Trial Shows Short Antibiotic Course Superior to Standard Longer One in Children With Nonsevere Pneumonia

Antibiotics are essential, lifesaving drugs that kill bacteria or slow their growth. Some bacteria have developed ways to resist antibiotics (a process called antibiotic resistance); it is critical to use antibiotics properly to minimize this serious risk.[1]

Appropriate use of antibiotics can be defined as the use of the right antibiotic at the right dose for the proper duration for a specific condition.[2] Particularly, when supported by research evidence, shortening the duration of antibiotic therapy is advantageous for treating infections only for as long as needed, thereby reducing unnecessary antibiotic exposure and the risk of related adverse effects.[3]

The standard duration of antibiotic therapy for community-acquired pneumonia — a common condition in children under five years of age — has been 10 days, according to the most recent guidelines of the Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA).[4] Although the PIDS/IDSA guidelines suggested that shorter antibiotic courses “may be just as effective” as standard courses, such shorter courses had not been adequately studied in children at the time these guidelines were issued in 2011. Since then, a 2021 Canadian randomized clinical trial showed that a five-day antibiotic course is not inferior to the standard 10-day course in children with community-acquired pneumonia who did not require hospitalization.[5]

Moreover, a recent U.S. randomized, placebo-controlled clinical trial demonstrated even better results with five-day antibiotic treatment in children with community-acquired pneumonia who were improving with the treatment and did not require hospitalization.[6] These findings are reassuring given that caregivers generally prefer shorter treatments.

This recent trial was funded by the National Institutes of Health and its findings were published in the March 1, 2022, issue of the Journal of the American Medical Association (JAMA) Pediatrics.

Community-acquired pneumonia and related antibiotic treatment

Community-acquired pneumonia is a common and potentially serious illness that typically is characterized in children under five years of age by cough, rapid breathing or other signs of difficulty breathing; fever may or may not be present.[7],[8] It is caused by an infection of the parts of the lung that contain small sacs called alveoli, which normally expand with air when inhaling, in individuals who have acquired the infection in the community (as opposed to in a hospital or similar setting).

Community-acquired pneumonia generally is treated in an outpatient setting unless it is severe (signs of severe infection in children include grunting, nasal flaring, inability to drink or eat, lethargy and unconsciousness)[9] or is associated with complications (including pleural effusion [fluid accumulation around the lung]), which is known as complicated pneumonia.[10]

The oral beta-lactam antibiotic amoxicillin (AMOXIL, LAROTID), which is chemically similar to penicillin, is the drug of choice in otherwise healthy children under five years of age with community-acquired bacterial pneumonia who do not require hospitalization.[11] Other beta-lactam antibiotics also can be used for community-acquired pneumonia, such as amoxicillin and clavulanate (AUGMENTIN) and the cephalosporin cefdinir (available in generic only).[12] Children’s responsiveness to antibiotics within the first two to three days of treatment initiation helps to determine whether additional evaluation or changes in therapy are warranted.

The JAMA Pediatrics trial[13]

The 2022 trial involved 380 racially diverse children between the ages of six months to six years (mean age was three years, and 51% were male) who had been diagnosed with uncomplicated community-acquired pneumonia in an outpatient clinic, urgent care center or emergency department. These children had been prescribed twice-daily doses of an oral beta-lactam antibiotic by their health care professionals. Amoxicillin was the prescribed antibiotic for 91% of these children, and the remaining 9% were prescribed either a combination amoxicillin and clavulanate drug or cefdinir.

Trial staff randomized the children, who had been experiencing early clinical improvement of pneumonia by the sixth day of their originally prescribed antibiotic therapy, to one of two groups. The first group (191 subjects) was given five additional days of their initial antibiotic (standard 10-day antibiotic strategy) and the second group (189 subjects) received five days of a matching placebo only (five-day antibiotic strategy). The placebos were identical to the initial antibiotic in appearance and taste. To minimize bias, the subjects and their parents or guardians, investigators and trial staff were blinded to antibiotic-strategy assignment throughout the trial, a procedure known as double-blinding.

The children were otherwise healthy, did not require hospitalization and did not have an abnormally rapid breathing rate (more than 50 breaths per minute for children younger than two years or more than 40 breaths per minute for older children), fever over 101oF or severe cough.

The trial researchers found no statistically significant differences in the end-of-treatment response among subjects in both treatment-strategy groups. Specifically, the proportions of inadequate clinical response did not exceed 1% and no children died or required hospitalization or surgery for persistent or worsening pneumonia in either group. The proportions of subjects who had persistent symptoms were 7% and 8% in the five-day and 10-day antibiotic groups, respectively. Although antibiotic-associated adverse effects were common among subjects, they were typically mild (such as diarrhea and irritability) and did not differ by treatment strategy.

However, when the researchers incorporated the duration of antibiotic treatment into their analysis, they found that the five-day strategy had a 69% probability of a more desirable outcome by the tenth day of the trial than the 10-day strategy. Therefore, they concluded that the five-day strategy was superior to the standard 10-day strategy.

Another advantage of the five-daystrategy is that it resulted in a significantly lower abundance of bacterial antibiotic-resistance genes, as determined by an analysis of the bacteria in throat swabs collected from a subset of subjects from both groups.

In summary, the trial indicates that otherwise healthy, young children with uncomplicated community-acquired pneumonia generally do well with a five-day antibiotic course as long as they are monitored for continued improvement.

What You Can Do

If you have a child with pneumonia who is otherwise healthy, discuss this article with their doctor. If the doctor prescribes an antibiotic for your child, it is important to give the drug to the child as directed; do not skip doses or stop it without talking with the doctor. Tell the doctor if your child experiences new or unusual symptoms or develops significant adverse effects.
 

References

[1] Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2019. December 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. Accessed July 7, 2022.

[2] Dryden M, Johnson AP, Ashiru-Oredope D, Sharland M. Using antibiotics responsibly: right drug, right time, right dose, right duration. J Antimicrob Chemother. 2011;66(11):2441-2443.

[3] Rice LB. The Maxwell Finland Lecture: for the duration—rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile. Clin Infect Dis. 2008;46(4):491-496.

[4] Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76.

[5] Pernica JM, Harman S, Kam AJ, et al. Short-course antimicrobial therapy for pediatric community-acquired pneumonia: The SAFER randomized clinical trial. JAMA Pediatr. 2021;175(5):475-482.

[6] Williams DJ, Creech CB, Walter EB, et al. Short-vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: The SCOUT-CAP randomized clinical trial. JAMA Pediatr. 2022;176(3):253-261.

[7] Barson WJ. Community-acquired pneumonia in children: Outpatient treatment. UpToDate. May 31, 2022.

[8] World Health Organization. Pneumonia fact sheet. November 11, 2021. https://www.who.int/news-room/fact-sheets/detail/pneumonia. Accessed July 7, 2022.

[9] Ibid.

[10] Quinonez R. Community-acquired pneumonia. In: American Academy of Pediatrics Section on Hospital Medicine. Gershel JC, Rauch DA, eds. Caring for the Hospitalized Child: A Handbook of Inpatient Pediatrics. American Academy of Pediatrics. 2nd ed. American Academy of Pediatrics; 2017:751-756.

[11] Barson WJ. Community-acquired pneumonia in children: Outpatient treatment. UpToDate. May 31, 2022.

[12] Ibid.

[13] Williams DJ, Creech CB, Walter EB, et al. Short-vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: The SCOUT-CAP randomized clinical trial. JAMA Pediatr. 2022;176(3):253-261.