–2.2) and blood urea nitrogen (BUN) of 217 mg/dl (RI 18–33). Persistent hyperkalemia (7.8 mmol/l, RI 3.6–4.9) was present, suggestive of ongoing LUTO. Ultrasonography revealed multiple uroliths, including a large urolith located in the caudal trigone and proximal urethral. There was marked echogenic debris visible in the urinary bladder lumen (Figure 2). The urinary catheter was positioned within the urethra, with its opening just distal to the obstructive urolith. The bladder was of moderate size, and the urinary catheter was not draining effectively at this time.

Figure 2

Abdominal ultrasound of urinary bladder revealing marked urinary bladder suspended echogenic debris

As a result of the ongoing LUTO, a hydrophilic coated guidewire measuring 0.018 inch × 150 cm (Weasel Wire; Infiniti Medical) was inserted in a retrograde fashion through the previously placed Slippery Sam catheter. The catheter was then removed over the guidewire, and a new 5 F × 25 cm urinary catheter (Tomcat Urinary Catheter; MILA) was advanced over the wire and into the urinary bladder. The guidewire was then removed. The bladder was flushed with sterile saline through the urinary catheter to remove the debris. A closed collection system was then connected to the urinary catheter. The treatment for the cat was continued with IV fluids, ampicillin-sulbactam, enrofloxacin and buprenorphine as previously described. Over the course of 48 h, the cat’s hyperkalemia resolved and creatinine concentration decreased to 2.3 mg/dl (RI 1.1–2.2).

Two days after hospitalization and once the cat was stable, a cystotomy was performed. The bladder mucosa appeared irregular and gray, with significant mucoid debris present in the bladder lumen (Figure 3). Three uroliths were removed using a bladder spoon and the urethra was flushed in an antegrade fashion using an 8 F red rubber catheter. A bladder wall specimen was collected with Metzenbaum scissors and submitted for both aerobic and anerobic bacterial culture. The bladder was closed using 3-0 polydioxanone (PDS) in a simple interrupted pattern, and the body wall was closed using routine standard techniques. C urealyticum was isolated from the bladder wall, matching the susceptibility pattern of the initial urine specimen. Crystallographic stone analysis (Antech Diagnostics) revealed that the stones were composed of 94% struvite and 6% calcium phosphate, with no nidus or shell observed.

Figure 3

Intraoperative cystotomy image revealing gray appearance to the bladder mucosa

The cat was hospitalized for an additional 2 days after the cystotomy and continued to receive IV fluids, ampicillin-sulbactam, enrofloxacin and buprenorphine. The urinary catheter was removed 24 h postoperatively. The cat urinated normally after removal of the catheter and was discharged 24 h later. After discharge, a 21-day course of enrofloxacin (5 mg/kg PO q24h) and amoxicillin-clavulanic acid (14.7 mg/kg PO q12h, Clavamox; Zoetis) was prescribed along with gabapentin (10 mg/kg PO q8–12h) for postoperative pain relief.

The cat was re-evaluated 3 weeks later, and the owner reported the cat was well clinically. A physical examin-ation revealed no abnormalities, and serum creatinine and BUN concentrations were within the laboratory’s RI: creatinine 1.4 mg/dl (RI 1.1–2.2) and BUN 27 mg/dl (RI 18–33). A point-of-care abdominal ultrasound exam-ination showed no visible cystoliths or echogenic debris in the urinary bladder. The cat was subsequently lost to follow-up.

Discussion

This report documents a case of LUTO in a female cat due to struvite urolithiasis associated with C urealyticum infection. Most struvite uroliths in cats form in sterile urine ¹⁸ ; however, infection-induced struvite urolithiasis has been reported in cats, primarily associated with Staphylococcus species. ¹⁹ The uroliths in this case report were likely formed secondary to C urealyticum infection, with a recent study finding that strong urease-producing bacteria increased the odds of struvite urolith formation by 11.93 times in feline patients. ²⁰ Submissions for struvite uroliths from cats have increased over time, and approximately 5% of infection-induced struvite uroliths in our laboratory were caused by C urealyticum. ¹⁹ Nonetheless, the authors cannot completely rule out the possibility of sterile struvite stone formation leading to a subsequent C urealyticum infection. The etiology of sterile struvite urolithiasis in cats is multifactorial and likely involves genetic and environmental risk factors including diet and stress. Urine pH may have been helpful in this case to determine the sequence of events, with a more alkaline urine supporting the presence of a urease-producing bacteria, potentially indicating that infection preceded stone formation. Unfortunately, urinalysis could not be performed in this case because of the urine viscosity. Dilution of the urine sample could have been considered to facilitate analysis, although this may have affected pH and subsequent interpretation.

In previous reports of C urealyticum urinary tract infections (UTIs) in dogs and cats, underlying comorbidities such as micturition disorders, ²¹ previous urethral catheterization ¹⁶ or historical LUTO ²² were frequently noted. The cat in this report had no history of urethral catheter-ization or known comorbidities. However, it did experience intermittent periuria during the 2 years before presentation, but this issue resolved without any intervention. C urealyticum is a normal component of the genital flora in cats ²³ , and it is possible that impaired underlying host defense mechanisms contributed to the UTI, although this aspect was not investigated.

C urealyticum UTIs are often multidrug-resistant^16,24,25; however, the isolate in this case was highly susceptible to the antimicrobials tested in our laboratory. The cat was treated with dual antimicrobial therapy; however, de-escalation to solely amoxicillin/clavulanic acid or amoxicillin should have been implemented once culture results were available. The authors also acknowledge that dual antimicrobial therapy before culture results were available did not represent judicious antibiotic stewardship. The antibiotic decision-making in this case deviated from evidence-based prescribing practices, and the authors do not recommend this approach for other cases or patients. The International Society for Companion Animal Infectious Diseases recommends short-term (3–5 days) treatment for most cats and dogs with sporadic bacterial cystitis. ²⁶ In cases where animals have comorbidities, longer duration treatment may be required, although specific guidelines for these situ-ations are not published. In this case, the large amount of mucus and mineral material could act as a nidus for bacterial growth, prompting a longer course of antibiotics. Further studies are needed to ascertain appropriate antimicrobial duration in cats with C urealyticum-associated urolithiasis. An acidifying diet to minimize reformation of struvite uroliths and dietary weight management strategies could have been offered to this cat at discharge; however, the attending clinician wanted to ensure the cat fully recovered before making any dietary changes.

Although LUTO was probably secondary to urolith-iasis in this case, the viscosity of the urine and the presence of mucinous debris may have also played a role. LUTO can occur solely because of the build-up of inflammatory debris, ⁴ which is frequently observed in cats with sterile obstructive FIC. Thickening of the bladder wall and the accumulation of sediment are common findings in ultrasound examinations of cats diagnosed with C urealyticum UTIs. ²¹

Long-term follow-up and management were not available in this case. For infection-induced struvite urolithiasis, investigating both structural and functional risk factors for infection is recommended. ²⁷ Prevention of sterile struvite stones can be supported by feeding therapeutic diets that are low in phosphorus and magnesium, ²⁷ providing high-moisture foods and increasing water intake. ²⁷ In addition, an increased BCS is a known risk factor for urethral obstruction, ²⁸ and weight management could have been considered for the cat in this report.

Conclusions

Although LUTO is rare in female cats, we have documented a case linked to the effects of C urealyticum and associated struvite urolithiasis. Although infection-associated struvite uroliths are rare in cats, urease-producing pathogens like C urealyticum should be considered in cases of LUTO, even without underlying comorbidities.