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Antibiotics for pediatric outpatients with communityacquired pneumonia 

Updated 2012 Dec 31 10:14:00 AM: no randomized trials identified to guide antibiotic selection for community-acquired pneumonia in patients with sickle cell disease (Cochrane Database Syst Rev 2012 Oct 17) view updateShow more updates

Related Summaries:     

Pneumonia (list of topics) Pneumonia in children Antibiotics for pediatric inpatients with community-acquired pneumonia Antibiotics for adult outpatients with community-acquired pneumonia Antibiotics for adult inpatients with community-acquired pneumonia

Overview:  

various antibiotics may have similar efficacy for pneumonia in children (level 2 [mid-level] evidence) guideline recommendations regarding the need for antibiotic therapy differ between organizations o Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) recommend that antimicrobial therapy not routinely required for preschool-aged children because viral pathogens are responsible in most cases (PIDS/IDSA Strong recommendation, Highquality evidence) o British Thoracic Society (BTS) recommends all children with clear clinical diagnosis of pneumonia should receive antibiotics (BTS Grade C) for children < 5 years old with nonsevere pneumonia o for presumed bacterial pneumonia -- oral amoxicillin usually recommended as first-line empiric treatment o amoxicillin for 3 days may have limited efficacy for children < 5 years old with nonsevere pneumonia in developing countries (level 2 [mid-level] evidence) o amoxicillin and co-trimoxazole appear to have similar efficacy in children aged 2-59 months treated as outpatients (level 2 [mid-level] evidence) o 3-day course of antibiotics is as effective as 5-day course for children aged 2-59 months with nonsevere pneumonia (level 1 [likely reliable] evidence) o double-dose amoxicillin appears no more effective than standard dose in children < 5 years old with nonsevere pneumonia (level 2 [mid-level] evidence) o specific guidelines for dosing vary  World Health Organization (WHO) recommendations for children aged 2-59 months


amoxicillin 50 mg/kg/day orally in 2 divided doses for 3 days (5 days in areas with high HIV prevalence)  co-trimoxazole as trimethoprim 8 mg/kg/day orally in 2 divided doses for 3 days may be acceptable first-line alternative in areas with clear evidence that local resistance is infrequent  PIDS and IDSA recommendations for children aged 3 months to < 5 years  for presumed bacterial pneumonia amoxicillin 90 mg/kg/day in 2 divided doses orally (PIDS/IDSA Strong recommendation, Moderate-quality evidence), alternative is amoxicillin-clavulanate orally  macrolides recommended for presumed atypical pneumonia (not as common in this age group)  BTS recommends  oral amoxicillin as first-line treatment; alternatives are amoxicillin-clavulanate, cefaclor, and macrolides (BTS Grade B)  macrolide antibiotics if no response to first-line empiric therapy, if Mycoplasma or Chlamydia suspected, or if very severe disease (BTS Grade D)  amoxicillin-clavulanate for influenza-associated pneumonia (BTS Grade D)  Cincinnati Children's Hospital Medical Center (CCHMC) recommendations for children aged 60 days to 5 years  high-dose amoxicillin (80-90 mg/kg/day) for 7-10 days when bacterial cause likely (CCHMC Evidence A/S/E)  macrolide may be added to amoxicillin therapy if Mycoplasma pneumoniae or Chlamydia pneumoniae suspected at 24-48 hour follow-up (CCHMC Evidence A/E)  if unable to tolerate liquids, consider single initial dose of ceftriaxone before starting oral antibiotics (CCHMC Evidence C/D/E) for children ≥ 5 years old o recommendations for first-line therapy vary between amoxicillin and macrolides o macrolide antibiotics (erythromycin, clarithromycin, and azithromycin) appear to have similar efficacy for community-acquired pneumonia (level 2 [mid-level] evidence) o PIDS and IDSA recommends  for presumed bacterial pneumonia - amoxicillin 90 mg/kg/day in 2 divided doses (maximum 4 g/day) (PIDS/IDSA Strong recommendation, Moderate-quality evidence)  for presumed atypical pneumonia - macrolide antibiotic (PIDS/IDSA Weak recommendation, Moderate-quality evidence)  macrolide can be added to beta-lactam antibiotic if no evidence that distinguishes bacterial and atypical pneumonia


o

 

Alberta Clinical Practice Guidelines Working Group for Antibiotics recommends the following for children aged 5-16 years  azithromycin 10 mg/kg/day for 1 day (maximum 500 mg/day), then 5 mg/kg/day orally (maximum 250 mg/day) for 4 days  clarithromycin 15 mg/kg/day in 2 divided doses (maximum 1,000 mg/day) for 7-10 days  erythromycin 40 mg/kg/day in 4 divided doses (maximum 2,000 mg/day) for 7-10 days  in children > 8 years old - doxycycline 4 mg/kg/day in 2 divided doses (maximum 200 mg/day) for 7-10 days o BTS recommends  oral amoxicillin as first-line treatment; alternatives are amoxicillinclavulanate, cefaclor, and macrolides (BTS Grade B)  macrolide antibiotics if no response to first-line empiric therapy, if Mycoplasma or Chlamydia suspected, or if very severe disease (BTS Grade D)  amoxicillin-clavulanate for influenza-associated pneumonia (BTS Grade D) o CCHMC recommends macrolide antibiotic for 7-10 days, but 5-day course of azithromycin may be used (CCHMC Evidence A/S/E) for severe pneumonia (WHO definition is cough or difficulty breathing plus lower chest wall indrawing, nasal flaring grunting, or age < 2 months and no signs of very severe pneumonia) o WHO recommends trial of rapid-acting inhaled bronchodilator in children with wheeze and fast breathing and/or lower chest indrawing before diagnosing pneumonia and prescribing antibiotics o WHO recommends (if injection not available) to increase amoxicillin to 45 mg/kg/dose orally twice daily for 5 days o home-based treatment with high-dose oral amoxicillin appears at least as effective as hospitalization with parenteral ampicillin for children with severe pneumonia (level 2 [mid-level] evidence) o CCHMC recommends considering combination of macrolide and betalactam agent (such as high-dose amoxicillin or ceftriaxone) for more severe pneumonia o BTS recommends IV amoxicillin, amoxicillin-clavulanate, cefuroxime, and cefotaxime or ceftriaxone in children with signs of septicemia or complicated pneumonia or if unable to absorb oral antibiotics (BTS Grade D) o for very severe pneumonia (WHO definition is cough or difficulty breathing plus central cyanosis, inability to maintain hydration, seizure, altered mental status, or severe respiratory distress) WHO recommends gentamicin 7.5 mg/kg intramuscularly plus ampicillin 50 mg/kg intramuscularly prior to referral to higher-level care none of the guidelines provide specific recommendations regarding antibiotic selection in children with recent antibiotic exposure for treatment failure (WHO recommendations for outpatients aged 2-59 months) o on amoxicillin


o o o

switch to high-dose amoxicillin-clavulanate (amoxicillin 80-90 mg/kg/day) for 5 days  if > 3 years old consider adding macrolide or azalide antibiotic to existing treatment for 5-7 days (for example, erythromycin 50 mg/kg/day in 4 divided doses for 7 days) on co-trimoxazole switch to amoxicillin 50 mg/kg/day for 5 days in children with HIV infection refer to hospital for broad-spectrum parenteral antibiotics if treatment with first-line drugs fails in children living in areas where higher-level care not available use broaderspectrum coverage such as ceftriaxone, penicillin plus gentamicin, or chloramphenicol

Recommendations World Health Organization (WHO) guidelines for children aged 2-59 months: Definitions: 

WHO severity classifications o very severe pneumonia defined as cough or difficulty breathing plus any of  central cyanosis  inability to breastfeed, drink, or vomiting everything  convulsions, lethargy, or unconsciousness  severe respiratory distress o severe pneumonia defined as cough or difficulty breathing plus  any of  lower chest wall indrawing  nasal flaring  grunting (in young infants)  age < 2 months  no signs of very severe pneumonia o nonsevere pneumonia defined as  age ≥ 2 months  cough or difficulty breathing accompanied by tachypnea (respiratory rate ≥ 50 breaths/minute in infant aged 2-11 months, ≥ 40 breaths/minute in child aged 12-59 months)  no signs of severe or very severe pneumonia WHO definition of treatment failure includes o development of signs of severe or very severe pneumonia o persistently raised respiratory rate at 72 hours (48 hours in area with high HIV prevalence)

Treatment recommendations: 

nonsevere pneumonia


o

first-line treatment is amoxicillin 50 mg/kg/day in 2 divided doses for 3 days (5 days in areas with high HIV prevalence) o in children with persistently increased respiratory rate after 72 hours on amoxicillin (48 hours in areas with high HIV prevalence) but without indications for inpatient treatment (that is, signs of severe or very severe pneumonia)  switch to high-dose amoxicillin-clavulanate (amoxicillin 80-90 mg/kg/day) for 5 days  if > 3 years old consider adding macrolide or azalide antibiotic to existing treatment for 5-7 days (for example, erythromycin 50 mg/kg/day in 4 divided doses for 7 days) o co-trimoxazole (trimethoprim 8 mg/kg in 2 divided doses) for 3 days may be acceptable alternative as first-line treatment in areas with clear evidence that local resistance is infrequent o if treatment failure on co-trimoxazole, switch to amoxicillin 50 mg/kg/day for 5 days o special considerations  children with HIV infection or clinical suspicion of HIV infection  amoxicillin recommended whether or not patient is taking cotrimoxazole for Pneumocystis carinii pneumonia prophylaxis  refer to hospital for broad-spectrum parenteral antibiotics if treatment with first-line drugs fails  children living in malaria-endemic area  if malaria cannot be excluded, use first-line therapies for both nonsevere pneumonia and malaria  use caution if erythromycin given as second-line agent due to increased risk of arrhythmia in patients taking mefloquine or halofantrine for malaria  children with treatment failure in areas where higher-level care not available should receive broader-spectrum coverage such as ceftriaxone, penicillin plus gentamicin, or chloramphenicol o Reference - Lancet Infect Dis 2009 Mar;9(3):185 severe or very severe pneumonia in children with limited access to, or prior to referral for, inpatient treatment o trial of rapid-acting inhaled bronchodilator indicated in children with wheeze and fast breathing and/or lower chest indrawing before diagnosing pneumonia and prescribing antibiotics  recommendation based on concern of overdiagnosis of pneumonia with use of World Health Organization (WHO) guidelines  in prospective study in children aged 1-59 months wheeze and fast breathing and/or lower chest indrawing in Pakistan  of 1,004 with WHO defined non-severe pneumonia, 621 (62%) responded to up to 3 cycles of inhaled bronchodilator and could be treated without antibiotics; 93 (15%) responders had subsequent deterioration


o

o

o

of 618 with WHO defined severe pneumonia, 166 (27%) responded to bronchodilator; 63 (38%) responders had subsequent deterioration  Reference - Arch Dis Child 2004 Nov;89(11):1049 full-text  in similar study in Thailand  of 256 with non-severe pneumonia, 217 (85%) responded to bronchodilator; 14 (6%) responders had subsequent deterioration  of 265 with severe pneumonia, 189 (71%) responded to bronchodilator; 24 (13%) responders had subsequent deterioration children living in setting with difficult access to higher-level care and injection not available should receive amoxicillin 45 mg/kg/dose orally twice daily for 5 days very severe pneumonia in children aged 2-59 months can be treated with gentamicin 7.5 mg/kg intramuscularly and ampicillin 50 mg/kg intramuscularly prior to referral to higher-level care Reference - WHO technical updates of Integrated Management of Childhood Illness (IMCI) guidelines (WHO 2005 PDF)

Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) recommendations: 

antibacterial therapy not necessary for children with positive test for influenza virus in absence of clinical, laboratory, or radiographic findings that suggests bacterial coinfection in the outpatient or inpatient setting (PIDS/IDSA Strong recommendation, High-quality evidence) empiric outpatient therapy o preschool children (aged 3 months to < 5 years)  antimicrobial therapy not routinely required because viral pathogens are responsible for most clinical disease (PIDS/IDSA Strong recommendation, High-quality evidence)  for presumed bacterial pneumonia  amoxicillin 90 mg/kg/day in 2 daily doses orally is first-line therapy for previously healthy and appropriately immunized children < 5 years old with mild-to-moderate communityacquired pneumonia (PIDS/IDSA Strong recommendation, Moderate-quality evidence)  amoxicillin provides appropriate coverage for Streptococcus pneumoniae which is most prominent invasive bacterial pathogen  oral amoxicillin-clavulanate (amoxicillin component 90 mg/kg/day in 2 doses) is an alternative  for presumed atypical pneumonia (but less common in preschool children)  macrolides are treatment of choice (PIDS/IDSA Weak recommendation, Moderate-quality evidence)


o

azithromycin 10 mg/kg on day 1, then 5 mg/kg once daily on days 2–5  laboratory testing for Mycoplasma pneumoniae should be performed if available in a clinically relevant time frame  alternatives  clarithromycin 15 mg/kg/day divided in 2 doses orally for 7-14 days  erythromycin 40 mg/kg/day divided in 4 doses orally  for presumed influenza pneumonia  oseltamivir recommended as soon as possible (PIDS/IDSA Weak recommendation, Moderate-quality evidence)  see Influenza in children school-aged children and adolescents (≥ 5 years old)  S. pneumoniae is most prominent invasive bacterial pathogen but consider atypical bacterial pathogens (such as M. pneumoniae) and less common lower respiratory tract bacterial pathogens in management decisions  for presumed bacterial pneumonia  amoxicillin 90 mg/kg/day divided in 2 doses orally (maximum 4 g/day) is first-line therapy for previously healthy and appropriately immunized children > 5 years old with mild-to-moderate community-acquired pneumonia due to S. pneumoniae (PIDS/IDSA Strong recommendation, Moderate-quality evidence)  macrolide can be added to beta-lactam antibiotic if no clinical, laboratory, or radiographic evidence that distinguishes bacterial from atypical community-acquired pneumonia  alternative - oral amoxicillin-clavulanate (amoxicillin component 90 mg/kg/day divided in 2 doses [maximum 4 g/day])  for presumed atypical pneumonia  macrolides are treatment of choice (PIDS/IDSA Weak recommendation, Moderate-quality evidence)  azithromycin 10 mg/kg on day 1, then 5 mg/kg once daily on days 2–5 (maximum 500 mg on day 1, then 250 mg on days 2–5)  laboratory testing for M. pneumoniae should be performed if available in a clinically relevant time frame  alternatives  clarithromycin 15 mg/kg/day divided in 2 doses (maximum 1 g/day)  erythromycin 40 mg/kg/day divided in 4 doses orally  doxycycline for children > 7 years old  for presumed influenza pneumonia


oseltamivir (all ages) or zanamivir (for children > 7 years old) recommended as soon as possible (PIDS/IDSA Weak recommendation, Moderate-quality evidence)  see Influenza in children o for allergy to amoxicillin  alternatives for children with history of possible nonserious allergic reaction to amoxicillin include  amoxicillin trial under medical supervision  trial of oral cephalosporin with antipneumococcal activity (such as cefpodoxime, cefprozil, or cefuroxime) under medical supervision  linezolid  clindamycin (if susceptible organism)  macrolide (if susceptible organism)  alternatives for children with more serious allergies  respiratory fluoroquinolone, such as levofloxacin  linezolid  macrolide (if susceptible organism)  clindamycin (if susceptible organism) parenteral outpatient therapy o conversion to oral outpatient step-down therapy preferred over parenteral outpatient therapy when possible (PIDS/IDSA Strong recommendation, Low-quality evidence) o offer outpatient parenteral antibiotic to children no longer requiring skilled nursing care in acute care facility but with need for ongoing parenteral therapy (PIDS/IDSA Weak recommendation, Moderate-quality evidence) o offer outpatient parenteral antibiotic therapy through skilled pediatric home nursing program or through daily intramuscular injections at appropriate pediatric outpatient facility (PIDS/IDSA Weak recommendation, Lowquality evidence) antibiotic selection for specific pathogens in children > 3 months old Pathogen-directed Antibiotics:

Pathogen

Preferred Parenteral Therapy

Alternative Parenteral Therapy o

o

Streptococcus pneumoniae with MICs for penicillin ≤ 2.0 mcg/mL

o

Ampicillin 150–200 mg/kg/day divided every 6 hours IV penicillin 200,000–250,000 units/kg/day divided every 4–6 hours

o

Ceftriaxone 50– 100 mg/kg/day in 1 or 2 divided doses (preferred for parenteral outpatient therapy) Cefotaxime 150 mg/kg/day divided every 8 hours

Preferred Oral Therapy*

o

Amoxicillin 90 mg/kg/day in 2 divided doses or 45 mg/kg/day in 3 divided doses


Pathogen-directed Antibiotics: Pathogen

Preferred Parenteral Therapy

Alternative Parenteral Therapy

Preferred Oral Therapy*

May also be effective: o

o

o

o

Streptococcus pneumoniae resistant to penicillin with MICs ≥ 4.0 mcg/mL

o

Ceftriaxone 100 mg/kg/day in 1 or 2 divided doses

o

Clindamycin 40 mg/kg/day divided every 6–8 hours Vancomycin 40–60 mg/kg/day divided every 6–8 hours)

Ampicillin 300– 400 mg/kg/day divided every 6 hours IV levofloxacin  16–20 mg/kg/day divided every 12 hours for children 6 months to 5 years old  8–10 mg/kg/day once daily for children 5–16 years old (maximum daily dose 750 mg) Linezolid  30 mg/kg/day divided every 8 hours for children < 12 years old  20 mg/kg/day divided every 12 hours for children ≥ 12 years old

May also be effective:

o

o

Oral levofloxacin, if susceptible  16–20 mg/kg/day in 2 divided doses for children 6 months to 5 years old  8–10 mg/kg/day once daily for children aged 5-16 years (maximum daily dose 750 mg) Oral linezolid  30 mg/kg/day in 3 divided doses for children < 12 years old  20 mg/kg/day in 2 divided doses for children ≥ 12 years old


Pathogen-directed Antibiotics: Pathogen

Preferred Parenteral Therapy

Alternative Parenteral Therapy o

o

o

o o

Group A Streptococcus

o

o

Staphylococcus aureus, methicillin susceptible

o

o

S. aureus, methicillin resistant but susceptible to clindamycin

o

Clindamycin 40 mg/kg/day divided every 6–8 hours** Vancomycin 40–60 mg/kg/day divided every 6–8 hours Ceftriaxone 50– 100 mg/kg/day in 1 or 2 divided doses Cefotaxime 150 mg/kg/day divided every 8 hours

IV Penicillin 100,000–250,000 units/kg/day divided every 4–6 hours May also be effective: Ampicillin 200 mg/kg/day divided o Clindamycin 40 every 6 hours mg/kg/day divided every 6–8 hours, if susceptible o Vancomycin 40–60 mg/kg/day divided every 6–8 hours*** Cefazolin 150 mg/kg/day divided o Clindamycin 40 every 8 hours mg/kg/day divided every Semisynthetic 6–8 hours** penicillin such as o Vancomycin 40–60 oxacillin 150–200 mg/kg/day divided every mg/kg/day divided 6–8 hours every 6–8 hours o Linezolid Vancomycin  30 40–60 mg/kg/day mg/kg/day divided divided every 6–8 every 8 hours for hours or dosing to children < 12 years achieve an AUC/MIC old ratio of > 400  20 Clindamycin mg/kg/day every 40 mg/kg/day divided 12 hours for every 6–8 hours children ≥ 12 years old

Preferred Oral Therapy*

o

o

Amoxicillin 50–75 mg/kg/day in 2 divided doses Penicillin V 50–75 mg/kg/day in 3 or 4 divided doses

o

Oral cephalexin 75– 100 mg/kg/day in 3 or 4 divided doses

o

Oral clindamycin 30-40 mg/kg/day in 3 or 4 divided doses


Pathogen-directed Antibiotics: Pathogen

Preferred Parenteral Therapy

Alternative Parenteral Therapy o

o

S. aureus, methicillin resistant and resistant to clindamycin

Vancomycin 40–60 mg/kg/day divided every 6–8 hours or dosing to achieve an AUC/MIC ratio of > 400

o o

Haemophilus influenza, typeable (A-F) or nontypeable

o

o

o

Mycoplasma pneumoniae

Chlamydia trachomatis or

o

Ampicillin 150-200 mg/kg/day divided every 6 hours (if beta-lactamase negative) Ceftriaxone 50-100 mg/kg/day in 1 or 2 divided doses if beta-lactamase producing Cefotaxime 150 mg/kg/day divided every 8 hours

IV Azithromycin 10 mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible

IV Azithromycin 10

o

o

o

o

Linezolid  30 mg/kg/day divided every 8 hours for children < 12 years old  20 mg/kg/day every 12 hours for children ≥ 12 years old IV ciprofloxacin 30 mg/kg/day divided every 12 hours IV levofloxacin  16-20 mg/kg/day divided every 12 hours for children 6 months to 5 years old  8-10 mg/kg/day once daily for children 5-16 years old (maximum daily dose 750 mg)

IV erythromycin lactobionate 20 mg/kg/day divided every 6 hours IV levofloxacin 1620 mg/kg/day divided every 12 hours (maximum daily dose 750 mg)

IV erythromycin lactobionate 20 mg/kg/day

Preferred Oral Therapy* o 

o

o

Oral linezolid 30 mg/kg/day in 3 divided doses for children < 12 years old 20 mg/kg/day in 2 divided doses for children ≥ 12 years old

Amoxicillin 75-100 mg/kg/day in 3 divided doses if beta-lactamase negative Amoxicillinclavulanate (amoxicillin component 45 mg/kg/day in 3 divided doses or 90 mg/kg/day in 2 divided doses) if beta-lactamase producing

o

Azithromycin 10 mg/kg on day 1 followed by 5 mg/kg once daily on days 2–5

o

Azithromycin 10 mg/kg on day 1 followed by


Pathogen-directed Antibiotics: Preferred Parenteral Alternative Parenteral Therapy Preferred Oral Therapy* Therapy Chlamydophila mg/kg on days 1 and 2 divided every 6 hours 5 mg/kg once daily on days pneumoniae of therapy; transition o IV levofloxacin 2–5 to oral therapy if  16-20 possible mg/kg/day divided every 12 hours for children 6 months to 5 years old  8-10 mg/kg/day once daily for children 5-16 years old (maximum daily dose 750 mg) Abbreviations: AUC, area under the time vs. serum concentration curve; MIC, minimum inhibitory concentration. Pathogen

* Dose for oral therapy should not exceed adult dose.

** Clindamycin resistance increasing in certain geographic locations among Staphylococcus aureus and Streptococcus pneu *** For children allergic to beta-lactams. 

appropriate duration of antimicrobial therapy o treatment courses of 10 days have been best studied, shorter courses may be just as effective, particularly for more mild disease managed on outpatient basis (PIDS/IDSA Strong recommendation, Moderate-quality evidence) o infections caused by certain pathogens, notably community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), may require longer treatment than those caused by S. pneumoniae (PIDS/IDSA Strong recommendation, Moderate-quality evidence) to minimize antibiotic resistance o limit exposure to any antibiotic whenever possible as antibiotic exposure selects for antibiotic resistance (PIDS/IDSA Strong recommendation, Moderate-quality evidence) o limit spectrum of activity of antimicrobials to that specifically required to treat identified pathogen (PIDS/IDSA Strong recommendation, Low-quality evidence) o use proper dose to be able to achieve minimal effective concentration at site of infection (PIDS/IDSA Strong recommendation, Low-quality evidence) o treat for shortest effective duration to minimize exposure of both pathogens and normal microbiota to antimicrobials and to minimize selection for resistance (PIDS/IDSA Strong recommendation, Low-quality evidence)


Reference - PIDS/IDSA recommendations on management of community-acquired pneumonia in infants and children older than 3 months of age (Clin Infect Dis 2011 Oct;53(7):e25 PDF)

British Thoracic Society (BTS) recommendations:  

oral antibiotics are safe and effective for children with community-acquired pneumonia, even if severe (BTS Grade A+) give antibiotics to all children with clear clinical diagnosis of pneumonia (due to inability to reliably distinguish between bacterial and viral pneumonia) (BTS Grade C) children aged < 2 years with mild symptoms of lower respiratory tract infection do not usually have pneumonia and do not need antibiotics (BTS Grade C) o especially if history of conjugate pneumococcal vaccination o persistent symptoms may require reevaluation antibiotic selection o amoxicillin is first choice oral antibiotic therapy in all children (BTS Grade B)  effective against majority of community-acquired pneumonia pathogens  well-tolerated and cheap  alternatives include amoxicillin-clavulanate, cefaclor, and macrolide antibiotics o macrolide antibiotics (erythromycin, clarithromycin, and azithromycin)  may be added at any age if no response to first-line empirical therapy (BTS Grade D)  use if either Mycoplasma or Chlamydia pneumonia suspected (BTS Grade D)  use if very severe disease (BTS Grade D) o amoxicillin-clavulanate recommended for influenza-associated pneumonia (BTS Grade D) considerations for IV therapy o use IV antibiotics in children unable to tolerate oral fluids or absorb oral antibiotics (for example, due to vomiting) or with signs of septicemia or complicated pneumonia (BTS Grade D) o options for severe pneumonia include IV amoxicillin, amoxicillinclavulanate, cefuroxime, and cefotaxime or ceftriaxone (BTS Grade D) o in patient receiving IV antibiotic therapy, consider switching to oral treatment after clear evidence of improvement (BTS Grade D) Reference - BTS guideline for management of community-acquired pneumonia in children (Thorax 2011 Oct;66 Suppl 2:ii1 PDF)

Cincinnati Children's Hospital Medical Center (CCHMC) guidelines for children aged 60 days to 17 years:  

antibiotic selection usually based on patient's age and severity of illness children aged 60 days to 5 years


o

high-dose amoxicillin (80 to 90 mg/kg/day) for 7-10 days when bacterial cause likely (CCHMC Evidence A/S/E) o in children with penicillin allergy - consider macrolide or cephalosporin (CCHMC Evidence C/S/E) o macrolides are not considered first-line therapy (CCHMC Evidence C)  Mycoplasma pneumoniae or Chlamydia pneumoniae are less common cause of pneumonia in children < 5 years old  macrolide may be added to amoxicillin therapy if M. pneumoniae or C. pneumoniae suspected at 24-48 hour follow-up (CCHMC Evidence A/E) o in infant or child unable to tolerate liquids, consider single dose of ceftriaxone before starting oral antibiotics (CCHMC Evidence C/D/E) children ≥ 5 years old o macrolide antibiotic for 7-10 days, although 5-day course of azithromycin may be used (CCHMC Evidence A/S/E) o no evidence that one macrolide is more effective than any other for treating M. pneumoniae or C. pneumoniae (CCHMC Evidence A/S/E) for more severe pneumonia - consider combination of macrolide and beta-lactam agent (such as high-dose amoxicillin or ceftriaxone) to provide better coverage for resistant organisms and mixed infections (CCHMC Evidence C/E) Reference - CCHMC evidence-based guideline for community-acquired pneumonia in children aged 60 days to 17 years (CCHMC 2006 Jul PDF )

Alberta Clinical Practice Guidelines Working Group for Antibiotics recommendations for outpatients aged 3 months to 16 years:   

antibiotic selection based on age, clinical presentation, and local resistance patterns of predominant bacterial pathogens for infants, outpatient treatment only recommended if age ≥ 3 months infants and children aged 3 months to 5 years o oral amoxicillin for 7-10 days  standard dose if no daycare attendance or antibiotics in last 3 months - 40 mg/kg/day in 3 divided doses (maximum 500 mg/dose)  high dose if daycare attendance or antibiotics in last 3 months - 90 mg/kg/day in 3 divided doses (maximum 1 g/dose) o if beta-lactam allergy - choose 1 of following oral regimens  azithromycin 10 mg/kg/day for 1 day (maximum 500 mg/day), then 5 mg/kg/day (maximum 250 mg/day) for 4 days  clarithromycin 15 mg/kg/day in 2 divided doses (maximum 1,000 mg/day) for 7-10 days  erythromycin 40 mg/kg/day in 4 divided doses (maximum 2,000 mg/day) for 7-10 days for children aged 5-16 years choose 1 of following oral regimens o azithromycin 10 mg/kg/day for 1 day (maximum 500 mg/day), then 5 mg/kg/day orally (maximum 250 mg/day) for 4 days o clarithromycin 15 mg/kg/day in 2 divided doses (maximum 1,000 mg/day) for 7-10 days


o

erythromycin 40 mg/kg/day in 4 divided doses (maximum 2,000 mg/day) for 7-10 days o in children > 8 years old - doxycycline 4 mg/kg/day in 2 divided doses (maximum 200 mg/day) for 7-10 days Reference - Alberta Clinical Practice Guidelines Working Group for Antibiotics recommendations for pediatric outpatients aged 1 month to 16 years with community-acquired pneumonia 2008 update PDF

Comparative Efficacy Comparisons of different antibiotics: 

various antibiotics may have similar efficacy for pneumonia in children (level 2 [mid-level] evidence); amoxicillin and co-trimoxazole appear to have similar efficacy in children aged 2-59 months treated as outpatients (level 2 [mid-level] evidence) o based on Cochrane review with limited evidence o systematic review of 27 randomized trials with 11,928 children < 18 years old comparing antibiotics for community-acquired pneumonia in hospital or ambulatory settings, results for outpatient settings summarized here o no trial compared antibiotic vs. placebo o only 5 trials were double-blinded o amoxicillin-clavulanate had higher cure rate than amoxicillin in 1 open-label trial in 100 children aged 2-12 years o no significant differences in comparisons of  azithromycin vs.  erythromycin (4 trials with 623 children)  amoxicillin-clavulanate (2 trials with 283 children < 5 years old), except fewer side effects with azithromycin  amoxicillin (1 trial with 47 children aged 1 month to 14 years)  co-trimoxazole vs.  amoxicillin (3 trials with 3,952 children aged 2-59 months)  procaine penicillin (2 trials with 723 children aged 3 months to 12 years)  single-dose procaine penicillin followed by oral ampicillin for 5 days (1 trial with 134 children aged 1 month to 4 years)  cefpodoxime vs. amoxicillin-clavulanate (1 trial with 348 children aged 3 months to 11.5 years)  clarithromycin vs. erythromycin (1 trial with 260 children aged 3-12 years)  amoxicillin vs. procaine penicillin (1 trial with 170 children aged 6 months to 18 years) o Reference - Cochrane Database Syst Rev 2010 Mar 17;(3):CD004874

no randomized trials identified to guide antibiotic selection for communityacquired pneumonia in patients with sickle cell disease


o o

based on Cochrane review Reference - Cochrane Database Syst Rev 2012 Oct 17;(10):CD005598

Comparisons of antibiotic duration: 

3-day course of antibiotics is as effective 5-day course for children aged 2-59 months with nonsevere pneumonia (level 1 [likely reliable] evidence) o based on Cochrane review o systematic review of 4 randomized trials comparing 3-day course vs. 5-day course of antibiotic therapy (amoxicillin or co-trimoxazole) in 6,177 children aged 2-59 months with nonsevere community-acquired pneumonia o no significant differences in comparisons of 3 vs. 5 days of antibiotics in  clinical cure in analysis of 3 trials with 5,763 children  treatment failure in analysis of 3 trials with 5,763 children  relapse rate after 7 days of clinical cure in analysis of 4 trials with 5,469 children  subgroup analyses evaluating impact of different antibiotics o Reference - Cochrane Database Syst Rev 2011 Apr 13;(2):CD005976

Amoxicillin Amoxicillin efficacy: 

amoxicillin for 3 days may have limited efficacy for children < 5 years old with nonsevere pneumonia in developing countries (level 2 [mid-level] evidence) o based on 2 randomized trials with conflicting results o amoxicillin for 3 days appears to modestly reduce clinical failure rate at 4 days in children < 5 years old with nonsevere pneumonia (level 2 [midlevel] evidence)  based on randomized trial with inadequate statistical power to exclude lack of clinical efficacy  1,671 children aged 2-59 months with wheeze and nonsevere pneumonia in India were randomized to amoxicillin 31-54 mg/kg/day orally in 3 divided doses vs. placebo for 3 days  all children received albuterol 1 mg (2.5 mL for ages 2-11 months) or 2 mg (5 mL for ages 12-59 months) orally 3 times daily  clinical failure defined as  development of World Health Organization (WHO)-defined severe pneumonia or very severe disease  oxygen saturation < 90% on pulse oximetry < 90%  axillary temperature > 38.3 degrees C (101 degrees F)  persistence of WHO-defined nonsevere pneumonia by day 4  presence of wheeze on day 4  clinical relapse defined as clinical cure on day 4 (absence of clinical failure) but signs of WHO-defined pneumonia at days 11-14  comparing amoxicillin vs. placebo


clinical failure rate 19.9% vs. 24% (p < 0.05, NNT 24, 95% CI 12-430)  clinical relapse rate (among those cured) 6.1% vs. 6.9% (not significant)  using 5% absolute difference in clinical cure rates as "test for equivalence," confidence intervals did not establish or rule out equivalence between amoxicillin and no antibiotics  Reference - PLoS ONE 2008 Apr 23;3(4):e1991 full-text o amoxicillin for 3 days does not reduce treatment failure rate at 3 days in children < 5 years old with nonsevere pneumonia (level 1 [likely reliable] evidence)  based on randomized trial  900 children aged 2-59 months with WHO-defined nonsevere pneumonia in Pakistan randomized to amoxicillin 15 mg/kg every 8 hours for 3 days vs. placebo  therapy changes initiated at 3 days in children with treatment failure (children with placebo began amoxicillin, children with amoxicillin received chloramphenicol)  comparing amoxicillin vs. placebo  treatment failure at day 3 in 7.2% vs. 8.3% (not significant, 95% CI does not include 5% absolute difference)  cumulative treatment failure rate by day 5 was 13.5% vs. 17.6% (p = 0.09)  risk factors for treatment failure by day 5  history of breathing difficulty (odds ratio [OR] 2.86, 95% CI 1.29-7.23)  temperature > 37.5 degrees C (100 degrees F) (OR 1.99, 95% CI 1.37-2.9)  Reference - Clin Infect Dis 2011 Feb 1;52(3):293 home-based treatment with high-dose oral amoxicillin appears at least as effective as hospitalization with parenteral ampicillin for children < 5 years old with severe pneumonia (level 2 [mid-level] evidence) o based on randomized trial in Pakistan with baseline differences o 2,100 children aged 3-59 months with severe pneumonia were randomized to home-based treatment vs. initial hospitalization  home-based treatment group given oral amoxicillin 80-90 mg/kg/day in 2 divided doses for 5 days  initial hospitalization group given parenteral ampicillin 100 mg/kg/day in 4 divided doses for 48 hours, then oral amoxicillin 8090 mg/kg/day for 3 days o children excluded if known asthma or very severe pneumonia (unable to drink, convulsions, central cyanosis, abnormally sleepy or difficult to wake, stridor in calm child, or clinically severe malnutrition) o follow-up assessments at 1, 3, 6, and 14 days after enrollment o treatment failure defined as any of  inability to take oral medication due to persistent vomiting  development of comorbid condition requiring antibiotic


o

o o

persistence of fever > 38 degrees C (100.4 degrees F) with lower chest indrawing from days 3-6  fever or lower chest indrawing alone  hospitalization due to pneumonia  any serious adverse event  left against medical advice or lost to follow-up  voluntary withdrawal of consent or death comparing home-based vs. hospital-based treatment in intention-to-treat analysis  treatment failure by 3 days in 4.5% vs. 7% (NNT 40, 95% CI for difference -4.5% to -0.5%)  treatment failure by 6 days in 8.5% vs. 10% (95% CI for difference 4% to +0.9%)  death within 14 days in 1 vs. 4 children Reference - Lancet 2008 Jan 5;371(9606):49 DynaMed commentary -- hospitalized children were more likely than homebased group at baseline to have diarrhea, vomiting, previous antibiotic use, and audible wheeze (absolute differences of about 5% in these variables might affect results and might question adequacy of randomization)

Amoxicillin dose: 

double-dose amoxicillin appears no more effective than standard dose in children < 5 years old with nonsevere pneumonia (level 2 [mid-level] evidence) o based on randomized trial with allocation concealment not stated o 900 children aged 2-59 months with nonsevere pneumonia in Pakistan were randomized to amoxicillin 45 mg/kg/day vs. 90 mg/kg/day orally (in 3 times daily doses) for 3 days o nonsevere pneumonia defined as  cough and/or difficulty breathing  respiratory rate at least 40/minute in children aged 12-59 months or at least 50/minute in infants aged 2-11 months  no lower chest indrawing o treatment failure defined as development of lower chest indrawing, central cyanosis, inability to drink, abnormal sleepiness, or convulsions o relapse defined as any sign of pneumonia after fast breathing disappeared o treatment failure by day 5 or relapse was treated with second-line antibiotic o 24 children (2.7%) lost to follow-up o comparing standard-dose vs. double-dose amoxicillin (no significant differences)  failure at 3 days in 3% vs. 4.1%  failure or relapse by 5 days in 4.6% vs. 5.7%  failure or relapse by 14 days in 5.9% vs. 8% o Reference - Arch Dis Child 2007 Apr;92(4):291

Macrolide Antibiotics


Comparisons of macrolides: 

macrolide antibiotics (erythromycin, clarithromycin, and azithromycin) appear to have similar efficacy for community-acquired pneumonia (level 2 [mid-level] evidence) o based on 6 small comparison trials in children and adults o erythromycin least expensive but has highest rate of adverse effects o Reference - J Fam Pract 2004 Mar;53(3):229 azithromycin appears as effective as erythromycin or amoxicillin-clavulanate orally for 10 days (level 2 [mid-level] evidence) o based on randomized trial with randomization method not reported o 456 children aged 6 months to 16 years with community-acquired pneumonia randomized to azithromycin for 5 days vs. conventional therapy for 10 days  azithromycin 10 mg/kg then 5 mg/kg orally once daily for 5 days  conventional therapy was erythromycin estolate (amoxicillinclavulanate if ≤ 5 years old) 40 mg/kg/day in 3 divided doses for 10 days o comparing clinical response (defined as clinical improvement or cure) with azithromycin vs. conventional therapy  at 15-19 days in 94.6% vs. 96.2% (not significant)  4-6 weeks after therapy in 90.6% vs. 87.1% (not significant)  treatment-related adverse events in 11.3% vs. 31% (p < 0.05, NNH 5 for conventional therapy) o Reference - Pediatr Infect Dis J 1998 Oct;17(10):865, commentary can be found in Am Fam Physician 1999 Mar 1;59(5):1302

Considerations for Mycoplasma pneumoniae: 

older age and longer fever duration associated with higher likelihood of Mycoplasma pneumoniae as causative agent in community-acquired pneumonia in children (level 2 [mid-level] evidence) o based on derivation cohort study without validation o prospective cohort study of 253 children with radiographically confirmed community-acquired pneumonia o 32 (13%) had M. pneumoniae infection based on paired serology o scoring system for M. pneumoniae risk based on age and fever duration  age < 6 months - 0 points  age 6-24 months - 1 point  age 2-4 years - 2 points  age 4-7 years - 3 points  age 7-10 years - 4 points  age > 10 years - 5 points  fever < 1 day - 0 points  fever 1-3 days - 1 point  fever 3-5 days - 2 points  fever 5-7 days - 3 points


 

o

o 

fever 7-14 days - 4 points fever > 14 days - 5 points risk of M. pneumoniae based on score  score 0-3 in 99 patients - 2% had M. pneumoniae  score 4-5 in 91 patients - 6.8% had M. pneumoniae  score 6-7 in 46 patients - 28% had M. pneumoniae  score 8-10 in 17 patients - 65% had M. pneumoniae Reference - Arch Pediatr Adolesc Med 2002 Oct;156(10):1005 full-text

insufficient evidence to guide selection of antibiotics for community-acquired lower respiratory tract infection due to Mycoplasma pneumonia in children o based on Cochrane review o systematic review of 7 randomized trials evaluating antibiotics for community-acquired lower respiratory tract infections secondary to M. pneumoniae infection in children o data interpretation severely limited due to inability to extract data specific to children with M. pneumoniae o no significant differences in clinical response comparing macrolide vs. nonmacrolide antibiotics in children o Reference - Cochrane Database Syst Rev 2012 Sep 12;(9):CD004875

Guidelines and Resources Guidelines: World Health Organization (WHO) guidelines: 

World Health Organization (WHO) evidenced-based recommendations on treatment of childhood nonsevere pneumonia can be found in Lancet Infect Dis 2009 Mar;9(3):185

United States guidelines: 

Pediatric Infectious Diseases Society/Infectious Diseases Society of America (PIDS/IDSA) clinical guideline on management of community-acquired pneumonia in infants and children older than 3 months of age can be found in Clin Infect Dis 2011 Oct;53(7):e25 full-text or at National Guideline Clearinghouse 2012 Jan 23:34433, executive summary can be found in Clin Infect Dis 2011 Oct;53(7):617

Cincinnati Children's Hospital Medical Center (CCHMC) evidence-based guideline on community-acquired pneumonia in children aged 60 days to 17 years can be found at CCHMC 2006 Jul PDF Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group convened at Centers for Disease Control and Prevention (CDC) in 1998 consensus statement on management of community-acquired pneumonia in the era of pneumococcal resistance can be found in Arch Intern Med 2000 May 22;160(10):1399, commentary can be found in Arch Intern Med 2001 Jul 9;161(13):1681


United Kingdom guidelines: 

British Thoracic Society (BTS) guideline on management of community-acquired pneumonia in children can be found in Thorax 2011 Oct;66 Suppl 2:ii1 PDF or at National Guideline Clearinghouse 2012 Dec 3:37287, summary can be found in Thorax 2011 Oct;66(10):927

Canadian guidelines: 

Alberta Clinical Practice Guidelines Working Group for Antibiotics recommendations on pediatric inpatients aged 1 month to 16 years with communityacquired pneumonia 2008 update can be found at Toward Optimized Practice PDF

Asian guidelines: 

Infectious Diseases Society of Taiwan/Taiwan Society of Pulmonary and Critical Care Medicine/National Health Research Institute (NHRI) joint guideline on pneumonia can be found at NHRI 2008 Apr 19 PDF [Chinese (Traditional) 正體中文] Taiwan Pediatric Working Group guideline on management of community-acquired pneumonia in children can be found in Acta Paediatr Taiwan 2007 JulAug;48(4):167

Review articles:  

  

review of community-acquired pneumonia in infants and children can be found in Am Fam Physician 2004 Sep 1;70(5):899 full-text review of community-acquired pneumonia in children can be found in N Engl J Med 2002 Feb 7;346(6):429, commentary can be found in N Engl J Med 2002 Jun 13;346(24):1916 review of community-acquired pneumonia can be found in Am Fam Physician 2002 Jul 1;66(1):135 full-text review of community-acquired pneumonia with focus on atypical causes can be found in Am Fam Physician 2004 Apr 1;69(7):1699 full-text review of diagnosis and treatment of community-acquired pneumonia can be found in Am Fam Physician 2006 Feb 1;73(3):442 full-text, commentary can be found in Am Fam Physician 2006 Sep 15;74(6):921 full-text, Am Fam Physician 2006 Nov 1;74(9):1479 full-text review of pneumonia and other respiratory infections can be found in Pediatr Clin North Am 2009 Feb;56(1):135

References Recommendation grading systems used: 

Pediatric Infectious Diseases Society/Infectious Diseases Society of America (PIDS/IDSA) grades of recommendation


o

o

o

strength of recommendation  Strong recommendation - desirable effects clearly outweigh undesirable effects, or vice versa  Weak recommendation  if high-quality or moderate-quality evidence - desirable effects closely balanced with undesirable effects  if low-quality evidence - uncertainty in estimates of desirable effects, harms, and burden; desirable effects, harms, and burden may be closely balanced  very low-quality evidence - major uncertainty in estimates of desirable effects, harms, and burden; desirable effects, harms, and burden may be closely balanced quality of evidence  High-quality evidence - consistent evidence from well-performed randomized controlled trials (RCTs) or exceptionally strong evidence from unbiased observational studies  Moderate-quality evidence - evidence from RCTs with important limitations (inconsistent results, methodologic flaws, indirect, or imprecise) or exceptionally strong evidence from unbiased observational studies  Low-quality evidence - evidence for ≥ 1 critical outcome from observational studies, RCTs with serious flaws or indirect evidence  Very low-quality evidence - evidence for ≥ 1 critical outcome from unsystematic clinical observations or very indirect evidence Reference - PIDS/IDSA clinical practice guideline on management of community-acquired pneumonia in infants and children older than 3 months of age (Clin Infect Dis 2011 Oct;53(7):e25 PDF)


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