Mycoplasma Pneumonia

Introduction

Mycoplasma pneumoniae is a unique, pleomorphic bacterium belonging to the class Mollicutes. It is a major cause of community-acquired pneumonia (CAP) in school-aged children and adolescents, often referred to as "primary atypical pneumonia" or "walking pneumonia."

• Microbiology: It is one of the smallest self-replicating organisms (150–250 nm). A key distinguishing feature is the complete absence of a cell wall, which renders it intrinsically resistant to beta-lactam antibiotics (penicillins, cephalosporins) that target cell wall synthesis. It is enclosed only by a three-layered cell membrane containing sterols.
• History: Initially identified as the "Eaton agent" in 1944 and thought to be a virus, it was later cultivated on cell-free media and identified as a bacterium.

Epidemiology

• Incidence: M. pneumoniae is endemic worldwide, responsible for up to 40% of CAP in older children and adolescents. While traditionally considered rare in children under 5 years, recent data using sensitive PCR techniques indicates it is a significant pathogen in preschool children as well.
• Cyclicity: Infections occur year-round but often peak in fall and winter. Epidemics tend to occur cyclically every 3 to 7 years.
• Transmission: Spread occurs via person-to-person transmission through respiratory droplets. The incubation period is relatively long, approximately 2 to 3 weeks. Attack rates in closed populations (schools, military barracks, families) are high.
• Carriage: Asymptomatic carriage can persist for weeks to months, even after treatment, complicating infection control.

Pathogenesis

The pathogenicity of M. pneumoniae involves three main mechanisms:

1. Cytoadherence: The organism possesses a specialized attachment organelle containing the P1 adhesin protein. It attaches firmly to neuraminic acid receptors on the ciliated respiratory epithelium. This attachment inhibits ciliary motility (ciliostasis) and leads to the destruction of the ciliated layer, causing the characteristic prolonged cough.
2. Toxin Production: M. pneumoniae produces a unique exotoxin called the Community-Acquired Respiratory Distress Syndrome (CARDS) toxin. This toxin has ADP-ribosylating and vacuolating activity, causing direct damage to the respiratory epithelium, inflammation, and airway hyperreactivity (wheezing). It also generates hydrogen peroxide and superoxide radicals, causing oxidative stress to host cells.
3. Immune-mediated Injury: Much of the disease pathology, especially extrapulmonary manifestations, is believed to be immune-mediated. The infection triggers a robust inflammatory response (cytokine storm) and the production of autoantibodies (e.g., cold agglutinins) due to molecular mimicry between bacterial glycolipids and host tissues.

Clinical Manifestations

The clinical spectrum ranges from asymptomatic infection to severe pneumonitis with extrapulmonary complications.

1. Respiratory Manifestations

• Onset: Typically gradual and insidious with headache, malaise, and fever, followed by the onset of respiratory symptoms.
• Cough: The hallmark symptom. It is initially non-productive but becomes intractable and paroxysmal later. It may persist for 3–4 weeks.
• Pharyngitis: Sore throat is common; pharyngitis may be present but is usually non-exudative.
• Pneumonia ("Walking Pneumonia"):
  • Clinically, the child often appears less ill than the chest radiograph suggests.
  • Physical examination may be unrevealing or show only fine crepitations or wheezing. Signs of frank consolidation are less common than in typical bacterial pneumonia.
• Wheezing: M. pneumoniae is a well-recognized trigger for acute wheezing episodes and asthma exacerbations in children.

2. Extrapulmonary Manifestations

These occur in up to 25% of cases and can affect almost any organ system.

• Dermatologic: Maculopapular rashes are common. Severe forms include Stevens-Johnson Syndrome (SJS) and a distinct entity termed Mycoplasma-Induced Rash and Mucositis (MIRM). MIRM typically presents with prominent mucositis (oral, ocular, urogenital) and variable skin lesions, often with a milder course than drug-induced SJS. Erythema nodosum and urticaria are also seen.
• Neurologic: Encephalitis, aseptic meningitis, cerebellar ataxia, Transverse Myelitis, and Guillain-Barré syndrome. CNS involvement can be severe and result in permanent sequelae.
• Hematologic: Autoimmune hemolytic anemia mediated by Cold Agglutinins (IgM antibodies against the I antigen on RBCs). Thrombocytopenia and hypercoagulability (risk of thrombus/embolism) may occur.
• Others: Myocarditis/pericarditis, hepatitis, pancreatitis, arthritis, and nephritis.

Diagnosis

Diagnosis is challenging as clinical features overlap with viral and other bacterial pneumonias.

1. Nonspecific Labs: Leukocyte count is usually normal or slightly elevated. ESR and CRP are elevated.
2. Radiology: Chest X-ray findings are variable. Classically shows bilateral, diffuse, reticular or interstitial infiltrates (peribronchial cuffing). Unilateral lobar consolidation and small pleural effusions (up to 20%) can also occur.
3. Specific Microbiological Tests:
   • PCR (Polymerase Chain Reaction): The diagnostic test of choice. It is highly sensitive and rapid. It detects DNA in nasopharyngeal aspirates or throat swabs. It does not distinguish between active infection and carriage.
   • Serology:
     • IgM ELISA: Commonly used. IgM appears 7–9 days after infection and persists for months. It may be negative in the first week of illness or in reinfections.
     • Paired Sera: A four-fold rise in IgG titers between acute and convalescent sera (2–4 weeks apart) is the gold standard for retrospective diagnosis.
   • Cold Agglutinins: Bedside test or titer >1:32 or 1:64. Present in ~50% of cases. It is nonspecific (also seen in EBV, Adenovirus) but supports the diagnosis in the right clinical context.
   • Culture: Requires specialized media (SP4), slow-growing (1–3 weeks), and insensitive. Not useful for routine clinical management.

Treatment

Since M. pneumoniae lacks a cell wall, it is intrinsically resistant to beta-lactams (penicillins, cephalosporins).

1. Antimicrobial Therapy

Empiric treatment is often initiated based on clinical suspicion (school-aged child, gradual onset, interstitial pneumonia).

• Macrolides (First-line):
  • Azithromycin: 10 mg/kg on Day 1, followed by 5 mg/kg/day for 4 days (Total 5 days). Preferred for ease of dosing and tolerability.
  • Clarithromycin: 15 mg/kg/day divided BD for 10 days.
  • Erythromycin: 40–50 mg/kg/day divided QID for 10–14 days (less preferred due to GI side effects).
• Tetracyclines: Doxycycline (2–4 mg/kg/day) is highly effective and is the drug of choice for older children (>8 years). It is also used in macrolide-resistant cases.
• Fluoroquinolones: Levofloxacin or Moxifloxacin are alternatives for skeletal maturity (adolescents) or severe macrolide-resistant infections, used with caution in young children.

2. Macrolide Resistance

Macrolide-resistant M. pneumoniae (MRMP) is a growing concern, particularly in Asia (rates >90% in some areas) but also in Europe and North America. Resistance is due to mutations in the 23S rRNA gene. Patients with MRMP may have prolonged fever and persistent symptoms. In such cases, switching to Doxycycline or a Fluoroquinolone is recommended.

3. Adjunctive Therapy

• Corticosteroids: Systemic steroids (e.g., Prednisolone, Methylprednisolone) are often used as adjunctive therapy in severe pneumonia (e.g., refractory to antibiotics), SJS/MIRM, and severe CNS complications to dampen the immune-mediated damage.
• Supportive Care: Hydration, antipyretics, and oxygen supplementation if hypoxic.

Prognosis

The prognosis is generally excellent. Most infections are self-limiting. Recovery from "walking pneumonia" is the rule, although cough may linger for weeks. Severe courses are more common in children with sickle cell disease (Acute Chest Syndrome), Down syndrome, or immunodeficiency.