Pneumonia%20-%20community-acquired%20(pediatric) Treatment

• Therapy is usually empiric and is based on age-specific causes of community-acquired pneumonia (CAP), disease severity and local resistance patterns of predominant pathogens
  • If blood or respiratory tract specimen culture has identified the causative agent, a safe, narrow-spectrum and effective therapy should be given
• Empiric treatment may be given for 7-10 days  
• Oral route is safe and effective for outpatients with bacterial pathogen that most commonly cause lower respiratory tract infections 
• Parenteral route is preferred in patients with severe disease or are unable to tolerate oral drug intake (eg vomiting) to ensure adequate blood and tissue concentrations
• Antimicrobials are not warranted, may cause drug toxicity, and may facilitate development of antimicrobial resistance in young patients with clinical features suggestive of upper and lower respiratory tract viral infections
• Empiric therapy for some children require both antimicrobial and antiviral agents

Indications for Hospital Admission

• Children and infants who have moderate to severe community-acquired pneumonia (CAP), as defined by the presence of respiratory distress (eg tachypnea, dyspnea, suprasternal/intercostal/subcostal retractions, grunting, nasal flaring, apnea, altered mental status, pulse oximetry measurement <90% on room air)
• Patients <3-6 months old with possible bacterial CAP
• Children and infants with suspected or documented CAP caused by an agent with increased virulence [eg community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)]
• Patients whom there is concern about careful observation at home or who may be unable to comply with medications or cannot be followed-up
• Presence of significant comorbid conditions
• Presence of dehydration, vomiting, inability to take oral medications
• Patients with unsuccessful outpatient oral antimicrobial treatment, and those with new and progressive respiratory distress

Indications for Intensive Care Unit (ICU) Admission¹

• Patient with ≥1 major or ≥2 minor criteria should be transferred to an ICU or a unit with continuous cardiorespiratory monitoring
  • Major criteria: Invasive mechanical ventilation, fluid refractory shock, acute need for noninvasive positive pressure ventilation (NIPPV), hypoxemia requiring fraction of inspired oxygen (FiO₂) > inspired concentration
  • Minor criteria: Tachypnea, apnea, retractions, dyspnea, nasal flaring, grunting, arterial oxygen pressure (PaO₂)/FiO₂ <250, multilobar infiltrates, Pediatric Early Warning Score (PEWS) >6, altered mental status, hypotension, presence of effusion, comorbid conditions, unexplained metabolic acidosis
• British Thoracic Society indications for referral to a pediatric ICU² include respiratory failure needing assisted ventilation and pneumonia with septicemia 
  • Clinical features include presence of shock, raised RR and HR together with severe respiratory distress and exhaustion with or without increased pCO₂, slow irregular breathing or recurrent apnea, and inability to maintain oxygen saturations >92% with FiO₂ 60%

¹Reference: Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011 Oct;53(7):e5.
²Reference: Harris M, Clark J, Coote N, et al, on behalf of the British Thoracic Society Standards of Care Committee. British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011. Thorax. 2011 Oct;66(2):ii16.

Penicillins

Amoxicillin

• 1st-line agent at any age if S pneumoniae is the likely pathogen
  • May also be given to patients with pneumonia caused by β-lactamase-negative strains (eg H influenza)
• Has broader spectrum of activity, better oral pharmacokinetics (better absorption from gastrointestinal tract) and tolerability (less frequent dosing and better taste) as compared with Penicillin
• Preferred step-down oral therapy for hospitalized patients initially treated with Ampicillin for S pneumoniae or β-lactamase negative H influenza infection
  • May also be given as step-down therapy in patients initially treated with broad-spectrum antimicrobials in whom no cultures are obtained or were only obtained after starting antibiotics

Ampicillin or Penicillin G

• Recommended for hospitalized, fully immunized infants and school-aged children when local epidemiologic data shows lack of resistance for invasive S pneumoniae
  • Also considered as 1st-line option in hospitalized patients with group A Streptococcus infections
• Ampicillin is the preferred agent for infections caused by β-lactamase negative H influenza
• Penicillin G represents the most narrow-spectrum and effective antibiotic for pneumococcal infections but requires a more frequent dosing interval
• Also active against S pyogenes that causes severe necrotizing pneumonia

Antistaphylococcal Penicillin

• Eg Oxacillin [intravenous (IV)], Nafcillin (IV)
• Used for patients admitted in the hospital for methicillin-susceptible S aureus (MSSA) infection

Penicillin with Beta-lactamase Inhibitor

• Eg Amoxicillin/clavulanic acid, Ampicillin/sulbactam
• Amoxicillin/clavulanic acid is the preferred oral step-down therapy for infections caused by β-lactamase producing H influenza
  • May also be given through intravenous route in patients with severe CAP which has been shown to be as effective as Ceftriaxone for strains with Amoxicillin minimum inhibitory concentration (MIC) of up to 2 mcg/mL

Macrolides

• Eg Azithromycin, Clarithromycin, Erythromycin, Roxithromycin
• 1st-line agent in school-aged children and adolescents with atypical pneumonia eg M pneumoniae or C pneumoniae
• Recommended 1st-line treatment for Penicillin-allergic pediatric patients 
• May be added at any age if without improvement with 1st-line therapy after 48 hours of treatment
• Not advised as empiric therapy for pneumococcal CAP because currently isolated strains of S pneumoniae have shown significant resistance against macrolides
• Azithromycin is the preferred agent for M pneumoniae, C pneumoniae or C trachomatis infections

Cephalosporins

• 1st generation drugs (eg Cefazolin IV) may be used for inpatients with MSSA infection
• 2nd generation (eg Cefuroxime) or 3rd generation (eg Ceftriaxone, Cefotaxime) agents are active against both β-lactamase-negative and -positive strains
  • Parenteral Ceftriaxone or Cefotaxime are recommended in hospitalized infants and children that are incompletely immunized, in places where local epidemiology shows lack of resistance for invasive S pneumoniae, or in infants and children with life-threatening infection (eg empyema)
    • Also the preferred agent for infections caused by β-lactamase producing H influenza
  • IV Ceftriaxone is the preferred agent for penicillin-resistant S pneumoniae
  • Intramuscular (IM) injection of Ceftriaxone may be given once a day as an outpatient therapy
  • Oral Cefpodoxime, Cefprozil or Cefuroxime may be considered as alternative agents in patients with allergies to Amoxicillin
• Also active against S pyogenes causing severe necrotizing pneumonia

Quinolones

• Eg Levofloxacin
• May be used as an alternative to patients with history of severe allergy to Amoxicillin
• Have comparable effect as with macrolides and tetracyclines in treating patients with M pneumoniae infection
• Preferred oral step-down therapy in patients infected with Penicillin-resistant S pneumoniae

Tetracyclines

• Eg Doxycycline
• For children >8 years with macrolide-resistant M pneumoniae

Other Antibiotics

• Vancomycin is the 1st-line agent for infections caused by community-acquired methicillin-resistant S aureus (CA-MRSA)
• Linezolid is the preferred oral step-down therapy and an alternative parenteral agent for CA-MRSA infections
  
  • Useful especially in patients with pre-existing renal impairment or is receiving other nephrotoxic drugs
  • May be given to children with severe allergy to β-lactam drugs who can not tolerate Vancomycin or Clindamycin but should be used with caution since it has relatively high adverse effect profile
• IV Clindamycin may be used as an alternative agent in patients with infections caused by susceptible MSSA or MRSA but is not recommended in patients with empyema

Influenza Antiviral Therapy

• Should be administered as soon as possible to patient with moderate to severe CAP caused by influenza virus infection, specifically to those with clinically worsening CAP during outpatient visit
• Should not wait for the results of confirmation test since early treatment has been shown to provide maximal advantage
• May still be of benefit when used after 48 hours of symptomatic infection in patients with more severe disease

Combination Therapy

• Macrolide plus β-lactam antibiotic may be given to inpatients with probable M pneumoniae and C pneumoniae
• Vancomycin or Clindamycin should be added to β-lactam antibiotic in patients highly considered to have S aureus infection, depending on local susceptibility data
  • Clindamycin plus β-lactam is recommended in children with toxic-like syndrome

Duration of Therapy

• 10-day treatment course has been well studied but shorter period may be similarly effective for mild CAP
• CA-MRSA infections may require longer treatment duration than those caused by S pneumoniae