Antibiotic use for community-acquired pneumonia in neonates and children: WHO evidence review

Figures & data

Table 1. Comparison of international guidance for antibiotic therapy of community-acquired pneumonia in children.

Guideline	Last update	Recommendation
British National Formulary for Children (BNFc) [8]	2016	• Benzylpenicillin with gentamicin for neonatal sepsis of all causes • For children aged 1 month to 18 years, oral amoxicillin is recommended as first-line for CAP and clarithromycin is recommended if there is no response to treatment • For suspected staphylococcal infection, oral amoxicillin and flucloxacillin or amoxicillin clavulanate alone are recommended. • In complicated pneumonia or if oral administration is not possible, treatment for 7 days with intravenous amoxicillin or amoxicillin clavulanate or cefuroxime or cefotaxime is recommended. • For children aged 1 month–18 years who are allergic to penicillin, clarithromycin for 7 days is recommended
RCPCH/ESPID Manual of Childhood Infections, ‘Blue Book’ [9]	2016	• For children aged <5 years, oral amoxicillin for a standard course of 5 days is the first-choice antibiotic. • Macrolides are recommended if either M. pneumoniae or Chlamydia pneumoniae is suspected. • Intravenous antibiotics for severe pneumonia include penicillin/amoxicillin, amoxicillin clavulanate, cefuroxime and cefotaxime/ceftriaxone
British Thoracic Society [7]	2011	• Amoxicillin is first choice for oral antibiotic therapy in all children because it is effective against the majority of pathogens, is well tolerated and is cheap Alternatives are amoxicillin clavulanate, cefaclor, erythromycin, azithromycin and clarithromycin • Macrolide antibiotics may be added at any age if there is no response to first-line empirical therapy • Macrolide antibiotics should be used if either mycoplasma or C. pneumoniae is suspected or in very severe disease. • Amoxicillin clavulanate is recommended for pneumonia associated with influenza
Canadian Paediatric Society [11]	2015	• Oral amoxicillin is recommended for outpatients with lobar or broncho-pneumonia. • Patients who require hospitalisation but do not have a life-threatening illness should be commenced empirically on intravenous ampicillin. • Empirical therapy with a third-generation cephalosporin is recommended for children who experience respiratory failure or septic shock associated with pneumonia. • Ceftriaxone or cefotaxime are recommended for β-lactamase-producing H. influenzae and high-level penicillin-resistant pneumococcus. • For rapidly progressing multilobar disease or pneumatocoeles, the addition of vancomycin is suggested empirically with de-escalation to ampicillin with subsequent oral amoxicillin. • Vancomycin is recommended for empyema owing to S. aureus. • If S. pneumoniae is detected in blood or respiratory secretions and is penicillin-susceptible, treatment with either intravenous ampicillin or penicillin is recommended, followed by oral therapy with amoxicillin. • Treatment of M. pneumoniae and C. pneumoniae is azithromycin for 5 days. Doxycycline for children aged ≥8 years
ESPID [10]	2012	• For children <1 month, ampicillin/amoxicillin and gentamicin are recommended empirically. If Listeria monocytogenes or enterococcus is suspected, ampicillin with an alternative of a cephalosporin is recommended. Third-generation cephalosporins should be avoided in neonates because of the risk of candidiasis. For critically ill patients, an anti-staphylococcal penicillin and clindamycin or vancomycin are recommended. • For children aged 1–3 months, β-lactam antibiotics with anti-staphylococcal penicillin for the critically ill are recommended. In children with no fever or severe cough, C. trachomatis and Bordetella pertussis should be suspected and treated with macrolides. • For children aged 3 months to 5 years, penicillin G or aminopenicillins, e.g. amoxicillins are recommended to ensure adequate cover of S. pneumoniae and more atypical pathogens in this age group. For unimmunised children, treatment with amoxicillin clavulanate or a third-generation cephalosporin is recommended. Second-generation cephalosporins may be used in areas of low penicillin resistance. • For atypical pathogens, combined therapy with β-lactams (e.g. amoxicillin clavulanate) and macrolides (e.g. clarithromycin) are recommended as well as anti-staphylococcal antibiotics for the critically ill
IDSA/PIDS [12]	2011	• For children under 5 years of age, the guidelines recommend amoxicillin, amoxicillin clavulanate for presumed bacterial pneumonia and macrolides (azithromycin, clarithromycin or erythromycin) for presumed atypical pathogens. • For children over 5 years of age, amoxicillin, amoxicillin clavulanate and a macrolide can be added. The IDSA/PIDS guidelines recommend doxycycline for children >7 years

Table

A number of emerging themes have been identified:

(1) The optimal dosing recommendation for amoxicillin remains unclear. There are concerns from recent adult pharmacokinetic data about twice-daily dosing in settings of high pneumococcal resistance. Do 250 mg amoxicillin dispersible tablets cover all the paediatric dosing requirements? (2) It is unclear whether amoxicillin or broader-spectrum antibiotics are most commonly being used to treat CAP in different WHO regions. It is difficult to assess the uptake and implementation of the 2014 WHO CAP guidance (3) There remains no globally relevant head-to-head pragmatic trial directly comparing the effectiveness of amoxicillin with an oral cephalosporin and a macrolide in the ambulatory setting (4) The optimal antibiotic management of hospitalised children with severe and very severe pneumonia as well as severe pneumonia in older hospitalised children remains unclear

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