Submitted by: Margie Scherk, DVM, DABVP (Feline)
J Feline Med Surg. 2020: 22(8) 678–684. DOI:10.1177/1098612X19874141
Subclinical bacteriuria in a mixed population of 179 middle-aged and elderly cats: a prospective cross-sectional study.
Moberg FS, Langhorn R, Bertelsen PV, Pilegaard LM, Sørensen TM, Bjørnvad CR, Damborg P, Kieler IN, Jessen LR.
The Vet J. 2019 May 1;247:8-25. DOI: 10.1016/j.tvjl.2019.02.008
International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats.
Weese JS, Blondeau J, Boothe D, Guardabassi LG, Gumley N, Papich M, Jessen LR, Lappin M, Rankin S, Westropp JL, Sykes J.
J Feline Med Surg. 2007 Apr;9(2):124-32. DOI: 10.1016/j.jfms.2006.09.004
Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease.
Mayer-Roenne B, Goldstein RE, Erb HN.
Vet Clin Path. 2008 Sep;37(3):317-22. DOI: 10.1111/j.1939-165X.2008.00065
Evaluation of urine specific gravity and urine sediment as risk factors for urinary tract infections in cats.
Bailiff NL, Westropp JL, Nelson RW, Sykes JE, Owens SD, Kass PH.
Vet Microbiol. 2009 Apr 14;136(1-2):130-4. DOI: 10.1016/j.vetmic.2008.10.019
Occult bacterial lower urinary tract infections in cats—urinalysis and culture findings.
Litster A, Moss S, Platell J, Trott DJ.
J Feline Med Surg. 2017 Dec;19(12):1238-44. DOI: 10.1177/1098612X16688806
Subclinical bacteriuria in cats: prevalence, findings on contemporaneous urinalyses and clinical risk factors.
Puchot ML, Cook AK, Pohlit C.
J Feline Med Surg. 2013 Jun;15(6):459-65. DOI:10.1177/1098612X12469522
Urinary tract infections in cats with chronic kidney disease.
White JD, Stevenson M, Malik R, Snow D, Norris JM.
J Vet Intern Med. 2016 Nov;30(6):1824-9. DOI: 10.1111/jvim.14598
Subclinical bacteriuria in older cats and its association with survival.
White JD, Cave NJ, Grinberg A, Thomas DG, Heuer C.
Co-morbidities are common in older cats. Many conditions result in a low urine specific gravity (usg) and, in the case of diabetes mellitus (DM), glucosuria as well. It is commonly believed that dilute urine and glucosuria may predispose to bacterial urinary tract infection (UTI). Mayer-Roenne et al (JFMS 2007) reported UTIs in 12% of 90 cats with hyperthyroidism and 57 cats with DM, and 22% of 77 cats with chronic kidney disease (CKD) and concluded that whether a cat presented with clinical signs or urinalysis results supportive of lower urinary tract (LUT) disease or not, that urine cultures should be part of a work-up for patients with these diagnoses.
This is in contrast with subsequent recommendations. Baliff et al (Vet Clin Path 2008) evaluated whether a urine culture was warranted based on the presence of isosthenuria or not in 614 cats with these same findings (low usg, glucosuria). Bacteria were cultured in 21.7% of cats with hyperthyroidism, 13.2% of cats with DM, and 16.9% of cats with chronic kidney disease (CKD), however a low usg was NOT associated with positive urine culture. Factors that were associated with positive aerobic growth were pyuria, bacteriuria, and hematuria, Persian breed, older age, female sex, and decreased body weight.
A paper in Vet Microbiology by Litster et al (2009) evaluated urinalysis and culture findings from routinely collected samples in cats without LUT signs (subclinical bacteriuria [SB]). 28.7% of 132 cats had positive urine cultures and this was associated with pyuria, hematuria, older age, and female sex.
Looking specifically at cats with CKD, White et al (JFMS 2013), found 18/25 (72%) cats with CKD had SB i.e., no clinical signs of LUT disease or pyelonephritis and that being female and older were risks for positive culture. Interestingly, there was no association between SB or severity of azotemia and longer-term survival. IN JVIM 2016, the same author looked prospectively at 67 nonazotemic cats > 7 years of age to determine the prevalence of, and risk factors associated with, SB and outcome without treatment. Over 3 years, the cats were tested 5 times. The prevalence of SB was 10-13% with none of the cats being treated. Again, females were at higher risk, being 21 times more likely than male cats to develop SB. There was no association with survival or outcome despite not being treated.
Puchot et al (JFMS 2017) determined in a retrospective study that of 6.2% of 500 urine cultures in cats without clinical signs were positive. Again, female cats were at higher risk and SB was associated with bacteriuria and pyuria. However, when positive cultures from cats with LUT signs were included, SB was significantly associated with a usg < 1.030 and CKD.
Moberg et al (JFMS 2020) approached the question of SB prospectively, looking at middle-aged and elderly cats specifically to determine whether age, a body condition score (BCS), sex, health/illness, comorbidities (hyperthyroidism, DM, CKD, hepatic or gastrointestinal diseases) predisposes cats to SB. Over four years they included cats > 6 years of age presented for problems unrelated to their LUT. They defined overweight as a BCS of > 6/9 and obese as > 8/9. Of the 179 cats enrolled, only 11 (6.1%) had SB. BCS was not associated with infection, however, as in other studies, female sex was a risk factor. Interestingly, of the comorbidities, only hepatic disease appeared to be associated with increased risk, however, due to the overall low prevalence of SB in this population, this finding needs to be studied further.
Taken together, these findings are relevant at many levels. For the clinician, there are two questions:
- When should urine be cultured?
- If the culture is positive, should the cat be treated if they are not showing any clinical signs of lower or upper urinary tract disease?
For the client, administration of medication and cost play a role and for the patient, antimicrobials may have immediate negative effects on the gastrointestinal tract. On a global scale, unwarranted antimicrobial use results in serious medical risk of antimicrobial resistance development across species.
The updated International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for diagnosis and management of bacterial urinary tract infections (2019) provides guidance.
Regarding the diagnosis of subclinical bacteriuria this document states that:
- The diagnosis of bacteriuria requires not just cytologically visible bacteria on examination of the urinary sediment, but also a positive culture from a sample collected by cystocentesis.
- While lower than in dogs, the prevalence of SB in cats appears to be between 1-13% in clinically healthy cats.
- There does not appear to be any association between SB and risk of development of cystitis or other infectious complications, however more study is needed.
- In human medicine, antimicrobial therapy is not needed for SB in all but a subset of specific complicated patient diagnoses.
- Urine culture in patients without clinical signs might be considered when pyelonephritis is suspected, to investigate a source of septicemia, if surgery involving the urinary tract is planned, in poorly controlled diabetic patients, in patients with spinal cord disease.
- Urine culture in the face of SB in cats without clinical signs should not be performed even when comorbidities exist.
- Even with isolation of the same bacterial species on subsequent urine cultures, unless clinical signs are exhibited, there is no indication to treat with antimicrobial agents. Retesting for confirmation is also not warranted unless clinical signs develop.
- The presence or absence of pyuria does not indicate whether bacteria grown are clinically relevant or not.
- Bacterial colony count does not differentiate SB from bacterial cystitis regardless of the number of colony forming units/ml. Heavy bacterial growth does not imply greater risk to the patient.
As per Puchot, the decision to culture the urine of a cat without clinical signs of LUT disease and an unremarkable sediment, or even one with pyuria, should be considered on a case-by-case basis and may not be routinely necessary.
Regarding treatment of subclinical bacteriuria, the ISCAID document states that:
- Treatment of SB is discouraged. Should clinical signs possibly reflect LUT disease, a short 3-5 day course of antimicrobials might be considered, discontinuing them if no improvement is seen within 3 days. The selection of specific antimicrobials is described in the document.
- While treatment of a given event may eliminate bacteriuria it does not prevent recolonization.
- Antimicrobial use is not warranted in the face of pyuria without clinical signs.
- Isolation of multidrug resistant organisms also doesn’t warrant treatment of SB.
- Treatment might be considered when there is concern that the bladder might be the source of systemic infection.
- Should imaging or other modalities reveal a lesion that requires treatment (e.g., bladder neoplasia) in an otherwise asymptomatic patient, all other parameters and clinical findings should collectively be taken into consideration when deciding whether or not to use antimicrobials.
Based on current understanding in veterinary medicine, we can apply the rationale for not treating SB in humans, in cats, namely:
a) Lack of evidence for improved outcomes;
b) Responsibilities of antimicrobial stewardship;
c) The benefits of reducing unnecessary treatments (cost, adverse effects of antimicrobials).
Submitted by: Ashlie Saffire, DVM, DABVP (Feline)
J Fel Med Surg 2020; 22:376-383. DOI: 10.1177/1098612X19851303
Assessment of compounded transdermal mirtazapine as an appetite stimulant in cats with chronic kidney disease.
Quimby JM, Benson KK, Summers SC, Saffire A, Herndon AK, Bai S, Gustafson DL.
Cats with chronic kidney disease often experience dysrexia and weight loss which are associated with a poorer prognosis. Appetite management is an important therapeutic goal in feline CKD patients as dysrexia has been perceived as a poor quality of life indicator and can cause emotional distress to owners. Mirtazapine has been demonstrated to be an effective appetite stimulant in cats at a dose of 1.88 mg PO q 48 h, with positive effects on appetite, weight gain, and a reduction in vomiting.
The purpose of this study was to assess the appetite stimulation properties of compounded transdermal mirtazapine (CTM) in client-owned cats. Compounded transdermal mirtazapine was used in this study prior to the release of an FDA-approved product currently available. All cats enrolled were classified as stable International Renal Interest Society (IRIS) stage 2 or 3 chronic kidney disease with a history of decreased appetite and completed a double-blind placebo-controlled crossover prospective study. Nine cats were enrolled in the 3.75 mg arm and 10 cats were enrolled in the 1.88 mg arm. This study had a two-treatment two-period crossover design with a predetermined sequence of AB or BA. The randomly predetermined gel (A or B) was administered to the inner ear pinna every other day for 3 weeks. After a 4-day washout, the other gel (B or A) was administered every other day for another 3 weeks. Owner’s kept records of appetite, rate of food ingestion, begging behavior, activity and vocalization. Physical examination, body weight, body condition score (WSAVA), muscle condition score (WSAVA), and serum biochemistry panel were performed at the end of each treatment period. Serum was collected on day 21 of compounded transdermal mirtazapine administration for measurement of mirtazapine steady-state drug serum concentration.
Results of this study showed that at a dose of 3.75 mg, a statistically significant increase in weight, BCS, appetite, and rate of food consumption was seen. No significant difference in activity or vocalization was seen, however 2 of the 10 cats experienced excessive vocalization as described by owners in the daily log. Weight gain occurred in 100% of the CKD cats during CTM administration, and 67% of the cats lost weight during the placebo phase. Significant increase in serum BUN concentration was seen after CTM administration but no significant changes in serum creatinine, phosphorous or potassium were seen.
Of the cats that received the lower dose of 1.88 mg q48h, a statistically significant increase in weight, increase in BCS, increase in appetite, increase in rate of food consumption, and increase in begging behaviors was seen. No significant difference in activity or vocalization was seen, however 2/10 cats experienced excessive vocalization as described by owners in the daily log. Weight gain occurred in 90% of the CKD cats during CTM administration. Significant increases in serum BUN concentration and serum phosphorus were seen, but no significant changes in serum creatinine or potassium were observed.
In both groups there was no significant correlation between vocalization score and serum mirtazapine level. Serum BUN was the only parameter that displayed a significant period effect in both groups, however the BUN subsequently decreased in the period when placebo was administered, suggesting increase in food consumption may have contributed to the increase in BUN.
In conclusion, transdermal application of CTM at a dose of both 3.75 mg and 1.88 mg was effective in stimulation of appetite in cats with CKD and promoting weight gain. Additionally, the data implies that similar to oral mirtazapine, the lowest effective dose of CTM should be used, and 3.75 mg is not recommended. In some individual cases, the development of excessive vocalization may warrant dose reduction. Although CTM was effective at stimulating appetite and promoting weight gain in this study, concerns regarding the consistency of the compounded product remained a major limitation. Furthermore, the availability of the FDA-approved mirtazapine transdermal ointment for the management of unintended weight loss in cats now makes it unnecessary (and illegal) to compound the medication in the US.
Submitted by: Ashlie Saffire, DVM, DABVP (Feline)
J Fel Med Surg 2020, 22:800–804. DOI: 10.1177/1098612X19873197
Ultrasonographic honeycomb pattern of the spleen in cats: correlation with pathological diagnosis in 33 cases.
Quinci M, Sabattini S, Agnoli C, Bettini G and Diana A.
The ultrasonographic honeycomb pattern of the spleen, sometimes also referred to as ‘moth-eaten’ or ‘Swiss cheese’, is characterized as having a diffuse parenchymal inhomogeneity with multiple small, well-defined hypoechoic foci. Splenomegaly may also be associated with this condition. Lymphoma is often the cause of a moth-eaten pattern in dogs, although occasionally it may be associated with other benign or malignant conditions. In cats, there have been discrepant reports as to the cause of this ultrasonographic appearance with some showing correlation to lymphoma and others showing the appearance associated with non-neoplastic disorders.
The purpose of this study was to evaluate the relationship between the ultrasonographic diffuse honeycomb pattern of the spleen and a pathological diagnosis in cats, determine the prevalence of lymphoma in cats with splenic honeycomb pattern, and to assess the influence of transducer type on the honeycomb pattern visualization.
In this retrospective study, thirty-three cats met inclusion criteria of receiving a complete abdominal ultrasound, evidence of a splenic honeycomb pattern (from retrieved ultrasound images and reports), and cytological or histological examination of the spleen performed within 1 week of ultrasound. Any cat with splenic diffuse ultrasound changes other than honeycomb pattern and solitary masses or multi-focal nodules >1 mm and non-uniform distribution were excluded. Ultrasonography was performed using high-frequency linear transducers and/or micro-convex transducers and a subjective evaluation on image quality of the spleen was made. Ultrasound guided fine-needle aspirates of the spleen were taking using a non-aspiration technique and reviewed by a pathologist. In the presence of a cytologic diagnosis or suspicion of lymphoma, PCR for antigen receptor rearrangements, in the T- or B- cell receptor genes, was performed. In cases where histological samples were available, examination by a pathologist and immunohistochemistry was performed, if necessary.
Results of this study revealed that lymphoproliferative disorders accounted for nearly 70% of feline patients with a honeycomb pattern in the spleen. Among them, 8/33 cases (24.2%) was represented by lymphoma. The remaining conditions included splenitis, extramedullary hematopoiesis and in one case histiocytic sarcoma. Splenomegaly was the most frequent ultrasonographic feature associated with a honeycomb pattern (found in 100% of lymphoma cases), and in all cases where the spleen was of normal size, a non-neoplastic disorder was diagnosed (lymphoid hyperplasia and splenitis). Splenic lymphadenopathy was found to be infrequent in this study.
In conclusion, both benign and malignant disorders can be associated with a honeycomb appearance of the spleen and although still a potential cause, the prevalence of splenic lymphoma is low (24%) in comparison with dogs. Cytologic or histopathologic examination is always recommended, possibly supplemented by PCR for antigen receptor rearrangements, for diagnostic support. Additionally, high-frequency linear transducers were found to be most accurate at recognizing subtle changes in splenic parenchyma as the honeycomb pattern was evident in all the images acquired with a linear transducer, whereas it was not recognized in 37.5% of cases using a micro-convex transducer. High-frequency transducers should always be used in the ultrasound assessment of the spleen.