This document summarizes several studies that compare the efficacy of shorter courses of antibiotic therapy (3 days) to traditional longer courses (5 days or more) for treating community-acquired pneumonia. Two studies found that 3 days of antibiotics was as effective as 5 days for treating non-severe pneumonia in children. However, another study found 3 days was less effective than 5 or 10 days for treating pediatric pneumonia. Additionally, one study suggested 3 days of IV antibiotics followed by 5 days of oral antibiotics was not inferior to 8 days of treatment for mild to moderate pneumonia in hospitalized adults.

1. Kimberly Treier
11 April 2016
3-Day versus 5-Day Antibiotic Therapy for Community-Acquired Pneumonia
Current guidelines, such Infectious Diseases Society of America/America
Thoracic Society1, recommend treatment of community acquired pneumonia with
antibiotic therapy for a minimum duration of 5. However, concerns for cost,
compliance and antibiotic resistance prompt the question of efficacy of shorter
antibiotic therapy in this disease management. Minimal data evaluating this
question exists at this time, however, a few studies published conflicting results as
to the effectiveness of shorter therapy in children younger than the age of 5. One
additional study suggests this may be an alternative option in adults requiring
hospitalized for pneumonia.
Previous studies of outpatient pediatric patients suggest a shorter course of
antibiotic therapy may be comparable to more traditional recommendations.
A randomized, double-blind, placebo-controlled trial2 of 2000 children aged 2-59
months with WHO-defined non-severe pneumonia in the outpatient setting of seven
Pakistani hospitals assessed the efficacy of 15 mg/kg oral amoxicillin every 8 hours
for three days (n=1000) versus five days (n=1000). Participants receiving antibiotic
for only three days received placebo in the same manner for the following two days.
Children with chronic illnesses, asthma or previous antibiotic use within the
preceding 48 hours were included and baseline characteristics were similar
between the two groups. Treatment failure, the primary outcome, occurred in 21%
of the three-day treatment group compared to 20% of the five-day group via
intention-to-treat analysis and no significant differences were identified. Of those
cured by day 14 of follow-up, disease relapse, the secondary outcome, occurred in
12/803 (1.5%) of children in the 3-day treatment group compared to 13/811
(1.6%) of the five-day group. Characteristics significantly associated with treatment
failure (p<0.0001) included age 2-11 months (OR 1.61, 95% CI 1.27-2.04), vomiting
(OR 1.56, 95% CI 1.14-2.13, p 0.004), illness duration of ≥ 3 days, respiration rate
above age-specific criteria (OR 1.81, 95% CI 1.43-2.27), and non-adherence in the
five-day group (OR 3.96, 95% CI 2.12-7.39). Though not statistically significant,
more participants in the five-day group reported side effects (8% versus 7%) at the
first follow-up (day 3) (OR 0.94, 95% CI 0.66-1.33, p=0.698). Thus, these results
suggest three days of amoxicillin therapy in children aged 2-59 months with WHO-
defined non-serious pneumonia is just as effective as five days of therapy.
After publication of the aforementioned trial, another study published similar
findings. This randomized, double blind, placebo controlled trial3 of 2188 children
aged 2-59 months with non-severe pneumonia in the outpatient setting of seven
Indian hospitals evaluated the efficacy of amoxicillin 31-54 mg/day for three days
followed by two more days of therapy (n=1093) or placebo (n=1095). Children with
severe pneumonia, other conditions requiring antibiotics, chronic diseases and a
penicillin allergy were excluded. Baseline characteristics were similar between the
two groups. The proportion of children recovering after three days compared to five

2. days of antibiotic therapy, the primary outcome, was 980/1095 (89.5%) and
983/1093 (89.9%), respectively, in the intention-to-treat analysis. The proportion
of relapse within the next 6-14 days, one of the secondary outcomes, was 58/1095
(5.3%) in the three-day treatment group and 48/1093 (4.4%) in the five-day group.
Characteristics significantly associated with treatment failure included non-
adherence at day 5 (OR 11.57, 95% CI 7.4-18.0), excess respiratory rate of >10
breaths/minute (OR 2.89, 95% CI 1.83-4.55) and nasopharyngeal swab positive for
respiratory syncytial virus (OR 1.95, 95% CI 1.0-3.8). Adverse effects occurred
similarly between the two groups. Thus, results from this study support the
hypothesis that three days of amoxicillin treatment in children aged 2-59 months
with non-severe pneumonia is as effective as five days of treatment.
A more recent study of outpatient pediatric patients presents data supports
traditional recommendations for antibiotic duration but shorter therapy may
be less effective.
A randomized, double-blind placebo-controlled trial4 of 140 children aged 6-
59 months with community-acquired alveolar pneumonia (CAAP) treated at a
regional hospital in Israel evaluated the efficacy of amoxicillin 80 mg/kg/day for
three, five or ten days. Children receiving antibiotics within the previous 14 days,
impaired immunity, more than one pneumonia episode within the past year, chronic
illness and/or presence of another condition requiring antibiotic therapy were
excluded. More children aged <24 months (58.3%) and males (75%) were included
in the three-day group. Baseline presentation characteristics did not differ with
statistical significance. Treatment for three (n=12) versus ten (n=13) days were
compared (Stage I) and five (n=56) versus ten (n=59) days (Stage II) were
compared. Stage I was discontinued due to four treatment failures all occurring in
the three-day group. Absence of treatment failure within 30 days, the primary
outcome, occurred among all participants in the five-day and ten-day treatment
groups in Stage II. These results suggest five and ten days of amoxicillin therapy are
comparable, whereas, three days of treatment may be associated with an
unacceptable failure rate.
A study suggests shorter antibiotic therapy may be non-inferior to
conventional recommendations in adult patients admitted for pneumonia.
A randomized, double blind, placebo-controlled non-inferiority trial5 of 119
adults with mild to moderate-severe pneumonia admitted to hospitals in the
Netherlands evaluated the efficacy of three-day intravenous amoxicillin treatment
followed by oral amoxicillin 750 mg (n=63) or placebo (n=56) three times daily for a
total of eight days. Only individuals with radiologic evidence of pneumonia, no
confounding co-infections and clinical improvement after the initial intravenous
therapy were included. Characteristics at baseline and during follow-up occurring
more in the three-day treatment group include underlying disease (70% vs 64%),
diabetes mellitus (16% vs 11%), smoker (55% vs 27%), pleural effusion (13% vs
3.2%) and detected pathogen at study entry (59% vs 49%). Those occurring more in
the eight-day treatment group include more than one pneumonia episode per year
(18% vs 14%) and median community acquired pneumonia score (39 vs 18). Cure

3. rate, the primary outcome measure, did not differ between the two groups at Day10
in both the intention-to-treat and per protocol analyses and differed only marginally
on Day 28 (secondary outcome measure). Four treatment failures occurred in both
the three-day and eight-day treatment groups (7% and 6%, respectively) and mild
adverse events occurred in six (11%) patients in the three-day and thirteen (21%)
patients in the eight-day groups. Additionally, the estimated length of stay differed
by one day (7.9 vs 8.9 days) favoring shorter treatment. Though some differences
exist between the two treatment groups, such as comorbidities, episode
characteristics and frequency of pneumonia, these results suggest that treatment of
mild to moderate-severe pneumonia in hospitalized individuals with three days of
amoxicillin is not inferior to eight days of treatment.
References
1 Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of
America/American Thoracic Society Consensus Guidelines on the Management of
Community-Acquired Pneumonia in Adults. Clinical Infectious Diseases 2007;
44:S27-72
2 Pakistan Multicentre Amoxicillin Short Course Therapy (MASCOT) Pneumonia
Study Group. Clinical Efficacy of 3 Days Versus 5 Days of Oral Amoxicillin for
Treatment of Childhood Pneumonia: A Multicentre Double-Blind Trial. Lancet
2002;360:835-841
3 Agarwal G, Awasthi S, Kabra SK, et al. Three Day Versus Five Day Treatment With
Amoxicillin For Non-Severe Pneumoia In Young Children: A Multicenter
Randomised Controlled Trial. BMJ 2004;328:791-4
4 Greenberg D, Givon0Lavi N, Sadaka Y, et al. Short-Course Antibiotic Treatment for
Community-Acquired Alveolar Pneumonia in Ambulatory Children: A Double-Blind,
Randomized, Placebo-Controlled Trial. The Pediatric Infectious Disease Journal
2014;33(2):136-142
5 el Moussaoui R, de Borgie CA, van den Broek P, et al. Effectiveness of discontinuing
antibiotic treatment after three days versus eight days in mild to moderate-severe
community acquired pneumonia: randomized, double blind study. BMJ
2006;332:1355