We observed a significant reduction in antibiotic use in young children with a respiratory infection after physician training in the use of a simple evidence-based management algorithm. However, the study was greatly impacted by COVID-19 restrictions, which affected the numbers recrutied to the post-intervention period. Importantly, the reduced use of antibiotics was not associated with increased risk for disease progression or representation to hospital during active follow-up. Given that many children with respiratory symptoms in Vietnam and Asia receive antibiotics without a strong clinical indication (1, 9, 10), implementation of this algorithm may provide clinicians with a practical method to re-evaluate established practices and to encourage more judicious antibiotic use.
Studies in both African (11) and Asian settings (12) have demonstrated that wheeze is strongly associated with asthma or viral infections. Similar to the algorithm used in the intervention, revised WHO guidance for community acquired pneumonia recommends that a child with wheeze and no fever or danger signs, should not receive antibiotic treatment (13). Digital auscultation used in the multi-centre PERCH study, conducted in seven Asian and African countries, reported low mortality and reduced likelihood of radiographic pneumonia in children with an audible wheeze (14). In settings where special tests are available, a CXR and full blood count and/or CRP could provide clinicians with additional confidence to withhold antibiotics in a child with respiratory symptoms (15, 16).
Physicians in Asian countries prefer to have radiology and blood test results to guide the clinical management of children with ARIs (5, 15). Previous studies have identified a raised neutrophil count (≥ 10x109/L) and an abnormal CXR as markers of potential bacterial pneumonia (17–19), but the specificity is low. Although dense alveolar consolidation on CXR shows a consistent association with bacterial pneumonia (20, 21), these findings are often influenced by inclusion bias if CXR interpretation influenced disease classification and some studies have questioned the strength of the association (22). In the PERCH study, dense alveolar consolidation on CXR or the presence of pleural fluid were associated with Streptococcus pneumoniae or Staphylococcus aureus infection, but it was also observed in children who only had proof of a viral infection (19). The management algorithm used a CRP cut-off of 50mg/l, since a randomised controlled trial in Vietnam demonstrated that it is safe to withhold antibiotics in children with acute lower respiratory tract infections if the CRP is < 50mg/l (15).
It was hoped that the management algorithm would also reduce unnecessary hospital admission, but this could not be demonstrated in the current study. Due to parental pressure and hospital policy preference, clinicians often feel that hospitalisation is the ‘safe option’ (5). However, unnecessary hospitalisation poses can be harmful and increases health service costs (23, 24). Recent studies have shown that Vietnam is rapidly transitioning to become a middle income country with low child mortality (25) and bacterial pneumonia rates more comparable to high-income settings (26–29). A common perception among health workers is that the WHO clinical case-management approach for childhood pneumonia was developed for low-income countries, which is not applicable to Vietnam (30). Hence, an algorithm that differentiates children who present to hospital with ‘unlikely bacterial pneumonia’ from those with ‘likely bacterial pneumonia’ and which takes CXR and blood test results into account has more appeal in settings where these tests are readily available (30).
The ‘WHO danger signs’ was the strongest predictor of pneumonia mortality in the PERCH study (31) and ‘consolidation on CXR have also been shown to be a strong predictor of ‘adverse pneumonia outcome’ in Vietnam (8). We incorporated both these factors in the algorithm and have shown that their consideration is highly feasible in a hospital-based setting, where CXR findings provide clinicians with another important line of information and reduces parental anxiety (32). Given the sharp decrease in the number of hospital presentations and the change in patient profile due to the COVID-19 lockdown, we could not assess the impact of algorithm training on hospital admisison rates. Perceived parental pressure and physician’s reluctance to miss potentially serious disease have been reported as the main drivers of unnecessary antibioitc use in Vietnam (33).
There are major study limitations to emphasise. Firstly, patient numbers after the intervention were greatly reduced, due to strict COVID-19 lockdowns implemented during this time. We acknowledge that the epidemiology of other ARIs may also have changed, due to strict COVID-19 social distancing and health system disruption (34, 35), as well as effects of the SARS-CoV-2 virus (36). Although clinical symptoms were broadly comparable between the two periods, more children were excluded after the intervention reflecting thefact that more older children refered from district hospitals during this time. In general the children included after the intervention were expected to be a sicker cohort, which would have biased against observing a signficant reduction in antibiotic use. Secondly, less CXRs were done during COVID-19 restrictions, but again the expectation is that this might have increased antibiotic use if physicians felt that it was more difficult to rule out bacterial pneumonia. Data collection for baseline study period fell in a winter-spring season, whereas the two-month intervention period were summer season, but Vietnam does not display clear seasonal patterns in the frequency of acute respiratory tract infections (1).
In conclusion, we observed a significant reduction in antibiotic use among children with ARIs after doctors were trained in the use of a simple management algorithm and no major risks were documented. However, given the confounding impact of the COVID-19 pandemic that emerged during the study period, our findings need to be interpreted with caution and further evaluation to confirm the impact and safety of the proposed intervention is required.