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Actinomycosis
Synonyms, Key Words, and Related Terms: Actinomycetales, Actinomycetaceae, Actinomycetes, Actinomyces, Actinomyces israelii, keratoactinomycosis, canaliculitis

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INTRODUCTION

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Background: The bacterial order Actinomycetales comprises 3 families: Actinomycetaceae, Mycobacteriaceae, and Streptomycetaceae. Genus Actinomyces, a member of the family Actinomycetaceae, grows as a fragile branching filament that tends to fragment into bacillary and coccoid forms producing chains of either conidia or arthrospores. Actinomyces israelii species is a gram-positive, cast-forming, non-acid-fast, non-sporeforming anaerobic bacillus that is difficult to isolate and identify. Its filamentous growth and mycelialike colonies have a striking resemblance to fungi. They are soil organisms, often found in decaying organic matter (eg, wet hay, straw). It is primarily a commensal microbe found in normal oral cavities, in tonsillar crypts, in dental plaques, and in carious teeth. Pathophysiology: Keratitis Most reported cases of Actinomyces keratitis (keratoactinomycosis) are caused by A israelii. It is characterized by a dry ulceration with central necrosis, surrounded by a gutter of demarcation, usually accompanied by iritis and hypopyon. In severe cases, descemetocele and perforation may occur. A primary corneal ulcer attributable to Actinomyces species is rare and usually follows corneal trauma. A rare case of keratoactinomycosis developing in the absence of any known ocular trauma was reported in Kuala Lumpur. Canaliculitis Primary chronic canaliculitis is an uncommon problem caused by A israelii (Streptothrix). McKellar presented a 10-year-old girl with a 6-month history of intermittent conjunctivitis and discharge from her pouted left lower punctum. Topical treatment with chloramphenicol/polymyxin sulphate failed despite a diagnosis of probable A israelii infection confirmed by microbiology. Surgical exploration revealed a canalicular diverticulum and 3 canaliculiths demonstrating solid casts of Actinomycetes on histologic examination. A therapeutic triad of punctoplasty, cast removal, and adjunctive topical cefazolin resulted in resolution. Other ocular involvement Actinomycetes have been described as causative organisms in conjunctivitis,

blepharitis, dacryocystitis, postsurgical endophthalmitis, and infected porous orbital implant. Cervico-facial actinomycosis also has been reported. Endophthalmitis, attributable to Actinomyces viscosus, developed in a 78-year-old man after cataract surgery. Postoperative endophthalmitis with this organism is a rare occurrence. Inflammation was characterized by anterior segment and vitreous cellular debris in cases of chronic postoperative endophthalmitis associated with Actinomyces species. Frequency: In the US: Primary chronic canaliculitis is an uncommon problem that can be overlooked; however, it may account for approximately 2% of all tearing problems. Actinomycosis may form in up to 2% of all lacrimal disease. Its occurrence probably is much less in other areas.

Race: No racial predilection exists. Sex: No gender predisposition exists. Age: No age predisposition exists. <TBODY> CLINICAL vlida.</TBODY> History: Keratitis Symptoms Progressive visual haze Increasing ocular pain Photophobia Constant watering Redness Past ocular history Corneal trauma, especially when contaminated by vegetable matter Ongoing, nonresponsive treatment Personal history - Outdoor laborer Symptoms Chronic or recurrent conjunctivitis Chronic mucopurulent discharge Epiphora Ocular surface irritation Medial eyelid and canthal pain Pouting punctum
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Canaliculitis

 Physical:

Failure to resolve despite topical treatment Past ocular and medical history similar to keratitis

Keratitis Gross observations Some conjunctival congestion Gray-white corneal lesion Slit lamp findings A dry ulceration with central necrosis, surrounded by a gutter of demarcation, usually accompanied by iritis and hypopyon may be present. Gray-white satellite stromal infiltrates adjacent to advancing edges may be present. In severe cases, descemetocele and perforation may occur. Gross observations Chronic discharge, swollen and pouted punctum A pouted punctum is clinically diagnostic, although it occurs in less than 50% of all affected patients. Typically, the discharge is particulate and contains concretions. The plica may be swollen and congested, and canalicular swelling and overlying lid erythema often are present. The lower lid more commonly is affected, and the lacrimal sac and the duct usually are not involved. Slit lamp findings Pouted punctum Plica may be swollen and congested. Particulate canalicular discharge with or without concretions

Canaliculitis

Causes: Infectious Actinomyces species See Background.

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<TBODY> DIFFERENTIALS vlida.</TBODY> Blepharitis, Adult Cellulitis, Preseptal

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Chalazion Conjunctivitis, Bacterial Contact Lens Complications Dacryocystitis Endophthalmitis, Fungal Endophthalmitis, Postoperative Keratitis, Fungal Nasolacrimal Duct, Obstruction Ulcer, Corneal Other Problems to be Considered: Propionibacterium propionicus canaliculitis Candida species canaliculitis <TBODY> WORKUP vlida.</TBODY> Lab Studies: Canalicular discharge and canaliculiths may be sent for the following studies: Gram stain/Giemsa stain Cultures and sensitivities (ie, blood agar, Sabouraud, anaerobic) Special stains (ie, Calcofluor white)
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Imaging Studies: Distension dacryocystography: Contrast material is used to visualize the anatomic details of the lacrimal drainage system. Scanning electron microscopy Probing may be performed with a lacrimal probe to check for a diverticulum and remaining casts. Perform a 2-snip punctoplasty under anesthesia. Curettage also may be helpful in removing any adherent casts from the canaliculus. Subsequent lacrimal irrigation with 2 MU penicillin in 20 mL sterile water may be helpful.

Other Tests:

Procedures:

Histologic Findings: Histologic examination of the canaliculiths demonstrated that they

consisted of solid casts of Actinomycetes with typical branching and filamentous structures. The organisms were found by using a Gram stain on the histopathologic preparations and by using a scanning electron microscopy. Electron-microscopic results of an actinomycosis of the lacrimal canaliculus were presented in 1980. The interior of the actinomycotic conglomerate showed no evidence of a cellular defense reaction, but, in the loosely woven outer network of hyphae, it was observed that a massive granulocytic reaction was present. After phagocytosis, the structure of the actinomycotic microorganisms within the granulocytes was not significantly damaged. Within the tissue of the lacrimal canaliculus, adjacent to the actinomycotic conglomerate, it was observed that an increased number of plasma cells were present; however, no organisms were present. <TBODY> TREATMENT vlida.</TBODY> Medical Care: Keratitis: Actinomycetes usually are susceptible to penicillins and cephalosporins. The treatment of keratoactinomycosis used to be excision of necrotic tissue, followed by cauterization. However, good results have been obtained by subconjunctival penicillin coadministered with systemic iodides. Alternatively, topical sulfacetamide or penicillin can be used. Canaliculitis: Actinomycetes usually are susceptible to penicillins and cephalosporins. Postoperatively, patients may be treated with topical cefazolin for 1 month. Adjunctive hyperbaric oxygen therapy for actinomycotic lacrimal canaliculitis has been reported. Keratitis: All reported cases of keratoactinomycosis responded to therapy, which included intraocular, topical, and systemic antibiotics, as well as pars plana vitrectomy and partial iridectomy. Urgent keratoplasty for a corneal infection by Actinomyces species was reported in a 41-year-old man. Canaliculitis: Failure to resolve canaliculitis by using topical treatment requires surgical exploration of the canalicular system and removal of any casts. Extensive surgery is not always required. A 2-snip punctoplasty, cast removal, curettage, probing, and adjunctive antibiotic therapy usually results in resolution of the canaliculitis. Cultivation of the surgically obtained dacryoliths and secretion enables reliable proof of Actinomyces and allows for an appropriate therapy for canaliculitis. Even though Actinomyces is sensitive to penicillin, cure of canaliculitis will not occur until all the concretions and granulations that are present in the canaliculus are removed meticulously.
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Surgical Care:

Consultations: An oculoplastics consult may be required. <TBODY> MEDICATION vlida.</TBODY> Error!Referencia de hipervnculo no

Actinomyces organisms usually are susceptible to penicillins and cephalosporins. Good

results have been obtained by subconjunctival penicillin coadministered with systemic iodides. Alternatively, topical sulfacetamide or penicillin can be used.

Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive

and should cover all likely pathogens in the context of the clinical setting. <TBODY>Drug Name Penicillin G (Pfizerpen) -- Exerts bactericidal action against penicillin-susceptible microorganisms during stage of active multiplication. Acts by inhibiting biosynthesis of cell wall mucopeptide, rendering the cell wall osmotically unstable. Not active against penicillinase-producing bacteria, which include many strains of staphylococci Adult Dose Topical: 100,000-333,000 U/mL in topical Subconjunctival: 0.5-1.0 million U/mL <IG> Intravitreal: 2,000 U and probenecid 0.5 g PO qid (possible retinal toxicity)<IG> Oral: 400,000 U PO qid (rarely used; poor stomach absorption)<IG> IV: 2-6 million U IV q4h and probenecid 0.5 g PO qid<IG> IM: Depends on formulation Pediatric Dose Topical: 10,000-20,000 U/mL<IG>

IV: 50,000 U/kg/d IV divided bid/tid Contraindications Documented hypersensitivity Interactions Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Caution in impaired renal function</TBODY> <TBODY>Drug Name Cefazolin (Ancef, Kefzol, Zolicef) -- First-generation cephalosporin with excellent activity against gram-positive cocci, including penicillinase-producing S aureus, penicillinase-producing S epidermidis, group A b-hemolytic streptococci (S pyogenes), and group B streptococci (S agalactiae) and S pneumoniae. Ineffective against Bacteroides fragilis and have only weak activity against gram-negative organisms. Adult Dose Topical: 133 mg/mL<IG> Subconjunctival: 100 mg/mL<IG>

Intravitreal: 2.25 mg plus probenecid 0.5 g PO qid<IG> IV/IM: 500-1,000 mg IV/IM q6h Pediatric Dose 25-100 mg/kg/d IV/IM divided q6-8h depending on severity of infection; not to exceed 6 g/d Contraindications Documented hypersensitivity Interactions Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin Pregnancy B - Usually safe but benefits must outweigh the risks. Precautions Prolonged use may result in overgrowth of nonsusceptible organisms; caution in GI disease, particularly colitis</TBODY>

Drug Category: Antiparasitic agents -- Parasite biochemical pathways are

sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses. <TBODY>Drug Name Sulfacetamide sodium 10% (Sulamyd, Bleph-10) -- N`-acetyl-substituted derivative; at 30% solution, topical sulfacetamide has pH of 7.4 and has good tissue penetration. Adult Dose Solution: Instill 1-3 gtt q2-3h in affected eye, while awake, with less frequent administration at night Ointment: Apply 0.5-inch ribbon into the conjunctival sac 1-4 times/d Pediatric Dose <2 months: Not established<IG>

>2 months: Administer as in adults Contraindications Documented hypersensitivity Interactions Effects of sulfonylurea hypoglycemic agents, hydantoin anticonvulsants, and oral anticoagulants increase when administered concurrently with sulfacetamide sodium; PABA antagonizes effects of sulfonamides; PABA esters (eg, procaine) may inhibit antibacterial effect of these agents; trimethoprim enhances effects of sulfacetamide Pregnancy C - Safety for use during pregnancy has not been established. Precautions Caution in severely dried eye; ointment may retard corneal epithelial healing; if inflammation or pain persists >48 h or becomes aggravated, reevaluate therapy; adverse effects include local irritation, brow ache, blurred vision, transient burning and stinging, and sensitivity reactions, including rare cases of Stevens Johnson syndrome and exfoliative dermatitis have been reported; GI upset and bone marrow depression also have been described</TBODY>

<TBODY> FOLLOW-UP vlida.</TBODY> Further Outpatient Care:

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Patients should receive follow-up care as needed. Postoperatively, patients may be treated with topical cefazolin for 1 month. Prognosis is excellent once the organism is positively identified and appropriately treated. Wear protective eye gear when working with vegetable matter.

In/Out Patient Meds: Prognosis:

Patient Education:

<TBODY> MISCELLANEOUS Section 9 of 11 Error!Referencia de hipervnculo no vlida.</TBODY> Medical/Legal Pitfalls: Failure to identify the organism properly with subsequent appropriate medical and surgical management may lead to a persistent epiphora; intermittent, mucopurulent discharge; and a localized, tumorlike swelling on the involved site. ADDITIONAL AUTHOR INFORMATION <IG>

Special Concerns: Manolette Rangel Roque, MD, was a Fellow and affiliated with the Ocular Immunology and Uveitis Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School while performing this work.