28
Antimicrobial Therapy in Dogs and Cats

Jane E. Sykes and Peter Damborg

Veterinarians who treat dogs and cats work in a wide variety of situations, from rural one‐person practices with limited small animal caseloads to specialized multi‐veterinarian canine and feline hospitals and advanced referral centers. The range of facilities and services available, and the pet owners’ ability to pay, are correspondingly varied, although the veterinarian’s goal remains the same – to provide effective, safe, and economical treatment for patients in their care. Antimicrobial drugs often form part of the treatment regimen chosen, but the decision to use them must not be made lightly; these are not placebos or antipyretic agents, nor do they replace the fundamental diagnostic skills of history taking, physical examination, and logical analysis of clinical findings.

Concerns continue to increase regarding the use and misuse of antimicrobial drugs in companion animals, including the emergence of methicillin‐resistant staphylococci and multidrug‐resistant Gram‐negative bacteria in companion animals, and the potential for spread of these bacteria between humans and their pets. A policy of selective and restricted use of antimicrobials is important to avoid potential criticism and externally imposed restrictions on the veterinary use of these drugs. Widespread, inappropriate use of these agents can reduce efficacy and create problems with infections that are more difficult and expensive to treat. This has been demonstrated repeatedly by outbreaks of nosocomial infections in human and veterinary hospitals, attributable in part to selection pressure applied by overuse of antimicrobials, especially for prophylaxis in surgical and nonsurgical patients. Overuse of antimicrobials can also lead to other unanticipated adverse effects such as hepatotoxicity, esophageal stricture formation, or immune‐mediated reactions.

At the time of writing, guidelines have been developed by the International Society for Companion Animal Infectious Diseases (ISCAID) for treatment of urinary tract infections in dogs and cats (Weese et al., 2019), superficial pyoderma (Hillier et al., 2014), and respiratory infections (Lappin et al., 2019). The reader is referred to these open‐access documents for more information. In addition, readers should consult national treatment guidelines when available. Unlike international or generic guidelines such as this chapter, national guidelines can take into consideration important local factors such as resistance patterns, availability of antimicrobial drugs, legislation on animal drug use, owner economy, and even traditions and culture for antimicrobial use.

Antimicrobial Drug Chemotherapy

The principles that govern selection and therapeutic use of antimicrobial drugs are outlined in Chapter 6 and apply to all animal species, which includes dogs and cats. An adequate clinical assessment is of prime importance in deciding (i) whether to treat with antimicrobials; (ii) the choice of antimicrobial; and (iii) the estimated duration of treatment. This should suggest presence of infection, the body systems involved, and the pathogens likely to be responsible.

There are many causes of an increased rectal temperature other than bacterial infection. Increased rectal temperatures also occur in other pathological conditions (e.g., viral infections, neoplasia, drug reactions, immune‐mediated disorders, other nonspecific inflammatory diseases such as pancreatitis, heat stroke and pathologically increased muscle activity) and some physiological states (e.g., exercise, excitement, high ambient temperature, and humidity). Conversely, dogs or cats with normal rectal temperatures may have life‐threatening systemic infections, and cats with septic shock are frequently hypothermic. Leukocytosis is also not indicative of infection and occurs commonly with nonspecific inflammatory processes such as pancreatitis, immune‐mediated diseases, neoplasia, trauma, excitement, stress, and glucocorticoid administration.

Wherever possible, treatment with broad‐spectrum antimicrobials should be postponed until the results of further laboratory tests confirm that infection is present. The one exception to this rule is if signs of severe sepsis or septic shock are present, such as fever together with prolonged capillary refill time, tachycardia, tachypnea, and brick red mucous membranes in dogs; and fever or hypothermia, bradycardia, and/or tachypnea in cats. In this case, initial blood cultures should be collected, followed by immediate parenteral treatment with broad‐spectrum antimicrobials.

If the infection site is accessible for specimen collection, the most rapid and inexpensive way to identify the presence of infection is to examine smears of fine needle aspirates treated with Gram stain and/or a Romanovsky method (Giemsa^{^®}, Diff‐Quik^{^®}). This can indicate whether bacteria are present and whether they are rods or cocci, as well as whether they are Gram positive or Gram negative. The identification of phagocytized bacteria within neutrophils or monocytes also supports infection, as opposed to contamination. In the absence of Gram staining, most cocci that infect dogs or cats are Gram positive and, with a few exceptions, rods are usually Gram negative.

A decision on possible treatments can then be made by (i) considering these findings alongside the known spectrum of activity of various antimicrobial drugs; (ii) the ability of these antimicrobial drugs to penetrate the site of infection; and (iii) information on the regional prevalence of drug resistance, which should be based on the results of culture and susceptibility testing for other animals seen in the practice in the recent past (e.g., for staphylococci, whether methicillin resistance is widespread or rare). If the site of infection is not accessible for specimen collection, initial drug selection can be based on knowledge of the site of infection, the pathogens more frequently implicated there, and the likely drug susceptibility of those organisms. This process can be based on personal experience or on published information like that shown in Table 28.1 for dogs and Table 28.2 for cats. In many routine or less serious infections, treatment on this “best‐guess” basis will prove satisfactory, without the need for additional investigation.

The drug with the narrowest antimicrobial spectrum should be selected, to reduce effects on untargeted microflora. Cost, route of administration, drug penetration in target tissue, risk of owner/patient noncompliance, and the potential for adverse effects are other factors to consider. Examples of adverse effects that might lead to selection of alternate drugs include, although rare, the potential for development of acute blindness in cats treated with enrofloxacin, and the prevalence of hypersensitivity reactions in Doberman Pinschers treated with trimethoprim‐sulfonamide combinations. Drug selection may also have to be modified in renal failure, liver failure, pregnancy, or neonatal patients (Table 28.3) (see also Chapter 4).

Table 28.1 Antimicrobial drug selection for selected infections in dogs.^a

Site	Diagnosis	Common infecting organisms	Comments	Suggested empirical therapy^b
Skin and subcutis	Superficial pyoderma	Staphylococcus (especially S. pseudintermedius).	Attempt to identify underlying causes (most often allergic dermatitis, but also endocrinopathies). Prolonged treatment may be needed. Culture of lesions (preferably pustules) is particularly indicated in regions where methicillin‐resistant S. pseudintermedius is widespread or if disease is refractory or recurrent.	First choice is topical treatment, e.g., with antiseptic shampoos, as an alternative to systemic antimicrobial drugs. Clindamycin or first‐generation cephalosporins (e.g., cephalexin, cefadroxil). Alternatives include amoxicillin‐clavulanate, trimethoprim and trimethoprim‐sulfonamides, lincomycin, or erythromycin. Use of other drugs should be based on culture and susceptibility.
	Deep pyoderma	Staphylococcus, E. coli, Proteus, Pseudomonas.	Attempt to identify underlying causes. Prolonged treatment may be needed. Culture of skin lesions strongly recommended.	See superficial pyoderma, although often topical antimicrobial treatment cannot be used alone. Drugs that are active against Gram‐negative bacteria may be required based on culture and susceptibility.
	Surface pyoderma	Staphylococcus, Streptococcus.	Often secondary to skin folds or self‐trauma. Local cleansing and topical antibacterials are sufficient.
	Malassezia dermatitis	Malassezia pachydermatis.	Identify and eliminate underlying causes. Topical treatment with shampoos is recommended.	Itraconazole or fluconazole.
	Dermatophytosis	Microsporum, Trichophyton.	Topical treatment and environmental clean‐up required. Localized lesions may not require systemic treatment.	Itraconazole or fluconazole. Alternatives include griseofulvin or terbinafine.
	Bite wounds, traumatic and contaminated wounds	Staphylococcus, Streptococcus, Enterococcus, Pasteurella, E. coli, Pseudomonas, anaerobes.	Wound irrigation and debridement. Antibiotics of questionable prophylactic benefit for contaminated wounds.	Amoxicillin‐clavulanate or ampicillin‐sulbactam. For serious infections that may involve resistant Gram‐positive and Gram‐negative bacteria, consider a combination of an aminoglycoside and ampicillin‐sulbactam.
	Anal sac inflammation/abscessation	E. coli, Enterococcus, Proteus, anaerobes.	Local treatment is usually indicated. Systemic antimicrobials can be used if severe infection is present.	Amoxicillin‐clavulanate.
Ear	Otitis externa	Staphylococcus, and less often streptococci, Pseudomonas, E. coli, Proteus or Malassezia.	Identify and address underlying causes (allergic dermatitis, foreign bodies, ear mites). Ear cleaning. Consider topical glucocorticoid and analgesic.	Topical antimicrobial treatment is preferred. For mild cases, treatment with antiseptic ear cleaner is often sufficient. For antibiotics, choice should be based on ear cytology and if possible, integrity of the tympanic membrane. Topical enrofloxacin solutions may be considered or if rods are present, topical preparation that contains aminoglycosides, polymixin B, or ticarcillin‐clavulanate. Ointments that contain clotrimazole, miconazole, or posaconazole may be required if Malassezia is present.
	Otitis media and interna	As for otitis externa.	Otitis externa also often present. Identify and address underlying causes. Treat as for otitis externa but additional systemic treatment indicated. Avoid ototoxic drugs.	Treatment should be based on ear cytology and culture and susceptibility. If cocci are present, cephalexin is recommended, but if rods are present, consider a fluoroquinolone. Systemic antifungal drug treatment is indicated if Malassezia is present.
Eye	Superficial ocular infection	Staphylococcus, Streptococcus, E. coli, Proteus.	Identify and correct underlying causes (e.g., poor eyelid conformation, dystichiasis, allergies, keratoconjunctivitis sicca).	Topical neomycin‐polymixin‐bacitracin, fusidic acid or chloramphenicol.
Upper respiratory	Bacterial rhinitis	Usually resident bacteria that invade opportunistically. In crowded environments, Bordetella bronchiseptica, Streptococcus equi subsp. zooepidemicus, or Mycoplasma (especially M. cynos) may be involved.	Treatment with antibiotics alone is rarely curative unless infection is caused by transmissible bacteria (e.g., shelter environments). For other situations, underlying causes (neoplasia, aspergillosis, foreign bodies, nasal mites) must be identified and addressed.	If transmissible bacterial infections are suspected, doxycycline is the treatment of choice because it is active against Bordetella, Streptococcus, and Mycoplasma. Amoxicillin‐clavulanate is an alternative but is not active against Mycoplasma.
	Fungal rhinitis	Usually Aspergillus spp.	Rule out nasal neoplasia. Secondary bacterial infection may be present.	Debridement and topical clotrimazole or enilconazole. Systemic itraconazole or voriconazole are alternatives if cribriform plate destruction is present.
Lower respiratory	Canine infectious respiratory disease complex	Viruses, Bordetella bronchiseptica, Streptococcus equi subsp. zooepidemicus, Mycoplasma (especially Mycoplasma cynos).	Most recover untreated in 7–10 days. Treat if mucopurulent discharges are severe or systemic illness is present. Consider the possibility of distemper pneumonia.	Doxycycline. Amoxicillin‐clavulanate is an alternative but is not active against Mycoplasma spp.; consider nebulized gentamicin if refractory to treatment and if infection with B. bronchiseptica has been confirmed with culture.
	Bacterial pneumonia	Single or mixed infections that involve various facultative (especially Gram‐negative) bacteria and anaerobes if aspiration pneumonia is present.	Aerobic culture and susceptibility testing on transtracheal wash or bronchoalveolar lavage indicated. Consider anaerobic culture if aspiration suspected.	A combination of clindamycin and enrofloxacin is a suitable initial choice pending the results of culture and susceptibility testing. If anaerobes are suspected, a beta‐lactam/beta‐lactamase inhibitor combination may be more appropriate (such as ampicillin‐sulbactam and enrofloxacin).
	Pneumocystis pneumonia		Secondary to inherited or acquired immunodeficiency.	Trimethoprim‐sulfonamide combinations.
	Pyothorax	Various and often mixed, which includes anaerobes, Actinomyces, Nocardia, etc.	Culture and susceptibility testing on pleural fluid indicated. Chest tube placement required to drain pus; surgery may be indicated.	Ampicillin‐sulbactam and enrofloxacin are suitable initial choices that should be adjusted based on results of culture and susceptibility testing; regardless of culture results, anaerobes should also be targeted. If Nocardia is suspected based on history or cytology, trimethoprim‐sulfonamide should be used.
Gastrointestinal and abdominal	Periodontitis, gingivitis	Resident anaerobic and facultative bacteria.	Dental cleaning, scaling, other dental treatment may be needed.	Clindamycin or amoxicillin‐clavulanate.
	Malar or carnassial abscess	Resident oral flora.	Dental extractions, alveolar bone curettage, drainage.	Clindamycin or amoxicillin‐clavulanate.
	Bacterial enteritis	Salmonella spp.	Can be found in healthy and sick dogs. When present with diarrhea and systemic illness is not present, treatment is not indicated.	If systemic infection is present (i.e., with fever, lethargy, changes on the CBC, positive blood cultures), parenteral fluoroquinolones indicated.
		Campylobacter spp.	Often present in healthy dogs	If systemic infection is present (i.e., with fever, lethargy, changes on the CBC, positive blood cultures), macrolide indicated.

		Clostridium perfringens, Clostridioides difficile.	Present in many healthy dogs. Diagnosis of clostridial diarrhea requires demonstration of toxin production by toxin ELISA assays in association with diarrhea. Significance may still be unclear even when toxin is detected.	If systemic infection is present (i.e., with fever, lethargy, changes on the CBC, positive blood cultures), metronidazole indicated.
	Giardiasis	Giardia	Infection often subclinical. Some assemblages/species may be zoonotic.	Fenbendazole. Alternatives are metronidazole, tinidazole, or ronidazole.
	Coccidiosis	Cystoisospora	Clinical illness usually associated with young age or co‐infections with other enteric pathogens.	Sulfonamide +/‐ trimethoprim. Alternatives are ponazuril or toltrazuril (Europe).
	Parvoviral enteritis	Secondary facultative and anaerobic bacteria from the gastrointestinal tract.	Parenteral antimicrobial drug treatment is important to counteract opportunistic bacterial invasion.	Ampicillin‐sulbactam or cefazolin (mild disease); ampicillin‐sulbactam and a fluoroquinolone (severe disease).
	Cholecystitis, cholangiohepatitis	E. coli, Salmonella, Enterococcus, anaerobes.	Address underlying causes (e.g., disrupted bile flow). Consider ultrasound‐guided collection of bile for aerobic and anaerobic culture and susceptibility.	Beta‐lactam and beta‐lactamase inhibitor combination with an aminoglycoside or a fluoroquinolone
	Bacterial peritonitis	Mixed anaerobes and facultative enteric bacteria.	Surgical exploration and lavage may be needed. Culture and susceptibility testing indicated.	As for cholecystitis/cholangiohepatitis.
Urinary and urogenital	Lower urinary tract infection/bacterial cystitis	E. coli, Staphylococcus, Proteus, Streptococcus, Enterococcus, Enterobacter, Klebsiella, Pseudomonas	Identify and address underlying cause whenever possible (calculi, tumor, incontinence, hyperadrenocorticism).	Trimethoprim‐sulfonamide or amoxicillin. Amoxicillin‐clavulanate could be used where the regional prevalence of beta‐lactamase production is high.
	Pyelonephritis	See lower urinary tract infection.	Culture and susceptibility recommended. Prolonged treatment required.	Amoxicillin and a fluoroquinolone.
	Prostatitis	See lower urinary tract infection.	Culture and susceptibility recommended. Prolonged treatment required. Surgery may be needed for prostatic abscessation or for castration.	Trimethoprim‐sulfonamide or a fluoroquinolone. Chloramphenicol is an alternative.
	Orchitis/epididymitis	E. coli, Brucella spp.	May be associated with urinary tract infection and prostatitis. Castration may be required.	Trimethoprim‐sulfonamide or a fluoroquinolone. Doxycycline and an aminoglycoside (streptomycin or gentamicin) for Brucella; addition of a fluoroquinolone and rifampin could also be considered for treatment of brucellosis.
	Vaginitis/ balanoposthitis	Resident bacteria, herpesvirus, Mycoplasma, Brucella.	Identify predisposing factors. Local cleaning usually sufficient. Puppy vaginitis resolves with maturity.
	Metritis, pyometra	E. coli, Streptococcus, Staphylococcus, other Gram‐negative bacteria, sometimes anaerobes.	Ovariohysterectomy recommended. Culture uterine contents at surgery. Prostaglandin and antibiotic treatment may be successful for open pyometra.	Ampicillin‐sulbactam and either a fluoroquinolone or an aminoglycoside.
	Mastitis	E. coli, Staphylococcus, Streptococcus.	Do cytology and culture and susceptibility testing.	If weaning possible, use chloramphenicol (unaffected by milk pH). Otherwise, amoxicillin‐clavulanate pending results of culture and susceptibility.
Musculoskeletal	Osteomyelitis, septic arthritis	Staphylococcus and to a lesser extent Streptococcus, Enterococcus, E. coli, Proteus, Pseudomonas, Klebsiella, anaerobes.	Culture and susceptibility strongly recommended. Requires debridement and drainage and prolonged treatment with antimicrobial drugs. Local antimicrobial treatment (impregnated beads) may also be useful.	Withhold treatment until results of culture and susceptibility testing are available. If empirical treatment is considered necessary, clindamycin or clindamycin and an aminoglycoside (if Gram‐negative bacteria or methicillin‐resistant staphylococci) could be considered. Chloramphenicol is an alternative in regions where the prevalence of methicillin‐resistant staphylococci is high, but some may be resistant to chloramphenicol.
	Diskospondylitis	Staphylococcus, Streptococcus, Brucella, E. coli, Aspergillus.	Blood culture and susceptibility recommended, also Aspergillus antigen and Brucella antibody serology. Disk aspiration or urine culture may also yield a causative organism.	Amoxicillin‐clavulanate or cephalexin; consider addition of a fluoroquinolone if there is no response after a week, and diagnostic test results are negative.
Nervous system	Bacterial meningitis	Staphylococcus, Pasteurella, Actinomyces, Nocardia, sometimes anaerobes.	CSF culture and susceptibility recommended.	Consider a combination of ampicillin and metronidazole (which has improved penetration). Alternatives are trimethoprim‐sulfonamide or chloramphenicol.
	Tetanus	Clostridium tetani.	Nursing care, antitoxin, wound debridement.	Metronidazole or penicillin.
	Botulism	Clostridium botulinum.	Nursing care.	Not indicated.
	Hepatic encephalopathy	Normal intestinal flora.	Oral antimicrobial drugs to suppress ammonia production by gastrointestinal bacteria; add lactulose and restricted protein diet.	Ampicillin or neomycin.
Other bacterial	Actinomycosis	Actinomyces.	Mostly with other bacteria in infections of the subcutaneous tissues, thorax, abdomen, retroperitoneum. Drainage, debridement, prolonged treatment needed. Identify and remove any plant foreign bodies.	Penicillin G or ampicillin.

	Bacteremia, infective endocarditis	Various Gram‐positive and Gram‐negative facultative bacteria, Bartonella, rarely anaerobes.	Blood culture and susceptibility testing indicated.	Penicillin and an aminoglycoside or fluoroquinolone pending the results of culture and susceptibility.
	Bartonellosis	Primarily Bartonella vinsonii subsp. berkhoffii or Bartonella henselae.	Bartonella serology and culture (low sensitivity) indicated. Significance as a cause of disease may be unclear unless endocarditis is present.	Penicillin and an aminoglycoside for endocarditis. Prognosis guarded to poor as valve replacement often required.
	Brucellosis	Brucella canis.	Potential zoonosis.	Doxycycline plus dihydrostreptomycin or gentamicin; consider addition of rifampin.
	Leptospirosis	Various serovars of Leptospira.	Potential zoonosis. Fluid therapy essential, dialysis may be required.	Penicillin, ampicillin, or doxycycline; oral doxycycline recommended once vomiting ceases for elimination of the carrier state.
	Lyme borreliosis	Borrelia burgdorferi.	Consider nonsteroidal antiinflammatory drugs for analgesia.	Doxycycline.
	Nocardiosis	Nocardia.	Pulmonary, systemic, or cutaneous lesions.	Trimethoprim‐sulfonamide.
	Neonatal bacteremia	Streptococcus, E. coli, Staphylococcus.		Ampicillin‐sulbactam, first‐generation cephalosporin. Consider cautious use of an aminoglycoside if Gram‐negative bacteria are suspected.
	Rapidly growing mycobacteria	Mycobacterium fortuitum, Mycobacterium smegmatis.	Cutaneous‐subcutaneous and less often systemic infections.	High‐dose doxycycline or a fluoroquinolone; aminoglycosides could also be considered.
	Slow‐growing opportunistic mycobacteria	Mycobacterium avium.	Usually systemic infections in immunocompromised dogs.	Three‐drug combination of a macrolide (such as clarithromycin) with rifampin, ethambutol, doxycycline, and/or a fluoroquinolone suggested.
	Tuberculous mycobacteria	Mycobacterium tuberculosis, Mycobacterium bovis.	Prolonged combination drug treatment; potential zoonosis.	Combination of isoniazid, rifampin, and clarithromycin, with or without ethambutol. Isoniazid may cause seizures.
Other protozoal	Babesiosis	Babesia canis, Babesia rossi, Babesia vogeli.		Imidocarb dipropionate or a combination of atovaquone and azithromycin.
		Babesia gibsoni, Babesia conradae, Babesia vulpes.		Atovaquone and azithromycin.
	Cryptosporidiosis	Cryptosporidium.	Infection often subclinical and self‐limiting. Potential zoonosis.	No uniformly successful treatment; some improvement may be seen with paromomycin or azithromycin.
	Hepatozoonosis	Hepatozoon americanum, Hepatozoon canis.	Treatment may reduce signs without resolving infection. Use nonsteroidal antiinflammatory drugs to control inflammation and pain.	H. americanum: acute ‐ clindamycin, sulfonamide, trimethoprim, pyrimethamine; chronic ‐ decoquinate H. canis: imidocarb dipropionate.
	Leishmaniosis	Leishmania spp.	Complete resolution of infection may not occur.	Meglumine antimonate and allopurinol. Alternatives are amphotericin B or miltefosine.
	Neosporosis	Neospora caninum.		Clindamycin. Alternative is sulfonamide plus pyrimethamine.
	Toxoplasmosis	Toxoplasma gondii.		Clindamycin. Alternative is sulfonamide plus pyrimethamine or azithromycin.
	Trypanosomiasis, American	Trypanosoma cruzi.	Potential public health risk.	Nifurtimox or benznidazole.
Rickettsial, ehrlichial, and hemotropic mycoplasma infections	Rocky Mountain spotted fever	Rickettsia rickettsii, other pathogenic Rickettsia spp.		Doxycycline.
	Ehrlichiosis, anaplasmosis	Ehrlichia canis, Ehrlichia ewingii, Anaplasma phagocytophilum, Anaplasma platys.	Ehrlichia canis infections require prolonged treatment (6–8 weeks). Dogs with chronic E. canis infections may not respond to treatment.	Doxycycline.

	Hemoplasmosis	Mycoplasma haemocanis, Mycoplasma haematoparvum.	Usually only of pathogenic significance in splenectomized or immunocompromised dogs.	Doxycycline or a fluoroquinolone.
Systemic mycoses	Aspergillosis, disseminated	Aspergillus terreus, Aspergillus deflectus.	Genetic immunodeficiency suspected in German Shepherds and Rhodesian Ridgebacks. Any immunosuppression should be removed if possible.	Itraconazole or itraconazole and amphotericin B; voriconazole or posaconazole are alternatives but may be expensive. Consider addition of terbinafine for refractory cases. Do not use fluconazole.
	Blastomycosis	Blastomyces.		Itraconazole or fluconazole, with or without amphotericin B.
	Coccidioidomycosis	Coccidioides.		Itraconazole or fluconazole, with or without amphotericin B. Voriconazole may also be effective and has CNS penetration but is expensive.
	Cryptococcosis	Cryptococcus neoformans or Cryptococcus gattii species complex.	Dogs often develop severe disseminated disease with C. neoformans, possibly due to an underlying immunodeficiency.	Fluconazole with or without amphotericin B; itraconazole may be effective when fluconazole fails.
	Histoplasmosis	Histoplasma.		Itraconazole with or without amphotericin B.
	Sporotrichosis	Sporothrix schenckii species complex.		Itraconazole with or without amphotericin B; supersaturated potassium iodide is an alternative.

^a These selections reflect personal opinion based on review of the literature, discussion with colleagues, and clinical experience. They are intended to guide drug selection when laboratory data are lacking.

^b Laboratory data (Gram stain of exudate or aspirate, preferably with culture and susceptibility test) should be used to guide drug selection if available. Selection may change once culture and drug susceptibility test results are known. See Greene C. 2012. Infectious Diseases of the Dog and Cat, 4th edn. Elsevier Saunders, for additional information.