Bacterial Infections

Summary

Cocci
Staphylococci	Gram positive	Aerobic Facultatively anaerobic	Belong to Micrococcaceae family All types produce catalase S. aureus cause haemolysis on blood agar - S. epidermidis don't Divides in two planes	Coag positive: S. aureus, S. intermedius, S hyicus S. aureus - yellow colony S. epidermidis - white colony. Associated with hypersensitivity marginal keratitis
Streptococci (rare ocular pathogens)	Gram positive	AerobicFacultatively anaerobic	Catalase negative Slightly oblong cell shape Divides in one plane	Strep pyogenes (beta-haemolytic): scarlet fever Strep pneumoniae (alpha-haemolytic): pneumonia and meningitis (associated with C3 deficiency) Crystalline keratopathy
Neisseria	Gram negative	Aerobic	IgA proteases cleave immunoglobulins N. gonorrhoea ferments glucose N. meningitidis ferments glucose and maltose	N. meningitidis: meningococcus (associated with C5-9 deficiency) N. gonorrhoea: gonococcus (ophthalmia neonatorum). CAN breach intact epithelium Grow on chocolate agar Have endotoxin activity
Bacilli
Mycobacteria	Ziehl-Neelson stain	Aerobic		M. tuberculosis: man is the primary host. Resists destruction by intracellular enzymes. Caseating granuloma of macrophages
Bacillus genus	Gram positive	Aerobic	Catalase-positive, spore-forming	Bacillus anthracis: anthrax Bacillus cereus: food poisoning Post-traumatic endophthalmitis (25% of cases especially with intraocular foreign bodies and rural settings). Causes a fulminant endophthalmitis with rapid/severe vision loss. Treat with intravitreal vancomycin or clindamycin
Clostridia	Gram positive	Obligate anaerobes	Can produce powerful exotoxins. Tetanus toxin affects presynaptic terminals of inhibitory interneurones, preventing normal inhibitory control of motor neurones	C. tetani: tetanus. Toxin travels beyond the wound but the bacteria do not. Tetanus can occur weeks after infection. Antitoxin is ineffective once nervous tissue affected C perfringens: gas gangrene, conjunctivitis, necrotizing keratitis, panophthalmitis (detected by positive Nagler reaction) *these produce disease if implanted deep in tissues
Propionibacterium acnes	Gram positive	Obligate anaerobe		CommensalBlepharitis, (delayed post-op, chronic) endophthalmitis
Actinomyces	Gram positive	Facultative/obligate anaerobe		Chronic canaliculitis Sensitive to penicillin Discharges contain yellow sulphur granules
Haemophilus influenzae	Gram negative	Facultative anaerobe. Depends on haematin which is produced by many bacteria	Type b capsule antigen is key determinant of virulence. It is not always encapsulated but increased virulence if so as it can avoid phagocytosis	Commonly isolated in preseptal/orbital cellulitis in infants/toddlers. CAN breach intactcorneal epithelium Meningitis, sinusitis,  and epiglottitis
Enterobacteriaceae	Gram negative	Aerobic	GI commensals	E. coli (motile) Klebsiella (non-motile) Salmonella (urease neg) Proteus (urease pos)
Moraxella lacunata	Gram negative		Grows on MacConkey agar Sensitive to chloramphenicol	Central corneal ulcers, chronic conjunctivitis, angular blepharitis
Pseudomonas	Gram negative	Aerobic. Dependent on iron for growth	Proteases allow penetration through traumatised epithelium (note cannot pass through intact epithelium).Toxin A destroys protein glycol matrices	Risk factors: trauma, burns, vitamin A deficiency, immunosuppression
Bartonella henselae	Gram negative		Transmitted via a cat scratch or bite	Cat-scratch neuroretinitis (macular star with optic disc swelling) and Parinaud’s oculoglandular syndrome (unilateral granulomatous conjunctivitis with ipsilateral swollen preauricular nodes) Treatment: oral doxycycline or erythromycin (with or without rifampicin)
Other
Chlamydia trachomatis(ovoid shape)	Gram negative (weak)	Obligate intracellular bacteria	No cell wall Grow within eukaryotic cells: cannot produce energy alone. Glycogen positive	Serotypes A, B and C: trachoma Serotypes D to K: inclusion conjunctivitis (STI) Serotypes L1, 2 and 3: lymphogranuloma venereumDiagnosis: Giemsa staining, ELISA, antibody in serum (immunofluorescent staining), PCR or NAAT
Borrelia burgdorferi	spirochaete		Rodents are the main reservoir (humans are incidental hosts via ticks)	Lyme disease
Treponema pallidum	spirochaete	Temperature sensitive	Enclosed in cytoplasmic membrane and peptidoglycan cell wall and envelope. Motile	T. pallidum: SyphilisT. pertenue: yaws

Conjunctivitis and blepharitis

• Streptococcus pneumoniae
• Staphylococcus aureus
• Moraxella 
• Neonatal conjunctivitis
• Neisseria gonorrhoeae
• Chlamydia trachomatis
• Herpes simplex virus (rare)

• Typically treated with systemic antibiotics and regular irrigation of the conjunctival sac (topical therapy may be added)

Pseudomonas aeruginosa

• Most common cause of bacterial keratitis worldwide (60% of CL-related keratitis)
• Gram negative bacillus
• GI commensal
• Common in freshwater
• Risk factors:
• CL wear
• Corneal injury
• Virulence factors

• Exotoxins via type III secretion system (T3SS). T3SS acts like a needle, creating a pore-forming complex with the host plasma membrane through which effector proteins (exotoxins) are “injected” into the cytosol.

• ExoU causes rapid cell lysis and severe corneal disease 

• Host response is primarily innate immunity driven although adaptive immunity does play a role in later stages of infection

• LPS and flagellin activate TLR4 and TLR5 on macrophages producing a chemotactic and proinflammatory response

Streptococcus

• S. pyogenes is a common Gram positive throat commensal
• S. pneumoniae is an upper respiratory commensal and commonly found in the conjunctiva
• Common cause of bacterial keratitis
• Corneal injury allows opportunistic infection (often aggressive)
• Exotoxins are produced: pneumolysin is the most potent
• Forms pores in host cell membranes leading to leakage and death

Staphylococcus aureus

• Gram positive, coagulase positive, phosphatase positive
• Produces exotoxins
• Ferments mannitol
• Colonies have a golden appearance
• Less severe disease compared to streptococcus and pseudomonas
• Causes peripheral ulcers
• Most common cause of carbuncle and phage types I and II cause boils
• Resistant strains can be difficult to treat: MRSA
• Virulence factors: haemolysins facilitate bacterial survival.
• Other coagulase positive staph include S. intermedius and S. hyicus

Trachoma

• Most prevalent microbial cause of blindness worldwide
• Caused by chlamydia trachomatis subgroup A, B, Ba, and C
• Serotypes D-K cause an inclusion conjunctivitis
• Replicate in conjunctival epithelium
• Forms spores that are transmitted
• Clinical features
• Mixed papillary conjunctivitis and follicular response
• Tarsal conjunctival scarring

• Entropion due to contraction of the scar and trichiasis

• Blinding corneal opacity due to corneal scratch from lashes
• Stages
• I: involvement of conjunctival stroma
• II: involvement of the cornea with pannus formation
• III: fibrous replacement of inflamed tissue
• IV: contraction with entropion and trichiasis
• IFN-gamma plays a role
• Treatment
• Azithromycin
• Hygiene/facial cleanliness to prevent transmission
• Lid surgery for entropion and trichiasis
• Environmental health

Reiter’s syndrome

• May follow chlamydial urethritis or Gram negative dysentery
• Commoner in people with HLA-B27
• Males > females
• Triad:
• Non-gonococcal urethritis
• Conjunctivitis
• Arthritis
• Systemic findings
• Keratoderma blennorrhagica
• Aphthous ulcers
• Circinate balanitis

Moraxella lacunata

• Gram negative bacillus
• Chronic conjunctivitis
• Angular blepharitis
• Keratitis in frail patients

Spores

• Central cortex with layered outer coat of keratin
• Mostly produced by Gram positive bacilli
• Function as a resting and defensive form for bacteria to exist (NOT for reproduction)
• Resistant to antibiotics
• Can be killed by temperatures of 120 degrees for 20 minutes
• Cannot be identified with Gram staining

Chlamydia life cycle

• Two forms:
• Elemental body (infectious form)
• Reticulate body (replicate form)
• Elemental body penetrates cell
• Enclosed in cytoplasmic vesicle to avoid lysosomal destruction
• Organises into reticulate body
• Divides for 24 hours
• Regresses to elemental form
• Chlamydia can cause latent infection

Syphilis

• Caused by Treponema pallidum (a spirochaete)
• Treponema dies quickly in the outside environment

• VDRL (Venereal Disease Research Laboratory test) is a screening test but can also be positive in leprosy, malaria and connective tissue diseases including RA, SLE and APS

• Detects anti-cardiolipin antibodies
• Produces a titre which can be used to monitor the response to treatment
• FTA-ABS (fluorescent treponemal antibody absorption test) is the confirmatory test
• More sensitive 
• Remains positive for life
• No titre
• Treatment: high-dose penicillins, doxycycline or erythromycin

Borrelia burgdorferi

• Spirochaete
• Helical structure with flagella
• Can be visualised with dark-ground (aka dark-field) microscopy
• ELISA can be used to detect IgG and IgM antibodies
• Transmitted by ticks: causes Lyme disease

Endophthalmitis

• Present 2-5 days postoperatively and is generally caused by an organism of the patient’s lid flora

• Most commonly cause by Gram positive organisms

• Coagulase negative staphylococci (eg. Staph. epidermidis): best visual prognosis

• Staphylococcus aureus
• Beta-haemolytic streptococci
• Enterococcus faecalis: worst visual prognosis
• Gram negative culprits
• Haemophilus influenzae
• Pseudomonas aeruginosa

Encapsulated organisms

• Staphylococcus
• Streptococcus pneumoniae
• Haemophilus influenzae type B
• Neisseria meningitidis
• Group B streptococcus
• Klebsiella pneumoniae
• Salmonella typhi
• Pneumocystis carinii