Sinonasal Nocardia farcinica in a cat with comorbidities

Abstract

A 15-year-old spayed female domestic shorthair cat was referred because of a chronic history of swelling over the right eye that had progressed to an open, exudative wound. The lesion had not responded to prolonged antimicrobial treatments that were chosen based on superficial culture results. Before this development, the cat had been diagnosed with International Renal Interest Society (IRIS) stage 2 chronic kidney disease with no other significant health issues. Computed tomography revealed fluid to soft-tissue attenuating material in the sinonasal cavities and concurrent bony lysis. Cytology and biopsy of the frontal sinus cavity were suggestive of nocardiosis, which culture confirmed as Nocardia farcinica. Treatment using sulfonamide antibiotics was instituted and resulted in resolution of the clinical signs but did not provide a cure. The cat spontaneously died 1 y following the start of therapy due to causes unrelated to the N. farcinica infection, as confirmed by necropsy.

Key clinical message:

Nocardia spp. sinonasal infections are rare in small-animal patients but should be considered in cases of rhinosinusitis not responsive to empirical therapy. This report details management of a case of sinonasal nocardiosis in a cat with comorbidities.

This report outlines the diagnostic and treatment approaches in a cat with nocardial rhinitis and sinusitis. Chronic feline rhinosinusitis is a common disorder affecting cats (1). Cats are presented with a myriad of symptoms, including sneezing, stertorous breathing, snoring, and nasal discharge (1,2). The cause of idiopathic (lymphoplasmacytic) chronic rhinosinusitis is unknown, but it is speculated that underlying viral disease may result in turbinate destruction, which subsequently predisposes to secondary bacterial infections (1–3). Treatment with antibiotics often leads to a temporary improvement of clinical signs but does not provide a long-term cure (1,2). Before making a diagnosis of chronic rhinosinusitis, other causes of rhinosinusitis, including neoplasia, nasopharyngeal polyps, foreign bodies, and fungal infections, should be excluded (1,2,4). Primary bacterial infections are thought less likely (1). This case report describes a cat with primary bacterial sinonasal disease caused by Nocardia farcinica.

CASE DESCRIPTION

A 15-year-old spayed female domestic shorthair cat was referred because of a 5-month history of focal facial swelling over the right eye that subsequently progressed into an exudative, open wound (Figure 1). This animal was predominantly an indoor cat, but she was allowed supervised outdoor access and was known to hunt rodents. Before development of the lesions, no trauma or penetrating wounds had been appreciated. Initial treatment using amoxicillin-clavulanic acid was instituted. When no response was noted, a culture was done from the draining tract and Stenotrophomonas spp. isolated. Based on those results, treatment with pradofloxacin followed by chloramphenicol palmitate (54 mg/kg, q12h) was started. There was a small reduction in the amount of swelling present, but the draining tract and exudate did not improve, and so the cat was referred for more extensive diagnostics while still receiving chloramphenicol.

FIGURE 1.

Photograph of the cat’s face, showing the draining tract on initial presentation.

Apart from the draining tract, the cat had begun to snore ~6 mo before developing the lesions. Thoracic radiographs were obtained immediately before referral, with no abnormalities appreciated. The cat also had a previous history of International Renal Interest Society (IRIS) stage 2 chronic kidney disease (CKD) that was being managed with a chitosan-based phosphate binder.

On initial presentation [Day (D) 0], a grade 3/6 left-sided parasternal heart murmur was appreciated with no abnormal lung sounds. Swelling was noted over the bridge of the nose and a focal, open wound with thick, mucoid discharge was present above the right eye.

In-house swab cytology from the draining tract revealed neutrophils and macrophages without infectious organisms or neoplastic cells. The serum chemistry panel revealed mild azotemia, consistent with the previous diagnosis of CKD. Urea was elevated [14.0 mmol/L, reference interval (RI): 6.0 to 11.4 mmol/L], as was creatinine (220 μmol/L, RI: 78 to 178 μmol/L.) A complete blood count (CBC) was unremarkable. Results of a rapid immunoassay test for feline leukemia virus antigen and antibody to feline immunodeficiency virus (Idexx; Westbrook, Maine, USA) were negative. Urinalysis was not done. Chloramphenicol treatment was continued pending the results of further diagnostics.

On D52, a computed tomography (CT) scan (Canon Aquillion Prime SP, Model TSX-303b; Canon, Tokyo, Japan) (120 kVp, 300 mAs) was obtained without IV contrast, given the history of renal disease. The cat was placed in sternal recumbency. Images were acquired using a soft-tissue and bone convolution algorithm and 1-millimeter transverse slices. The entire right frontal sinus was filled with fluid to soft-tissue attenuating content (average Hounsfield unit: 35) containing subtle stippled mineralization. Diffuse, moderate, irregularly marginated, and sclerotic hyperostosis of the right frontal bone was present, with multifocal lytic foci and cortical incongruities. Within the left frontal sinus, a solitary, irregular, soft-tissue, lobular, mass-like structure was present, likely a granulomatous proliferation of the same nature as the right frontal sinus. However, no left frontal bone hyperostosis or lysis were present. Confluent with the rostroventral aspect of the right frontal sinus, this fluid to soft-tissue attenuating content also extended into the caudodorsal aspect of the right nasal meatus, causing regional nasal turbinate lysis (Figure 2). The nasal septum remained intact and the left nasal cavity remained aerated. The cribriform plate and remaining calvarial osseous structures remained intact. The CT findings were consistent with predominantly right-sided sinonasal disease, with considerations given to infectious rhinosinusitis (bacterial or fungal) over neoplasia (Figure 3).

FIGURE 2.

Axial image in bone window from the initial computed tomographic scan at the level of the caudal nasal cavity. Note the fluid to soft-tissue attenuating content with mild volume expansion in the caudodorsal aspect of the right nasal meatus, causing regional nasal turbinate lysis (arrows). The nasal septum remains intact and the left nasal cavity remains aerated.

FIGURE 3.

A 3D reconstruction of the cat’s skull from the initial computed tomographic scan. Note the asymmetry of the frontal bones, with multifocal lytic regions of the right frontal bone (arrows). The left frontal bone is intact and smoothly marginated.

Samples for cytology, aerobic and anaerobic bacterial culture, and fungal culture were obtained via fine-needle aspiration through the defect in the right frontal bone. Cytology revealed mostly degenerate neutrophils, macrophages, and aggregates of branching chains of organisms. Samples of bone and sinus cavity were obtained by making an incision adjacent to the draining tract. The bone was exposed using periosteal elevators, and once identified, the bony defect was widened using rongeurs. The bone fragments and sinus contents were then submitted for histopathologic examination, and sinus contents were submitted for aerobic and anaerobic bacterial culture and fungal culture. Histopathologic assessment revealed chronic neutrophilic and macrophagic inflammation within the sinus and draining tract, without evidence of neoplasia. Mats of filamentous bacteria were observed with hematoxylin and eosin staining. The bacteria were beaded in appearance, stained weakly positive with a Gram stain, and partially acid-fast with a Fite stain.

Samples were inoculated onto 5% Columbia sheep blood agar and MacConkey agar, and then incubated at 35 ± 1°C under both aerobic and anaerobic conditions for 24 to 48 h. White, small, nonhemolytic colonies demonstrating pure growth were recovered on blood agar. Bacterial identification was done using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS; Bruker Daltonik, Bremen, Germany). Results were consistent with Nocardia farcinica with antibiotic susceptibility to chloramphenicol, trimethoprim sulfonamide, and amoxicillin-clavulanic acid. Resistance to amoxicillin, cephalexin, and marbofloxacin was reported, with intermediate susceptibility to enrofloxacin and cefovecin. As the cat previously had limited to no response to prolonged treatment using chloramphenicol and amoxicillin-clavulanic acid, the chloramphenicol was discontinued and treatment with trimethoprim sulfamethoxazole (15.6 mg/kg, q12h) was started. A sinusotomy was recommended but, due to owner financial constraints, this was declined pending response to therapy. A baseline Schirmer tear test was obtained before starting therapy (right eye: 23 mm/min; left eye: 25 mm/min) and repeated monthly. Serum chemistry and CBC testing were done every 1 to 4 mo, to monitor for adverse side effects related to chronic sulfonamide administration. Gabapentin was started for pain management at an initial dose of 10 mg/kg, q12h but, due to excessive lethargy, the dose was decreased to 4.5 mg/kg, q12h.

Over the following months, progressive improvement of clinical signs was noted. The swelling receded, with complete resolution of the exudate and open wound. On D169, a CT scan was repeated with no appreciable changes noted in comparison to the original study. An ultrasound-guided fine-needle aspiration of the frontal sinus for cytology and repeat culture was recommended, but the owner declined. Given the clinical improvement appreciated, trimethoprim sulfamethoxazole at the same dosage was continued.

On D230, the cat was presented because of recent onset polyuria and polydipsia. A urinalysis, CBC, and serum chemistry were done and diabetes mellitus diagnosed. Abnormalities included hyperglycemia (27.8 mmol/L, RI: 3.5 to 8.1 mmol/L) and increased fructosamine (873 μmol/L, RI: 219 to 347 μmol/L). Urinalysis abnormalities included moderately concentrated urine (specific gravity: 1.027) and glucosuria (4+ glucose) without accompanying ketonuria. A urine culture was negative. Glargine insulin therapy was started at a dosage of 2 units, q12h. Routine monitoring both at home and through routine veterinary assessments confirmed prolonged appropriate control with this therapy.

On D344, an ultrasound-guided fine-needle aspiration of the frontal sinus was done under sedation, to reassess treatment progress and determine if ongoing antibiotic therapy was needed by procuring samples for cytology, aerobic and anaerobic bacterial culture, and fungal culture. Cytology revealed predominantly neutrophilic inflammation with fewer macrophages and mats of basophilic, thin, branching, rod-shaped bacteria. Despite the presence of organisms cytologically, culture results were negative for Nocardia spp. Due to the persistence of disease, a sinusotomy was again recommended to remove exudate from the sinus cavities and facilitate treatment.

On D407, a CT scan was repeated. The sinonasal pathologies remained static overall, with minimal remodeling of the right frontal bone lytic regions, which exhibited progressive and mild rounding of the margins. A bilateral frontal sinusotomy was completed. Both sinuses had noticeably thickened epithelium with yellow mucoid discharge containing green-yellow granules. Histopathologic assessment of the frontal sinuses revealed normal respiratory epithelium and bacterial colonies. Swab cultures from the frontal sinuses were negative for Nocardia spp. Molecular sequencing of 16S mRNA was done and N. farcinica identified. Based on these results and the clinical response appreciated, treatment with trimethoprim sulfamethoxazole was continued.

On D551, the cat was presented on an emergency basis in cardiopulmonary arrest. Resuscitative efforts were not successful. The pathologist unfortunately was not apprised of the previous history of sinonasal nocardiosis. Therefore, neither the frontal sinuses nor the nasal cavity was sampled. Postmortem examination identified no evidence of disseminated nocardiosis on histopathologic examination of the lungs, liver, spleen, kidneys, intestines, heart, duodenal lymph node, thyroid, and adrenal glands. However, persistent sinonasal disease could not definitively be ruled out as an ongoing disease process, despite the previous sinusotomy.

DISCUSSION

This case report describes the medical management of N. farcinica in a cat. Although clinical remission was not achieved, substantial improvement in quality of life was noted.

Nocardia spp. are aerobic, Gram-positive, partially acid-fast, filamentous organisms that are ubiquitous in the environment (5,6). Clinical disease has been reported in humans and many veterinary species, including dogs, cats, and cattle (5–9). The organism is introduced via a penetrating wound or through inhalation and is often associated with immunosuppressive conditions (5,6). In veterinary medicine, reported conditions predisposing to disease include feline infectious virus, morbillivirus, and the use of immunosuppressive medications, including corticosteroids and cyclosporine (7,10–12). In this case, the cat had a previous history of renal disease. Whether this contributed to the development of disease is unknown, but it was considered as a potential factor. In cats with fungal rhinosinusitis, CKD was identified as a noted comorbidity, though this may have been an incidental finding in a population of older cats and not necessarily indicative of causality (4). Once developed, diabetes mellitus may have contributed to ongoing disease, despite the diabetes being well controlled.

Nocardial disease is classified as cutaneous-subcutaneous, pulmonary, or disseminated (6). In cats, the cutaneous-subcutaneous form is the most common presentation (6). Other, less commonly noted presentations of nocardiosis include osteomyelitis, CNS disease, keratitis, and sinonasal disease (6,10,13–16). Sinonasal disease has rarely been described in veterinary medicine, and details regarding treatment and prognosis for this disease presentation are scarce. A previous description of treatment involved radiation therapy and prolonged systemic antibiotics, which resulted in clinical improvement (15). Cases of Nocardia sinusitis have also been reported in humans. Described treatment used antibiotic therapy in conjunction with surgical intervention (17).

Clinical suspicion of nocardiosis should be considered when there are persistent pyogranulomatous inflammatory lesions with filamentous bacteria observed cytologically (6,18) (Figure 4). Granules can sometimes be appreciated in the exudate (6). Imaging may be needed to assess for more extensive disease. Diagnosis of nocardiosis is dependent on culture; however, culture can be challenging in some cases. Nocardia spp. is a slow-growing organism requiring 2 to 4 wk of plate incubation in some cases (6,18). This could lead to premature discarding of the sample. In mixed bacterial populations, there can be overgrowth of contaminant bacteria resulting in false negative results. Deep samples are potentially needed to isolate the organism from cutaneous lesions (18). As was noted in this case, sampling from more superficial sites, such as a draining tract, resulted in the overgrowth of contaminant organisms, leading to a misdiagnosis and false negative results for Nocardia spp. When organisms are unculturable, PCR from the 16S rRNA gene can be beneficial, as also noted in this case (19). This not only is important for making an accurate diagnosis but also can be beneficial in predicting pathogenicity and antimicrobial susceptibility based on species when culture is not diagnostic (6). Culture is still recommended, when possible, as antimicrobial resistance can occur and conventional therapies may not be beneficial.

FIGURE 4.

Photomicrograph of a fine-needle aspiration cytology smear, demonstrating multiple, filamentous, intracytoplasmic bacteria in degenerate neutrophil (red arrow). Degenerate neutrophil (black arrow). Stain: modified Wright-Giemsa; magnification: 100× objective.

Treatment of nocardiosis is dependent on prolonged antimicrobial therapy and possible surgical intervention. Resolution of any immunosuppressive conditions, including discontinuing immunosuppressive drug therapy, if possible, should be implemented (6). Traditionally, sulfonamides have been a first-choice antimicrobial agent for treating Nocardia spp. pending culture results (6). Sulfonamides may also be associated with improved clinical outcomes in cats with nocardiosis (7). However, use of sulfonamides in dogs and, to a lesser extent, cats, can result in fever, thrombocytopenia, hepatopathy, neutropenia, hemolytic anemia, keratoconjunctivitis sicca, arthropathy, and cutaneous drug reactions, making them an unfavorable choice for some patients (6,20). Cats treated with sulfonamides can also develop clinical hypothyroidism (16).

Although sulfonamides are a first-choice antimicrobial agent, culture and antibiotic susceptibility testing is still recommended, as resistance to antimicrobials can occur. In a study reviewing antimicrobial resistance patterns in 14 dogs and cats with nocardiosis, 75.3% of samples obtained from dogs were susceptible to trimethoprim sulfamethoxazole, whereas 8.3% had intermediate susceptibility and 16.4% of isolates were resistant. In cats, 100% of isolates (n = 2) had intermediate susceptibility to trimethoprim sulfamethoxazole. Multidrug resistance was present in 36% of the isolates (13). In the present case, in vitro antibiotic susceptibility was noted to amoxicillin-clavulanic acid and chloramphenicol, but these medications did not result in a significant response in vivo, even with prolonged appropriate administration of chloramphenicol. The reason for this is unknown, but the phenomenon has been previously noted in cats with nocardiosis (6).

Nocardiosis is a challenging disease to treat due to the need for prolonged antimicrobial therapy and the potential need for surgical intervention. The prognosis can be guarded; however, the location of the disease and presence of immunosuppressive conditions can influence treatment outcome. If treatment is discontinued prematurely, clinical signs can recur within months (7). Significant studies regarding nocardiosis in small animals are rare, but in 1 retrospective study of seventeen cats, only 3 achieved clinical cure (7). Due to costs associated with the condition and prolonged use of therapies, treatment may not be a reasonable consideration for all owners. In this case, the cat did not achieve a clinical cure; however, prolonged therapy resulted in significant clinical improvement of her condition, with improved quality of life for both cat and owner. Whether clinical cure could have been achieved had surgical intervention been pursued earlier is unknown. In cases of cats with N. farcinica, combination drug therapy has been suggested for more aggressive treatment (6). This approach was discussed in this case but, due to limited therapeutic options, cost concerns, and comorbidities including hyporexia, the owner elected not to pursue additional antimicrobial therapy.

In summary, although nocardiosis is a rare infection affecting veterinary patients, it can occur, especially in those with immunosuppressive conditions. Disease recognition via appropriate diagnostics is important, as delay in diagnosis and treatment can result in more refractory disease (7). Owners should be advised that prognosis is guarded and prolonged treatment is needed if this disease is diagnosed. This case highlights the importance of thorough diagnostics in cats with rhinosinusitis and the fact that achieving clinical cure in cats with severe rhinosinusitis can be challenging without invasive diagnostics and/or therapies. CVJ