Pathogens>Bacteria>

MICROBIOLOGY

• Mycobacteria spp. are divided into rapid growers (<7 days) and slow growers (>7 days) based on the time to mature growth on agar plates.
• M. genavense: very slow growing. Alert lab: requires incubation in broth media for at least 8 wks.
• Rapid grower: M. fortuitum: (3 to 7 days) and M. chelonae.
• Slow growing: M. gordonae (7-10 days), "tap water bacillus," M. malmoense, M. marinum (7-10 days), M. ulcerans and M. xenopi (3 to 8 wks in culture).
• M. haemophilum: "blood-loving," slow growing. Alert lab: requires ferric iron supplementation and temperature 30C.

CLINICAL

• M. abscessus: causes skin & soft tissue disease, lymphadenitis, & pulmonary disease.
• M. chelonae: causes skin & soft tissue disease & lymphadenitis.
• M. fortuitum: cutaneous disease (cellulitis, abscesses, ulcers) most common and can have contiguous spread to bones/joints; catheter-related infections, disseminated disease, lymphadenitis less common; pulmonary disease rare. Institutional/nosocomial disease outbreaks due to contaminated water have been reported.   
• M. genavense:  typically CD4 <50. Similar manifestations to MAC--fever, weight loss, abdominal pain, anemia, lymphadenopathy, diarrhea, splenomegaly. Abdominal lymphadenopathy and splenomegaly often more pronounced than MAC. Also causes cutaneous infections. Can be associated with IRIS. Cx of liver or bone marrow more sensitive than blood Cx.   
• M. gordonae: rare cause of human disease--isolation from clinical specimen usually represents environmental contamination from water.
• M. haemophilum: Cutaneous disease with multiple papules, nodules, or ulcerations, often overlying joints. Also causes arthritis, osteomyelitis, pulmonary disease, and disseminated infection. Suspect if prior clinical specimens AFB smear positive but Cx-negative (requires iron enriched culture media)  
• M. marinum: Cutaneous plaques
• M. malmoense: rare cause of pulmonary, lymphadenitis, disseminated infection. Most reports of disease in northern and western European Union.    
• M. ulcerans: causes "Buruli ulcer" cause of subcutaneous nodules which progress to indurated plaques & eventually undermined ulcerations, and, rarely, osteomyelitis. Mostly occurs in tropical Africa. No difference in presentation noted between HIV-uninfected and HIV-infected individuals. Not transmitted person-to-person. 
• M. xenopi  : occurs at low CD4, pulmonary most common, may resemble TB. Disseminated disease can occur. However, is often a contaminant. Outbreaks associated with hot water taps, bronchoscopes in institutions. Significance of positive respiratory Cxs should be carefully considered. In symptomatic patients with abnormal CXR, repeated isolation from respiratory specimens usually indicates disease if no alternative etiology.   

TREATMENT

• No consensus. Clarithromycin 500 mg bid for 6 months. For serious infections, add tobramycin + imipenum for 1st 2- 6 wks.

• Localized, limited skin disease: monotherapy with clarithromycin 500 mg bid, or trimethoprim/sulfamethoxazole DS 1 tab bid, or doxycycline 100 mg bid; duration typically 3-4 mos
• Severe disease: amikacin (15 mg/kg qd) plus either beta-lactam (cefoxitin 2 gm q6h or imipenem 1 gm q6h) or fluoroquinolone (moxifloxacin 400 mg qd) until clinical improvement, then oral therapy with at least 2 drugs, duration typically 6-12 mos
• Use in vitro susceptibility tests to guide antibiotic selection

• Clarithromycin 500 mg bid + rifampin 600 mg qd + moxifloxacin 400 mg qd +/- amikacin 15-20 mg/kg qd
• Cycloserine (250 mg bid) active in vitro

• Clarithromycin 500 mg bid + rifampin 600 mg qd + ethambutol 15 mg/kg qd
• Duration: indefinite if no immune reconstitution. If immune reconstitution consider stopping if treated >1 yr plus CD4 >100 for 3-6 mos plus asymptomatic
• M. genavense associated with IRIS: treat as for IRIS with MAC. Typically can continue ART and antimycobacterial treatment, treat Sx with NSAIDS. Some patients require steroids.

• No consensus. Isoniazid 300 mg qd + rifampin 600 mg qd + ethambutol 15 mg/kg qd + streptomycin 15 mg/kg qd (Clin Infect Dis 1992;14:1229)
• Clarithromycin active in vitro.

• Clarithromycin 500 mg bid or rifampin 600 mg qd + ethambutol 15 mg/kg qd. All therapy for at least 3 mos.

• Clarithromycin 500 mg bid + rifampin 600 mg qd + ethambutol 15 mg/kg qd
• Alternatives: streptomycin 15 mg/kg qd; isoniazid 300 mg qd (+ vitamin B6 50 mg qd)
• Duration: prolonged (at least 18 to 24 mos), and indefinite if no immune reconstitution

• Surgical excision. Antimicrobial therapy not successful.

• Clarithromycin 500 mg bid + rifampin 600 mg qd + ethambutol 25 mg/kg qd for 2 mos then 15 mg/kg qd +/- streptomycin 15 mg/kg thrice weekly (Am J Respir Crit Care Med 1997;156:S1)
• Duration: prolonged (2 years or more). High rates of failure and relapse.
• Moxifloxacin active in vitro.

Drug Comments

FOLLOW UP

• M. genavense: follow for improvement in symptoms, and conversion of blood cultures to negative. monitor LFTs on rifampin, monitor visual acuity and color vision monthly on ethambutol.
• M. gordonae: monitor LFTs on isoniazid, rifampin; visual acuity and color vision monthly on ethambutol; vestibular and renal function on streptomycin.
• M. haemophilum: monitor LFTs on rifampin, renal function on amikacin.
• M. malmoense: monitor LFTs on rifampin and isoniazid; monitor visual acuity and color vision monthly on ethambutol.
• M. xenopi: monitor sputum cultures monthly until 3 consecutive negatives. Monitor LFTs on rifampin; visual acuity and color vision monthly on ethambutol; vestibular and renal function on streptomycin.

REFERENCES