Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial

Abstract

Background

Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule.

Methods and findings

In a stepped-wedge cluster randomised trial, we included children aged 1–60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently ( p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study.

Conclusions

In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule.

Trial registration

Netherlands Trial Register NTR5326.

Abstract

In a stepped-wedge cluster randomized trial, Josephine van de Maat and colleagues evaluate a clinical decision rule to guide antibiotic prescription in children suspected of lower respiratory tract infections in The Netherlands.

Author summary

Why was this study done?

• Symptoms of lower respiratory tract infections (RTIs) are very common in children, and the most common reason for children to receive antibiotics in the emergency department (ED).

• A large number of these antibiotic prescriptions may be unnecessary, because most respiratory infections in children are caused by viruses, which are not susceptible to antibiotic treatment.

• Currently, there is no good test to determine whether an infection is caused by a virus or by bacteria, resulting in over-prescription of antibiotics, which in turn can lead to side effects and antibiotic resistance.

What did the researchers do and find?

• We introduced a clinical decision rule for children with suspected lower RTI in the ED, advising doctors about the child’s risk of having a bacterial infection (based on their symptoms), so that they would not prescribe antibiotics to children who had a low or intermediate risk.

• We found that this decision rule did not reduce antibiotic prescriptions when we looked at all children, but that it was safe to use the rule.

• It seemed that, with this decision rule, a higher number of children responded well to their initial treatment (for example, fewer children needed antibiotics in the week after the ED visit, and more children recovered quickly) and that the antibiotic prescriptions shifted from children at low/intermediate risk towards children at high risk of bacterial infection.

What do these findings mean?

• We observed that it was safe to use the decision rule for guiding antibiotic treatment in children with a suspected lower RTI in the ED.

• It also seemed that, with the decision rule, antibiotics were more often prescribed to children who actually needed them, leading to better recovery from the disease.

• Limitations of our study were that it took more time than expected to organise the logistics of the trial before introduction of the decision rule, and that not all children received a C-reactive protein blood test in the usual care (control) period of the trial, which may have influenced the power of the study.