Professional Documents
Culture Documents
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Pathology of Bacterial Infections
Final outcome determined by host & bacterial pathogen: can direct Tx towards both
Examples: think about what bacteria has to overcome to get in!
Respiratory entry: eyes (blinking, tears, lysozyme, secreted IgA, lactoferrin sequesters iron); nasopharynx
(microflora, secretions); lungs (resident macrophages)
GI tract entry: mouth (sloughing cells, flow of saliva, lysozyme, sIgA, microflora, lactoferrin); stomach (low pH,
proteolytic enzymes), small intestine (fast flow, mucous, sloughing cells); colon (slow flow, sloughing cells,
mucus, lots of resident microflora)
Chronic inflammation:
Key: Lymphocytes & Macrophages (= histiocytes)
1. Granulomas: aggregates of lymphocytes & histiocytes; often with fibroblasts & giant cells
2. Granulomatas: poorly aggregated infiltrates of lymphocytes / histiocytes
3. Chronic nonspecific inflammation: mostly infiltrates of lymphocytes, fewer histiocytes
o When do granulomas form and when does general chronic inflammation happen?
Cytokines IL-1B, IFN-γ, CXCL, CCL granuloma forms
Different cytokines IL-4, IL-10 chronic inflammation
Each type of cytokine suppresses the other response
3. Cytopathic
o Most typical of viral infections
o Can be seen with intracellular bacterial infections
Chlaymydia trachomatis – U/G infections
Cervix red, swollen; purulent mucoid exudates
Chlamydia grows within vacuoles intracellularly
4. Cytoproliferative inflammation
o Bartonella spp. (henslae) – angioproliferative responses (cause blood vessels to overgrow)
Esp. in HIV patients, causes dermis to be replaced by vascular structures
From cats (also causes cat scratch fever)
5. “Null reaction”
o Absence of inflammatory, necrotizing, or cytopathic responses
o Rare in bacterial infections
o Can occur with neutropenia, immune compromise (HIV, cancer chemo, genetic defects) or by rapid,
unrestricted bacterial growth
o Vibrio vulinficus with neutropenia: tons of Gram (-) bacteria but just a few inflammatory cells
o Bacillus anthracis (anthrax): skin, meninges, inhalational. Bacteria grows faster than immune response
is mounted (also suppress immune response)
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Effects of alterations in host defense, inflammation, immunity
1. Physiologic defects
Cystic fibrosis (no appropriate mucous production = ↑ lung infiltrates)
Achlorhydria (can’t generate acid in stomach = ↑ lower GI infections)
2. Host can’t make inflammatory cells: no inflammatory infiltrates (congenital neutropenia, etc.)
3. Host inflammatory cells can’t accumulate: no inflammatory infiltrates
Leukocyte adhesion molecule deficiency (don’t see WBC at site of infection)
4. Host immune suppressed (HIV, Rxs): modified inflammatory response
Chronic granulomatous disease (↓ superoxide radicals in phagocytes: see bacteria ingested but not
destroyed)
Complement deficiency, asplenia = ↑ susceptibility to encapsulated bacteria (need C’ to opsonize)
Hypogammaglobulinemia = ↓ opsonization
HIV, cancer therapy, corticosteroid, immune suppressive therapy = ↓ T-cell responses
Interferon-γ receptor deficiencies = recurrent Mycobacteria and Salmonella infections
Hosts that lack inflammatory response = not well protected against effects of infection
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Streptococci (I & II)
General Features of Streptococci:
Structure Streptococci: Major Pathogens
Gram (+) cocci (GPC) in very nice Str. pyogenes Group A Most frequent cause of bacterial
chains and pairs (division in 1 plane). infection globally
Remain attached via thin cell wall Str. agalactiae Group B Peri-natal & opportunistic
bridges Str. pneumoniae Primary cause of pneumonia &
Non-motile, non-spore bearing meningitis globally
Gram (+) cell wall +/- capsule (major Viridans group Relative wimps
pathogens do have capsule)
Physiology Organism Normal flora in…
Fastidious: enriched media, narrow pH/temp ranges Viridans #1 aerobic colonizer of upper
Aerobic & facultative anaerobes resp tract (#2 aerobic on skin)
Fermentative metabolism (glucose lactic acid, not Group A Small #s of individuals
Krebs cycle) Group B Normal below the belt
Catalase NEGATIVE Str. pneumoniae Depends on country & season
o No cytochrome oxidative system (Gram
negatives, S. aureus, etc. do have)
Classification
Hemolytic reaction
Hemolysis Examples Blood agar
Beta (produce H2O2, lyse RBC) Groups A & B (also C,D,F,G) Clear
Alpha (degrade Hb to met-Hb) Viridans group Green
Str. pneumoniae
Non-hemolytic (“gamma”) Red
Immunologic
o Grouping: based on C-polysaccharide antigen on cell wall
o Typing (for Group A): based on M-protein
Genetic: 45+ strains known
Str. pyogenes
Group A strep virulence factors: Cytolysis and spreading factors
Cell-associated:
Hyaluronic acid capsule (unusual – most just complex
polysaccharide) – INHIBITS PHAGOCYTOSIS
M-protein (typing)
1. Inhibits C’ fixation
2. Major adherence factor: binds with LTA so cells can adhere
to pharynx, skin & not be washed away
Protein F: binds to fibronectin, adherence factor
Lipoteichoic acid (LTA): binds with M-protein; adherence factor
Cell-bound peptidase: inhibits C’
Peptidoglycan layer
Has fimbrae (M-protein + LTA) to help adhere
Extracellular:
Hemolysins O (oxygen labile) and S (oxygen stable)
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o Large zone of beta-hemolysis; most strains have both but if they’ve only got one, it’s O
o O: very antigenic (make Ab)
Endonucleases: digest nucleic acids, nuclei of leukocytes.
o Fewer WBC around than Staph infections, etc. because of endonucleases
Streptokinase: liquefies material around cells; dissolves clots
Pyrogenic exotoxins (A, B, C)
Toxic shock toxin (like S. aureus toxin)
Many others (so organism can diffuse throughout body)
Clinical features: Local manifestations: edema, heat, erythema, pain, spreads with extreme rapidity, few PMN-rich
abscesses, systemic manifestations too
Disease presentations:
Pharyngitis (also other URI: otitis, sinusitis). Pus; grayish-white discharge; edematous tonsils. Complications:
clotting / obstruction / jugular vv infections. Common in children, closed populations (college, military). 3-5
days: transmissibility decreases
Skin / soft tissue: erythema, edema, pain
o Impetigo: frequently staph/strep mix; painful, swelling, little clear fluid-filled vesicles if strep only.
Different M-protein types than pharyngitis types
o Celulitis: superficial skin infection. rapid spread, advances up lympathics (reddish streaks). Huge
vesicles with clear fluid later
o Necrotizing fasciitis / myositis (killing skin / muscle cells). Abx don’t reverse damage – need surgical
intervention. Path: dead mm cells, no PMNs
Puerperal (post-delivery) sepsis – more historically no.
Scarlet fever
o Str. pyogenes strain producing pyrogenic toxin (plasmid-mediated). Usually pharyngitis-associated
o Scarlatiniform sandpaper rash (upper chest to trunk, extremities); strawberry tongue
o Desquamation follows
Toxic shock syndrome: strep TSS parallels S. aureus’
Post-streptococcal diseases (immunologic cross-reactions between strep antigens & heart or kidney)
o Rheumatic fever (9-10d post-infection)
Any M-protein type; reinfection has same latency
Heart (myocarditis, valves); joints (arthraligias, arthritis), skin (erythema marginatum), CNS
(Sydenham’s chorea)
o Glomerulonephritis (few days post-infection)
Specific M-types implicated
Proliferative disorder of renal glomerulus
Edema, hypertension, hematuria, proteinuria
Can have no sequellae or progress to end-stage renal disease
More likely to transmit if high amount, in nose/throat; less likely if you’ve been a carrier for a while.
Str. agalactiae
Regular polysaccharide capsule (inhibits phagocytosis & C’)
9 serotypes (M-proteins) with different capsule composition
CAMP factor (hemolysin)
Small zone of B-hemolysis
Found in normal GI flora; vaginal tract of 5-30% sexually active women
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Can be primary or co-pathogen in immunocompromised
Clinical presentation: causes neonatal sepsis and meningitis (early & late forms)
Associated with prolonged rupture of membranes in colonized mother
Early onset: 1st 6 days. Septicemia (60%), also pneumonia (30%), meningitis (10%). 10% mortality
Late onset: 7d-3mo. Majority due to type III; may be fulminant with septic shock & severe meningitis
Neurologic sequellae: 25-50% children
Prevention:
Maternal screening
Prophylactic antibiotics (if colonized mother or any mother with prolonged membrane rupture)
Str. viridians Group
General characteristics:
Alpha-hemolytic (green pigment)
Relatively non-virulent
Normal flora of respiratory tract, vaginal tract, skin, other
Pathogenicity
Endocarditis: relatively indolent, really needs damaged setting (e.g. IV drugs, then lands on already damaged
heart valve)
Abcesses(most common cause of liver abscesses. Complications: rupture hemorrhage, high mortality rate.)
o Str. anginosis, Str. intermedius, Str. constillatus
Dental caries: Str. mutans (part of gingival flora, clings to enamel)
o To get caries: need right microflora, diet, and host/teeth situation.
o Str. viridians is most common aerobe in oral flora
o Virulence: from high acid production
Septicimia in immunocompromised patients
Co-pathogens in mixed flora infections (e.g. Gram + and – together)
Non-infectious events: chronic gingivitis atherosclerotic plaques?
Genetic features
Transfer of DNA via transformation, phages, conjugation
o Transformation ability varies with capsule type, inflammation (cytokine activation), other types of
stress, antibiotics, starvation, chemical exposure. E.g. Abx can induce ability to acquire resistance!
Virulence factors: major one is the capsule (blocks phagocytosis if specific antibody not present).
Need capsule for virulence (capsule + rest of pneumococcus too)
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Cell-surface-associated:
o pili (adherence)
o cell wall polysaccharides (induce inflammation, activate C’)
o surface protein A: inhibits activation of C’,
o autolysin (how pneumococci commit suicide when they don’t like where they are)
Cytoplasmic (release of these as cells lyse are primary cause of death within 48 hours despite abx):
o Autolysin: releases pnemolysin & cell wall products
o Pneumolysin: cytotoxin, activates C’/cytokines
o Neurominidase: exposes host cell receptor sites
o Peptide permeases: enhance adhesion
o Others (hemolysin, hydrogen peroxide, etc.)
Normal flora in 20-100% individuals (colonization: normally host makes protective Ab preventing blood-based
spread, from this normal exposure)
o Direct infections (otitis, sinusitis) can still occur
Facultative pathogen; produces intense inflammatory response without necrosis
Major cause of death at age extremes
Pneumonia
Occurs with newly acquired type that patient doesn’t have Ab to
Typical case: respiratory viral infection, fever recurs 4-7d post viral infection, pneumonia sets in
o Virus damages ability to clear tracheobronchitic tree, destroys ciliary epithelial cells, produces excess
mucus & fluid, blocking normal clearance
Often begins with aspiration of oropharyngeal contents (alcoholism, neurologic impairment, etc.)
Purulent nasal discharge, lobar pneumonia, intact alveolar structure, inside of alveoli jammed with
inflammatory cells. Radiology: alveolar infiltrate
Little residual morbidity – can resolve well (not destroying alveoli)
Pneumococcal septicemia: especially common in sickle cell children (give PCN prophy until vaccination possible)
Management:
1. Antibiotics (Penicillins, others).
a. Rapidly emerging resistance
i. PBP mutations: “intermediate” resistance, can overcome with ↑ dose sometimes. Increasing
doses doesn’t help for endocarditis or meningitis (just can’t get *drug+ high enough in there)
ii. B-lactamase development
b. Less active: cephalosporins (used to be 2nd line, now resistance emerging too)
c. Varies with location
2. Prevention (vaccines)
a. 23-component vaccines (23 different types / polysaccharides)
b. Different kinds: peds vs adults
c. Vaccine works less well in older patients (although mandated to offer to all pts > 55yo on discharge
from hospital & document reasons for refusal)
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Enterococci
General features:
Look like strep (GPC in chains); metabolism like strep (facultative anaerobes, fermentative metabolism)
Catalase negative (but can make a little bit if they receive DNA from other spp)
Not fastidious (permissive pH range, no enriched media required, etc.).
o Survive heating, dessication, resistant to disinfectant products (good at health care spread)
o Not damaged by gastric pH
Part of normal gut flora (E. faecalis & E. faecium are most prevelant)
Mostly non-hemolytic (some spp alpha-hemolytic; very rare strains beta-hemolytic)
Grow as small grayish colonies on blood agar
Infectivity:
Commensals (below diaphragm – colonic flora, vaginal flora, external genitalia)
Facultative pathogens
Virulence factors (importance unknown): adherence factors, cytolysins, permeability factor, gelatinase, aggregation
factor (clumping), superoxide production
LTA: can exhibit endotoxin-like features of septic toxicity (incl. hypotensive shock) in large amounts
Biofilm formation (especially hearty)
Diseases:
E. faecalis (60-70%) & E. faecium (10-20%)
Most commonly: mixed infections (e.g. abscesses below the diaphragm)
o Intra-abdominal abscesses, colonic diverticulitis, urinary tract, gall bladder
Enterococcal endocarditis
o Classic presentation: elderly male with obstructive uropathy
o Unlike S. aureus, symptoms commonly indolent; low grade fever often ignored
o (especially big abx diffusion problem)
Septicemia (predominantly in debilitated / immunocompromised; mortality 42-68%)
Resistance:
VRE: vancomycin-resistant enterococci (esp. E. faecium). Hospitals, nursing homes (where abx are used
commonly); hand-spread; 50%+ mortality
o Some strains have developed resistance to all new alternatives – no effective antimicrobial choices
Can transmit resistance genes to S. aureus: MAJOR CONCERN
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Listeria & Other Gram-Positive Rods
Listeria Monocytogenes
Characteristics:
Short, gram-positive rods, can live intracellularly
Survives & grows at low temp (fridge), low pH (stomach acid), high [salt]: overcomes food prep barriers
Colonizes: animals, humans, soil, vegetative matter
Food-borne illness (listeriosis): contaminated meat, dairy, fruits, vegetables (rinse!)
Pathogenesis:
GI tract blood meninges
Invades, survives in variety of cell types
Intestine: provokes active endocytosis (“internalins”) to cross mucosal barrier; survives intracellularly
o Escapes death in lysozome: formes pores to get out of phagolysosomes
o Replicates in cytoplasm (molecular mimicry: proteins look like host proteins)
o Promotes actin polymerization, makes “comet’s tail” that pushes organism out into adjacent cell
o Covered by host cell membrane (more molecular mimicry) in
next cell Lab diagnosis of Listeria:
Spread hematogenously Culture: grows well (30-37 °C best)
Virulence factors: many; survival & invasion. Internalin helps Blood agar:
internalize, listeriolysin O (LLO) helps organism escape from o small white colonies
phagocytic vacuoles (inserts pore), Act A induces actin polymerization o beta-hemolytic
Catalase positive
Epidemiology: major cause of bacteremia & meningitis
Characteristic tumbling motility
Immunocompromised (especially cell-mediated immunity) and
elderly patients
Colonized mothers (can be asymptomatic) can pass to fetus
High mortality (500-600 deaths; 2500 cases in US/yr)
Clinical presentation:
Febrile gastroenteritis (6-48h incubation) in healthy persons. Self-limited. Many asymptomatic.
o Fever/chills, abdominal pain, diarrhea, nausea/vomiting, myalgias
Bactermia: (pregnancy or immunocompromise)
o “bactermia without an obvious source”
o Fever/arthalgias, headache, GI symptoms, backache: or asymptomatic.
Meningitis: 2nd most common cause of bactermia in adults > 50 yo; 5th overall
o Usual presentation of meningitis (stiff neck, headache) but:
CSF glucose not low
Mononuclear cells can predominate (intracellular; others = PMNs)
Pregnancy: somewhat immunocompromised (predisposition)
o Can be infected in last ½ 2nd trimester & 3rd trimester
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o Listeria can proliferate in placenta (infect child in utero)
o Stillborn / neonatal death: up to 20%
Neonatal infection
o Disseminated form of disease: granulomatosis infantisepticum
o Late onset up to 2 wks post-partum; meningitis
o Hepatomegaly
Treatment: Ampicillin; TMP+SMX for PCN allergic (but watch out for kernicterus!?)
Bacillius spp.
General Characteristics:
Aerobic, Gram positive rod
Spore forming; ubiquitous
Major pathogens: B. anthracis (anthrax), B. cereus (bacteremia, wound / eye infections, food poisoning)
Bacillus anthracis
Acquisition: Soilherbivoreshumans acquire via inoculation with spores:
Inhalation*, ingestion*, or trauma (*=more lethal)
Mostly in agrarian societies
Category A biological terrorism agent (easy dissemination, high mortality, social disruption)
Pathogenesis
Spores skin, GI tract, lung germinate in Mφ to regional lymph nodes local production of
toxinsedema, necrosis bacteremia, toxemia
Virulence factors:
o Capsule: inhibit phagocytosis
o Protective antigen: binds to cell membranes (better binding/transport of edema factor & lethal factor)
o Edema factor:
↑ cellular cAMP; ↑membrane permeability (↑edema)
↓PMN function, ↓cytokine pathways (↑ proliferation, bacteremia, systemic infection)
o Lethal factor: Zn-dependent protease. Cleaves MAP kinases, oxygen radicals released
Leads to Mφ lysis and cell death
Pruritic: itchy
Eschar: scab
Clinical presentations: Papule: circumscribed, solid elevation
Cutaneous anthrax: of skin with no visible fluid, varying in
o Pruritic papule enlarges (round ulcer) painless, black size from a pinhead to 1 cm
eschar (dries, falls off); regional lymphadenitis FYI: Anthracis = “coal” (black eschar)
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o Ingestion of vegetative bacteria (not spores) from poorly cooked, contaminated meat ulcers in all
areas of GI tract regional lymphadenopathy nausea, vomiting, bloody diarrhea, sepsis
(excruciating pain)
o Pathology: intense submucosal hemorrhage
Treatment:
EARLY administration of antibiotics is crucial
Penicillin, doxycycline, ciprofloxacin
Vaccine: military use only unless exposed to spores (lots of side effects; anthrax is rare)
Bacillus cereus
Soil organism; broad range of clinical syndromes
B. cereus Dx:
Gram’s stain: GPR in chains
Clinical presentations:
Culture
Food-borne illness (especially rice that was left sitting out)
o Grows well on 5% sheep’s blood
o Diarrheal type: heat-labile enterotoxin; 8-16h post exposure
o Large, feathery, spreading colonies
o Emetic type: heat-stable enterotoxin; 1-5h post-exposure
o Beta-hemolytic (not anthrax)
Ocular disease (penetrating trauma: bacteria in soil; almost always
o Organisms are motile, lecthinase
lose eye) & Wound infections (healthy persons): extensive damage,
(+) (not anthrax)
liquefactive necrosis
Bacteremia, endocarditis, abscesses in immunocompromised pts & IV drug users
Treatment:
Food poisoning: usually self-limited
Produces broad-spectrum β-lactamase: resistant to PCNs & cephalosporins
Vancomycin, clindamycin are active
Cornyebacterium diptheriae
General characteristics of Cornyebacterium spp.
Aerobic bacteria, non-spore forming, Gram-positive bacilli
Curved or club-shaped (corney = club)
Catalase positive
Normal flora of skin, mucous membranes of mammals; hard to distinguish colonization/contamination/infection
Need to ID to species level when isolated from normally sterile sites, urine (if lots), clinical material
Pathogenesis
Non-invasive
Exotoxin: major virulence factor
o 2-segment polypeptide
B-segment (binding): bind to receptors on susceptible cells
A-segment (active): inhibits protein synthesis in mammalian cells
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o Can affect all cells in body (heart, nerves, kidney most common)
o Also contributes to pseudomembrane production
Clinical presentation:
Respiratory tract disease: 2-4d incubation period; can have local inflammation at various sites
o Pharyngeal (most common)
1. Abrupt onset (fever, malaise, sore throat)
2. Pseudomembrane forms & spreads
one or both tonsils oropharynx, nasopharynx, soft palate
white then dirty gray with black necrosis
Can compromise & distort lower airway: “bull’s neck”
o Systemic complications from toxin: myocarditis, neurotoxicity (cranial neuropathies)
Cutaneous:
o Non-healing ulcers, dirty gray membranes, C. diptheriae Dx:
superinfected with other bacteria Presumptive dx: clinical
o Outbreaks among alcoholic homeless, impoverished
Definitive dx: isolate, ID organism
(no boosters, poor sanitation)
Notify state lab (reportable) & send
o Rarely associated with toxigenic illness
material
Others: can have invasive disease (e.g. endocarditis) with
Lab dx: sheep’s blood & selective medium
non-toxigenic C. diptheriae
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Introduction to Gram-negative Bacilli
Gram negative bacilli: rods that stain red by Gram’s stain;
large, diverse group
Classification: growth requirements, phenotypic or genotypic characteristics, disease associations
Can use selective material which is inhibitory to Gram (+), e.g. MacConkey agar, to isolate Gram (-)
Red/pink: acid produced, lowers pH, lactose fermenter
Clear: non-lactose fermenter; diarrheal pathogens
No growth: not Gram (-)
Remember the gram (-) cell wall: has porins in OM; antimicrobial resistance: mutate porin so drugs can’t get in
Proteus spp.
Associated with UTIs, urolithiasis (stones) Proteus: Lab Dx
Proteus mirabilis, Proteus vulgaris Non-lactose fermenter
Cycle: Proteus produces urease, hydrolyzes urea to CO2 + NH3 Very motile (swarming over
neutralize/alkalinize urine inorganic compounds fall out of solution & agar plate)
crystallize stones become embedded & reinfected
Klebsiella pneumoniae
UTIs, pneumonia; hospital-acquired infections with multidrug resistance Klebsiella pneumoniae: Lab Dx
Mucoid capsule (important for virulence) Non-lactose fermenter
Get in lungs/urine; huge inflammatory response Non-motile
Disgusting mucoid colonies
Gram-Negative Pneumonia
Predisposing factors: Gram (-) pneumonia Pneumonia
NON-HOSPITALIZED HOSPITALIZED 1. Rapid growth
Underlying cirrhosis (↑ encapsulated infections) Diminished cough reflex, anesthesia 2. Inflammation (intense,
Loss of consciousness, alcoholism, drug abuse Mechanical ventilation PMNs)
Elderly, immunocompromised Immunocompromised 3. Inefficient killing of organism
(varies with host)
Klebsiella pneumoniae 4. Obstruction, obliteration of
Pneumonia: necrotizing, develop cavitation in areas of consolidation lung tissue
o If you survive: chronic lung disease (pulmonary fibrosis) 5. Death (tissue / host)
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Intestinal infections
Salmonella (S. enterica = most pathogens; also S. bongori)
Various virulence factors (Vi = salmonella typhi) Salmonella: Lab Dx
Exposure: poultry or products (eggs) Gram (-), non-motile
Stays in vacuoles inside cells; enters submucosa, basal membrane; goes to Produces H2S (black colonies)
mesenteric lymphocytes blood stream Use selective media to
Clinical presentations: recover from stool
o Gastroenteritis (S. typhimurium mostly)
6-24h post-exposure: nausea, vomiting, abd. pain, diarrhea; 50% have fever
o Bacteremia (non-typhoidal): much more frequently found in blood than Shigella
o Typhoid fever (S. typhi, S. paratyphi)
1-4wk incubation; fever, multi-organ system infection, may or may not have diarrhea
Multiplication in spleen, liver gall bladder during infection
Shigella
Four serotypes: S. sonnei (major in US), S. flexneri, S. boydii, S. dysenteriae (epidemic dysentery, produces
Shiga toxin),
Presentation: fever, severe, cramping abd. pain, bloody diarrhea Shigella: Lab Dx
Virulence factors plasmid associated; LPS in all Gram (-), non-motile
More severe pain than Salmonella, lower abd. (colon)
Pathogenesis:
o Through stomach acid & small bowel terminal ileum/colon
o Engineers own phagocytosis
o Escapes from vacuole! Stays in mucosa(fecal WBC confined to mucosal layer)
o Non-motile; cause invasive infection by spreading cell-cell via actin polymerization.
o Destroys colonic epithelial cells in process (blood, pus in stool); self-limiting 2-5d
E. coli
EnteroToxigenicEC (traveler’s diarrhea), EnteroInvasiveEC
(uncommon, invasive) EnteroPathogenicEC (infantile, ST E. coli: Lab Dx
childhood diarrhea), EnteroAggregativeEC (traveler’s Gram (-)
diarrhea): from previous lecture Hand-deliver quickly!
Direct detection of SLT in STEC pts’ stool
Shiga-toxin-producing E. coli: STEC Culture: grows well on standard lab material;
o Hemorrhagic Colitis selective material can be usd
o Hemolytic-Uremic Syndrome (thrombocytopenia, PMNs + GNRs: think this family!
renal failure, hemolytic uremia) – associated with production of Stx-2 (Stx-1 only: EPEC)
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Fastidious Gram Negative Rods
Haemophilus sp
Characteristics: normal resp flora of humans & animals
Pleomorphic, GNRs
Invasive strains = encapsulated
Requires special growth factors in vitro: X factor, V factor. Optimal growth on chocolate agar
Lots of different kinds. No capsule = not invasive (H. influenza non-typeable for instance)
H. influenzae type b (a-f are other types).
o Type b causes epiglottitis, sinusitis, meningitis, pneumonia, septic arthritis, etc.
H. influenzae non-typeable (unencapsulated): now #1 cause pediatric acute otitis media; sinusitis too
o Replaced S. pneumoniae
Treatment/prevention:
33% produce plasmid-mediated beta-lactamase (PCN resistant)
Invasive disease: 3rd gen cephalosporin
Non-invasive disease: amoxicillin + clavulanate
HiB Vaccine x 4: 2,4,6,12-15 mo of age
Bordetella pertussis
Gram (-) coccobacilli (single or pairs; faintly-staining); strict aerobe; needs special media (have to ask for it)
Treatment / Prevention
Supportive care (vent, ICU, fluids, etc.)
Erythromycin: doesn’t alter course but decreases bacterial load (less infective)
Vaccine:
o used to use whole cell (DTP); high reactogenicity, 50-90% efficacy, wanes in adolescents/adults
o Discontinued in some countries pertussis outbreaks
o Acellular vaccine now in use: DTaP (diphtheria, tetanus, aceullular pertussis)
Immunogens of B. pertussis, no endotoxins (less side effects) with equal efficacy
5 doses (2mo-5yr); one-time booster for adults (Tdap)
Legionella
General characteristics:
thin, poorly-staining GNRs
Require L-cysteine for growth; use AA for growth (non-fermenters)
Biochemically inert (weak oxidase rxn; catalse positive, liquefy gelatin)
Motility: polar flagella
Epidemiology: tons of species; L. pneumophila is responsible for >90% disease (rest named by where they’re from)
Ubiquitous, widely distributed in environment (aquatic settings: natural or man-made)
Wide temperature range (0-63C)
Parasitize & survive in free-living amoebae!
Form biofilms in water systems
Transmission: inhalation of droplets; aspiration of water; wound infection (more rare) by contaminated water
Pathogenesis:
1. Adhere to resp epithelium Risk factors for Legionella infections
2. Phagocytosed Cigarette smoking, chronic lung
3. Intracellular survival / multiplication disease, alcoholism
a. Inhibits acidification of lysosome Immunosuppresion (corticosteroids,
b. No fusion of lysosome with phagosome malignancies, HIV, transplantations)
c. Lysosome associates with rER (molecular mimicry; lined Diabetes, end-stage renal dz, CV dz,
with ribosomes); bacteria replicates here advanced age
4. Cell rupture & release
24 kD protein macrophage infectivity potentiator (mip): target of many Legionella: Lab Dx
molecular tests Culture: need special medium
(request!) to inhibit normal flora (abx,
Clinical presentations: etc). Can take up to 7 days (slow
Legionella pneumonia: 2-15% cases of CAP growing)
Legionnaire’s disease: systemic illness with pulmonary and Legionella urinary antigen: only
extrapulmonary manifestations (rare to have extrapulmonary serotype 1, but that causes most dz
alone) Nucleic acid amplification (no FDA but
o Radiologically indistinguishable from other some in-house depending on lab)
pneumonias
Direct fluorescent antibody
unilateral, lower-lobe alveolar infiltrates; some
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pleural effusion
cavities/abscesses can occur if immunocompromised
o Slight, non-productive cough (no PMNs because intracellular)
o GI: watery diarrhea; abd. pain
o CNS: mental confusion, headache
o Bradycardia; hyponatremia, hypophosphatemia, elevated CK, increased transaminases
o Doesn’t respond to beta-lactams
Getting a sample: no special transport, room temp OK, refrigeration if delayed.
Send sputum, aspirates, BAL fluids, pleural, lung tissue.
Treatment: 10-14d
Newer macrolides (azithromycin, clarithromycin); quinolones (levofloxacin)
Can also use tetracyclines or TMP+SMX
Prevention:
Routine culture surveillance of hospital water distribution systems
Treat If pathogenic legionella found (hard to get biofilm out). Chemicals, heating, etc.
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Non-fermentative Gram Negative Bacteria
General features:
White on MacConkey agar = non-fermenter (pink=fermenter)
Complex mix (opportunistic pathogens of plants, animals, (most) Non-Fermentive Gram (-)s:
humans) Aerobic, Non-spore forming, Bacilli
75% in clinical specimens are one of these four Cytochrome oxidase positive
1. Psudomonas aeruginosa Catalase positive
2. Acinetobacter baumanii Don’t ferment CHOs; may oxidatively
3. Burkholderi cepecia metabolize some sugars
4. Stenotrophomonas maltophilia Motile, nutritionally versatile
Opportunistic pathogens: most often hospital-acquired Grown on MacConkey Aga
Pseudomonas spp
Pseudomonas aeruginosa
Aerobic, straight/slightly curved, non-spore forming, Gram(-) rod
Motile (1+ polar flagella)
Grows well on SBA, chocolate, MacConkey; wide temp range; Pseudomonas aeruginosa: definitive Lab Dx
Catalase positive Gram (-) rod
Makes both pyoverdin & pyocyanin Oxidase positive (rapid oxidase test)
Grape-like or corn-tortilla odor
Virulence: multifactorial (structural components, toxins, enzymes) Recognizable colony morphology
Structural: o SBA/chocolate: large colonies, metallic
sheen, mucoid/rough/pigmented
o LPS (endotoxin), Pili (adhesion; neuraminidase to remove
o MacConkey: lactose negative; green
sialic acid from pili receptor); capsule (adhesion &
pigmentation or metallic sheen
suppression of phagocytosis / immune response);
pyocyanin (tissue damage: hydroxyl radical products; IL-8 stimulus)
Toxins/enzymes:
o Exotoxin A & S(inhibits protein synthesis); cytotoxin (leukocydin) (cytotoxic for eukaryotic membranes;
microvascular injury); Elastase (disrupts elastin-containing tissues, collagen)
Clinical presentation:
Bacteremia, pneumonia top 2
Others: pretty much all sites of body but particularly adapted to respiratory tract
o CF patients; chronic colonizer of pts with chronic lung P. aeruginosa: Predisposing factors
disease
Chronic debilitating illness (lots of hosp)
o #1-2 cause of Ventilator-Associated Pneumonia (VAP)
Prior therapy with broad-spectrum abx
Can produce disease far away from initial site of tropism
Breach of airway (tracheostomy,
Intact host defenses: not at much risk (opportunist) endotracheal tube)
Imparied host immunity (primary disease
Pulmonary infections in CF patients: colonization tracheobronchitis or iatrogenic)
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necrotizing bronchopneumonia
Tropism for CF epithelial cells; actually switches to a CF phenotype (rough LPS, mucoid, less motility)
o Increased Abx resistance because of prior broad-spectrum abx in CF pts
Treatment, prevention, control: recognize high level antimicrobial resistance worldwide; carbapenems may be driving
emerging resistance; lots of MDR Pseudomonas.
Might be able to use old drug (colistin) despite bad side effect profile
Can’t eliminate from hospital environment: need infection control (safeguard patients)
o Keep equipment sterile; prevent health care worker pt transfer; responsible ABx use
Acinetobacter spp
Widely distributed (nature & hospital)
2nd most common non-fermenter found in humans after P. aeruginosa Acinetobacter spp
Can survive on moist & dry surfaces; present in food & on skin Gram(-) coccobacillary rods
Increased frequency: immunocompromised, debilitated pts Strictly aerobic
Grow on MacConkey (colorless)
Acinteobacter baumanii: Non-motile, non-fermentative
Most frequently isolated from human specimens >> Oxidase negative << (key)
Most often responsible: hospital-acquired infections Usually nitrate negative
Tx & prevention: Need Abx susceptibility testing for every clinically significant isolate!
Intrinsic resistance to cephalosporins; carbapenem resistance ~ 20%; high frequency of MDR
Ampicillin-sulbactim, ticarillin-clavulanate or imipenem are most effective
Also: TMP-SMX, quinolones, doxycycline. Can add aminoglycoside if severe infection; colistin possible if MDR
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Stenotrophomonas maltophilia
Similar profile to Burkholderia cepacia
Widely distributed: nature & hospital S. maltophilia
Can colonize resp tract in pts. with prolonged hospitalization (e.g. Gram(-) rod
immunocompromised) Motile, non-fermentative
Virulence factors unknown, opportunistic human pathogen Grows well on MacConkey
Oxidase negative
Clinical presentation:
Nosocomial; high morbidity/mortality
o Bacteremia, pneumonia, UTI, wound infctions
o Increasing incidence: resp tract infections in CF patients
Treatment:
Intrinsic resistance to almost every antimicrobial commonly used (B-lactams, AGs, others)
TMP+SMX is primary choice for treatment
Burkholderia pseudomalli
Found in soil, water, vegetation: SE Asia, Northern Australia (watch out for travelers)
Wrinkled colonies on plate
Acquisition: inhalation or inoculation (trauma/wounds); Potential bioterrorism agent
Neisseria gonorrhoeae
Same characteristics as other Neisseria
Nutritionally: more fastidious
Requires cysteine for growth; other requirements too
Pathogenesis: adherence cell entry/transport evade stimulate PMN host response (pyogenic)
Special features of surface structure:
o Oligosaccharide endotoxin (smaller than LPS)
o Pili (attachment), peptidoglycan (toxic to fallopian tubes), membrane proteins (survival & invasion)
Adheres to non-ciliated cells (e.g. fallopian tubes); adjacent ciliated cells damaged, slough off, more can attach
o Loss of ciliated cells obstruction, infertility, ectopic pregnancy, etc.
Culture: selective media; supplemented with growth factors; 72h, small, glistening, raised.
Glucose metabolizer(not maltose or sucrose)
Treatment:
Uncomplicated: Ceftriaxone IM or Cefixime PO
o Treat for CHLAMYDIA TRACHOMATIS (lots of coinfection): AZI PO x1 dose or doxycycline PO bid x 7d)
Report & contact-trace infected persons
Prevention: sex ed, abstinence, condoms, no vaccine
use 1% silver nitrate or macrolide antibiotic prophylax for newborns
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Neisseria meningitidis (“meningococcus”)
All age groups, both individual (sporadic) & epidemic
Multiple serotypes: B,C,Y most severe in US
Immunization possible (esp. closed populations)
Epidemiology
All age groups, both individual (sporadic) & epidemic
Multiple serotypes: B,C,Y most severe in US
Asymptomatic nasopharyngeal carriage (8-25%), precedes infection
o Colonization ↑ in closed populations (college, military) need vaccination
Terminal C’ deficiency (C5-9): recurrent, severe infections
Worldwide: Epidemics in some countries (at end of rainy season)
USA: Vast majority sporadic with localized outbreaks
o Case fatality: 10-14% !!
Pathogenesis
Virulence factors: Pili, engulfment, transport in host cells; Polysaccharide capsule (↓ phagocytosis, C’); Lipo-
oligosaccharide endotoxin (very toxic!)
Process: HAPPENS REALLY FAST
1. Pili adhere to non-ciliated resp epithelium invades submucosa
2. Capsule prevents phagocytosis
3. Replicates in submucosa; evades
4. Spreads into bloodstream
5. Endotoxin in blood: cytokine & alternative C’ activation
Meningitis Meningococcemia
Like other meningitis but faster.
Sudden onset: Fever, chills, myalgias, arthralgias, headache, confusion, nuchal rigidity
CSF: 1200 WBC/mL, Glc↓, protein ↑
Meningococcemia
o Rash: palpable purpura (infection of endothelial cells DIC, small hemorrhages)
o Can get peripheral gangrene; lose digits
Adrenal hemorrhage can cause insufficiency (W-F syndrome)
Treatment:
Meningitis/meningococcemia: Penicillin (alternatives: ceftriaxone, chloramphenicol in other countries)
o Not PCN resistant!
Prophylaxis (close contacts) – trace! Rifampin, cipro, ceftriaxone
Vaccines:
Old: polysaccharide tetravalent (poor immunogenicity, not long-lasting, no reduction in NP carriage)
New: tetravalent conjugate vaccine (Menactra) for 2-55yo (give 11-12 or entry to HS; should have for college)
o Capsular polysaccharide conjugated to diphtheria toxin; induces T-cell dep response (good for infants)
o Reduces Asx carriage
o Indications: asplenia, C’ deficient, traveling to endemic areas, closed pops, prevention, lab workers
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Anaerobic Gram Positive Bacteria
General characteristics:
Don’t grow in presence of oxygen
Anaerobic infections (Clinical Dx)
Two groups:
Foul-smelling discharge
o Obligate anaerobes (strict or moderate)
Proximity to mucosal surface
o Aerotolerant anaerobes
Gas in tissues
Tons of different kinds (many part of normal microflora, protective)
Negative aerobic cultures
Classification (pathogenic): shape, gram, spore formation, toxin
production
Widespread: environment (soil, sewage, foods, etc.)
o animals & humans: oral cavity around teeth, GI tract, skin (some), G/U tract
o habitats with low oxygen tension & reduced oxidation reduction potential
Pathogenesis:
Disruption of normal mucosal barriers
Anaerobic infections often mixed (synergy with aerobes, other anaerobes)
Virulence factors: capsules, adhesions, enzyme production, toxin production (some very potent toxins)
Presentations:
brain abscess (usually anaerobes or microaerophilic strep)
bacteremia (need virulence factors to get into bloodstream)
lots of others (mixed) – e.g. empyema (pus in pleural cavity)
Lab Dx:
Get a good specimen (not anything where anaerobes would be in normal flora; Exception: C. diff & feces)
o gastric washings, urine, vagina/cervix, feces, upper resp. secretions, etc. are bad
Swabs are bad specimens, aspirates & tissue biopsies are best (transport immediately)
o Inject into anaerobe transport media
Semi-solid, 5% CO2, reducing agent shows anaerobiosis
o Culture in complex media: supplemented; chopped meat glucose; use anaerobe chamber
Propionibacterium spp
(Major metabolic product = propionic acid)
Anaerobic, Gram (+) rods, highly pleomorphic (curved, clubbed, pointed ends)
Normal flora of skin, mucous membranes; major contaminant of blood cultures
Non-spore forming
Importance: acne, also opportunist with medical devices(shunts, caths, prosthetic valves)
Actinomyces
Anaerobic, Gram (+) rods, pleomorphic (short/club shaped, long/thin/beaded rods, branching)
Slow-growing – makes a “ molar tooth” colony. Reason why labs hold AnO2 cultures for up to 1 wk
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Actinomycosis
Indolent, progressive infection that progresses across tissue boundaries
Purulent foci with dense fibrotic tissue around
Can look like neoplasia/tumor (mass)
Later: sinus tract; drainage with “sulfur granules” (yellowish)
E.g. cervical actinomycosis (cervicofacial is most common)
Clostridium perfringens
Clostridial myonecrosis (“gas gangrene”)
Pathogenesis: production of phospholipase C (very potent alpha toxin)tissue destruction
Diagnosis: clinical: septic appearance, gas in tissues (palpable bubbles),
o Necrosis with gas & no inflammatory cells: phospholipase C kills them too quickly!
Treatment: need extensive surgical debridement! (can’t contain with abx & host immune system)
o Supportive care
o Abx: penicillin G + clindamycin
o Hyperbaric oxygen for some locations
Food poisoning: toxin made after food ingested
Necrotizing enterocolitis: beta-toxin production after poorly cooked pork, rare in US
Clostridium difficile
Pseudomembranous colitis & antibiotic associated diarrhea;
Pathogenesis: Toxin A (enterotoxin), Toxin B (cytotoxin)
o Extra toxins: epidemic strain
Clinical presentation: bloody diarrhea; can include toxic megacolon (distended)
Diagnosis: DIRECT DETECTION OF TOXIN IN STOOL is major way to diagnose
Treatment:
o Withdraw offending antibiotic
o Metronidazole PO or vancomycin
o Surgery if toxic megacolon, intestinal perforation, severe illness
Clostridium botulinum
Botulinum toxin: most potent neurotoxin known; bioterrorism agent
Botulism: three types
1. Foodborne: typically adults; from ingestion of preformed toxin in contaminated food (poorly-made jams, etc)
2. Infant: organism in GI tract; toxin produced in vivo, most common form of disease
3. (Wound) – rare
Pathogenesis: toxin production; potent neurotoxin that blocks Ach release at neuromuscular junctions
Clinical presentation:
1. Incubation: 18-36h, dose dependent
2. Afebrile, alert, oriented, normal sensory exam; early nausea/vomiting, diarrhea
3. Cranial nerve symptoms (ptosis, blurry/double vision, trouble swallowing/talking, ↓ salivation)
4. Progressive motor symptoms: BILATERAL DESCENDING FLACCID PARALYSIS resp paralysis
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5. Death in 60% (untreated; 5% with Tx)
Treatment:
1. Supportive care (airway support)
2. Administer antitoxin (equine serum for adults – 9-20% hypersensitivity – or human botulism Ig for infants)
3. (if wound: debride too)
Clostridium tetani
VACCINE PREVENTABLE!
Widespread distribution of spores in soil & aquatic environments
Pathogenesis:
1. Spores contaminate puncture wounds, etc.
2. Spores germinate (low oxidation-reduction from poor vascular flow)
3. Vegetative cells multiply; release tetanospasmin (attaches to peripheral nerve endings; travels up to CNS)
4. Toxin: binds gangliosides in CNS and blocks inhibitory impulses (PROLONGED MUSCLE SPASMS)
Clinical presentation
Spastic muscle contractions
Difficulty opening the jaw (“lock-jaw”)
Characteristic smile (“risus sardonicus”)
Contractions of back muscles can result in arching – can actually snap spine!
Treatment:
1. Supportive care (airway maintenance, antispasmodics)
2. Antitoxins: human tetanus Ig, tetanus toxoid
3. Antibiotics: metronidazole
Prevention: vaccine!
Clostridium septicum
Bacteremia associated with malignancy
Pathogenesis: high dose chemo damages GI; organisms translocate at site of mucosal damage
Blood cultures positive
Treatment: Penicillin G, supportive care, sometimes surgery
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Emerging and Re-emerging Bacterial Zoonoses
Zoonosis: any infectious disease that may be transmitted from other animals (wild & domestic) to humans or
from humans to animals
Vector: any animal that transmits an agent of human disease or plays an essential role in the agent’s life cycle
o E.g. mosquitos / malaria; snail hosts / schistosomiasis; rodents / leishmaniasis
o Typically arthropod vectors (mosquitos, ticks, flies, lice, fleas)
Emerging infections: diseases that have recently appeared or are growing in incidence. Lots!
o Zoonotic, vector-borne, bacterial high RR for disease to emerge
Leptospirosis
Leptospira: spirochete (spiral-shaped); Enormous taxonomic group
Leptospirosis:
Estimated >10M cases worldwide, uncommon in US
(Hawaii, Wisconsin?), more common in tropics
Acquisition: contaminated animal or rodent urine: lives in
bladder, urinary tract of asymptomatic animals
o Water/soil
o Skin abrasions; conjunctivae
o Domestic pets (dogs) / livestock too
Clinical presentation:
Fever, headache, myalgia, abdominal pain, conjunctival suffusion (inflammation / red eyes)
5-10%: Icteric form (Weil’s disease)
o Can precede worse outcomes: renal failure, pulmonary hemorrhage, cardiac arryhmias
Uveitis (late manifestation, can lead to blindness)
Death in 5-15% (esp old age)
Histopathology:
Cholestasis: brown pigment in liver (jaundice too)
Pulmonary hemorrhage(mechanism not known)
Interstitial nephritis: chronic inflammatory cells in interstitial around tubules
Pathogenesis:
urine contaminated water mucous membrane / skin abrasion liver, CNS, kidney, all organs localized in
kidneys patient sheds Leptospira in urine
Virulence factors: motility, hemolysins, adhesions / invasions (bind & localize), hemostasis & coagulation genes
Immunologic pathogenesis:
o Proinflammatory response to LPS (via TLR2); activates host inflammation
o Multi organ-system failure due to DIC
o Pulmonary hemorrhage (Ig, C’ fixation on host cells; more common with high Ab titers)
o Ocular disease: uveitis during “immune phase” – Ig & C’? uvea = iris, choroid, ciliary body
Dx: can culture during acute phase (1st week); IHC / microscopy / PCR not great.
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Microagglutination test (MAT): detect Abs as early as 5-7d post-onset;
o single high titer acceptable; seroconversion preffered
Tx: doxycycline, penicillin, cefotaxime.
Jarisch-Herxheimer reaction (proinflammatory cytokine cascade; like sepsis, should anticipate possibility)
Pathogenesis:
1. Enters via mucosa, endocytosed by phagocytes
2. Survives in acidified phagolysosome; enters into ER (abx resistant), delays apoptosis
3. Regulates TNFα by translocating a protein into cell’s cytoplasm
Clinical presentations
Complications:
Osteoarticular disease
o Peripheral arthritis (acute infection, non-erosive, knees, hips, ankles, wrists)
o Sacroilitis (acute infection)
o Spondylitis (lumbar spine; often irreparable damage)
Epididymoorchitis (granulomatous inflammation with lots of lymphocytes in epididymis; enlarged testicles)
Abortion in pregnant females, liver, CNS (meningitis, etc grave prognosis)
ENDOCARDITIS: main cause of mortality, usually aortic valve, generally requires surgery
Relapse: inadequate treatment; usually 1st year
Diagnosis:
Blood or bone marrow culture: need Biosafety level 3 (easily aerosolized)
Detect Abs (serum agglutination test: draw pt serum, add antigens for Brucella). Safer, for presumptive Dx
Treatment:
Doxycycline + rifampin (or streptomycin/netilomycin) for 4-6 weeks
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Bartonella spp
Small, Gram (-) rods; facultative intracellular bacterium; α-2 proteobacteria, related to Brucella
Mammalian, arthropod reservoirs (rodents, felids, lice, fleas, ticks)
Infects erythrocytes & endothelial cells
Epidemiology:
↑risk: kitten exposure, ownership, bites/scratches
Cats: often seropositive; persistently infected with B.
henselae (“normal blood flora”-ish)
Fleas: vector between cats, not humans (except maybe
immunocompromised?)
Clinical diagnosis:
Regional lymphadeopathy with or without fever
Cat/kitten scratch/bite
Papule at inoculation site (small, red, elevated lesion)
Characteristic histopathological features
o Stellate microabscess in granuloma (in lymph nodes)
Apoptotic cells, macrophages, PMNs, epitheliod histiocytes, etc.
o Clusters of bartonella inside lesions
Pathogenesis:
Fleas on infected cats defecate; cats clean, flea feces under claws
Inoculation of bacteria in cat scratch
Spread: draining lymph nodes infection
Occasional: systemic spread but resolves spontaneously in most cases
Clinical manifestations:
Cat-scratch episcleritis (Parinaud’s oculoglandular syndrome)
o Inoculation in/around eye; drains to post-auricular node
o Neuroretinitis: CNS involved; fluffy infiltrates (bacteria in retina)
Usually in immunocompromised pts:
o Bacillary angiomatosis / peliosis
Proliferation of blood vessels & capillaries in skin (angiomatosis) or liver/spleen (peliosis)
Inflammatory cells in interstitium; bacteria cluster there
o Endocarditis – very important
Thrombus-like material forms; most of necrotic lesion filled with Bartonella
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Pathology of Mycobacteria Infection
M. leprae: Leprosy
Caused by M. leprae (acid-fast; obligate aerobe)
Prefers cooler parts of body (lesions on skin prominences, nose, URT, peripheral nerves, testes)
o Neuropathy secondary damage to fingers, etc – secondary infection; loss of digits.
2 types: tuberculoid (nothing to do with TB) & lepromatous
LEPROMATOUS TUBERCULOID
Weak host immune response Strong host immune response
Numerous bacilli (MB: multibacillary) Few bacilli (PB: paucibacillary)
Sheets of macrophages, not granulomas Granulomatous reaction
Non-reactive lepromin (skin) test Reactive lepromin (skin) test
o Note how immune reaction is responsible for other differences
Extremely rare in USA; more common in other countries (esp. Africa, Nepal) – usually travelers if in US
M. tuberculosis: TB
Epidemic waves of morbidity/mortality: sharp rise; peak, gradual decline over 100s of years
Worldwide: #2 ID killer (HIV, 2.7M; TB: 2.2M; Malaria: 1.1M)
o 2 billion infected with M. tb; 8M new cases/yr, 1 death every 10 seconds; 500k infected with HIV too
o One untreated pt infects 10-15 new pts / yr
Epidemiology: poverty, overcrowded housing, undernourishment (airborne)
o Slums of US, etc. where poor, elderly together
Mycobacterium tuberculosis:
Acid-fast bacteria (high lipid content of cell walls; Ziehl-Neelsen stain)
o Red dye, washed away from other cells by acid alcohol, counterstain blue
Obligate aerobes, hard to detect in tissue, slow to grow in culture
Can survive intracellularly
Transmission:
Person-person (small airborne droplet nuclei)
o Have to be small to avoid mucociliary apparatus
o Produced when coughing/sneezing/speaking/singing
o Remain airborne; disperse uniformly throughout enclosed space (can’t use regular surgical mask)
Expt: guinea pigs in cages on roof infected via aerosolization; distance didn’t matter
MDR-TB is more easily spread!
Primary TB:
Initial spread & development of Ghon focus / complex
1. Goes to middle, lower lung fields (in periphery) – greatest
volume of air goes there
2. Nuclei implant on respiratory bronchioles/ alveoli (past
mucociliary system, way out into lungs)
3. Initially: non-specific PMN response (usually not observed)
4. Alveolar Mφ engulf mycobacteria multiply within Mφ
5. Some mycobacteria are killed by Mφ process/present
antigen to T-helper lymphocytes release lymphokines to
attract more Mφ & activate monocytes infiltrate;
activated histiocytes granuloma forms
o Caseous center, etc. If you hear caseous or AFB,
think TB!
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6. Some Mφ with M. TB transported to regional lymph nodes, then throughout body
o Ghon focus: initial site of implantation
o Ghon complex: Ghon focus + lymph node (classic for primary TB)
Simon foci: some bacteria lung apacies (higher oxygenation, lower blood flow so lymphostasis)
Apical scars: common in tuberculin + pts; harbor more bacilli (dormant) than other areas of lung
1st part driven by anatomy/physiology; this is driven by metabolic character of the organism
Progressive Primary TB
5-10% of patients (especially lowered immunity, kids, elderly) progress to primary progressive TB
If granulomata erode, can discharge into different spaces
1. Miliary TB: erode into vessel
Characteristics:
tons of evenly-sized, tiny foci throughout lung (bacteria well mixed in blood)
larger foci towards apex (better oxygenation)
Worst prognosis
Pulmonary vein: left heart; to rest of body: new lesions in both lungs
Pulmonary artery: back into that lung; new lesions in one lung
2. TB Bronchopneumonia: erode into airway
Characteristics: larger pieces of granuloma breaking off unevenly sized, clustered nodules
3. TB empyema: erode into pleural space
Characteristics: can see granulomatous change, caseation in former pleural space
Post-primary TB
Infections which develop in individuals with immunity to bacillus.
1. Reactivation of previously healed TB (Simon foci)
a. Begins in posterior segment of upper lobe
b. About 1-2% untreated PPD + pts will reactivate <
5yrs
2. Reinfection of previously infected individual (with
different strain)
a. Not totally prevented; suggests BCG vaccine not
effective
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Non-Tuberculous Mycobacteria
A.k.a. “atypical” mycobacteria, “anonymous” mycobacteria, “pseudotubercule bacilli”
Classified into 4 groups, don’t produce disease in guinea pigs
Acquired from ENVIRONMENT (soil, water) – not person-person like M. tb
Opportunists: usually infect people with underlying lung dz or decreased immunity
HIV patients & TB: TB usually diagnosed 6mo before opportunistic infections (more virulent); now an AIDS-defining dz
More often extrapulmonary TB
TB in lungs often non-apical, non-cavitary; poorly-developed granuloma (no good immune response)
Drug-resistance higher; PPDs more often negative
Complications: crushing spine (Pott’s disease); ocular involvement
Rest of world: TB is leading cause of death in HIV+ individuals
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Vector-Borne Zoonoses
Vector: any animal that transmits an agent of human disease or plays an essential role in the agent’s life cycle
typically refers to arthropod vectors (mosquitos, ticks, fleas, flies, lice, etc.)
Vector transmission only: Lyme disease, RMSF
Direct-contact and vector transmission: plague
Yersinia pestis (Plague)
Gram-negative coccobacillus; stains in a bipolar pattern; facultative intracellular bacterium
Ecology: endemic foci maintained; persistant rodent hosts; flea vector active year round
Epizootic hosts; low resistance to infection (squirrels / chipmunks), high mortality/population density
Rural rats fleas urban rats fleas humans(bubonic) humans(pneumonic)
Potential bioterrorism agent (pneumonic)
Transmission:
Flea bite: bubonic plague
1. Rat flea bites patient
2. Inoculate flea material into wound drain to local lymph nodes bubo (hyperplasia & necrosis of LN)
3. Fever, headache, chills, malaise, painful lymphadenopathy (2-6d later)
4. With Tx: cure in 3-5 days
Aerosol: pneumonic plague
Pulmonary infection rapid spread & septicemia
Either: septicemic plague
Invade blood without buboes; high frequency of death
Endotoxin / cytokine release / Gram (-) sepsis; resp. distress syndrome (ARDS); SIRS
Complications: endophthalmitis, mmeningitis, tissue abscesses
Epidemiology: endemic in Africa, Asia, N/S America; >2,000 cases / yr in world, high case fatality rate
Human transmission: depends on environment, host mammals, arthropods
Clinical presentation:
Early localized infection: erythema migrans (“bull’s eye”)
o EM +/- draining lymphadenopathy; usually 1st week post-tick bite. EM not always present!
o Nonspecific inflammation; perivascular lymphocytes: looks like chronic inflammation
Early disseminated infection: systemic manifestation (disseminates to lymphatics, blood vessels, capillaries)
o Fever (infrequent in early-localized)
o Multiple erythema migrans
o CN VII palsy, Carditis (arrhythmias), Oligoarticular arthritis, Meningitis
Late infection: oligoarticular, chronic arthritis, encephalopathy (very rare), chronic pain/memory loss/etc.
Post-Lyme disease syndrome: no response to antibiotics, not present in vaccine placebo group from trial,
independent of serological results, no resistance to Abx: NO EVIDENCE FOR LONG TERM ABX and this cluster of
symptoms really seems unrelated to Borrelia!
Diagnosis: Clinical (Hx exposure; endemic region, erythema migrans), culture, SEROLOGY
Serology: enyzme immunoassay (sensitive, not specific) first, then western blot to confirm
Treatment: amoxicillin, doxycycline, ceftriaxone (CNS infections)
Prevention:
Vaccine no longer available
Prophylatic doxycycline for tick bites in highly endemic areas (85-90% effective < 24 hrs)
Remove attached ticks, avoid areas, etc.
Treatment: doxycycline (or tetracycline; doxy has better outcome than chloramphenicol; tooth-staining uncommon
with these doses in kids)
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