The primary objectives of this session are to review the known bacterial and viral causes of the feline upper respiratory disease complex followed by a discussion of optimal diagnostic tests, treatments and preventions. Please see the ISCAID respiratory treatment guidelines for further information on this very important topic (Lappin et al. 2017).

Bacterial Causes

Almost all cats with mucopurulent or purulent nasal discharge have a bacterial component to their disease. Primary bacterial disease is rare but may be associated with Bordetella bronchiseptica, Mycoplasma spp. and Chlamydia felis. Streptococcus equi var. zooepidemicus may also be associated with clinical illness in some cats. In one Morris Animal Foundation-sponsored study, we showed Mycoplasma to be more common than FHV-1 and were associated with illness. Recently it was shown that Bartonella spp. are not causes of rhinitis in cats. Both B. bronchiseptica and Mycoplasma spp. can be associated with bronchitis in cats. Chlamydiosis, in general, is a mild infection resulting only in conjunctivitis.

If primary infections are suspected, doxycycline 10 mg/kg, PO, once daily (or divided BID) or topical administration of tetracyclines (conjunctivitis) are usually effective. Amoxicillin is the other empirical treatment recommended for management of bacterial rhinitis of <10 days duration (Lappin et al. 2017). Cats with acute disease only need to be treated for 7 to 10 days. Most cases of bacterial rhinitis are secondary to other diseases including trauma, neoplasia, inflammation induced by viral infection, foreign bodies, inflammatory polyps, and tooth root abscessation. Thus, if routine antibiotic therapy fails, a diagnostic workup should be performed. After other primary causes are excluded, rescue drugs like quinolones, azithromycin, potentiated penicillins, or cephalosporins can be considered. Pradofloxacin has been shown to be a good choice as a rescue drug for treatment of chronic bacterial rhinitis as this quinolone is effective against anaerobes and aerobes and enhanced activity against Mycoplasma spp. (Spindel et al. 2008).

Since bacterial rhinitis leads to chondritis and osteomyelitis, antibiotic therapy may be required for days to weeks and should be continued for weeks in cats with chronic disease.

Viral Diseases

Herpesvirus 1 (rhinotracheitis; FHV-1) and calicivirus (FCV) are the most common viral causes of sneezing and nasal discharge in the cat. If oral ulcers are present, calicivirus is most likely. If corneal ulcers are present, herpesvirus 1 is most likely. FHV-1 has now also been associated with chronic stomatitis, facial dermatitis, and endogenous uveitis. Viral rhinitis with or without secondary bacterial infection can be recurrent. FHV-1 can be documented by direct fluorescent staining of conjunctival scrapings, virus isolation, or polymerase chain reaction. Since FHV-1 DNA can be detected in conjunctival cells of approximately 25% of healthy cats, the positive predictive value of these tests in diseased cats is low. Quantitative PCR may ultimately prove to correlate to the presence or absence of disease. Currently used PCR assays also detect vaccine strains of FHV-1. RT-PCR assays can be used to amplify the RNA of FCV. However, these assays have the same problems with predictive value as those to detect DNA of FHV-1. In one recent publication, we showed that PCR assay results for FHV-1 or Mycoplasma failed to correlate to treatment responses to either an antiviral drug or an antibiotic (Zirofsky et al. 2018). Thus, performance of these PCR assays has low positive predictive value.

Feline viral rhinitis with or without secondary bacterial infection can be recurrent. There are no consistently effective primary therapies. For FHV-1, lysine at 250–500 mg, PO, once or twice daily may be helpful in some cats and has been shown to be safe but should be given as a dose, not fed with food. Lysine has been shown to be ineffective for prevention of upper respiratory tract infections in 2 separate shelter studies and so should probably not be used for this purpose.

Administration of human alpha 2b interferon at 50 U, PO, daily may help some cats with suspected chronic calicivirus or FHV-1 infection. This can now be formulated for practitioners by prescription at some pharmacies (www.roadrunnerpharmacy.com) in the USA. Topical administration of alpha interferon in saline to the eyes of cats with conjunctivitis or the nose may aid in the management of some cats but has not been proven in a controlled study. Lysine and alpha interferon are unlikely to lead to a cure, but hopefully will lessen clinical signs of disease. Intranasal administration of modified live, intranasal FHV-1 and FCV vaccines may lessen disease in some chronically infected cats. If there is a positive response to intranasal vaccination in a cat with chronic disease, I will use this form of immunotherapy up to 3 times per year (Fenimore et al. 2015). The intranasal vaccine has been shown to potentiate cell-mediated immunity to FHV-1 better than parenteral vaccination.

Acyclovir is an anti-herpesvirus drug for use in people but can be toxic to cats and so should not be used.

Famciclovir is safer and more effective than acyclovir and is now being used for long-term therapy. One dose that has been used is 1/2 tablet of a generic 250-mg tablet (125 mg), PO, q8–12 h. The drug is safe at up to 90 mg/ kg, PO, q8h and so the dose should be increased if the initial response is suboptimal and FHV-1 is still suspected. However, it is now known that famciclovir is excreted in high levels in the tears for 4 hours after a dose and so topical treatment with anti-FHV-1 drugs may not be needed if famciclovir is prescribed at 90 mg/kg, PO 2–3 times daily. Administration of one dose of famciclovir (125 or 500 mg) on admission to an animal shelter was ineffective in lessening clinical signs of disease. Topical cidofovir (product for humans) can be used for the treatment of FHV-1 conjunctivitis twice daily and was effective in a controlled research project. The drug was easier to administer (twice daily) than idoxuridine or other anti-FHV-1 ocular therapies and does not cause as much irritation. This drug is available in some compounding pharmacies (www.rxfixer.com) (VIN editor: link is not relevant, does not lead to compounding pharmacies as of 1/29/19).

Many of the cats with chronic recurrent signs of disease are likely to be infected by FHV-1 or FCV. Stress reactivation of feline viral infections is thought to be common, in particular for FHV-1. All the principles of stress relief for management of feline interstitial cystitis also apply to cats with recurrent signs of URI. In a recent published study, we showed that use of a facial pheromone diffusor could lessen recurrent signs of FHV-1 in a mild stress model in experimentally inoculated cats (Contreras et al. 2017). The commercially available probiotic Enterococcus faecium SF-68 (FortiFlora, Purina) is a known immune stimulant in cats and feeding this probiotic to cats with FHV-1 infection lessened recurrent disease in a stress model (Lappin et al. 2009).

Feline leukemia virus and feline immunodeficiency virus can induce immunosuppression predisposing to bacterial rhinitis. However, there is no universally effective treatment. Interferon alpha as described can be tried. In addition, AZT at 5 mg/kg, PO, twice daily can be tolerated and improved clinical parameters in some cats with FIV. Both FIV and FeLV have been associated with nasal lymphoma and so if upper respiratory tract signs occur in retrovirus-positive cats, this neoplasm should be excluded.

References

1.  Contreras ET, Hodgkins E, Tynes V, Beck A, Olea- Popelka F, Lappin MR. Effect of a pheromone on stress-associated reactivation of feline herpesvirus-1 in experimentally inoculated kittens. J Vet Intern Med. 2017 Dec 8. doi: 10.1111/jvim.14894. [Epub ahead of print].

2.  Fenimore A, Carter K, Fankhauser J, Hawley JR, Lappin MR.^. Evaluation of intranasal vaccine administration and high-dose interferon-α 2b therapy for treatment of chronic upper respiratory tract infections in shelter cats. J Feline Med Surg. 2015 Aug 12. pii: 1098612X15596199. [Epub ahead of print].

3.  Lappin MR, Blondeau J, Boothe D, Breitschwerdt EB, Guardabassi L, Lloyd DH, Papich MG, Rankin SC, Sykes JE, Turnidge J, Weese JS. Antimicrobial use guidelines for treatment of respiratory tract disease in dogs and cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases. J Vet Intern Med. 2017;31:279–294.

4.  Lappin MR, Veir JK, Satyaraj E, et al. Pilot study to evaluate the effect of oral supplementation of Enterococcus faecium SF68 on cats with latent feline herpesvirus 1. J Feline Med Surg. 2009;11:650.

5.  Spindel ME, Veir JK, Radecki SV, et al. Evaluation of pradofloxacin for the treatment of feline rhinitis. J Feline Med Surg. 2008;10:472.

6.  Thomasy SM, Shull O, Outerbridge CA, Lim CC, Freeman KS, Strom AR, et al. Oral administration of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease attributed to feline herpesvirus type 1: 59 cases (2006–2013). J Am Vet Med Assoc. 2016;249:526–538.

7.  Zirofsky D, Rekers W, Powell C, Hawley J, Veir J, Lappin M. Feline herpesvirus 1 and Mycoplasma spp. conventional PCR assay results from conjunctival samples from cats in shelters with suspected acute ocular infections. Top Companion Anim Med. 2018;33:45–48.