Is five days just as effective a treatment period as 10 days?
It’s been a busy shift as you go down the hall to see the five-year-old in bed 3. Per the resident’s report, this is a previously healthy, fully-immunized boy who is here with a fever of 102.
His mother reported that he had come down with a cough, runny nose and nasal congestion five days ago. He had a low-grade fever in the first 48 hours of symptoms, but none since until today. He had gone to see his PCP on the second day of illness and had a negative PCR for COVID-19. He was also tested for influenza and that too was negative. His mother thought he had been getting better until today’s fever spike.
Here his temperature was 38.9 at triage with a heart rate of 130, respiratory rate of 40 and a blood pressure of 105/70. His oxygen saturation was 94% on room air. The nursing note indicates ibuprofen was given shortly after arrival and the mother feels he is already looking better. He is sitting and playing with an electronic toy and looks happy and engaged. He is certainly not toxic appearing. He is no longer tachycardic, but his respiratory rate remains slightly elevated at 38 and he has mild retractions and some focal crackles in the left base.
Based on his history and examination, your clinical diagnosis is pneumonia. Given that this new fever developed late in the course of a viral upper respiratory illness, this sounds like a bacterial superinfection. So the usual questions apply. What bugs, what drugs and what testing would be appropriate in this scenario?
The majority of pediatric pneumonia is caused by Streptococcal pneumoniae, despite the wide-spread us of the S. pneumoniae vaccine. So the odds-on best empiric treatment remains amoxicillin. You remember that you need to give a high-dose regimen to reach the MIC (minimum inhibitory concentration). And you also recall that a thrice-daily dosing schedule will provide more killing time (the serum concentration over the MIC).
So the optimal dosing schedule would be 90 mg/kg/day divided TID. [[1]] (At this point your resident looks confused. Don’t we dose amoxicillin BID for ear infections? That’s because of the prolonged half-life of the medication in middle ear fluid. [[2]] You can’t extrapolate this to lung infections).
The resident wants to know about blood work and chest imaging. Based on the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America Guidelines on the treatment of community-acquired pneumonia in children, neither is necessary.[[3]] And treatment for Mycoplasma pneumoniae is controversial and may not be necessary either. [[4]]
So, you have decided that this well-appearing child can be diagnosed clinically based on his history and physical exam. You recall that there is an increasing amount of adult literature supporting short-courses of antibiotics for pneumonia.[[5]] Can you do this for our patient? What does the literature say in children?
A recent study was published in JAMA Pediatrics assessing this very issue.[[6]] The study, which took place in Canada, aimed to see if five days of amoxicillin was as good as 10 days in reaching a clinical cure. The study design was a randomized clinical trial that took place in two centers. Participants were aged six months to 10 years with community-acquired pneumonia (CAP) who were well enough to be treated as outpatients.
CAP was defined as having all of the following: fever, tachypnea, a positive chest x-ray per the ED physician and a primary diagnosis of CAP per the ED physician. Patients were excluded if they had significant co-morbidities, needed admission to the hospital or if they had recently been on beta-lactam antibiotics.
The study started out as a pilot in a single center and then ran in parallel at two separate centers. Patients were given either 10 days of amoxicillin or a five-day course of amoxicillin followed by five days of a placebo.
Clinical cure was defined as: initial improvement in the first four days, including resolution of fever, significant improvement of dyspnea and increased work of breathing with complete resolution of tachypnea, no more than one fever spike after day 4, and no requirement for additional antibiotics, admission or further intervention. Caregivers kept a diary and were phoned at day 3, day 5, once between day 7 and 10 and were seen in follow-up sometime around day 14-21.
The results mirrored those of the adult trials. There was no significant difference in the rates of clinical cure between the short-course and long-course antimicrobial groups.
Now we have some good evidence that five days work as well as 10 for the treatment of CAP in children. What are the advantages of a shorter course? It reduces selection pressure for the development of resistant organisms for one thing.
In the SAFER study they noticed less absenteeism in the short course group, likely reflecting fewer side effects. Indeed fewer side effects have been shown in other studies comparing short to long courses of antibiotic treatment.[[7]]
Are there any other studies to support short treatment courses for CAP in pediatric patients? A systemic review of four studies involving 6,177 children ages 2-59 months with non-severe CAP was published in 2008. [[8]] The studies reviewed also showed no significant difference in clinical cure rates, treatment failure or relapse.
Your decision is made. You send the child home with a prescription for five days of high-dose, TID amoxicillin, supportive care and plans for close follow-up. On to the next patient.
References
[1] Messinger AI, Kupfer O, Hurst A, Parker S. Management of pediatric community-acquired bacterial pneumonia. Pediatrics in Review. 2017;38:394-407.
[2] Ibid, Messinger et al.
[3] 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. CID 2011:53.
[4] Ibid, Messinger et al.
[5] Gundersen KM, Jensen JN, Bjerrum L, Hansen MP. Short-course vs long-course antibiotic treatment for community-acquired pneumonia: a literature review. Basic Clin Pharmacol Toxicol. 2019;124:550-559.
[6] Pernica JM, Harmon S, Kam AJ, et al. Short-course antimicrobial therapy for pediatric community-acquired pneumonia. The SAFER randomized clinical trial. JAMA Pediatri.doi:10.1001/jamapediatrics.2020.6735. Published online March 8, 2021.
[7] Dawson-Hahn EE, Mickan S, Onakpoya I, et al. Short-course versus long-course oral antibiotic treatment for infections treated in outpatient settings: a review of systemic reviews. Family Pract, 2017;34:511-519.
[8] Haider BA, Saeed MA, Bhutta ZA. Short-course versus long-course antibiotic therapy for non-severe community-acquired pneumonia in children aged 2-59 months. Cochrane Database Syst Rev 2008;2:CD005976.
1 Comment
What was the number of patients in the
Journal of pediatrics article that was quoted?