– treatment duration

– antibiotic treatment

-Systematic Review

-Randomized Control Trial

Last 5 Years

– antibiotic duration for CAP

-last 5 years

-Last 5 years

–

-last 5 years

-last 5 years

-last 5 years

Antibiotics are among the most frequently prescribed medicines for children worldwide, and the most common indication is acute respiratory tract infection. Community-acquired pneumonia (CAP) accounts for a substantial proportion. Although the majority of pneumonia deaths occur in low- and middle-income countries, CAP is a major cause of morbidity in Europe and North America.

According to current guidance, including guidance from the British National Formulary for Children (BNFc) and the British Thoracic Society (BTS) in the UK, amoxicillin is the recommended treatment for childhood CAP. Twice-daily dosing is widely recommended internationally, but the BNFc currently recommends amoxicillin (250 mg) three times daily for children aged 1–5 years, with a total daily dose similar to countries using twice-daily dosing. Owing to this age-banded dose selection, there is considerable variability in the effective total daily dose for treated children in the UK. In terms of duration, the 2019 National Institute for Health and Care Excellence treatment guidelines for childhood pneumonia recommend a 5-day course be prescribed, European and World Health Organization guidance has suggested that a 3- to 5-day course be prescribed and the BTS recognises that there are no robust data to inform duration. Overall, there is insufficient evidence to inform optimal amoxicillin dose or duration for childhood CAP.

Streptococcus pneumoniae is the bacterial pathogen most commonly associated with childhood CAP. The pneumococcal conjugate vaccination (PCV13) covers 13 serotypes of S. pneumoniae and was introduced in the UK in 2010, with an uptake of nearly 95%. Despite this, there has not been a significant reduction in CAP-related hospital admissions in young children. S. pneumoniae resistance to penicillin in the UK is relatively rare and generally low level, reported to be identified in approximately 15% of respiratory isolates and 4–6% of blood culture isolates. To the best of our knowledge, there are virtually no data on the impact of duration and dose of antibiotic treatment on colonisation with resistant bacteria in children, but the relationship is likely to be dynamic and highly complex.

Although there is clear agreement that amoxicillin should be used as the first-line agent in children requiring antibiotic treatment, there are insufficient data on the impact of amoxicillin dose and duration on clinical cure, drug toxicity and resistance to key bacteria, including S. pneumoniae.

Objectives

The main objective CAP-IT (Community-Acquired Pneumonia: a protocol for a randomIsed controlled Trial) was to determine the following for young children with uncomplicated CAP treated after discharge from hospital if:

a 3-day course of amoxicillin is non-inferior to a 7-day course, determined by receipt of a clinically indicated systemic antibiotic other than trial medication for respiratory tract infection (including CAP) in the 4 weeks after randomisation up to day 28

lower-dose amoxicillin is non-inferior to higher-dose amoxicillin under the same conditions.

Secondary objectives were to evaluate the impact of lower-dose and shorter-duration amoxicillin on antimicrobial resistance, severity and duration of parent/guardian-reported CAP symptoms and specified clinical adverse events (AEs) (i.e. rash and diarrhoea).

Methods

Trial design

CAP-IT was a multicentre clinical trial with a target sample size of 800 participants conducted in hospitals in the UK and Ireland. It was a randomised, double-blind, placebo-controlled, 2 × 2 factorial, non-inferiority trial that evaluated amoxicillin dose and duration in young children with CAP.

Interventions

Amoxicillin suspension was orally administered by parents/guardians twice daily. All children were weighed during eligibility screening to determine dose volume according to seven weight bands. Children were randomised to receive either a lower (35–50 mg/kg/day) or a higher (70–90 mg/kg/day) dose, and to receive either 3 or 7 days of amoxicillin at the point of discharge from hospital.

Randomisation and blinding

Patients underwent two simultaneous factorial 1 : 1 randomisations (dose and duration), resulting in their allocation to one of the four amoxicillin regimens (low dose, short duration; low dose, long duration; high dose, short duration; or high dose, long duration) using computer-generated random permuted blocks of size eight, stratified according to whether or not they had received non-trial antibiotics in hospital before being enrolled. Initially, stratification was by paediatric ED or ward group, reflecting whether participants were admitted to inpatient wards or observation units or discharged directly from the ED. Following an amendment for the joint analysis of these groups, stratification was effectively based on whether or not participants had received in-hospital antibiotics prior to randomisation. Blinded investigational medicinal product (IMP) labels were applied to each treatment pack and participants were randomised by dispensing the next sequentially numbered pack in the active block.

All treating clinicians, parents/guardians and outcome assessors were blinded to the allocated treatment. Dose blinding was achieved by using otherwise identical amoxicillin products of two different strengths (125 mg/5 ml and 250 mg/5 ml). A placebo manufactured to match oral amoxicillin suspension was used to blind the duration. One brand of amoxicillin was used for the first 3 days, followed by either a second brand of amoxicillin or placebo for days 4–7. Parents were informed to expect a taste change between bottles, but they did not know whether this was because of placebo or alternative amoxicillin.

Conclusions

In summary, we found a 3-day treatment course of amoxicillin to be non-inferior to a 7-day course of amoxicillin, and a lower daily dose of amoxicillin to be non-inferior to a higher daily dose of amoxicillin, in terms of antibiotic retreatment for respiratory tract infection within 28 days. Time to resolution of parent/guardian-reported symptoms was similar in randomisation arms, except that mild cough lasted, on average, 2 days longer in participants in the shorter-duration arm than in participants in the longer-duration arm. AE rates and health-care services use within the 28-day follow-up period and penicillin non-susceptible pneumococcal colonisation rates at 28 days were similar in all dose and duration randomisation groups. No penicillin-resistant pneumococci were identified in samples from CAP-IT participants. Based on these findings, 3 days could be considered for the duration of amoxicillin treatment for children with uncomplicated pneumonia treated in the ambulatory setting. Current BNFc age-banded dosing in the UK results in a wide range of total daily doses, spanning both the lower and higher doses investigated in CAP-IT.

Social Context: The UK and the US are both diverse nations hosting a variety of people of different cultures and ethnicity. 

Economic Context : This study may also be affected by access to health care in both countries. The UK has universal access to healthcare so most patients will likely comply with treatment instructions.

Language: Besides slight changes in accent, pronunciation, vocabulary and spelling, both countries speak english.

https://pneumonia.biomedcentral.com/articles/10.1186/s41479-017-0039-9

The optimal treatment duration of community-acquired pneumonia (CAP) in children has been controversial in high-income countries. We conducted a meta-analysis to compare short antibiotic treatment (3–5 days) with longer treatment (7–10 days) among children aged ≥6 months.

Methods

On 31 January 2022, we searched PubMed, Scopus, and Web of Science databases for studies published in English from 2003 to 2022. We included randomized controlled trials focusing on antibiotic treatment duration in children with CAP treated as outpatients. We calculated risk differences (RDs) with 95% confidence intervals and used the fixed-effect model (low heterogeneity). Our main outcome was treatment failure, defined as need for retreatment or hospitalization within 1 month. Our secondary outcome was presence of antibiotic-related harms.

Results

A total of 541 studies were screened, and 4 studies with 1541 children were included in the review. Three studies had low risk of bias, and one had some concerns. All 4 studies assessed treatment failures, and the RD was 0.1% (95% confidence interval, −3.0% to 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% to 5.0%) with moderate quality of evidence. The diagnostic criteria varied between the included studies.

Conclusions

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. We suggest that short antibiotic courses can be implemented in treatment of pediatric CAP.

Social Context: Finland places high attention on social equality. They collect funds through welfare programs and taxation to provide for the rest of the community

Economic Context: Finland has universal healthcare and has less of a concern for antibiotic resistance when compared to the US

Language: The US language is predominantly English speaking but has other languages such as Spanish, French and Chinese. The primary language of Finland is Finnish but 70% speak English as well.

https://www.oecd.org/els/health-systems/Antimicrobial-Resistance-in-G7-Countries-and-Beyond.pdf

https://www.nordictrans.com/is-english-widely-spoken-in-finland/

Methods

A search of PubMed, EMBASE, and Cochrane Central was conducted to identify randomized controlled trials (RCTs) comparing 5-day and 10-day courses of Amoxicillin for the treatment of CAP in children older than 6 months in an outpatient setting. Studies involving overlapping populations, lower-than-standard antibiotic doses, and hospitalized patients were excluded. The outcome of interest was clinical cure. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed using the Cochran Q test and I2 statistics. Two independent authors conducted the critical appraisal of the included studies according to the RoB-2 tool for assessing the risk of bias in randomized trials, and disagreements were resolved by consensus. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool to evaluate the certainty of evidence of our results. Three RCTs and 789 children aged from 6 months to 10 years were included, of whom 385 (48.8%) underwent a 5-day regimen. Amoxicillin-based therapy was used in 774 (98%) patients. 

Results

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%). The GRADE tool suggested moderate certainty of evidence.

Conclusion:

 These findings suggest that 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.

Cultural context: antibiotic treatment for pediatrics with pneumonia in Germany and the US do not differ much in terms of macrolides, beta-lactams and fluoroquinolones. These are guidelines issued under the Responsibility of the German Society for Pediatric Infectious Diseases (DGPI) and the German Society for Pediatric Pulmonology (GPP).

Economic Context: As stated, Germany has universal healthcare as long as pension programs. Since there is adequate access to healthcare, the results of the study are less likely to be skewed by ineffective methods, procedures and trials.

Language: The primary language spoken in Germany is German compared to English in the United States.

https://europepmc.org/article/med/32823360

To identify practice patterns in the duration of prescribed antibiotics for the treatment of ambulatory children with community-acquired pneumonia (CAP) and to compare the frequency of adverse clinical outcomes between children prescribed short-vs prolonged-duration antibiotics.

Study design

We performed a retrospective cohort study from 2010-2016 using the IBM Watson MarketScan Medicaid Database, a claims database of publicly insured patients from 11 states. We included children 1-18 years old with outpatient CAP who filled a prescription for oral antibiotics (n = 121 846 encounters). We used multivariable logistic regression to determine associations between the duration of prescribed antibiotics (5-9 days vs 10-14 days) and subsequent hospitalizations, new antibiotic prescriptions, and acute care visits. Outcomes were measured during the 14 days following the end of the dispensed antibiotic course.

Results

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.

Conclusions

Most children treated for CAP as outpatients are prescribed at least 10 days of antibiotic therapy. Among pediatric outpatients with CAP, no significant differences were found in rates of adverse clinical outcomes between patients prescribed short-vs prolonged-duration antibiotics.

(# of  subjects/ studies, cohort definition etc. )

 Ten participants received no trial medication and were excluded. Participants [median age 2.5 (interquartile range 1.6–2.7) years; 52% male] were randomised to either 3 (n = 413) or 7 days (n = 401) of trial medication at either lower
(n = 410) or higher (n = 404) doses. There were 51 (12.5%) and 49 (12.5%) primary end points in the 3- and 7-day arms, respectively (difference 0.1%, 90% confidence interval –3.8% to 3.9%) and 51 (12.6%) and 49 (12.4%) primary end points in the low- and high-dose arms, respectively (difference 0.2%, 90% confidence interval –3.7% to 4.0%), both demonstrating non-inferiority 

 lower daily dose of amoxicillin to be non-inferior to a higher daily dose of amoxicillin

Time to resolution of parent/guardian-reported symptoms was similar in both doses (except mild cough, on average 2 days longer)

Adverse effect rates and health-care services use within the 28-day follow-up period and penicillin non-susceptible pneumococcal colonization rates at 28 days were similar in all doses and duration randomisation groups.

Received 08 March 2022; editorial decision 30 April 2022; published online 17 May 2022

from 2003 to 2022. Researchers included randomized controlled trials focusing on antibiotic treatment duration in children with CAP

treated as outpatients. They calculated risk differences (RDs) with 95% confidence intervals and used the fixed-effect model (low

heterogeneity). Their main outcome was treatment failure, defined as need for retreatment or hospitalization within 1 month.

Their secondary outcome was presence of antibiotic-related harms.

(current) recommendation of 7–10 days in children aged ≥6 months with CAP. We suggest that short antibiotic courses can be implemented in treatment of pediatric CAP.

Shorter antibiotic treatments for pediatric CAP cases have, at least in theory, several potential benefits over current treatment strategies. Shorter courses may prevent development of antibiotic resistance by minimizing exposure of both pathogenic and nonpathogenic microbes of normal flora to antibiotics.

The need for retreatment was 8.3% in the short-course and 7.7% in the long-course group.

Two studies with 1194 children assessed all antibiotic-related adverse events. There were no differences between the groups

half of the patients were from a single study [16], but this

should not cause bias in the estimates, given that the results

were similar in all studies. 

Medicaid Database, a claims database of publicly insured patients from 11 states. They included children 1-18 years

old with outpatient CAP who filled a prescription for oral antibiotics (n = 121 846 encounters).

between patients prescribed short-vs prolonged-duration antibiotics.

apy, 0.2% of patients were hospitalized, 6.2% of patients, filled a new antibiotic prescription, and 5.1% of patients

had an acute care visit.

Patients receiving prolonged-duration therapy, patients

receiving short-duration therapy had a decreased risk of

filling a new antibiotic prescription.

and an increased risk of having a subsequent urgent/emer-

gency care visit but did not have

an increased risk of hospitalization

is the differing definition of CAP in the included studies, be-

cause 2 of them required chest radiographs and 2 did not.

and Evaluation) tool to evaluate the certainty of evidence of our results. Three RCTs and 789 children aged from 6 months to

10 years were included, of whom 385 (48.8%) underwent a 5-day regimen. Amoxicillin-based therapy was used in 774 (98%)

patients.

(10 days) for uncomplicated CAP in children under 10 years old.

-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.

-Generalizations should be made with caution considering the socioeconomic context of the population within the included studies

In the outpatient setting, a few international guidelines recommend a 10-day Amoxicillin course as first-line treatment for community-acquired pneumonia (CAP). “What is new:” When comparing 5-day to 10-day Amoxicillin regimens, evidence suggests no significant difference in clinical cure rates for uncomplicated CAP in outpatient settings.