Shorter Versus Longer Antibiotic Treatment in Children With Community-Acquired Pneumonia

A Systematic Review With Meta-Analyses

Background: Excessive antibiotic use promotes resistance and side effects and increases healthcare costs. Antibiotics are often prescribed to treat community-acquired pneumonia (CAP). The optimal duration of treatment is debated. In this study, we compare the efficacy of shorter and longer antibiotic treatment for CAP in the outpatient setting and evaluate the pertinent economic, environmental, ethical, and societal issues.

Methods: Relevant articles published up until 5 February 2024 were identified by searches in the electronic databases MEDLINE, Embase, and CENTRAL as well as in trial registries and in reference lists of systematic reviews, including health technology assessment (HTA) reports. All randomized controlled trials (RCTs) comparing short- and long-term antibiotic treatment in children with outpatient CAP were included in the benefit assessment. A 10% difference was set as the non-inferiority margin.

Results: Seven RCTs that studied a total of 8590 children were included. In young children with clinically diagnosed CAP, a three-day course of amoxicillin was non-inferior to 5-, 7-, or 10-day courses with respect to treatment success (relative risk [RR] 0.99; 95% confidence interval [0.96; 1.02]). Shorter treatment was associated with fewer (non-severe) adverse events (0.87, [0.78; 0.96]). Relapses and deaths were rare overall. Where shorter treatment was equally effective, it also had economic and ecological benefits.

Conclusion: Three days of antibiotic treatment with amoxicillin may be just as effective as longer treatment, and also better tolerated, in younger children with clinically diagnosed, outpatient, non-severe CAP, and would conserve resources. These findings can be taken into account in the formulation of guideline recommendations.

Cite this as: Benkendorff A, Puntscher S, Flatscher-Thöni M, Mühlberger N, Göhner A, Beck S, Bergt AC, Krabbe L, Heise TL, Gorenflo L, Rieg S, Hufnagel M, Breuer C, Kunzler AM, Siebert U, Meerpohl JJ, Schmucker C: Shorter versus longer antibiotic treatment in children with community-acquired pneumonia: A systematic review with meta-analyses. Dtsch Arztebl Int 2026; 123: 240–7. DOI: 10.3238/arztebl.m2025.0238

Bacterial resistance to commonly used antibiotics is a growing global problem, further aggravated by their inappropriate use (1). For a long time, it was assumed that a sufficiently long course of treatment could guard against such resistance by fully eradicating the bacteria (2). However, this has not been confirmed. On the contrary, given that each administration of antibiotics can induce resistance (3) and cause adverse reactions (4), many scientists now advocate a “shorter is better” approach to antibiotic treatment duration (3, 4, 5). Furthermore, pharmaceuticals contribute substantially to resource use, costs, and emissions in the healthcare sector (6, 7, 8, 9), and these could be reduced by shorter treatment durations.

Community-acquired pneumonia (CAP) is a widespread infectious disease in childhood, especially in children under ten (10). Despite its low mortality in Germany (<1/100 000/year) (11), pediatric CAP is a common reason for medical consultations and antibiotic treatment (12). The most common bacterial pathogens are Streptococcus pneumoniae and Haemophilus influenzae. (13). The diagnosis of CAP is usually made on purely clinical grounds (14). In practice, it is often difficult to differentiate this condition from viral pneumonia or bronchitis, for which antibiotic treatment is not indicated (14). These conditions are particularly prevalent among younger children (15). Supportive care alone may be sufficient, especially when signs of viral etiology are present (14).

If antibiotic treatment is indicated, then the drug of first choice is oral amoxicillin for five days, while macrolide therapy is recommended if atypical bacteria are suspected (14). Alternatives to this include amoxicillin–clavulanic acid, clarithromycin, or doxycycline (from eight years of age). The duration of antibiotic treatment is a current topic of debate in national and international guidelines (14, 16). Previous systematic reviews have pooled various treatment durations (17) with different antibiotic agents (17, 18). This significantly limits the applicability of the findings to specific treatment decisions. Also, other implications of a shorter course of antibiotic treatment remain unaddressed.

The aim of the present systematic review was to assess whether a shorter course of antibiotics in children with CAP in the outpatient setting yields treatment outcomes comparable to those of longer antibiotic treatment. In addition, the safety of shorter treatment and other non-medical, for example, economic, impacts of both treatment regimens are explored. The present study also undertook a literature review of CAP in adults in the outpatient setting. However, no appropriate studies were found, so the current evidence base remains unchanged. The following report, therefore, presents the results of antibiotic use in children with CAP.

Methods

The present systematic review was registered in advance in PROSPERO (CRD42024519113) and is reported here in accordance with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines (e1, e2).

On February 6, 2024, the electronic databases MEDLINE, Embase, and CENTRAL, along with four trial registries and the reference lists of systematic reviews, were searched and screened. Randomized controlled trials (RCTs) comparing a shorter with a longer outpatient course of oral antibiotic treatment in children with CAP were included. Studies were excluded if they used different antibiotics or doses, or if participants were treated in hospital because of the severity of their condition.

The assessment of risk of bias, statistical analysis, and the conduct of meta-analyses, as well as assessment of the certainty of evidence were based on the General Methods of the IQWiG (Institute for Quality and Efficiency in Health Care) (e3) Following the recommendations of the European Medicines Agency (EMA), a deviation of 10% was considered acceptable for all relevant clinical outcomes (e4, e5) and was therefore defined as the non-inferiority margin. For positive outcomes, such as “treatment success”, a relative risk (RR) greater than 0.9, including the 95% confidence interval (CI), is considered indicative of non-inferiority. With negative outcomes, such as “disease recurrence“, “mortality”, or “occurrence of adverse events” (AEs), non-inferiority is established when RR is less than 1.1 (including CI). After demonstrating non-inferiority, possible superiority of the shorter treatment regimen (RR <1.0; including CI) was also assessed for the outcome AEs.

The methodological details are presented in the eMethods section, in eTable 1 (search strategies), and in the ThemenCheck report protocol of the IQWiG (e6).

Results

Benefit assessment

The eFigure presents the flow diagram of the study selection process. Of 3874 records, seven studies (ten publications) involving 8590 children met the inclusion criteria (Table 1). No completed studies with unpublished results were identified in study registries.

Table 1

Characteristics of the included studies

eFigure

Flow diagram of study selection according to the PRISMA 2020 statement PRISMA, Preferred Reporting Items for Systematic reviews and Meta-Analysis; IC, Inclusion criteria; AOM, acute otitis media; CAP, community-acquired pneumonia

All included studies analyzed amoxicillin in children and compared various treatment durations (3 versus 5 days, 3 versus 7 days, 3 versus 10 days, or 5 versus 10 days). One study with two study phases examined treatment durations of 3 days versus 10 days and 5 days versus 10 days, independently (19). Three studies were conducted in countries with low middle income, and four studies in countries with high middle income. One study also included hospitalized children but provided stratified outcomes for the endpoint “treatment success” for children treated under outpatient conditions (20). The included studies, together with their key characteristics, are presented in Table 1, stratified by duration of antibiotic treatment. At study level, six studies were assessed as having a low risk of bias (20, 21, 22, 23, 24, 25), and one as having a high risk of bias (19) (eTable 2).

eTable 2

Outcome-specific risk of bias for the outcomes treatment success, recurrence, mortality and adverse events (AE) (according to the general methods of the IQWiG (e3))

Seven studies reported the outcome “treatment success“, six of which had a low (20, 21, 22, 23, 24, 25) and one a high (19) outcome-specific risk of bias (eTable 2). Treatment success was usually defined as improvement in clinical signs and symptoms, absence of pneumonia-related complications, and no need for subsequent or altered antibiotic use (eTable 3). Disease recurrence and death up to the time of data collection were also recorded as treatment failure. In the pooled effect estimate of the three studies that examined 5 days versus 10 days of amoxicillin treatment in children aged up to ten years, there was evidence for non-inferiority of the shorter treatment duration (RR: 1.00 [0.93; 1.08]; Figure, Table 2). Five studies involving preschool children compared amoxicillin therapy for three days with longer treatments (5, 7, or 10 days). The pooled assessment demonstrated non-inferiority of the shorter antibiotic treatment (RR: 0.99 [0.96; 1.02]; Figure, Table 2). Non-inferiority was also confirmed for the other time points reported in the studies (Table 3; eSupplement Figures S1 and S2) and in the sensitivity analyses conducted (Table 3; eSupplement Figures S3 and S4). The latter analyses did not include the MASCOT trial (23), as only a small number of children presented radiographic evidence of pneumonia.

Figure

Forest plots of the meta-analyses for the outcome “Treatment success” comparing 3 days versus 5/7/10 days (top) and 5 versus 10 days (bottom) of treatment duration. The dotted line indicates the non-inferiority margin (RR: 0.9). CI, confidence interval; RR, relative risk

Table 2

Summary of the findings in children with CAP

Table 3

Findings of the secondary assessment time points and sensitivity analyses

eTable 3

Definition of the outcome treatment success for CAP

Five studies reported the clinical outcome “disease recurrence” – two with a low (22, 24) and three with a high (19, 21, 23) outcome-specific risk of bias (eTable 2). For the comparison of 5 versus 10 days, CAP recurrences occurred in only one study (RR: 0.89 [0.41; 1.94]; eSupplement Graph S5). The same applied to three studies comparing three days with a longer treatment duration (pooled RR: 1.16 [0.72; 1.89]) (eSupplement Graph S6).

Seven studies also recorded mortality – six with a low (20, 21, 22, 23, 24, 25) and one with a high (19) outcome-specific risk of bias (eTable 2). Overall, deaths were rare, however, and occurred in only two studies (3 days versus longer duration of treatment, pooled RR: 0.43 [0.06; 2.91], eSupplement Graph S7; no deaths for 5 versus 10 days, eSupplement Graph S8).

Six studies reported the occurrence of AEs – four with a low (21, 23, 24, 25) and two with a high (19, 22) outcome-specific risk of bias (eTable 2). AEs were reported heterogeneously across the studies. For the most part, this included common adverse drug reactions, such as rash or gastrointestinal side effects, even though a (presumed) causal relationship was not always required (eSupplement Table S1). As regards hospitalization, a distinction was not always made between admission for pneumonia and admission for adverse effects of treatment. In most studies, there was no statistically significant difference between groups with respect to treatment duration (eSupplement Table S1). However, the wide confidence intervals usually did not allow any conclusions to be drawn about the non-inferiority of the shorter treatment duration (Table 2, eSupplement Table S1, eSupplement Graph S9). For the comparison of 3 versus 5 days of amoxicillin treatment, on the other hand, beyond non-inferiority shorter treatment even demonstrated superiority for non-severe AEs (RR: 0.87 [0.78; 0.96], Table 2, eSupplement Graph S10).

None of the identified studies collected data on health-related quality of life.

There was no difference in adherence between the treatment groups when the duration of drug administration was kept the same in both groups through the use of placebo (21, 22, 24, 25). One study showed that adherence declines with increasing treatment duration, regardless of placebo or active drug treatment (22) (eSupplement Table S2). Microbiological outcomes at completion of treatment were reported in only one study and differed only slightly across study arms (22) (eSupplement Table S3).

Further aspects

One study conducted in hospital outpatient clinics in India (22) showed lower costs for the shorter three-day treatment compared with the longer five-day treatment, with comparable efficacy. When applied to the German context, calculations indicated potential savings for the statutory health insurance system ranging from €0 to approximately €35 per disease course, depending on treatment duration and available pack sizes (e7, e8, e9) (eSupplement Tables S4–S6). Shorter antibiotic treatment could also potentially reduce environmental impacts and CO₂ emissions. Metabolites enter the environment during production, use, and disposal of antibiotics, thereby promoting resistance (e10, e11, e12, e13). In addition, CO₂ is generated during production: for example, 14.3 g of CO₂ is released per gram of amoxicillin (7). Apart from shorter duration of antibiotic treatment, the use of tablets instead of liquid forms also reduces CO₂ emissions (e14).

When deciding between different antibiotic treatments, it is important to maintain a fair distribution of resources among patients and to balance individual interests against interests of society – such as overall societal resource use, costs, or antibiotic resistance (e15, e16, e17). This is particularly relevant in the context of social disadvantage, which is associated with a higher risk of disease, while the disease itself can in turn have social consequences (e18, e19, e20, e21). Acceptance of, and adherence to, shorter treatments may also be improved by directly addressing fears and reservations among sick children and their caregivers and by engaging affected individuals in treatment decisions and advocacy groups in guideline-development processes (e22, e23, e24, e25, e26).

Discussion

The results of the present systematic reviews are presented in Table 2 and are consistent with previous systematic review findings (17, 18, 26). Comparable treatment outcomes were achieved with antibiotic treatment reduced to three days compared with a longer treatment duration in young children with clinically diagnosed CAP in the outpatient setting.

No formal non-inferiority was demonstrated for the outcomes “disease recurrence“ and “mortality”. However, this was due above all to the small number of such events and the resulting high statistical uncertainty, reflected in the wide confidence intervals of the relative risk. When considering the absolute values, no clinically relevant differences were apparent between the treatment groups. After accounting for absolute effect sizes, the overall analysis of all outcomes indicates non-inferiority in the studied patient population (Table 2). In addition, both recurrence and mortality were included in the evaluation of the composite outcome “treatment success”, for which the shorter treatment duration was clearly non-inferior.

A shorter treatment duration was even associated with an advantage with respect to non-serious adverse events. With a shorter treatment, more participants also appeared to take their medication as prescribed. In contrast, there was no clear advantage with respect to bacterial resistance. However, it should be noted that the present review did not include studies involving children who required hospital admission due to the severity of their illness. Therefore, the findings of the present publication are applicable only to the outpatient care setting for non-severe pneumonia. In addition, the studies included here used only amoxicillin as an antibiotic and treated only preschool children (up to around 5 years and 24 kg body weight) with clinically diagnosed CAP (19, 20, 21, 22, 23). Younger children are more commonly affected by viral pneumonia than older children (15), which may limit the applicability of the findings to other age groups or to radiographically diagnosed pneumonia.

Given the comparable diagnostic criteria, the usually absent signs of a viral etiology, and the patient symptoms, it can nevertheless be assumed that the majority of the study participants would also have been considered for antibiotic treatment in the German healthcare setting (14). However, given the high proportion of viral pneumonia among young children, the question also arises as to whether antibiotic treatment is indicated at all in those with clinically diagnosed CAP treated on an outpatient basis, or whether a watchful-waiting approach might be more beneficial (15).

Current German guidelines for the treatment of pediatric CAP without signs of viral etiology currently recommend a five-day course of antibiotics (14) (Box). The present review also demonstrated the non-inferiority of a five-day compared with a ten-day course of amoxicillin in children. Here, children up to ten years of age were also included. No data were available on health-related quality of life.

Box

Implications for the treatment of pediatric CAP

The results of three studies (21, 22, 23) conducted in countries with lower middle income and demonstrating non-inferiority of the shorter treatment duration were applicable to the German healthcare context for the following circumstances:

• comparable prevalence of viral pneumonia (15)
• comparable diagnostic criteria
• a small number of children with signs and symptoms of viral pneumonia (obstructive symptoms, evidence of respiratory syncytial virus [RSV]), and
• known risk factors for bacterial pneumonia, such as underweight (27) and no pneumococcal vaccination (28).

The results remained unchanged, even after sensitivity analyses excluding the MASCOT trial (23), in which fewer patients presented with radiological signs of pneumonia. The ISCAP study (22) also frequently detected colonization with Streptococcus pneumoniae and Haemophilus influenzae. Although these pathogens are cited as the most common causes of pneumonia, both globally (29) and in Germany (13), differences in pathogen and resistance spectra may arise from the different temporal and geographical contexts of the studies. Four studies (19, 20, 24, 25) were conducted in the treatment context of countries with high middle income and also reported largely comparable results for a shorter course of treatment.

The limitations of the present review arise from:

• the different definitions of the outcomes and times of data collection in the included studies
• the possible inclusion of viral pneumonia cases in the studies
• the rarity of some reported events, and
• absent data on health-related quality of life.

Furthermore, questions of non-inferiority present particular challenges: biocreep refers to the phenomenon in which multiple small yet acceptable differences within the non-inferiority margin accumulate across serial comparisons, finally resulting in a substantial difference that remains unrecognized due to serial testing (30). Bias can also develop from the uncritical use of the intention-to-treat analyses (31), although per-protocol analyses in the included studies yielded comparable results. In view of the methods adopted in the present review and the clear evidence of non-inferiority in the examined comparisons, it seems unlikely that these limitations or publication bias would have caused any significant distortion overall.

In the context of medical decision-making, however, the general application of a 10% non-inferiority margin, without regard to the clinical context, should be viewed critically when explicitly weighing efficacy against adverse events. For this purpose, the importance of efficacy outcomes relative to the severity of adverse events for patients should be critically assessed and ideally supplemented by formal benefit–risk assessments (32) based on absolute risk reductions and, where appropriate, decision-analytic modeling (33), which were not included in the present systematic review.

Conclusions:

In preschool children with clinically diagnosed non-severe CAP, treated on an outpatient basis, a shorter three-day course of amoxicillin was demonstrated to be non-inferior to a longer duration of treatment with respect to efficacy. In addition, the shorter treatment was shown to be better tolerated and may improve adherence. In the absence of RCTs, the effects of short antibiotic treatment in older children and adolescents, and of using antibiotics other than amoxicillin, remain uncertain. With largely comparable treatment outcomes and fewer adverse reactions, shorter treatment is also cost-effective, environmentally friendly, and resource-conserving, and appears to be ethically and socially sustainable.

Acknowledgments

We would like to thank Eberhard Thörel Institute for Evidence in Medicine, Medical Center – University of Freiburg / Medical Faculty – University of Freiburg, Germany) for his support in preparing the review protocol.

Funding

This systematic review is based on the ThemenCheck report (T23–04 “Antibiotic therapy -

Does shorter compared to longer-duration therapy lead to comparable treatment results?”), which was commissioned and funded by the Institute for Quality and Efficiency in Healthcare (IQWiG).

Conflict of interest statement

Alexander Benkendorff has shares in Fresenius Medical Care AG.

Nikolai Mühlberger has shares in the following pharmaceutical and biotechnology companies: AbbVie, BB Biotech, BioNTech, Fuji Pharma, Gilead Sciences, Merck & Co., Moderna, Novartis, Novo-Nordisk, Orion Corp., Pfizer, Roche, Sandoz Group, Sanofi, and Siemens Healthineers.

Siegbert Rieg has received lecture fees from the Academy for Infectious Medicine, Pfizer, bioMérieux, GSK, Falk Foundation, Med Update, streamedup!, Forum for Continuing Medical Education, Meet The Experts Academy, Publishing House of German Pharmacists, and German Consulting Center for Hygiene. He is a member of the Executive Committee of the German Society for Infectiology.

Markus Hufnagel has received professional fees for lectures from the German Academy for Development Promotion and Child and Adolescent Health.

The other authors declare that no conflict of interest exists.

Manuscript received on June 18, 2025, revised version accepted on December 15, 2025

Translated from the original German by Dr. Grahame Larkin

Corresponding authors:
Alexander Benkendorff

Jörg J. Meerpohl

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