Infectious Diseases of the Dog and Cat, 3rd Edition ACTINOMYCOSIS

Infectious Diseases of the Dog and Cat, 3rd Edition
49 CHAPTER
49 Actinomycosis and Nocardiosis
David F. Edwards
49.1
ACTINOMYCOSIS
49.1.1
Etiology and Epidemiology
Actinomycosis is a chronic, pyogranulomatous disease characterized by pleural and peritoneal exudates, dense
fibrous masses, frank abscesses, and fistulous tracts with draining sinuses. The disease is caused by anaerobic
actinomycetes that are endogenous saprophytes of mucous membranes and members of the family
Actinomycetaceae. Actinomyces bowdenii, Actinomyces canis, Actinomyces catuli, Actinomyces
67a
hordeovulneris, Actinomyces odontolyticus, Actinomyces turicensis, Actinomyces viscosus, and
Arcanobacterium pyogenes (formerly Actinomyces pyogenes) have been recovered from infected dogs.* A.
bowdenii, A. viscosus, Actinomyces meyeri, and A. pyogenes have been recovered from infected
12,13,90,91,108
Anaerobic actinomycetes are part of the normal bacterial flora of the mucous membranes. In
cats.
addition to streptococci, actinomycetes colonize the peridontal mucosal surfaces and adhere to the tooth surface
145
to form plaque. A. viscosus, A. odontolyticus, Actinomyces israelii, Actinomyces bovis, and Actinomyces
naeslundii have been cultured from the dental plaque of dogs, and Actinomyces colecocanis has been cultured
64
from the canine vagina.
A. viscosus, A. hordeovulneris, and Actinomyces denticolens have been cultured from
452
92
normal feline gingiva. These endogenous saprophytes are not normally pathogenic, but if Actinomyces species
are inoculated into tissues with associated bacteria, an insidious pyogranulomatous disease can develop. (Use of
the term “Actinomyces species” refers to [1] species currently classified in the genus Actinomyces and [2]
related Actinomyces-like bacteria classified in other genera but that cause the clinical disease recognized as
actinomycosis.)
Actinomycosis occurs most commonly in young adult to middle-age large-breed male dogs that are used or kept
58,74
in an outdoor environment.
Hunting dogs have the highest prevalence of disease, and males and females
seem to be affected equally. Actinomycosis in outdoor dogs is related in large part to their chronic exposure to
19,46,47,67,106
Inhaled or ingested florets or awns contaminated in the oropharynx migrate to various
grasses.
sites and act as the nidus of infection. Although infrequently reported in cats, actinomycosis is often attributed
90
to bite wounds. Because of the difficulty in culturing Actinomyces species and their susceptibility to many
antibiotics, the true prevalence of actinomycosis in dogs and cats is greater than that suggested by the literature.
*
49.1.2
References 13, 24, 37, 43, 49, 63, 65, 67a, 108, 123.
Pathogenesis
Actinomyces species are opportunistic pathogens that depend on mechanical disruption of normal mucosal
barriers. Because of the organism's normal habitat, infections must somehow be linked to the mucous
membranes, usually the oropharyngeal area. The disease characteristically spreads by direct extension and is
67a
unimpeded by normal tissue planes; however, rare instances of hematogenous dissemination occur. The most
common clinical forms of actinomycosis in cats and dogs involve the cervicofacial region, thorax, abdomen,
retroperitoneal space, and subcutaneous tissue.* Infection of the cervicofacial region can develop from bite
wounds, perforation of the oropharynx by a foreign body, or chronic gingivitis-periodontitis. Pulmonary
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
infections can develop by aspiration of oropharyngeal material, which may include inhalation of a contaminated
42
grass awn. Preexisting lung disease (e.g., neoplasia) can act as a nidus for infection. Alternative routes of
thoracic infection include involvement of the mediastinum from esophageal perforation and direct extension of
cervicofacial or abdominal disease. Intraabdominal actinomycosis develops from swallowed organisms or plant
material penetrating the gastrointestinal (GI) mucosa. In people, GI disease, abdominal trauma, or surgery often
precedes infection. Penetration of the GI tract by a bullet or other foreign bodies, including plant material, also
increase the risk of infection for animals. Like thoracic infections, abdominal involvement can occur by direct
extension. Infection of the retroperitoneal space in dogs is often associated with grass foreign bodies.
Theoretically, contaminated grass florets or awns migrate to the space by migrating through the lung and up the
crus of the diaphragm to its dorsal attachment, or by perforating the intestinal wall and migrating via the
mesentery to its dorsal attachment. Actinomycosis of the limbs is caused by bite wounds, foreign bodies, and
lacerations contaminated by licking. Infection of the subcutaneous tissue in dogs usually represents an
extension of cervicofacial, thoracic, or retroperitoneal disease, whereas in cats it is caused by bite wounds.
Central nervous system (CNS) infections develop from hematogenous or lymphatic dissemination from a
primary site or direct extension from a contiguous infection.
Actinomycosis is characteristically a polymicrobial infection, and the pathogenicity of Actinomyces species is
dramatically increased in mixed infections. The associated bacteria are commensal organisms from the oral
cavity or intestinal tract that produce and maintain an anaerobic tissue environment. Inoculation of pure cultures
of Actinomyces species or the associated bacteria alone often do not produce infection. Actinomyces species
with fimbriae bind to specific cell surface receptors on other bacteria. This coaggregation markedly inhibits
107
neutrophil phagocytosis of and bactericidal activity on the bacterial complex. If not bound to other bacteria,
actinomycetes bind to specific receptors on neutrophils, initiating phagocytosis and degranulation. Additionally,
Actinomyces species induce neutrophil chemotaxis, activate macrophages, and stimulate B-lymphocyte
hyperplasia. These bacterial-cellular interactions produce the characteristic actinomycosis lesion—a dense mat
of Actinomyces species and associated organisms surrounded by neutrophils, macrophages, and plasma cells.
Proteolytic enzymes from the associated bacteria, macrophages, and degranulated neutrophils destroy
145
connective tissue, facilitating extension of the disease through normal tissue planes.
*
49.1.3
49.1.3.1
References 12, 37, 47, 58, 67, 74, 90, 91, 106.
Clinical Findings
Dog
Cervicofacial actinomycosis produces acute to chronic subcutaneous soft tissue swelling in the head or neck
37,42,106,128
The lesion can be fluctuant or firm, may be indurated, and can be ulcerated or have
region.
draining sinuses. The mandible, submandibular region, and ventral or lateral cervical area are most
frequently affected, but infections involving the face, retrobulbar space, and temporal area have been
reported. Radiographically, adjacent bone can have periosteal new bone formation, and a chronic infection
may be characterized by osteomyelitis. Ultrasonography and magnetic resonance imaging can be used to
46a,124a
Material aspirated from fluctuant masses or discharged from
identify linear grass awn foreign bodies.
sinuses appears serosanguineous to purulent and may contain macroscopic, yellow-tan granules (i.e., sulfur
granules), which are small, soft macroscopic colonies of actinomycetes that are often present in exudates or
infected tissue. The term sulfur granule was derived from the frequently seen yellow pigmentation of the
granule; however, granule color can vary from white to tan to gray (Fig. 49-1). Aspiration of firm lesions
may yield only a few drops of blood.
CHAPTER 49 Actinomycosis and Nocardiosis
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Actinomycosis involving the thoracic or abdominal cavity is characteristically chronic and progressive;
weight loss, often severe, and fever are the most common clinical signs. Thoracic actinomycosis may be
limited to the lung parenchyma but can involve multiple structures within the thorax, including the
mediastinum, pleura, heart, and chest wall.* Other clinical features include cough, tachypnea, dyspnea,
decreased lung sounds (from empyema or a mass lesion), and subcutaneous soft tissue masses on the lateral
thorax. Thoracic wall masses often develop a draining sinus. Radiographically, lung disease appears as
alveolar and interstitial infiltrates with consolidation. Variable findings include pleural thickening, pleural
effusion (often loculated to one side), pericardial effusion, widening of the mediastinum, mass lesions, and
periosteal new bone formation or osteomyelitis involving adjacent ribs, vertebral bodies, or sternebrae.
Clinical features of abdominal actinomycosis include palpable masses and abdominal distention
452
453
29,43,49,58
Subcutaneous masses, which may have draining sinuses, are rarely present unless the
(effusion).
abdominal disease develops from an extension of thoracic or retroperitoneal infections. Radiographic
manifestations include variable amounts of peritoneal effusion and mass lesions that incorporate or displace
adjacent structures. Pleural, pericardial, and peritoneal effusions resemble the exudate from cervicofacial
abscesses.
Fig 49-1 Thoracic exudate in Petri dish containing numerous macroscopic
sulfur granules. (Courtesy David F. Edwards, University of Tennessee,
Knoxville, Tenn.)
37,47,67,77
Retroperitoneal actinomycosis is characterized by back pain and rear leg paresis or paralysis.
A
subcutaneous mass with a draining sinus involving the caudal thorax or flank area is often present.
Radiographic findings include periosteal new bone formation involving the ventral aspects of two or three
adjacent vertebral bodies (usually T-13 through L-3); involvement of disk spaces is uncommon (Fig. 49-2).
Chronic disease may cause the vertebral bodies to develop osteomyelitis and compression fractures. This
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
finding contrasts with diskospondylitis caused by embolic spread of bloodborne bacteria or fungi to the disk
space (see Chapters 40, 64, and 86).
Cutaneous-subcutaneous actinomycosis is characterized by a soft to firm mass, which may have a draining
37,47,74,106,128
sinus.
These infections are typically located in the head and neck area, lateral thoracic wall,
and flank region and are usually extensions of cervicofacial, thoracic, or retroperitoneal actinomycosis.
Rare cases of actinomycosis involving the extremities and CNS have been reported. Lameness, mass lesions
20,58
with draining sinuses, and periosteal new bone formation are characteristic of limb involvement.
128,5,34
Actinomycosis of the brain is rare,
whereas involvement of the spinal cord is a common sequela to
43,67,77
Clinical findings associated with brain infections are nonlocalizing and
subvertebral infections.
include altered behavior, decreased consciousness, neck pain, ataxia, abnormal reflexes, and seizures. With
spinal cord involvement, pain, paresis, paralysis, and abnormal reflexes are noted, and radiographic evidence
of a bony change in adjacent vertebral bodies is present. Cystitis in dogs has been associated with
Arcanobacterium pyogenes and a Nocardia-like organism, which most likely represents A. turicensis, a
13,66,68,117
common isolate from wogenital tract infections.
Fig 49-2 Spinal radiograph of an 8-year-old pointer with retroperitoneal
actinomycosis. Periosteal new bone growth (arrows) is present on
ventral aspect of vertebral bodies of L-2 and L-3. (Courtesy David F.
Edwards, University of Tennessee, Knoxville, Tenn.)
*
49.1.3.2
References 18, 28, 37, 43, 46, 47, 58, 89, 115, 124, 128.
Cat
Pyothorax and subcutaneous bite wound abscesses are the most common disorders in cats from which
90,91
The abscesses have a malodorous, yellow to sanguineous exudate
Actinomyces species are isolated.
without a granulomatous mass, and the Actinomyces species is always mixed with two to five other
pathogens. Actinomycosis as described in the dog has been reported infrequently in cats. The feline cases
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
have involved the cervicofacial region,
12,127
the spinal canal.
49.1.4
49.1.4.1
30,84,147
60
thoracic cavity,
and subcutaneous tissue with extension to
13
Otitis external secondary to A. pyogenes has been reported in a cat.
Diagnosis
Clinical Laboratory Findings
Hematologic test results in animals with actinomycosis vary according to the location and duration of
disease. Animals with focal lesions (e.g., cervicofacial and limb infections) may have few abnormal results,
whereas animals with more extensive, chronic disease have mild to moderate nonregenerative anemia,
leukocytosis with a left shift and monocytosis, hypoalbuminemia, and hyperglobulinemia (sometimes
marked). Dogs with body cavity effusions may be hypoglycemic. Aspirates of abscesses or effusions,
tracheal lavages, and sinus discharges are suppurative to pyogranulomatous, whereas aspirates of firm
masses may reveal only blood. In some specimens, especially those from effusions, sulfur granules are
visible macroscopically (see Fig. 49-1). Microscopically, mixed bacterial populations containing rods and
cocci are common. The actinomycetes appear individually or in dense aggregates (sulfur granules) as
gram-positive, non–acid-fast filamentous organisms that are occasionally branched (Fig. 49-3). Nocardia
species and Filifactor villosus– gram-positive filamentous rods can be confused with Actinomyces
species.
91,135
Fig 49-3 Smear of thoracic fluid. Dense mat of infrequently branched,
filamentous rods (i.e., sulfur granule). Note presence of other
bacterial species (×198). (Courtesy David F. Edwards, University of
Tennessee, Knoxville, Tenn.)
453
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
49.1.4.2
453
454
Bacterial Isolation and Identification
The disease is confirmed by culture of the organism, but frequently culture results are negative or contain
only associated bacteria. Actinomyces species either are facultative (A. canis, A. catuli, A. coleocanis, A.
bowdenii, A. denticolens, A. hordeovulneris, A. naeslundii, A. odontolyticus, A. viscosus, A. pyogenes) or
16,63-65,108
Specimens should be collected and processed
obligate (A. bovis, A. israelii, A. meyeri) anaerobes.
anaerobically and cultured on blood agar or enriched thioglycolate media in the presence of 5% to 10%
carbon dioxide. Species that are facultatively anaerobic are variably aerotolerant and can grow aerobically.
A. viscosus actually grows best in aerobic conditions. All species cultured aerobically require carbon dioxide,
except A. bowdenii, A. naeslundii, and A. odontolyticus.
61
Growth of Actinomyces species can be observed within 48 hours but usually requires 5 to 7 days. It may be
necessary to hold plates 2 to 4 weeks. Colonies on blood agar are flat to convex, circular with entire or
irregular margins, and translucent to opaque and white; surfaces are smooth and moist or rough (bread
crumb or molar tooth surface). Some strains of A. israelii produce aerial filaments, resulting in a powdery, or
cotton ball, appearance. Microscopically Actinomyces species are gram-positive, non–acid-fast short rods
and filaments. The filaments are less than 1 μm wide, vary considerably in length, may branch, and can stain
18,29,43,58,74
irregularly, producing a beaded appearance.
Actinomyces species are heterogeneous, and species
120
identification using traditional biochemical tests is difficult. Results of 16S rRNA gene sequence analysis
of previously identified species indicates that several genera in addition to Arcanobacterium and
31,56,112
Variants of A.
Actinobaculum will emerge from the species now classified in the genus Actinomyces.
hordeovulneris that are cell wall deficient have been produced in culture, suggesting that L forms of
Actinomyces species may be associated with clinical disease; however, because of special culture
23
requirements, these variants would be isolated infrequently.
Actinomycosis is characteristically a mixed bacterial infection.* Three to five associated bacteria are
typically recovered from properly handled specimens. The most commonly isolated organisms are resident
flora of the oral cavity or intestinal tract and include Bacteroides species, Corynebacterium species,
Escherichia coli, Eubacterium species, Fusobacterium species, Pasteurella multocida, Peptostreptococcus
species, Staphylococcus aureus, and Streptococcus species. Most of the associated bacteria are facultative or
obligate anaerobes, therefore isolation requires appropriate specimen handling. Unfortunately, the growth of
a mixed microflora can impair the isolation of Actinomyces.
61
Because Actinomyces species are sensitive to many antibiotics, the treatment of animals before obtaining
specimens for culture can prevent recovery of the organisms. This fact, compounded by improperly handled
specimens and polymicrobial growth, accounts for the frequent failure of Actinomyces isolation from
infected animals. The diagnosis is often based on the cytologic or histologic identification of the organism in
specimens from animals with appropriate clinical signs. Because Actinomyces is a commensal oral bacteria,
it is commonly swallowed, inhaled, and transferred by licking, therefore culture of the organism from the
airways, GI tract, or skin does not necessarily constitute infection.
*
References 19, 47, 58, 74, 90, 91, 134.
CHAPTER 49 Actinomycosis and Nocardiosis
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49.1.5
Pathologic Findings
†
Actinomycosis is characterized by a poorly defined, often indurated mass that incorporates adjacent structures.
The mass may contain one or more pockets of a reddish-brown exudate. Fistulas and sulfur granules may be
found. Thoracic and abdominal infections produce a diffuse, red, velvety to granular thickening of the parietal
pleura and peritoneum and omentum. The visceral pleura and peritoneum may be less affected. A variable
amount of a reddish-brown exudate that may contain sulfur granules is present. Lung involvement is usually
localized and may appear as a consolidation or mass; infrequently, multiple pulmonary nodules are present.
Masses can affect multiple internal structures (e.g., heart, mediastinum, lung, diaphragm, and chest wall) and
produce an external subcutaneous swelling that may have a draining sinus. With abdominal disease, only one
29,43,49
organ may be affected (e.g., liver), but typically a mass or masses involve multiple adjacent structures.
Subcutaneous masses may be ulcerated and in dogs are usually an extension of cervicofacial, thoracic, or
37,47,67
retroperitoneal disease.
The histologic reaction to Actinomyces species infection is characterized by a core of neutrophils encapsulated
by fibrosing granulation tissue. The granulation tissue contains macrophages, plasma cells, and lymphocytes in
a dense, fibrous tissue matrix. The centrally located actinomycotic (sulfur) granule or grain can be very difficult
to find, so multiple tissue sections may be needed to confirm the diagnosis. When associated with appropriate
clinical signs, identification of true actinomycotic granules is diagnostic of actinomycosis. In tissue sections
stained with hematoxylin and eosin (H and E), the granules appear as round, oval, or scalloped amphophilic
solid masses with an outer basophilic band (Fig. 49-4, A). The granules vary in size (from 30 to 3000 μm in
diameter) and often are rimmed by partially confluent radiate, eosinophilic serrate, or club-shaped structures
(i.e., the Splendore-Hoeppli phenomenon). Neutrophils frequently contact or appear enmeshed in this material.
Individual actinomycete filaments are not delineated by H and E stain or Gridley's fungal or periodic
acid-Schiff reactions, whereas Gram staining of tissues (i.e., the Brown-Brenn procedure) reveals clumps of
tangled, intermittently branched, thin (less than 1 μm in diameter) filaments that are gram-positive and slightly
beaded (Fig. 49-4, B). Gram-positive or gram-negative nonfilamentous bacteria can be mixed with the
Actinomyces species. Actinomyces species are non–acid-fast when stained by the Fite-Faraco modification of
the Ziehl-Neelsen technique, which uses a weaker decolorizing agent of 1% sulfuric or 1% hydrochloric acid.
With the rare exception of some Nocardia species, other fungi and bacteria that produce tissue granules can be
reliably distinguished from Actinomyces by tinctorial and morphologic properties.
distinguish it from actinomycosis are listed in Table 49-1.
†
49.1.6
27
Features of nocardiosis that
References 28, 29, 43, 60, 89, 128, 134.
Therapy
Successful treatment of actinomycosis involves prolonged administration of antibiotics; the role of surgery
varies with the form of the disease. Large doses of penicillin given for prolonged periods (weeks to months) is
81
the treatment of choice (Table 49-2). No strains of Actinomyces species have shown in vitro resistance to
easily attainable serum concentrations of penicillin, and acquired resistance in vivo has not been confirmed.
Poor drug penetration of the dense granulomatous tissue reaction necessitates the prolonged, high-dose therapy.
A minimal dose of penicillin G (benzyl penicillin) or penicillin V (phenoxymethyl penicillin) of 40 mg/kg
43
every 8 hours is recommended. Units of penicillin equivalency per milligram depend on the formulation (see
Appendix 8). The therapeutic advantage of initial parenteral administration is questionable, therefore if the
43,105
animal is stable clinically, oral therapy can be started from the outset.
Because food reduces the
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
absorption of most penicillins, medication should be given 1 hour before or 2 hours after feeding. Therapy must
be extended significantly (weeks to months) beyond resolution of measurable disease to prevent relapse; in
43,58
454
456
Drugs other than penicillin that are effective against most
some cases, treatment can exceed 1 year.
Actinomyces species include erythromycin, clindamycin, ampicillin, tetracycline, minocycline, doxycycline,
chloramphenicol, imipenem, and first-generation cephalosporins and ceftriaxone.
81,123,146
Anecdotal success
94
with ciprofloxacin was reported in a human patient with recalcitrant actinomycosis of 20 years’ duration;
however, recently described Arcanobacterium bernardiae and Actinomyces neuii are resistant to ciprofloxacin,
and in vitro resistance to fluorinated quinolones was reported for an Actinomyces species isolate from a dog
16,41
Oxacillin, dicloxacillin, cephalexin, metronidazole, and aminoglycosides have poor
with thoracic disease.
in vitro activity against most Actinomyces species; however, A. pyogenes is sensitive to aminoglycosides (other
55
than streptomycin) but resistant to tetracycline, minocycline, and doxycycline.
Poor response to appropriate
81
doses of penicillin may be attributable to poor surgical drainage and failure to eliminate associated bacteria.
Infections by these organisms usually resolve with penicillin, but on occasion they require broader spectrum
antibiotics during the initial treatment period followed by long-term administration of penicillin. Cats with
pyothorax or subcutaneous abscess that have not developed a granulomatous tissue reaction often can be cured
with drainage and a shorter duration of antibiotic treatment.
Fig 49-4 A, H and E stained section of abdominal mass from 5-year-old
neutered female boxer dog. Actinomycotic tissue granule is
surrounded by neutrophils. Encapsulating fibrous tissue has
mononuclear cell infiltrate. (The long dimension of the granule
measures 695 μm; ×13.2). B, Tissue section (Gram stain, Brown-Brenn
procedure) of intrathoracic mass from 4-year-old German shorthaired
pointer. Actinomycotic tissue granule showing infrequently branched,
filamentous rods characteristic of Actinomyces organisms (×132). (A,
Courtesy David F. Edwards, University of Tennessee, Knoxville, Tenn.)
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
Table 49-1 Comparison of Actinomycosis Versus Nocardiosis
ACTINOMYCES SPECIES
Culture
1. Facultative or obligate anaerobe
2. Fastidious growth requirements; often not cultured
3. Two to five associated microbes usually recovered
NOCARDIA SPECIES
1. Aerobe
2. Usually cultured
3. Sole isolate unless from contaminated sample (e.g.,
tracheal wash, ulcerated skin)
Staining Characteristics
1. Irregular staining that can produce slight beading
2. Gram-positive and non–acid-fast using Fite-Faraco
modification of Ziehl-Neelsen technique
Cytopathologic Characteristics
1. Suppurative to pyogranulomatous inflammation with a
mixed bacterial population; macroscopic and microscopic
dense mats of long filamentous bacteria often present (see
Fig. 49-3)
Histopathologic Characteristics
1. Pyogranulomatous inflammation with marked
encapsulating fibrosis (see Fig. 49-4)
2. Variable presence of tissue granules (30–3000 mm
diameter)
Clinical Disease
1. In adult outdoor dogs (especially hunting breeds); with
bite wounds and pyothorax in cats
2. Direct spread to adjacent structures
3. Sensitive to high doses of penicillin
4. Low mortality
1. Irregular staining that can produce marked beading
2. Gram-positive and partially acid-fast using Fite-Faraco
modification of Ziehl-Neelsen technique
1. Suppurative to pyogranulomatous inflammation; long
filamentous bacteria typically present singly or in loose
aggregates (see Fig. 49-6); infrequently macroscopic and
microscopic dense mats of long filamentous bacteria present
1. Pyogranulomatous inflammation; significant fibrosis
present only in chronic skin infections (see Fig. 49-7)
2. Granules present only in skin infections (15–200 mm
diameter)
1. In dogs younger than 2 years old; from fight wounds in
cats
2. Hematogenous spread; can see lesions at noncontiguous
sites
3. Variable sensitivity to sulfonamides
4. Moderate to high mortality
Table 49-2 Drugs Used to Treat Actinomycosis in Dogs and Cats
SPECIES
a
DRUG
Penicillin G
Penicillin G
Penicillin V
B
B
c
B
Clindamycin
Erythromycin
Chloramphenicol
Rifampin
Minocycline
c
B
B
D
C
D
B
B
b
DOSE
100,000 U/kg
ROUTE
INTERVAL (HOURS)
d
IV, IM, SC
PO
d
PO
8
SC
PO
PO, IV, IM, SC
PO, IV, IM, SC
PO
IV, PO
IM, SC, PO
12
8
8
12
12
12
6
40 mg/kg
40 mg/kg
5 mg/kg
10 mg/kg
50 mg/kg
50 mg/kg
10 mg/kg
5–25 mg/kg
20–40 mg/kg
Ampicillin (amoxicillin)
B, Dog and cat; D, dog; C, cat; IV, intravenous; IM, intramuscular; SC, subcutaneous; PO, by mouth.
a
See Appendix 8 for more information on these drugs.
b
Dose per administration at specified interval. For duration, see text.
c
Give at least 1 hr before or 2 hr after feeding to facilitate GI absorption.
d
Minimum recommended dose (see text); 1 mg = 1600 U (see Appendix 8).
CHAPTER 49 Actinomycosis and Nocardiosis
6–8
8
Page 9 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
Surgery has a controversial role in the treatment of acti-nomycosis. Draining of abscesses and effusions
58,60,115
(thoracic, abdominal, and pericardial) should always be used as an adjunct to antibiotic treatments.
46,134
Continuous suction and intermittent drainage techniques have been used for thoracic effusions in dogs.
Drain tubes are removed when the purulent exudate changes to a serosanguineous transudate, usually within 4
to 10 days. Daily lavage with fluids containing crystalline penicillin G may be beneficial. Using sodium
penicillin rather than potassium penicillin in the lavage fluid prevents the development of cardiotoxicity from
6
hyperkalemia. (Crystalline potassium penicillin G contains 1.7 mEq potassium per 10 U.) Complications of
drainage include pneumothorax and subcutaneous abscess formation at the drain tube insertion site. Animals
46,115,134
In animals
not responding to drainage and appropriate antibiotic therapy warrant exploratory surgery.
with pulmonary abscesses, diseased lung lobes often require removal. The characteristic invasive fibrotic
lesions obliterate tissue planes, preventing conservative dissection, and the tissue is well vascularized, therefore
moderate to severe bleeding is common. With diffuse disease involving body cavities, tissue resection should
be restricted to decrease the chance of death. In dogs with solitary masses involving the thoracic and abdominal
46
walls, radical surgical excision has a high cure rate, although repeat surgeries may be needed. The masses
often can be reduced and better defined by an initial period of antibiotic therapy. Frequently, grass florets or
46,46a,67,124a
awns are found in these lesions and during surgical exploration of diseased retroperitoneal regions.
Surgery should never be performed in lieu of and should always be followed by appropriate antibiotic therapy.
Appropriate treatment of dogs with actinomycosis, which can involve extremely prolonged use of antibiotics
43,46,58
and surgery, results in a cure rate of greater than 90%.
Because of the infrequent documentation of
actinomycosis in cats, a meaningful cure rate is not available, but it is likely similar to the cure rate in dogs.
49.1.7
Public Health Considerations
No reports exist of actinomycosis being transmitted from clinically infected animals to humans or to other
113
animals; however, humans bitten by dogs, cats, or other people can develop actinomycosis. Nevertheless,
animal care workers handling infected tissues or discharge should wear protective gloves to avoid inadvertent
contact by inoculation or through damaged skin.
49.2
NOCARDIOSIS
49.2.1
Etiology and Epidemiology
Nocardiosis is a suppurative to granulomatous, localized or disseminated bacterial infection caused by aerobic
10,11
Nocardia asteroides is the most commonly
actinomycetes that are members of the family Nocardiaceae.
isolated species in dogs and cats, but infections by Nocardia brasiliensis (in the dog and cat), Nocardia
otitidiscaviarum (in the dog and cat), Nocardia nova (in the cat), and N. africana (in the cat) have been
reported.* As historically defined, N. asteroides,
126,116
N. brasiliensis,
136
N. nova,
33
456
457
108a
N. otitidiscaviarum
142
and Nocardia transvalensis consist of several subtypes and species. Recent publications cite approximately
34 valid species of Nocardia; to date, at least 20 species have been implicated in human infections. It is certain
previous reports of nocardiosis in dogs and cats understate the number of species producing disease. These
aerobic actinomycetes are ubiquitous soil saprophytes that degrade organic matter and are found in soil, in
10,99
Infections are considered opportunistic, occurring by either inhalation of organisms or
water, and on plants.
inoculation through puncture wounds.
CHAPTER 49 Actinomycosis and Nocardiosis
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Infectious Diseases of the Dog and Cat, 3rd Edition
In a survey of 53 dogs with nocardiosis, males were infected three times more frequently than females; 65.4%
of the dogs were younger than 1 year, 82.7% were younger than 2 years, and only 7.8% were older than 6 years;
11
26.9% had an underlying condition, most often canine distemper. Apparently in dogs, like in people,
predisposing factors (i.e., diseases) increase susceptibility to nocardiosis. Approximately 40% of people with
nocardiosis have primary disorders that involve immunosuppressive drug therapy, obstructive pulmonary
disease, metabolic disorders (e.g., hyperadrenocorticism, diabetes mellitus), neoplasia (lymphosarcoma,
leukemia), immunologic disease (systemic lupus erythematosus, dysgammaglobulinemia), or infectious
10,99
diseases (e.g., acquired immunodeficiency syndrome).
In 20 reported cases of feline nocardiosis, 15
†
involved males and 4 involved females. Ages ranged from 2 to 15 years (with a median age of 7 years).
Fourteen of the cats had draining wounds or abscesses that were associated with scratches or bite wounds.
49.2.2
*
References 2, 11, 59, 62, 93.
†
References 2, 3, 6, 9, 26, 38, 59, 62, 78, 93, 95, 102, 109, 131, 141.
Pathogenesis
Similar to the systemic mycoses, pulmonary nocardiosis probably results from inhalation of soil organisms.
Nocardial lesions develop in alveolar spaces and frequently erode into blood vessels, resulting in systemic
spread of the disease. Secondary lesions from systemic spread can develop in any tissue. Involvement of
contiguous structures within the thorax (e.g., pleura, mediastinum, pericardium) is also common. Localized
cutaneous, subcutaneous, and regional lymph node infections result from inoculation through a puncture wound
(e.g., bite, scratch, foreign body). Other solitary extrapulmonary sites of infection are likely caused by
10,99
localization from a transient bacteremia. The primary source may be an inapparent pulmonary infection.
Pathogenicity of Nocardia species is influenced by the strain and growth phase of the organism and host
susceptibility. Normal host response to infection is characterized by an initial neutrophil mobilization that may
inhibit growth but not kill the organism. Subsequent cell-mediated immunity consisting of activated
macrophages and T lymphocytes is normally bactericidal. Diminished host resistance is a primary factor in
nocardiosis, but not all diseased animals have identifiable predisposing conditions. Virulent strains of Nocardia
are facultative intracellular pathogens that inhibit phagosome-lysosome fusion, neutralize phagosomal
acidification, resist oxidative burst, and alter lysosomal enzymes within neutrophils and macrophages. These
effects are partly related to the content and structure of mycolic acids within the bacterial cell wall, which vary
among strains and during the growth phase. Some strains exhibit organ-specific trophism (e.g., brain), and the
filamentous, logarithmically growing organisms are 10 times more virulent than the coccoid stationary-phase
cells.
49.2.3
49.2.3.1
10,99
Clinical Findings
Dog
Pulmonary nocardiosis can have a peracute onset characterized by inspiratory dyspnea, hemoptysis,
85
hypothermia, collapse, and death ; however, subacute to chronic clinical symptoms are more
1,26,36,76,96
The signs are often similar to those of distemper and include mucopurulent
characteristic.
oculonasal discharge, anorexia, weight loss (often emaciation), cough, dyspnea, diarrhea, and hyperthermia.
Lung sounds may be increased (from bronchopneumonia) or decreased (from a mass lesion or empyema).
CHAPTER 49 Actinomycosis and Nocardiosis
Page 11 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
11
Coinfection by the canine distemper virus is commonly reported. The radiographic appearance of lesions
varies and includes multiple, diffuse pulmonary nodules, intrapulmonary or extrapulmonary solitary masses,
focal or diffuse bronchointerstitial to alveolar infiltrates, lobar consolidations, pleural effusions, and often,
dramatic hilar lymphadenopathy (Fig. 49-5).
Systemic, or disseminated, nocardiosis, defined by lesions at two or more noncontagious sites within the
body, is typically associated with pulmonary disease and rarely develops without obvious associated
pulmonary disease.* The most frequently involved extrathoracic organs are skin and subcutaneous tissue, the
kidney, the liver, the spleen, lymph nodes, the CNS, bone, and joints. The cutaneous-subcutaneous lesions
are characterized by firm to fluctuant swellings that may ulcerate or develop fistulous tracts through which a
reddish-brown exudate is discharged. Involvement of the liver, the spleen, and lymph nodes is detected
because of organomegaly. CNS lesions may cause seizures. Bone or joint infection results in swelling and
lameness; radiographic findings include soft tissue swelling, bone lysis, and periosteal new bone growth.
Solitary extrapulmonary nocardiosis develops infrequently and usually occurs as a cutaneous-subcutaneous
8
20,119
40
abscess or an actinomycotic mycetoma.
A case of humeral osteomyelitis has been reported.
Mycetoma is a localized, subcutaneous granulomatous tumor that contains organized aggregates (grains or
granules) of free-living or exogenous, geophilic actinomycetes (actinomycotic mycetoma) or fungi
(eumycotic mycetoma). Mycetomas usually develop on extremities, may involve underlying bone, and
typically form abscesses that result in fistulas to the skin. Because Actinomyces is endogenous, tumorous
infections of subcutaneous tissues are not classified as mycetomas. Nocardia infections have been reported
66
in 10 dogs with thoracolumbar vertebral osteomyelitis and in one dog with cystitis ; however, many of these
dogs were probably infected with Actinomyces species (see Actinomycosis, Clinical Findings, in this
chapter).
*
49.2.3.2
17,103,122,125
References 1, 8, 72, 73, 76, 96, 114, 121, 129.
Cat
The clinical forms of feline nocardiosis (pulmonary, systemic, and solitary extrapulmonary) are similar to
those described in the dog; however, in cats, cutaneous-subcutaneous disease (abscesses and actinomycotic
mycetomas) is the most common clinical form. Of 20 reported cases of nocardiosis, 14 cats had
†
5,59,62,102
cutaneous-subcutaneous lesions involving the extremities, inguinal area,
3,6,78,95,109
had pulmonary disease (nodules or empyema),
131
one had peritonitis,
2,3,59,95,141
and neck.
23,62
Five cats
and five had systemic
All those with systemic disease had a primary cutaneous-subcutaneous lesion.
nocardiosis.
Macroscopic sulfur granules were noted in the exudate of five cats (representing all three forms of clinical
disease).
26,38,62,131
CHAPTER 49 Actinomycosis and Nocardiosis
457
458
Page 12 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
Fig 49-5 Right lateral thoracic radiograph of 8-month-old male Labrador
retriever with pulmonary nocardiosis. Radiographic abnormalities
include bronchointerstitial pattern and marked hilar
lymphadenopathy. (Courtesy Royce Roberts, University of Georgia
Veterinary Teaching Hospital, Athens, Ga.)
†
49.2.4
49.2.4.1
References 72, 38, 62, 93, 95, 141.
Diagnosis
Clinical Laboratory Findings
Animals with nocardiosis have nonregenerative anemia, neutrophilic leukocytosis with a left shift,
monocytosis, and hyperproteinemia. Hypercalcemia associated with granulomatous disease has been
102
reported. Pleural effusions, bronchial lavages, and aspirates of abscesses are suppurative to
pyogranulomatous. Gram-positive, partially or weakly acid-fast, beaded, branching filamentous organisms
are often observed individually or in loose aggregates (Fig. 49-6). Macroaggregates (i.e., sulfur granules)
have been noted infrequently in effusions. Unlike actinomycosis, mixed bacterial populations from deep
tissue sites are rare and probably caused by contamination of the sample (e.g., bronchial lavage, ulcerated
skin abscess).
1,8,76,96
CHAPTER 49 Actinomycosis and Nocardiosis
Page 13 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
49.2.4.2
Bacterial Isolation and Identification
The presence in clinical specimens of a gram-positive, partially acid-fast, beaded, branched filamentous
organism 0.5 to 1 μm in diameter warrants specific therapy for nocardiosis, but the diagnosis is confirmed by
culture of the organism. Nocardia species grow aerobically at a wide temperature range on simple media
(e.g., Sabouraud's glucose agar, blood agar). Growth is enhanced by 10% carbon dioxide, modified
Thayer-Martin medium and buffered charcoal-yeast extract agar but is retarded by inhibitory medium used
for fungal isolation. Organisms are usually recovered in pure cultures, and colonies are often visible after 2
days. However, 2 to 4 weeks of incubation may be necessary, especially if samples contain multiple bacterial
species (e.g., bronchial lavage) or are from animals receiving antibiotics. Colonies can be smooth and moist
or rugose with a powdery surface from aerial filaments. Because most Nocardia species produce
10,82,99
Microscopically,
carotenoid-like pigments, colony color varies (cream, yellow, orange, pink, or red).
Nocardia species grown on solid media appear as branched filaments that fragment into pleomorphic,
rod-shape, or coccoid elements. Nocardia species are gram-positive and variably acid-fast. In clinical
specimens or primary isolates, Nocardia species are often partially acid-fast, but a Fite-Faraco modification
of the Ziehl-Neelsen technique decolorized with 1% sulfuric or 1% hydrochloric acid must be used. Not all
pathogenic strains of Nocardia species are acid-fast—a characteristic that may disappear after
subculture.
10,82,99
Fig 49-6 Impression smear of chronic (15 months duration), ulcerated
cutaneous lesion on lateral thorax of 3-year-old female domestic
shorthaired cat. Loose aggregate of infrequently branched,
filamentous rods with beading from irregular staining is typical of
Nocardia organisms (×330). (Courtesy David F. Edwards, University of
Tennessee, Knoxville, Tenn.)
CHAPTER 49 Actinomycosis and Nocardiosis
Page 14 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
Identification of the species of Nocardia isolates is important for prediction of antimicrobial susceptibility.
Traditionally, species have been distinguished by phenotypic features, including growth characteristics and
antibiotic susceptibility patterns; however, modern molecular methods have provided a more reliable and
32,75,138
Restriction fragment length polymorphism (RFLP) analysis of polymerase
rapid means of speciation.
chain reaction (PCR) products from the 16S rRNA gene identifies most pathogenic Nocardia organisms at a
level of therapeutic relevance, but ultimate differentiation of closely related Nocardia species may require
RFLP analysis of hsp gene products, 16S rRNA and hsp gene sequencing, or DNA-DNA
hybridization.
33,116,142
L-form
22
disease in people and a dog.
Nocardia spp., cell wall–deficient variants, have been associated with clinical
458
459
These bacteria require special media for isolation and culture (see Chapter 33).
Pathogenic Nocardia species are not common laboratory contaminants, therefore the isolation of a single
colony from a closed lesion is significant. Because Nocardia organisms are ubiquitous in soil and in certain
circumstances may act as respiratory saprophytes, the isolation of small numbers of organisms from
10,82,99
ulcerated skin lesions or the respiratory tract must be interpreted in conjunction with clinical signs.
49.2.5
Pathologic Findings
Nocardiosis is characterized by suppurative necrosis and abscess formation and infrequently produces
granulomas. The gross lesions on internal organs typically are numerous small (1 mm) to large (1 cm), discrete
72,114,121,129
The nodules are usually subserosal and when cut
to coalescing, raised white or gray-white nodules.
appear caseous to purulent. Affected lung tissue may appear congested. Lymph nodes are enlarged, often
36,76,114
massively, and are firm to fluctuant with a caseous to purulent core.
1,8,128
present in the pleural or peritoneal space or within abscesses.
noted.
A reddish-brown exudate may be
Yellow granules in the exudate have been
76,131
The histologic reaction to nocardial infection is characterized by a central region of necrosis and suppuration
114,121,129
Clusters of epithelioid macrophages and
surrounded by macrophages, lymphocytes, and plasma cells.
multinucleated giant cells may be observed. Except with some skin infections, fibrous tissue is usually poorly
structured, producing thin or incomplete encapsulation of the lesion. In chronic cutaneous-subcutaneous
20,36
infections, pyogranulomatous foci may be interspersed within a dense fibrous tissue matrix.
Nocardial organisms are usually present and often abundant in the necrotic and suppurative tissue reactions.
Gram staining of tissue (e.g., the Brown-Brenn procedure) is best for seeing the filaments, but tissues can also
be stained by methenamine silver preparations, especially with prolonged silver nitrate exposure (i.e., 80 to 100
minutes). Nocardia filaments are not visible in tissue sections stained with H and E or with Gridley's fungal or
periodic acid-Schiff reactions. The organisms are characteristically but not invariably partially acid-fast when a
weak decolorizing solution is used (i.e., 1% sulfuric or 1% hydrochloric acid). Nocardia species appear as
beaded, branching filaments that are 10 to 30 μm or more long and 0.5 to 1.0 μm wide. The filaments usually
appear individually or in tangled, loose aggregates. In chronic skin infections, tissue granules characterized by
colonies arranged in large, rosette-like arrays have been reported (Fig. 49-7). In human nocardiosis, tissue
granules are uncommon; when present, the granules are small (15 to 200 μm), usually not associated with the
Splendore-Hoeppli phenomenon, and usually produced in chronic skin infections by N. brasiliensis.
CHAPTER 49 Actinomycosis and Nocardiosis
Page 15 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
49.2.6
Therapy
Sulfonamides, including trimethoprim-sulfonamide combinations, are the primary drugs for treating nocardiosis
(Table 49-3). Most Nocardia species, with the possible exception of N. otitidiscaviarum, are susceptible to
sulfonamide therapy, but treatment must be continued for a prolonged period. From 1 to 3 months is
recommended in people with cutaneous infections, up to 6 months for uncomplicated pulmonary infections, and
12 months or longer for systemic infections or infections in those who are immunocompromised. Clinical
improvement should be observed within 7 to 10 days of starting treatment. Abscesses or empyema usually must
82,99
be surgically drained to cure the patient.
Antibiotics in addition to or other than sulfonamides may be needed because not all Nocardia isolates are
sensitive to sulfonamides, in vitro susceptibility may not be associated with clinical response, and resistance can
develop during treatment.
administration.
133
82,99,111
459
460
Adverse drug reactions may prevent prolonged sulfonamide
High doses of trimethoprim-sulfadiazine given for long periods to dogs and cats produces
35,88
Drug susceptibility testing of Nocardia isolates is
reversible myelosuppression (anemia and leukopenia).
technically difficult and should be done at experienced laboratories. The National Committee for Clinical
143
Laboratory Standards has approved a standard for susceptibility testing by broth microdilution,
and a
4
comparative study of several conventional susceptibility testing methods has been published. PCR
identification and drug susceptibility testing of Nocardia species can be done at the University of Texas Health
Center at Tyler.*
CHAPTER 49 Actinomycosis and Nocardiosis
Page 16 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
Fig 49-7 A, H and E–stained section of chronic, ulcerated cutaneous lesion on
flank of 3-year-old male domestic longhaired cat. Nocardia tissue
granules are surrounded by pyogranulomatous inflammatory reaction.
(Long dimension of largest granule is 110 μm; ×66.) B, Acid-fast stain
(Fite-Faraco modification of Ziehl-Neelsen technique) of same tissue
section (×132). (Courtesy David F. Edwards, University of Tennessee,
Knoxville, Tenn.)
CHAPTER 49 Actinomycosis and Nocardiosis
Page 17 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
Table 49-3 Drugs Used to Treat Nocardiosis in Dogs and Cats
a
DRUG
Triple sulfa no. 4
Sulfadiazine
d
DOSE
ROUTE
b
c
60 mg/kg
80 mg/kg
50 mg/kg
a
INTERVAL (HOURS)
IV
12
PO
PO
8
8
Sulfasoxazole
Amikacin
8–12 mg/kg
IV, IM, SC
Imipenem-cilastatin 2–5 mg/kg
IV
Cefotaxime
20–80 mg/kg
IV, IM
Minocycline
5–25 mg/kg
IV, PO
Erythromycin
10 mg/kg
PO
Ampicillin
20–40 mg/kg
IV, IM, SC, PO
Linezolid
8–20 mg/kg
PO
IV, Intravenous; PO, by mouth; IM, intramuscular; SC, subcutaneous.
8
8
6
12
8
6
24
a
See Appendix 8 for more information on these drugs.
b
Dose per administration at specified interval. For duration, see text; usually a minimum of 6 weeks is
required with all the drugs.
c
120 mg/kg IV initially.
d
Also sulfamethizole.
CHAPTER 49 Actinomycosis and Nocardiosis
Page 18 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
Table 49-4 Percentage of Pathogenic Nocardia Species Isolates with Sensitivity
or Intermediate Sensitivity to Various Drugs In Vitro
a
a
DRUG
ISOLATE
N. asteroides complex
AMK
A-C
AMP
CTX
CTA
CIPRO
ERY
S
S
S
S
—
R
I
S
—
—
—
S
S
S
S
S
S
S
S
S
—
S/I
—
—
S
—
100
6
84
96
96
0
100
100
— 100
98
88
—
N. africana
N. veterana (5)
—
—
100
—
—
—
100
—
0
—
—
—
0
S
I/S
S
I/R
R/I
R
S
S
S/R
S
I
S
—
Type V: N.
99
79
7
6
17
80
9
83
3
100
96
76
95
S
R/S
—
I/S
I/S
R
—
I/R
— 100
I
S
S
S
—
—
—
S
—
—
S
—
—
S
100
100
<10
100
29
10
pseudobrasiliensis
N. otitidiscaviarum
100
15
10
9
COMPLEX
N. transvalensis
—
—
10
COMPLEX
N. transvalensis
0
0
12
33
3
87
140
Type I: N. abscessus
(1)
IMP GENTLNZMINOT-SSULFA
b
Type II: N. brevicatena
c,44,140
N. paucivorans
(3)
Type III: N. nova type
21,101,137,140
strain
144
33,52,110,14
21,101,132,139,140
farcinia
Type IV: N. asteroides
sensu stricto (3)
21,104
132
N. cyriacigeorgici (1)
N. brasiliensis COMPLEX
21,54,137
N. brasiliensis
N.
21,14
e,14,21,45,51,140
e,21,100
142
—
—
<17
0
<10
100 100
98
97
83
95
—
<10
— 100
26
94
—
29
78
55
f
57
86 100 100f 31
31
50
50
60
50
90
— 100
54
82
90
—
—
—
—
—
—
20
—
—
—
—
87
—
—
—
—
—
—
12
—
—
—
—
100
R
S
S
S
—
—
0
—
S
—
S
—
—
—
—
100
—
4
—
—
—
—
d
94/<50 92/<50
78
9
d
sensu stricto
142
New taxon 1
87,142
New taxon 2 (1)
Type IV: N. asteroides
126,142
COMPLEX
AMK, Amikacin; A–C, amoxicillin-clavulanate;; AMP, ampicillin; CTX, cefotaxime; CTA, ceftriaxone; CIPRO, ciprofloxacin;
ERY, erythromycin; IMP, imipenem; GENT, gentamicin; LNZ, linezolid; MINO, minocycline; T-S,
trimethoprim-sulfamethoxazole; SULFA, sulfonamides; S, sensitive; I, intermediate sensitivity; R, resistant.
a
If data from only a small number of clinical isolates were available, the number of isolates is
indicated in parentheses following the species name and susceptibility patterns are designated by S
(sensitive), I (intermediate sensitivity) and R (resistant). When 2 letters (e.g., S/I) are present the first
letter represents the susceptibility pattern of the majority of isolates.
b
To date, no clinical isolates have been tested.
c
N. paucivorans has tentatively been categorized as a type II N. asteroides complex based on a 99.7%
16S rRNA gene sequence similarity to N. brevicatena. (Yassin AF, et al. 2000. Int J Sys Evol
Microbiol 50:803–809.)
CHAPTER 49 Actinomycosis and Nocardiosis
Page 19 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
d
Cited references report significantly different susceptibility patterns to third-generation
cephalosporins.
e
Susceptibility data for N. otitidiscaviarum and N. transvalensis complex isolates are confounded by
lack of separation of more recently identified species.
f
Approximately 50% of isolates were of only intermediate sensitivity.
460
Susceptibility studies have identified relatively characteristic species-associated resistance patterns (Table 49-4)
and led to the use of various antibiotics other than or in conjunction with sulfonamides to treat nocardiosis in
people. In vitro, combinations of imipenem with cefotaxime or trimethoprim-sulfamethoxazole and amikacin
with trimethoprim-sulfamethoxazole were synergistic, increasing minimum inhibitory concentrations four times
or more for the majority of 26 isolates of N. asteroides complex. Combinations of amikacin with imipenem or
53
cefotaxime were predominantly additive.
Nocardia species tested.
21,33,54
461
Linezolid, an oxazolidinone, had in vitro activity against all
Based on in vitro data, topical imidazoles and ketaconazole may be effective
41
against some Nocardia species. Treatment success has been reported with amikacin, ampicillin,
broad-spectrum cephalosporin, clarithromycin, doxycycline, erythromycin, imipenem, minocycline, ofloxacin,
82,99,83,104,130
Nocardiosis in animals that are severely ill, have systemic
and linezolid alone or in combination.
diseases, or have predisposing conditions may warrant initial combination drug therapy. If CNS disease is
present, use of drugs with excellent CNS penetration, which include third-generation cephalosporins,
imipenem, and linezolid, may be more effective than sulfonamides alone. Longer term use of linezolid in
50
humans produces a reversible myelosuppression (anemia and thrombocytopenia)
and rarely has been
79,80
Ideally, drug selection should be based on susceptibility
associated with optic and peripheral neuropathies.
studies of the isolate but if the information is not available, logical choices can be made using the in vitro data
in Table 49-4. Substitution of antibiotics within a class of drugs may not provide effective treatment; for
example, although sensitive to amikacin, Nocardia farcinia isolates are resistant to gentamicin (see Table 49-4),
54
and although sensitive to minocycline, N. brasiliensis isolates are mostly resistant to doxycycline. Drug
susceptibility patterns of Nocardia species more recently isolated from human patients (Nocardia abscessus,
Nocardia asiatica, Nocardia cyriacigeorgici, Nocardia inohanensis, Nocardia yamanashiensis, Nocardia
48,68-71
niigatensis, and Nocardia beijingensis) have not yet been fully characterized.
11
In a review of 53 dogs with nocardiosis, 50% of the dogs died and 38.5% were euthanized. Nine of 19 cats
with nocardiosis either were euthanized or died.* The high mortality rate is partly attributable to predisposing
conditions (distemper in dogs), delayed diagnosis, and inappropriate therapy. With earlier diagnosis and
multidrug therapy, mortality of nocardiosis in animals may decrease to the rate reported in people. Only 19.8%
of people with primary infections died, whereas 42.4% of patients with predisposing conditions and more than
10
50% of patients with either systemic or CNS nocardiosis died.
49.2.7
*
Mycobacteria/Nocardia Research Laboratory, Department of Microbiology, University of Texas Health
Center at Tyler, 11937 US Highway 271, Tyler, TX 75708. Phone: 903-877-7685; Fax: 903-877-7652.
*
References 2, 3, 6, 9, 26, 38, 59, 62, 78, 93, 95, 102, 109, 131, 141.
Public Health Considerations
No cases of human nocardiosis acquired from direct contact with an infected dog or cat have been reported;
however, several cases of cutaneous nocardiosis transmitted to people by a scratch or bite from clinically
healthy cats and dogs have been documented.
7,15,45,86,118
Nocardia species, which are ubiquitous in the soil,
CHAPTER 49 Actinomycosis and Nocardiosis
Page 20 of 21
Infectious Diseases of the Dog and Cat, 3rd Edition
can contaminate the claws and teeth of dogs and cats, although the risk of a person contracting nocardiosis by
an animal bite or scratch wound is no greater than the risk associated with getting a puncture wound while
gardening. Special precautions are warranted when a person with suppressed immunity (e.g., who is receiving
immunosuppressive drug therapy, who has human immunodeficiency virus infection) is caring for a dog or cat
with nocardiosis.
49.3
Acknowledgment
The author would like to thank Barbara Brown-Elliott, Mycobacteria/Nocardia Research Laboratory, Department
of Microbiology, University of Texas Health Center at Tyler, for her comments regarding the methods used for
speciation of Nocardia isolates.
49.4
*
Suggested Readings
* See the CD-ROM for a complete list of references.
31. Clarridge, JE III , Zhang, Q: Genotypic diversity of clinical Actinomyces species: phenotype, source,
and disease correlation among genospecies. J Clin Microbiol. 40, 2002, 3442–3448.
108. Pascual, C, Foster, G, Falsen, E, et al.: Actinomyces bowdenii sp. nov., isolated from canine and feline
clinical specimens. Int J Syst Bacteriol. 49, 1999, 1873–1877.
116. Roth, A, Andrees, S, Kroppenstedt, RM, et al.: Phylogeny of the genus Nocardia based on reassessed
16S rRNA gene sequences reveals underspeciation and division of strains classified as Nocardia asteroides
into three established species and two unnamed taxons. J Clin Microbiol. 41, 2003, 851–856.
124. Sivacolundhu, RK, O'Hara, AJ, Read, RA: Thoracic actinomycosis (arcanobacteriosis) or nocardiosis
causing thoracic pyogranuloma formation in three dogs. Aust Vet J. 79, 2001, 398–402.
135. Walker, AL, Jang, SS, Hirsch, DC: Bacteria associated with pyothorax of dogs and cats: 98
cases,1989-1998. J Am Vet Med Assoc. 216, 2000, 359–363.
CHAPTER 49 Actinomycosis and Nocardiosis
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