Periocular Atypical Mycobacterium Infections

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Disease Entity

  • Cutaneous mycobacterial infection ICD-10 A31.1
  • Other mycobacterial infections ICD-10 A31.8

Disease

Atypical mycobacterium ocular infections are rare, most commonly seen in keratitis following LASIK procedures, corneal surgery, or contact lens wear; however, periocular, adnexal, and intraocular infections have also been reported, particularly following lacrimal surgeries.[1][2][3][4][5][6] Recent investigations predict an increase in ocular and periocular infections due to atypical mycobacteria with one study reporting a four-fold increase in the number of eyes infected with atypical mycobacteria from 1980-1989 (13.4%) to 2000-2007 (56.3%).[3][7][8]

While ocular surface infections are the most commonly cited, periocular skin is the most common periocular location, usually following trauma, surgery, or disseminated disease. Cutaneous atypical mycobacterium infections are most commonly seen following blepharoplasty, ptosis repair, and dacryocystorhinostomy (DCR).[9][10][11][12] Although staphylococcal and pseudomonal infections are more typical following these procedures, atypical mycobacterium infections are often difficult to identify and can cause a delay in diagnosis with potentially detrimental outcomes.

Etiology

Atypical mycobacteria, also referred to as non-tuberculous mycobacterial (NTM) are acid-fast bacteria endemic in the Southeastern United States, commonly found in soil, dust, swamps, lakes, rivers, aerosols, and domestic water supplies.[7][13][14] Atypical mycobacteria are classified into Runyon groups I-IV (Table 1).[15] The most commonly implicated pathogens belong to Runyon Group IV and include Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium smegmatis, which are characterized by their rapid growth and lack of pigmentation.[16]

Their ability to form biofilms under low nutrient conditions suggest that inadequate disinfection of surgical equipment and fluids in healthcare environments can lead to accumulation and transmission of the mycobacterium.[14][17]

Table 1: Runyon Classification of Nontuberculous Mycobacteria[15]
Runyon Group Phenotype Species
I Photochromogens M. marinum, M. kansasii, M. simiae, M. asiaticum
II Scotochromogens M. scrofulaceum, M. szulgai, M. gordonae, M. xenopi, M. flavescens
III Nonchromogenis M. avium, M. intracellulare, M. haemophilum, M. paratuberculosis, M. gastri, M. malmoense, M. nonchromogenicum, M. terrae, M. triviale
IV Rapid growers M. fortuitum group: M. fortuitum, M. peregrinum, M. muco-genicum, M. Senegalese, M. septicum

M. chelonae-abscessus group: M. chelonae, M. abscessus, M. immunogenum

M. smegmatis group: M. smegmatis, M. goodii, M. wolinskyi

Risk Factors

Recent periocular surgery, trauma, presence of ocular biomaterials, nasolacrimal duct obstruction, and immunosuppression appear to be the most common risk factors for periocular atypical mycobacterium infections.[2][18] One study emphasizes the strong association of atypical mycobacterium infections and the presence of a biomaterial due to the ability of atypical mycobacteria to form biofilms, including nasolacrimal silicone stents, punctal plugs, and prosthetics.[2] There is no established gender predominance in the literature; however, some studies have found that women and patients greater than 50 years of age appear to be affected more, although this represents the most common demographic population for blepharoplasty and ptosis repair.[2][3]

Pathophysiology

Atypical mycobacteria can form biofilms on surfaces under low nutrient conditions and resist routine disinfectants such as chlorine suggesting that a variety of water sources can serve as a reservoir and route of transmission.[17][19][20] Identifying the source can be challenging; however, cutaneous atypical mycobacterium infections have been linked to tap water, gentian violet skin-marking solution, and improper sterilization of instruments.[13][21][22][23] The pathogenicity of atypical mycobacteria is thought to be dependent on and enhanced by the presence of fat.[24][25][26] Further, almost all reports on atypical mycobacterium infection following blepharoplasty involve intraoperative fat manipulation or removal.[9][10][11][25] This lipid sequestration also likely contributes to evasion of host response and poor antibiotic penetration.[15]

Primary prevention

Proper sterilization of surgical instruments, intraoperative sterile techniques, sterilization of skin and eyelids with povidone-iodine, and appropriate prophylactic antibiotics are recommended for reducing incidence of cutaneous atypical mycobacterium infections. One study demonstrated a significant reduction in the incidence of infection by implementing a prevention protocol that exchanged reusable gel packs and bottled or distilled water for ice compresses and tap water after an isolated outbreak in North Carolina, suggesting local tap water as the source of infection.[27]

Diagnosis

Diagnosis of atypical mycobacterium infection is challenging and often delayed due to low index of clinical suspicion, delayed laboratory identification, use of corticosteroids or broad spectrum antibiotics, and initial misdiagnosis.[2][3] Delay in diagnosis from presentation has been reported anywhere from 1 to 12 weeks. Diagnosis is typically made on culture or histopathologic examination.[2]

History

The time of onset, duration of symptoms, environmental exposures, and a thorough review of systems are necessary. Presentation is often subacute, ranging from 1 week to 12 weeks postoperatively, in contrast to acute bacterial infections.[3] Other relevant medical history such as clinical immunodeficiency due to disease or immunosuppressive therapy is useful in assessing risk. History of exposure to soil, swamps, lakes, ponds or rivers should also be elicited.

Symptoms

The appearance of multiple firm nodules or bumps, swelling, and discharge near the area of surgery are common presenting symptoms. Other symptoms can include pain, pruritus, erythema, or blurry vision.

Physical examination

Palpation of the affected area should be performed to assess for nodules, warmth, and tenderness. Single or multiple erythematous or non-erythematous nodules along surgical wounds are usually seen on initial presentation although cellulitis can precede this. Purulent discharge is usually minimal and when present is often associated with a draining abscess or on incision and drainage. Progressive edema, preseptal cellulitis and rarely post-septal involvement can occur.[24] The appearance of new lesions is not uncommon. Specimens should be collected using a swab if discharge is present, incision and drainage, or biopsy of nodular lesions.

Diagnostic procedures

Cultures of tissue specimens or purulent material with resistance testing should be performed. This can be obtained by swab, incision and drainage, or biopsy. Acid-fast stain is a helpful and fast technique to identify atypical mycobacteria but is often not positive. Alternative stains including fluorescent acid-fast staining can be helpful.[15]

Cultures should be performed on multiple media to increase identification of these species, including blood agar, chocolate agar, MacConkey agar, Lowenstein Jensen medium and liquid media such as Middlebrook 7H9 broth. Atypical mycobacteria characteristically exhibit rapid growth within 5-7 days and do not produce pigmentation; however, it is recommended that such cultures be kept for up to 8 weeks.[15] PCR testing is also being increasingly utilized due to its ability to identify specific species of atypical mycobacteria.[28]

Histopathologic findings include chronic granulomatous inflammation with congregations of atypical mycobacteria bacilli within lipid vacuoles . Giant cells and central caseation or an acute polymorphonuclear response associated with necrosis and microabscesses may also be seen.[15][18]

Differential diagnosis

Differential diagnosis includes:

Management

Management of cutaneous atypical mycobacterium infections can be challenging due to slow response to therapy, poor drug penetration, and the need for prolonged therapy. A combined medical and surgical approach is often required with frequent follow up. Consultation with an infectious disease specialist may be helpful to aid in diagnosis and selection of therapy.

General treatment

Systemic antibiotic therapy guided by organism sensitivities is the initial treatment in most cases and is often combined with surgical debridement and removal of any foreign bodies. Rarely, excision of lesions alone can result in resolution.[11] Atypical mycobacteria are resistant to conventional agents used for M. tuberculosis and are multidrug resistant. M. fortuitum is less drug resistant and easier to treat than M. abscessus and M. chelonae.[11] Therefore, identification of atypical mycobacteria species is paramount for appropriate antibiotic selection. Empiric treatment using a combination of amikacin, clarithromycin, with or without a fluoroquinolone until susceptibilities are available is recommended and commonly used as first-line therapy for cutaneous atypical mycobacterium infections.[2][3][9][15]

Present research indicates excellent in vitro activity of amikacin and clarithromycin against M. fortuitum, M. abscessus, and M. chelonae.[16] M. fortuitum demonstrates a greater susceptibility to amikacin and fluoroquinolones while M. abscessus and M. chelonae, are highly susceptible to clarithromycin.[29] Girgis et al, the largest study of ocular atypical mycobacterium infections to date, found that ocular atypical mycobacteria isolates were most sensitive to clarithromycin (93%) and amikacin (81%) followed by linezolid (36%), gatifloxacin (31%), moxifloxacin (21%) and ciprofloxacin (10%).[2]

Monotherapy should be avoided due to its potential to increase antibiotic resistance, particularly if a fluoroquinolone is being used. Steroid therapy can lead to a prolonged course and should be also be avoided. Smith et al reported one case of M. chelonei infection after nasolacrimal duct probing in a patient on systemic prednisone therapy for asthma.[30]

Surgery

Surgical treatment involves incision and drainage of abscesses. Rarely, excision alone is sufficient; however, combination therapy with antibiotic agents is recommended.

Medical and Surgical follow up

Cutaneous atypical mycobacterium infections usually require frequent follow up to ensure a response to medical and/or surgical therapy. There are no guidelines for duration of treatment for cutaneous atypical mycobacterium infections. Generally, duration of treatment has ranged from 4 to greater than 24 weeks with most requiring greater than 5 weeks of therapy.[2][3][11]

Complications

Complications described in the literature include residual scarring, hyperpigmentation, lower eyelid retraction, cicatricial ectropion, and enophthalmos, requiring surgical repair.[3][9][11][15] Steroid therapy can also lead to a prolonged course with higher risk for complications.

Prognosis

With appropriate treatment using surgical debridement and systemic antibiotics, the majority of patients with cutaneous atypical mycobacterium infectious have a relatively good prognosis with no sequelae.[15] Kheir et al reported a resolution of infection in 22/28 (78.5%) cases, with six cases exhibiting a prolonged course, all recovering without vision loss or eyelid abnormalities.[3]

References

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