Table 1.

Characteristics of included studies 1

1a. Systematic review
Title, author, year of publication	Number and type of studies included, population included	Aim of the review	Main outcomes	Results	Conclusions	Contributing Evidence
Treatment of mycoplasma pneumonia: A systematic review Biondi et al., 2014 [29]	4294 children (< 18 years of age) from 17 studies included studies for the qualitative evaluation 723 children included from 8 studies for the meta-analysis 445 children included from 5 randomized trial included in the meta-analysis	The objective was to provide a more comprehensive review of all available published literature on the use of antibiotics in children to treat CA-LRTI secondary to M. pneumoniae.	The primary outcome was clinical improvement or cure at follow-up. Clinical improvement or cure could include resolution of fever; resolution or improvement in symptoms such as cough, congestion, shortness of breath, fatigue, or chest pain; or improvement or cure as defined by the authors of the individual studies.	A meta-analysis using only the 5 RCTs demonstrated a pooled risk difference of 0.12 (95% confidence interval [CI], -0.04 to 0.20). This finding suggests that 12% of children treated with a macrolide will have more rapid clinical improvement, corresponding to a number needed to treat of 8.33, but the confidence interval overlapping 0% negates statistical significance. There remained significant heterogeneity between the studies (P = 0.02). The funnel plot revealed potential for publication bias against small studies that show a treatment effect.	The majority of studies included did not show a significant clinical benefit of M. pneumoniae spectrum therapy in CA-LRTI. Of the 9 studies that specifically examined the issue of M. pneumoniae treatment in children with CA-LRTI secondary to M. pneumoniae, almost all the prospective studies showed no clinical benefit. The remaining studies generally suggest a statistical, but not necessarily clinically relevant, decrease in fever duration, and most of these are rated as low- or lowest-quality evidence.	Question 1 Question 2
Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children Gardiner et al., 2015 [30]	1912 children (< 18 years of age) from 7 studies included studies for the qualitative evaluation	To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community.	Primary outcomes 1. Proportions of participants who were not improved at follow-up. Secondary outcomes 1. Mean difference in symptoms and signs (mean improvement in clinical state). 2. Proportions requiring hospitalisation. 3. Proportions experiencing pulmonary complications (empyema, pleural effusion, air leak). 4. Proportions experiencing non-pulmonary complications. 5. Proportions experiencing adverse effects (for example, nausea, diarrhoea, abdominal pain, rash). 6. Proportions experiencing complications (for example, requirement for medication change).	This review failed to find any randomised controlled trials (RCTs) that specifically looked at the effectiveness of antibiotics for lower respiratory tract infection (LRTI) secondary to M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic.	There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events.	Question 1 Question 2
Antibiotics for community-acquired pneumonia in children Lodha et al., 2013 [31]	14.188 children (< 18 years of age) from 29 included trials (Only 7 articles conducted in high income countries)	To identify effective antibiotic drug therapies for CAP of varying severity in children by comparing various antibiotics.	Clinical Cure and Treatment failure rates Secondary outcomes: relapse rate, hospitalization rate, length of hospital stay, need for change in antibiotics, additional interventions used, mortality rate	In ambulatory settings, for treatment of World Health Organization (WHO) defined non-severe CAP, amoxycillin compared with co- trimoxazole had similar failure rates (odds ratio (OR) 1.18, 95% confidence interval (CI) 0.91 to 1.51) and cure rates (OR 1.03, 95% CI 0.56 to 1.89). Three studies involved 3952 children.	For treatment of patients with CAP in ambulatory settings, amoxycillin is an alternative to cotrimoxazole. With limited data on other antibiotics, co-amoxiclav acid and cefpodoxime may be alternative second-line drugs. Children with severe pneumonia without hypoxaemia can be treated with oral amoxycillin in an ambulatory setting.	Question 3 Question 4
Antibiotic Treatment Duration for Community-Acquired Pneumonia in Outpatient Children in High-Income Countries—A Systematic Review and Meta-Analysis Kuitunen et al., 2022 [32]	4 RCTs, all conducted in high income countries (SCOUT-CAP, CAP-IT, SAFER, Greenberg et al.) 1541 children aged ≥ 6 months with CAP	To compare short antibiotic treatment (3–5 days) with longer treatment (7–10 days)	The need for antibiotic retreatment, hospitalization, or treatment failure (including either need for retreatment or hospitalization) within 1 month after the randomization. Secondary outcomes were antibiotic-related adverse effects.	All 4 studies assessed treatment failures, and the risk differences (RD) was 0.1% (95% confidence interval, − 3.0–2.0%) with high quality of evidence. Two studies (1194 children) assessed adverse events related to antibiotic treatment, and the RD was 0.0% (− 5.0–5.0%) with moderate quality of evidence	A short antibiotic treatment duration of 3–5 days was equally effective and safe compared with the longer (current) recommendation of 7–10 days in children aged ≥ 6 months with CAP. Short antibiotic courses can be implemented in treatment of pediatric CAP.	Question 6
Short-Course vs. Long-Course Antibiotic Therapy for Children With Nonsevere Community-Acquired Pneumonia A Systematic Review and Meta-analysis Li et al., 2022 [33]	Nine randomized clinical trials (4 from high income countries, SCOUT-CAP, CAP-IT, SAFER, Greenberg et al., the same included in the review published by Kuitunen; 5 from low and middle income countries, Glinsburg et al., ISCAP, Kartasasmita, MASCOT, Lupisan) 11,143 children with CAP	To determine whether a shorter course of antibiotics was noninferior to a longer course for childhood non-severe CAP	Treatment failure, defined by persistence of pneumonia or the new appearance of any general danger signs of CAP (e.g., lethargy, unconsciousness, seizures, or inability to drink), elevated temperature (> 38 °C) after completion of treatment, change of antibiotic, hospitalization, death, missing more than 3 study drug doses, loss to follow-up, or withdrawal of informed consent.	Treatment failure occurred in 12.8% vs. 12.6% of participants randomized to a shorter vs. a longer course of antibiotics. Shorter course of oral antibiotic was noninferior to a longer course with respect to treatment failure for children with nonsevere CAP (risk ratio, 1.01; 95%CI, 0.92–1.11; risk difference, 0.00; 95%CI, − 0.01 to 0.01; I2 = 0%). A 3-day course of antibiotic treatment was noninferior to a 5-day course for the outcome of treatment failure (risk ratio, 1.01; 95%CI, 0.91–1.12; I2 = 0%), and a 5-day course was noninferior to a 10-day course (risk ratio, 0.87; 95%CI, 0.50–1.53; I2 = 0%). A shorter course of antibiotics was associated with fewer reports of gastroenteritis (risk ratio, 0.79; 95%CI, 0.66–0.95) and lower caregiver absenteeism (incident rate ratio, 0.74; 95%CI, 0.65–0.84).	A shorter course of antibiotics was noninferior to a longer course in children aged 2 to 59 months with nonsevere CAP. Clinicians should consider prescribing a shorter course of antibiotics for the management of pediatric nonsevere CAP. High-quality evidence from the review showed that in high income countries a 5-day regimen might be sufficient for the management of children with CAP	Question 6
Shorter Versus Longer-term Antibiotic Treatments for Community-Acquired Pneumonia in Children: A Meta-analysis Gao et al., 2023 [34]	Sixteen trials (9 from high income countries, CAP-IT, Gomez Campdera 1996, Greenberg, Harris 1998, SAFER, Ronchetti 1994, Roord 1996, SCOUT-CAP, Wubbel 1999) 7 from low income countries, from 1994 to 2022, 1 conference abstract) 12 774 children with CAP under 18 years of age with diagnosed CAP according to investigator-defined definitions treated as outpatients with oral antibiotics	To compare the efficacy and safety of shorter versus longer duration of antibiotic treatment	Clinical cure, treatment failure, relapse, duration of hospital stay, mortality, need for change in antibiotics, ICU admission, duration of hospital stay, duration of ICU stay, hospital readmission, invasive ventilation, for trials enrolling outpatients the need for hospitalization, severe adverse events, and all adverse events.	Considering the high income countries, there are probably no substantial differences between shorter-duration and longer duration antibiotics in clinical cure (odds ratio 1.29, 95% confidence interval [CI] 0.95 to 1.77; moderate certainty), treatment failure (relative risk [RR] 0.82, 95% CI 0.48 to 1.40; moderate certainty), and relapse (RR 0.99, 95% CI 0.45 to 2.17; moderate certainty). Compared with longer-duration antibiotics, shorter-duration antibiotics do not appreciably increase mortality (RD 0.0%, 95% CI 0.2 to 0.1; high certainty), and probably have little or no impact on the need for hospitalization moderate certainty), and severe adverse events	Duration of antibiotic therapy likely makes no important difference in patient important outcomes.	Question 6
Shorter versus longer duration of Amoxicillin‑based treatment for pediatric patients with community‑acquired pneumonia: a systematic review and meta‑analysis Marques et al., 2022 [35]	Three RCTs (SCOUT-CAP, SAFER, Greenberg) 789 children older than 6 months with CAP in an outpatient setting	To compare 5-day and 10-day courses of Amoxicillin	The outcome of interest was clinical cure	No differences were found between 5-day and 10-day therapy regarding clinical cure (RR 1.01; 95% CI 0.98–1.05; p = 0.49; I2 = 0%). Subgroup analysis of children aged 6–71 months showed no difference in the rates of the same outcome (RR 1.01; 95% CI 0.98–1.05; p = 0.38; I2 = 0%).	A short course of Amoxicillin (5 days) is just as effective as a longer course (10 days) for uncomplicated CAP in children under 10 years old. Nevertheless, generalizations should be made with caution considering the socioeconomic settings of the studies included.	Question 6
1b. RCT and Observational Studies
Title, author, year of publication	Study design	Population ( N °, Country, setting)	Exposure	Primary outcome	Follow-up	Results	Contributing Evidence
Comparative Effectiveness of Beta-lactam vs. Macrolide monotherapy in Children with Pneumonia Diagnosed in the Outpatient Setting Ambroggio et al., 2015 [42]	Retrospective cohort study	N = 1,999 children with CAP treated in the outpatient setting, of whom 1,164 were matched in the treatment group. USA Children from 1 to 18 years of age with uncomplicated CAP	Beta-lactam or macrolide monotherapy.	Treatment failure, defined as a follow-up visit with an ICD-9 code for a respiratory-related diagnosis accompanied by a change in antibiotic therapy either in the outpatient setting (in-person or via phone), in the emergency department, or as a hospital admission	14-days	Patients who received macrolide monotherapy had no statistical difference in treatment failure regardless of age when compared with patients who received beta-lactam monotherapy. Among children younger than 6 years, there was no statistically significant difference in treatment failure within 14 days between those receiving beta-lactam monotherapy and those receiving macrolide monotherapy (Adjusted Odds Ratio (AOR): 0.90; 95% Confidence Interval: 0.37, 2.22)). Among those who were 6 years of age and older, children who received macrolide monotherapy had a non-statistically significant lower odds of treatment failure within 14 days compared with children 6 years of age and older who received beta-lactam monotherapy (AOR: 0.48; 95% CI: 0.22, 1.01).	Question 1 Question 2 Question 4
Beta-Lactam Versus Beta-Lactam/Macrolide Therapy in Pediatric Outpatient Pneumonia Ambroggio et al., 2016 [44]	Retrospective cohort study	N = 717 children with uncomplicated CAP treated in the outpatient setting. USA Children from 1 to 18 years of age	Beta-lactam monotherapy or beta- lactam/macrolide combination therapy	Treatment failure, defined as a follow-up visit within 14 days of diagnosis resulting in a change in antibiotic therapy.	14-day	Of 717 children in the analytical cohort, 570 (79.4%) received beta-lactam monotherapy and 147 (20.1%) received combination therapy. Of those who received combination therapy 58.2% of children were under 6 years of age. Treatment failure occurred in 55 (7.7%) children, including in 8.1% of monotherapy recipients, and 6.1% of combination therapy recipients. Treatment failure rates were highest in children 6–18 years receiving monotherapy (12.9%) and lowest in children 6–18 years receiving combination therapy (4.0%). Children 6–18 years of age who received combination therapy were less likely to fail treatment than those who received beta-lactam monotherapy (propensity-adjusted odds ratio, 0.51; 95% confidence interval, 0.28, 0.95).	Question 1 Question 2
Effects of clinical pathway implementation on antibiotic prescriptions for pediatric community-acquired pneumonia Donà et al., 2018 [45]	Before and after	97 children with non-complicated CAP evaluated in PED Italy	CP for CAP to increase the use of narrow spectrum antibiotics and reduce the days of therapy	Change in antibiotics prescriptions and treatment duration Treatment failure, prescription of broad-spectrum antibiotics	30 days	Before implementation 50% of children (28/56) received exclusively amoxicillin, compared with 73.2% (30/41) after CP release. Pre-intervention median LOT was 10 (range 3–15), while post-intervention median LOT was 8 (range 5–10) (p < 0.0001) as recommended in the CP, with a decreasing trend over all sub-periods after implementation. In the pre-CP period, treatment failure occurred in 2.3% (1/44) of cases, while 11.8% (4/34) failed treatment in the post-CP period (p = 0.29)	Question 1 Question 2 Question 6
Antibiotic Choice and Clinical Outcomes in Ambulatory Children with Community- Acquired Pneumonia Lipsett et al., 2021 [46]	Retrospective cohort study	N = 252.177 outpatient pneumonia visits USA Children from 0 to 18 years of age diagnosed with CAP from 2010 to 2016	Narrow-spectrum (aminopenicillins), broad-spectrum (amoxicillin/clavulanate and cephalosporins), macrolide monotherapy, macrolides with narrow-spectrum antibiotics, or macrolides with broad-spectrum antibiotics.	Hospitalization, development of severe pneumonia and change in antibiotic therapy	7 days	Among 252,177 outpatient pneumonia visits, macrolide monotherapy was used in 43.2%, narrow-spectrum antibiotics in 26.1%, and broad-spectrum antibiotics in 24.7%. A total of 1488 children (0.59%) were subsequently hospitalized and 117 (0.05%) developed severe pneumonia. Compared with children receiving narrow-spectrum antibiotics, the odds of subsequent hospitalization were higher in children receiving broad-spectrum antibiotics (aOR = 1.34 [95%CI 1.17–1.52]) and lower in children receiving macrolide monotherapy (aOR = 0.64 [95%CI 0.55–0.73]) and macrolides with narrow-spectrum antibiotics (aOR = 0.62 [95%CI 0.39–0.97]). Children receiving macrolide monotherapy had lower odds of developing severe pneumonia than children receiving narrow-spectrum antibiotics (aOR = 0.56, 95%CI 0.33–0.93). However, the absolute risk difference was < 0.5% for all analyses.	Question 1 Question 2 Question 4
Comparative Effectiveness of Empiric Antibiotics for Community-Acquired Pneumonia Queen, 2014 [49]	OR	492 children, USA, inpatient, uncomplicated CAP	Empiric treatment with narrow- spectrum therapy versus broad-spectrum therapy	LOS Treatment failure, duration of fever and oxygen therapy	7-days	Narrow-spectrum therapy was not inferior to broad-spectrum antibiotics in all measured outcomes including LOS, duration of oxygen, duration of fever, daily standardized pharmacy and overall costs, or readmission rates within 7 days.	Question 1 Question 2
Narrow Vs Broad-spectrum Antimicrobial Therapy for Children Hospitalized With Pneumonia Williams, 2013 [51]	OR	15,564 Children > 6 months, vaccinated, USA, inpatient, uncomplicated CAP	Empiric treatment with narrow- spectrum therapy versus broad-spectrum therapy	LOS Admission to intensive care (after the first 2 calendar days), 14- day all-cause readmission, and total costs for the admission and the entire episode of illness (accounting for 14-day readmissions)	14 days	There was no difference in length of stay, admission in PICU or readmission within 14 days of discharge	Question 1 Question 2
Management of Pediatric Pneumonia: A Decade After the Pediatric Infectious Diseases Society and Infectious Diseases Society of America Guideline Ambroggio et al., 2023 [48]	Quasi-experimental study	Children aged 3 months–18 years with CAP who visited 1 of 28 participating hospitals in USA from 2009 to 2021 USA 315 384 children with CAP, 71 804 (22.8%) were hospitalized	Impact of IDSA guideline on the use of aminopenicillin in children with CAP treated as outpatient and inpatient	Change in antibiotic prescription For children hospitalized: hospital length of stay (LOS) in days, admission to an ICU, death during hospitalization, and readmission to the hospital within 7, 14, and 30 days. For children discharged from the ED: revisits occurring within 7, 14, and 30 days.	30 days	Among hospitalized children, there was an increase in aminopenicillin prescribing (1.1% per quarter). Among children discharged from the emergency department (ED), there was an increase in aminopenicillin prescription (0.45% per quarter). Hospital length of stay, ED revisit rates, and hospital readmission rates remained stable.	Question 1 Question 2
Evaluation of a Pediatric Community-Acquired Pneumonia Antimicrobial Stewardship Intervention at an Academic Medical Center Puzz et al., 2023 [53]	Before and after	540 patients Children admitted for mild-moderate CAP during three time periods (pre-intervention and post-intervention groups 1 and 2) USA (Missisipi)	Local pediatric CAP treatment guidelines, and antimicrobial stewardship pharmacists, handshake stewardship (prospective audits with feedback and rounding in person)	Changes in inpatient antibiotic selection and duration following the interventions Discharge antibiotic regimens, length of stay, and 30-day	30 days	Antibiotic selection significantly improved, with prescriptions for ceftriaxone decreasing (p < 0.001) and ampicillin increasing (p < 0.001) following the interventions. Azithromycin prescribing also significantly decreased from the pre-intervention group to the post-intervention groups for monotherapy and combination therapy. Antibiotic duration decreased from a median of ten days in the pre-intervention group and post-intervention group 1 to eight days in post-intervention group 2. Length of stay decreased from a mean of 4.9 days to a mean of 2.07 and 1.92 in group 1 and 2 respectively. 30-day readmission was stable during the 3 periods (2%, 7%, 5% respectively)	Question 1 Question 2 Question 6
Effectiveness of β-Lactam Monotherapy vs. Macrolide Combination Therapy for Children Hospitalized With Pneumonia Williams et al., 2017 [52]	OB (multicenter retrospective cohort study)	1418 children (693 girls and 725 boys) children (up to 18 years of age) who were hospitalized with radiographically confirmed pneumonia USA	β-lactam monotherapy (oral or parenteral second- or third-generation cephalosporin, penicillin, ampicillin, ampicillin-sulbactam, amoxicillin, or amoxicillin-clavulanate) vs. β-lactam plus macrolide combination therapy	LOS Intensive care admission, rehospitalizations, and self-reported recovery at follow-up.	3 to 10 weeks following hospital discharge	In the unmatched cohort, there was no statistically significant difference in length of hospital stay between children receiving β-lactam monotherapy and combination therapy (median, 55 vs. 59 h; adjusted hazard ratio, 0.87; 95%CI, 0.74–1.01). The propensity-matched cohort (n = 560, 39.5%) showed similar results. There were also no significant differences between treatment groups for the secondary outcomes.	Question 1 Question 2
Comparative Effectiveness of Empiric b-Lactam Monotherapy and b-Lactam–Macrolide Combination Therapy in Children Hospitalized with Community-Acquired Pneumonia Ambroggio et al., 2012 [43]	OB (multicenter retrospective cohort study)	20,743 children aged 1–18 years who were hospitalized with CAP USA	Empiric β-lactam monotherapy monotherapy (aminopenicillins, penicillin, second- and third-generation cephalosporins) versus β-lactam-macrolide combination therapy	LOS Readmission within 14 days of the index hospital discharge	14 days	Compared with children who received b-lactam monotherapy, children who received b-lactam plus macrolide combination therapy were 20% less likely to stay in the hospital an additional day (adjusted relative risk 0.80; 95% CI, 0.75–0.86) but did not have a different readmission rate (relative risk 0.69; 95% CI, 0.41–1.12). An effect of combination treatment on reduced length of stay was not evident in children < 6 years of age but increased with increasing age groups thereafter.	Question 1 Question 2
Impact of a Guideline on Management of Children Hospitalized With Community-Acquired Pneumonia Newman et al., 2012 [50]	Before and after	1033 children, USA, inpatient, uncomplicated CAP (vaccine status not known)	clinical practice guideline (CPG) for uncomplicated CAP: use of narrow-spectrum antibiotics (ampicillin, amoxicillin) for 5–7 days	Impact on antibiotic management in children hospitalized with uncomplicated CAP Treatment failure	30 days	Before the CPG, 13% of patients empirically received ampicillin and 72% received ceftriaxone. In the year after the CPG, 63% empiric received ampicillin and 21% received ceftriaxone. Overall, 8 (1.5%) pre- CPG patients and 5 (1%) post-CPG met failure criteria (P = 0.28).	Question 3
Antibiotic Treatment of Children With Community-Acquired Pneumonia: Comparison of Penicillin or Ampicillin Versus Cefuroxime Dinur-Schejter et al., 2012 [54]	OR	319 children, 3 months- 2 years, Israel, Inpatient, not complicated CAP, NOT vaccinated Further, they analyzed children with not complicated CAP 3 months-6 years	1° center IV cefuroxime (100 mg/kg/24 hr tid) 3 months-2 years 2° center IV penicillin (400,000 IU/kg/24 hr qid) or ampicillin (100–200 mg/kg/24 hr tid-qid)	LOS Treatment failure, duration of fever and oxygen therapy	None	Treatment outcomes were similar between the penicillin or ampicillin group and the cefuroxime group. The number of patients with treatment failure (defined as requiring a change of first-line treatment) was also similar between the two groups (7.6% vs. 4.7%). There were no difference also for children between 3 months and 6 years	Question 3
Amoxicillin duration and dose for community-acquired pneumonia in children: the CAP-IT factorial non-inferiority RCT Bielicki et al., 2021 [38]	Multicentre randomised double-blind 2 × 2 factorial non-inferiority trial	824 children aged > 6 months, weighing 6–24 kg, with a clinical diagnosis of community-acquired pneumonia	Oral amoxicillin syrup at a dose of 35–50 mg/kg/day compared with a dose of 70–90 mg/kg/day, and 3 compared with 7 days’ duration.	Any clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including community-acquired pneumonia), other than trial medication, up to 28 days after randomisation. Phenotypic resistance to penicillin at day 28 measured in nasopharyngeal S. pneumoniae isolates, severity and duration of parent/guardian-reported CAP symptoms (including fever, cough, phlegm, fast breathing, wheeze, disturbed sleep, eating/drinking less, interference with normal activity and vomiting), adherence to trial medication, the occurrence of specified clinical AEs (including skin rash, thrush and diarrhoea) and serious adverse events (SAEs)	28 days	The observed number of primary end points was similar in the lower-dose arm (n = 51, 12.6%) and in the higher-dose arm (n = 49, 12.4%). The estimated risk difference at day 28 was 0.2% (90% CI − 3.7–4.0%), meeting the criterion for non-inferiority Of the 14 prespecified secondary end points, the only significant differences were 3-day vs. 7-day treatment for cough duration (median 12 days vs. 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = 0.04) and sleep disturbed by cough (median, 4 days vs. 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = 0.03	Question 5 Question 6
Short versus prolonged-duration antibiotics for outpatient pneumonia in children Shapiro et al., 2021 [47]	Retrospective cohort study	N = 121,846 Children from 1 to 18 years of age with outpatient CAP who filled a prescription for oral antibiotics USA	Short-vs prolonged-duration antibiotics	To determine associations between the duration of prescribed antibiotics (5–9 days vs. 10–14 days) and subsequent hospitalizations, new antibiotic prescription, and acute care visits.	14 days following the end of the dispensed antibiotic course	The most commonly prescribed duration of antibiotics was 10 days (82.8% of prescriptions), and 10.5% of patients received short-duration therapy. During the follow-up period, 0.2% of patients were hospitalized, 6.2% filled a new antibiotic prescription, and 5.1% had an acute care visit. Compared with the prolonged-duration group, the aORs for hospitalization, new antibiotic prescriptions, and acute care visits in the short-duration group were 1.16 (95% CI 0.80–1.66), 0.93 (95% CI 0.85–1.01), and 1.06 (95% CI 0.98–1.15), respectively.	Question 6
Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia. The SAFER Randomized Clinical Trial Pernica et al., 2021 [39]	2-center, parallel-group, blinded, noninferiority randomized clinical	281 Children aged 6 months to 10 years with CAP well enough to be treated as outpatients	Five days of high-dose amoxicillin therapy followed by 5 days of placebo (intervention group) vs. 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin (control group).	Clinical cure at 14 to 21 days. Number of days the participant was absent from school or daycare, the total number of days that caregiver work was disrupted, the number of days of mild adverse reactions to the drug, the incidence of serious adverse reactions to the drug (including anaphylaxis), participant adherence to the study medications, and recurrence of presumed bacterial respiratory illness after the primary outcome visit in the month after enrollment; post hoc, clinical cure not requiring additional intervention	21 days	Clinical cure was observed in 101 of 114 children (88.6%) in the intervention group and in 99 of 109 (90.8%) in the control group in per-protocol analysis (risk difference, − 0.016; 97.5% confidence limit, − 0.087). Clinical cure at 14 to 21 days was observed in 108 of 126 (85.7%) in the intervention group and in 106 of 126 (84.1%) in the control group in the intention-to-treat analysis (risk difference, 0.023; 97.5% confidence limit, − 0.061).	Question 6
Short- vs. Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children; The SCOUT-CAP Randomized Clinical Trial (Williams, 2022, RCT) [40]	Multicenter randomized double-blind placebo-controlled superiority clinical trial	385 healthy children aged 6 to 71 months with nonsevere CAP demonstrating early clinical improvement	On day 6 of their originally prescribed therapy, participants were randomized 1:1 to receive 5 days of matching placebo or 5 additional days of the same antibiotic.	End-of-treatment response adjusted for duration of antibiotic risk (RADAR), a composite end point that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects in an ordinal desirability of outcome ranking (DOOR) Treatment failure RADAR at OAV2 as well as DOOR and its components (adequate clinical response, resolution of symptoms, and antibiotic-associated adverse effects) at OAV1 and OAV2.	25 days OAV1 6–10 days OAV2 19–25 days	A 5-day antibiotic strategy was superior to a 10-day strategy. There were no significant differences between treatment strategies in proportions of inadequate clinical response at OAV1 (1% vs. < 1%; difference in proportion, 0.5%; 95% CI, − 2.4 to 3.7) or OAV2 (1% vs. 2%; difference in proportion, − 0.5%; 95% CI, − 3.9 to 2.8) When duration of antibiotic treatment was incorporated, the short-course strategy was superior, with an estimated probability of a more desirable RADAR for the short-course strategy of 0.69 (95% CI, 0.63–0.75) at OAV1. At OAV2, the probability of a more desirable RADAR in the short-course strategy was 0.63 (95% CI, 0.57–0.69).	Question 6
Short-course Antibiotic Treatment for Community-acquired Alveolar Pneumonia in Ambulatory Children. A Double-blind, Randomized, Placebo-controlled Trial Greenberg, 2014, RCT [41]	A double-blind, randomized, placebo-controlled trial	140 healthy children aged 6 to 59 months not vaccinated with non severe CAP	Stage 1: 3-day course vs. 10-day course of amoxicillin treatment Stage 2: 5-day course vs. 10-day course.	Absence of treatment failure within 30 days Temperature, difficult breathing, restlessness, coughing, loss of appetite and sleep disturbances assessed daily by the parents; laboratory tests: complete WBC counts and CrP at days 5–7 and 10–14	30 days	3-day oral treatment was associated with high treatment failure 5-day oral treatment with high-dose amoxicillin (80 mg/kg/d divided to 3 daily doses) is as effective as a 10-day treatment in children 6–59 months of age with nonsevere CAP	Question 6
Antibiotic Treatment for Children Hospitalized With Community-Acquired Pneumonia After Oral Therapy Breuer et al., 2015 [55]	Retrospective observational study	All children aged 3 months-18 years with uncomplicated CAP who received oral antibiotics prior to admission	Narrow spectrum antibiotics (penicillin, ampicillin, amoxicillin) versus broad spectrum antibiotics (ceftriaxone, cefuroxime, cefazolin)	Clinical outcome of previously healthy children with non-complicated CAP Duration of fever, duration of intravenous (IV) antibiotic therapy, and total hospital length of stay (LOS) Treatment failure (defined as a change in the antibiotic therapy after the first 24 h of treatment) and number of days of oxygen treatment.	Not specified	The broad spectrum-treated group had significantly better outcomes in terms of number of febrile days (1.2 ± 1.1 vs. 1.7 ± 1.6, p < 0.001), number of days treated with intravenous antibiotics (3.1 ± 1.3 vs. 3.9 ± 2.0, p < 0.001), and days of hospitalization (3.5 ± 1.5 vs. 4.2 ± 2.0, p < 0.001). The odds ratio for remaining hospitalized at 72 h and 7 days was significantly higher for the narrow spectrum group (2.0 and 5.5 respectively, p < 0.05)	Question 7

No study was sponsored or funded by pharmaceutical companies