PCT-guided algorithm does not reduce IV antibiotic treatment duration in children, study finds

3rd February 2025

Using procalcitonin (PCT) levels to guide intravenous antibiotic use in children hospitalised with bacterial infections does not shorten the duration of therapy compared with usual care, a large UK study finds.

Previous research had suggested that PCT – a rapid response biomarker for bacterial infection – could guide antibiotic discontinuation, but the test was not routinely used in the NHS, the study authors wrote in The Lancet Child & Adolescent Health.

In a multicentre trial at 15 hospitals in England and Wales, researchers assessed whether a PCT-guided algorithm would safely reduce the duration of antibiotic therapy in children hospitalised with confirmed or suspected bacterial infections compared with usual care, which commonly used C-reactive protein as a biomarker.

Children aged 72 hours to 18 years who were hospitalised and being treated with intravenous antibiotics for more than 48 hours were eligible for the trial.

Between 11 June 2018 and 12 October 2022, a total of 15,282 children were screened for eligibility, with 1,949 randomly assigned (1:1) to receive either current clinical management alone (usual care group) or clinical management with the addition of a PCT-guided algorithm (PCT group).

In the PCT group, plasma PCT levels were tested at baseline and every one to three days during intravenous antibiotic treatment.

Assay results were fed into an algorithm which provided guidance on antibiotic management; however, clinicians could decide to over-rule the algorithm.

PCT cost versus benefit

The study found the addition of a PCT-guided algorithm was non-inferior in terms of safety but did not reduce the duration of intravenous antibiotic use compared with usual care.

In addition, a cost-effectiveness analysis showed that PCT-guided antibiotic management was more costly than usual care.

The median intravenous antibiotic duration was 96 hours in the PCT group and 99.7 hours in the usual care group (hazard ratio 0.96 [95% CI 0.87–1.05]), data showed.

Of the 917 participants in the PCT group, 78 (9%) had at least one event covered by the composite safety outcome measure compared with 85 (9%) of 904 participants in the usual care group (estimated adjusted risk difference –0.81% [95% CI upper bound 1.11]).

Among the study limitations, the researchers noted low adherence to the PTC-guided algorithm (36% at first clinical review and 54% at any clinical review).

In addition, the four hospitals who recruited the most participants had already implemented antimicrobial stewardship programmes.

Clinician workflow challenges

Concluding, the authors recommended PCT-guided algorithms should be tested in subgroups of paediatric patients to establish whether they can reduce the duration of intravenous antibiotic treatment among patients with specific clinical characteristics.

Study chief investigator Professor Enitan Carrol, professor of paediatric infection at the University of Liverpool, UK, noted the study was a pragmatic trial in which clinicians did not have to adhere to the diagnostic algorithms.

‘Adherence to the algorithm was low in our study, and there were challenges in integrating the test into routine clinical workflows,’ he said.

‘The study highlights the importance of including behaviour change and implementation frameworks into pragmatic trial designs.’

The research, known as the ‘Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection’ (BATCH) trial, was led by the University of Liverpool and conducted in collaboration with Cardiff University’s Centre of Clinical Trials Research, with funding from the National Institute for Health and Care Research (NIHR).

It followed a National Institute for Health and Care Excellence recommendation for further studies to assess the effectiveness of adding PCT algorithms to guide antibiotic treatment in hospitalised adults and children with suspected or confirmed serious bacterial infections.

Late last year, a large NIHR-funded and commissioned trial in adults found PCT-monitoring could significantly reduce antibiotic overuse in sepsis.

Point-of-care test identifies bacterial and viral causes of acute respiratory infections

27th October 2022

A point-of-care test shows good sensitivity for identifying both bacterial and viral pathogens in patients with acute respiratory infections

A point-of-care test has been found to correctly distinguish between bacterial and viral infections based on the host’s immune response, among patients with acute respiratory infections according to the results of a diagnostic study by team of US researchers.

Respiratory symptoms are the motive for a third of emergency room visits by both adult and paediatric patients. Acute respiratory infections due to either acute bronchitis, sinusitis, pneumonia and the common cold often present with overlapping symptoms leading to over-prescribing of antibiotics. Although multiplex PCR systems are available for the identification of bacterial and viral pathogens, an alternative strategy is to use a point-of-care test based on the host’s immune response to myxovirus resistance protein A (MxA) and C-reactive protein (CRP) in a finger-stick whole blood sample. To test the value of this approach in helping clinicians to decide on whether or not to prescribed antibiotics, in the present study, the US team examined the ability of the FebriDx^® which is a rapid, point-of-care diagnostic test that is designed to aid in the differentiation of bacterial and viral acute respiratory infections. The test can provide a result within 10 minutes by identifying myxovirus resistance protein A, which is induced by type 1 interferon due to viral infections and CRP, a non-specific acute-phase protein produced in response to inflammation and infection. While CRP is not specific for bacterial infections, if only MxA levels are elevated (i.e., no change in CRP) this is indicative of a viral infection. Similarly, elevated CRP in the absence of MxA, indicates a bacterial infection.

The US team recruited patients from emergency departments and outpatient settings who presented with new-onset respiratory symptoms including rhinorrhoea, nasal congestion, sore, throat, hoarseness, cough or shortness of breath and a recent fever and an asymptomatic control group. The point-of-care test was administered to both groups of patients although the treating physicians were blind to the test results. The primary outcome was set as a bacterial or viral-associated systemic host response. In addition, patient samples were collected and analysed by multiplex PCR for either viral or bacterial identification and which served as independent assessment of the point-of-care test result.

Point-of-care test and bacterial or viral identification

A total of 520 symptomatic patients with a mean age of 35.3 (44.2% male) were included and 170 in the asymptomatic group.

Final diagnostic information was available for 496 individuals and of whom, 14.7% had a confirmed bacterial and 59.7% a viral infection with the remainder classed as negative. The point-of-care test correctly identified 93.1% of bacterial infections giving a sensitivity of 93.2% (95% CI 84.9 – 97%), a specificity of 88.4% (95% CI 85 – 91.1%) and a positive predictive value of 58.1%.

For viral infections, the point-of-care test had a sensitivity of 70.3% (95% CI 64.8 – 75.2%), a specificity of 88% (95% CI 82.8 – 91.8%) and a positive predictive value of 89.7%. Interestingly, none of the participants had a co-infection which was defined as both a bacterial and viral pathogen plus a host response based on the independent assessment.

The authors concluded that the rapid diagnostic point-of-care test could help inform clinicians when assessing for either bacterial or viral causes for acute respiratory infections.

Citation
Shapiro NI et al. Diagnostic Accuracy of a Bacterial and Viral Biomarker Point-of-Care Test in the Outpatient Setting JAMA Netw Open 2022