EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 ·...

13
M. Jackson Eye August 22, 2001 1 of 13 EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters 18, 27, & 50 Staphylococcus aureus I. Virulence factors relevant to Eye Infections A. α-toxin is primary virulence factor of S. aureus B. Teichoic acid aids colonization C. Antiphagocytic components II. Etiology / Pathogenesis A. S. aureus is principal cause of eye infections due to high carriage rate in humans B. Staphylococcal eye infections: 1. Blepharitis: Infection of eyelid margin or sebaceous gland 2. Dacrocystitis: Inflammation of lacrimal sac 3. Conjunctivitis a. Inflammation of conjunctiva, may extend to cornea, eyelids, sclera b. Keratoconjunctivitis involves conjunctiva and cornea c. Colonization of cornea often requires some trauma, e.g. scratch 4. Endophthalmitis a. Infection of aqueous or vitreous humor b. Requires ulceration or penetrating injury to compromise cornea and sclera III. Clinical identification of organism A. Specimen collection of surface material or removal of infected humor (endophthalmitis) B. Gram positive cocci in clusters C. Catalase test positive to differentiate from Streptococci D. Coagulase positive to speciate S. aureus E. Antimicrobial susceptibility testing

Transcript of EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 ·...

Page 1: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20011 of 13

EYE INFECTIONSBACTERIA CAUSING EYE INFECTIONS

Reading Assignment: Chapters 18, 27, & 50

Staphylococcus aureusI. Virulence factors relevant to Eye Infections

A. α-toxin is primary virulence factor of S. aureusB. Teichoic acid aids colonizationC. Antiphagocytic components

II. Etiology / PathogenesisA. S. aureus is principal cause of eye infections due to high carriage rate in humansB. Staphylococcal eye infections:

1. Blepharitis: Infection of eyelid margin or sebaceous gland2. Dacrocystitis: Inflammation of lacrimal sac3. Conjunctivitis

a. Inflammation of conjunctiva, may extend to cornea, eyelids, sclerab. Keratoconjunctivitis involves conjunctiva and corneac. Colonization of cornea often requires some trauma, e.g. scratch

4. Endophthalmitisa. Infection of aqueous or vitreous humorb. Requires ulceration or penetrating injury to compromise cornea and sclera

III. Clinical identification of organismA. Specimen collection of surface material or removal of infected humor (endophthalmitis)B. Gram positive cocci in clustersC. Catalase test positive to differentiate from StreptococciD. Coagulase positive to speciate S. aureusE. Antimicrobial susceptibility testing

Page 2: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20012 of 13

Streptococcus pneumoniaeI. Virulence factors relevant to Eye Infections

A. Polysaccharide capsule1. Primary virulence factor of S. pneumoniae2. Interferes with classical and alternate complement pathways3. 84 different capsular serotypes

B. Pneumolysin is membrane-damaging cytolysin related to SLOC. Cell wall teichoic acid and peptidoglycan contribute to inflammatory response

II. Etiology / PathogenesisA. S. pneumoniae may cause Dacrocystitis (inflammation of lacrimal sac)B. S. pneumoniae may cause Conjunctivitis, Keratoconjunctivitis (Conjunctiva, cornea)

III. Clinical identification of organismA. S. pneumoniae also referred to as pneumococcus or diplococcusB. Gram positive, lancet-shaped, diplococciC. Pneumococcus is not part of Lancefield grouping schemeD. Biochemical tests

1. Capsular serotyping2. Quellung reaction:

Capsular swelling induced by mixing pneumococci + anti-capsule antibodies3. Optochin (P disk) susceptibility & Bile solubility to differentiate from Strep. viridans

Page 3: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20013 of 13

Haemophilus influenzaeI. Virulence factors relevant to Eye Infections

A. Polysaccharide capsule1. Most important virulence factor of H. influenzae2. Antiphagocytic and subject to antigenic variation3. Differentiates H. influenzae into 6 different serotypes: a-f

B. Strains of serotype b most virulent1. Capsule of type b composed of polyribitol phosphate (PRP)2. Hib vaccine given from 2 months of age since 1990

a. PRP conjugated with diphtheria toxoid or Neisseriae outer membrane proteinb. Caused dramatic drop in H. influenzae type b colonization and infection

II. Etiology / PathogenesisA. H. influenzae found exclusively in humans

1. High carriage rate in upper respiratory tracta. 80% in childrenb. 50% in adults

2. Normal flora strains usually lack capsuleB. H. influenzae may cause Conjunctivitis, Keratoconjunctivitis (Conjunctiva, cornea)

III. Clinical identification of organismA. Morphology

1. Gram negative, coccobacillary shape2. Among the smallest of bacteria at 1.0-1.5 µ

B. H. influenzae require blood products for growth1. Hematin (X factor) and/or NAD (V factor) required2. X and V factor either added to media or supplied by lysed erythrocytes in chocolate agar3. Diagnostic feature is growth on chocolate agar but not on blood agar

C. Serotyping of capsule using anti-capsular antibodies

Page 4: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20014 of 13

Pseudomonas aeruginosaI. Virulence factors relevant to Eye Infections

A. Exotoxin A1. A/B cytotoxin that binds receptor and enzymatically inactivates protein synthesis2. Enzymatic subunit catalyzes ADP-ribosylation of elongation factor 23. Reaction: NAD + EF2 ↔ADPR-EF2 + nicotinamide + H+

4. Same enzymatic activity as diphtheria toxin5. Exotoxin A promotes tissue invasion and facilitates evasion of immune response

B. Exotoxin S1. Mechanism and contribution to virulence similar to exotoxin A2. ADP-ribosylates several different proteins

C. Elastase1. Protease with elastin, human IgA, IgG, complement, collagen as substrates2. Primary cause of corneal perforation during eye infection

D. Adhesin for colonization of human tissue1. Associated with pili that belongs to a family found on gonococcus and Vibrio cholerae2. Adhesion of P. aeruginosa to cornea requires trauma (scratch) to expose receptors

Page 5: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20015 of 13

F. Genetic regulation of virulence factors1. Iron regulates Exotoxin A; iron is common regulator of virulence factors (cytotoxins)2. LasR is transcriptional activator of Exotoxin A and elastase genes

a. LasR responds to environmental signals in human hostb. Signals that environmental pathogen it is in human host (analogy: Vibrio cholerae)

II. Etiology / PathogenesisA. P. aeruginosa found free-living in most environments

1. Opportunistic pathogen, breach in the 1st line of defense (wound) initiates infection2. Contaminates water and contact lens solutions⇒ eye infection3. Iatrogenic infection (physician activity): contaminated ophthalmologic equipment

B. Diseases of eye caused by P. aeruginosa1. Conjunctivitis: infection of conjunctiva2. Keratitis: infection of cornea

a. Colonization of cornea requires trauma to expose receptorsb. Extended wear contact lenses can contribute to colonization of corneac. P. aeruginosa can progress rapidly and destroy cornea in 24-48 hoursd. Inflammatory response PMNs damages cornea, can lead to perforation

3. Endophthalmitis: infection of aqueous or vitreous humora. Requires ulceration or penetrating injury to compromise cornea and sclerab. Inflammatory response can lead to corneal perforation and infection of humor

III. Clinical identification of organismA. Gram negative rod, motile in wet mountB. Growth characteristics

1. Aerobic, but will grow anaerobically if supplied with nitrate as electron acceptor2. Tolerates wide variety of temperatures and high salt content3. Has fruity odor on solid media4. Blue-green fluorescence under ultraviolet light due to pigment pyoverdin

C. Biochemical tests1. Produces high levels of cytochrome oxidase⇒ Positive oxidase test2. OF Dextrose tubes demonstrate aerobic growth

Page 6: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20016 of 13

Chlamydia trachomatisI. Virulence factors relevant to Eye Infections

A. Life cycle1. Infectious elementary body2. Intracellular replicative reticulate body

B. Endocytosis1. Elementary body carries adhesins for attachment to epithelial cell receptors2. Endocytosed elementary bodies do not stimulate lysosomal fusion3. Organism may remain in dormant state but elicit inflammatory response

II. Etiology / PathogenesisA. Primarily sexually transmitted infection; role in eye infections alsoB. Mother→ newborn (inclusion conjunctivitis) or person→ person (trachoma) transmission

1. Conjunctivitis, keratitis, keratoconjunctivitis2. Ophthalmia neonatorum

C. Trachoma1. Chronic follicular conjunctivitis2. Most often in less developed countries (Africa & Asia), affects ~500 million3. Trichiasis is inward growth of eyelashes that continually scrape cornea4. Begins in childhood, recurrent infection from fingers & contaminated objects

Page 7: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20017 of 13

5. Chronic inflammation of eyelidsa. Interleukin-1 is mediator of inflammation and scarringb. Vascularization of corneac. Severe corneal scarring and deformities⇒ blindness

D. Inclusion conjunctivitis1. Acute infection of newborns and adults worldwide2. Associated with genital serotypes of C. trachomatis3. Most common form of neonatal conjunctivitis, occurring in 2-6% of newborns in US4. Direct contact with cervical secretions of mother during delivery5. Acute, mucopurulent eye discharge 2-25 days postpartum

III. Clinical identification of organismA. Characteristics

1. Gram negative outer membrane but lacking peptidoglycan, coccobacillary2. Chlamydiae are intracellular parasites

B. Diagnosis by conjunctival scrapings1. C. trachomatis is isolated by cell culture for 3-7 days

a. Cytoplasmic inclusions detected by iodine staining of glycogenb. Immunofluorescent staining of outer membrane proteins

2. Methods not requiring cell culturea. Direct fluorescent antibody staining & enzyme assaysb. DNA or RNA detected using probes and PCR

SPECIAL CASE BACTERIAL EYE INFECTIONSBacteria Classification SyndromeStreptococcus pyogenes Gram pos. cocci KeratoconjunctivitisNeisseria gonorrhoeae Gram neg. diplococci Keratoconjunctivitis,

Ophthalmia neonatorumMoraxella lacunata Gram neg. coccobacillary Angular conjunctivitisBacillus cereus Gram pos. rod Environmental, Opportunistic

infections

Page 8: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20018 of 13

EYE INFECTIONSFUNGI CAUSING EYE INFECTIONS

Candida albicansI. Virulence factors relevant to Eye Infections

1. Adhesins and invasive hyphae bind to fibronectin, collagen, and laminin2. Proteases and elastases may have role in the invasion process

II. Etiology / PathogenesisA. C. albicans is commensal of oral cavity and urogenital tractB. Endophthalmitis

1. Originates as a result of injury2. White cotton ball expanding on retina or floating in vitreous humor

C. Chorioretinitis1. Occurs in immunocompromised patients2. Manifestation of systemic disease; can lead to blindness

III. Clinical identification of organismA. Blood culture required for detection of disseminated diseaseB. KOH or Gram stains reveal budding round or oval yeast cells with hyphae

Histoplasma capsulatumI. Virulence factors relevant to Eye Infections

A. Dimorphic growth phases1. Mold in the environment, at 22 °C2. Conversion to pathogenic yeast form in tissue, at 37 °C (heat shock response)

B. Evasion of immune system1. Capacity to enter dormant stage once inside human host2. Capacity to grow inside phagocytes, survival of oxidative burst, lysosome fusion

II. Etiology / PathogenesisA. Mold form grows in soil under humid conditions

1. Associated with bird (starling, chicken) and bat droppings2. Infectious conidia enter host by inhalation, convert to yeast form

B. Predominantly a pulmonary disease with possible dissemination⇒ chorioretinitis1. Pulmonary lesions with granulomatous inflammation in lungs, liver spleen2. Dissemination via reticuloendothelial system⇒ chorioretinitis3. Infection elicits delayed type hypersensitivity

a. Immunity is T-cell dependentb. Immunocompromised patients develop chronic infections

Page 9: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 20019 of 13

III. Clinical identification of organismA. Examination of blood culture, biopsy, or bone marrow for yeast cells

1. Grows slowly (weeks) on blood and Sabouraud’s agar2. Can be cultured for identification of dimorphic fungus

B. Immunodiffusion test available to detect mycelial antigen

Coccidioides immitisI. Virulence factors relevant to Eye Infections

A. Mold form produces arthroconidia {arthro ≡ joint; conidia ≡ spores} that are infectiousB. Dimorphic growth phases

1. No yeast form, round spherule is the invasive tissue form2. Spherule contains endospores that are released and serve as reproductive unit

II. Etiology / PathogenesisA. Geographically limited to hot, dry regions of the Southwestern USB. Primarily a pulmonary infection with dissemination

1. Dissemination to CNS and to eye⇒ chorioretinitis2. < 1% pulmonary cases disseminate3. Dissemination more common in the immunocompromised

C. Immune response1. Inhaled arthroconidia engulfed by PMNs2. Spherules induce inflammatory, granulomatous response3. T-cell activated macrophages engulf endospores4. Ultimately, there is delayed type hypersensitivity response to infection

III. Clinical identification of organismA. Blood and biopsy samples

1. Observation of large spherules in specimens2. Organism may be cultured to observe mold form

B. Skin and serologic tests are available

SPECIAL CASE FUNGAL EYE INFECTIONSFungus SyndromeAspergillus spp. Keratoconjunctivitis,

EndophthalmitisFusarium spp. Keratomycosis

Page 10: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 200110 of 13

PARASITES CAUSING EYE INFECTIONSAcanthamoeba spp.

I. Etiology / PathogenesisA. Life cycle

1. Free living Trophozoites (ameba)2. Cysts (≡ spores) that are infectious stage

B. Inhabit soil, fresh and brackish water; isolated from throats of healthy individualsC. Ulcerative keratitis

1. Amebas invade ocular tissue through break in corneal epithelium2. Infection follows mild corneal trauma, e.g. improperly sterilized hard contact lenses3. Ulcerative keratitis follows failed response to anti-bacterial, -fungal, or -viral treatments4. Trophozoites and cysts penetrate corneal stroma⇒ granulomatous inflammation5. Corneal ulcerations, chronic progressive ulcerative lesion that may lead to blindness6. Normal immune defenses insufficient for amebic keratitis

D. Acanthamoeba can cause encephalitis1. Infectious cysts transmitted to pulmonary sites by dust and aerosols2. Ameba reaches brain ⇒ encephalitis, primarily in elderly & immunocompromised

a. Hematogenous dissemination from unknown primary siteb. Primary infection of respiratory tract, eye, and skin suspected

II. Clinical identification of organismA. Trophozoites and cysts may be seen in corneal biopsies

1. Light and electron microscopy2. Immunofluorescence

B. Amebas may be cultured using media containing Gram-negative bacteria (= food)

Toxoplasma gondiiI. Virulence factors relevant to Eye Infections

A. Life cycle in cats1. Obligate, intracellular protozoan, warm-blooded mammals are host2. Sexual stage in intestinal tract of cats, oocysts passed in feces

B. Life cycle in humans1. Oocysts accidentally ingested or tissue cysts by eating infected meat2. Trophozoite (tachyzoite) asexual stage for cell invasion; resists phagocytic killing3. Tissue cyst are invasive stage that exist in host organs (brain, muscle)

Page 11: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 200111 of 13

II. Etiology / PathogenesisA. Congenital toxoplasmosis

1. ~1/2 of US population has been infected; may be passed in utero2. Infection may spread to CNS in utero

B. Chorioretinitis caused by T. gondii1. Accounts for 1/4 of all granulomatous uveitis (middle eye: iris, ciliary body, choroid)2. Most common delayed manifestation of congenital toxoplasmosis3. Reactivation of dormant tissue cysts in 20-40 yr. olds, with immunosuppression4. Toxoplasma proliferates in retina leading to inflammation of choroid5. Bilateral and focal lesions; inflammatory exudate may cloud vitreous humor

II. Clinical identification of organismA. Tissue biopsy and blood samples to demonstrate trophozoites by immunofluorescenceB. Serology to demonstrate rise in IgG titers to Toxoplasma antigens⇒ acute infection

Page 12: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 200112 of 13

Toxocara canisI. Virulence factors relevant to Eye Infections

A. Life cycle in canines (resembles Ascaris lumbricoides infection of humans)1. Eggs ingested→intestinal mucosa→ liver→ heart →lung2. Larvae coughed up and re-ingested to complete maturation in small bowel3. Larvae may enter pulmonary capillaries and go systemic, encysting in tissue4. 200,000 eggs released by E worm into feces; eggs can live years in the soil

B. Lifecycle in humans (injured accidental host) 1. Eggs ingested, larvae pass through pulmonary capillaries→ systemic circulation

2. Larvae grow in capillaries where they penetrate wall and enter tissue

II. Etiology / PathogenesisA. Infection rates in dogs and humans

1. 80% of puppies, 20% of older dogs infected2. 10-30% of soil samples (esp. Southeastern U.S.) contain eggs3. 4-20% of human population has ingested eggs4. Incidence highest in children 1-6 yr., history of geophagia or pica (eating dirt)

B. T. canis is a tissue nematode causing visceral larva migrans & chorioretinitis in humans1. Eosinophilic granulomas & tissue necrosis: liver, lung, heart, brain, skeletal muscle, eye2. Ocular larva migrans more common in older children and adults3. Retinal granuloma ⇒ unilateral strabismus, decreased visual acuity4. Localized lesions in the retina may cause detachment

III. Clinical identification of organismA. Biopsy sample to demonstrate larvaeB. Leukocytosis and elevated antibody titers to Toxocara antigensC. Enzyme immunoassay to larval antigens is available

Page 13: EYE INFECTIONS BACTERIA CAUSING EYE INFECTIONS Reading Assignment: Chapters … · 2001-11-13 · B. Gram positive, lancet-shaped, diplococci C. Pneumococcus is not part of Lancefield

M. JacksonEye

August 22, 200113 of 13

CASE STUDYFOR

EYE INFECTIONS

A 24-year-old woman reported to the emergency department with severe pain and vision lossin her right eye. She wore contact lenses and had left them in her eyes during a 16-hour shift asan air traffic controller. Her eyes were irrigated and she was sent home with antibiotic eye drops.The woman was brought to the same emergency department the following day suffering fromcorneal perforation of the right eye. Prior to surgical removal of the infected eye, swabs of thecornea and conjunctiva were collected for identification of the pathogen.

Questions:1. What are the most likely pathogens causing this infection?2. Identify a bacterial virulence factor that contributed to the corneal perforation.3. Why were the antibiotic eye drops ineffective?