Abstract
Corynebacterium urealyticum is an uncommon cause of urinary tract infections in cats. However, it is difficult to diagnose and if left untreated it may result in irreversible bladder lesions. C urealyticum is a multiantibiotic-resistant bacterium whose culture requires special care. Risk factors for the occurrence of this infection include urological procedures, foreign bodies, bladder mucosa abnormalities, immuno-suppressed states and antibiotic treatment. This report describes an unusual case of C urealyticum urinary infection in a young cat with pre-existing urethral obstruction. C urealyticum was isolated in pure cultures from two urine samples. Clinical and ultrasound features, results of the urinalysis and urine culture are described as well as therapeutic treatment and eventual favourable outcome to treatment with amoxycillin–clavulanic acid.
A 1-year-old, neutered male European cat, living in an apartment and fed with commercial cat food, was presented with urethral obstruction which had developed secondary to feline idiopathic cystitis. The owner reported a 1-week history of dysuria, stranguria and pollakiuria accompanied by intermittent gross haematuria. The cat had been inappetent and weak for 2 days. On physical examination, its bladder was enlarged and painful and the cat was depressed and tachypnoeic; its heart rate was 180 beats/min with a normal rhythm and the cat's systolic blood pressure was 120 mmHg (Doppler method). Blood samples were taken for routine laboratory evaluation. Serum biochemistry revealed increased concentrations of potassium, phosphate, creatinine, and urea. Haematology and other serum biochemistry parameters were unremarkable (Table 1). Tests for feline leukaemia virus and feline immuno-deficiency virus were negative. The cat was anaesthetised to resolve the obstruction. It was treated with diazepam (Diazepam; Intervet, 0.2 mg/kg, IV) and fentanyl (Fentanest; Pharmacia, 3 μg/kg, IV), and induced with propofol (Rapinovet; Schering–Plough, 2 mg/kg, IV). Anaesthesia was maintained with isofluorane (Isoba; Schering–Plough) by endotracheal tube. The perineal area was clipped and cleansed. A sterile, flexible catheter was passed through the urethra to the bladder. Haemorrhagic urine was removed and analysed. Urinalysis revealed pH 7.5 and the presence of some struvite crystals (Table 2). The bladder was rinsed with sterile physiological saline solution 0.9%. The urethral catheter was sutured to the perineal skin and attached to a sterile closed collection system. The cat was given physiological saline solution 0.9% (27 ml/kg/h, IV for 8 h, followed by 18 ml/h for 24 h, and then 9 ml/kg/h) to resolve the postrenal uraemia, plus ranitidine (Zantac; GlaxoSmithKline, 2 mg/kg, bid, IV) to reduce gastric acidity, prazosin (Hypovase; Pfizer, 0.25 mg/cat, bid, OS) to reduce urethral spasm, buprenorphine (Temgesic; Schering–Plough, 10 μg/kg, tid, IV) for analgesia, and tolfenamic acid (Tolfedine; Vetoquinol, 4 mg/kg, sid, OS) as an anti-inflammatory agent. On day 2, the urethral catheter was removed and the cat was urinating on its own. On day 6, haematology and serum biochemistry parameters were within reference ranges. Urinalysis revealed pH 6.5, with white blood cells (WBCs), and some bacilli being present, but no crystals (Table 2). A urine sample obtained by cystocentesis, plated onto Trislide E (Cled agar, MacConkey agar, Bile-esculine agar, Oxoid, Milan, Italy), was incubated under aerobic conditions at 37°C and after 72 h there was no visible growth. The cat was discharged from hospital. At home, it was fed with a wet diet (feline c/d, Hill's) to prevent struvite crystals formation and it was given palmidrol to reduce mast cells degranulation (Urys; Innovet, 50 mg/cat, sid, OS) and glucosamine (Urys; Innovet, 100 mg/cat, sid, OS) to replace the glycosaminoglycan layer of the bladder urothelium. One week later, the cat was re-examined for persistent haematuria, pollakiuria and stranguria. Abdominal ultrasound examination detected a bladder with acoustic shadows associated with sediment, but no calculi, mass, thickening or mineralisation of the wall was observed. Both kidneys presented normal form, size, and echogenicity. Urinalysis revealed the urine to be pH 8.5. At sediment pyuria, haematuria, many struvite crystals and numerous intracellular rods were present (Table 2). Urine culture was performed and the sample was inoculated on brain heart infusion (BHI, Oxoid, Milan, Italy) and on a Columbia agar plate supplemented with 5% sheep blood (Oxoid, Milan, Italy). Both were incubated at 37°C in normal atmosphere and in 5% carbon dioxide atmosphere. On day 5, we observed small, opaque, white, non-haemolytic colonies in the plate and opacity in the BHI tube. A suspension drop was placed on Columbia agar in an agar plate to check for purity and to maintain in culture. The bacteria were identified as catalase-positive, Gram-positive, pleomorphic rods and were characterised by using the API Coryne system (API bioMérieux, Montalieu Vercieu, France) as Corynebacterium urealyticum. Antimicrobial susceptibility was tested by the agar diffusion method (Bauer et al 1966) for the following antimicrobial agents (Oxoid, Milan, Italy): ampicillin, amoxycillin–clavulanic acid, cephalothin, cefuroxime, cefoperazone, ceftiofur, cefquinome, clindamycin, erythromycin, gentamicin, nitrofurantoin, piperacillin, trimethoprim/sulphonamide, florphenicol, doxycycline, enrofloxacin, marbofloxacin, neomicine and kanamicin. The strain was tested on Mueller–Hinton agar with 5% sheep blood and plates were incubated for 72 h at 35°C in normal atmosphere. This revealed the bacteria were susceptible to doxycycline, mildly susceptible to amoxycillin–clavulanic acid and resistant to other tested antibiotics. The cat was treated with doxycycline (Vibravet; Pfizer, 5 mg/kg, bid, OS), methionine (Stien; Teknofarma, 240 mg/cat, bid, OS,) and ammonium chloride (Stien; Teknofarma, 160 mg/cat, bid, OS,) as acidifiers. There were clear signs of clinical improvement during the first week and the treatment was continued for 3 weeks. During this period two further urine samples were collected by cystocentesis and analysed (Table 2). Urinary pH ranged between 7 and 7.5. At sediment struvite crystals were present but no WBCs, red blood cells (RBCs) or microrganisms were seen. Ten days after beginning therapy, urine culture was negative, but at day 20 the culture again yielded C urealyticum. Antimicrobial susceptibility tests showed analogous results to the previous test. Therapy with amoxycillin–clavulanic acid (Synulox; Pfizer, 20 mg/kg, bid, OS) was started and continued for 1 month. To determine treatment efficacy, urinalysis and urine culture were performed 10 days after beginning therapy and every 2 weeks. After 3 months, during which six urine samples were examined, the cat was clinically normal, with no recurrence of infection or evidence of WBCs, RBCs, microrganisms or struvite crystals in the urinary sediment. The urine pH ranged between 6 and 7 (Table 2).
Serum biochemistry and complete blood count at the time of obstruction relief
Urinalysis and urine culture results during treatment and follow-up
Urethral obstruction in male cats is a common medical problem but cats rarely present with a urinary tract infection (UTI) at the time of obstruction relief (Gunn-Moore 2003). Injury induced by bladder over-distention, parenteral fluid therapy, urological procedures, prolonged urinary catheterisation, foreign bodies and immuno-suppressed states are risk factors for the occurrence of UTI (Garcìa-Bravo et al 1995, Bailiff et al 2005). In humans, previous prolonged antibiotic therapy can increase the pathogenic role of commensal corynebacteria of the skin and lead to development of UTI (Aguado et al 1987, Meria et al 1998, Meria and Jungers 2000). Few data exist on the role of C urealyticum in small animals (Elad et al 1992, Gomez et al 1995, Suarez et al 2002) and moreover, to the authors' knowledge, only one report describes two cases of UTI caused by this organism in cats (Bailiff et al 2005). C urealyticum, previously known as the Corynebacterium group D2 (Pitcher et al 1992), is a commensal microrganism of the human skin whose opportunistic pathogenic role in urine has been demonstrated in vitro and in vivo (Meria and Jungers 2000). The source for cats is less clear, but microrganisms identified as Corynebacterium species have been isolated as part of the normal flora of the feline genital tract (Strom Holst et al 2003). In our case, the source of the C urealyticum is unknown. Foreign bodies and immuno-depressant factors were not observed and previous antimicrobial drugs were not given. Bacteria could potentially originate from human or environmental sources following bladder catheterisation. C urealyticum is a non-haemolytic, Gram-positive, aerobic, non-spore-forming bacteria with high urease activity and marked tropism for uroepithelial cells (Marty et al 1989, Meria and Jungers 2000). Infected urine, which is typically alkaline with a pH≥8, becomes saturated with struvite and calcium phosphate crystals which then precipitate, resulting in mucosal encrustations, are may be associated with free stones. These encrustations can involve the urethra, bladder, ureters, or renal pelvises (Meria et al 1998). Haematuria, pyuria and bacteriuria are variably seen in urine sediment (Bailiff et al 2005). The absence of microrganisms on direct examination or after culture with the usual media often explains the delayed diagnosis (Meria and Jungers 2000). C urealyticum grows slowly in vitro and the requirement of prolonged culture has led to the development of a polymerase chain reaction-based assay to detect this infection in humans (Simoons-Smit et al 2000). C urealyticum culture requires special care and should be performed at 37°C at least for 48–72 h on selective media associated with 5% carbon dioxide atmosphere (Garcìa-Bravo et al 1997, Meria et al 1998). Treatment is based on antibiotic therapy, acidification of urine and in some instances, surgical resection of plaques of calcified encrustation (Meria et al 1998). C urealyticum is a multiantibiotic-resistant bacterium (Aguado et al 1987). Constant sensitivity to glycopeptides, vancomycin and teicoplanin, makes these antibiotics the first-line treatment in humans (Soriano et al 1995). However, veterinary experience with these drugs is limited (Jackson et al 1994, Pressel et al 2005) and alternatives may be considered only after in vitro assessment of other antibiotics (Meria and Jungers 2000). In our case, due to local difficulties in sourcing glycopeptides, these drugs were not tested. Although a recent study has reported that doxycycline is present in a satisfactory urinary concentration to be effective against common feline urinary tract pathogens (Wilson et al 2006), the use of doxycycline in this cat was not successful, probably because the minimal inhibitory concentration of C urealyticum was higher than urinary doxycycline concentration attained. It is well established that the results of disc susceptibility testing are not necessarily reliable for assessment of susceptibility of urinary tract bacteria to antimicrobial agents because disc concentrations reflect the serum concentrations rather than urinary concentrations (Ling et al 1981). Besides, the in vivo activity of tetracyclines is lowered by urine alkaline pH (Meria et al 1998). Although C urealyticum is generally resistant to penicillin (Bailiff et al 2005) prolonged administration of amoxycillin–clavulanic acid resolved the infection. In conclusion, C urealyticum should be considered as a possible aetiological agent of UTI when urine is markedly alkaline and has struvite crystals, especially in cats undergoing urological manipulation and bladder catheterisation. In these situations, specific urine cultures might be recommended to identify C urealyticum.