195.1 🎓 醫孞生版

195.1.0.1 📌 䞀頁重點

  • NTM: > 200 species of Mycobacterium outside M. tuberculosis complex
  • Environmental (water, soil, biofilms, hospital water systems)
  • Person-to-person rare (except M. abscessus CF cluster spread, M. ulcerans localized)
  • Major species:
Species Disease Key
M. avium complex (MAC) = M. avium + M. intracellulare + M. chimaera Disseminated in AIDS (CD4 < 50), pulmonary in middle-age bronchiectasis, lymphadenitis in children Most common NTM disease
M. abscessus complex (subsp. abscessus, massiliense, bolletii) CF pulmonary, post-surgical, soft tissue MDR — very hard to treat
M. kansasii Pulmonary mimics TB Photochromogen (yellow in light)
M. marinum Fish-tank / aquarium granuloma — skin/joint “Swimming pool granuloma”
M. ulcerans Buruli ulcer (Africa, Australia) — chronic painless skin ulcer Mycolactone toxin
M. fortuitum, M. chelonae Skin / soft tissue (rapid grow), post-surgery, cosmetic Cosmetic procedure outbreaks
M. xenopi, M. malmoense Pulmonary, sporadic Sometimes underdiagnosed
M. genavense Disseminated AIDS, GI Slow grow
M. haemophilum Cutaneous/joint immunocompromise Iron + low temp grow
  • Treatment: multi-drug, prolonged (months-years); species-specific
  • MAC pulmonary: macrolide (azithro / clarithro) + rifampin + ethambutol ≥ 12 months after culture-neg
  • Disseminated MAC AIDS: same regimen + ART + secondary prophylaxis until immune recovery
  • M. abscessus: amikacin IV + cefoxitin/imipenem + clarithromycin/azithromycin + clofazimine + 
 multi-drug long course

195.1.0.2 1⃣ 现菌孞

  • AFB stain + (like TB)
  • Slow grow (most) — culture 1-6 weeks
  • Rapidly growing (M. abscessus, M. fortuitum, M. chelonae) — culture < 7 days
  • Slow growers: MAC, M. kansasii, M. marinum, M. ulcerans
  • Environmental ubiquity — water, soil, biofilm
  • Resistance to standard disinfectants
  • BSL-2 (vs TB BSL-3)
195.1.0.2.1 Identification
  • AFB smear (cannot distinguish from TB)
  • Culture + MALDI-TOF or molecular ID (16S rRNA, hsp65)
  • AST critical — species-specific patterns
  • GeneXpert MTB/RIF can distinguish from TB (negative for NTM)

195.1.0.3 2⃣ Mycobacterium avium Complex (MAC)

195.1.0.3.1 Species
  • M. avium + M. intracellulare = MAC traditionally
  • M. chimaera — newly recognized, water source (heater-cooler units in cardiac surgery)
  • All clinically similar
195.1.0.3.2 Sources
  • Water (tap, hot tub, hospital water systems)
  • Soil
  • Aerosol from showers, indoor pools
195.1.0.3.3 A. Disseminated MAC in AIDS
  • CD4 < 50 primary risk
  • Fever + weight loss + night sweats + diarrhea
  • Anemia (severe), thrombocytopenia, hepatosplenomegaly
  • Lymphadenopathy
  • Mortality high without ART
  • Blood culture (mycobacterial blood culture bottles + MGIT)
195.1.0.3.4 B. Pulmonary MAC
195.1.0.3.4.1 Patterns
  • Fibrocavitary (old man with COPD/EToH): like TB
  • Nodular bronchiectasis (“Lady Windermere syndrome”): middle-aged thin Caucasian women, RML/lingula bronchiectasis + small nodules; pectus excavatum / scoliosis common
  • Hot tub lung: hypersensitivity pneumonitis-like (M. avium), resolves without treatment after avoidance
195.1.0.3.4.2 Diagnosis Criteria (ATS/IDSA 2020)
  • Clinical pulmonary + radiographic AND
  • Microbiologic: 2 positive sputum cultures OR 1 BAL/lung biopsy positive OR biopsy granulomas + 1 positive sputum
  • Need all 3 criteria (clinical + radiographic + microbiologic)
195.1.0.3.5 C. Lymphadenitis (Children)
  • Cervical “scrofula”-like in 1-5 yr-olds
  • Unilateral painless cervical mass
  • Differential: cat scratch (Bartonella), TB scrofula, lymphoma
  • Excisional biopsy preferred (better than antibiotic alone for cure)
  • 無 need long antibiotic if excised
195.1.0.3.6 Treatment
195.1.0.3.6.1 Disseminated AIDS
  • Clarithromycin 500 mg bid OR azithromycin 500-600 mg qd + Ethambutol 15 mg/kg/d + Rifabutin 300 mg/d (or rifampin 600 mg/d)
  • ART concurrent
  • Continue ≥ 12 months after CD4 > 100 + viral suppression > 6 months
  • Side effects: hepatotoxic, optic neuritis (EMB), uveitis (rifabutin + clarithro combo)
195.1.0.3.6.2 Pulmonary
  • Clarithromycin 500 mg bid OR azithromycin 500 mg qd + Ethambutol 15 mg/kg/d + Rifampin 600 mg/d
  • Severe fibrocavitary: add streptomycin or amikacin IM/IV × 8-12 wk
  • 2-3× weekly intermittent dosing option for nodular bronchiectasis
  • Continue ≥ 12 months after culture-neg (typically 18-24 mo total)
  • Resistance testing: macrolide R common during failure
195.1.0.3.6.3 Lymphadenitis (Children)
  • Excisional biopsy preferred (cure)
  • If incomplete excision: clarithromycin + ethambutol or rifampin × 3-6 mo

195.1.0.4 3⃣ M. abscessus Complex

195.1.0.4.1 Species
  • M. abscessus subsp. abscessus, massiliense, bolletii
  • Rapidly growing
  • Highly drug-resistant
195.1.0.4.2 Source
  • Water (hot tub, hospital, contaminated dialysate)
  • Person-to-person spread documented in CF clinics (segregation!)
195.1.0.4.3 Clinical
  • CF: chronic pulmonary infection, accelerates FEV1 decline; can preclude lung transplant
  • Post-surgical wound (cosmetic procedure outbreaks, breast augmentation, liposuction)
  • Skin/soft tissue
  • Disseminated (immunocompromise)
195.1.0.4.4 Treatment — Very Difficult
  • Multi-drug, prolonged, often partially successful
  • Intensive phase: IV amikacin + cefoxitin or imipenem + macrolide (if inducible R neg)
  • Continuation: oral macrolide + clofazimine + linezolid + others
  • subsp. massiliense better outcome (no inducible macrolide R)
  • subsp. abscessus: erm(41) gene → inducible macrolide R → macrolide may not work
  • Surgical resection for localized
  • Cure < 50% for pulmonary

195.1.0.5 4⃣ Other NTM

195.1.0.5.1 M. kansasii
  • Pulmonary, mimics TB radiographically (upper lobe cavitary)
  • USA Texas, Louisiana, Florida
  • “Photochromogen” — yellow pigment in light
  • Treatment: rifampin + INH + EMB × 12-18 mo (good response)
195.1.0.5.2 M. marinum
  • “Fish-tank granuloma” / “swimming pool granuloma”
  • Aquarium owner, fishermen
  • Skin papule → nodular → ulcer on hand
  • Tenosynovitis, septic arthritis in deeper
  • Treatment: clarithromycin + ethambutol × 3-6 mo (or doxycycline + rifampin)
195.1.0.5.3 M. ulcerans (Buruli Ulcer)
  • Africa (W Africa most), Australia (Victoria)
  • Standing water exposure
  • Mycolactone toxin — immunosuppressive
  • Chronic painless skin ulcer (extensive)
  • Treatment: rifampin + clarithromycin × 8 wk (WHO regimen)
  • Surgical debridement for advanced
195.1.0.5.4 M. fortuitum + M. chelonae
  • Rapidly growing
  • Cosmetic procedure outbreaks (breast augmentation, liposuction, tattoo)
  • Pedicure foot infections
  • Post-cardiac surgery (sternum)
  • Treatment: combinations including imipenem, amikacin, macrolide × 6-12 mo
195.1.0.5.5 M. xenopi, M. malmoense
  • Pulmonary, sporadic
  • Often missed (slow grow)
  • Treatment: rifampin + ethambutol + clarithromycin × 12 mo
195.1.0.5.6 M. genavense
  • Disseminated AIDS GI predominant
  • Slow grow (specialty)
  • Rifabutin + clarithromycin + ethambutol
195.1.0.5.7 M. haemophilum
  • Cutaneous/joint, immunocompromise
  • Iron-requiring (heme), low-temp grow (30-32°C) — special media + low incubation temp
  • Treatment: rifampin + clarithromycin + ciprofloxacin
195.1.0.5.8 M. chimaera (Cardiac Surgery)
  • Heater-cooler units contamination during open-heart surgery
  • Late infection (1-6 yr post-op) — fever, cytopenia, hepatitis, endocarditis, sternal osteo
  • Treatment: prolonged combination + sometimes prosthetic explant
  • Global outbreak 2014-2017 + ongoing alerts

195.1.0.6 5⃣ Treatment Principles for NTM

  • Multi-drug (always 2+) — prevent resistance
  • Prolonged (months to years)
  • Species-specific AST guidance
  • Macrolide cornerstone for MAC, M. kansasii, M. marinum
  • Rifamycin for MAC, M. kansasii
  • Aminoglycoside for severe / refractory MAC, M. abscessus
  • Avoid macrolide monotherapy — selects resistance
  • Surgical resection for localized refractory disease
  • Side effects: optic neuritis (EMB), ototoxicity (aminoglycoside), uveitis (rifabutin + clari)