Endogenous endophthalmitis

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

Overview

Endogenous endophthalmitis is caused by either the hematologic dissemination of bacterial or fungal infections to the eyes or direct spread from adjacent contagious sites. Most common extraocular foci of infection include liver abscess, pneumonia, endocarditis, and soft tissue infection.

Classification

endogenous enophthalmitis may be classified according to causative organisms into 2 subtypes: bacterial or fungal.

Pathophysiology

Pathogenesis

Endogenous bacterial endophthalmitis is caused by either the hematologic dissemination of an infection to the eyes or direct spread from adjacent infectious sites. 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. Most common extraocular foci of infection include liver abscess, pneumonia, endocarditis, and soft tissue infection. Under normal circumstances, the blood-ocular barrier provides a natural resistance against invading organisms. In the high risk patients, following bacteremia the blood-borne organisms permeate the blood-ocular barrier by:

• Direct invasion (septic emboli reaches the eye through the posterior segment vasculature)
• Change in vascular endothelium (caused by inflammatory mediators released during infection)

Direct spread from contagious sites can also occur in cases of central nervous system (CNS) infection via the optic nerve.

Endogenous candida endophthalmitis is commonly associated with procedures or conditions that increase the risk for blood-borne infections, such as abdominal surgery, diabetes mellitus and indwelling central venous catheter. It is thought immunosuppression alone does not increase the risk of fungemia and subsequent fungal endophthalmitis.

Following inhalation of the airborne organisms, the aspergilli spores enter the terminal alveoli of the lung. Under normal circumstances, the lung provides a natural resistance against invading organisms. However, in the high risk patients, such as those patients with history of chronic pulmonary diseases, history of organ transplant, intravenous drug abuse, cardiac surgery, and alcoholism, disseminated aspergillosis may result in endogenous aspergillus endophthalmitis.

Gross Pathology

• On gross pathology, eyelid swelling, eyelid erythema, conjunctival injection, chemosis, and mucoprulunt dischage are characteristic findings of endogenous endophthalmitis.

Microscopic histopathological analysis

• On microscopic histopathological analysis, infiltration of polymorphonuclear leukocytes and destruction of ocular structures are characteristic findings of endogeouse bacterial endophthalmitis.
• On microscopic histopathological analysis, random vitreous, choroid , and retinal lesions (which demonstrate polymorphonoclear leukocytes, lymphocytes, budding yeast, pseudohyphae) are characteristic findings of candida endophthalmitis.
• On microscopic histopathological analysis, angiocentric retinal and choroidal lesion, mixed acute and chronic inflammatory cells infiltration, retinal and choroidal vessel invasion, and subretinal pigment epithelial infection are characteristic findings of aspergillus endophthalmitis.

Causes

Bacterial

Common causes of endogenous bacterial endophthalmitis include:ref name="pmid23438028">Durand ML (2013). "Endophthalmitis". Clin Microbiol Infect. 19 (3): 227–34. doi:10.1111/1469-0691.12118. PMC 3638360. PMID 23438028. </ref>

• 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 (in the Asian population with liver abscess)

Fungal

Common causes of endogenous fungal endophthalmitis include:ref name="pmid23438028">Durand ML (2013). "Endophthalmitis". Clin Microbiol Infect. 19 (3): 227–34. doi:10.1111/1469-0691.12118. PMC 3638360. PMID 23438028. </ref>

• • Candida albicans
  • Candida tropicalis
  • Aspergillus
  • Fusarium

Differentiating endogenous Endophthalmitis from Other Diseases

Endogenous bacterial endophthalmitis must be differentiated from:

• Aspergillus endophthalmitis
• Candida endophthalmitis

Candida endophthalmitis must be differentiated from:

• Cytomegalvirus retinitis
• Toxoplasmosis retinochoroiditis
• Primary intraocular lymphoma
• Syphilitic choroiditis
• Aspergillus endophthalmitis
• Endogenous bacterial endophthalmaitis

Aspergillus endophthalmitis must be differentiated from:

• Cytomegalvirus retinitis
• Toxoplasmosis retinochoroiditis
• Coccidiomycosis choroiditis
• Endogenous bacterial endophthalmitis

Epidemiology and Demographics

Incidence

The incidence of endogenous endophthalmitis is estimated to be 50 cases per 100,000 hospitalized patients.

Age

Endogenous bacterial endophthalmitis affects 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 cases per 100,000 individuals with endogenous endophthalmitis.

Risk Factors

Endogenous bacterial endophthalmitis

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

• Recent hospitalization
• Immunosuppression
• Diabetes mellitus
• Urinary tract infection
• Immunosuppression (associated with underlying malignancy, neutropenia, and HIV)
• Intravenous drug use
• Catheterization
• Long-term use of broad-spectrum antibiotics or immunosuppressive drugs
• Liver abscess
• Infective endocarditis (IE)

Endogenous candida endophthalmitis

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

• Recent abdominal surgery
• Diabetes mellitus
• Indwelling central venous catheter.
• Chemotherapy
• Organ transplantation (cardiac and liver transplants)
• Immunosuppressive therapy for hematopoietic stem cell transplantation (HSCT)
• History of chronic pulmonary diseases
• Intravenous drug abuse
• Alcoholism

Natural History, Complications, and Prognosis

Prognosis

The prognosis of endogenouse endophthalmtis varies with the offending organism and the systemic status of the patient.

• Late detection and late treatment of systemic infection of endogenouse bacterial endophthalmtis is associated with a poor prognosis.
• The prognosis of candida endophthalmiaits is good if prompt systemic amphotericin B treatment is received.
• Despite of aggressive treatment, aspergillus endophthalmitis is associated with poor prognosis.

Diagnosis

The diagnosis of endogenous endophthalmitis may be difficult because of the variability in the clinical signs and symptoms.

History

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

• History of diabetes mellitus
• Immunosuppression (associated with underlying malignancy, neutropenia, and HIV)
• History of cardiac disease
• History of abdominal surgery
• intravenous catheters
• Intravenous drug abuse.
• Immunosuppressive therapy
• History of chronic pulmonary diseases

Symptoms

Symptoms of endogenous endophthalmitis may include the following:

• Decreased vision
• Eyelid edema
• Conjunctival injection
• Eye pain
• Photophobia
• Presence of floaters

Physical Examination

• Patients with endogenous endophthalmtis usually appear extremely ill and lethargic. Therefore, eye examination in extremely ill patients, such as those in intensive care units (ICU), seems necessary.
• A thorough examination seems necessary to identify the primary source of infection in patient with endogenous endophthalmitis.

Eye examination

Ophthalmologic examination of patients with endogenoous endophthlamitis is usually remarkable for:

• Decreased vision
• Conjunctival injection
• Eyelid edema
• Hypopyon
• Cloudy cornea
• Decreased red reflex
• Roth's spots and retinal periphlebitis
• White and fluffy choriodoretinal lesions (candida endophthalmitis)
• Snowball-like opacities in vitreous (candida endophthalmitis)

Laboratory Findings

Candida endophthalmitis

• Positive cultures of blood, catheter tips, surgical wounds, and body fluids for Candidia
• Vitreaus cultures and biopsy (required to confirm the diagnosis)
• Vitreous polymerase chain reaction (PCR)

Aspergillus endophthalmitis

• Pars plana vitreous biopsy and cultures (Grocott or Periodic acid-Schiff)
• Anterior chamber and vitreous aspiration alone are unreliable
• Coexisting systemic aspergillosis

Treatment

• 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.
• Systemic antibiotics are recommended in endogenous bacterial endophthalmitis because the source of the infection is distant from the eye.
• Bacterial and fungal cultures from vitreous samples are necessary in the management of endophthalmitis
• Vitrectomy is recommended in severe cases of endogenous endophthalmitis with marked vitreous infiltration

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
• Candida spp.
• Aspergillus spp.
• Fusarium spp.

• 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: In addition to antimicrobial therapy, vitrectomy is usually necessary

• 3.4 Candida spp.

• Preferred regimen: (Fluconazole 400-800 mg IV/PO qd for 6-12 weeks OR Voriconazole 400 mg IV/PO bid for 2 doses followed by 200-300 mg IV/PO bid for 6-12 weeks OR Amphotericin B 0.7-1.0 mg/kg IV qd for 6-12 weeks) AND Amphotericin B 5-10 microgram in 0.1 mL in normal saline intravitreal injection, single dose
• Note (1): In addition to antimicrobial therapy, vitrectomy is usually necessary

• 3.5 Aspergillus spp.

• Preferred regimen: Amphotericin B 5-10 microgram in 0.1 mL normal saline intravitreal injection, single dose AND Dexamethasone 400 microgram intravitreal injection, single dose
• Note (1): In addition to antimicrobial therapy, vitrectomy is usually necessary
• Note (2): Repeat antimicrobial regimen in 2 days post-vitrectomy

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 in severe cases of endogenous endophthalmitis with marked vitreous infiltration (either fungal or bacterial)

The benefits of vitrectomy include:

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

References

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