lect 27-36 Flashcards
MORAXELLA AND
CHLAMYDIA characterstics
-moraxella BCL 2
-clamydia BCL 2/3
* Moraxella
* Gram negative, strict aerobes: small clusters
* Chlamydia: large reticulate bodies.
* Obligate intracellular parasites
* Genome reduction – rely on host metabolic machinery rather than having their own!
* Biphasic development
chalmdia mechanism on cells
- Elementary bodies (EB) bind to cell surface
- Endocytosis occurs, formation of
inclusion bodies - Organism becomes metabolically active
- Reticulocyte bodies (RB) divide
- RB then differentiate back into EB
- EB escape by lysis or extrusion and infect other cells
MORAXELLA AND
CHLAMYDIA natural habitat
Moraxella
* Found on the mucous membranes of mammals
* Don’t survive well outside of host
* May be transmitted by insects
* Chlamydia
* Elementary bodies somewhat resistant to environmental conditions
* Can survive for several days outside hose
* Avian GI tract is natural site for C. psittaci
* Asymptomatic infections are common
moraxella and chamydiaceae virulence
- Moraxella
- Type IV pilli
- Cytotoxin
- Transferring and lactoferrin binding proteins
- Chlamydia
- Virulence genes comprise ~10% of their genome!
- Various secretion systems (type II, III and V) – secretion of effector
molecules involved in cellular invasion - Cytotoxin – slows down cell cycle, the organism wants to control when
the cell dies/ruptures
moraxella bovis
- Cause of infectious bovine keratoconjunctivitis (pink eye)
- Incubation period of 2 days – 3 weeks
- Clinical signs:
- Copious watery lacrimation
- Blepharospasm, photophobia, in severe cases eye ruptures.
- Cattle are the reservoir
- Transmission via mechanical vectors (insects)
-treat: topical antimicrobials
-control: fly control
Chlamydia psittaci
-causes pistattcosis (brids)
-* Clinical signs:
* Nasal and ocular discharges
* Conjunctivitis
* Green-yellow feces
* Inactivity, anorexia
-if acute: * Hepatomegaly
* Serofibrinous polyserositis
* Petechial hemorrha* Hepatomegaly
* Serofibrinous polyserositis
* Petechial hemorrhages on liver and spleen
necrotizing hepatitis
-fecal-oral or vetrical transmission
-reportable disease in USA
Chlamydia psittaci
zoonosis
- This is an important zoonoses
- Infection through exposure to aerosolized organisms
- In people pneumonia is the most common presentation
- Varies from very mild to severe acute and fulminant
- Culture negative endocarditis
- Persons at risk
- Pet birds/pigeon fanciers
- Veterinarians
- Zoo keepers
farmers,
Chlamydia abortus sheep
- Cause of enzootic abortion of ewes “EAE”
- Abortions typically occur without prior signs
- Typically occur in last month of pregnancy
- Infection remains latent until 3-4 months
-vaginal discharge after abortpion
-common in Uk and USA - Can affect up to 60% of animals in naïve flocks
- Control:
- Isolate aborting animals and clean up abortuses
-zoonosis to people: abortions, avoid eweing lambs
Chlamydia pneumoniae
people
- Cause of respiratory tract infections
- Laryngitis, pharyngitis, fever, headache
- May or may not cause pneumonia
- 2-5% of individuals have asymptomatic infections
- Affects people of all ages
- Those in crowded settings are at highest risk
- Students, military, nursing homes, hospitals, prisons
- Quite common, koala conjuctivitis.
Chlamydia suis
- Associated with infections of the reproductive and respiratory tract
- Conjunctivitis, rhinitis, pneumonia
- Return to estrus, inferior semen quality
- Can survive up to 30 days in environment
- Treatment
- Antimicrobials
- Tetracyclines
-control: cleaning and management
Chlamydia trachomatis
people
- Sexually transmitted disease
- Often no overt clinical signs
- Can cause reproductive system damage and lead to infertility
- Burning on urination or discharge
- Transmitted from mothers to newborns
- Conjunctivitis, pneumonia
- Treatment: Azithromycin
Resistant drug for moraxella and chlamydiaceace
- Moraxella and Chlamydia
- No standardized methods available for determining or interpreting
antimicrobial susceptibility - For Chlamydia this is impossible!
- Moraxella catarrhalis intrinsically resistant to trimethoprim
- Probably best to avoid trimethoprim monotherapy for Moraxella spp. of
veterinary interest
rickettsiales characteritics
- Obligate intracellular parasites
- Bacteria are rod shaped
- Rickettsiaceae family are Gram-negative
- Anaplasmataceae family lack cell wall components of other
Gram negatives - Biocontainment level:
- Level 3 when working with infectious tissues
-level 2 if blood
-cant culture using normal methods
rickettsiales habitat
- These organisms are arthropod associated
- Replication of organism in tick (gut, ovaries, salivary glands)
- Sylvatic cycle
- Vector ↔ Reservoir
- Tick to tick transmission
- Transstadial
- Vertical (female → eggs)
- Horizontal (venereal)
tissue tropisms of rickettsiales
- Rickettsia – Vascular endothelium
- Anaplasma – Erythrocytes, platelets, leukocytes
- Ehrlichia – Leukocytes
- Neorickettsia – Leukocytes
Rickettsia rickettsii dogs
-rocky mountain spotted fever
-1980s from travelers west (trail fever)
-dogs and people
-high mortality
* Clinical signs:
* Fever most common
* Edema or extremities
* May develop petechial or ecchymotic haemorrhages
* Can get necrosis associated with vasculitis
* Seasonality – March-October
Rickettsia rickettsii vector and geographical
- Vectored by hard (Ixodidae) ticks
- West - Dermacentor andersoni, SK, AB
- East – Dermacentor variabilis SK, MB, ON
Rickettsia rickettsii human clinical
- Rash is classical
- Also see fever, headache, nausea, vomiting, injected conjunctiva
- Long term consequences related to vascular inflammation and thrombosis
- Hemorrhage or thrombosis of organs or brain
-treat docyclyline
Rickettsia prowezakii
-Epidemic Typhus (people)
* Clinical Disease
* Begins with flu like symptoms
* Rash, neurological signs (headache to coma)
* Untreated takes 2-3 months to recover fully
* Mortality rate variable (up to 40%)
* Spread by Pediculus humanus corporis
* Human body louse
* Human is reservoir
* Infected lice die within weeks
* Also associated with flying squirrels in southern USA
-disease in WWI with dirty + high density.
Anaplasma
marginale bovine
-bovine anaplasmosis
* In young animals (<1year) infection is usually subclinical
* Disease more severe the older the animal is
* >2 years = severe disease
* Severely affected animals
* Icterus, anemia (extravascular hemolysis!)
* Fever
* Decreased milk production
* Severe infections can be rapidly fatal
-treat: tetracyclines
-vaccination.
Anaplasma phagocytophilum dogs
- Canine granulocytotropic anaplasmosis
- Vectored by Ixodes ticks
- Mirrors distribution of Lyme disease
- Clinical signs are non-specific
- Pyrexia, lethargy, depression and anorexia
- Also reported to affect cats, small mammals, horses, mountain lions, coyotes
-treat: doxyclicine
-avoid: ticks, acaricides
Ehrlichia canis
- Multi-systemic disease
- Cause of canine monocytotrophic ehrlichiosis
- Depression, lethargy
- Bleeding and petechiation possible
- Lymphadenopathy and splenomegaly in ~20-25% of affected dogs
- Ocular signs
- Change in eye colour, blindness,
-neuro signs
-polyarthritis (lameness) - Vector:
- Dermacentor variabilis
- Rhipicephalus sanguineous
- Treatment: Doxycycline
Neorickettsia
helminthoeca dogs clinical
- Cause of Salmon poisoning in dogs
- Highly fatal disease of dogs found in California → B.C.
- Clinical signs
- Sudden febrile illness 5-7 days after eating parasitized fish
- Gradually become hypothermic 4-8 days after signs begin
- Marked anorexia and wasting
- Develop diarrhea and vomiting ~14 days after signs begin
- Hematochezia may occur before death
- Adult flukes (Nanophyetus
salmincola) in dog intestine -> metacercaria in fish muscle
Neorickettsia
helminthoeca dogs treatment
- Treatment”
- Tetracyclines
- Praziquantal
- Anti-trematode therapy
- Supportive therapy
- Fluids
- Anti-emetics
- Prevention:
- Vaccines not effective
- Preventing exposure most important
- Organism survives in rotting fish carcases for months
potomac horse fever cause and clinical
-caused by neorickettsia risticii
* Clinical signs:
* Mild colic
* Fever
* Diarrhea – watery
* Abortion in pregnant mares
-think trematode vector (snails with metacercaria)
-case fatality is 5-30%
potomac fever treatment
- Treatment
- Oxytetracycline!
- Supportive care
- Possibly NSAIDS
- Fluid therapy
- Control
- Inactivated vaccines are available
rickettsiales zoonosis between species
- R. akari – Rickettisalpox
- House mouse reservoir
- Zoonotic via mites
- Urban areas
- R. felis – cat flea typhus
- Opossums identified as one reservoir
- Worldwide distribution
- Zoonotic via cat flea
rickettsiales zoonosis humans
- Potential biological weapon due to:
- Non-specific initial presentations
- High morbidity and mortality rate
- Ability to aerosolize
- Requires specialized laboratory to diagnose
- Not notifiable diseases in Canada
- R. prowazekii was weaponized by the US, Japan and the Soviet
Union - Therapy generally relies upon the tetracyclines
- In people macrolides, penicillins and aminoglycosides NOT
effective
coxiella/ borrelia/ bartonella morph
- Obligate intracellular parasites
- Doesn’t stain using the Gram-stain
- Worldwide distribution EXCEPT New Zealand
-borrelia: * Large spirochetes - Small linear chromosome
- Bartonella
- Small Gram-negative coccobacilli
- Biocontainment level 2 – Borrelia, Bartonella spp.
- Biocontainment level 3 – Coxiella burnetii
- Coxiella requires specialized conditions to cultivate in vitro
coxiella/ borrelia/ bartonella host habitat
- Coxiella:
- Obligate parasite
- Infects wide variety of species
- Shed in milk, urine, feces and amniotic fluids
-* Borrelia - Obligate parasites – host associated
- Associated with reservoir hosts and arthropod vectors(tick bites)
-* Bartonella - Facultative intracellular parasite
- Erythrocyte and endothelial cell pathogens
-spread through vectors (cat fleas)
- Borrelia burgdorferi virulence factors
- Outer surface proteins (Osp) – attachment in tick host, allows organism
to persist in gut between meals - Surface lipoproteins – stimulating inflammation, persistence in ticks
- Porin-like proteins – adhesion
- Flagella – motility
Virulence Factors
* Bartonella spp.
- Type 4 secretion systems
- Bartonella effector proteins (BEPS), secreted into host cells and
modulate physiology in favour of bacteria - Induction of phagocytosis by host cells (entry)
- Prevention of apoptosis (keep host cells alive)
Coxiella burnetii disease and mechanism
- Generalist parasite of eukaryotic cells
- Found in arthropods, reptiles, birds and mammals
- Agent of Q fever
- Short for ‘query’ fever
- When present, high concentrations in placenta and fetal tissues
- Animals frequently eat these tissues after birth
- Passes through GIT
- Excreted in feces
-aerosolized in dust gets into lungs and replicated and disseminates throughout the body.
Coxiella burnetii domestic species (sheep, cattle, horse)
- Most often, infections in domestic animals are mild or non-apparent
- Clinical signs related to sites of localization
- Reproductive tract and mammary tract – abortions/shedding in milk.
-placentitis, hepatitis, myocardial. - Control:
- Segregation of parturient ruminants
- Careful disposal of tissues (abortuses and placentas)
- Vaccination
- Inactivated vaccines available
Coxiella burnetii
dog and cat
- Most common subclinical
- In affected dogs splenomegaly is the most common
- In affected cats abortion has occurred
- Has been associated with human outbreaks
- See fever, lethargy, anorexia 2 days following experimental infection
q-fever people clinical
-caused by coxiella borrelia
-can have lab aquired infections/ fatal
* Incubation period is up to 3 weeks
* 50% of infected people asymptomatic
* Acute febrile illness (flu like)
* Typically, mild disease but serious complications occur
* Pneumonia
* Granulomatous hepatitis
* Myocarditis
* Abortion
* Case fatality rate <2% of hospitalized patients
-neatherlands large outbreaks from living DOWNWIND of infected dairy/ goat farm.
-vaccination, manure management, culling.
q-fever people transmission/ treatment
- Acquired as occupational disease
- Farmers
- Abattoir workers
- Veterinarians
- Laboratory workers
- Foodborne
- Unpasteurized products (goat cheese)
- Rarely associated with cats
- Treatment - doxycycline
- Prevention - vaccine for high risk workers
lyme disease
-caused by borrelia burgorferi
* Ticks are the only competent vectors
* In North America:
* Ixodes scapularis
* Ixodes pacificus
-most cases NE USA
* Ticks primarily infected by biting reservoir host
* Transmission of the organism isn’t instantaneous
* Can take up to 24 hours for transmission to occur, co-infections common
lyme disease in dogs
-ususally No signs
* In affected dogs can see:
* Intermittent recurrent lameness – polyarthritis is best documented
syndrome
* Fever
* Anorexia
-maybe renal failure.
* Treatment
* Early: Doxycycline, amoxicillin, azithromycin
* Control:
* Acaricides
* Removing ticks promptly
* Vaccination
lime disease people clinical
- Symptoms 3-30 days post infection
- Fever, chills, swollen lymph nodes
- Characteristic erythema migrans rash (target)
- Chronic signs occurring days to months later
- Severe headache, arthritis, facial palsy, pain, heart palpitations
-in western CAD BC and MB, highest in ON, NS
Bartonella spp.
dogs clinical
- Endocarditis
- Seen with B. vinsonii and other species
- Hepatitis
- Seen with B. henselae
- Flea and tick prevention is important
- If clinical signs, treat with long duration antimicrobials
- Enrofloxacin, doxycycline
Bartonella henselae people
- Important zoonoses, people infected following cat scratches
- Symptoms develop 1-3 weeks post exposure
- Fever
- Papule or pustule at site of scratch
- Enlarged, painful lymph nodes
- Can see bacillary angiomatosis
- Angiogenesis, and lesions in the skin
Bartonella quintana
people
- Bartonella quintana
- Cause of trench fever, name comes from effects on soldiers in WW1
- Bacteremia, localized tissue infection, endocarditis
- Reemerging in people affected by extreme poverty in developing
countries and in the homeless (developed countries) - Vectored by human body louse
- Humans only confirmed reservoir
Bartonella baciliformis people
- Cause of Carrion’s disease
- Hemolytic anemia, localized tissue infection, angiomatosis
- Biphasic disease
- First phase is erythrocyte infection, anemia and transient
immunosuppression - In the second phase nodular dermal eruptions occur as a result of
vascular proliferation - Transmitted by sandflies in Andes Mountains
treatment and samples for coxiella, borrelia, and bartonella
- Susceptibility testing impossible!
- C. burnetii Treatment:
- Doxycycline!, PCR
- Borrelia: serology
- Doxycycline, β-lactams
- Bartonella spp: PCR
- treat doxycycline
mycoplasma charactertistics
- Smallest self-replicating prokaryotes
- Lack cell wall, only have a cellular membrane
- Don’t stain well with Gram-stains
- Round, pear shaped or filamentous
- Example of genome reduction, heavy reliance on host cells
-Colonies often have “fried egg” appearance - Some species slow growing
- Biocontainment level 2
- M. bovis, heaemofelis
- Biocontainment level 3
- M. capricolum, mycoides
mycoplasma habitat
- Host associated
- Found on the mucous membranes
- Upper respiratory tract
- Genital tract
- Intestinal tract
mycoplasma virulence factors
- Variable surface proteins (Vsps) - antibody evasion, immune modulation
- Adhesins - some species express protein adhesins
- Lipoproteins - adhesion, stimulate release of proinflammatory
cytokines - Capsule - persistence and dissemination
- Biofilm - some species do this, although interesting classical biofilm-associated genes are lacking
mycoplasma. mycoides bovine causes
- Contagious bovine pleuropneumonia
- Very old disease, syndrome first described in 1550!
- Three major eradication efforts globally
- Currently notifiable disease to OIE
- Control in Canada would be about STAMPING OUT! Call CFIA
Contagious bovine pleuropneumonia
-caused by m. mycoides
* Disease characterized by severe fibrinous pneumonia
-classic “marbeling” appearance on lung lobules.
* High morbidity (up to 70%) and mortality (up to 50%)
* Major production losses
* Acute disease
* High fever, severe respiratory distress
* Sub-acute - chronic disease
* Incubation period 3 weeks - 6 months
* Transmission through prolonged contact with carriers
mycoplasma capricolum
- Contagious caprine pleuropneumonia
-mouth breathing and saliva - High morbidity (100%), mortality (60-100%) in affected herds
- Disease characterized by
- Cough, hyperpnea, pyrexia
-transmitted via aerosols up to 50m. in africa, middle east
-CFIA in canda
mycoplasma bovis
- Variety of clinical syndromes associated with this organism
- Arthritis
- Pneumonia - caseonecrotic pneumonia - often polymicrobial
- Genital infections/abortion
- Mastitis
- Once inside host, M. bovis disseminates hematogenously
- Organism maintained by carriers
- Sub-clinical disease, recovered, identified in colostrum and semen
-can be intracellular infections (hard to treat)
control: isolate, treat with antimicrobials.
mycoplasma. gallisepticum
- This is the most pathogenic Mycoplasma species in birds
- Turkeys more severely affected than chickens
- Turkeys - infectious sinusitis - mucopurulent sinusitis and airsacculitis
- Broilers - chronic respiratory infections
- Layers - usually subclinical, reductions in number of eggs
- Transmitted vertically (within eggs) and horizontally (aerosols)
- Control - good biosecurity
- Treatment - tetracyclines and macrolides
mycoplasma. hyopenumania pigs
-causes enzoonotic pneumonia
* Chronic, mild disease
* Endemic pneumonia
* Persistent dry cough
* Reduced feed efficiency/growth rate
* Flare ups of disease seen with poor management
* Such as poor ventilation aerosol transmission
-lung lesions at slaughter
control: vaccintaes
treat: macrolides and tetracyclines
mycoplasma felis
- Member of upper respiratory microbial community or conjunctivitis
- Can find in healthy cats and in association with disease
- Lower respiratory tract disease
- If you find M. felis it is probably clinically significant
- Pneumonia in kittens
- Tetracyclines, macrolides,
mycoplasma. haemofelis
- Parasitizes erythrocytes
- Several species in cats, although M. haemofelis most common
- Anemia is a hallmark of infection, immune-mediated process
which can be fatal. Characterized by: - Lethargy, weakness, depression
- Tachycardia, dyspnea
- Hepatosplenomegaly, lymphadenopathy
- Incubation period of 2-30 days
-transmission via biting (vertical) from queens. or fleas.
-control: keep cats inside, no fighting
-treat: tetra/ fluro
mycoplasma treatment and resistance
- Intrinsically β-lactam resistant
- Tetracyclines and fluoroquinolones generally good choices
mycology basics
- Nucleated
- Fungal hyphae
- Cell walls composed of chitin
- Cell membranes
- Contain ergosterol as the primary sterol
- Visualization: KOH wet prep
mycology lifestyles
- Aerobic
- Most fungi grow at low temperatures
- 20-30⁰C
- Tolerant of high pressures and low pH
- Capable of growing in a wide variety of environments
- Play a very important function in the carbon cycle
- Very good at degrading polymers
- Fungi have been found at the Chernobyl site which utilize radiation as an energy source
mycology uses
-food, don’t let you dog eat (mushroom poisoning)
-make antimicrobials
virulence factors of mycology
-tissue invasion (ex guttural pouch mycosis)
-mycotoxicosis: toxic production
* Aflatoxicosis – aflatoxins in feed affect poultry
* Fusariotoxicosis – zearalenone is non-toxic for poultry but causes disease in pigs
* Ergotism – alkaloids produced by fungi growing on cereals
-hypersensitivities: ect moulds in damp buildings, makes asthma worse.
fungi clinical significance
-not many are pathogenic
-oppertunistics
* Dermatophytes both common and contagious
* Common cause of disease in ectotherms
* Plants, insects, fish and amphibian
-grow best below the body temp
fungi types of clinical cases
- In mammals, fungi are typically considered
- Commensal/host-associated
- Candida, Malassezia
- Disease happens in states of immunosuppression
- Environmentally acquired
- Many of the dimorphic fungi (Blastomyces etc.)
- Disease typically follows exposure to large inoculum
Fungal Disease and Extinction
- White nose syndrome in North American bats from - Pseudogymnoascus destructans, in eastern USA
- Chytridiomycosis in
amphibians – threatening
amphibians on every
continent caused by Batrachochytrium dendrobatidis - Snake fungal disease – emerging disease in US
- Ophidiomyces ophiodiicola
mycology (fungi) clinical in people
- Most commonly infections associated with identifiable risk factors:
- Immunosuppression
- Organ transplant recipients
- SLE (Lupus), vascular diseases, diabetes mellitus, alcoholics or IV drug users
- Iatrogenic factors including prolonged antimicrobial, steroid or cytotoxic therapy
- AIDS – oral candidiasis is an AIDS defining condition
dermatophytes characteritstics
- Septate fungi
- Microsporum – boat shaped macroconidia
- Trichophyton – cigar shaped macroconidia
- Utilize keratin for growth
- Relatively slow growing
-BCL 2
dermatophyte fungi natural habitat
- Can be described as geophilic or zoophilic
- Geophiles – free living saprophytes in the soil
- M. gypsum
- Zoophiles – adapted to survival in host skin
- Microsporum canis - cats
- Trichophyton verrucosum – cattle
dermatophyte fungi transmission
- Depending on species, transmission can be:
- animal → animal
- animal → human
- human → human
- Direct contact with infected hair, or contaminated environment
- Fleas from infected animals can serve as mechanical vectors
- Infectious dose is unknown, but thought to be ≥100 spores
dermatophytes virulence factors
- Infective arthrospores germinate following adherence to keratinized
structure - Trauma, moisture and maceration of the skin facilitates infection
- Keratin hydrolyzing ability allows invasion of skin, hair and feathers
- Incubation period is 1-3 weeks
- Host inflammatory response leads to lesions
* Classical round lesion “ringworm”
* Alopecic - Clinical disease more common in warm humid climates
clinical significance ringworm dogs
-caused by dermatophytes fungi
* Clinical signs are not pathognomonic, lesions are typically:
* Foci of alopecia
* Follicular papules
* Scales, crusts
* Lesions may have central area of pigmentation
-puritis
-generalized lesions or focal
ringworm cats
-wide spectrum clinically:
* Inapparent, silent infection
* Lesions may be focal or multi focal
* May or may not have scaling
* May or may not be pruritic
* Erythema and scaling of outer pinna are common presentations
* In kittens may see erythema and scaling
* Muzzle, ears, face and forelegs are most common sites
* Granulomatous dermatitis also possible (poor prognosis)
* Ulcerated nodules
ringworm control
- Generally self-limited infection
- Clipping the hair coat is key
- Prevents additional contamination of environment
- Topical therapy is possible
- Whole body shampooing
- Systemic therapy
- Decontaminating the environment is key
- Can persist in the environment for long period
ringworm horses
-caused by dermatophytes
* Trichophyton equinum is the most common species
* Infections typically superficial
* Lesions most commonly occur on the axilla or rump
* Lesions begin as reddened, raised areas
* After ~7 days hair falls out
* Becomes scabby and crusty
* Hair re-growth begins in 24-30 days
-dermatophysis
ringworm cattle
- Trichophyton verrucosum is the most common species
- Lesions are most commonly on the head/neck
- There are heavy grey crusts over the lesions
- Alopecic spots develop
- Not typically pruritic
Bovine dermatophytosis
ringworm people
- Ringworm is very common
- Presentation depends on site of infection
- Can occur at variety of body sites
- Risk factors include:
- Use of public showers
- Contact sports (wrestling)
- Tight shoes
- Excessive sweating
- Some animal contact
control: clean dry skin, dont use public lockers, towels, clean hands after animals.
dermatophytes samples and control
- PLUCK hair from lesions
- Fungi are more likely to be in base of hair
- Preferentially pluck damaged looking hair
- Scabs from the edge of the lesion
- Brushings
- Collect using a toothbrush
-KOH of wet hairs, nails, scabs
-woods lamp test 50% will glow under UV.
-treat: usually self limiting, dogs and cats all 3: environmental decon, topical therapy, systemic (azoles)
-horses: shampoos
-cattle and rumiants: enticonazole rinses
dermatophytes zooonosis
- Ringworm should always be considered zoonotic
- 3.5% of human dermatophytes caused by M. canis
- Patients at risk of more severe disease
- Children, elderly, transplant and cancer patients
- Estimated that 50% of people living in household with infected cats
develop lesions - Cats have been shown to carry T. rubrum, the agent of athlete’s foot
-between cats and ag animals
ESKAPE organisms which have resistance
- Enterococcus faecium
- Staphylococcus aureus (pseudintermedius)
- Klebsiella pneumoniae
- Acinetobacter baumannii
- Pseudomonas aeruginosa
- Enterobacter spp
how bacteria resist
- Decreased permeability
- Active Efflux
- Enzymatic Degradation/Alteration
- Target Modification
- Alternate Pathways
- Resistance by Absence
-Bacteria can deploy these strategies intrinsically or after gaining genetic competence
how do we determine susceptibility
- Phenotypic susceptibility tests
- Categorical
- Quantitative
- Molecular*
- Look for the resistance gene
- Other phenotypic tests*
- Look for gene products
what is antimicrobial resistance
- “Resistance” has a very specific meaning
- Designed to predict clinical outcomes
- Predicated on certain assumptions:
- Species
- Achievable drug concentration in target tissue
- Intrinsic resistance is constitutive for an organism
- Acquired resistance is not inherent to the organism, it is a decrease in susceptibility compared to the wild typ
intrinsic resistance
- A good grasp of normal allows lab data to be interpreted
- What do all of those “R’s” really mean?
- Intrinsic resistance is independent of antibiotic exposure
- “Wild-type” phenotype
- Mycoplasma spp. intrinsically resistant to penicillin
- They lack a cell wall and therefore don’t have the drug target
spice organisms
- SPICE organisms
- Serratia
- Providentia
- Indole positive Proteae*
- Citrobacter
- Enterobacter
- Produce AmpC β-lactamases
- Can become de-repressed (over-produced) with therapy
- Intrinsic 3 rd generation cephalosporin resistance
- In a veterinary context I would recommend avoiding all β-
lactams
Intrinsic Resistance Non-Fermenters
-many intrinsic resistances to many drugs
intrinsic resistance of gram pos
enterococcus: resistant to all cephlosporins and some to vacomycin
where does resistance come from
- Natural phenomenon - resistance is often a byproduct of something else:
- Soil organisms survive in an environment that contains antimicrobial compounds
- Enteric organisms need to survive in the presence of bile acids
-resiatance for all drugs is already out there, make sure using drug is worth it.
-bacteria adept very quick.
ways bacteria become resistant
-mutation
-conjugation
-transduction
-transformation
B lactamalses- degradation enzymes which dont let the drug work.
Tetracycline Resistance
- Efflux:
- Common in Gram positive and negative
- Resistance not necessarily across class…
- Ribosomal protection
- S. pseudintermedius (tetM)
- Conformational change in tetracycline binding site on 30S subunit of
ribosome - Ribosomal mutations, enzymatic inactivation also occur
Aminoglycoside Resistance
- Enzymatic inactivation
- Aminoglycoside modifying enzymes
- Most common mechanism of resistance
- Decreased permeability
- Cross resistance to other antimicrobials
MLSbK resistance
- Target Modification
- Ribosomal methylases
- erm gene family
- Be aware of inducible resistance
- Active Efflux
- Enzymatic Inactivation
Fluoroquinolone Resistance
- Target mutations (Gram positive and
negative) - gyrA and parC particularly
- Step-wise resistance
- Can see MIC creep
- Efflux
- mar operon
- multidrug resistance
- Plasmid mediated (target protection)
Sulfonamide Resistance
- Hyper-production of PABA
- Altered enzymes
- dfr genes (trimethoprim resistance)
- Gram positive and negative
- sul genes (sulfa resistance)
- Gram negative bacteria
what is stewardship
- Treating a diagnosis rather than a syndrome
- Concatenating laboratory evidence and your clinical exam into a diagnosis
- Asking questions when you need more information
- Using evidence-based empiric therapy
- Likely pathogens, local resistance epidemiology
- Applying your knowledge of
- Intrinsic resistance
- Drug mechanisms of action and spectrum of activity
- Mechanisms of resistance
- Recognizing the evolving world of infectious diseases
- Resistance is emerging
- Be nimble enough to adapt
- Lifelong learning - sounds cliché but:
- Professional duty
- If you’re not up to date you’re out of date
- Utilizing recognized therapeutic guidelines
prescribing decisions
- Pathogen identified (or likely pathogen)
- Susceptibility of organism: Knowledge of local resistance epidemiology
- Animal species
- Signalment
- Site/type of infection
- Co-morbidities
- Route of administration
factors which you need to consider in prescribing
-cost
-complience
-label indication
-withdrawl time
-business factors
-fear factors
-habitual practice factors
-pharmaceutical factors
aspergillus characteristics
-rapidly growing fungi
-blue colonies look like dandi lions but with conidiophores unbranched. very small
-natural habitat in decomposing matter
-respiratory or hypersensitivity reactions
aspirgillus birds
Brooder pneumonia in young chickens
* Seen in young chicks exposed to large number of spores
*granulatamous Nodules in lungs and air sacs
* Associated with dirty environments
-in mature birds: emaciation, lung nodules.
**penguins very suseptible
aspirgillus horses
-causes guttural pouch mycosis
-aspirgillus fumigatus
-clinically: epistaxis, dysphagia, laryngeal nerve paralysis, horners syndrome
-fungus invades neuro structures
-diagnosis based on endoscope
-case fatality 1/3
-treatment: poor, debridegment, topical antimicrobials (eniconazole or miconazole)
* Iatrogenic thrombosis and embolization of
carotid= Prevents bleeding following debridement
aspirgillus in bovine
-cause mycotic abortion
-sporadic disease
-6-8 months in preg, with poor feed quality.
-reach placenta hematogenously
-ringworm like lesions on abortuses
-thickened placenta with necrotis cotyledons
nasal aspirgillosis dogs
- A. fumigatus nasal disease
- Clinical signs include
- Mucopurulent nasal discharge, epistaxis
- Sneezing
- Nasal discomfort
- A. fumigatus can produce osteolytic toxins
- Destruction of the turbinates
- Erosion of the cribriform plate
-can see on rhinoscopic exam, physical
treatment of nasal aspergillosis dogs
- Treatment
- Systemic therapy does not have a good success rate, ~40-60%
-debride fungal plaques - Topical antifungal therapy
- Enilconazole or clotrimazole
- Trephination of sinus
- Fill with clotrimazole cream
- Close hole with bone wax
- Be sure the cribriform is intact
aspergillosis people
- Most commonly affect respiratory system
- A. fumigatus or flavus
1. Allergic bronchopulmonary aspergillosis - Similar signs to asthma
2 aspergilloma: cough, hemoptysis
3. invasive aspergillosis: fever, chest pain - Very high mortality rates
- 94% mortality in bone marrow transplant patients
- Aspergillus has an affinity for invading blood vessels
lab identification of aspergillosis
-koh of tissues
-culture
- Galactomannan is a component of the cell wall of Aspergillus spp.
* In people a quantitative galactomannan ELISA is used to monitor response to therapy
* If levels decreasing this indicates successful clinical strategy
aspergillosis zoonosis
-not much transmission, more in environment
* Possible occupational exposure
* Waste management workers who work with organic waste
* Large number of Aspergillus spores in degrading plant material
* Susceptible to developing allergic bronchopulmonary aspergillosis
aspirgillosis treatment
- Azoles drugs are the treatment of choice
systemically - Itraconazole, voriconazole
- NOT fluconazole
Other filamentous fungi (Mucor and Rhizopus
spp.) intrinsically voriconazole resistant
