Bacterial Infections Flashcards
What factors play a role in the development of a bacterial disease?
not an inevitable consequence of the pathogenic bacteria on body surface
related to many factors including:
response of the host
presence of damaged tissue
location of the bacteria
bacterial virulence
What are some of the basic functions of virulence factors?
penetrate the epithelium
bind to cell surfaces
acquire iron
evade immune responses
hide within cells
promote transmission to another host
What does IFN-a/b do during bacterial invasion?
boosts macrophage response and enhances their production of IFN-y, nitric oxide, and TNF-a
What is the role of vitamin D in immunity against Mycobacterium in diurnal animals?
Mycobacteria interact with TLR 1/2 –>
activates a gene encoding a Vit D receptor –>
receptor is upregulated on macrophages –>
binding of Vit D to receptor upregulates expression of cathelicidin –>
can kill intracellular mycobacteria
*serum Vit D levels are linked to resistance against mycobacteria
How can platelets aid in bacterial resistance when activated?
release AMPs and nitric oxide, bind to neutrophils and enhance activity
What are the 5 mechanisms by which the adaptive immune responses combat bacterial infections?
1) neutralize toxins or enzymes with antibodies
2) kill bacteria by activating classical complement pathway
3) opsonize bacteria
4) destroy intracellular bacteria with activated macrophages
5) kill bacteria with CD8+ T cells
(relative importance of each depends on the bacteria)
What is the heat-shock protein (HSP) response?
low levels of HSPs are present in bacteria at normal temp
mild stress like low fever induces HSP production
when bacteria is phagocytized even more HSP is produced
HSP 60 is predominant one in mycobacteria infections
HSPs are highly antigenic and activate the immune system
What happens if an animal mounts an inappropriate Th2 instead of Th1 response to invading bacteria?
M2 but not M1 macrophages may be activated
least to chronic progressive disease
can have disorganized granulomas and bacteria-laden macrophages
(tuberculosis infections will often swing between Th1 and Th2 responses)
How do bacteria evade innate immunity by interfering with TLR signaling and inflammasome activation?
- production of modified PAMPs
- masking of PAMPs
- blockage of TLR signaling pathways
- destruction of signaling molecules
- destruction of NFkB
- misdirection of signaling pathways towards anti-inflammatory
How do bacteria evade innate immunity by resisting AMPs?
- staphylokinase can bind and neutralize defensins
- aureolysin destroys cathelicidin
- change the negative charge and fluidity of cell membrane to decrease defensin binding
How do bacteria evade innate immunity by blocking phagocytosis?
- binds Fc region of IgG
- encapsulated bacteria have hydrophilic capsules
- evade opsonization
- switching from planktonic growth to biofilm production
- avoid being phagocytized by killing phagocytes
- resistance against lysosomal enzymes
- resistance against respiratory burst
- interfere with phagosomal maturation
- break down NETs and METs
What does staphylococcus Protein A do?
binds Fc region of IgG
- antibodies can’t bind to phagocytic cells or activate complement
upregulates keratinocyte adhesion molecules
What does staphylococcus Protein M do?
prevents opsonization by binding fibrin and masking C3b-binding sites
What does staphylococcus Factor H do?
prevents opsonization by inactivating bound C3b
What does streptolysin O do?
on Strep canis
lyses neutrophil cell membranes
What does the specialized peptidoglycan in the S. aureus cell wall do?
resist lysozyme
What do endonucleases secreted by S. aureus do?
degrade DNA NETs
further dephosphorylated to trigger apoptosis in nearby macrophages
How do bacteria evade innate immunity by avoiding metabolic privation?
- activate their own tryptophan synthesis
- produce siderophores to capture available iron
How do bacteria evade adaptive immunity?
- changing surface coat
- secrete proteases to destroy immunoglobulins or cytokines
- live within macrophages (pathogenic mycobacteria)
–> either alive (virulent) or as “cellular corpses” (avirulent) - interfere with macrophage polarization by switching to M2 and IL-10
Why do pigs with Erysipelothrix get arthritis?
Type III hypersensitivity
Why do horses get purpura hemorrhagica?
Type III hypersensitivity to Strep equi equi (causative agent of strangles)
may also be associated with Rhodococcus equi, equine influenza virus, or equine herpesvirus type 1
Do antibiotics “cause” resistance?
not technically
typical infection consists of wild-type and resistant strains
antibiotic exposure can select for resistant bacteria, which multiply because the competition from more susceptible bacteria is reduced during antibiotic administration
What are the most common bacteria producing resistant infections in small animals?
Escherichia coli
Pseudomonas aeruginosa
methicillin-resistant Staphylococcus species
Enterococcus species
What virulence factors does Staphylococcus pseudintermedius have?
cytotoxins
exfoliative toxins
superantigens
cell wall–associated (CWA) proteins
ability to form biofilms
accessory gene regulator (agr) quorum-sensing system
potentially Staph ammonification
(includes things like proteases, thermonucleases, coagulases, DNAase, lipase, hemolysin, clumping factor, leukotoxin, enterotoxin, protein A, and exfoliative toxin)
What are staphlococcal superantigens?
a family of potent immunostimulatory exotoxins
more than 20 distinct superantigens from S. aureus
classically associated with food poisoning and toxic shock syndrome
- causative agents (enterotoxins and toxic shock syndrome toxins)
- 6 serotypes of enterotoxins (A-G)
heat-stable proteins that exhibit pyrogenicity, superantigenicity and capacity to induce lethal hypersensitivity
What are staphylococcal leukotoxins?
pore-forming toxin that targets immune system cells such as neutrophils and monocytes
What are staphylococcal phenol-soluble modulins?
family of peptides that have cytolytic activity against a variety of cells including neutrophils and erythrocytes
What do staphylococcal exfoliative toxins do within the skin?
digest desmoglein (Dsg) 1
causes intraepidermal splitting
involved in bullous impetigo, staphylococcal scalded skin syndrome and swine exudative epidermitis
What do staphylococcal hemolysins do?
are pore forming toxins that target a variety of cells including RBCs
What gives S. aureus its golden color?
Staphyloxanthin which is an antioxidant to protect the cell from ROS produced by host immune cells
What do pathogenic staph species due to the pH of the skin?
neutralize it by down-regulates organic acid production and up-regulates purine biosynthesis and ammonia production, increasing urease and arginine deiminase activity
What is associated with dogs having a significantly higher risk of
carrying ESBL- and/or AmpC-resistant E. coli?
history of antibiotic treatment in the past year
dogs from shelters/breeders
feeding of diets that contain raw meat
Which drugs are most often cited for driving MRSA acquisition and
transmission in humans?
cephalosporins and fluoroquinolones
What does clavulanic acid do when combined with amoxicillin?
is a a β-lactamase inhibitor to help overcome β-lactamase resistance
What is the mecA gene?
in staphylococcal species
encodes an altered penicillin-binding protein (PBP-2a)
- a transpeptidase that helps form the bacterial cell wall
- has a lower affinity for β-lactam antibiotics
- don’t bind to the ringlike structure of penicillin-like antibiotics
- enables transpeptidase activity in the presence of β-lactams
- prevents β-lactams from inhibiting cell wall synthesis
spread through the staphylococcal chromosome cassette (SCCmec)
phenotypic expression of methicillin resistance is variable
What is the mecC gene?
in staphylococcal species
shares only 70% similarity to mecA
encodes resistance to β-lactam antibiotics and some non-β-lactams
What mobile genetic element type accounts for the greatest portion of resistance spread between organisms?
Plasmid-induced resistance
What are the mechanisms of horizontal gene transfer between bacterial cells?
1) transformation (DNA fragments are released and taken up)
2) transduction (uses bacteriophages)
3) conjugation (bacteria dock together and share gene)
4) transfection (disruption of the cell wall, happens in experimental settings)
What are transposons?
responsible for the microbial genome flexibility
are capable of changing their position within the same DNA molecule or jump between diverse DNA molecules, including plasmids
What are integrons?
associated with great benefits for bacterial fitness and robustness
provide “tools” that enable survival under varying environments
can be mobilized both by the bacterial chromosome and plasmids
can be propagated and integrated far from their original site
What are some non-mobilizable non-heritable contributors of bacterial resistance?
growing in biofilm
swarming adaptation
persister cells
What is phenotypic persistence?
the condition where bacterial cells are not killed by the dose/type of antibiotic administered but are in a quiescent status (persister cells) that is reversed once the stressor is removed
(but the antibiotic susceptibility is reverted along with the bacterial growth and second exposure to the antibiotic results in the bactericidal or bacteriostatic effect)
How does biofilm growth preserve bacterial cells from antibiotic treatment?
are fixed microbial communities in extracellular polymeric substances
- stick to each other and surfaces (irreversible attachment)
- may be a single organism or a mixture
provide an excellent and stable homeostasis environment
matrix might reduce antibiotic efficacy by diminishing its diffusion
- and host immune response
matrix may neutralize antimicrobial agents
matrix may seize antibiotic molecules through its complex structure
- different regions of the biofilms are featured by subpopulations
- may have bacterial populations with dynamic susceptibility to antibiotics
have a communication mechanism, called the quorum sensing system
What is swarming movement of bacteria?
strategy to shield themselves from antibiotic treatments
complex physiological adaptation processes
- increased codification for porins and efflux pumps
several proteases affecting swarming are relevant for forming biofilms
What is penicillinase?
produced by more than 90% of staphylococcal isolates
directly inactivates penicillin and penicillin-derived antibiotics
What is blaZ?
gene that encodes β-lactamase in Staphylococcal species
What is β-lactamase?
encoded by blaZ in Staph species
predominantly extracellular enzyme
synthesized when staph are exposed to β-lactam antibiotics
hydrolyzes the β-lactam ring, rendering the β-lactam inactive
How does fluoroquinolone resistance develop?
spontaneous chromosomal mutations in the target of the antibiotic
- topoisomerase IV - gyrA/gyrB
- DNA gyrase (topoisomerase II) - parC and parE
or by the induction of a multidrug efflux pump
What happens after exposure of a quinolone-resistant isolate to a quinolone?
increases the organism’s expression of fibronectin-binding protein, a surface protein that mediates adherence to tissue surfaces
Does susceptibility testing always match with clinical outcomes of use?
there is potential disparity between in vitro susceptibility testing and in vivo therapeutic efficacy
What are the mechanisms of Staph resistance to macrolide antibiotics?
modification of the target site for the antibiotic (most common)
- carried out by methyltransferase Erm
- coded by erm gene (usually ermA or ermC)
- may be expressed in a constitutive manner = inducible resistance
- D-test
Synthesis of efflux pumps proteins such as ABC proteins
Synthesis of MLS-B-inactivating enzymes
mutations in chromosomal genes encoding ribosomal proteins
What is a D-test?
test for inducible resistance in clindamycin
disks for erythromycin and clindamycin are placed on a plate
- plate is coated with bacteria
incubated overnight
should make a perfect circle around clindamycin if not present
positive D-test has blunting of the growth by the erythromycin side
What is the most common mechanism of resistance to aminoglycosides in S. aureus?
synthesis of enzymes of the transferase group that modify the aminoglycoside molecule
What is the most common mechanisms of resistance to tetracyclines in staph species?
Active removal of the antibiotic from the bacterial cell
- membrane protein Tet(K): resistance except to minocycline
- membrane protein Tet(M): resistance including minocycline
Ribosomal protection
What is the cause of chloramphenicol resistance in staph species?
synthesis of chloramphenicol acetyltransferases (CATA7, CATA8, CATA9)
removal of chloramphenicol by membrane proteins (MFS superfamily)
may also result from mutations in genes encoding ribosomal proteins
What is the cause of trimethoprim resistance in staph species?
synthesis of dihydrofolate reductase
Why do Mycolicibacterium spp. (former Mycobacterium spp.) tend to cause panniculitis?
they are attracted by lipid-rich environments
Which types of bacterial infections are considered epidermal disease on histopathology?
Dermatophilosis
Exudative epidermitis
Superficial pyoderma
Surface pyoderma
Impetigo
Which types of bacterial infections are considered hair follicle diseases on histopathology?
Deep pyoderma
Post-grooming furunculosis
Interdigital furunculosis
Canine acne
GSD pyoderma
Which types of bacterial infections are considered dermal and pannicular diseases on histopathology?
Botryomycosis
Nocardiosis
Actinomycosis
Mycobacteriosis
Glanders
Necrotizing faciitis
Which drug is associated with increased risk of toxic shock syndrome in dogs?
enrofloxacin can cause a bacteriophage induced lysis of S.canis and superantigen expression (via the SOS response)
Which dog breeds are at most risk of toxic shock syndrome?
Shar Pei, racing greyhounds, Great Dane
Which bacteria is most commonly associated with toxic shock syndrome in dogs?
Streptococci (same for people)
but genes coding for TSS toxins have been demonstrated in canine S. pseudintermedius
Which types of bacterial infections are considered vascular diseases on histopathology?
Erysipelas
Rocky mountain spotted fever
Lyme disease
Purpura hemorrhagica
Porcine ear necrosis syndrome
What is the relative diversity of the animal microbiota compared to humans?
animals have a higher diversity of their microbiota
What is an individual’s microbiota primarily influenced by?
In general: host taxonomic order and geographical location
Canine: mainly by individual variability and body site
Horse: body site
What are the most common bacterial phyla found on dog skin?
Proteobacteria
Actinobacteria
Firmicutes
Bacteroidetes
Fusobacteria
What are the most common bacterial phyla found on cat skin?
similar bacterial phyla as dogs
- Proteobacteria
- Actinobacteria
- Firmicutes
- Bacteroidetes (one of most prevalent, from mouth, related to grooming)
- Fusobacteria
What are the most common bacterial genera on equine skin?
Psychrobacter
Macrococcus
Pseudomonas
Acinetobacter
Planomicrobium
Arthrobacter
Carnobacterium
Desemzia
Corynebacterium
What do commensal species such as Cutibacterium acnes (formerly Propionibacterium acnes) and Staphylococcus epidermidis do to the pH of the skin?
metabolize lipids, leading to the production of antimicrobial metabolites and decreased cutaneous pH –> hostile environment for pathogenic organisms
What do S. epidermidis, S. hominis, and S. felis have to do with production of AMPs?
they directly produce AMPs that inhibit the growth of Staphylococcus aureus and S. pseudintermedius
S. epidermidis can also induce the production of AMPs by the host
What are the two models that explain why dysbiosis could occur?
(1) dysbiosis driven by microbial communities
- a shift in microbial composition alters the immune response
(2) dysbiosis driven by host biology/pathology
What are the primary pathogens associated with superficial pyoderma in dogs?
Staphylococcus spp. (primarily S. pseudintermedius)
S. delphini
S. schleiferi
S. coagulans
What are some characteristics of the canine stratum corneum that make them more susceptible to superficial pyodermas?
it is thinner and more compact than in other species
they lack a lipid follicular plug
it has decreased intercellular lipids
it has a higher pH (more neutral than humans)
What is impetigo?
a superficial pustular dermatitis
commonly caused by coagulase-positive staphylococci
- S. pseudintermedius in dogs
- S. aureus in other species
Which non-human animal species are most likely to be affected by impetigo?
Dogs, cats, cattle, goats, and sheep
What are the lesions of classical impetigo like?
small, papules and pustules affecting the interfollicular epidermis
- frequently rupture
usually occur at the time of puberty
- can also happen in some lactating females
nonpruritic, nonpainful, and frequently heal spontaneously
What are predisposing factors for classical impetigo?
moist environment, skin abrasions, parasitism, stress, or poor nutrition
Milking equipment and lack of sanitization
Where do lesions associated with classical impetigo occur most frequently in dogs?
axillary and inguinal regions
Where do lesions associated with classical impetigo occur most frequently in cats?
areas that are in contact with the mouth of the queen
Where do lesions associated with classical impetigo occur most frequently in cows, does, and ewes?
base of the teats and intermammary sulcus of the udder, ventral abdomen, perineum, vulva, medial thighs, and ventral tail
What is bullous impetigo?
more severe form of impetigo
can also affect adult dogs
results in larger, pan-follicular pustules
often have underlying conditions (ex. endocrinopathies)
What is the primary histopathologic change associated with impetigo?
subcorneal pustules with neutrophils, not associated with hair follicles
cocci are seen within pustules
- can be highlighted with Gram stain or GMS
may have acantholytic keratinocytes
- due to exfoliative toxins cleaving Dsg 1
What is dermatophilosis?
rain rot/rain scald
caused by Dermatophilus congolensis
- gram-positive facultative anaerobic bacterium
What type of bacteria are Staph species?
gram-positive, catalase-positive facultative anaerobic organisms
- primarily considered aerobic
can be coagulase positive or negative
What does coagulase positive mean?
has an enzyme that enables the conversion of fibrinogen to fibrin
usually associated with pathogenic species
“clumping factor” can be detected by carrying out a slide coagulase test
free coagulase can be detected using a tube coagulase test
- uses rabbit plasma
Where is dermatophilosis most common?
tropical and subtropical climates
- especially in these climates it may be generalized/cause systemic illness
What are the two staph species that are considered normal skin flora in most food animals?
S. aureus
S. hyicus
What animals are most often affected with dermatophilosis?
Cattle
temperate climates, goats and sheep
occasionally horses and camels
zoonotic and reported in a bearded dragon
What are the main predisposing factors for dermatophilosis?
wet conditions/prolonged wetting
- results in softening of stratum corneum and dissolving of lipid film
- causes release of motile zoospore form
- easier for zoospores/coccoid bodies to overcome barrier
trauma to the skin (eg, due to ticks, insects, or UV damage)
- can survive on the mouthparts of flies and ticks for 24h
Where on the animal’s body do lesions of dermatophilosis and what do they look like?
dorsum, distal extremities, and teats are most commonly affected
consist of papules, pustules, and domed, adherent crusts
- often coalesce to form a line or polycyclic pattern
- tend to be painful but not pruritic
- “paint brushes”
- may have while to green purulent discharge under crusts
How long can Dermatophilus congolensis remain viable in crusts?
at 28-30 C they can last up to 42 months
if freeze-dried, up 13 to 26 years
How long is the incubation period of Dermatophilus congolensis?
~2 weeks
What happens once zoospores of Dermatophilus congolensis penetrate the skin barrier?
Zoospores then produce branching filaments –>
infiltrate into the epidermis and outer root sheath –>
keratinocytes begin to cornify and neutrophils accumulate –>
cycle repeats, resulting in layered, thick crusts
How do you diagnose dermatophilosis?
cytology
- stain with Diff-Quick, Gram stain, or new-methylene blue
histopathology
aerobic culture
- can be difficult to culture
- grows well on blood agar, brain heart infusion, an tryptone broth
- at 37 C it is white/filamentous and at 22 C it is orange/coccoid
- can be easily overrun by contaminants
What are the histopathologic features of dermatophilosis?
a thick crust with alternating layers (palisading crusts) of orthokeratosis and parakeratosis, and inflammatory cells and necrotic debris +/- pustules
typical “railroad track” bacteria consist of parallel rows of coccoid bodies
- Gram stain, Giemsa
What is the treatment for dermatophilosis?
Topicals (frequently for 3-5 consecutive days and then weekly)
- iodophores
- 2-5% lime sulfur
- 1-4% chlorhexidine
+/- systemic antibiotics (usually penicillin, erythromycin, TMS)
- may be more resistant to TMS
Control spread and reinfection
What is exudative epidermitis?
“greasy pig disease”
an acute, exudative, vesicopustular disease
divided into acute/peracute, subacute/acute, and chronic/subacute forms
Morbidity varies from 10 to 100%
Mortality from 5 to 90% (average: 25%)
What is the common causative agent of exudative epidermitis?
Staphylococcus hyicus hyicus that express exfoliative toxins targeting Dsg1
- ExhA
- ExhB
- ExhC
- ExhD
- SHETA
- SHETB
What is the acute form of exudative epidermitis?
seen in suckling piglets
1) dark‐brown, greasy exudate appears periocularly
2) vesicopustular eruption on snout, lips, tongue, gums, and coronets
3) red‐brown macules behind ears, on the ventral abdomen, in axillae
4) entire body covered by erythema, a greasy exudate, and thick brown crusts
5) piglets have depression, anorexia, and dehydration –> death
- within 1 to 5 days
- pruritus and pyrexia are usually absent
What is the subacute form of exudative epidermitis?
seen in suckling piglets
follows general pattern of acute
but skin becomes thickened and wrinkled –>
total body exudate becomes hardened and cracked
- moist, erythematous skin in between (“furrows”)
death often occurs within a week to 10 days
What is the chronic form of exudative epidermitis?
seen in weaned piglets
erythema and waxy brown crusts confined to the ears and head
piglets are usually otherwise healthy
What are the histopathologic findings associated with exudative epidermitis?
earliest lesions = subcorneal vesicles and neutrophilic pustules
- a few acantholytic keratinocytes
- may involve hair follicles
as it progresses = superficial serocellular crusting with large numbers of neutrophils, exfoliated stratum corneum and numerous colonies of gram-positive coccoid bacteria
chronic = marked orthokeratosis and parakeratosis; the underlying epidermis is acanthotic with hyperplastic rete pegs
dermatophilosis
Gram stain, from a horse with crusts
dermatophilosis
Exudative epidermitis
bacterial furunculosis (d shows bacteria in follicular lumen)
Which organism is typically associated with furunculosis due to contaminated devices, shampoos and grooming products, disinfectants, ear-cleaning solutions, and contaminated surgical cold sterile solution (not traditional post-grooming furunculosis)?
Burkholderia cepacia (formerly known as Pseudomonas cepacia)
What organism is typically associated with a severe type of deep folliculitis, furunculosis, and pyoderma associated with vigorous grooming with contaminated bathing products and instruments (post-grooming furunculosis)?
Pseudomonas aeruginosa
S. pseudintermedius, S. epidermidis, Enterobacter cloacae, S. hominis, Klebsiella oxytoca, B. cepacia, Proteus sp., E. coli, and Serratia marcescens have also been reported
How long after grooming do lesions due to post-grooming furunculosis appear?
acute onset of 2 days after grooming or water immersion, but they may take up to 7 days to develop
frequently causes pain, fever, and inappetence
occasionally causes sepsis and death
What is botryomycosis?
uncommon, chronic, deep dermatitis that occurs in several species, including dogs, cats, pigs, cattle, horses, laboratory animals, and humans
also known as bacterial pseudomycetoma
most often occurs as a result of trauma
What are the common causative agents of botryomycosis?
most common agent is S. aureus
other bacteria such as Streptococcus spp., Pseudomonas spp., E. coli, Proteus spp., and Pasteurella spp. have been isolated
What are the typical clinical signs of botryomycosis?
solitary to multiple, firm, nonpruritic SC nodules with draining tracts
center may contain white granules
horses may rarely have disease that follows the lymphatic vessels
- more common if they have PPID
What are the histopathologic findings associated with botryomycosis?
pyogranulomatous subcutaneous inflammation
clusters of bacteria in the center
deeply eosinophilic club-like, Splendore–Hoeppli reaction
- corresponds to the macroscopic white grains
Botryomycosis
What is the recommended treatment of botryomycosis?
complete surgical excision +/- antibiotics (usually TMS or enro in horses)
may need >4 months of antibioitic treatment
- could also try B-lactamase-resistant antibiotic, rifampin
Botryomycosis
From crusts on a horse
Suggestive of dermatophilosis
palisading crust formed by alternating horizontal layers of hyperkeratosis (black arrow) and pus (green arrow)
What is cellulitis (phlegmon) in horses?
severe, deep diffuse suppurative infection wherein the process spreads through the dermis and subcutis along the tissue planes
overlying skin may be friable, darkly discolored, and devitalized
affected tissues may slough, leaving large ulcers
legs are most commonly affected
most are are febrile
leukocytosis, neutrophilia, and hyperfibrinogenemia are common
What predisposes horses to cellulitis?
no apparent age or sex predilections
Thoroughbreds and race horses seem predisposed
many cases of leg cellulitis do not have a history of recent trauma
coagulase-positive staphylococci are isolated in >80% of cases
What is the treatment of cellulitis in horses?
Initial treatment often includes an IV b-lactam and aminoglycoside
up to 25% of the horses with leg cellulitis are euthanized
recurrence happened in 23% of discharged horses
In horses, which anatomic location of pyoderma carries a poor prognosis?
Tail pyoderma
may reflect failure to:
(1) employ aggressive systemic antibiotic therapy
(2) control underlying or associated diseases
usually follows the cutaneous trauma produced by tail rubbing provoked
by insect-bite hypersensitivity, atopic dermatitis, food allergy, chorioptic ange, psoroptic mange, pediculosis, oxyuriasis, and behavioral abnormalities
What are the virulence factors of S. equi equi?
a hyaluronic acid capsule
M(SeM) protein
- inhibits phagocytosis and complement deposition
What causes pigeon breast/pigeon fever/false strangles in horses?
Corynebacterium pseudotuberculosis
mostly in western United States
believed to be spread by biting flies
characterized by deep subcutaneous abscesses
can also affect cows, goats, sheep, llamas
with appropriate treatment via drainage, abscesses take 2-3 months to heal
can also cause ulcerative lymphangitis in people, cows, horses
- is zoonotic
- not the only cause of ulcerative lymphangitis
What is ulcerative lymphangitis?
bacterial infection of the cutaneous lymphatics
most commonly associated with poor hygiene and insect transmission
develop hard to fluctuant nodules, which abscess, ulcerate,
and develop draining tracts, regional lymphatics are often corded
can be associated with many species of bacteria
In addition to skin lesions, what organs do Nocardia commonly affect?
companion animals: lungs and pleura
cows: mastitis
How do animals contract Nocardia?
it is ubiquitous in the environment (soil, water, and plants)
can be inoculated into the skin via puncture wounds or inhalation
- cutaneous lesions or pulmonary (most common in humans)
more common in immunosuppressed individuals
- decreased cell-mediated immunity
can have hematogenous spread
What are the most common species of Nocardia affecting the skin?
from the Nocardia asteroides complex
- some can survive intracellularly
What is the appearance of Nocardia?
gram-positive, partially acid-fast, branching filamentous bacteria
- modified acid-fast Fite-Faraco may be better than Ziehl-Nielsen
aerobic
What is a problem that can occur when culturing Nocardia?
Most are visible after 2 days but may grow slowly
- aerobic on Sabouraud’s glucose agar or blood agar
- sometimes weeks to form colonies
- can be overgrown by contaminants
What is a problem that can occur when culturing Actinomyces?
not happening in anaerobic or micro-aerophilic conditions
- 5% to 10% carbon dioxide
even in correct culture environment they can be fastidious
- very specific nutritional requirements
- if the do grow, often taking weeks to form visible colonies
if culturing esp from oral cavity, it doesn’t always mean disease
What are the histopathologic findings associated with Nocardia?
nodular to diffuse pyogranulomatous inflammation in dermis/subcutis
aggregates around tangled colonies of beaded and filamentous bacteria
- poorly staining on H&E
uncommon for them to have tissue grains
don’t tend to be surrounded by the Splendore–Hoeppli reaction
colonies in tissues may be sparse and multiple sections may be needed
- use acid-fast stain!
Biopsy from a cat. Last picture is stained with Fite-Faraco.
Nocardia
Where can Actinomyces normally be found and in what circumstances does it tend to cause infections?
Mouth
occurs most often in hunting dogs/animals that have access to outdoors
- associated with bite wounds or foreign material
can be associated with pyothorax in cats
frequently causes cervicofacial disease
can have hematologic spread
Which bacteria can sometimes for interlesional colonies that can be clinically visualized as yellow-tan sand-like granules?
Actinomyces
look like “sulfur granules” but don’t have sulfur
What are the histopathologic findings associated with Actinomyces?
nodular to diffuse pyogranulomatous inflammation in dermis/subcutis
aggregates around tangled colonies of beaded and filamentous bacteria
- doesn’t stain well with H&E, better with Gram, Giemsa, and GMS
may have have tissue grains
frequently have Splendore–Hoeppli reaction
can form narrow branched hyphae-like filaments in tissues
- in culture can also form spore, spore chain, sporangia, and mycelium
colonies in tissues may be sparse and multiple sections may be needed
Last picture is gram stain
Actinomyces
What is the appearance of Actinomyces?
gram-positive, non-acid-fast, filamentous bacteria
- anaerobic to microaerophilic
- can be branching or have a beaded appearance
Which bacterial organism causes “lumpy jaw” in cows?
Actinomyces bovis
lesions most commonly seen on mandible and maxilla
Which bacterial organism causes fistulous withers and poll evil in horses?
Actinomyces
What is Actinobacillus lignieresii?
gram-negative, aerobic to facultatively anaerobic coccobacillus to rod-shaped commensals of the oral and upper respiratory mucosa
may cause pyogranulomas (often on face) and “wooden tongue”
- not common in companion animals
can make sulfur granules and have Splendore-Hoeppli phenomenon
best seen with Gram stain gram-negative or GMS stain
What is Pseudomonas luteola?
a rare gram negative pathogen described in cats and ferrets
associated with septicemia and pyogranulomatous inflammation affecting the panniculus, pleura, mediastinum, salivary glands, and lungs
1- to 3-μm-diameter oval organisms with a 3-μm PAS-positive capsule
Stains weakly with Grocott’s methenamine silver
Mayer’s mucicarmine is negative
Can look like leishmaniasis, histoplasmosis, and even cryptococcosis
Is Actinomyces or Norcardia more likely to be associated with a mixed bacterial infection?
Actinomyces
(Nocardia is likely to be sole isolate unless contaminated sample)
What is the treatment of Actinomyces?
Prolonged antibacterial therapy (6-12+ months)
- potentially high dose penicillin/amoxicillin
- cephalexin, metronidazole, and aminoglycosides are poor in vitro
+/- surgery to debulk
cure rate can be up to 90% though other sources say many can be refractory to treatment or recur once therapy is stopped
What is the Splendore-Hoeppli reaction?
A formation of immune complexes (antigen-antibody complexes, complement, and major basic protein of eosinophils) around agent
Eosinophilic, radiating, club shaped
“sulfur granules” due to Actinomyces
Which form of Nocardia has been associated with clinical disease in people and dogs and require special media for isolation and culture?
L-form Nocardia (without a cell-wall)
What is the treatment and prognosis of Nocardia?
Surgery + medical management
- 1-3 months for people with cutaneous disease
- 6 months for people with pulmonary disease
- 12+ months for people with immune suppression
typically TMS 30 mg/kg Q12
- may be resistant to Clavamox but ok with amoxicillin
- other antibiotics can be tried
- fluoroquinolones appear to have limited therapeutic potential
in 53 dogs with nocardiosis, 50% of dogs died and 39% were euthanized
in 36 cats with disease, 16 died or were euthanized
What is the structure of Streptococcus species?
gram-positive, catalase negative, facultative to strict anaerobe cocci
- often form pairs or chains
What is necrotizing fasciitis?
a rapidly progressive and potentially life-threatening condition characterized by deep necrotizing panniculitis and fasciitis
- usually caused by bacterial inoculation to the deep tissues
- source of infection may not be apparent
Can lead to septicemia, DIC, and toxic shock syndrome
- in 70%–80% of dogs with NF
What organisms are typically associated with necrotizing fasciitis in dogs?
most commonly associated with Streptococcus canis
also S. pseudintermedius, E. coli, S. zooepidemicus, and P. multocida
What organisms are typically associated with necrotizing fasciitis in cats?
most commonly associated with Streptococcus canis
also Prevotella bivia, S. pneumoniae, and Acinetobacter baumannii
What are the histopathologic findings associated with necrotizing fasciitis?
severe necrosis and suppurative inflammation involve the dermis, panniculus, fascia and muscles, occasionally osteomyelitis
- blood vessels are usually necrotic with dermal necrosis
Which stain will highlight a Splendore-Hoeppli reaction?
PAS stain
What are fast-growing mycolicibacterial/mycobacteroidal/mycobacterial infections?
formerly mycobacteria but reclassified
opportunistic infections caused by species of the genera Mycolicibacterium or Mycobacteroides which grow rapidly in culture
- often in less than 7 days
included within the Runyon Group IV
found in soil and water throughout the world
- infections can be result of traumatic penetration
Which species are included within the Runyon Group IV/fast-growing mycobacteria?
M. smegmatis complex
M. fortuitum
M. flavescens
M. thermoresistible
M. Chelonae-Abscessus complex
Where are fast-growing mycolicibacterial/mycobacteroidal/mycobacterial infections typically seen in cats?
ventral abdominal region, involving the inguinal fat pads
What is the clinical appearance of fast-growing mycolicibacterial/mycobacteroidal/mycobacterial infections?
cutaneous and subcutaneous abscesses, which may fistulate and form draining tracts
What are the histopathologic findings associated with fast-growing mycolicibacterial/mycobacteroidal/mycobacterial infections?
Pyogranulomas /neutrophils centered on clear zones
- Lipocysts = residual lipid from adipocyte drop out/breaking
- Caution: Lipocysts not always present
Peripheral lymphoid nodules
Bacteria often difficult to visualize
- Fite’s stain is helpful (could also use GMS)
- Look for them inside lipocysts and/or inside macs
- Caution: small numbers so look carefully
Confirm by culture (since it can look like Nocardia spp)
fast-growing mycobacterial infection
What are slow-growing mycobacterial infections?
cutaneous nodules caused by mycobacteria that are fastidious, taking 4–6 weeks to grow and often failing to grow in culture
What species typically cause slow-growing mycobacterial infections in veterinary medicine?
tuberculous agents
- Mycobacterium tuberculosis
- M. microti
nontuberculous agents
- Mycobacterium avium
- M. genavense
- M. xenopi
- M. ulcerans
Which species is most likely to have cutaneous lesions associated with Mycobacterium tuberculosis?
cats (also non-tuberculosis ones)
other species are more likely develop pulmonary or alimentary infections
What are the clinical signs associated cutaneous infections caused by slow-growing mycobacterial organisms?
cutaneous infections are characterized by plaques, nodules, or abscesses that form draining tracts and may involve the head and limbs
common to have systemic disease with fever and anorexia
Which dogs are predisposed to M. avium infections?
Inherited defect in CARD9
- Miniature Schnauzers
- Basset hounds
What are the histopathologic findings associated with slow-growing mycobacterial organisms?
granulomatous to pyogranulomatous inflammation is characterized by sheets of epithelioid macrophages with few scattered multinucleated giant cells and neutrophils
Large numbers of bacteria are often seen in the cytoplasm of epithelioid macrophages with acid-fast stains, especially for lesions caused by the M avium complex
Biopsy from a cat. Second picture is a Fite’s stain.
Mycobacteria avium
What is the appearance of mycobacterial species?
nonflagellated, predominantly rod-shaped, about 0.5 μm wide, and variable in length (aerobic)
- chemically gram positive but often resist Gram stain due to lipid rich wall
- stained with carbolfuchsin (acid-fast)
What is Mycobacterium leprae?
a peculiar human pathogen that is considered an obligate intracellular pathogen as it has never been grown in vitro
has been grown in armadillos
causes leprosy and can attach the peripheral nervous system
What is M. avium subsp. paratuberculosis?
gent of Johne’s disease in ruminants
associated with Crohn’s disease in humans
What is the treatment of mycobacterial organisms?
multimodal therapy
rifampin +/- quinolone +/- clarithromycin/azithromycin +/- surgery
- maybe start with clarithromycin and quinolone while culture pending
- M. fortuitum tends to be very resistant
- treatment is frequently 3 to 12 months (1-2 months after resolution)
acepromazine has been used for to inhibit mycobacterial cell growth
Dogs/cats diagnosed with M. tuberculosis should be euthanized
- public health risk
may consider only treating saprophytic versions
What breed of dog is predisposed to canine leproid granulomas?
short-coated breed dogs, especially Boxers
What is the clinical appearance of canine leproid granulomas?
nodules on the ear margins (feet occasionally affected)
What causes canine leproid granulomas?
causative agent has yet to be identified
- appears to be a member of the Mycobacterium genus
- 16S rRNA gene sequencing shows similar agent world-wide
- seems to fall in the M genovense group
speculated that these infections may be transmitted by insect bites
- housemates have also been affected so it may be transmissible
What is the treatment of canine leproid granulomas?
complete surgical excision
may be self-limiting in some immunocompetent individuals
may consider adding systemic antibiotics if have many lesions
- lesions usually regress in 4 to 8 weeks
What is are the histopathologic findings of canine leproid granulomas?
formation of confluent pyogranulomatous inflammation
sheets of epithelioid macrophages admixed with other WBCs
sparse, 2–5 µm acid-fast positive bacilli in some macrophages
- likely to stain with Fite-Faraco acid-fast
What is feline leprosy?
often seen in cats that have access to outdoor environments
three different presentations, which are caused by different pathogens
1) M. lepraemurium
2) Novel Mycobacterium within the M. simiae complex
What is the form of feline leprosy that is caused by M. lepraemurium?
can be found in rats (thought to be the cause)
not a zoonotic agent, not transmissible
few to numerous nodules within the skin/subcutaneous tissue
- primarily on the head and limbs
- infrequently generalized
mainly in cats < 3 years
infection has an indolent course and a good prognosis
What is the form of feline leprosy that has been attributed to a novel Mycobacterium within the M. simiae complex (strain Tarwin)?
lesions seen in the head, especially involving periocular tissues
believed that cats get this during fights with cats or prey
has an indolent course with a favorable prognosis
almost entirely confined to the Victoria region in Australia
What is the form of feline leprosy that is caused by Candidatus “Mycobacterium lepraefelis”?
much more severe presentation of feline leprosy
identified in Australia and New Zealand (one case in Canada)
affects middle-aged to older, preferably male, cats with outdoor access
present with widespread cutaneous lesions
can be followed by systemic involvement
infection may lead to death or result in euthanasia
What are the histopathologic findings of feline leprosy?
may cause lepromatous leprosy
- sheets of epithelioid macrophages with other WBCs
- large numbers of organisms in the cytoplasm of macrophages
or tuberculoid leprosy
- dermal to subcutaneous granulomas with central caseous necrosis
- low numbers of organisms are seen within necrotic areas
In addition to culture, what is a good test to perform if you suspect a mycobacterial infection?
PCR
Fresh frozen tissue is best sample to submit; formalin-fixed paraffin-embedded tissue can also be used, but not as repeatably
What is farcy?
chronic skin disease in cattle that causes lymphangitis and dermatitis that is primarily distributed within Sub-Saharan Africa
caused by M. senegalensis and M. farcinogenes
can be zoonotic but lesions mimic tuberculosis
What is glanders?
zoonotic infection seen in equids caused by Burkholderia mallei
- related to meliodosis caused by Burkholderia pseudomallei
highly contagious and can be fatal in humans
- category B bioterrorism agents
eradicated in many countries
causes nodular ulcers in a “crate-like” pattern that appears as chains
- develop draining tracts
What is Erysipelothrix rhusiopathiae?
gram-positive bacillus
occurs in pig 3 mo to 3 yrs
cause several syndromes in pigs, such as septicemia, arthritis, vegetative endocarditis, cutaneous vasculitis, and abortion
with acute septicemia, pigs develop cyanotic or erythematous extremities snf erythematous diamond plaques on skin due to vasculitis
pathogen is zoonotic
- also reported in dogs
Erysipelas
What are the histopathologic findings of erysipelas?
dermal neutrophilic vasculitis with thrombosis with cutaneous necrosis and suppurative hidradenitis
Which ticks transmit Rocky Mountain spotted fever (Rickettsia rickettsii)?
*Dermacentor variabilis
Rhipicephalus sanguineus
Amblyomma sculptum
What are the cutaneous signs that can be seen with Rickettsia rickettsii?
erythema, petechiae, necrosis, ulceration, and edema
due to neutrophilic small vessel vasculitis
Which ticks transmit Lyme disease (Borrelia burgdorferi)?
Ixodes spp
What are the histopathologic findings associated with cutaneous lesions caused by Lyme disease (Borrelia burgdorferi)?
densely cellular infiltrates consisting of large, lymphoblastic cells, intermixed with small, mature lymphocytes are observed
- has a Grenz zone
What is porcine ear-tip necrosis (ETN)?
progressive loss of the ear helix in the nursery and early-grower pigs
Risk factors such as high stocking rate, fully slatted flooring without straw, high ambient temperature, poor air quality, and high humidity have been associated with outbreaks of ETN
etiology and pathogenesis of ETN has been fully elucidated
vasculitis is not a consistent finding in ETN
Erysipelas
What is Clostridium and what are the typical signs of infection?
ubiquitous, anaerobic, spore-forming, gram-positive rods
produce a wide variety of toxins and disease
- a-toxin is a lecithinase (necrotizing, leukocidal, and hemolytic)
- b-toxin is a deoxyribonuclease that is toxic to leukocytes
- γ-toxin is a hyaluronidase
if spores are introduced into tissue can cause gas gangrene
- associated with IM injection (esp. flunixin meglumine in horses)
- blackleg in cattle
Clinical signs are typically noted 12-48 h after the inciting factor
- animals are typically ill
- gas pockets form –> skin becomes necrotic and sloughs
Treatment is typically IV penicillin
What do staphyloferrins do?
Lyse RBC and steal iron to use for growth
What virulence factors does Pseudomonas have?
Alginate (AlgR) = biofilm formation!
- Increases MIC, present in 40% otitis externa isolates
- could make it more susceptible to UV
Pyocyanin and pyoverdine - proinflammatory blue-green pigment
- also other pigments
elastases (LasB) - cleaves collagen
Alkaline proteases (LecA, PlcH)
Exotoxins (ToxA, ToxR)
Eflux pump system (Mex)
AmPc β-lactamase
Type 3 Secretion System (T3SS) with 4 cytotoxins (Exo)
Hemolysins
Adherins and twitching motility
Lipases and phospholipases
What virulence factors does Dermatophilus have?
Ceramidase cleaves ceramides into FAs and PS
What virulence factors does Nocardia have?
Thick peptidoglycan layer, superoxide dismutase, catalase
What do anaerobic bacteria lack?
superoxide dismutase so cannot grow in the presence of oxygen
What is Rhodococcus equi?
mostly associated with pyogranulomatous pneumonia in foals
causes cervical lymphadenitis in cattle & swine
may cause abscessed in cats without systemic sings
- check immunosuppression status
has a virulence protein VapA
- allows survival in macrophages
treatment is macrolide + rifampin
- consider surgical excision if cutaneous
What is Treponema paraluiscuniculi?
“Rabbit Syphilis”
- Venereal disease in rabbits
a Gram-negative, spiral-shaped bacterium
Crusts, erythema, edema, vesicles, ulcers, proliferative lesions
- primarily face and perineum
Metritis, abortion and neonatal death
Dx: microscopic visualization from scrapes on dark field
- with special silver stains on biopsy
- ok to use humanlab serology
Tx: Penicillin G, chloramphenicol, azithromycin
What are the pathogens that most commonly contribute to abscesses in reptiles?
Those found in the digestive tract
Pseudomonas, Aeromonas, Salmonella, etc.
How are abscesses in reptiles best treated?
removal, rather than lancing and draining
material is granulomatous in consistency, not liquid
usually need to be on abx for months if using that to treat them
What is Devriesea agamarum?
a Gram-positive bacterium
causative agent of devrieseasis
chronic proliferative dermatitis and septicemia
- especially in desert-dwelling and dry land lizard species
subcutaneous abscesses
- tropical species
Treatment is adequate basking temperatures (43-48.5 degrees C), systemic antibiotics (ceftiofur but NOT fluoroquinolones [resistant]), keeping vivarium dry and clean all crusts/debris that form from lesions
What is Citrobacter freundii?
related to septicemic cutaneous ulcerative disease in chelonians
- can affect shells
Which bacteria is most commonly associated with “sore hocks”/pododermatitis in rabbits?
Staphylococcus aureus
Which bacterial infection is associated with otitis in chelonians and lizards?
Proteus morganii
Which staphylococcal species are most common in birds?
Staphylococcus aureus and Staphylococcus intermedius
What is “strawberry foot rot” in sheep?
Dermatophilosis around coronet and pastern
May associated with things like orf
What is the most common cause of fleece rot in sheep?
Pseudomonas aeruginosa, may appear blue-green
What is Bacillus anthracis?
a gram-positive, spore-forming, rod-shaped bacteria
causes Anthrax
can have cutaneous, GI, inhalation, peracute
What antibiotics are typically used to treat Pseudomonas infections?
aminoglycosides (including gentamicin, amikacin)
carbapenems
cephalosporins (ceftazidime and cefepime)
fluoroquinolones
penicillins combined with β-lactamase inhibitors
phosphonic acids (specifically Fosfomycin)
polymyxins
What antibiotics does Pseudomonas have intrinsic resistance to?
many penicillins and cephalosporins
- imipenem and meropenem usually ok
- maybe ceftazidime is ok
- ticaricillin is sometimes ok
fluoroquinolones
- enrofloxacin and some newer quinolones are sometimes ok
tetracyclines
aminoglycosides
- still often used with success
lincosamides
What type of bacteria is Pseudomonas aeruginosa?
gram-negative, aerobic, motile, non-spore forming rod
- can grow anaerobically
- is ubiquitous in many niches
How does β-lactams resistance occur in in Gram-negative microbes?
β-lactamases
inducible expression of AmpC
permeability alteration
extrusion by efflux pumps
to a lesser extent, PBP alteration
What is Mycoplasma haemofelis?
a gram-negative epierythrocytic parasitic bacterium
usually the causative agent of feline infectious anemia in the US
Arthropod vectors are thought to be the primary source of infection
- can also be transmitted from queen to kitten and transfusion
fever, depression, anorexia and macrocytic hemolytic anemia
cutaneous hyperesthesia and alopecia areata reported in cats
What is the vector for Ehrlichia canis?
Rhipicephalus sanguineus
What is Ehrlichia canis?
Gram negative obligate intracellular bacteria
causes thrombocytopenia, anemia, fever, lethargy, weight loss, mono or polyarthropathy, vasculitis
Skin lesions are very rare but include crusting bridge of nose dermatitis, vasculitis, and intensely pruritic papulocrusted dermatitis
Can look like SLE
Erlichia
What types of immune reactions are involved in staphylococcal hypersensitivity?
types I, III, and IV hypersensitivity responses may be involved
Gram stain
Gram positive
Peptidoglycan took up crystal violet
Gram stain
Gram negative
Took up safranin but LPS didn’t take up crystal violet
What is the major source of endotoxins?
Gram negative bacteria
What are the Staphylococcal species typically associated with skin infections in horses?
S. aureus
S. hyicus subsp. hyicus
S. delphini
