Wigney Di

Cryptococcosis in cats : clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole

Twenty-nine cats with naturally occurring cryptococcosis were evaluated prior to commencing oral fluconazole therapy (25-100 mg every 12 h). Affected cats ranged from 2 to 15 years-of-age. Male cats (19; 66%) and Siamese cats (5; 21%) appeared to be over-represented in comparison to the hospitals cat population. Mycotic rhinitis was observed in 24 (83%) of the cases, although nasal cavity involvement was subtle in four animals. Disease of the skin and subcutaneous tissues was present in 15 cases (52%) and amongst these the nasal plane (seven cats) and bridge of the nose (seven cats) were most commonly involved. Primary infection of the central nervous system was not encountered, although one cat developed meningoencephalitis and optic neuritis as a sequel to longstanding nasal cavity disease. Antibodies against the feline immunodeficiency virus (FIV) were detected in eight cats (28%), and these cats tended to have advanced and/or disseminated disease. There was a tendency for cats to develop cryptococcosis during the Australian summer. Organisms were cultured from 27 cases. Cryptococcus neoformans var. neoformans was isolated from 21 cats, while C. neoformans var. gattii was identified in the remaining six. The response to oral fluconazole was excellent in this series, which included many cats with advanced, longstanding or disseminated disease. The fungal infection resolved in all but one advanced case which died after only 4 days of therapy. A dose of 50 mg per cat, given every 12 h, produced a consistently good response without side effects. Lower doses were effective in some cases, while 100 mg every 12 h was required to control the infection in one cat. Serum fluconazole levels obtained during chronic dosing (50 +/- 18 mg l-1, mean +/- SD; 50 mg per cat every 12 h) were highly variable (range 15-80 mg l-1). Concurrent FIV infection did not impart an unfavourable prognosis, although affected cats often required prolonged courses of therapy.

Retrospective study of feline and canine cryptococcosis in Australia from 1981 to 2001: 195 cases

A retrospective study of 155 cats and 40 dogs diagnosed with cryptococcosis between 1981 and 2001 was undertaken. Age, sex, breed, clinical findings, feline immunodeficiency virus and feline leukaemia virus status (in cats), species of Cryptococcus causing disease and region of domicile were recorded. Associations between variables were tested. Male and female cats were affected equally. Age ranged from 1 to 16 years, with a preponderance of cats aged between 2 and 3 years. Siamese, Himalayan and Ragdoll breeds were over-represented. Rural cats were more frequently infected with Cryptococcus gattii. Retroviral infection was not identified as a predisposing condition and was not correlated with either species of Cryptococcus or physical findings. Most cats had signs of nasal cavity infection, which was typically localised for a substantial period before invasion of adjacent structures or dissemination. Male and female dogs were affected equally. A marked preponderance of young, large breed dogs was noted. Border Collies, Boxers, Dalmatians, Dobermann Pinschers, Great Danes and German Shepherds were over-represented. Cryptococcus species involved was not affected by place of domicile. Although nasal cavity involvement was important, the canine cohort had a greater propensity to develop secondary central nervous system involvement and disseminated disease than feline cases. There were no clinical findings in either cats or dogs which could be reliably used to distinguish disease caused by Cryptococcus neoformans variety grubii from disease caused by Cryptococcus gattii. Both Cryptococcus species appear to be primary pathogens of cats and dogs, with the upper respiratory tract presumed to be the predominant primary site of inoculation in most but not all cases.

Cryptococcosis in dogs: a retrospective study of 20 consecutive cases

The clinical and mycological findings in 20 consecutive cases of cryptococcosis evaluated between 1981 and 1995 were analysed retrospectively. Typically, young adult dogs (median age 2 years) of either sex were affected. Dobermann Pinschers and Great Danes were significantly over-represented in relation to other breeds and crossbred dogs, and there was no trend for cryptococcosis to be acquired at a particular time of year. Cryptococcus neoformans was cultured from 18 dogs, with 16 isolates further characterized. Of these, C. neoformans var. neoformans was isolated from 12 cases, while the remaining four strains were C. neoformans var. gattii. Dogs with C. neoformans var. gattii infections resided in rural (two cases) or suburban (two cases) environments. Ten dogs were presented as a result of infection of structures inside, adjacent to, or contiguous with the nasal cavity. Seven dogs were presented primarily for signs of central nervous system disease, of which at least three also had cryptococcal rhinosinusitis. One dog had cryptococcal pneumonia and also possible mycotic rhinitis, another had disseminated disease with lymph node and skin involvement, while the last dog was presented for vomiting referable to cryptococcal mesenteric lymphadenitis. Treatment consisting of surgery and/or antifungal drug therapy was successful in the majority of animals in which it was attempted, including two of three cases with meningo-encephalitis.

Asymptomatic carriage of Cryptococcus neoformans in the nasal cavity of dogs and cats

Nasal washings, obtained from a random source of dogs and cats, were concentrated by centrifugation and plated onto bird seed agar containing antibiotics. Cryptococcus neoformans var. neoformans was isolated from eight of 56 dogs (14%) and three of 45 cats (7%). More than 100 colonies of C. neoformans were present on the plates from seven of the 11 positive animals. Absence of cryptococcal antigen in the serum of these animals, and failure to demonstrate yeast-like organisms or significant pathology in nasal biopsies, suggests that the nasal cavity of these animals was not infected by C. neoformans but rather that blastoconidia and/or basidiospores were carried asymptomatically. These findings are discussed in relation to the likelihood of the upper respiratory tract being the primary site for cryptococcal infection in dogs and cats.

Infection of the subcutis and skin of cats with rapidly growing mycobacteria: a review of microbiological and clinical findings

Mycobacteria were isolated and characterised from 49 cats with extensive infections of the subcutis and skin. Cats were generally between 3 and 10 years of age, and female cats were markedly over-represented. All isolates were rapid-growers and identified as either Mycobacteria smegmatis (40 strains) or M fortuitum (nine strains). On the basis of Etest for minimum inhibitory concentration and/or disc diffusion susceptibility testing, all strains of M smegmatis were susceptible to trimethoprim while all strains of M fortuitum were resistant. M smegmatis strains were typically susceptible to doxycycline, gentamicin and fluoroquinolones but not clarithromycin. All M fortuitum strains were susceptible to fluoroquinolones, and often also susceptible to gentamicin, doxycycline and clarithromycin. Generally, M smegmatis strains were more susceptible to antimicrobial agents than M fortuitum strains. Treatment of mycobacterial panniculitis involves long courses of antimicrobial agents, typically of 3–6 months, chosen on the basis of in vitro susceptibility testing and often combined with extensive surgical debridement and wound reconstruction. These therapies will result in effective cure of the disease. One or a combination of doxycycline, ciprofloxacin/enrofloxacin or clarithromycin are the drugs of choice for long-term oral therapy.

Disseminated Mycobacterium Genavense Infection in a FIV-Positive Cat

An 8-year-old FIV-positive Australian cat was presented with coughing, periocular alopecia, pyrexia and inappetence. Skin scrapings demonstrated Demodex cati mites. Antibiotics were administered and it was treated successfully for periocular demodectic mange, but the cat continued to exhibit respiratory signs and lose weight. Further investigation revealed an ascarid infection and active chronic inflammation of undetected cause affecting the lower airways. Repetitive treatment with pyrantel failed to eradicate the ascarid infection. The cat became cachectic and developed moist ulcerative dermatitis of the neck, severe non-regenerative anaemia, leucopenia and thrombocytopenia. Necropsy and histopathology revealed mycobacteriosis affecting skin, lungs, spleen, lymph nodes, liver and kidney. Attempted culture of frozen tissues at a mycobacteria reference laboratory was unsuccessful. Paraffin-embedded, formalin-fixed tissue was retrieved and examined using PCR to amplify part of the 16S rRNA gene. A diagnosis of disseminated Mycobacterium genavense infection was made based on the presence of acid fast bacteria in many tissues and partial sequence of the 16S rRNA gene. Although M genavense has been identified previously as a cause of disseminated disease in AIDS patients, this is the first report of infection in a cat. It was suspected that the demodecosis, recurrent ascarid infections and disseminated M genavense infection resulted from an immune deficiency syndrome consequent to longstanding FIV infection.

Limited Diversity among Human Isolates of Bartonella henselae

ABSTRACT A study of 59 isolates of Bartonella henselae reveals relatively limited diversity among those of human origin (n = 28). Either of two distinct alleles of both gltA and 16S ribosomal DNA (rDNA) was found in all isolates, with a high level of congruity between 16S and gltA inheritance among proven human pathogens. Human isolates from all over Eastern Australia were most commonly 16S rDNA (Bergmans) type I, with the same gltA allele as the type strain (Houston-1). Comparable feline isolates were more commonly 16S type II, with less congruity of inheritance between 16S and gltA alleles. Previously described arbitrarily primed PCR and EagI-HhaI infrequent restriction site PCR fingerprinting techniques separated Bartonella species effectively but lacked discriminating power within B. henselae. Examination of the 16-23S intergenic spacer region revealed for several strains several point mutations as well as a repeat sequence of unknown significance which is readily detected by HaeIII restriction fragment length polymorphism analysis. The bacteriophage-associated papA gene was present in all isolates. Enterobacterial repetitive intergenic consensus PCR proved to be a useful and robust typing tool and clearly separated human isolates (including imported strains) from the majority of feline isolates. Our data are consistent with published evidence and with previous suggestions of intragenomic rearrangements in the type strain and suggest that human isolates come from a limited subset of B. henselae strains. They strengthen arguments for careful exploration of genotype-phenotype relationships and for the development of a multilocus enzyme electrophoresis and multilocus sequence typing-based approach to the phylogeny of B. henselae.

Vegetative endocarditis in six cats

Between 1990 and 1997 vegetative endocarditis was diagnosed in six neutered cats (three males, three females) aged between 3 and 9 years. Two cats were purebred (one Persian and one Tonkinese), the remaining four being domestic short haired cats. The diagnosis was made using echocardiography (five cases) or at necropsy (one case). Concurrent involvement of the aortic and mitral valve was noted in four cats, the aortic valve alone was affected in one case, and the tricuspid valve in another. A likely microbiological diagnosis was obtained in three cats: a Bartonella species in two cats based on positive blood culture and a Streptococcus species in one cat based on Gram stain of valve lesions at necropsy. In another cat, Gram-positive cocci were demonstrated histologically in tricuspid vegetations. Invariably, cats had signs of congestive heart failure (left-sided in five cats, right-sided in one), and this was the major factor contributing to mortality in four cases. Signs referable to sepsis were prominent in only two patients. Appropriate medical therapy, consisting of antimicrobials and drugs to treat congestive heart failure, resulted in survival for 5 and 11 months, respectively, in two cases. The other cats died within 2 weeks of diagnosis, including two which received aggressive treatment in hospital.

Susceptibility of rapidly growing mycobacteria and Nocardia isolates from cats and dogs to pradofloxacin

Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory infections in cats and dogs. Prolonged antibacterial therapy is required to cure these infections. As fluoroquinolones have been used in combination therapy for treating RGM infections, isolates from the Mycobacterium smegmatis cluster (n=64), Mycobacterium fortuitum cluster (n=17), and M. mageritense cluster (n=2), collected from feline and canine patients, underwent susceptibility testing to pradofloxacin. The MIC(50), MIC(90) and tentative epidemiological cut-off (ECOFF) values as determined by microbroth dilution susceptibility testing that inhibited growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and ≤ 0.25; and 0.125, 0.250 and ≤ 1.0 μg/mL, respectively. E-Test results showed similar trends but MICs were lower than those for microbroth dilution. In summary, pradofloxacin demonstrated effective in vitro activity against RGM isolates. Additionally, veterinary isolates of Nocardia nova (n=18), Nocardia farcinica (n=3) and Nocardia cyriacigeorgica (n=1) underwent microbroth dilution testing to ciprofloxacin, enrofloxacin and pradofloxacin. The MIC(50) and MIC(90) of pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of Nocardia nova isolates were 2 (4), 8 (16), 16 (32) μg/mL, respectively. The tentative ECOFF values for pradofloxacin and ciprofloxacin were 32 μg/mL and for enrofloxacin 64 μg/mL. The MIC or MIC range for the three N. farcinica isolates of pradofloxacin, ciprofloxacin and enrofloxacin were 0.25-0.5, 2 and 2 μg/mL and for the single N. cyriacigeorgica isolate were 1, 4 and 4 μg/mL, respectively. On the basis on these results, fluoroquinolones appear to have limited therapeutic potential for most Nocardia infections.

Susceptibility of rapidly growing mycobacteria isolated from cats and dogs, to ciprofloxacin, enrofloxacin and moxifloxacin.

Rapidly growing mycobacteria (RGM) cause infections in cats and dogs which require prolonged antibacterial medication for resolution. In Australia, pathogens from the Mycobacterium fortuitum and Mycobacterium smegmatis clusters are responsible for most of the RGM infections in cats and dogs. As fluoroquinolones are often recommended for treating such infections, 14 M. fortuitum isolates, 51 isolates from the M. smegmatis cluster and 2 M. mageritense isolates, collected from feline and canine patients, underwent susceptibility testing to the second generation fluoroquinolones ciprofloxacin and enrofloxacin and the newer generation fluoroquinolone moxifloxacin. Using microbroth dilution, the MIC(90) of ciprofloxacin, enrofloxacin, and moxifloxacin that inhibited growth of M. fortuitum isolates were 0.500, 0.250 and 0.063 μg/mL respectively. For the M. smegmatis cluster isolates the corresponding MIC(90) was 0.500, 0.250 and 0.125 μg/mL respectively. E-test results showed similar trends but MICs were lower than those determined by microbroth dilution. Additionally, moxifloxacin was administered to 10 clinically normal cats (50mg per cat, once daily for 4 days). The plasma moxifloxacin concentration 2h after the last dose was determined by liquid chromatography as 2.2 ± 0.6 μg/mL. The plasma concentration at 2h:MIC(90) ratios for moxifloxacin for M. fortuitum and M. smegmatis cluster was 34.9 and 17.6 respectively which exceeded the recommended threshold of 10, indicating that moxifloxacin has good theoretical efficacy for treatment of those M. fortuitum and M. smegmatis infections in cats and dogs that have become refractory to other antibacterial drug classes.