micro final review 2

• Most human anaerobic bacterial pathogens are RELATIVELY aerotolerant
• identification: Commercial packaged microsystems

• Anaerobiosis
• Spore formation
• Toxin production

• Gram-positive, anaerobic
• spore forming rod
• producing gas (gas gangrene)
• Found in soil, and as a significant component of the normal flora of the colon of humans and animals

• disease:
• food poisoning
• epigastric pain and watery diarrhea, 8-12 hours following consumption of contaminated food (usually meats)

• pathogenesis:
• organisms survive initial cooking by sporulation
• spores germinate on cooling or reheating of food
• toxin released by sporulating organisms in small intestine
• meat products, common cause of diarrheal illness, high attack rate
• **myonecrosis** (gas gangrene) --> Shock, renal failure, coma, death

• dx:
• high numbers of C. perfringens in food

• tx:
• maintain hydration, antibiotics not indicated

Anaerobic, gram-positive, spore forming rods, found in soil, feces

• disease:
• tetanus – spastic paralysis
• Incubation period days to weeks after introduction of spores by puncture wound, cut or burn
• Trismus (spasms of jaw muscle) initial sign of generalized form of disease, progresses
• Mortality: untreated disease - >50%
• Most deaths occur in first week, from pulmonary infection, aspiration.
• With proper treatment, mortality <20%
• Deaths from autonomic dysfunction resulting in hypo/hypertension. tachy/bradycardia, cardiac arrest
• Adult survivors show complete recovery

Neonatal tetanus: Entry of spores at umbilical stump

• pathogenicity:
• Spores introduced by trauma, germinate in necrotic tissue
• Toxin produced, transmitted to CNS via motor neuron
• Tetanus toxin inhibits release of inhibitory neurotransmitter (glycine, GABA) into synaptic cleft
• Toxin is a protease specific for synaptic vesicle protein required for fusion with cytoplasmic membrane.

• tx:
• antitoxin
• supportive
• Immunization: primary in infancy (DPT), booster every ten years (Tetanus toxoid) for life

Anaerobic, motile, Gram-positive, spore-forming rod

• disease: botulism
• Flaccid paralysis
• ingestion of toxin
• Neurologic symptoms: cranial nerves affected first, descending symmetrical weakness, respiratory muscle weakness

• pathogenesis:
• Spores survive improper food preparation, germinate in food – toxin produced
• Toxin absorbed in stomach, small intestine, slowly in colon, circulated in bloodstream
• Toxin binds to peripheral neuromuscular junctions
• Toxin acts by blocking neurotransmitter (acetylcholine) release at peripheral cholinergic synapses.
• Toxin is a protease specific for synaptic vesicle proteins required for fusion with cytoplasmic membrane.
• Heat labile

tx: antitoxin

• both Clostridia toxin-producers
• Different effects of the toxins presumably due to differences in binding domains
• Active domain transported into neuron, specifically cleaves membrane protein of synaptic vesicle, preventing fusion with cell membrane

• botulism: stays at NMJ
• tetanus: transported to CNS via retrograde axonal transport --> crosses synapse to inhibitory neurons

• Gram-positive, spore-forming, anaerobic rod
• Occasional member of normal intestinal flora

• diseases:
• Antibiotic-associated diarrhea (AAD) (30%)
• Antibiotic-associated colitis (70%)
• Pseudomembranous colitis (100%)

• pathogenesis:
• Alteration of normal flora by antibiotic therapy
• Production of toxin in lumen, no invasion
• Toxins A and B: Glycosylation of Rho - family GTPases
• Binary toxin

tx: antibiotics (metronidazole)

• Risk factors:
• Old age , hospitalization, antibiotics, proton pump inhibitors
• Nosocomial outbreaks may occur
• Increasing incidence, recent series of severe hospital outbreaks

• Gram-negative bacillus, obligate anaerobe
• Minor component of normal fecal flora

• disease:
• Intra-abdominal abscesses
• Skin and soft tissue infections
• surgical wound infections: necrotizing fascitis

• Pathogenesis:
• Zwitterionic capsular polysaccharides - Induce abscess formation by direct interaction with T cells

• dx:
• Gram stain, culture

• tx:
• Drainage of abscess
• antibiotics

Facultative Gram-positive spore-forming bacilli Widespread in environment

• disease:
• mild food poisoning – wide variety of food types
• 2 distinct forms: vomiting without diarrhea type (emetic toxin); diarrhea type (enterotoxin)
• clinically similar to C. perfringens

• pathogenesis:
• production of emetic toxin (vomiting)
• production of enterotoxins (diarrhea)

• dx:
• culture of organisms in large numbers from implicated food
• culture from blood, wound, CSF

• tx:
• diarrhea: antibiotics not indicated
• invasive infections: antibiotics (vancomycin + clindamycin)

• Gram-positive filamentous bacilli
• microaerophilic or strictly anaerobic
• normal flora
• A. israelii most common species associated with invasive disease

• disease:
• Indolent inflammatory lesion: masses consisting of purulent center surrounded by dense fibrosis
• extensive sinus tract formation
• sulfur granules
• Oral-cervicofacial disease most common manifestation
• thoracic disease
• pelvic disease: associated with IUD

• dx:
• gram stain
• sulfur granule

• tx:
• antibiotics
• long course of therapy
• drainage of abscesses

• Filamentous Gram-positive bacilli
• Weakly acid-fast staining
• Obligate aerobes
• Ubiquitous in environment, particularly soil
• N. asteroides complex (former designation): invasive disease
• N. braziliensis: progressive lymphocutaneous diseasemycetoma

• invasive disease: pulmonary (masses, pneumonia) and CNS (brain abscesses); in immunocompromised; slowly progressive
• N. brasiliensis: cutaneous lessions, cellulitis, progressive lymphocutaneous disease

• dx:
• Gram stain and culture of sputum
• acid fast-staining

• therapy:
• antibiotics
• long course
• surgical

• Family of obligate intracellular bacteria
• forms: elementary body; reticulate body

• Chlamydia trachomatis: urogenital infections, ocular infections
• Chlamydophila (Chlamydia) pneumoniae: respiratory tract infections
• Chlamydophila (Chlamydia) psittaci: pneumonia and systemic infections usually acquired through exposure to birds

• Most commonly reported infectious disease in U.S.
• Highest incidence in sexually active 15-19 y.o. women

• diseases:
• Urethritis/Cervicitis: most asymptomatic; mucopurulent discharge
• epididymitis
• Neonatal infections: Inclusion conjunctivitis; pneumonia
• Perinatal infections
• Ocular infections: inclusion conjunctivitis
• Lymphogranuloma venereum
• Trachoma : Severity due to repeated reinfections; Chronic follicular conjunctivitis --> trichiasis causes corneal scratching
• inguinal lymphadenopathy
• PID --> tubal infertility, ectopic pregnancy

• pathogenesis:
• EB induces epithelial cell internalization
• Inclusion associates with Golgi secretion apparatus
• RBs obtain host nucleotides, amino acids, and lipids from host cell
• Inflammatory response induced in infected epithelial cells
• Tissue damage associated with inflammation

• dx:
• nucleic acid amplification techniques (NAAT)

screen all women under 25 y.o.

tx: antibiotics

Common cause of community acquired pneumonia

• disease:
• Pneumonia, URI

dx: Problematic, lack of agreement between methods

• Systemic febrile disease and pneumonia acquired from birds
• fever, pneumonia, hepatoslenomegaly
• Untreated disease can become protracted and severe

• Consider the diagnosis in persons with a history of exposure and compatible illness.
• Order cultures, obtain biopsy for histology if feasible, and send histo antigen from urine and serum for Dx.
• Treatment depends on severity of illness, with no treatment for mild infections.
• where you find histo you also find blasto geographically
• Histo: oHio and Mississippi river valleys

• Agent: Penicillium marneffei
• Penicilliosis in AIDS patients in Asia can mimic disseminated histoplasmosis

• Dimorphic fungus
• where you find histo you also find blasto geographically
• BlastoW: Big, Broad Based Budding yeast, Wet Wisconsin and mid-West

• Endemic to desert areas: lower Sonoran life-zone of Southwestern US, Mexico, Central and South America
• Hot, arid, alkaline soil
• Cocci is one of few fungal diseases where Ab detection useful
• Endemic mycosis of desert southwest can produce pneumonia and meningitis (spherule), diagnosed with serology, treat more severe dz
• Cocci: Large Cocciod yeasts from Crispy California (dry desert) and TuCson

• Agent: Paracoccidioides brasiliensis
• Granulomatous lesions: GI, skin, oral mucosa, lymph nodes, liver, spleen
• pilot’s wheel yeasts

• Agent: Lazazia loboi (aka Loboa loboi)
• Chronic subcutaneous infection
• Treatment: surgery

• Agent: Rhinosporidium seeberi
• Not a true fungus, but traditionally considered such

• Disease:
• tumor-like lesions of mucous membranes
• Nose: nasal polyps, bleeding, obstruction
• Eye: conjunctival growths
• Granulation tissue: acute and chronic inflammation

Cryptococcosis

Sporotrichosis

• The endemic mycoses are caused be dimorphic fungi
• Asymptomatic infections are the rule; common
• Pneumonia is most frequent clinical presentation
• Immunocompromised have higher risk of disease
• Exposure helps define risk: travel history
• Know the geographic distribution of endemic fungi
• Common pathogenesis: cell mediated immunity
• Diagnosis: Know the different diagnostic approaches
• Treatment: Itraconazole has antifungal activity for most of the endemic mycoses, though fluconazole is the treatment of choice for cocci meningitis.
• For severe disease use an amphotericin B compound.

• opportunistic:
• Aspergillus
• Non-Aspergillus mould (Zygomycetes, Fusarium, Scedosporium, Alternaria, etc.)
• Candida
• Pneumocystis
• Cryptococcus

• primary pathogens:
• Histoplasma
• Coccidioides
• Blastomyces
• Sporothrix
• Paracoccidioides
• Cryptococcus

• Cellular immunity is critical for fungal infections!
• fungal cell wall: glucan
• Antifungal medications: Topical; Systemic

• Chromoblastomycosis, phaeohyphomycosis, and mycetoma are rare in the United States, but consider in immigrants or immunocompromised hosts (phaeohyphomycosis)
• The subcutaneous mycoses are more common in the tropics with the exception of sporotrichosis which is widespread and which tends to be more acute
• Diagnosis by tissue biopsy and culture
• Treatment depends on syndrome and fungus

• Polyenes: amphotericin B
• Azoles: voriconazole
• Echinocandins: micafungin
• Nucleoside analogue: 5-FC
• Microtubule inhibitor: Griseofulvin
• Squalene epoxidase inhibitors: Terbinafine
• Other agents which are topicals

• Ampho B (polyene): perforation of cell membrane
• Azoles: inhibit ergosterol synthesis
• Echinocandins: inhibit cell wall synthesis (glucan)
• Flucystosine: inhibits DNA and RNA synthesis

• mycoses: mould; Ubiquitous moulds in the environment
• Aspergillus fumigatus most common isolate

• disease: opportunistic
• invasive asperillosis: pneumonia, sinusitis, angioinvasion --> common cause of death and morbidity in immunocompromised patients such as recipients of transplants

dx: cannot rule in by histology; similar appearance of other fungi

• tx: Don’t use fluconazole, it has no activity!
• Voriconazole is the treatment of choice for IA

for septated, acute angle hyphae, voriconazole as intitial therapy

• Zygomycetes
(agents of mucormycosis)
• Free iron promotes the growth of the mucorales

disease: mucormycosis (eye infection)

• Suspect mucormycosis in patients who are immunosuppressed or have diabetes (DKA), particularly with organ appropriate disease (rhinocerebral; sino-orbital)
• Radiographic changes lag behind clinical disease; initiate empirical treatment, obtain tissue via early surgical consultation and intervention, and use lipid based amphotericin for empiric and directed therapy

• Gram-negative aerobic diplococci
• Pathogens: N. meningitidis, N. gonorrhoeae

• pathogenesis:
• Adhesive fimbriae
• Porins
• Opa outer membrane proteinsm multiple, variable
• IgA protease
• Lipo-oligosaccharide (LOS): endotoxin secreted by bacteria

• Gram-negative diplococcus, microaerophilic
• Transient component of nasopharyngeal flora
• Highest incidence in 6 months - 2 year age group
• 14-20 year old age group at risk – higher mortality
• Epidemics occur

• Diseases:
• Meningococcemia: Acute onset of fever, rash,
• Fulminant meningococcemia: Rapid progression, shock; Purpuric, hemorrhagic lesions
• meningococcal sepsis
• Meningitis: same as other bacterial meningitis
• Overall mortality: 5 –15% despite antibiotic therapy

• pathogenesis:
• Antiphagocytic polysaccharide capsuleL Serotypes A,B,C,W-135,Y (B identical to E. coli K1 – non immunogenic)
• Endotoxin-mediated effects - sepsis
• Endotoxin released from bacterial cell surface

• dx:
• Gram stain of CSF
• Culture of organism from blood or CSF

treatment: antibiotics

• prevention:
• vaccine: Conjugate vaccine against type all serotypes except B
• antibiotic prophylaxis

• Gram-negative diplococcus, microaerophilic
• Gonorrhea is frequently transmitted by asymptomatic women
• Highest incidence in urban, black heterosexuals

• disease:
• Urethritis, cervicitis, with discharge
• Complications: Male - epididymitis; Female - PID (10-20% of untreated women)
• Neonatal gonorrhea: Acute conjunctivitis
• Disseminated gonococcal infection: Acute arthritis, skin lesions

• Pathogenesis:
• Invasion of epithelial cells
• Survival in neutrophils
• Antigenic variation during course of infection
• Colonization of epithelial cells mediated by adhesive fimbriae
• Antigenic variation of fimbriae associated with DNA rearrangement

• dx:
• Gram-stain, culture from exudate
• Nucleic acid-based detection

• tx:
• Combination therapy to cover Chlamydia

• Neonate:
• E. coli (K1 serotype)
• Group B Streptococcus
• Listeria monocytogenes

• Infants (6 months – 2 years):
• Neisseria meningitidis
• Streptococcus pneumoniae
• Haemophilus influenzae (essentially eliminated in U.S. by vaccine)

• Young adults:
• Neisseria meningitidis (epidemics)

Vaccines: H. influenzae, N. meningitidis, S. pneumoniae

• opportunistic fungal pathogen
• most commonly causes interstitial pneumonia and is a common AIDS defining condition
• Cultivation is not useful
• Diagnosis by histology/cytology
• Treatment uses agents that are outside the usual antifungal spectrum
• Steroids used for severe hypoxia
• Prophylaxis for at risk populations

• Obligate intracellular Gram-negative bacteria
• Transmission by arthropod vectors
• sx: Fever, rash
• Patients remain latently infected after recovery, and reactivation disease may occur years later

• Gram-negative
• transmitted by bites from ticks
• Highest incidence in South Atlantic and South Central States
• G6PD deficiency (10% of black males) at risk for fulminant, fatal infection
• Transmission takes about 24 hours

• disease:
• Rocky Mountain Spotted Fever: Fever, myalgia, severe headache; Maculopapular rash
• Severe disease involves multiple organ systems

• pathogenesis:
• vascular endothelial cells
• actin-based motility

• Ehrlichia chaffeensis (order Rickettsiales)
• Transmitted by Amblyomma americanum (Lone Star Tick)
• Survival in monocytes/macrophages

• Anaplasma phagocytophilum (order Rickettsiales)
• Transmitted by Ixodes scapularis (Deer Tick)
• Survival in neutrophils

• Obligate intracellular Gram-negative coccobacillus
• Most infections associated with exposure to sheep, goats, cattle

• Disease:
• Q fever – most cases mild and self-limiting
• Acquired by inhalation of contaminated aerosols associated with animal exposure
• Intracellular survival in monocytes/macrophages

• Cat-scratch Disease – B. henselae
• cutaneous papule or pustule at site of cat scratch or bite
• cat-flea vector
• regional lymphadenitis

• Spiral shaped, poorly staining
• Periplasmic flagella
• Variability, multiple stages
• Cytokine induction
• Immune mediated pathology
• Tropism for CSF

• disease:
• recurring/relapsing fevers (louse form more severe than tick form)
• Jarisch-Herxheimer reaction associated with antibiotic treatment of all spirochaetal infections

• spirochete
• Slow growth (6-8 weeks) on primary isolation using specialized media
• Persists in renal tubules of animals
• Most human disease occurs in tropical and subtropical developing countries
• Most important sources of infection in U.S.dogs, cattle, rodents (inner city cases)
• most cases unrecognized

• disease:
• Anicteric leptospirosis (>90% of cases)
• Icteric leptospirosis (Weil's disease): high mortality rate

• pathogenesis:
• Entry into circulation through skin abrasions, mucous membranes
• Tubular damage in kidneys

• tx:
• Early antibiotic therapy most effective
• Antibiotics associated with Jarisch-Herxheimer reaction (Doxycycline, penicillin, ceftriaxone)

• spirochete
• slow growth
• Most common vector-borne infection in U.S.
• Transmitted by ticks (Ixodes scapularis)
• Highest incidence in NE U.S.

• disease:
• Lyme disease: Disease occurs in three stages: Localized infection; Disseminated infection; Persistent infection
• Erythema migrans = stage 1
• disseminated infection = stage 2 (Headache, stiff neck, fever, myalgias, arthralgias, malaise and fatigue; secondary EM lesions)
• persistent infection = stage 3 (recurring arthritis; Acrodermatitis chronica atrophicans)

• pathogenesis:
• Antigenic variation of major surface lipoprotein

• prevention:
• early detection
• antibiotic prophylaxis
• avoid ticks
• vaccine removed from market

Spirochete, cannot be cultured in vitro

• Disease: syphilis
• Sexually transmitted disease characterized by 4 stages
• 1. (Genital) ulceration: chancre
• 2. Disseminated disease - rashes, fever, mylagias, meningitis
• 3. Latent syphilis - silent; Infection of fetus in utero can occur
• 4. Late syphilis - neurological, cardiovascular, granulomatous manifestations

• pathogenesis:
• Entry via minor skin lesions
• Large numbers of spirochetes in blood, CSF, and tissues
• Progressive inflammatory disease

• dx:
• non-specific and specific (remains positive after therapy) tests

• Small, fastidious, Gram-negative coccobacillus
• Important agent of genitial ulceration in AfricaContributes to transmission of HIV
• sporadic outbreaks

• Disease:
• chancroid
• Genital ulceration
• inguinal lymphadenopathy

dx: Culture difficult, insensitive

tx: macrolides

• Yeasts:
• Candida species
• Cryptococcus neoformans
• Cryptococcus gattii

• Superficial mycoses (usually caused by moulds):
• Dermatophytes
• Malassezia species
• Trichosporon species
• Others

• Don’t use fluconazole for C. krusei or glabrata
• Candida is most common fungal opportunist
• Candida species are the 4th most common cause of bloodstream infection in the U.S.
• Candida albicans is a common cause of superficial and deep/disseminated disease
• Candida krusei and C. glabrata are increasing in frequency as pathogens related to the increased use of fluconazole
• Echinocandins are the newest class of antifungals with excellent activity against most Candida species (Candida parapsilosis is less susceptible)

• disease:
• Oropharyngeal Candidiasis (OPC)
• Vulvovaginal Candidiasis (VVC)
• Urinary Candidiasis

Risk factors: AIDS, diabetes, surgery, catheters, antibiotics, neutropenia, burns, dialysis, chemotherapy, radiation therapy, prolonged ICU stay, liver transplant

• disease:
• Vulvovaginal Candidiasis (VVC)

• C. albicans --> most common cause of human infection
• C. tropicalis
• C. glabrata
• C. krusei
• C. lusitaniae and guilliermondii
• C. parapsilosis

• Candida albicans is a common cause of superficial and deep/disseminated disease
• opportunistic pathogen producing a wide diversity of infections at different sites
• Candida albicans is germ tube positive
• Pneumonia is uncommon

• environmental yeast with thick capsule
• Narrow budding, capsule is antiphagocytic
• Common pathogen in AIDS: meningitis with elevated intracranial pressure
• Outbreak of C. gattii in Pacific Northwest
• Both a primary pathogen (normal host) and an opportunist (AIDS, Transplant)

• disease:
• lung
• CNS

• Pathogenesis: Primary pulmonary infection after inhalation of yeasts with self-limited disease in most patients.
• Pneumonia, meningitis, or disseminated disease (skin) possible.

Risk factors for disease: AIDS, hematological malignancy, steroids

• Variety of fungal pathogens implicated
• Very common infections
• Remember the dermatophytes (3 genera): Geophilic, Zoophilic, Anthropophilic (person to person)
• Diagnosis is usually clinical, with empiric use of OTC topical or prescription oral antifungals
• Can do scraping for KOH microscopy, culture
• Tinea capitis usually treated with oral agents such as terbinafine or griseofulvin
• Onychomycosis: difficult to eradicate, topicals don’t work, need months of oral therapy: itraconazole, terbinafine