Bacterial endophthalmitis

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For the main page on endophthalmitis, please click here
For more information on post-operative endophthalmitis, please click here
For more information on post-traumatic endophthalmitis, please click here
For more information on bleb-related endophthalmitis, please click here
For more information on endogenous endophthalmitis, please click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Overview

Bacterial endophthalmitis is a bacterial infection inside the eye. It involves the vitreous and/or aqueous humor. Most cases of endophthalmitis are exogenous, and organisms are introduced into the eye via trauma or surgery. Endogenous endophthalmitis occurs when the eye is seeded via the bloodstream. Patients usually have symptoms from their underlying systemic infection, but sometimes present only with eye symptom.

Historical Perspective

In 1916, Dr. Leonard Weakly published a case report which detailed a patient with bacterial endophthalmitis concurrent with meningitis.

Classification

Based on how infectious agents are introduced to the anterior and posterior segments of the eye, bacterial endophthalmitis may be classified into:

• Exogenous bacterial endophthalmitis
  • Acute post-operative bacterial endophthalmitis
  • Delayed post-operative bacterial endophthalmitis
  • Post-traumatic bacterial endophthalmitis (following a penetrating injury of the globe)
  • Post-intravitreal injection bacterial endophthalmitis
• Endogenous bacterial endophthalmitis

Pathophysiology

Exogenous bacterial endophthalmitis

Pathogenesis

• Acute post-operative bacterial endophthalmitis

Acute post-operative bacterial endophthalmitis is an ocular inflammation resulting from the introduction of an infectious agent, most commonly coagulase-negative staphylococci, into the posterior segment of the eye. Nearly every type of ocular surgery, such as cataract (approximately 90% of all cases), glaucoma, retinal, radial keratotomy, and intravitreal injections, may be able to disturb eye globe integrity and contaminate the aqueous humor and/or vitreous humor. Preoperative topical antimicrobial agents may decrease colony counts in the tear film, but they do not sterilize the area. The exact incidence of clinical infection following eye surgery is not fully understood. It is thought that low incidence of clinical infection following surgical procedure is due to low inoculum levels, low pathogenicity, and the innate ocular defenses against infection.

• Delayed post-operative bacterial endophthalmitis

Post-operative bacterial endophthalmitis may also occur weeks to years following surgery. It presents as a low-grade inflammation in the anterior chamber. The exact pathogenesis of delayed postoperative bacterial endophthalmitis is not fully understood. It is thought that delayed post-operative bacterial endophthalmitis is caused by either sequestration of low-virulence organisms introduced at the time of surgery or delayed inoculation of organisms to the eye through wound abnormalities, suture tracks, or filtering blebs. Propionibacterium acnes is the most common microorganism encountered in delayed post-operative bacterial endophthalmitis.

• Post-traumatic bacterial endophthalmitis

Post-traumatic bacterial endophthalmitis occurs following penetrating ocular injuries. Following penetrating injury, the eye globe integrity is disturbed. Penetrating ocular injuriesare associated with a higher incidence of infection compared to ocular surgery. The broad prevalence range is due to factors such as:

• Presence of an intraocular foreign body
• Delayed primary globe repair
• Location and extent of laceration of the globe

Post-traumatic endophthalmitis is associated with a greater variety of organisms. The most common isolated organisms include gram-positive Staphylococcus epidermidis and Streptococcus (as a part of the normal skin flora and regularly contaminate open wounds). Bacillus cereus is also common and some cases of polymicrobial infections are observed.

• Post-intravitreal injection bacterial endophthalmitis

Post-intravitreal injection bacterial endophthalmitis occurs following intravitreal injection of either triamcinolone acetone or anti-vascular endothelial growth factors (anti VEGF).

Gross Pathology

On gross pathology, eyelid swelling, eyelid erythema, injected conjunctiva and sclera, hypopyon, chemosis, and mucoprulunt dischage are characteristic findings of bacterial endophthalmitis.

Microscopic Pathology

On microscopic histopathological analysis, infiltration of polymorphonuclear leukocytes or chronic inflammatory cells (depending on the duration of the inflammation) and destruction of ocular structures are characteristic findings of bacterial endophthalmitis.

Endogenous bacterial endophthalmitis

Pathogenesis

Endogenous endophthalmitis is caused by the hematologic dissemination of an infection to the eyes. The most common extraocular foci of infection include liver abscess, pneumonia, endocarditis, and soft tissue infection. Endogenous endophthalmitis is commonly associated with immunosuppression or procedures that increase the risk for blood-borne infections, such as diabetes, HIV, malignancy, intravenous drug use, transplantation, immunosuppressive therapy, and catheterization. Under normal circumstances, the blood-ocular barrier provides a natural resistance against invading organisms. Following bacteremia, the blood-borne organisms permeate the blood-ocular barrier by:

• Direct invasion (septic emboli)
• Changes in the vascular endothelium (caused by inflammatory mediators released during infection)

Gross Pathology

On gross pathology, eyelid swelling, eyelid erythema, injected conjunctiva and sclera, hypopyon, chemosis, and mucoprulunt dischage are characteristic findings ofbacterial endophthalmitis. ====Microscopic Pat====hology On microscopic histopathological analysis, infiltration of polymorphonuclear leukocytes or chronic inflammatory cells (depending on the duration of the inflammation) and destruction of ocular structures are characteristic findings of bacterial endophthalmitis.

Causes

Post-operative Bacterial Endophthalmitis

Post-operative endophthalmitis has been reported following nearly every type of ocular surgery. Common causes of post-operative bacterial endophthalmitis include:

• Gram-positive bacteria (95%)
  • Coagulase-negative staphylococci (70%)
    • Staphylococcus epidermidis (most of the cases)
  • Staphylococcus aureus (10%)
  • Streptococcus (9%)
  • Enterococcus and mixed bacteria (5%)
• Gram-negative bacilli (6%)
  • Proteus spp (30%)
  • pseudomonas aeruginosa
  • Haemophilus spp.

Delayed Post-operative Bacterial Endophthalmitis

Common causes of delayed post-operative bacterial endophthalmitis include:

• Propionibacterium acnes (most common)
• Streptococcus species

Post-traumatic Bacterial Endophthalmitis

Common causes of post-traumatic bacterial endophthalmitis include:

• Gram-positive bacteria
  • coagulase-negative staphylococci
  • Bacillus cereus
  • Streptococcus
• Gram-negative bacilli
  • Klebsiella
  • Pseudomonas
• Polymicrobial

Endogenous bacterial endophthalmitis

Common causes of endogenous bacterial endophthalmitis include:

• Gram-positive bacteria
  • Streptococcus pneumoniae
  • Staphylococcus aureus
  • Bacillus cereus (primary bacterial cause in intravenous drug abusers)
• Gram-negative bacteria
  • Neisseria meningitidis (pre-antibiotic era)
  • Escherichia coli
  • Klebsiella

Differentiating Bacterial Endophthalmitis from Other Diseases

Bacterial endophthalmitis must be differentiated from:

• Fungal endophthalmitis
• Post-operative inflammation
• Intraocular foreign body
• Acute retinal necrosis
• Keratitis (interstitial)
• Uveitis
• Hyphema
• Toxic anterior segment syndrome (TASS)
• Vitreous hemorrhage
• Autoimmune disorders (Ankylosing Spondylitis, Spondyloarthropathy, acute complications of Sarcoidosis, and HLA-B27 Syndromes)

Epidemiology and Demographics

• Post-operative bacetrial endophthalmitis accounts for approximately 60,000 per 100,000 cases of exogenous endophthalmitis.
• Endogenous endophthalmitis is a rare disease that tends to affect immunocompromised patients and patients with chronic disease.
• Endogenous endophthalmitis accounts for approximately 5000 to 10000 cases per 100,000 cases with endophthalmitis.

Prevalence and Incidence

• The incidence of post-traumatic endophthalmitis was estimated to range from 3,300 to 30,000 per 100,000 individuals with penetrating ocular trauma.
• The incidence of post-traumatic endophthalmitis was estimated to range from 1,300 to 61,000 per 100,000 individuals with intraocular foreign body.
• The incidence of endogenous endophthalmitis is estimated to be 50 cases per 100,000 hospitalized patients.

Age

• Post-operative bacterial endophthalmitis (following cataract surgery) commonly affects patients older than 85 years.
• Patients of all age groups may develop endogenous bacterial endophthalmitis.

Gender

• Bacterial endophthalmitis affect men and women equally.

Geographical Distribution

• In East Asian populations, liver abscess caused by Klebsiella pneumoniae is estimated to be the source of 60,000 per 100,000 individuals with endogenous endophthalmitis.

Developed countries

• In the United States, post-cataract endophthalmitis is the most common form of bacterial endophthalmitis.
• In the United States, the incidence of cataract endophthalmitis was estimated to range from 80 to 360 cases per 100,00 individuals with ocular surgery.
• In the United States, the incidence of culture-proven postoperative endophthalmitis caused by cataract surgery with or without intraocular lens (IOL) was estimated to be 80 cases per 100,000 individuals.
• In the United States, the incidence of culture-proven postoperative endophthalmitis caused by penetrating keratoplasty was estimated to be 170 cases per 100,000 individuals.
• In the United States, the incidence of culture-proven postoperative endophthalmitis caused by secondary IOL placement was estimated to be 360 cases per 100,000 individuals.

Risk Factors

Post-operative bacterial endophthalmitis

Common risk factors in the development of post-operative bacterial endophthalmitis include:

• Secondary intraocular lens placement
• Intra-ocular lenses (IOLs) with polypropylene
• Clear corneal incisions
• Vitreous contamination following cataract surgery (break in the posterior lens capsule)
• Implantation of an intraocular lens without a heparinized surface
• Diabetes
• Immunosuppressive therapy
• Wound dehiscence or leak
• Age ≥85
• Eyelid abnormalities such as (blepharitis, conjunctivitis, cannuliculitis, lacrimal duct obstructions, and contact lens wear)

Post-traumatic bacterial endophthalmitis

Common risk factors in the development of post-traumatic bacterial endophthalmitis include:

• Retained intraocular foreign bodies
• Delay in repair more than 24 hours
• Disruption of the lens

Endogenous bacterial endophthalmitis

Common risk factors in the development of endogenous bacterial endophthalmitis include:

• Immunosuppression
• Diabetes
• HIV
• Malignancy
• Intravenous drug use
• Catheterization
• Long-term use of broad-spectrum antibiotics or immunosuppressive drugs

Screening

Screening for bacterial endophthjalmitis is not recommended. There is insufficient evidence to recommend routine aqueous culture in all cases of open globe injury.

Natural History, Complications, and Prognosis

Natural History

Bacterial endophthalmitis is a medical emergency. If left untreated, it may lead to panophthalmitis, corneal infiltration, corneal perforation, and permanent vision loss. Endogenous endophthalmitis can be a life-threatening condition. If systemic infection is left undetected, it may progress to sepsis and mortality.

Complications

Common complications of bacterial endophthalmitis include:

• Panophthalmitis
• Decrease or loss of vision
• Chronic pain
• Cataract development
• Retinal detachment
• Vitreous hemorrhage
• Hypotony and phthisis bulbi
• Proptosis and a corneal abscess (specific for post-traumatic)
• Sepsis (endogenous endophthalmit)
• Suprachoroidal hemorrhage (endogenous endophthalmitis)

Prognosis

Bacterial endophthalmitis is often associated with poor prognosis. Early diagnosis and treatment with antimicrobial therapy is fundamental to optimizing visual outcome.

Post-operative bacterial endophthalmitis caused by any type of streptococci is associated with very poor visual outcome. Post-operative bacterial endophthalmitis caused by coagulase-negative staphylococcus (cause milder endophthalmitis) is associated with better visual outcome than strepcocci. Overall, 50% of eyes with post-cataract endophthalmitis obtain a final visual acuity of 20/40 vision, and 10% obtain a final visual acuity of 20/400.

Post-traumatic bacterial endophthalmitis is associated with particularly poor visual outcome. Only 22% to 42% patients with post-traumatic bacterial endophthalmitis obtain a final visual acuity of 20/400 or better.

Delayed post-operative endophthalmitis is associated with particularly good prognosis with treatment.

Endogenous bacterial endophthalmitis has a varying prognosis depending on the offending organism and the immune status of the patient. Late detection and late treatment of systemic infection in endogenouse bacterial endophthalmtis is associated with a poor prognosis.

Diagnosis

Diagnostic Criteria

Endophthalmitis is a clinical diagnosis supported by culture of intra-ocular fluids.

History

A detailed and thorough history from the patient is necessary. Specific areas of focus when obtaining a history from the patient with exogenous endophthalmitis include:

• History of previous intraocular surgery
• History of eye trauma
• History of chronic, recurrent, steroid responsive idiopathic uveitis (most patients with delayed post-operative endophthalmitis are characterized by this presentation)

Specific areas of focus when obtaining a history from the patient with endogenous endophthalmitis include:

• History of diabetes mellitus
• History of HIV infection
• History of cancer
• History of renal failure requiring dialysis
• History of cardiac disease
• History of immunosuppressive drugs
• History of major surgery
• History of intravenous catheters
• History of intravenous drug abuse

Symptoms

• Acute bacterial post-operative endophthalmitis may occur within hours to days after surgical procedures in 75% of cases. Symptoms include fever, decreased vision, red eye, and eye pain.
• Delayed post-operative endophthalmitis may occur several weeks or months after surgery and often involve less virulent bacteria. Symptoms include insidious decrease of vision, gradually increasing redness, and minimal or no pain.
• Posttraumatic bacterial endophthalmitis may occur within hours after the trauma or up to several weeks after injury. Symptoms include decreased vision, pain greater than expected, and lid swelling.
• Endogenouse bacterial endophthalmtis presents with (eye pain, blurred vision, ocular discharge, and photophobia) rather than symptoms of their underlying infection.

Physical Examination

A thorough physical examination and a focused eye examination of the patient is necessary. Common ophthalmoscope examination findings of exogenous bacterial endophthalmitis include:

• Visual acuity less than 5/200
• Light perception
• No retinal vessel visible by indirect ophthalmoscopy
• Conjunctival injection
• eyelid edema
• Hypopyon
• Clumps of exudate in the anterior chamber (around the pupillary margin)
• Cloudy cornea
• Decreased red reflex
• Anterior chamber and vitreous inflammatory reactions
• Retinitis
• Ring corneal infiltrate (post-traumatic)
• Roth's spots and retinal periphlebitis (endogenouse endophthalmtis)

Patients with endogenouse bacterial endophthalmtis usually appear extremely ill and lethargic. A thorough examination is necessary to identify the primary source of infection in patient with endogenous endophthalmitis.

Laboratory Findings

Laboratory studies consistent with the diagnosis of bacterial endophthalmitis include:

• Culture and gram stain of aqueous humor as well as the vitreous humor
• Polymerase chain reaction (PCR) of aqueous humor as well as the vitreous humor
• Conjunctival and eyelid cultures in patients with blepharitis and wound dehiscence may be indicated
• Blood cultures (Positive in 75% of cases of endogenous endophthalmitis)

Vitreous cultures are more likely to be positive after vitrectomy than vitreous aspirate (90% vs. 75%), and aqueous cultures are positive in 40% of all cases with endophthalmitis.

Imaging Findings

X Ray

Chest X ray is helpful for detecting the source of infection in patients with endogenous endophthalmitis.

CT

• Post-traumatic endophthalmitis

Orbital CT scan is helpful for localization of metallic intra ocular foreign bodies (IOFBs) in the setting of trauma.

MRI

• Post-traumatic endophthalmitis

Orbital MRI scan is helpful for localization of non-metallic intra ocular foreign bodies (IOFBs) that may be radiolucent on CT in the setting of trauma (metallic IOFB must be excluded first with the help of CT).

Ultrasound

On ocular ultrasonography, endophthalmitis may characterized by anterior vitreous haze echoes and retinochoroidal thickening.

Other Imaging Findings

Orbital echography is helpful for assessment of vitreous opacification, presence of (IOFBs), status of the posterior hyaloid face, and retinal detachment in a patient with either post-operative or post-traumatic endophthalmitis.

Other Diagnostic Studies

Other diagnostic studies for endogenous endophthalmiatis include:

• Echocardiography (to rule out endocarditis).
• Testing for human immunodeficiency virus (HIV)
• Cultures of other sites (catheter tip)

Treatment

Medical Therapy

The patient needs urgent examination by an expert ophthalmologist and/or vitreo-retina specialist who will usually decide for urgent intervention to provide intravitreal injection of potent antibiotics and also prepare for an urgent pars plana vitrectomy as needed. Enucleation may be required to remove a blind and painful eye.

• Bacterial cultures from vitreous samples are necessary in the management of bacterial endophthalmitis
• In addition to intravitreal antibiotic therapy, immediate vitrectomy is often necessary
• Repeat antimicrobial regimen in 2 days post-vitrectomy is necessary
• In post-traumatic bacterial endophthalmitis, treatment should be aggressive (intravitreal antibiotics, systemic therapy, and vitrectomy)
• In delayed post-operative endophthalmitis, treatment should include vitrectomy with posterior capsulectomy and intravitreal injection.

Antimicrobial Regimens

• Infectious endophthalmitis

• 1. Causative pathogens

• Staphylococcus epidermidis
• Staphylococcus aureus
• Streptococci
• Enterococci
• Bacillus spp.
• Escherichia coli
• Neisseria meningitidis
• Klebsiella spp.
• Propionibacterium spp.
• Corynebacterium spp.
• Pseudomonas aeruginosa

• 2. Empiric antimicrobial therapy

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 1 g IV bid for 2 weeks AND Clindamycin 600-1200 mg IV bid to qid for 2 weeks
• Note (1): Re-injection should be considered if the infection does not improve beyond 48 hours of the first injection. Re-injection significantly increases the risk of retinal toxicity.
• Note (2): In addition to intravitreal and systemic antibiotic therapy, vitrectomy is usually necessary
• Note (3): Intravitreal and intravenous Amphotericin B may be added to the regimen if fungal endophthalmitis is suspected

• 3. Pathogen-directed antimicrobial therapy

• 3.1 Bacillus spp.

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks AND Clindamycin 600-1200 mg IV bid to qid for 2 weeks
• Note: In addition to antimicrobial therapy, vitrectomy is usually necessary

• 3.2 Non-Bacillus gram-positive bacteria

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks
• Note: In addition to antimicrobial therapy, vitrectomy is usually necessary

• 3.3 Gram-negative bacteria

• Preferred regimen: Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 1 g IV bid for 2 weeks
• Note (1): In addition to antimicrobial therapy, vitrectomy is usually necessary
• Note (2): Repeat antimicrobial regimen in 2 days post-vitrectomy

• 4. Special Considerations

• 4.1 Endogenous endophthalmitis

• 4.1.1 Empiric antimicrobial therapy

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Vancomycin 1 g IV bid for 2 weeks AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 1 g IV bid for 2 weeks AND Clindamycin 600-1200 mg IV bid to qid for 2 weeks
• Note (1): Re-injection should be considered if the infection does not improve beyond 48 hours of the first injection. Re-injection significantly increases the risk of retinal toxicity.
• Note (2): In addition to intravitreal and systemic antibiotic therapy, vitrectomy is usually necessary::* Note (3): Intravitreal and intravenous Amphotericin B may be added to the regimen if fungal endophthalmitis is suspected

• 4.2 Post-operative endophthalmitis

• 4.2.1 Empiric antimicrobial therapy

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose
• Note (1): In addition to intravitreal antibiotic therapy, vitrectomy is necessary
• Note (2): If there is no improvement in 48 h, a repeat intravitreal injection may be administered
• Note (3): Late post-operative endophthalmitis is often caused by Propionibacterium acnes (several years post-op)

• 4.2.2 Pathogen-directed antimicrobial therapy

• 4.2.2.1 Gram-positive bacteria

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose

• 4.2.2.2 Gram-negative bacteria

• Preferred regimen: Amikacin 0.4 mg per 0.1 mL normal saline intravitreal injection, single dose
• Note: Intravitreal amikacin is associated with the development of retinal microvasculitis

• 4.3 Post-traumatic endophthalmitis

• 4.3.1 Empiric antimicrobial therapy

• Preferred regimen: Vancomycin 1 mg per 0.1 mL normal saline intravitreal injection, single dose AND Ceftazidime 2.25 mg per 0.1 mL normal saline intravitreal injection, single dose AND Amphotericin B 5-10 microgram in 0.1 mL in normal saline intravitreal injection, single dose
• Note (1): Removal of foreign bodies and debridement of necrotic tissue is necessary
• Note (2): In addition to antimicrobial therapy, vitrectomy is necessary
• Note (3): Systemic broad spectrum antibiotics are recommended in post-traumatic endophthalmitis

Surgery

Vitrectomy

Vitrectomy surgically debrides the vitreous humor, similarly to draining an abscess, and is the fastest way of clearing infection in eyes with fulminant endophthalmitis.

• Vitrectomy is recommended for all patients who develop exogenous bacterial endophthalmitis.
• Vitrectomy is recommended in severe cases of endogenous bacterial endophthalmitis.

The benefits of vitrectomy include:

• Better vitreous sample
• Rapid and complete sterilization of the vitreous
• Removal of toxic bacterial products
• Enhancement of systemic antimicrobial penetration in to the eye

Prevention

Primary prevention

Effective measures for the primary prevention of post-operative endophthalmitis include:

• Proper sterile preparation of the surgical site
• Sterile preparation of the skin surrounding the surgical eye with Povidone-Iodine 10%
• Povidone-Iodine 5% onto the ocular surface (3-5 minutes prior to surgery)
• preoperative antibiotic propylaxis (timing, routs of delivery, and antibiotic choice in not clear)
• Proper construction of wound, injectable intraocular lenses
• Preoperative clinical assessment of the patient before proceeding for surgery

Effective measures for the primary prevention of post-traumatic endophthalmitis include:

• Primary globe repair within 24 h
• Removal of foreign bodies and debridement of necrotic tissue
• Intracameral or intravitreal antibiotic injection after penetrating eye injury

Effective measures for the primary prevention of endogenous endophthalmitis include:

• Effective treatment of underlining medical conditions

Secondary prevention

There are no secondary preventive measures available for bacterial endophthalmiatis. Bacterial endophthalmiatis is a medical emergency.