MYCOBACTERIUM ABSCESSUS Mycobacterium abscessus Rapid growing mycobacterium Environmental
MYCOBACTERIUM ABSCESSUS
Mycobacterium abscessus • Rapid growing mycobacterium • Environmental contaminant • Formerly part of “M. chelonae-complex” till 1992 • Subspecies of M. abscessus – M. abscessus senso strictu – M. massiliense – M. bolletii
Mycobacterium abscessus • Pulmonary disease most common • Cutaneous disease • Disseminated disease rare (mostly immunosuppressed w/ corticosteroids) • Bacteremia/ endocarditis: described in hemodialysis patients
Clusters of M. abscessus infection after cosmetic Rx or injection of alternative medicine Year Place Type of Rx received Outcome 1995 -96 US Injection of adrenal cortex extract Cutaneous infection 2001 Seoul, South Korea Acupuncture Cutaneous infection 2002 New York, US Intramammary injection of silicone Cutaneous infection 2003 -04 Dominican Republic Abdominoplasty Cutaneous infection 2012 Hong Kong CIK therapy Septicemia
Mycobacterium abscessus • Most pathogenic and chemotherapyresistant rapid-growing mycobacterium – Intrinsic resistance • • Low permeability of cell wall Drug export systems Antibiotic-modifying/ inactivating enzymes Genetic polymorphism of targeted gene – Acquired resistance • Macrolide resistance • Aminoglycoside resistance
Intrinsic resistance • Low permeability of cell wall – High lipid content (up to 60% of dry weight) • Drug export systems – Mycobacterial membrane protein large (Mmp. L) transporter family – ABC-type multidrug transporter family
Intrinsic resistance • Antibiotic-modifying/ inactivating enzymes – Rifampicin ADP-ribosyltransferase and monooxygenase → rifampicin resistance – Aminoglycoside 2 -N-acetyltransferase and phosphotransferases → aminoglycosiade resistance • Genetic polymorphism of target genes – Mutations in emb. B → ethambutol resistance – Mutations in quinolone resistance-determining regions (QRDRs) → fluoroquinolones resistance
Acquired resistance • Macrolide resistance – Macrolide → inhibit ribosomal translocation – Inducible ribosomal methylase erm(41) gene → modify ribosome binding site – Clarithromycin induces erm(41) to a significantly greater extent than azithromycin – ? ? azithromycin preferred over clarithromycin
Acquired resistance • Aminoglycoside resistance – Aminoglycoside → interfere proof-reading process, causing errors in synthesis with premature termination – Mutations affecting 16 S r. RNA
Treatment strategy • Limited, extra-pulmonary disease – Clarithromycin alone (Acquired mutational resistance not observed when treating localized infections with macrolide monotherapy) – Amikacin +/- cefoxitin/ imipenem may be added for two weeks until clinical improvement in more severe cases – Duration guided by clinical response: typically 4 months. Osteomyelitis: 6 month minimum recommended – Infected foreign bodies should be removed
Treatment strategy • Pulmonary or severe extrapulmonary disease – In vitro data not yielded effective regimen for treating pulmonary disease – May not achieve sputum culture negativity even with 12 months of therapy – Lung disease should be considered a chronic, incurable infection
Treatment strategy • Pulmonary or severe extrapulmonary disease – Combination therapy always recommended: • Clarithromycin 500 mg PO BD plus Amikacin IV (15 mg/kg/d) plus either cefoxitin IV (2 gm Q 4 H) or Imipenem IV (1 gm Q 6 H) • Duration: combination therapy w/ injectable agents + clarithromycin at least 2 -4 months but duration often limited by adverse effects • Maintenance: once with good effect with combination therapy, consider switch to oral clarithromycin OR azithromycin indefinitely ("suppressive treatment")
Treatment strategy • Pulmonary or severe extrapulmonary disease – Other agents: little good data to guide on selection or use in combination – Tigecycline 100 mg IV load then 50 mg IV Q 12 H • Little reported clinical data but may be in vitro susceptible and could be substituted as one of the injectables. Often poorly tolerated due to GI distress
Treatment strategy • Pulmonary or severe extrapulmonary disease – Linezolid 600 mg Q 12 H PO • potentially useful oral agent in pts in whom parental Rx not tolerated or feasible – Clofazimine • may have in vitro activity, little clinical experience
Mycobacterium abscessus • Most pathogenic and chemotherapyresistant rapid growing mycobacterium • Most commonly caused pulmonary disease • Clusters of cutaneous disease after cosmetic injections reported • Disseminated disease/ bacteremia is rare • ? related to severe DIC, but no case report identified
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