PCR Tests Don’t Predict Response to Antibiotics in Coughing Kids PCR Tests Don’t Predict Response to Antibiotics in Coughing Kids

Antibiotics generally don’t 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, an antibiotic regimen makes little if any difference in how quickly children recover.

One 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 testing 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 how soon children got better, regardless of whether they received amoxicillin or 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 benefit from using them,” study author Paul Little, MD, professor of primary care research at the University of Southampton, United Kingdom, told Medscape Medical News.

None of these children likely needed antibiotics to begin with, so the findings are not surprising, said Rebecca Same, MD, with Washington University School of Medicine in St. Louis, Missouri, who was not involved in the study. And to the extent that testing leads to inappropriate antibiotic use, the use of such tests might 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 (LRTIs) and who were seen at general practices in the United Kingdom.

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

They excluded children with coughs that were deemed to be noninfectious in origin, such as hay fever, or that were almost certainly linked to a virus. If a clinician thought a child likely had pneumonia or was severely ill, the patient was not enrolled in the trial but could be included in an observational study.

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

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

Bacterial pathogens potentially sensitive to amoxicillin — Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae — were detected among 51% of the participants who received placebo and 49% of the participants who received antibiotics.

“There were no clearly demonstrated effect of antibiotics on duration or severity of symptoms, nor on reconsultations, according to microbiological subgroups,” the authors report.

The median duration of symptoms that were rated moderately bad or worse was about 1 day shorter in the group of children who received the antibiotic than in the placebo group when potentially antibiotic-susceptible bacteria were present (99% CI for the median difference in symptom duration, -12.3 to 10.3 days) or absent (99% CI, -4.5 to 2.5 days). Median duration of symptoms was 4 or 5 days when bacteria were present and 5.5 or 7 days when not. Results from 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 there may be a limited role for microbiological point of care tests for children with uncomplicated LRTI in primary care,” Little and co-authors write.

It is possible that inflammation ― not the pathogens themselves ― is driving symptoms by the time a patient sees a doctor, the investigators say.

Molecular testing 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 told Medscape Medical News.

The findings from ARTIC-PC agree with those from a larger trial in adults known as GRACE.

In the adult population, as in the pediatric population, “simply identifying the presence of a bacterium was not sufficient to predict benefit from antibiotics,” Little added. The only adults who appeared to benefit from antibiotics were those “with both viral and bacterial organisms present — presumably an initial viral infection and then the bacterium taking advantage of the damaged mucosa. So it may be that at least some bacteria are commensal and either do not cause the infection or are facultative pathogens when the chance arises, or that sufficient numbers are resistant to the antibiotics.”

Possible Harm

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

“We already know that these children don’t need antibiotics,” Same said. “So this test does not really help me one way or another and could be harmful because it could convince people to give antibiotics for something that is not fundamentally a bacterial infection.”

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

By not prescribing antibiotics, clinicians also can prevent patient harm by avoiding drug side effects and potential long-term consequences, such as increased risk for obesity or allergies associated with the use of antibiotics, Same said.

She recently edited a special issue of Infectious Disease Clinics that focused on pediatric infections. One of the articles highlighted how antibiotics are commonly overprescribed to children in outpatient settings — most often for acute respiratory tract infections.

Keeping patients as comfortable as possible through their acute symptoms with treatments such as pain relievers for headache or nasal saline spray for congestion will help them more and would be “significantly 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 has received grants from the EU and the Netherlands Organization of Health Research and Development, as well as grants from Abbott, Becton Dickinson, bioMerieux, and Janssen Pharmaceuticals. Little and Same have disclosed no relevant financial relationships.

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

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