Editorial Type: Infectious Diseases
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Online Publication Date: 01 Nov 2005

Fungal Urinary Tract Infections in the Dog and Cat: A Retrospective Study (2001–2004)

DVM and
DVM, PhD
Article Category: Other
Page Range: 373 – 381
DOI: 10.5326/0410373
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Thirty-five animals (23 dogs, 12 cats) with fungal urinary tract infections (UTIs) were retrospectively studied. Dysuria, hematuria, increased frequency of micturition, anorexia, depression, and pyrexia were the most common clinical signs noted. Seven species of fungi were identified in the affected animals. Candida albicans was the most common isolate. Most animals diagnosed with fungal UTI also had other concurrent urinary tract or medical problems. Lower urinary tract diseases, diabetes mellitus, neoplasia, and renal failure were the most common concurrent or preceding diseases identified. Resolution of fungal UTI occurred in 12 animals that received specific antifungal treatment.

Introduction

Among the 50,000 to 250,000 species of fungi that have been described, fewer than 200 have been associated with human or animal disease.1 With few exceptions, fungal infections in animals originate from an external source in the environment and are acquired through inhalation, ingestion, or traumatic implantation.2 Certain fungi such as Candida spp. are benign colonizers of mucosal surfaces. For disease to occur, host defenses must be weakened.1

Candida spp., Rhodotorula mucilaginosa (also known as R. rubra), and Cryptococcus neoformans are opportunistic pathogens, becoming pathogenic when conditions favor excessive growth or when a patient’s immune system is compromised.3,4 Antibiotic administration, glucocorticoid administration, blood dyscrasias, diabetes mellitus, acidic urine pH, indwelling urinary catheters, and malignant tumors are all predisposing factors for fungal urinary tract infections (UTIs).3,57 Under some conditions, factors that affect adherence of yeast can predispose to fungal infections in the urinary tract.8

Diagnosis of fungal UTI is based upon clinical signs, laboratory tests, and microbial isolation. Sporadic case reports, retrospective studies, and summaries of clinical signs and laboratory tests in fungal UTIs have been published.3,4,813 The purposes of the study reported here were to examine the clinical signs, laboratory findings, possible predisposing factors, causative agents, treatments, and outcomes of fungal UTIs in dogs and cats in China, and to characterize the disease as it exists in Beijing.

Materials and Methods

Case Material

Medical records of all animals diagnosed with fungal UTIs at the Veterinary Teaching Hospital of China Agricultural University (VTH-CAU), Beijing, Peoples Republic of China, from April 2001 through April 2004 were reviewed. Criteria for inclusion were positive fungal urine cultures without evidence of concurrent fungal infection outside the urinary tract at the time of isolation; however, dogs and cats with positive fungal skin cultures on dermatophyte test medium were not excluded. If animals had fungi identified on urine sediment examination, but growth of fungi did not occur on appropriate agar plate media, they were excluded from the study.

Data retrieved from the medical records included signalment, month of diagnosis, concurrent diseases, drugs administered within 1 month preceding diagnosis of the fungal UTI, clinical signs, laboratory abnormalities, the presence of concurrent bacterial UTIs, fungal isolates and sensitivity testing results, specific treatments administered, identification and correction of predisposing risk factors, antifungal drugs administered, and treatment outcomes.

Laboratory Assays

The main study materials were urine and blood samples. Urine samples were obtained by cystocentesis (2 to 5 mL) and transported and preserved in sterile syringes. Urine samples were divided into two aliquots. One portion was centrifuged at 2500 to 3000 rpm. Sediments were cultured on Sabouraud’s dextrose plates (for fungi) and on CHROMagar Orientation agara (for bacteria) at 37°C.14 The fungal plates were observed for growth for a minimum of 7 days prior to being discarded. The bacterial plates were observed for growth for a minimum of 5 days before being discarded.14 Fungi were identified with a commercial test kit.b,15,16 Bacteria were identified via different color changes on the plates.

If fungal or bacterial growth was observed, in vitro susceptibility testing was performed on some isolates with commercial test strips.c,1719 Five antifungal drugs, including fluconazole, itraconazole, ketoconazole, 5-fluorouracil, and amphotericin were tested on Sabouraud’s dextrose plates. A normal sensitivity test range for fluconazole was 0.016 to 256 μg/mL, with values <256 μg/mL considered susceptible. Normal test ranges for 5-fluorouracil, itraconazole, amphotericin, and ketoconazole were 0.002 to 32 μg/mL, with values <32 μg/mL considered susceptible.

Eight antibiotics were tested on the bacterial nutrient agar plates, including sodium penicillin G, amoxicillin, cephalexin, cefadroxil, gentamicin sulfate, lincomycin hydrochloride, enrofloxacin, and norfloxacin. The minimal inhibitory concentration (MIC) was recorded for each drug. If conditions permitted, urine cultures were repeated at least 1 week after cessation of antifungal and antibiotic therapy. When urine cultures were negative on two successive samples (interval between cultures >2 days), the fungal UTI was considered resolved.

The second portion of the urine sample was submitted for urinalysis using urine analyzer and reagent stripsd and was centrifuged for examination of the sediment. Data from the reagent strips (e.g., pH, occult blood, protein, glucose, urobilinogen, bilirubin, ketones), results from examination of the sediment (e.g., red blood cells, white blood cells, bladder and renal epithelial cells, casts and fungal elements), and urine specific gravity were recorded. In general, urine sample handling and cultures were completed within 2 hours of collection.14

Blood samples were collected by venipuncture. Hematological values were tested with an automated hematology analyzer.e

Results

Biographical Data

Thirty-five animals met the criteria for inclusion, including 23 dogs and 12 cats. Of the dogs, 11 were purebred and represented six breeds. The most frequently affected breed was the Pekingese (n=4). Other breeds included the American cocker spaniel (n=2), pug (n=1), shih tzu (n=1), collie (n=1), Cavalier King Charles spaniel (n=1), and English bulldog (n=1). The Pekingese-cross was the most commonly encountered mixed-breed dog (n=9). The 12 cats included four domestic shorthairs and eight domestic longhairs. The genders of the animals are summarized in Table 1. Ages of dogs ranged from 4 to 13 years (mean 10 years). Ages of cats ranged from 4 to 15 years (mean 9 years).

Prevalence and Seasonality

A steady increase in the number of fungal UTI cases was noted during the 3 years of the study period (seven cases in 2001, 12 cases in 2002, 16 cases in 2003). In comparison, the total number of UTIs diagnosed at VTH-CAU for each of these years was 75 in 2001, 91 in 2002, and 133 in 2003. The total caseload at VTH-CAU for each of these years was 33,427 in 2001, 32,156 in 2002, and 32,519 in 2003. Twenty-four of 35 fungal UTI cases were diagnosed during the colder months (October, November, December, January), with the highest number occurring in November and December [see Figure].

Concurrent or Preceding Diseases

Many animals (97%; 34/35) with fungal UTIs also had concurrent or preceding diseases. Lower urinary tract diseases, diabetes mellitus, neoplasia, and renal failure were the most common diseases diagnosed within 1 month of initial isolation of fungi from the urinary tract [Table 2]. Lower urinary tract diseases included chronic bacterial cystitis (82%; 29/35), urolithiasis (57%; 20/35), atonic bladder, urethrospasm, traumatic urethral avulsion, urethral fistula, and prostatitis. Twenty animals (57%; 12 dogs, eight cats) had urethrostomies or indwelling cystotomy tubes inserted for the treatment of urinary calculi prior to the initial diagnosis of fungal UTI. In the dogs, analysis of uroliths showed them to be 100% calcium oxalate. In the cats, 37.5% of the uroliths were composed of calcium oxalate, and 62.5% were composed of struvite.

Neoplasms were diagnosed in the livers of two dogs and two cats, in the lungs of one dog and one cat, and in the skin of one dog. Five animals (two dogs, three cats) had positive skin cultures for fungi and had clinical signs of dermatophytosis. The fungi isolated from the skin were different from those isolated from the urine in these animals. Drugs administered within 1 month preceding the diagnosis of fungal UTI were mainly antibiotics, corticosteroids, gastrointestinal drugs, and antihistamines [Table 3].

Clinical Signs

Dysuria, hematuria, increased frequency of micturition, anorexia, dehydration, depression, and pyrexia were the most common clinical signs noted in the affected animals [Table 4]. Dogs often exhibited dysuria, pyrexia, anorexia, lethargy, increased micturition, hematuria, dehydration, weight loss, and generalized weakness. Cats often exhibited lethargy, anorexia, dehydration, weight loss, pyrexia, increased micturition, dysuria, hematuria, and generalized weakness.

Laboratory Findings

Aciduria (pH <6.5), proteinuria, hematuria, glucosuria, pyuria (>5 white blood cells per high-power field), and fungal components in urine sediments were the most common abnormalities found on urinalysis [Table 5]. Dogs often had aciduria, pyuria, proteinuria, hematuria, glucosuria, increased bilirubin, and bladder epithelial cells and fungal elements in the urine sediments upon urinalysis. Cats often had aciduria, pyuria, hematuria, proteinuria, glucosuria, and bladder epithelial cells and fungal elements in the urine sediment upon urinalysis. Other abnormalities included increased nitrite and decreased urine specific gravity. Abnormalities found in the hematological values included anemia, thrombocytopenia, leukocytosis (with a mature neutrophilia), and monocytosis [Table 5].

Five dogs were tested for the presence of canine distemper virus antigen in their serum, and six dogs were tested for canine parvovirus antigen in their feces using enzyme-linked immunosorbent assays (ELISA). Results of these tests were negative. Three cats were tested for the presence of feline leukemia virus antigen via ELISA, and all were negative. Based upon the results of prior published studies, four cats were tested for the presence of feline immunodeficiency virus antigen via ELISA, and one was positive.20,21

Microbial Isolates

Seven species of fungi were identified in the affected animals [Table 6]. Thirty-three (94%) of 35 animals had a single species of fungi isolated at the time of diagnosis. One dog with cystitis had two species, Candida (C.) albicans and Candida tropicalis, isolated from a cystocentesis-collected sample. One cat with cystitis had two species, C. albicans and Candida krusei, isolated from a cystocentesis-collected sample.

Candida albicans was the most common species isolated, found in 48% (11/23) of dogs and 42% (5/12) of cats. Rhodotorula mucilaginosa were rare isolates, found only in the dogs. Candida guilliermondii was isolated only from one cat. When fungal growth occurred on urine count plates, the number of colonies recorded ranged from 14 to >105 colony-forming units per mL of urine.

In vitro antifungal susceptibility testing was performed on 10 isolates (C. albicans [n=3], C. tropicalis [n=3], C. krusei [n=1], C. guilliermondii [n=1], Cryptococcus neoformans [n=1], and Rhodotorula mucilaginosa [n=1]) from five dogs and five cats. Eight of 10 fungal isolates were susceptible to fluconazole, with MICs ranging from 0.25 to 2.0 μg/mL. Six of 10 fungal isolates were susceptible to 5-fluorouracil, with MICs ranging from 0.125 to 0.75 μg/mL. Five of 10 fungal isolates were susceptible to itraconazole, with MICs ranging from 0.064 to 0.38 μg/mL. Four of 10 fungal isolates were susceptible to amphotericin, with MICs ranging from 0.094 to 0.50 μg/mL. Four of 10 fungal isolates were susceptible to ketoconazole, with MICs ranging from 0.125 to 0.25 μg/mL.

Twenty-nine of 35 urine cultures (in 18 dogs, 11 cats) yielded bacterial growth during the study [Table 7]. Bacterial isolates included Enterococcus spp. (n=14), Escherichia coli (n=8), Staphylococcus saprophyticus (n=6), Streptococcus spp. (n=5), Staphylococcus aureus (n=3), Klebsiella pneumoniae (n=3), and Proteus vulgaris (n=3). Twenty animals (12 dogs, eight cats) had a single concurrent bacterial species isolated. Nine animals (six dogs, three cats) had more than one concurrent bacterial species isolated. All animals with bacterial UTIs were administered appropriate antibiotics based on microbial susceptibility testing. Nine animals with concurrent bacterial infections had urine cultures repeated following administration of antibiotics, and all cultures were negative.

Treatments and Outcomes

The predisposing risk factors that can promote fungal UTI include antibiotic administration, glucocorticoid administration, diabetes mellitus, acidic urine pH, indwelling urinary catheters, and neoplasia.3,57 Identification and correction of predisposing risk factors were initially addressed in most of the affected animals. Fifteen dogs and four cats had antibiotics discontinued. Eleven dogs and six cats had glucocorticoids discontinued. Indwelling urinary catheters were removed from 10 dogs and eight cats. Two cats received treatment for diabetes mellitus.

All animals in this study were treated with antifungal drugs. Fluconazole was the initial therapeutic agent used in 23 animals (15 dogs, eight cats). Fluconazole was given orally twice daily (dogs, 3.5 to 7.0 mg/kg; cats, 3.5 to 6.0 mg/kg).13,22 One cat initially received 5-fluorouracil (50 mg/kg per os [PO] q 8 hours for 2 weeks). Five dogs and one cat received itraconazole twice daily (dogs, 7 mg/kg PO; cat, 5.5 mg/kg PO). One dog initially received 5-fluorouracil (50 mg/kg PO q 8 hours for 2 days), but was then switched to fluconazole twice daily (5 mg/kg PO for 1 week). Two dogs and two cats received ketoconazole twice daily (12.5 mg/kg PO for 3 weeks). Sixteen animals (nine dogs, seven cats) also received sodium bicarbonate (10 to 15 mg/kg PO q 8 hours) in an attempt to increase urine pH to ≥ 7.5.9

Twenty-nine animals (21 dogs, eight cats) had repeat fungal urine cultures performed following the initial diagnosis of fungal UTI. The cultures were performed between 1 and 7 weeks after treatment. Serial urinalyses were performed at 2- to 7-day intervals whenever possible. Based upon culture results, resolution of fungal UTI occurred in 12 animals (eight dogs, four cats). Two cats became infected with a different fungal species (initial species were C. albicans and C. krusei; secondary species were C. tropicalis and C. albicans, respectively) more than 5 months after resolution of their initial infections, and they were euthanized because neoplasia was also diagnosed.

In this study, follow-up intervals ranged from 2 weeks to 10 months (mean 9 weeks) after treatment. Seven animals (three dogs, four cats) were lost to follow-up. Seven animals in the study died from unresponsive fungal UTI (three dogs, one cat) or neoplasia (three cats). Six animals were euthanized because of the severity of the fungal UTI (one dog, one cat) or because of a malignant tumor (one dog, three cats). At the time of manuscript preparation, 15 animals were still alive. Two of the surviving cats and one dog have diabetes mellitus. Two cats and one dog are under treatment for urinary calculi, and one dog and one cat have malignant tumors.

Discussion

Fungal infections of the urinary tract have been uncommonly recognized in dogs and cats.4,10,13,23 In general, <1% of all urinary tract infections are thought to be caused by fungi.24 Because bacteria are commonly associated with urinary tract disorders, fungal cultures may not be performed. The number of urinary tract yeast infections reported in humans has greatly increased in recent times, probably because of alterations in the patients’ immune defenses from diseases such as human immunodeficiency virus (HIV); the use of broad-spectrum antibacterial agents; the use of immunosuppressive, corticosteroid, or anticancer agents; long-term intravenous therapy or inadequate catheter care; and other alterations in the host’s physiology.25

The incidence of fungal UTI increased each year during the time of the study reported here. This uptrend may have occurred because of diseases that arise in geriatric animals (e.g., possible immunosuppression, neoplasia, lower urinary tract diseases, diabetes mellitus), the abuse of broad-spectrum antibiotics, administration of immunosuppressive drugs, or the use of indwelling intravenous and urinary catheters.f These problems all predispose to opportunistic fungal infections and were present in many of the animals diagnosed with fungal UTIs in this study.8 Most of the animals in this study were older, as seen in prior reports.13

The pathogenesis of fungal infections includes implantation or contamination of tissues by fungi, adherence and invasion of the fungi, and incitement of a host response.26 The occurrence of predisposing factors, concurrent diseases, seasonality of infections, as well as some of the clinical signs and laboratory findings found in the study reported here may be explained by their influences on the pathogenesis of infection. The ascending route of infection (i.e., through the urethra) is the most important and common source of fungal UTI.27 The use of indwelling urinary catheters may allow the introduction of fungal elements to the urinary tract. Humans with indwelling bladder catheters are at increased risk for candidal infections. Retrograde spread of yeast organisms into the bladder may also further encourage the entry of bacterial pathogens.2830 Duration of catheter placement is directly related to the incidence of candiduria.31 In this study, 17 animals (49%; 10 dogs, seven cats) had urinary catheters in place at the time of or just prior to diagnosis. The duration of the catheters could not be determined in many of the cases.

In the study reported here, many cases were diagnosed in the colder months, with the highest number occurring in November and December. Most animals are believed to drink more during hot weather (May through September in Beijing) and drink less during the cooler months (October through February). Changes in water drinking may subsequently change the volume of urine produced and the frequency of micturition. Increased production of urine in the warmer months may result in flushing of the urinary tract, with decreased fungal contamination and decreased adherence of fungi.32

Adherence of Candida spp. and some other yeast-like fungi to mucosal epithelial cells is an important step in the process of colonization and invasion. Ability to adhere to mucosal cells is a characteristic of pathogenic C. albicans, as compared to some of the less pathogenic Candida spp.33 Factors that affect adherence include fungal cell surface hydrophobicity, environmental factors, phenotype of the organism, pH, temperature, pregnancy, and the presence of diabetes.26 Attachment of C. albicans to epithelial cells is minimal at acidic pH (i.e., in the range of 3 to 4) and maximal at a more neutral pH of 6.0.34 Aciduria and glucosuria were common laboratory findings in the animals in this study. Urine pH often ranged from 5.8 to 6.5. On the other hand, some fungi (e.g., Candida spp.) can alter glycometabolism and change the pH of the local environment to encourage proliferation; therefore, glucosuria and aciduria may also develop as a result of a fungal UTI.25

The presence of other colonizing microorganisms may affect adherence of Candida spp.; for example, oral streptococci and certain anaerobes may impair candidal adherence, whereas Escherichia coli may promote it.35,36 Alterations in immune defenses by fungal products may be an important aspect of the pathogenesis of C. albicans infections and possibly of other microbial isolates accompanying C. albicans. Extracts of C. albicans and whole, live organisms have been shown to increase the experimental susceptibility of animals to infections with bacteria such as Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Staphylococcus aureus.3739 In the study reported here, 29 (83%) of 35 urine cultures yielded bacterial growth, indicating coinfection with multiple microbial agents.

The interaction between Candida spp. and other microbial flora is perhaps the most important local environmental factor affecting the degree of colonization of mucosal surfaces with Candida spp. The two classes of agents restrict each other and maintain a certain balance of growth. The suppression of either flora may lead to the excessive multiplication of the other. Given the importance of normal microbial flora in suppressing colonization and growth of Candida spp., it is not surprising that use of antimicrobials has been frequently associated with clinical candidiasis.40 Antimicrobials that are broad spectrum and inhibit gram-negative bacteria are most likely to augment colonization with Candida spp.41,42 Similar to studies in humans, in the study reported here, the most common drugs administered within 1 month prior to the diagnosis of fungal UTI were antimicrobials.

Invasion of epithelial cells is another important step in the pathogenesis of C. albicans after colonization and attachment.43 The germ tube or hyphal stage of the organism directly penetrates the epithelial cell membrane. Once inside the cell, the organism continues the process of germination and growth; therefore, the status of local defense mechanisms is crucial in preventing fungal UTIs.44 In this study, fungal UTIs were often diagnosed in association with lower urinary tract diseases. These concurrent diseases may have predisposed to superinfection with multiple microorganisms or may have impaired local immune responses. Corticosteroids administration may also be a risk factor for fungal UTI.4548 Diabetes mellitus, malignant tumors, and other chronic diseases can also alter innate immunity by decreasing leukocyte phagocytosis in dogs.49 In the study reported here, diabetes mellitus, neoplasia, and renal failure were the most commonly diagnosed concurrent diseases.

The significance of the clinical signs and laboratory abnormalities noted in this study was difficult to interpret, as the abnormalities may have been associated with either the fungal infection or the concurrent diseases. In this study, it was difficult to determine whether any specific clinical sign or laboratory abnormality was a true marker of the fungal UTI. Historically, infection with some Candida spp. has been subclinical, although signs of UTI (i.e., hematuria, dysuria, pyrexia) have also been commonly noted.3 In the study reported here, weight loss, lethargy, dehydration, and weakness were more common in animals with fungal UTI than with bacterial UTI, and these signs may have reflected immunocompromise or chronic disease in the affected animals. Pyrexia was also a common finding and may have been associated with the fungal infection, the underlying disease, or both.

Abnormalities found in the urinalyses of animals in this study were similar to those of animals with only bacterial UTIs (e.g., proteinuria, hematuria, glucosuria, pyuria, increased bilirubin, and aciduria). Anemia and thrombocytopenia were considered to be nonspecific findings and may have been related to the presence of chronic infections or other diseases.27

The fungal agents most commonly isolated from urinary tract infections in humans are Candida spp., Cryptococcus neoformans, Geotrichum candidum, and Trichosporon spp.32 Urinary tract infections in small animals have been reported with Candida spp., Torulopsis spp., Cryptococcus spp., Blastomyces spp., Trichosporon spp., Aspergillus spp., Histoplasma spp., and Rhodotorula spp.3,11,50,51 Seven different species of fungi were isolated from the urinary tract samples of the animals in the study reported here. Similar to prior studies, C. albicans was the most common urinary fungal pathogen identified.3,10,13 Candida albicans, C. tropicalis, C. krusei, and C. glabrata were also isolated in the study by Pressler, et al., but isolates of C. guilliermondii, Cryptococcal neoformans, and Rhodotorula mucilaginosa were unique to this study.13 Differences in the isolates may be explained by differences in the geographic region, climate, number of samples studied, and the testing methods used in these studies.

In the yeast phase, Candida spp., especially C. albicans and C. parapsilosis, normally inhabit the alimentary, upper respiratory, and genital mucosae of mammals.3,8 Occasionally, C. tropicalis, C. pseudotropicalis, C. guilliermondii, and C. krusei have been found on human and animal body surfaces.1,4 There have been no reports of these fungi being isolated from the urine of healthy animals. Isolation of Cryptococcal neoformans from the urine of humans with disseminated infection is uncommon.7 Occasionally, people with cryptococcosis have clinical signs of pyelonephritis or prostatitis, and prostatic infection is a common cause of persistent UTI after apparently effective treatment for cryptococcal meningitis in humans with HIV infections.1 Similar findings have not been reported in animals, and the isolation of Cryptococcus spp. from the urine of animals is usually considered significant. In this study, the dog with Cryptococcus neoformans in the urine had no evidence of prostatitis or systemic disease, and the origin of the infection was never identified.

Yeast forms of the genus Rhodotorula are saprophytes, and they are rarely isolated from the urinary tract of small animals.11 Granulomatous epididymitis has been reported with Rhodotorula spp. infection in a dog.52 In humans, infections with Rhodotorula spp. are most often found in patients with cancer, bacterial endocarditis, various debilitating diseases for which indwelling intravenous catheters are used, and in people receiving chemotherapy.25 In this study, the dog with Rhodotorula infection had both diabetes mellitus and urinary calculi. Immunosuppression was considered the main predisposing factor for the fungal UTI of this case.

Experience with treatment of fungal UTI in animals is limited.4,10,13 Alkalinization of urine may be helpful, because Candida spp. grow best when urine pH is in the range of 5.1 to 6.4.8 Results of in vitro studies indicate that Candida spp. survive poorly at extremes of pH and that pseudohyphae formation is restricted in alkaline urine.53 Urine alkalization may be induced by oral administration of sodium bicarbonate or potassium citrate in a dose sufficient to increase urine pH to ≥ 7.5.9 Although administration of bicarbonate is commonly advocated, it had minimal impact on the pHs of urine in the study reported here. It was also the authors’ impression that alkalinization of the urine did not alter the clinical outcomes.

Humans with clinically symptomatic fungal UTIs or who have other debilitating or complicating disorders are often treated with intravenous or intravesicular amphotericin B, oral azoles, and oral flucytosine.57,54,55 No studies have been performed comparing the safety or efficacy of these agents for fungal UTIs in animals.54 Intravenous amphotericin B induces rapid resolution of candidal UTI; however, it is associated with substantial nephrotoxicity in the dog.9 Flucytosine has a narrow range of antifungal activity, and the development of resistance is common, especially when low doses are administered.5 Ketoconazole and itraconazole do not achieve therapeutic concentrations in the urine.7,56 Fluconazole may be a viable alternative therapy, because it is smaller, more water-soluble, less protein-bound than either ketoconazole or itraconazole, and is excreted in the urine.9,22,5759

The results of antifungal susceptibility testing offer potential criteria for the selection of antifungal drugs. Treatment choices for some of the cases in this study were based on the results of susceptibility testing (n=10); and for other cases, treatment choices were made empirically (n=25). Historically, fluconazole has been the initial therapeutic agent used for fungal UTIs in animals.5 In the study reported here, fluconazole induced more resolutions than the other drugs, and these results were similar to those reported by Pressler et al.13 Response to treatment requires monitoring with serial urine fungal cultures.4,13 Based upon the results of this and other studies, treatment should be continued until two successive negative urine cultures are obtained at 1- to 2-week intervals.4

Conclusion

Fungal UTIs were diagnosed with increasing frequency in Beijing between 2001 and 2004, and most cases were associated with predisposing factors. Dysuria, hematuria, increased frequency of micturition, anorexia, depression, and pyrexia were the most common clinical signs noted. The causative agents were mainly opportunistic fungi, with Candida spp. being the most common isolates. Resolution of fungal UTI was achieved with treatment of the predisposing factors and the use of fluconazole.

CHROMagar Orientation agar (identifies urinary bacteria by different colors of colonies on plates); CHROMagar Company, Paris, France

API 20C AUX; BioMerieux, Durham, NC 27712

Etest yeast; AB Biodisk, Solna, Sweden

Clintek 50 urinary analyzer and Multistix 10 SG reagent strip; Bayer Corporation, Diagnostic Division, Elkhart, IN 46515

MEK-6318K automated hematology analyzer; Nihon Kohden Corporation, Tokyo, Japan

Unpublished data from China Agricultural University, Beijing, China

Acknowledgment

The authors thank Dr. Mo Li for her help in preparation of the manuscript.

Table 1 Gender and Age Distribution of Animals With Fungal Urinary Tract Infections

          Table 1
Table 2 Diseases Concurrent With or Occurring Within 1 Month Prior to the Diagnosis of Fungal Urinary Tract Infections

          Table 2
Table 3 Drugs Administered Within 1 Month of the Diagnosis of Fungal Urinary Tract Infections

          Table 3
Table 4 Clinical Signs in Animals With Fungal Urinary Tract Infections

          Table 4
Table 5 Laboratory Abnormalities in Animals With Fungal Urinary Tract Infections

          Table 5
Table 6 Fungi Isolated From Urine of Animals With Fungal Urinary Tract Infections

          Table 6
Table 7 Bacteria Isolated From Urine of Animals With Fungal Urinary Tract Infections

          Table 7
Figure—. Distribution (by month) of fungal urinary tract infection cases.Figure—. Distribution (by month) of fungal urinary tract infection cases.Figure—. Distribution (by month) of fungal urinary tract infection cases.
Figure Distribution (by month) of fungal urinary tract infection cases.

Citation: Journal of the American Animal Hospital Association 41, 6; 10.5326/0410373

References

  • 1
    Richardson MD, Warnock DW. Fungal Infections. Oxford: Blackwell Scientific Publications, 1993:1–122.
  • 2
    Shiping C. Fungal Infection. Liaoning Scientific & Technical Publishers, 2000:80–81.
  • 3
    Greene CE, Chandler FW. Candidiasis, torulopsosis, and rhodotorulosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. 2nd ed. Philadelphia: WB Saunders, 1998:414–417.
  • 4
    Polzin D, Klausner JS. Treatment of urinary tract candidiasis. In: Kirk RW, ed. Current Veterinary Therapy VIII Small Animal Practice. Philadelphia: WB Saunders, 1983:1055–1057.
  • 5
    Fisher JF, Newman CL, Sobel JD. Yeast in the urine: solutions for a budding problem. Clin Infect Dis 1995;20:183–189.
  • 6
    Gubbins PO, McConnell SA, Penzak SR. Current management of funguria. Am J Health-Syst Pharm 1999;56:1929–1935.
  • 7
    Wong-Beringer A, Jacobs RA, Guglielmo J. Treatment of funguria. J Am Med Assoc 1992;267:2780–2785.
  • 8
    Greene CE, Chandler FW. Candidiasis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat. Philadelphia: WB Saunders, 1990: 723–727.
  • 9
    Lulich JP, Osborne CA. Fungal urinary tract infection. In: Kirk RW, ed. Current Veterinary Therapy XI Small Animal Practice. Philadelphia: WB Saunders, 1992:914–919.
  • 10
    Lulich JP, Osborne CA. Fungal infections of the feline lower urinary tract. Vet Clin North Am Small Anim Pract 1996;26:309–315.
  • 11
    Doster AR, Erickson ED, Chandler FW. Feline trichosporonosis. J Am Vet Med Assoc 1987;190:1184–1186.
  • 12
    Fulton Jr RB, Walker RD. Candida albicans urocystitis in a cat. J Am Vet Med Assoc 1992;200:524–526.
  • 13
    Pressler BM, Vaden SL, Lane IF, et al. Candida spp. urinary tract infections in 13 dogs and seven cats: predisposing factors, treatment, and outcome. J Am Anim Hosp Assoc 2003;39:263–270.
  • 14
    Zhou TY, Zhao H. Diagnosis and Illustration of Clinical Microbiology. Shanghai Scientific & Technical Publishers, 2001:215–216.
  • 15
    Chengappa MM, Maddux RL, Greer SC, et al. Isolation and identification of yeasts and yeastlike organisms from clinical veterinary sources. J Clin Microbiol 1984;19:427–428.
  • 16
    Bornand V. Bacteriology and mycology of otitis externa in dogs. Schweiz Arch Tierheilkd 1992;134:341–348 (French).
  • 17
    Rodrigues J, Poeta P, Martins A, et al. The importance of pets as reservoirs of resistant enterococcus strains, with special reference to vancomycin. J Vet Med B Infect Dis Vet Public Health 2002;49: 278–280.
  • 18
    Maia ML, Dos Santos JI, Viani FC, et al. Phenotypic characterization of Microsporum canis isolated from cats and dogs. Mycoses 2001;44:480–486.
  • 19
    Speakman AJ, Binns SH, Dawson S, et al. Antimicrobial susceptibility of Bordetella bronchiseptica isolates from cats and a comparison of the agar dilution and E-test methods. Vet Microbiol 1997;54:63–72.
  • 20
    Lshida TI, Washizu T, Toriyabe K, et al. Feline immunodeficiency virus infection in cats of Japan. J Am Vet Med Assoc 1989;194: 221–225.
  • 21
    Lippert AC, Fulton Jr RB, Parr AM. Nosocomial infection surveillance in a small animal intensive care unit. J Am Anim Hosp Assoc 1988;24:627–636.
  • 22
    Zhu M. Veterinary Grababin Medicinarum Particularum. Beijing: Chemical Industry Publishing, 2002:114–116.
  • 23
    Wooley RE, Blue JL. Bacterial isolates from canine and feline urine. Mod Vet Pract 1976;57:535–538.
  • 24
    Chew DJ. Chronic and recurrent urinary tract infections. www.Vetsuite.com.
  • 25
    Beneke ES, Rogers AL. Medical mycology and human mycoses. Belmont CA: Star Publishing, 1996:149–168.
  • 26
    Bodey GP. Candidiasis. New York: Raven Press, Ltd., 1993:6063,71–73.
  • 27
    Lage AL, Polzin DJ, Zenoble RD: Diseases of the bladder. In Morgan RV, ed. Handbook of Small Animal Practice. New York: Churchill Livingstone, 1988:605–619.
  • 28
    Turck M, Goffee B, Petersdorf RG. The urethral catheter and urinary tract infection. J Urol 1962;88:834–837.
  • 29
    Schaeffer AJ, Chmeil J. Urethral meatal colonization in the catheter-associated bacteriuria. J Urol 1983;130:1096–1099.
  • 30
    Daifuku R, Stamm W. Association of rectal and urethral colonization with urinary tract infection in patients with indwelling catheters. J Am Med Assoc 1984;252:2028–2030.
  • 31
    Hamory BH, Wezel RP. Hospital-associated candiduria: predisposing factors and a review of the literature. J Urol 1978;120:444–448.
  • 32
    Jacobs PH, Nall L. Fungal disease. New York: Marcel Dekker, Inc., 1997:322–327.
  • 33
    King RD, Lee JC, Morris AL. Adherence of Candida albicans and other Candida species to mucosal epithelial cells. Infect Immun 1980;27:667–674.
  • 34
    Sobel JD, Myers PG, Kaye D, et al. Adherence of Candida albicans to human vaginal and buccal epithelial calls. J Infect Dis 1981;14:76–82.
  • 35
    Samaranayake LP, MacFarlane TW. Factors affecting in vitro adherence of the fungal oral pathogen Candida albicans to epithelial cells of human origin. Arch Oral Biol 1982;27:869–873.
  • 36
    Makrides HC, MacFarlane TW. An investigation of the factors involved in increased adherence of Candida albicans to epithelial cells mediated by Escherichia coli. Microbios 1983;38:177–185.
  • 37
    Rogers TJ, Balish E. Immunity to Candida albicans. Microbiol Rev 1980;44:660–682.
  • 38
    Mankiewicz E, Miivak M. Effect of Candida albicans on the evolution of experimental tuberculosis. Nature (London) 1960;187: 250–251.
  • 39
    Carlson E. Synergistic effect of Candida albicans and Staphylococcus aureus on mouse mortality. Infect Immunol 1982;38:921–924.
  • 40
    Helstrom PB, Balish E. Effect of oral tetracycline, the microbial flora, and the athymic state on gastrointestinal colonization and infection of BALB/C mice with Candida albicans. Infect Immun 1976;23:764–774.
  • 41
    Odds FC. Candida and Candidosis: A Review and Bibliography. 2nd ed. London: Bailliere Tindall, 1988:68–92.
  • 42
    Scaringi L, Marconi P, Boccanera M, et al. Cell wall components of Candida albicans as immunomodulators: induction of natural killer and macrophage-mediated peritoneal cell cytotoxicity in mice by mannoprotein and glucan fractions. J Gen Microbiol 1988;134: 1265–1274.
  • 43
    Howlett JA, Squier CA. Candida albicans ultrastructure: colonization and invasion of oral epithelium. Infect Immun 1980;29:252–260.
  • 44
    Pugh D, Cawson RA. The cytochemical localization of phospholipase in Candida albicans infecting the chick chorioallantoic membrane. Sabouraudia 1977;15:29–35.
  • 45
    Pearsall NN, Lagunoff D. Immunological response to Candida albicans I. Mouse-thigh lesion as a model for experimental candidiasis. Infect Immun 1974;9:999–1002.
  • 46
    Diamond RD, Krzesicki R, Jao W. Damage to pseudohyphal forms of Candida albicans by neutrophils in the absence of serum in vitro. J Clin Invest 1978;61:349–359.
  • 47
    Wagner DK, Collins-Lech C, Sohnel PG. Inhibition of neutrophil killing of Candida albicans pseudohyphae by substances which quench hypochlorous acid and chloramines. Infect Immun 1986;51:731–735.
  • 48
    Balow JE, Rosenthal AS. Corticosteroid suppression of macrophage inhibition factor. J Exp Med 1973;137:1031–1041.
  • 49
    Latimer KS, Mahaffey EA. Neutrophil adherence and movement in poorly and well-controlled diabetic dogs. Am J Vet Res 1984;45: 1498–1500.
  • 50
    Clinkenbeard KD, Wolf AM, Cowell RL, et al. Feline disseminated histoplasmosis. Compend Contin Educ Pract Vet 1989;11:1223–1233.
  • 51
    Neer TM. Disseminated aspergillosis. Compend Contin Educ Pract Vet 1988;10:465–471.
  • 52
    Kadota K, Uchida K, Nagatomo T, et al. Granulomatous epididymitis related to Rhodotorula glutinis infection in a dog. Vet Pathol 1995;32:716–718.
  • 53
    Taola P, Schroeder SA, Davl AK, et al. Candida at Boston City Hospital. Clinical and epidemiological characteristics and susceptibility to eight antimicrobial agents. Arch Intern Med 1970;126: 983–989.
  • 54
    Kruger JM, Osborne CA. The role of uropathogens in feline lower urinary tract disease. Vet Clin North Am Small Anim Pract 1993;23:101–123.
  • 55
    Leu H, Huang C. Clearance of funguria with short-course antifungal regimens; a prospective, randomized, controlled study. Clin Infect Dis 1995;20:1152–1157.
  • 56
    Terrel CL. Antifungal agents. Part II. The azoles. Mayo Clin Proc 1999;74:78–100.
  • 57
    Jacobs LG, Skidmore EA, Freeman K, et al. Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients. Clin Infect Dis 1996;22:30–35.
  • 58
    Rex JH, Rinaldi MG, Pfaller MA. Resistance of Candida species to fluconazole. Antimicrob Agents Chemother 1995;39:1–8.
  • 59
    Graybill JR. New antifungal agents. Eur J Clin Microbiol Infect Dis 1989;8:402–412.
Copyright: Copyright 2005 by The American Animal Hospital Association 2005
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Figure

Distribution (by month) of fungal urinary tract infection cases.


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