Bacterial Endophthalmitis

Practice Essentials

Bacterial endophthalmitis (see the image below) is an inflammatory reaction of the intraocular fluids or tissues caused by microbial organisms. Bacteria may gain entry into the eye via corneal or scleral trauma (surgical or accidental) or hematogenously. If not properly treated, bacterial endophthalmitis can result in complete vision loss and persistent ocular pain.

View Image

Bacterial endophthalmitis. Hypopyon, 3 days after phacoemulsification.

Signs and symptoms

The clinical presentation depends on the route of entry, the infecting organism, and the duration of the disease. In general, patients complain of the following:

• Decreased vision
• A red eye
• Deep ocular pain

Bacterial endophthalmitis is classified on the basis of routes of entry (ie, exogenous or endogenous).^[1] Disease from exogenous sources includes the following:

• Acute postoperative (< 6 wk postoperative)^{[2, 3]} ; usually occurs 2-10 days after surgery
• Delayed onset or chronic pseudophakic postoperative (>6 wk postoperative)^[2]
• Filtering bleb associated
• Posttraumatic– History of trauma is present, and infection usually progresses rapidly^[4]

On physical examination, general findings in bacteria endophthalmitis are as follows:

• Visual acuity decreased below the level expected
• Lid edema
• Conjunctival hyperemia
• Corneal edema
• Anterior chamber cells and flare
• Keratic precipitates
• Hypopyon^[5]
• Fibrin membrane formation
• Vitritis
• Loss of red reflex
• Retinal periphlebitis if view of fundus possible^[6]

Specific physical examination findings are as follows:

• Delayed onset or chronic cases– Occasionally, a white plaque within the equator of the remaining lens capsule
• Filtering bleb associated– A purulent bleb is seen occasionally with areas of necrosis in the sclera from the use of antimetabolites
• Posttraumatic– Evidence of penetrating trauma is seen with the possibility of an intraocular foreign body^{[7, 8]}
• Endogenous– Patients may appear systemically ill

See Clinical Presentation for more detail.

Diagnosis

Perform culture and sensitivity studies on aqueous and vitreous samples to determine the type of organism and antibiotic sensitivity.^{[9, 10]} If endogenous bacterial endophthalmitis is suspected, a systemic workup for the source is required, with cultures of blood, sputum, and urine.^[11]

Sampling procedures

• Anterior chamber tap
• Vitreous tap
• Vitreous biopsy: A 23-gauge vitrectomy cutter may be used if available

For anterior chamber taps, a 30-gauge needle on a tuberculin syringe is used to obtain a 0.1-mL sample under topical anesthesia through the limbus. For vitreous taps, a sub-Tenon or retrobulbar block with lidocaine with epinephrine is given, and a 21-gauge needle on a tuberculin syringe is used to obtain an adequate vitreous sample of 0.1-0.2 mL.

B-scan ultrasound

• Perform B-scan ultrasound of the posterior pole if view of fundus is poor
• Typically, choroidal thickening and ultrasound echoes in the anterior and posterior vitreous support the diagnosis
• Occasionally, another source of inflammation other than or in addition to bacteria, such as retained lens material, may be seen
• The ultrasound also provides a baseline prior to intraocular intervention and allows assessment of the posterior vitreous face and areas of possible traction^[12]
• Rarely, a retinal detachment is seen concurrently with endophthalmitis

Other imaging studies

In traumatic cases, a CT scan may show thickening of the sclera and uveal tissues associated with various degree of increased density in the vitreous and periocular soft tissue structures. For possible endogenous cases, imaging modalities to rule out potential sources of infection include 2-dimensional echocardiography and chest x-ray.

See Workup for more detail.

Management

Bacterial endophthalmitis is an ocular emergency, and urgent treatment is required to reduce the potential of significant visual loss.^{[13, 14]} All patients should have therapy consisting of the following^{[15, 16, 17, 18]} :

• Intravitreal and topical antibiotics
• Topical steroids (eg, ophthalmic prednisolone, dexamethasone, triamcinolone)
• Cycloplegics (eg, atropine ophthalmic)

When the inflammation is severe, systemic and periocular therapy may be used in non–cataract-induced, delayed onset, filtering bleb–associated, and posttraumatic endophthalmitis. In endogenous endophthalmitis, systemic, topical, and possibly periocular therapy is usually required.^[8]

Antibiotics

• Vancomycin - For patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci; Assaad et al showed that vancomycin was effective against 99.6% of gram-positive bacterial endophthalmitis isolates tested^[19] ; Ahmed et reported that intravitreal, rather than intravenous, vancomycin is necessary for the treatment of bacterial endophthalmitis.^[20] It is not necessary to monitor vancomycin levels when administered via intravitreal injection.
• Ceftazidime - First-line choice for intravitreal gram-negative coverage; ceftazidime was effective against 100% of gram-negative bacterial endophthalmitis isolates in a study by Assaad et al^[19]
• Amikacin - Second-line choice for intravitreal injection for gram-negative coverage
• Ciprofloxacin/ofloxacin/levofloxacin/moxifloxacin/gatifloxacin ophthalmic - Fluoroquinolones with activity against Pseudomonas, streptococci, MRSA, S epidermidis, and most gram-negative organisms; may have limited activity against anaerobes

Surgical care

Surgical intervention is usually performed urgently; however, elective surgery may suffice in delayed-onset cases. Indications for surgical therapy include the following:

• Acute pseudophakic postoperative– When the presenting vision is light perception or worse^[21]
• Delayed onset or chronic postoperative– If marked inflammation or a subcapsular plaque is identified, surgical removal is required
• Filtering bleb–associated– If marked inflammation is present
• Posttraumatic– If marked inflammation or rapid onset occurs

See Treatment and Medication for more detail.

• References

Background

Bacterial endophthalmitis is an inflammatory reaction of the intraocular fluids or tissues caused by microbial organisms. See the images below.

View Image

Bacterial endophthalmitis. Retinopathy induced by Enterococcus faecalis endotoxin.

View Image

Bacterial endophthalmitis. Hypopyon, 3 days after phacoemulsification.

• References

Pathophysiology

The entry of bacteria into the eye occurs from a breakdown of the ocular barriers. Penetration through the cornea or sclera results in an exogenous insult to the eye. If the entry is through the vascular system, then an endogenous route occurs. After the bacteria gain entry into the eye, rapid proliferation occurs.

The vitreous acts as a superb medium for bacteria growth, and, in the past, animal vitreous was used as a culture medium. Bacteria, as foreign objects, incite an inflammatory response. The cascade of inflammatory products occurs resulting in an increase in the blood-ocular barrier breakdown and an increase in inflammatory cell recruitment. The damage to the eye occurs from the breakdown of the inflammatory cells releasing the digestive enzymes as well as the possible toxins produced by the bacteria. Destruction occurs at all tissue levels that are in contact with the inflammatory cells and toxins.

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Frequency

United States

Incidence after intraocular surgery is less than 0.1%. Incidence of culture-proven endophthalmitis is similar to that of extracapsular cataract extraction and phacoemulsification.

Europe

Creuzot-Garcher et al report an incidence of postoperative endophthalmitis after stand-alone cataract surgery in France of 0.102%, increasing to 0.149% when cataract surgery was combined with corneal, glaucoma, or vitreoretinal procedures.^[22]

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Mortality/Morbidity

If not properly treated, a risk of complete vision loss and the possibility of persistent ocular pain exist. Infection very rarely spreads beyond the confines of the sclera and tracks into surrounding tissue structures.

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Prognosis

The prognosis depends on the following:

• Duration of endophthalmitis
• Time to treatment
• Virulence of bacteria
• Etiology of entry
• Existing ocular diseases

From the EVS, the percentage of patients achieving a final visual acuity of 20/100 or better were as follows:

• Gram-positive, coagulase-negative micrococci - 84%
• S aureus - 50%^[23]
• Streptococci - 30%
• Enterococci - 14%
• Gram-negative organisms - 56%

A statistically significant number (P < 0.001) of poorer visual outcomes occurred with a positive Gram stain or when bacteria other than gram-positive, coagulase-negative cocci were found.^[13]

• References

Patient Education

Direct patients to maintain hygienic practice after surgery.

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History

The clinical presentation is dependent on the route of entry, the infecting organism, and the duration of the disease. In general, patients complain of a decrease in vision, often with a red eye. Most patients also may complain of a deep ocular pain. Classification is based on routes of entry.^[1]

Exogenous source

Acute postoperative (< 6 wk postoperative), as follows:^{[2, 3]}

• Infection usually occurs 2-10 days after surgery.
• Patients present with visual loss greater than expected in the usual postoperative course.
• Ocular pain is seen in 75% of patients.
• The use of postoperative antibiotic and anti-inflammatory drugs may blunt the severity of the disease and possibly delay medical attention.

Delayed onset or chronic pseudophakic postoperative (>6 wk postoperative), as follows:^[2]

• Patients typically present with mild-to-moderate inflammatory red eye, reduced vision, and photophobia.
• Chronic indolent course is present.
• Patients may be diagnosed with idiopathic uveitis and treated with topical steroids with temporary improvement.
• Fungal species must be ruled out.
• Filtering bleb associated: Clinical features are similar to acute postoperative infection with purulent bleb involvement.^[24]
• Posttraumatic: History of trauma is present, and infection usually progresses rapidly.^[4]

Endogenous source

No recent history of ocular surgery is present.

Confusion with delayed onset or chronic postoperative is possible if suspicion for endogenous route is not ruled out.

The symptoms are rarely bilateral.

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Physical

General findings include the following:

• Visual acuity decreased below the level expected
• Lid edema
• Conjunctival hyperemia
• Corneal edema
• Anterior chamber cells and flare
• Keratic precipitates
• Hypopyon^[5]
• Fibrin membrane formation
• Vitritis
• Loss of red reflex
• Retinal periphlebitis if view of fundus possible^[6]

Specific findings include the following:

• Delayed onset or chronic: Occasionally, a white plaque is visible within the equator of the remaining lens capsule.
• Filtering bleb associated: A purulent bleb is seen occasionally with areas of necrosis in the sclera from the use of antimetabolites.
• Posttraumatic: Evidence of penetrating trauma is seen with the possibility of an intraocular foreign body.^{[7, 8]}
• Endogenous: Patient may appear systemically ill.

• References

Causes

Causes are related to classification of exogenous and endogenous, as follows:^[25]

• • Ocular surgical procedure - Increased risk when complications arise
  • Trauma
  • Ocular surface infection (eg, corneal ulcer) - Zapp et al conclude that enucleation should be considered against the risk of systemic and local spread of the infection^[26]
  • Filtering bleb associated - Use of antimetabolites or contaminated contact lenses
  • Intravitreal injection - Injections of intravitreal agents to treat exudative macular degeneration, as well as macular edema due to diabetes or retinal vaso-occlusive disease, have an endophthalmitis rate of 0.019%-0.09%, according to Lau et al^[27]

   

  

   
• • Septicemia
  • Patients who are debilitated
  • Indwelling catheters
  • Intravenous drug use

   

  

   

Bacteria involved include the following^[28] :

• Acute pseudophakic postoperative - Coagulase-negative staphylococci, Staphylococcus aureus, and Streptococcus, Enterococcus, and gram-negative species^{[29, 8, 30, 31, 4]}
• Delayed onset or chronic pseudophakic postoperative -Propionibacterium acnes, and coagulase-negative and Corynebacterium species^{[29, 8, 30, 31, 4, 32]}
• Filtering bleb associated^[33] -Streptococcus and Staphylococcus species and Haemophilus influenzae
• Posttraumatic - Bacillus^[34] and Staphylococcus species^[35]
• Endogenous - S aureus, Escherichia coli, and Streptococcus species

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Complications

See the list below:

• Retinal necrosis
• Retinal detachment (see below)

  • Retinal necrosis
  • Vitreous tap
  • Vitrectomy

   

  

   
• Increased intraocular pressure
• Retinal vascular occlusion
• Optic neuropathy
• Panophthalmitis
• Hypotony (see below)

  • Ciliary body shutdown
  • Wound leakage
  • Retinal detachment
  • Cyclodialysis cleft
  • Medication

   

  

   

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Laboratory Studies

Perform culture and sensitivity studies on aqueous and vitreous samples to determine the type of organism and antibiotic sensitivity.^{[9, 10]}

Sjoholm-Gomez de Liano et al found that anterior chamber tap has too low a sensitivity and specificity to rely on alone, but could be helpful for therapeutic guidance if better methods of diagnosis are not available.^[36]

Polymerase chain reaction (PCR) has been shown to be sensitive and specific in detecting and identifying 12 major microbial species in postoperative endophthalmitis.^[37]

If endogenous bacterial endophthalmitis is suspected, a systemic workup for the source is required. This workup includes the following^[11] :

• Blood culture
• Sputum culture
• Urine culture

• References

Imaging Studies

B-scan ultrasonography

Perform B-scan ultrasound of the posterior pole if view of fundus is poor.

Typically, choroidal thickening and ultrasound echoes in the anterior and posterior vitreous support the diagnosis.

Occasionally, another source of inflammation other than or in addition to bacteria, such as retained lens material, may be seen.

The ultrasound is also important to provide a baseline prior to intraocular intervention and to assess the posterior vitreous face and areas of possible traction.^[12]

Rarely, a retinal detachment is seen concurrently with endophthalmitis.

CT scanning

A CT scan rarely is performed unless trauma is involved. Thickening of the sclera and uveal tissues associated with various degree of increased density in the vitreous and periocular soft tissue structures may be seen.

Endogenous

If an endogenous route is considered, perform other imaging modalities to rule out potential sources, as follows:

• Two-dimensional echocardiogram
• Chest x-ray

• References

Procedures

Anterior chamber tap

A 30-gauge needle on a tuberculin syringe is used to obtain a 0.1 cc sample under topical anesthesia through the limbus.

Vitreous tap

A retrobulbar block or a sub-Tenon block with lidocaine with epinephrine is given.

A sub-Tenon block has the advantage over a retrobulbar block because it does not create increased intraocular pressure that may cause recent surgical wounds to open.

A 21-gauge needle on a tuberculin syringe is used to obtain an adequate vitreous sample of 0.1-0.2 cc. Smaller gauge needles may be used but with increasing difficulty to create the aspiration vacuum necessary to obtain a sample.

Vitreous biopsy

A 23-gauge vitrectomy cutter may be used if available.

• References

Medical Care

Bacterial endophthalmitis is an ocular emergency, and urgent treatment is required to reduce the potential of significant visual loss.^{[13, 14]}

All patients should have therapy consisting of intravitreal and topical antibiotics, topical steroids, and cycloplegics.^{[15, 16, 17, 18]}

The Endophthalmitis Vitrectomy Study (EVS) identified that the use of periocular and intravenous antibiotics are not required in endophthalmitis following cataract surgery. Medical therapy was found to be statistically as effective as surgical intervention when the presenting vision was hand motion or better. Use caution in interpreting the data from the EVS; apply it cautiously to non–cataract-related endophthalmitis.^{[38, 39, 40, 41, 42, 43]}

When the inflammation is severe, systemic and periocular therapy may be used in non–cataract-induced, delayed onset, filtering bleb–associated, and posttraumatic endophthalmitis.

In endogenous endophthalmitis, systemic, topical, and possibly periocular therapy is usually required.^[8]

Storey et al reported that increased rates of antibiotic-resistant bacteria in culture-positive endophthalmitis cases may result from the use of prophylactic topical antibiotics following intravitreal injections,^[44] although, from 1999-2012, Gupta et al was unable to document emerging resistance to empirical antibiotics commonly used to treat bacterial endophthalmitis.^[45] Kodati et al performed a 23-year review that found vancomycin was still the optimal antibiotic for gram-positive endophthalmitis, and amikacin and ceftazidime offered equal protection for gram-negative endophthalmitis.^[46]

• References

Surgical Care

Surgical intervention is usually performed urgently except in the delayed onset category where elective surgery may suffice.

Indications for surgical therapy

Acute pseudophakic postoperative - When the presenting vision is light perception or worse^[21]

Delayed onset or chronic postoperative - If marked inflammation or a subcapsular plaque is identified, surgical removal is required.

Filtering bleb associated - If marked inflammation is present. Take care not to disturb the bleb if some function still exists. To allow the possibility of a shunt valve to be placed at a later time, make an attempt to minimize the disturbance to the superior conjunctiva. If the patient is aphakic, performing the pars plana vitrectomy from the temporal side using a limbal approach may be required.

Posttraumatic - If marked inflammation or rapid onset occurs

Technique

A 3-port core pars plana vitrectomy with intravitreal antibiotic injections is performed.^[47] If visualization is poor from anterior segment pathology, then a 2-port limited pars plana vitrectomy or endoscopic guided 3-port pars plana vitrectomy may be performed.^[48]

An increased risk for retinal tears and detachments occur when the vitreous close to the retina is removed aggressively due to the higher probability of retinal necrosis.

Intravitreal antibiotics usually are given after the completion of the vitrectomy; however, if an air-fluid exchange is to be performed, the antibiotics may be mixed into the vitrectomy solution. Dilute the antibiotics in the vitrectomy solution carefully to prevent possible toxic retinopathy from incorrect dosages.

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Consultations

In most exogenous cases of endophthalmitis, the ophthalmologist may manage the case sufficiently; however, in cases of less common or extremely virulent bacteria, consulting an infectious disease specialist may aid in the selection of antibiotics.

When endogenous cases of endophthalmitis are suspected, an internist should be consulted to look for a source.

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Prevention

See the list below:

• Identify high-risk patients before elective surgery (see below)

  • Blepharitis
  • Abnormal lacrimal drainage
  • Active infection elsewhere

   

  

   
• Preparation of operative field (see below)

  • Prep with 5-10% povidone-iodine solution in preoperative area
  • Prep with 5-10% povidone-iodine immediately before draping and allow solution to dry
  • Drape to cover lashes and lid margins

   

  

   
• Prophylactic topical and/or periocular antibiotics^{[14, 49]}
• Prophylactic intravitreal antibiotics in trauma cases

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Further Outpatient Care

Patients should receive follow-up care on a daily basis. Clinical features indicating improvement include the following:

• Reduced pain
• Decreased inflammation and hypopyon
• Increased red reflex
• Retraction of any fibrin
• Improved visual acuity

If no improvement occurs in 48-72 hours, consider the following:

• Repeat tap/biopsy and antibiotic injections
• Vitrectomy and injection of antibiotics, if no previous vitrectomy exists

If view is poor, B-scan ultrasound is useful to rule out retinal detachment.

• References

Further Inpatient Care

Patients may be admitted or may be treated as outpatients depending on the following:

• Severity of endophthalmitis and treatment modalities
• Underlying systemic diseases
• Patient reliability and compliance

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Inpatient & Outpatient Medications

Topical antibiotic coverage with dosage dependent on severity, as follows:

• Vancomycin 50 mg/mL 1 gtt qid to q1h
• Ceftazidime 50 mg/mL 1 gtt qid to q1h
• Prednisolone 1 gtt qid to q1h
• Atropine 1 gtt bid

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Medication Summary

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications. Various routes for drug administration are available. Intravitreous is the most effective.

• References

Vancomycin

• Dosing, Interactions, etc.

Clinical Context:  Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins or have infections with resistant staphylococci.

Ahmed et al reported that intravitreal, rather than intravenous, vancomycin is necessary for the treatment of bacterial endophthalmitis. It is not necessary to monitor vancomycin levels when administered via intravitreal injection.

• References

Ceftazidime (Fortaz, Tazicef)

• Dosing, Interactions, etc.

Clinical Context:  First-line choice for intravitreal gram-negative coverage. Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

• References

Amikacin

• Dosing, Interactions, etc.

Clinical Context:  Second-line choice for intravitreal injection for gram-negative coverage. For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Effective against Pseudomonas aeruginosa.

Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. Use the patient's IBW for dosage calculation.

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Ciprofloxacin ophthalmic (Ciloxan)

• Dosing, Interactions, etc.

Clinical Context:  Fluoroquinolone with activity against pseudomonas, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but may have limited activity against anaerobes. Inhibits bacterial DNA synthesis, and consequently growth. Provides gram-positive coverage. Uncertain benefit in noncataract causes.

• References

Ofloxacin ophthalmic (Ocuflox)

• Dosing, Interactions, etc.

Clinical Context:  A pyridine carboxylic acid derivative with broad-spectrum bactericidal effect, ofloxacin inhibits bacterial growth by inhibiting DNA gyrase. It is indicated for superficial ocular infections of the conjunctiva or cornea caused by susceptible strains of microorganisms.

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Levofloxacin ophthalmic (Iquix, Quixin)

• Dosing, Interactions, etc.

Clinical Context:  Levofloxacin is an S (-) enantiomer of ofloxacin. It inhibits DNA gyrase in susceptible organisms, thereby inhibiting relaxation of supercoiled DNA and promoting breakage of DNA strands.

• References

Gatifloxacin ophthalmic (Zymaxid)

• Dosing, Interactions, etc.

Clinical Context:  A fourth-generation fluoroquinolone ophthalmic indicated for bacterial conjunctivitis, gatifloxacin elicits a dual mechanism of action by possessing an 8-methoxy group, thereby inhibiting the enzymes DNA gyrase and topoisomerase IV. DNA gyrase is involved in bacterial DNA replication, transcription, and repair. Topoisomerase IV is essential in chromosomal DNA partitioning during bacterial cell division. Gatifloxacin is indicated for bacterial conjunctivitis.

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Moxifloxacin ophthalmic (Moxeza, Vigamox)

• Dosing, Interactions, etc.

Clinical Context:  Indicated to treat bacterial conjunctivitis. Elicits antimicrobial effects. Inhibits topoisomerase II (DNA gyrase) and IV enzymes. DNA gyrase is essential in bacterial DNA replication, transcription, and repair. Topoisomerase IV plays a key role in chromosomal DNA portioning during bacterial cell division.

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Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

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Prednisolone acetate (Pred Forte, Omnipred, Pred Mild)

• Dosing, Interactions, etc.

Clinical Context:  Treats acute inflammations following eye surgery or other types of insults to eye.

Decreases inflammation and corneal neovascularization. Suppresses migration of polymorphonuclear leukocytes and reverses increased capillary permeability.

In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely. Dosage dependent on severity of inflammation.

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Dexamethasone (Ozurdex, Maxidex)

• Dosing, Interactions, etc.

Clinical Context:  For various allergic and inflammatory diseases. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

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Triamcinolone (Triesence)

• Dosing, Interactions, etc.

Clinical Context:  Treats inflammatory dermatosis responsive to steroids. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability.

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Class Summary

Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

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Atropine ophthalmic

• Dosing, Interactions, etc.

Clinical Context:  DOC; acts at parasympathetic sites in smooth muscle to block response of sphincter muscle of iris and muscle of ciliary body to acetylcholine, causing mydriasis and cycloplegia.

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Class Summary

Reduces ciliary spasm that may cause pain. Anticholinergic agents are also mydriatics, and the practitioner should make sure that the patient does not have glaucoma. This medication could provoke an acute angle-closure attack.

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