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Infections Due to Mycoplasmas

Chapter 193 | Part 5: Infectious Diseases

KEY CLINICAL POINTS

  • Mycoplasma pneumoniae is a major cause of community-acquired atypical pneumonia, often presenting with nonproductive cough, fever, and radiographic findings of peribronchial pneumonia.
  • Diagnosis requires combination of PCR (respiratory tract secretions) and serology (paired acute/convalescent-phase IgM/IgG titers) due to poor sensitivity of individual tests.
  • First-line treatment includes macrolides (azithromycin, clarithromycin), doxycycline, or fluoroquinolones (levofloxacin, moxifloxacin), with resistance rates varying by region.
  • Extrapulmonary manifestations (neurologic, dermatologic, hematologic) occur in 5–7% of cases and may require prolonged therapy or specialist consultation.
  • Chronic Q fever (C. burnetii) requires doxycycline ± hydroxychloroquine for 18–24 months, with monitoring via PCR, serology, and imaging.

1. DEFINITION & OVERVIEW

Mycoplasmas are prokaryotes (class Mollicutes) lacking a cell wall, with sizes (150–350 nm) intermediate between viruses and bacteria. They are obligate parasites requiring host-derived nutrients. Mycoplasma pneumoniae, M. hominis, M. genitalium, U. urealyticum, and U. parvum are human pathogens causing respiratory, genitourinary, and extrapulmonary infections.

Table 193-1: Diagnostic Tests for Respiratory Mycoplasma pneumoniae Infection

TEST SENSITIVITY, % SPECIFICITY, %
Respiratory culture £60 100
Respiratory PCR 65–90 90–100
Serologic studiesb 55–100 55–100

Table 193-2: Antimicrobial Agents of Choice for Mycoplasma Infections

ORGANISM(S) DRUGS
Mycoplasma pneumoniae Azithromycin, clarithromycin, erythromycin, doxycycline, levofloxacin, moxifloxacin, gemifloxacin (not ciprofloxacin or ofloxacin)
Ureaplasma urealyticum, U. parvum Azithromycin, clarithromycin, erythromycin, doxycycline
Mycoplasma hominis Doxycycline, clindamycin
Mycoplasma genitalium Azithromycin, moxifloxacin, doxycycline

1.1 Taxonomy and Pathogenesis

Mycoplasmas lack cell wall components (lipopolysaccharide, peptidoglycan), rendering them resistant to β -lactam antibiotics. They adhere to respiratory epithelium via adhesins and cause injury via hydrogen peroxide and ADP-ribosylating cytotoxins. Lipoproteins activate TLR2 on macrophages, triggering innate immunity.

1.2 Clinical Spectrum

M. pneumoniae causes atypical pneumonia, upper respiratory infections, and extrapulmonary manifestations (neurologic, dermatologic, hematologic). Urogenital mycoplasmas (M. hominis, M. genitalium, U. urealyticum) are associated with genitourinary tract infections and neonatal disease.

2. EPIDEMIOLOGY

M. pneumoniae infection occurs worldwide, with incidence up to 20 times higher than pneumonia caused by this organism. Outbreaks are common in institutional settings (military, schools, camps). In adults, M. pneumoniae is the most frequently detected 'atypical' pathogen in community-acquired pneumonia (22.7% prevalence vs. 11.7% for C. pneumoniae).

2.1 Risk Factors

Close contact in crowded environments, immunocompromised status, and asymptomatic carriage in children. Urogenital mycoplasmas are transmitted sexually or vertically, with risk increasing with number of sexual partners.

2.2 Demographics

M. pneumoniae primarily affects children and young adults (ages 5–35). Urogenital mycoplasmas are more common in sexually active adults, with M. genitalium increasingly associated with sexually transmitted infections.

3. ETIOLOGY & PATHOPHYSIOLOGY

Mycoplasmas lack cell wall synthesis pathways, making them resistant to β -lactams. They adhere to respiratory epithelium via adhesins and produce hydrogen peroxide and cytotoxins. Lipoproteins activate TLR2, triggering innate immunity. Chronic infection may lead to dissemination (arthritis, meningitis) in immunocompromised hosts.

3.1 Virulence Factors

Adhesins (terminal organelles), hydrogen peroxide, ADP-ribosylating cytotoxin (similar to pertussis toxin), and lipoproteins (TLR2 agonists).

3.2 Immune Response

Innate immunity (TLR2-mediated) provides primary defense. Humoral immunity prevents dissemination, while cellular immunity may exacerbate immunopathology.

4. CLINICAL FEATURES

Acute infections present with pharyngitis, cough, fever, and radiographic findings of peribronchial pneumonia. Extrapulmonary manifestations include neurologic (meningitis, encephalitis), dermatologic (exanthems), and hematologic (cold agglutinins) symptoms. Chronic Q fever (C. burnetii) may present with valvular heart disease or vascular infections.

4.1 Respiratory Infections

Nonproductive cough, fever, malaise, and radiographic findings of interstitial infiltration. Pneumonia occurs in 3–13% of cases, with gradual onset.

4.2 Extrapulmonary Manifestations

Neurologic (Guillain-Barré syndrome, encephalitis), dermatologic (erythematous rashes, Stevens-Johnson syndrome), and hematologic (hemolytic anemia) complications occur in 5–7% of cases.

5. DIFFERENTIAL DIAGNOSIS

Differentiate M. pneumoniae pneumonia from C. pneumoniae (4.3% prevalence) and Legionella (2.8% prevalence) in community-acquired pneumonia. Consider viral respiratory infections, other bacterial pneumonias, and atypical pathogens in immunocompromised hosts.

5.1 Atypical Pneumonia

M. pneumoniae vs. C. pneumoniae: M. pneumoniae more common in children, with more frequent extrapulmonary manifestations. Legionella presents with more severe symptoms and higher mortality.

5.2 Urogenital Infections

Distinguish from other sexually transmitted infections (e.g., chlamydia, gonorrhea) using nucleic acid amplification tests (NAATs).

6. INVESTIGATIONS & DIAGNOSIS

Diagnosis requires PCR (respiratory secretions) and serology (paired IgM/IgG titers). Serologic testing is less sensitive (55–100%) and may require 2 weeks for antibody development. PCR is preferred for rapid detection.

6.1 Diagnostic Tests

PCR (respiratory tract secretions), serology (acute/convalescent-phase titers), and culture (special media). Cold agglutinin titers are no longer recommended.

6.2 Imaging

Chest radiography shows peribronchial pneumonia, interstitial infiltration, or segmental consolidation. Pleural effusions may be detected on lateral decubitus views.

7. MANAGEMENT & TREATMENT

Acute M. pneumoniae pneumonia is treated with macrolides (azithromycin 500 mg/day), doxycycline (100 mg BID), or fluoroquinolones. Chronic Q fever requires doxycycline ± hydroxychloroquine for 18–24 months. Avoid β -lactams due to resistance.

7.1 Acute Infections

First-line: azithromycin (500 mg/day), doxycycline (100 mg BID for 7–14 days), or fluoroquinolones. Avoid ciprofloxacin/ofloxacin due to high MICs.

7.2 Chronic Q Fever

Doxycycline 100 mg BID + hydroxychloroquine 200 mg TID for 18–24 months. Monitor with PCR, serology, and imaging. Surgical intervention may be required for vascular infections.

7.3 Special Populations

Pregnancy: Avoid tetracyclines. Neonates: Use erythromycin or azithromycin. Immunocompromised: Consider prolonged therapy and specialist consultation.

8. PROGNOSIS & COMPLICATIONS

Most patients recover within 2–3 weeks. Complications include prolonged fever, reactive airway disease, and rare critical illness. Chronic Q fever may lead to valvular heart disease or vascular infections requiring surgery.

8.1 Mortality

Low in acute infections (<1%), but higher in chronic Q fever (up to 50% without treatment).

8.2 Long-term Effects

Recurrent wheezing, reactive airway disease, and chronic fatigue syndrome may occur. Chronic infection may exacerbate asthma.

9. SPECIAL CONSIDERATIONS

Pregnancy: Avoid tetracyclines. Neonates: Use erythromycin or azithromycin. Immunocompromised patients require prolonged therapy. Urogenital mycoplasmas may require partner notification and contact tracing.

9.1 Antimicrobial Resistance

Macrolide resistance (10–22% in U.S.) necessitates alternative therapies (doxycycline, fluoroquinolones). Resistance testing is recommended in endemic areas.

9.2 Monitoring

Follow-up with PCR, serology, and imaging for 2–5 years post-treatment. Monitor for relapse or extrapulmonary complications.

10. KEY POINTS & CLINICAL PEARLS

  • Use PCR and serology for diagnosis of M. pneumoniae pneumonia.
  • Avoid β -lactams for mycoplasma infections.
  • Chronic Q fever requires prolonged doxycycline ± hydroxychloroquine.
  • Monitor for extrapulmonary manifestations in 5–7% of cases.
  • Macrolide resistance is increasing; consider alternative therapies in endemic regions.