May 20, 2022

PCR tests do not predict response to antibiotics in children with cough

Antibiotics usually do not help children with respiratory infections, many of which are caused by viruses. New research shows that even when throat swabs reveal the presence of bacteria, antibiotic treatment makes little or no difference in how quickly children recover.

A recent idea is to use polymerase chain reaction (PCR) testing to identify patients with acute cough who have bacterial infections amenable to antibiotic treatment.

But a new analysis of data from a randomized controlled trial found that PCR tests could not identify respiratory infections that warranted antibiotic treatment.

The tests often detected bacteria. However, neither the presence of bacteria nor the type of pathogen determined when children got better, whether or not they received amoxicillin or a placebo, the study authors report in Clinical microbiology and infection.

Clinicians should resist the temptation to use such tests “until it is clear that there is a benefit to using them,” said study author Paul Little, MD, Professor in primary care research at the University of Southampton, UK. Medscape Medical News.

None of these children likely needed antibiotics to begin with, so the results are not surprising, said Rebecca Same, MD, of Washington University School of Medicine in St. Louis, Missouri, who n did not participate in the study. And to the extent that the tests lead to inappropriate use of antibiotics, the use of such tests could be harmful, she said.

ARTIC PC

For their new analysis, Little and his colleagues focused on data from the ARTIC-PC trial, a placebo-controlled trial that included more than 400 children aged 6 months to 12 years who had acute lower respiratory tract infections. (IVRI) and which have been seen in GP surgeries in the UK.

The researchers included children who had had a cough for less than 21 days, along with other lower respiratory tract symptoms, such as shortness of breath, sputum or pain.

They excluded children with cough deemed to be of non-infectious origin, such as hay fever, or which were almost certainly related to a virus. If a clinician thought a child likely had pneumonia or was seriously ill, the patient was not enrolled in the trial but could be included in an observational study.

The children in the trial were randomly assigned to receive 50 mg/kg/day of amoxicillin in three divided doses for 7 days or a placebo. Clinicians also took throat swabs for multiplex PCR testing.

Researchers had swab results for 71% of trial participants (306 of 432). Swab data were also available for 59% of observational study participants (182 of 326).

Pathogenic bacteria potentially susceptible to amoxicillin — Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae — were detected in 51% of participants who received placebo and 49% of participants who received antibiotics.

“There was no clearly demonstrated effect of antibiotics on the duration or severity of symptoms, or on reconsultations, according to microbiological subgroups”, report the authors.

The median duration of symptoms rated moderately bad or worse was approximately 1 day shorter in the group of children who received the antibiotic than in the placebo group when bacteria potentially susceptible to antibiotics were present (99% CI for median difference in symptom duration, -12.3 to 10.3 days) or absent (99% CI, -4.5 to 2.5 days). The median duration of symptoms was 4 or 5 days in the presence of bacteria and 5.5 or 7 days in the absence of bacteria. The results of the observational study were similar, according to the researchers.

“The lack of clear evidence between microbiological findings in the upper tract, the only site that could be feasibly sampled in routine primary care, and the impact of antibiotics, suggests that point-of-care microbiological testing may have a limited role for children with uncomplicated LRTIs in primary care,” Little and co-authors write.

It’s possible that the inflammation — not the pathogens themselves — is causing symptoms by the time a patient sees a doctor, investigators say.

Molecular tests for lower respiratory tract infections may not be widely used currently, but “there is a lot of discussion in this area and a whole range of tests being developed,” Little said. Medscape Medical News.

ARTIC-PC’s findings are consistent with those of a larger trial in adults known as GRACE.

In the adult population, as in the pediatric population, “simple identification of the presence of a bacterium was not sufficient to predict the benefit of antibiotics,” Little added. The only adults who seemed to benefit from antibiotics were those “with both viral and bacterial organisms present – presumably an initial viral infection and then the bacteria taking advantage of the damaged mucosa. So it may be that at least some bacteria are commensal and either don’t cause not infection or are optional pathogens when the opportunity arises, or enough people are resistant to antibiotics.”

Possible damage

Although PCR tests find microbes, it’s unclear whether the results identify a bacterial infection or a person’s normal microbiome, Same said. The distinction is critical.

“We already know that these children don’t need antibiotics,” Same said. “So this test isn’t really helping me one way or the other and could be harmful because it could convince people to give antibiotics for something that isn’t basically a bacterial infection.”

Antibiotic stewardship programs aim to limit the unnecessary use of drugs to stop the development of antibiotic-resistant pathogens.

By not prescribing antibiotics, clinicians can also prevent harm to patients by avoiding medication side effects and potential long-term consequences, such as an increased risk of obesity or allergies associated with antibiotic use, says Same.

She recently edited a special issue of Infectious Disease Clinics focused on pediatric infections. One of the articles highlighted how antibiotics are commonly over-prescribed to children on an outpatient basis — most often for acute respiratory tract infections.

Keep patients as comfortable as possible during their acute symptoms with treatments such as painkillers to headache or nasal saline spray for congestion will help them more and would be “much less harmful in the long run than unnecessary antibiotics would be,” Same said.

The research was funded by the National Institute for Health and Care Research. A co-author received grants from the EU and the Netherlands Organization for Health Research and Development, as well as grants from Abbott, Becton Dickinson, bioMérieux and Janssen Pharmaceuticals. Little and Same have disclosed no relevant financial relationship.

Clin Microbiol Infect. Published online March 10, 2022. Full Text

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