Almost all cats with mucopurulent or purulent nasal discharge have a bacterial component to their disease. The bacterial agents that have most commonly been described as primary respiratory pathogens in cats include B. bronchiseptica, C. felis, Streptococcus spp., and Mycoplasma spp. Culture of nasal flush samples or tissue biopsy samples yield similar results, but aerobic and anaerobic cultures of nasal flushes were positive significantly more often in one study.15 Culture of nasal biopsies may be more representative of deep mucosal infections but this has not been definitively shown.²⁵ In another study, different organisms were isolated from each collection technique, so it may be most complete to culture both nasal flush and biopsy samples.¹⁴ However, it should be remembered that positive culture results may not correlate with the cause of the clinical signs due to the presence of normal flora and other superficial bacteria.

Although B. bronchiseptica is a well-defined primary pathogen in dogs, the organism can be isolated from both diseased and clinically normal cats.^26–28 Thus, the positive predictive value (PPV) of serologic test results, culture, and PCR assay is low in cats. Many cats have antibodies against B. bronchiseptica, the organism is commonly cultured from cats in crowded environments, and there are sporadic reports of severe lower respiratory disease caused by bordetellosis in kittens and cats in crowded environments or other stressful situations.^29,30 The organism was cultured on necropsy from the lower airways of several cats from shelters in Colorado, and in one shelter, the organism was cultured from 19 of 40 cats (47.5%) with upper respiratory disease.²⁸ However, the significance of infection in otherwise healthy pet cats appears to be minimal. B. bronchiseptica is easily grown, and culture is superior to PCR for this agent because antimicrobial susceptibility testing can be performed on isolates. Because the organism is not usually eliminated by treatment, follow-up culture or PCR assay after treatment has minimal benefit. The risk of transmission to humans is minimal unless there is an immunosuppressed family member.³¹

C. felis is a common differential diagnosis for cats with clinical evidence of conjunctivitis and rhinitis; it is not a common cause of lower airway disease.³² The organism is difficult to culture, so PCR detection of microbial DNA from conjunctival swabs can be useful clinically. In addition, PCR assay results can be used to prove a cattery has been cleared of the infection after treatment.

Mycoplasma spp. are normal commensal organisms of the mucous membranes of multiple species, including cats. Mycoplasma felis has been associated primarily with conjunctivitis but is suspected as a primary cause of rhinitis in cats as well.^15,25,33 There are multiple Mycoplasma species in cats, and the pathogenic potential for most is unknown. If other primary diseases are present, even nonpathogenic Mycoplasma spp. may be associated with the disease process. Mycoplasma spp. culture can be difficult and takes longer than routine bacterial culture; in addition, antimicrobial susceptibility is not provided by most laboratories. Culture of nasal biopsy samples rather than nasal flush samples may increase yield.¹⁵ Mycoplasma spp. PCR assays have some clinical utility, and some assays allow for speciation, which is helpful in assessing the pathogenic potential of the organism. However, because Mycoplasma spp. are common flora, positive PCR assay results often do not predict treatment responses.⁸ Because the organism is not usually eliminated by treatment, follow-up culture or PCR assay after treatment has minimal benefit.

If primary bacterial infection is suspected, oral doxycycline (10 mg/kg/day) is usually effective for cats with rhinitis with or without conjunctivitis (Table 33.1). Doxycycline is the treatment of choice for B. bronchiseptica, Mycoplasma spp., and C. felis infections and was the empiric antibiotic of choice for most panelists in the Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases.⁵ Tooth enamel discoloration in young kittens is less of a concern with doxycycline than tetracycline and the drug is labeled for use at 4 weeks of age in some countries. Doxycycline can also be administered orally at 5 mg/kg, every 12 hours if 10 mg/kg, once daily is associated with adverse effects such as vomiting, diarrhea, and anorexia.

Amoxicillin or amoxicillin–clavulanic acid are good choices in cats as well, particularly if there is secondary overgrowth of Pasteurella spp. due to other disease processes such as FHV-1. Concurrent treatment with a probiotic (Enterococcus faecium strain SF68) was shown to lessen antibiotic-associated diarrhea in cats given amoxicillin–clavulanate.34 However, the beta–lactam antibiotics are cell wall inhibitors and will not be effective for the treatment of Mycoplasma spp. because these organisms lack a cell wall. While cefovecin is easy to administer to cats, it is recommended as a rescue treatment rather than a first-line antibiotic as it is less effective than amoxicillin or doxycycline.^5,35

For cats with chronic rhinitis that fail to respond to doxycycline or amoxicillin, several other antibiotics may prove to be successful.⁵ Pradofloxacin has efficacy against Mycoplasma spp. and also has a gram-negative and anaerobic spectrum.^28,32 Clindamycin (10–15 mg/kg, every 12 hours) penetrates bone and tissue well and has an excellent anaerobic spectrum. Administering the liquid form of this drug orally is generally well-tolerated if given cold. Oral azithromycin (5–10 mg/kg, every 12 hours on the first day and then once every third day) can be tried for cats with suspected resistant bacterial infections.

Doxycycline hyclate (but not doxycycline monohydrate) and clindamycin have been associated with esophagitis and esophageal strictures in cats because of poor secondary esophageal contractions in this species.^36–38 The authors recommend never administering dry pill or capsule forms of any drug to cats. Drugs should be administered in liquid form when possible (compounding may be necessary for some drugs) and followed with food or a 6-mL liquid bolus. Pills or capsules should be administered coated with butter or a gel product (e.g., Nutri-Cal supplement, Vetoquinol) or administered in a pill-delivery treat (e.g., Greenies Pill Pockets, Mars).³⁹

Cats with acute upper respiratory tract signs are treated with an antibiotic for 7 to 10 days.⁵ Chronic bacterial disease may require treatment for 2 to 3 weeks to adequately clear the infection if osteomyelitis exists. Pulse therapy may help some chronically affected cats but may induce antimicrobial-resistant bacteria in other cats. Most cases of bacterial rhinitis are secondary to other diseases, including trauma, neoplasia, inflammation induced by viral infection, foreign body, inflammatory polyp, chronic rhinosinusitis, or tooth root abscessation. Thus, if routine short-term antibiotic therapy fails, a diagnostic workup should be performed.

The currently available B. bronchiseptica vaccine for intranasal administration can be administered as early as 4 weeks of age, has an onset of immunity as early as 72 hours, and has a minimum duration of immunity of 1 year.40 The American Association of Feline Practitioners Feline Vaccine Advisory Panel and the European Advisory Board on Cat Diseases recommend Bordetella vaccination should primarily be used in cats at high risk for exposure and disease, such as those with a history of respiratory problems and those living in shelters with culture-proven outbreaks.^40,41 However, because the vaccine is administered by the intranasal route, mild sneezing and coughing can result, which may influence case management for kittens housed in shelters or humane societies. Because the disease is apparently not life-threatening in adult cats, is uncommon in pet cats, responds to a variety of antibiotics, and is considered minimally zoonotic, routine use of this vaccine in client-owned cats seems unnecessary.

Killed and modified live C. felis–containing vaccines are available. The prevalence of C. felis in cats varies. In studies of client-owned cats, C. felis DNA was amplified from conjunctival swabs of 3.2% of cats with conjunctivitis but 0% of nasal discharges from cats housed in a humane society.^28,42 However, in another study of cats primarily from catteries with conjunctivitis, the agent was common.³³ Prevalence and disease incidence rates should be considered before administration of a vaccine containing C. felis as adverse effects (e.g., lethargy, anorexia, pyrexia) do occur. Because infection of cats by C. felis generally results only in mild conjunctivitis, is easily treated with antibiotics, has variable prevalence rates, and is of minimal zoonotic risk to humans, some have questioned whether C. felis vaccination is necessary in the United States. Duration of immunity for C. felis vaccines may be short-lived, so high-risk cats, such as those in multicat environments or where there is a history of chlamydial infection, should be immunized before a potential exposure whenever possible.

The most common viruses associated with feline respiratory disease are FCV and FHV-1. Coinfections can occur.43 Rarely, cats can be infected by influenza viruses or SARS-CoV-2.^11,44–46 In general, if cats develop signs of upper respiratory diseases after exposure to a sick dog (influenza H3N2) or owner (other type A influenza viruses, SARS-CoV-2), these agents may be higher on the differential list than normal.

Feline calicivirus can be extremely common, particularly in cats from crowded environments such as pet stores, catteries, and shelters.^7,27,47 There are many strains of FCV, and mutations resulting in new strains are common.^48,49 This organism is a common differential diagnosis for cats with evidence of rhinitis, stomatitis, oral ulceration (Fig. 33.7), and occasionally, conjunctivitis. Less commonly, FCV is associated with polyarthritis, lower airway disease in kittens, and virulent systemic disease. Some variants of FCV induce systemic vasculitis in cats (virulent systemic calicivirus [VS-FCV]), and clinical signs can be severe even in previously vaccinated cats.^48–50 The VS-FCV strains arise spontaneously from endogenous FCV strains, and outbreaks have resolved quickly after the initial cases were recognized. Currently, it is unknown how often these outbreaks occur and whether the number of outbreaks is increasing. The VS-FCV strains evaluated to date have been genetically and antigenically diverse.⁴⁸

Virus isolation can be used to document current infection with FCV, but it takes at least several days for results and it is not performed by all laboratories. Because of widespread exposure and vaccination, the PPV of serologic tests is poor. Reverse transcriptase (RT) PCR assays can be used to amplify the RNA of FCV, influenza viruses, calicivirus, and SARS-CoV-2; results can be made available quickly. However, these assays also amplify vaccine strains of FCV.51 Feline calicivirus RNA can be amplified from samples collected from normal cats as well as clinically ill cats, so molecular assays also have poor PPV. In addition, amplification of FCV RNA cannot be used to prove VS-FCV infection. False-negative results can occur with FCV molecular assays if inadequate RNA is present on the swab submitted or if the organism has been cleared to levels below the sensitivity limits of the assay by specific immune responses. Because treatment does not eliminate FCV infection, there is no benefit to follow-up testing by molecular methods.

Feline herpesvirus is a common differential diagnosis for cats with clinical evidence of rhinitis, stomatitis, conjunctivitis, keratitis, and facial dermatitis. Because of widespread exposure and vaccination, the PPV of serologic tests is poor. Infection with FHV-1 can be documented by direct fluorescence staining of conjunctival scrapings, virus isolation, or PCR.⁵² Herpesvirus DNA can be amplified from conjunctival cells of approximately 20% of healthy cats; therefore, the PPV of PCR assays for this agent is low. Current PCR assays also amplify vaccine strains of FHV-1, further lessening the PPV.^6,51 Quantitative PCR may ultimately prove to correlate with the presence or absence of disease but failed to correlate to presence of conjunctivitis in one small study in the authors’ laboratory.⁴² The negative predictive value of the FHV-1 PCR assays is also in question because many cats that are likely to have FHV-1–associated disease are PCR negative. This may relate to clearance of FHV-1 DNA from tissues by the immune response. Tissue biopsies have greater sensitivity than conjunctival swabs for detection of FHV-1 DNA but do not necessarily have greater predictive value.⁵³ Feline herpesvirus DNA can be amplified from the aqueous humor of some cats, but whether this indicates FHV-1–associated uveitis is unknown.⁵⁴ A randomized clinical trial failed to show an association between FHV-1 PCR assay results and response to treatment with topical cidofovir.⁸ These results suggest that veterinarians should base decisions to treat on clinical findings rather than PCR panel results. Because treatment does not eliminate FHV-1 infection, there is no benefit to follow-up virus isolation or PCR testing.

Therapy for FCV consists mainly of supportive care, which is often needed for cats with VS-FCV infections, and may consist of intravenous fluid therapy, antibiotics for concurrent bacterial infection, and interferon. Interferons may augment immune responses to viral infections by upregulating key cytokines and have shown clinical benefit for treatment of FCV in some studies.55,56 Feline interferon (not available in all countries) has been used to improve quality of life in cats with FeLV and FIV infections.⁵⁷ In one study, low-dose oral interferon-alpha therapy (10 U/kg/day, alternating 7 days on, 7 days off, for 6 months) improved quality of life in cats with FIV infections.⁵⁸ The effect of oral interferon is thought to be from mediation of inflammatory cytokines. There may also be effects against chronic FHV-1 or FCV infections, but controlled data are not available.

Antiviral drugs have become more popular in the management of cats with acute or chronic FHV-1 infections. Currently available antiviral medications are efficacious only for DNA viral infections such as FHV-1, and not RNA viruses such as FCV, because they interfere with viral DNA synthesis and thus viral replication. Famciclovir is the drug that has been studied the most and shown to be safe and effective in cats. It is used for acute and long-term therapy for cats with FHV-1 infections.^59–62 The most effective oral dosages are 40 mg/kg or 90 mg/kg, every 8 hours; 90 mg/kg is needed to give the best concentrations in tears.⁶² Treatment with famciclovir will be needed for several weeks in most cases; short durations are not always effective.⁶³ Not all cats with signs of upper respiratory infection will respond to famciclovir as there are other causes of this clinical syndrome.⁵⁹ In the future, subconjunctival implants of antiviral drugs such as penciclovir may be used to ease administration.⁶⁴ There are currently no drugs known to have efficacy against FCV in cats, but research on drugs such as nitazoxanide and mizoribine is ongoing, with some promising results in vitro and in research cats.⁶⁵

Historically, idoxuridine and trifluridine have been used topically in cats with conjunctivitis or keratitis from FHV-1 infection. However, these drugs are no longer indicated for use in cats if cidofovir is available as it has been shown to be safe and effective for FHV-1 associated ocular disease and it decreased FHV-1 shedding in one experimental study.⁶⁶ Cidofovir is formulated to a 0.5% solution in methylcellulose and applied every 12 hours to affected eyes. Studies for long term use of this drug are lacking.

Oral lysine (250 to 500 mg, every 12–24 hours) has been used in cats with suspected FHV-1 infection for many years. However, supplementation of cats housed in shelters with lysine has not been shown to lessen occurrence rates of upper respiratory tract disease.^67,68 These studies are complicated by the fact there are multiple causes of upper respiratory infections in cats in shelters and the only cause that might respond to lysine is FHV-1. If used in the management of FHV-1 associated diseases, lysine is likely to be more effective as a prophylaxis rather than as a treatment for active disease based on experience with herpes simplex infections in humans.⁶⁹

Intranasal modified live vaccines may have therapeutic effects. In one study, some cats with chronic rhinitis that had failed multiple other treatments had apparent treatment responses after one dose of an intranasal modified live FHV-1 and FCV vaccine was split between nares.⁵⁵ In that study, more cats had positive responses to vaccine immunotherapy than to 14 days of high-dose interferon therapy administered subcutaneously. If there is a positive response to intranasal vaccination in a cat with chronic disease, based on one author’s (ML) experience, this form of immunotherapy can be administered up to three times per year if clinical signs recur. There is evidence that stimulating the innate immune system may help lessens signs of FHV-1 in exposed cats.⁷⁰

Chronic administration of one commercially available probiotic (FortiFlora, Purina Veterinary Diets) was shown to enhance T-helper lymphocyte numbers in cats.⁷¹ When this probiotic was administered to cats with chronic FHV-1 infections before being subjected to mild stress, improved conjunctivitis scores were noted in some of the cats in the treatment group.⁷² See the section on chronic rhinosinusitis for a discussion of other nonspecific therapies.

Vaccination of kittens against FHV-1 and FCV can result in immunity that will lessen disease if exposed to the pathogens in the future. Inactivated and modified live vaccines containing FHV-1 and FCV for parenteral administration are available in most countries and modified live vaccines containing FHV-1 and FCV for intranasal administration are available in some countries. Specific pathogen-free cats inoculated with one dose of a modified live intranasal vaccine containing FHV-1, FCV, and panleukopenia virus had significantly less clinical signs than control cats as soon as 4 days when challenged with virulent FHV-1 in one study.73 In a follow-up study, administration of one dose of an intranasal vaccine containing modified live FHV-1 and FCV was shown to cross-protect against B. bronchiseptica challenge 7 days later which confirms the vaccination induced nonspecific immune responses.⁷⁴ Thus, the intranasal route of administration may be preferred for the primary or booster immunization of kittens housed in environments at high risk for exposure to FHV-1 or FCV, such as shelters, humane societies, catteries, boarding facilities, and multicat households. However, owners should be informed that administration of intranasal FHV-1 and FCV vaccines can rarely induce transient mild sneezing or coughing. Vaccine recommendations for FHV-1 vary slightly amongst different countries; the American Association of Feline Practitioners, the Advisory Board on Cat Diseases, and the World Small Animal Veterinary Association are excellent sources of information (Box 33.3).^40,52

Inactivated vaccines containing more than one FCV strain are available in some countries. In the United States, one product contains a traditional FCV vaccine strain as well as a VS-FCV strain. Cross-neutralization studies show that cats inoculated with more than one FCV strain inactivate more FCV strains in vitro than cats inoculated with one FCV strain.^75,76 In addition, one challenge study illustrated that kittens vaccinated with a dual-strain product were protected from clinical signs of VS-FCV.⁷⁷ Routine use of FCV containing vaccines generally mirror those of FHV-1 (Box 33.3).

As discussed, feeding lysine to cats in animal shelters to prevent upper respiratory tract disease has been ineffective. Similarly, in one study, administration of one oral dose of famciclovir on intake to a shelter was also ineffective.⁷⁸ In contrast, lessening stress may be helpful to decrease upper respiratory tract disease in homes and shelters.⁷⁹ See the section on chronic rhinosinusitis for more information.