Microbiology review week 5

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Microbiology review week 5

• efking_at_u.washington.edu

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What well cover today

• N. meningitidis
• STDs
• Obligate intracellular organisms
• There is a fungus amongus

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Neisseria meningitidis

• G- diplococcus
• Microaerophilic (what does that mean, again?)
• Transient part of nasopharyngeal flora
• These folks are carriers
• Spreads by respiratory secretions
• Virulence factors
• Adhesive fimbriae so can colonize respiratory
  epithelium
• Antiphagocytic capsule (serotypes)
• Endotoxin - blood vessel destruction, sepsis

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N. meningitidis

• Meningococcemia sepsis
• Bugs invade bloodstream from nasopharynx
• Acute onset fever, chills, n/v, myalgias,
  petechial rash due to endotoxin release
• Fulminant form septic shock rapid death in
  50-60
• Meningitis
• Bugs invade meningeal endothelium
• Groups at risk
• Infants 6 months - 2 years (like which bug?)
• Protected by moms Ab before 6 months
• 18-23 year olds (college students, military)
• Dx G/culture CSF, blood
• Rx antibiotics
• Vaccine purified polysaccharides (except B)

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Sexually Transmitted Diseases

• (well, mostly)

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Neisseria gonorrhoeae

• G- diplococcus
• Microaerophilic
• Virulence factors
• Adhesive fimbriae - antigenic variation by DNA
  rearrangement (which other bug?)
• IgA protease
• Invasion of epithelial cells via outer membrane
  porin protein
• Limited survival in PMNs

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N. gonorrhoeae

• Gonococcal disease in men
• Urethritis - usually painful urination
  w/discharge (pus)
• Complications epididymitis, prostatitis
• Gonococcal disease in women
• Urethritis - more likely to be asymptomatic,
  minimal discharge
• Cervicitis - may have dyspareunia, asymptom.
• Complications
• PID - endometritis, salpingitis, oophoritis
• Sterility, abscesses, peritonitis, ectopic
  pregnancy

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N. gonorrhoeae

• Gonococcal disease in both genders
• Disseminated gonococcal infection
• Septic arthritis - fever, pain/swelling of 1-2
  joints
• Most common septic arthritis in young people
• Skin lesions - usually on extremities
• (FYI rarely, peri/endocarditis, meningitis)
• Gonococcal disease in neonates
• Transmission from mom during delivery
• Acute conjunctivitis - corneal damage, blindness
• Dx culture on special medium (chocolate agar), G
  stain - see diplococci within WBCs
• Rx antibiotics - penicillins effective

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Haemophilus ducreyi

• Chancroid
• contributes to HIV transmission
• Painful genital ulcer (vs. syphilis)
• Painful inguinal lymphadenopathy (vs. C.
  trachomatis)
• No systemic symptoms (vs. Herpes)
• Dx culture is difficult
• Rx antibiotics

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Chlamydia

• Small, G- bacilli without peptidoglycan layer
• Strict intracellular energy parasites
• Makes culture tough must innoculate living cells
• Tropism for columnar epithelial cells
• Transmitted by person-person contact
• Life cycle
• Elementary body infectious, metabolically inert
• Infects columnar epithelial cell
• Phagocytosed prevents phagolysosomal fusion,
  becomes a
• Reticulate body non-infectious, metabolically
  active
• Divides by binary fission, then reorganize back
  into EBs and released from cell

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C. trachomatis

• STDs - most common cause in developed countries
  serotypes D-K
• Men
• urethritis - 1/2 asymptomatic. 1/2 dysuria
• epididymitis
• Reiters syndrome arthritis, uveitis,
  conjunctivitis Cant see, cant pee, cant
  climb a tree
• perihepatitis

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C. trachomatis

• Women
• Cervicitis 75 asymptomatic purulent exudate
• PID
• Urethritis, proctitis
• Perihepatitis
• Both lymphogranuloma venereum
• Serotypes L1-L3
• Primary phase painless papule on genitals
• Secondary phase regional lymphadenopathy
• Painful, may break open and drain pus
• Systemic Sx - fever, chills

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C. trachomatis

• Infants from delivery though infected mom
• Inclusion conjunctivitis
• Inclusions collections of reticulate bodies
• Pneumonia - usually in weeks 4-11 of life
• Everybody Trachoma - serotypes A-C
• 1 cause of blindness in world
• Chronic follicular keratoconjunctivitis
• Inflammation, scarring pulls eyelid inward
  eyelashes rub against cornea -gt corneal scarring
• Children are main reservoir transmission by
  hand-to-hand transfer of eye secretions

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C. trachomatis

• Dx
• DNA detection - PCR
• Cell culture
• DFA
• Serology for LGV
• Rx
• Cover both chlamydia gonorrhea with azithromycin

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C. pneumoniae

• Atypical pneumonia
• 3rd most important cause of pneumonia
• Fever, HA, dry cough, streaky CXR
• Person-to-person spread via respiratory route
• Possible etiologic roles in chronic diseases
• Alzheimers, lung cancer, asthma, atherosclerosis
• Dx culture not helpful PCR
• Rx tetracycline

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C. psittaci

• Birds are reservoir (parrots) very infectious
• Humans inhale dust from feathers, dried feces
• Transport to RE cells in liver, spleen
• Re-seeding of lung
• Psittacosis
• 1-2 week incubation
• Variable course of chills, fever, HA, cough
• Dx culture not available serology
• Rx tetracycline

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Rickettsia

• Small, G- bacilli
• Strict intracellular energy parasites
• Most escape phagosome, replicate in cytoplasm
  (except R. rickettsii)
• Tropism for endothelial cells
• Shows up as rash in skin
• Requires arthopod vector
• Zoonoses - humans are accidental hosts

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R. rickettsii

• Transmitted by hard ticks
• Ticks are reservoir and vector
• Requires 1-2 days of contact
• Most common April -gt October in OK, NC/SC
• Invades vascular endothelial cells
• Replicates in nucleus
• Rocky Mountain Spotted Fever
• Fever, conjunctival redness, severe HA, rash on
  soles palms -gt spreads to trunk
• Usually resolves 3 weeks can be fatal
• Dx IFA
• Rx tetracyclines

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R. prowazeki

• Transmitted by lice
• Humans primary reservoir
• Rare in US
• Associated with overcrowding
• Epidemic typhus
• High fever, chills, rash that spares the palms,
  soles and face
• Dx IFA
• Rx de-lousing, antibiotics
• Formaldehyde-deactivated vaccine

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R. typhi

• Transmitted by rat fleas
• Rodent reservoir
• Gulf states, Southern California
• Endemic typhus
• Similar to epidemic typhus, but less severe
• Dx IFA
• Rx tetracycline

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Orientia tsutsugamushi

• Transmitted by larvae of mites (chiggers)
• Mites live on rodents chiggers live in soil
• Asia, SW Pacific
• Scrub typhus
• Fever, HA, rash in 50

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Coxiella burnetti

• G- bacilli
• Strict intracellular bacteria
• Transmitted by inhalation of infected aerosols
  (sound familiar?)
• Reservoirs cattle, sheep, goats
• Low infectious dose
• Q fever
• Fever, chills, hepatomegaly, atypical pneumo Sx
  without rash
• Dx serology (rise in Ab titer)
• Rx tetracycline

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Ehrlichia

• G- bacilli
• Strict intracellular bacteria
• Transmitted by vector infects WBCs
• Prevents phagolysosomal fusion
• Spotless Rocky Mountain Fever
• E. equi (granulocytic)
• Transmitted by Ixodes tick (what other bug?)
• Small mammal reservoir
• E. chaffeensis (monocytic)
• Transmitted by Lone Star tick
• White tailed deer reservoir

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Ehrlichia

• Sx high fever, HA, malaise, no rash
• Dx morulae in WBCs, leukopenia
• Rx tick removal, tetracyclines
• Most common april -gt october

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Bartonella henselae

• G- bacilli
• Facultative intracellular bacteria
• Transmitted by cat scratch/bite, cat fleas
• Cat reservoir
• Cat scratch disease
• Febrile necrotizing lymphadenitis, possible rash
• Bacillary angiomatosis in immunocompromised
• Proliferation of blood vessels in skin, viscera
• Dx PCR
• Rx not responsive to antibiotics

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Bartonella quintana

• G- bacilli
• Facultative intracellular bacteria
• Transmitted by lice (which others?)
• Trench fever
• relapsing fever, rash, HA, myalgia, rash
• Dx culture, serology
• Rx gentamicin

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Intracellular bacteria recap
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Which of the following statements concerning
Bartonella is FALSE?

• It causes trench fever
• It causes cat scratch fever
• It is transmitted by ticks
• It can be grown on artificial media

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Which of the following statements concerning
Bartonella is FALSE?

• It causes trench fever
• It causes cat scratch fever
• It is transmitted by ticks
• It can be grown on artificial media

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Leptospirosis is usually diagnosed by

• Culture
• Enzyme immunoassay
• Serology
• Microscopic exam of liver biopsy
• PCR of urine specimen

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Leptospirosis is usually diagnosed by

• Culture
• Enzyme immunoassay
• Serology
• Microscopic exam of liver biopsy
• PCR of urine specimen

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Which of the following produces urethritis,
cervicitis, epididymitis, and septic arthritis?

• Neisseria gonorrhoeae
• Borrelia burgdorferi
• Neisseria meningitidis
• Chlamydia trachomatis
• Leptospira interrogans

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Which of the following produces urethritis,
cervicitis, epididymitis, and septic arthritis?

• Neisseria gonorrhoeae
• Borrelia burgdorferi
• Neisseria meningitidis
• Chlamydia trachomatis
• Leptospira interrogans

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Filamentous bacteria

• Low pathogenic potential opportunists
• G branching rods
• Dx acid fast stain, sulfur granules

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Filamentous bacteria

• Actinomyces israelii
• Colonizes human oropharynx, intestine
• Indurated abscesses with draining sinus tracts
• Cervicofacial, thoracic, abdominal, pelvic
• Dx not partially acid fast
• Rx parenteral penicillin, ID
• Nocardia asteroides
• Soil organisms - not human colonists
• Pulmonary nocardosis lung abscess, empyema if
  spreads
• Disseminated nocardosis brain, subQ
• Actinomycetoma (fungi also cause)
• Dx partially acid fast
• Rx sulfa, ID

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Sulfur granules
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FUNGUS
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General stuff

• Mainly cause disease in immunocompromised
• Eukaryotes
• Aerobes
• Yeast unicellular growth form budding
• If buds dont separate -gt pseudohyphae
• Molds multicelluar colonies, composed of hyphae
• Hyphae branching tubules, ? septae or pigment
• Dimorphic fungi can grow as either yeast or mold
• Usually yeasts at body temperature, molds in
  culture
• blastomycosis, histoplasmosis, coccidioidomycosis,
  paracoccidioidomycosis, sporotrichosis

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General stuff contd

• Propagule basic reproductive unit of fungus
• Conidium propagule produced asexually by mitosis
• Spore propagule produced sexually by meiosis,
  gamete fusion
• Except sporangiospore (Zygomycetes) -gt asexual
• Chlamyconidium storage unit
• Important in ID Candida
• Comensals normal flora, only cause disease in
  immunocompromised
• Saprophytes environmental, only cause disease in
  immunocompromised
• Pathogens cause disease in lots of people

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Major fungus groups

• Zygomycetes
• Most common pathogen (rhizopus) in this class
• Nonseptate, hyaline (colorless) hyphae
• Ascomycetes
• Some pathogenic spp (Coccidiodes, Histoplasma)
• Septate hyphae, hyaline or dermatiaceous
• Basidiomycetes
• Only one of medical importance -gt Cryptococcus
• Deuteromycetes
• Reproduce asexually several of clinical
  importance
• Septate hyphae, hyaline or dermatiaceous

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More on fungus

• Cell membrane contains ergosterol
• Cell wall surrounds membrane antigenic
• Capsule surrounds cell wall antiphagocytic
• Dx
• Direct G (esp yeasts) , KOH
• Culture mycologic media, bacterial agar
• Yeasts 35 degrees
• Molds 25-30 degrees

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Antifungal agents

• Ampho B
• Binds ergosterols, punches holes in cell membrane
• IV only use for invasive mycoses
• Toxicity infusion reaction, renal toxicity
• Reduced nephrotoxicity with lipid-complex
  formulation
• Nystatin
• Same MOA as ampho B
• Topical only

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Antifungal agents

• Azoles
• Interrupt ergosterol synthesis
• Important ones
• Ketoconazole - oral, topical GI side effects
• Fluconazole - oral, IV penetrates CSF
• Itraconazole - oral, IV less well tolerated than
  fluc.
• Terbinafine
• Same MOA as azoles oral for dermatophytes
• Tolnaftate
• Same MOA as azoles, at different point in pathway
• OTC topical for dermatophytes

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Antifungal agents

• Flucytosine
• Interferes with RNA and DNA
• Oral
• SE GI, heme, rash, BM suppression
• KI
• Oral for sporotrichosis
• Griseofulvin
• MOA unknown
• Oral for dermatophytes
• Echinocandins - caspofungin
• Inhibit cell wall glucan synthesis
• Works against Pneumocytis

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Exogenous opportunists
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Aspergillosis

• Spores are ubiquitous in the air
• Diseases in healthy people
• Allergic bronchopulmonary aspergillosis
• Chronic colonization of lower RT
• Increase in IgE
• Otomycosis benign colonization of ext auditory
  canal
• Chronic sinusitis
• Aflatoxin intoxication -gt associated with food,
  carcinogenic

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Aspergillosis

• Diseases in basically healthy people with
  pre-existing tissue damage
• Aspergilloma (ball o fungus)
• With cavitary lesion (TB, malignancy)
• Keratitis can lead to enucleation
• Burn and wound infection

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Aspergillosis

• Disease in the immunocompromised
• Begins in lungs
• Hyphae - invade blood stream
• Infarcts, necrosis of lung
• Metastasis
• Direct invasion into cranium from sinuses
• Dx 45 degree branching septate hyphae
  conidiophores (reproductive structure)
• Rx steroids for allergy, DC and ampho
  B/itraconazole for invasive dz/aspergilloma
• Some spp resistant to ampho B

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Zygomycosis

• Most human diseases caused by Rhizopus spp
• Spores are everywhere
• Rhinocerebral invades from sinuses -gt orbit,
  meninges, brain
• Uncontrolled DM, neutropenia at risk
• Pulmonary lungs -gt via blood to brain, other
  organs
• Uncontrolled DM, neutropenia
• High mortality rate
• Cutaneous wound burn infection
• Dx 90 degree branching, aseptate hyphae
  sporangiospores
• Rx ampho B resection

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Cryptococcus neoformans

• Found in soil, bird droppings
• Yeast form has large polysaccharide capsule
• Antibodies made to this to enhance phagocytosis
• Pulmonary infection follows inhalation of spores
• Healthy clear infection
• AIDS disseminates -gt meningitis, skin, bone,
  organs
• Dx
• CSF India ink - stains capsule latex
  agglutination
• Culture urease , phenol oxidase -gt melanin on
  birdseed agar
• Rx fluconazole for any disease in compromised
  ampho B ? flucytosine for disseminated

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Endogenous opportunists
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Candida albicans

• Most common mycosis
• Yeast forms pseudohyphae
• Part of normal mucosal flora disease with
• AIDS, immunosuppression
• Surgery
• Catheters
• Prolonged antibiotics
• Burns
• IVDA
• Female
• DM

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C. albicans

• Superficial diseases
• Skin - in intertriginous regions (folds)
• Thrush - oropharynx esp AIDS, BMT pts
• Vulvovaginitis - yeast infection
• Chronic mucocutaneous with genetic defects
  disfiguring
• Deep diseases
• Local esophagitis, GI, UTI
• Disseminated liver, kidney, eye, skin via blood
• Dx germ tube chlamydoconidia
• Rx
• Superficial topical/oral azoles, nystatin
• Deep ampho B or fluconazole

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Thrush
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Pneumocystis carinii

• P. jiroveci for human strains
• 2 stages
• Trophozoite - thin wall, in clusters
• Cyst - thick wall, contains intracystic bodies
• Healthy asymptomatic or mild respiratory disease
• Compromised life threatening pneumonia
• Alveoli filled with organisms -gt foamy
• Dyspnea, fever, cough, hypoxia, BIL diffuse
  infiltrates on CXR
• Can get extrapulmonary disease also
• Dx BAL or induced sputum (AIDS only) direct
  stain cannot culture
• Rx bactrim

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Candida albicans exists in a

• mold form in tissue, yeast form in culture
• Yeast form in tissue, mold form in culture
• Yeast form in tissue, yeast form in culture
• Mold form in tissue, mold form in culture

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Candida albicans exists in a

• mold form in tissue, yeast form in culture
• Yeast form in tissue, mold form in culture
• Yeast form in tissue, yeast form in culture
• Mold form in tissue, mold form in culture

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Regarding Pneumocystis carinii, which of the
following is false?

• Must be cultured for definitive ID
• Possesses two phases in its life cycle
• Is resistant to the usual antifungal agents
• May be visualized microscopically with any one of
  several stains
• Has high attack rates in the settings of AIDS and
  the severely malnourished infant

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Regarding Pneumocystis carinii, which of the
following is false?

• Must be cultured for definitive ID
• Possesses two phases in its life cycle
• Is resistant to the usual antifungal agents
• May be visualized microscopically with any one of
  several stains
• Has high attack rates in the settings of AIDS and
  the severely malnourished infant

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The antifungal drug flucytosine acts in which of
the following ways?

• Binds to cell membrane ergosterol, causing
  cytoplasmic leakage
• Acts as a nucleoside analog to interfere with
  nucleic acid functions
• Inhibits DNA replication by binding to DNA gyrase
• Blocks ergosterol synthesis
• Inhibits glucan synthase

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The antifungal drug flucytosine acts in which of
the following ways?

• Binds to cell membrane ergosterol, causing
  cytoplasmic leakage
• Acts as a nucleoside analog to interfere with
  nucleic acid functions
• Inhibits DNA replication by binding to DNA gyrase
• Blocks ergosterol synthesis
• Inhibits glucan synthase

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