189.1 🎓 醫學生版

189.1.0.1 📌 一頁重點

• 菌: Mycoplasma — NO cell wall → β-lactam, vancomycin 不 effective; pleomorphic, smallest free-living organism
• 3 主要 human species:
  • M. pneumoniae — atypical CAP, walking pneumonia, extrapulmonary syndromes
  • M. genitalium — STI (urethritis, cervicitis, PID); emerging resistance
  • Ureaplasma urealyticum — non-gonococcal urethritis, neonatal, premature
  • M. hominis — postpartum, immunocompromise
• M. pneumoniae 流行病學:
  • School-aged children + young adults main
  • Epidemic cycle every 3-7 years; 2023-2024 large global outbreak (post-COVID return)
  • Crowded settings: schools, military, dorms, family clusters
• Clinical (M. pneumoniae):
  • Pneumonia: gradual onset, dry cough, low-grade fever, “walking pneumonia” — patient ambulatory despite findings; CXR shows reticulonodular interstitial > consolidation
  • Tracheobronchitis, pharyngitis, bullous myringitis (rare classic)
  • Extrapulmonary:
    • Cold agglutinin disease (autoimmune hemolysis IgM Ab to I antigen on RBC, ~ 60% have detectable agglutinins)
    • Erythema multiforme / Stevens-Johnson (multi-system)
    • MIRM (Mycoplasma-Induced Rash and Mucositis) — distinct syndrome from SJS/TEN
    • Neuro: encephalitis (often post-infectious), transverse myelitis, GBS, ADEM
    • Cardiac: myocarditis, pericarditis
    • Hematologic: hemolysis, ITP, DIC, HLH
    • Arthritis: reactive, especially HLA-B27
• Dx:
  • PCR of nasopharyngeal / throat swab — most sensitive
  • Cold agglutinin titer ≥ 1:64 at bedside (refrigerated tube — RBC clumping on cold)
  • Serology IgM (limited utility)
  • Culture difficult (specialty)
• Treatment:
  • Azithromycin 500 mg day 1 → 250 qd × 4d OR clarithromycin 500 bid × 7d
  • Doxycycline 100 bid × 7-10d alt (rising macrolide R, especially Asia)
  • Fluoroquinolone (levofloxacin) alt (children avoided)
  • 7-10d typical; severe / extrapulmonary may extend
• Macrolide R:
  • Asia 50-90% (China) — game changer for empirical
  • USA / Europe 10-20% rising
  • 改 doxycycline or FQ
• M. genitalium:
  • STI (urethritis ♂, cervicitis ♀, PID, infertility)
  • Often asymptomatic
  • High resistance: azithromycin ~ 50%, moxifloxacin ~ 10-20%
  • Treatment: doxy 100 bid × 7d → azithro 1 g × 1 + 500 qd × 3d (sequential resistance-guided); pristinamycin emerging

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189.1.0.2 1️⃣ 細菌學

• No cell wall — fundamental feature
• → 不 stain on Gram (no peptidoglycan)
• → Insensitive to β-lactams, vancomycin, cell-wall agents
• Pleomorphic shape (filamentous, coccoid)
• Smallest self-replicating organism
• Slow grow on special media (PPLO agar) — not for clinical decision
• Cholesterol incorporation into membrane (most prokaryotes don’t)

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189.1.0.3 2️⃣ M. pneumoniae

189.1.0.3.1 流行病學

• ~ 2-30% of CAP (varies)
• All ages but school-age and young adult predominate
• Outbreaks every 3-7 yr cyclical
• 2023-2024 global outbreak — China, Europe, USA, increased disease and severity
• Crowded settings (schools, military, college dorms, family clusters)
• Incubation 2-3 wk

189.1.0.3.2 A. Pneumonia (“Walking Pneumonia”)

• Gradual onset over 2-3 wk
• Dry cough persistent
• Low-grade fever, malaise, sore throat, headache, ear pain
• Auscultation often unremarkable (vs CXR findings disproportionate)
• “Walking” — patient remains ambulatory and often working

189.1.0.3.2.1 Imaging

• Reticulonodular interstitial
• Often unilateral lower lobe
• Sometimes consolidation, atelectasis, hilar LAP
• Pleural effusion 25%

189.1.0.3.2.2 Severe / Complications

• Necrotizing pneumonia rare
• ARDS in severe (Asian outbreaks)
• Co-infection with viral / other bacterial worsens

189.1.0.3.3 B. Extrapulmonary

189.1.0.3.3.1 Cold Agglutinin Disease

• 60% have detectable cold agglutinins (anti-I IgM)
• ~ 1-5% have hemolytic anemia clinically significant
• Cold-induced acrocyanosis, Raynaud-like
• Refractory hemolysis: rituximab, steroid; cold avoidance

189.1.0.3.3.2 Skin / Mucosa

• Erythema multiforme (target lesions)
• MIRM (Mycoplasma-Induced Rash and Mucositis) — multiple mucosal involvement (oral, ocular, genital) ± skin; distinct from SJS/TEN; better prognosis
• Stevens-Johnson — rare

189.1.0.3.3.3 Neurological

• Acute encephalitis — usually post-infectious (immune-mediated)
• Transverse myelitis
• GBS (post-infectious)
• ADEM (acute disseminated encephalomyelitis)
• Cerebellar ataxia
• Cranial neuropathy
• Stroke (rare; antibody to vascular endothelium)

189.1.0.3.3.4 Cardiac

• Myocarditis, pericarditis, conduction abnormalities

189.1.0.3.3.5 Hematologic

• Hemolysis (cold agglutinin)
• ITP
• DIC, HLH (severe)

189.1.0.3.3.6 Arthritis

• Reactive (HLA-B27)
• Synovitis

189.1.0.3.4 C. Other

• Pharyngitis, otitis media, bullous myringitis (rare classic but described)

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189.1.0.4 3️⃣ 診斷

189.1.0.4.1 A. PCR

• Nasopharyngeal / throat swab — most sensitive (90%+)
• BAL in severe
• CSF in encephalitis
• Multiplex respiratory pathogen panels (BioFire FilmArray) include
• Quick results (hours)

189.1.0.4.2 B. Serology

• IgM (acute infection) — paired sera 4-fold rise
• Limited utility for acute decision-making
• Past infection vs active: difficult

189.1.0.4.3 C. Cold Agglutinin

• Bedside: room temp blood in EDTA tube → ice bath 30 sec → check for clumping
• High titer ≥ 1:64 suggests M. pneumoniae
• Not specific (also viral, lymphoma, mycoplasma-related)

189.1.0.4.4 D. Culture

• Specialty labs, slow
• Not for clinical

189.1.0.4.5 Lab

• WBC normal
• ESR / CRP ↑
• ↑ LFT in some
• Hyponatremia, anemia (hemolysis)

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189.1.0.5 4️⃣ Treatment

189.1.0.5.1 A. Antibiotic Choice

Drug	Note
Azithromycin 500 mg d1 → 250 d2-5	Preferred standard; rising R Asia (50-90%)
Clarithromycin 500 bid × 7d	Same class, similar R
Doxycycline 100 bid × 7-10d	Alternative; rising R less
Levofloxacin 500-750 qd × 7-10d	Alternative; avoid kids; QTc, tendon
Moxifloxacin 400 qd × 7-10d	Alternative

189.1.0.5.2 B. Macrolide R Considerations

• Asia (especially China): 50-90% azithro R
• USA / Europe: 10-20% (rising)
• Empirical macrolide failure → switch to doxy / FQ
• Resistance testing (PCR for 23S rRNA mutations) — emerging

189.1.0.5.3 C. Severe / Extrapulmonary

• IV doxy or FQ
• Steroids in encephalitis / severe pulmonary
• IVIG / plasmapheresis for severe neurological

189.1.0.5.4 D. Duration

• Pneumonia: 7-10d
• Extrapulmonary: extended (10-14d) per syndrome

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189.1.0.6 5️⃣ M. genitalium

189.1.0.6.1 Microbiology

• Smallest free-living bacterium (~ 580 kb genome)
• No cell wall (like M. pneumoniae)

189.1.0.6.2 流行病學

• STI — recognized 1980s; PCR-detection rise 2000s+
• Prevalence ~ 2-3% general population, 4-10% STD clinics
• MSM: rectal common
• Often asymptomatic carriers

189.1.0.6.3 臨床

189.1.0.6.3.1 Male

• Non-gonococcal non-chlamydial urethritis (NGU) — significant cause
• Persistent / recurrent urethritis after doxy
• Proctitis (MSM)

189.1.0.6.3.2 Female

• Cervicitis (~ 10-30% of cervicitis)
• PID — increasing recognition; long-term sequelae (infertility, ectopic, chronic pelvic pain)
• Possibly preterm birth

189.1.0.6.4 Dx

• PCR / NAAT — only diagnostic option (no serology, no culture routine)
• Urine (male) or endocervical swab
• Test with chlamydia / gonorrhea panels increasingly

189.1.0.6.5 Resistance + Treatment

• Azithromycin R: 50-80% globally (rapid spread)
• FQ (moxifloxacin) R: 10-20%
• Pristinamycin (streptogramin) — alternative in EU
• Lefamulin — emerging (pleuromutilin, FDA-approved CABP, off-label MG)

189.1.0.6.6 Sequential Algorithm (CDC 2024)

1. Resistance-guided if available (test for 23S rRNA mutations)
2. Macrolide-sensitive: doxy 100 bid × 7d → azithromycin 1 g day 1 → 500 mg qd × 3d
3. Macrolide-resistant or unknown: doxy 100 bid × 7d → moxifloxacin 400 mg qd × 7d
4. Moxifloxacin failure: minocycline, pristinamycin
5. Test of cure 3 wk after Tx
6. Partner notification + treatment

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189.1.0.7 6️⃣ Ureaplasma + M. hominis

189.1.0.7.1 Ureaplasma urealyticum / parvum

• Female genital flora 40-80%
• NGU in male
• Neonatal: chorioamnionitis, premature, BPD
• Treatment: macrolide or doxy

189.1.0.7.2 M. hominis

• Postpartum endometritis, bacteremia
• Immunocompromise
• Tetracycline or clindamycin

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