CONTEXT

Acute sinusitis is one of the leading causes of antibiotic prescriptions in children. No recent systematic reviews have examined the efficacy of antibiotics compared with placebo.

OBJECTIVE

We sought to determine if antibiotics are superior to placebo in the treatment of acute sinusitis in children.

DATA SOURCES

Medline and Embase were searched from their origin to July 2023.

STUDY SELECTION

We considered randomized placebo-controlled studies focusing on the treatment of acute sinusitis. In all studies, symptoms were present for <4 weeks and subjects were <18 years of age.

DATA EXTRACTION

Two authors independently extracted the data. We pooled data primarily using fixed-effects models.

RESULTS

Analysis of 6 included studies showed that antibiotic treatment reduced the rate of treatment failure by 41% (with a risk ratio of 0.59; 95% confidence interval 0.49–0.72) compared with placebo. There was substantial heterogeneity between the studies (I2 = 69.7%), which decreased substantially when the 1 study with a high risk of bias was removed (I2 = 26.9%). Children treated with antibiotics were 1.6 times more likely to have diarrhea than those who were not treated with antibiotics (risk ratio = 1.62, 95% confidence interval 1.04–2.51).

LIMITATIONS

A small number of studies were eligible for inclusion. Included studies differed in their methodology.

CONCLUSIONS

In children with clinically diagnosed acute sinusitis, antibiotics significantly reduced the rate of treatment failure compared with placebo. However, given the favorable natural history of sinusitis, our results could also support close observation without immediate antibiotic treatment.

Approximately 7.5% of upper respiratory tract infections in children are complicated by acute sinusitis,1 3  and, as such, it represents one of the most common indications for antibiotic prescription in children.4 6 

Antibiotics are currently recommended for children with severe or worsening symptoms of acute sinusitis. In children with persistent symptoms, defined as lasting more than 10 days without improvement, either immediate treatment or observation are acceptable treatment options. Children observed are recommended to receive antibiotics if they fail to improve within 72 hours.7  Determining the efficacy of antibiotics for acute sinusitis is important, both to ensure proper treatment and to possibly reduce unnecessary antibiotic use. The last systematic review8  examining the efficacy of antibiotics for the treatment of acute sinusitis was conducted in 2013 and new trials have since been conducted.9 ,10 

The aim of this systematic review and meta-analysis was to evaluate the efficacy of antibiotics for treatment of children with acute sinusitis.

We considered randomized controlled trials that evaluated the efficacy of antibiotics for acute sinusitis in children. We included studies of children from birth to 18 years of age with clinically diagnosed acute sinusitis. We excluded studies in which children had symptoms for longer than 4 weeks. The protocol for this review was submitted to PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) on December 12, 2022 (CRD42022380471).

We searched Medline and Embase on July 25, 2023. Search strategies are presented in the electronic supplement (Supplemental Table 3). We also reviewed the reference lists of all included articles and relevant systematic reviews to identify additional studies not found through the electronic search. We contacted authors when relevant data were not included in the published source. Two authors independently applied the selection criteria to all citations (titles and abstracts). The full text of all articles identified by either author was retrieved and reviewed. We limited the review to articles written in English, Spanish, or French.

For each study meeting the inclusion criteria, we extracted the following information: age range of children enrolled, diagnostic criteria, antibiotic used, dosage used, number of children in each arm, number of children with adverse events (diarrhea, complications of sinusitis), and number of children who experienced a treatment failure. Although the criteria used to define treatment failure differed slightly from one study to the next (Table 1), all studies evaluated whether the child failed to improve within 2 weeks of starting the study product. Information related to the incidence of diarrhea and rash, which were the 2 most frequently reported adverse events, was also collected. Two authors independently used the Cochrane Risk of Bias tool11  to assess the risk of bias in all studies meeting inclusion criteria. Differences were resolved by discussion.

TABLE 1

Characteristics of Included Placebo-Controlled Randomized Trials

Author, YearaAge Range, yearsNo. Placebo or AntibioticAntibiotic UsedDiagnostic CriteriaDefinition of Treatment FailureInstrument Used to Determine Treatment Failure
Wald, 198619  2 to 16 35/58 Low-dose amoxicillin ± clavulanateb Symptoms for ≥10 d that were not improving and an abnormal maxillary radiograph Worsening any time or lack of substantialc improvement on day 10 Unvalidated 10-item symptom scaled 
Garbutt, 200116  1 to 18 55/106 Low-dose amoxicillin ± clavulanate Symptoms for ≥10 d Lack of any improvemente on day 14 Unvalidated global rating of change scalef 
Kristo, 200518  4 to 10 37/35 Cefuroxime (250 mg per day) Symptoms (unspecified duration) that were not improving and an abnormal maxillary ultrasound Lack of improvementg by day 14 No scale used. Assessed overall clinical statush 
Wald, 200915  1 to 10 28/22i High dose amoxicillin or clavulanateb Symptoms for 11 to 30 d that were not improving, or worsening symptoms on or after day 6, or severe symptomsj Worsening any time, lack of significant improvement while on therapy, or lack of substantial improvementc on day 14 Unvalidated 8-item symptom scalek 
Wan, 20159  <18 20/50l High dose amoxicillin or clavulanate Symptoms ≤4 wk of purulent nasal drainage and nasal obstruction and/or facial pressure.20  All children included appear to have had a positive sinus CT scan. Lack of improvementm on day 14 Unvalidated symptom measure 
Shaikh, 202310  2 to 12 256/254 High dose amoxicillin or clavulanate Symptoms for 11 to 30 d that were not improving or worsening symptoms on day 6 to 10 Worsening any time, lack of significant improvement while on therapy, or lack of substantial improvementc on day 12 to 18 visit Validated scale administered electronicallyn,o 
Author, YearaAge Range, yearsNo. Placebo or AntibioticAntibiotic UsedDiagnostic CriteriaDefinition of Treatment FailureInstrument Used to Determine Treatment Failure
Wald, 198619  2 to 16 35/58 Low-dose amoxicillin ± clavulanateb Symptoms for ≥10 d that were not improving and an abnormal maxillary radiograph Worsening any time or lack of substantialc improvement on day 10 Unvalidated 10-item symptom scaled 
Garbutt, 200116  1 to 18 55/106 Low-dose amoxicillin ± clavulanate Symptoms for ≥10 d Lack of any improvemente on day 14 Unvalidated global rating of change scalef 
Kristo, 200518  4 to 10 37/35 Cefuroxime (250 mg per day) Symptoms (unspecified duration) that were not improving and an abnormal maxillary ultrasound Lack of improvementg by day 14 No scale used. Assessed overall clinical statush 
Wald, 200915  1 to 10 28/22i High dose amoxicillin or clavulanateb Symptoms for 11 to 30 d that were not improving, or worsening symptoms on or after day 6, or severe symptomsj Worsening any time, lack of significant improvement while on therapy, or lack of substantial improvementc on day 14 Unvalidated 8-item symptom scalek 
Wan, 20159  <18 20/50l High dose amoxicillin or clavulanate Symptoms ≤4 wk of purulent nasal drainage and nasal obstruction and/or facial pressure.20  All children included appear to have had a positive sinus CT scan. Lack of improvementm on day 14 Unvalidated symptom measure 
Shaikh, 202310  2 to 12 256/254 High dose amoxicillin or clavulanate Symptoms for 11 to 30 d that were not improving or worsening symptoms on day 6 to 10 Worsening any time, lack of significant improvement while on therapy, or lack of substantial improvementc on day 12 to 18 visit Validated scale administered electronicallyn,o 
a

Treatment was prescribed for 10 to 14 d in all included studies.

b

Low dose amoxicillin or amoxicillin or clavulanate is defined as 40 to 45 mg/kg per day. High dose is 90 mg/kg per day.

c

A decrease of <50% from the entry symptoms score.

d

Reported by the primary caregiver or patient. This outcome was also assessed on days 2, 3, 5, and 7. Data only reported for day 3.

e

Defined as a primary caregiver rating the patient’s symptoms as “a little” or “a lot” worse compared with entry symptoms.

f

Reported by the primary caregiver or patient. This outcome was also assessed on days 3, 7, 10, 21, and 28. In addition to this outcome, no differences were noted in a validated symptoms score (assessed on the same days as above), functional status, parent satisfaction, or relapse rates between treatment groups.

g

Based on the symptoms and signs assessed by 1 clinician and the primary caregiver’s opinion.

h

Determined by the physician with input from the parent based on signs and symptoms at time follow-up. Although a diary was used, its scores were not reported. One child in the placebo group failed because of development of otitis media; symptoms in all other children who failed were not sufficiently improved.

i

This excludes 6 children assigned to the antibiotic group who were lost to follow-up and had no data on their outcomes.

j

Defined as a temperature of at least 102°F and purulent nasal discharge present concurrently for at least 3 consecutive days.

k

Reported by the primary caregiver or patient. Outcome also assessed by phone on days 2, 3, 5, 7, 10, 20, and 30, but data not reported.

l

Of these 50 patients, 25 also had allergic rhinitis. Another cohort of patients treated with antibiotics and nasal steroids was not included here.

m

Defined as patients whose symptoms are unchanged or deteriorated compared with their entry symptoms.

n

Reported by primary caregiver on days 2 to 11. In addition to treatment failure, the study reported significantly higher daily symptom burden in the placebo group.

o

Pediatric Rhinosinusitis Symptom Scale (PRSS) is a validated scale designed to follow symptoms of children with acute sinusitis.

We pooled data primarily using fixed-effects models. We used the I2 statistic to assess the degree of heterogeneity between studies. We did not use meta-regression to investigate reasons for heterogeneity because the number of studies were limited. Instead, we conducted 2 sensitivity analyses. In the first sensitivity analysis, which was planned a priori, we included only studies that used the diagnostic criteria endorsed by the current guideline from the American Academy of Pediatrics (AAP).7  We did so because the clinical presentations of an uncomplicated upper respiratory infection and acute sinusitis have considerable overlap. Thus, studies that included children diagnosed using more stringent criteria might find different results compared with studies that used less stringent diagnostic criteria. Because of 1 study having a high risk of bias, we also conducted a second sensitivity analysis in which we included only studies with low risk of bias. We calculated the number needed to treat for the primary outcome, treatment failure, and the number needed to harm for significant adverse events. Finally, to assess whether differences in definitions of treatment failure influenced the results, we performed a third sensitivity analysis in which we excluded studies in which treatment failure could have only occurred on day 14 (in the rest of the studies, treatment failure could have occurred anytime during the first 14 days). The last 2 sensitivity analyses were not planned a priori. To pool the prevalence of major complications (ie, abscess, cellulitis, meningitis, empyema, Pott’s puffy tumor, cavernous sinus thrombosis), which we anticipated to be rare, we transformed the data before pooling.12 

The results of the search strategy are shown in Fig 1. Of the 678 records identified, 210 records were retrieved and reviewed based on the title and abstract. Upon full text review, 202 of these records were excluded. Of studies, 128 were not randomized controlled trials, 10 did not examine acute sinusitis, 54 did not investigate the use of antibiotic versus placebo, and 10 did not report data on children.

FIGURE 1

Study selection process.

FIGURE 1

Study selection process.

Close modal

A total of 8 studies met our inclusion criteria; 2 authors were contacted because their studies included both children and adults, but they were unable to provide the age-stratified data needed for inclusion.13 ,14  Thus, the meta-analysis included 6 studies (Fig 1). The characteristics of the 6 included studies are detailed in Table 1. All but 1 study were judged to have a low risk of bias based on the Cochrane risk-of-bias tool (Fig 2), and 3 out of the 6 included studies used the diagnostic criteria currently endorsed by the AAP Guideline.10 ,15 ,16  Testing for publication bias was not possible because of the small number of available studies.17 

FIGURE 2

Risk of bias analysis of included studies.

FIGURE 2

Risk of bias analysis of included studies.

Close modal

The primary analysis, which included 956 children, showed that antibiotic treatment reduced the relative rate of treatment failure by 41% (with a risk ratio of 0.59; 95% confidence interval [CI] 0.49–0.72, Table 2) compared with placebo. The absolute risk of treatment failure was 40.8% in the placebo group and 23.0% in the antibiotic group. Treatment failure was defined as a failure to improve within 2 weeks. Six additional children need to be treated to prevent 1 additional case of treatment failure. However, there was substantial heterogeneity between the studies (I2 = 69.7%, Fig 3). Results were similar when the 1 study with a high risk of bias was removed,9  but heterogeneity decreased substantially (I2 = 26.9%, Supplemental Fig 4). Results were also similar when the analysis was limited to studies that used the diagnostic criteria currently endorsed by the AAP (Supplemental Fig 5). Excluding the 2 studies9 ,16  in which treatment failure could have only occurred on day 14 did not change the conclusions (Supplemental Fig 6). For the primary outcome, we also present results of using random effect models in the online supplement, which was also generally consistent with the primary analysis (Supplemental Fig 7).

TABLE 2

Summary of Findings

Question: Antibiotics Compared With No Antibiotics for Children With Acute Sinusitis; Population: Children With Acute Sinusitis; Setting: Outpatient; Intervention: Antibiotic; Comparison: Placebo
Outcomes EvaluatedRelative RiskAbsolute RiskN of Participants (studies)Certainty of the Evidence (GRADE)
Risk Ratio (95% confidence interval)Risk in Placebo Group (assumed risk), % (n/N)Risk in Antibiotic Group (corresponding risk), % (n/N)
Treatment failurea 0.59 (0.49–0.72) 40.8 (176/431) 23.0 (121/525) 956 (6) ⊕⊕⊕⊝ Moderateb 
Diarrheac 1.62 (1.04–2.51) 7.2 (25/348) 13.4 (53/395) 743 (3) ⊕⊕⊕⊕ High 
Rashd 0.92 (0.37–2.24) 2.3 (7/311) 3.0 (11/361) 671 (2) ⊕⊕⊕⊝ Moderatee 
Complications of sinusitis 0 (0–0.23) 0 (0/411) 0 (0/475) 886 (5) ⊕⊕⊕⊝ Moderatee 
Question: Antibiotics Compared With No Antibiotics for Children With Acute Sinusitis; Population: Children With Acute Sinusitis; Setting: Outpatient; Intervention: Antibiotic; Comparison: Placebo
Outcomes EvaluatedRelative RiskAbsolute RiskN of Participants (studies)Certainty of the Evidence (GRADE)
Risk Ratio (95% confidence interval)Risk in Placebo Group (assumed risk), % (n/N)Risk in Antibiotic Group (corresponding risk), % (n/N)
Treatment failurea 0.59 (0.49–0.72) 40.8 (176/431) 23.0 (121/525) 956 (6) ⊕⊕⊕⊝ Moderateb 
Diarrheac 1.62 (1.04–2.51) 7.2 (25/348) 13.4 (53/395) 743 (3) ⊕⊕⊕⊕ High 
Rashd 0.92 (0.37–2.24) 2.3 (7/311) 3.0 (11/361) 671 (2) ⊕⊕⊕⊝ Moderatee 
Complications of sinusitis 0 (0–0.23) 0 (0/411) 0 (0/475) 886 (5) ⊕⊕⊕⊝ Moderatee 
a

Treatment failure defined by the lack of symptoms improvement. For exact definitions in each study see Table 1.

b

Inconsistency in diagnostic criteria for acute sinusitis across studies.

c

New onset diarrhea reported by parent or physician.

d

New rash reported by parent.

e

Downgraded because of imprecision of final pooled estimate.

FIGURE 3

Risk of treatment failure in children treated with antibiotics compared with placebo.

FIGURE 3

Risk of treatment failure in children treated with antibiotics compared with placebo.

Close modal

Three studies reported the incidence of diarrhea among trial participants. Children randomized to antibiotics were 1.6 times more likely to have diarrhea than those who were randomized to placebo (risk ratio = 1.62, 95% CI 1.04–2.51, I2= 48.5, Supplemental Fig 8). The absolute risk of diarrhea was 7.2% in the placebo group and 13.4% in the antibiotic group. The number needed to treat for 1 patient to have the additional harmful outcome of diarrhea was 16 patients. Two studies reported incidence of rash. No difference was apparent in incidence of rash between subjects who received antibiotics and those who didn’t (risk ratio = 0.92, 95% CI 0.37–2.24, I2 = 0%). The absolute risk of rash was 2.3% in the placebo group and 3.0% in the antibiotic group. There were no serious complications in the placebo group in the 5 studies reporting these data. The confidence interval around the proportion of children with complications in the placebo group ranged from 0% to 0.23%.

In this meta-analysis of 6 randomized controlled trials, which included 956 children, antibiotics reduced the relative risk of treatment failure in children with acute sinusitis by 41% (Table 2). In absolute terms, using the average risk of treatment failure among children treated with placebo in the included trials, the rate of treatment failure would be expected to decrease from 41 per 100 without antibiotics to 23 per 100 with the use of antibiotics (Table 2). Six additional children need to be treated to prevent 1 additional case of treatment failure. Our confidence in these results is high given robustness of the findings in the various sensitivity analyses performed (Supplemental Figs 4–8) and the low risk of bias in 5 of the 6 included studies.

Although our results clearly demonstrate the efficacy of antibiotics, treatment failure occurred, on average, in only 41% of children treated with placebo. Furthermore, none of the 431 children on placebo developed major sequelae. Accordingly, our results could also be viewed as supporting observation, provided that close follow-up with families could be ensured. Of note, treatment with antibiotics increased the risk of diarrhea to a small degree. The absolute risk of diarrhea in the antibiotic group was 13.4% compared with 7.2% in the placebo group. This means 16 children need to be treated with antibiotics for 1 additional child to develop diarrhea.

Several limitations are noteworthy. First, included studies differed in their methodology. Only 3 studies used current AAP criteria for diagnosing sinusitis. However, results were similar when we restricted the analyses to these studies. Moreover, only 1 study10  used a validated scale for assessing symptom resolution to determine the number of children who failed treatment. However, all but 1 study18  used rating scales that included symptoms associated with sinusitis. The studies also used varying definitions for treatment failure, which was a limitation. Excluding studies in which treatment failure could have only occurred on day 14 did not change the conclusions either. Second, there was substantial heterogeneity between studies. Much of the noted heterogeneity, however, was because of a single study that was judged to be at high risk of bias. In addition to a high-risk of bias, children in that study9  appear to have had more severe disease; they all appear to have been enrolled from a specialty clinic and all had a positive CT scan of the sinuses. Results were similar when we excluded that study from the meta-analysis. Third, although the small number of studies was a limitation, this was offset by the inclusion of 1 large recent trial.10  Although this trial contributed more than half of the participants included in analysis, it was deemed to have a low risk of bias and there is no reason to suspect the results are not generalizable. Fourth, no studies examined the effect of antibiotic use on the nasal or gut microbiomes. These data would have provided a more complete assessment of the risks and benefits of antibiotic treatment. Fifth, because of the small number of available studies, we cannot definitively conclude whether certain antibiotics were more effective than others. Drawing meaningful conclusions regarding treatment efficacy is further complicated by the changing resistance patterns over time. For example, it is unclear whether the relatively low dose of amoxicillin used by Garbutt et al16  contributed to the negative findings in that study. Similarly, high-dose amoxicillin clavulanate was always superior to placebo, but this does not mean that high dose amoxicillin would not have been similarly effective.

This review provides insights that could prove valuable in the design of future trials. First, measuring improvement in symptoms that parents consider important requires the use of a granular measure that has been shown to be sensitive to small changes in clinical status (ie, a validated scale with high responsiveness). Without use of such a measure, even treatments that differ in efficacy will appear equivalent. For example, Shaikh et al found a between-group difference of close to 2 points in the mean symptom scores (ie, PRSS scale scores) in children treated with antibiotic compared with placebo.10  This difference would be seen when comparing a hypothetical child with “an extreme amount” of irritability from day 2 to 11 versus a child with “some” irritability from day 2 to 11, assuming that the burden attributable to symptoms other than irritability was equivalent. They also found that symptoms resolved 2 days earlier in children randomized to antimicrobial agents compared with placebo (7 days for children in the antibiotic group and 9 days in the placebo group). Because these differences are modest, discussion with parents is advisable when deciding on whether antibiotics or observation should be recommended; findings from that study (2 days earlier resolution of symptoms and modest reduction in symptom severity) can be used in the discussion. Second, because of the large overlap between symptoms of acute sinusitis and the common viral upper respiratory tract infection, it is important to use stringent criteria for inclusion. Thus, it seems necessary to exclude children with only a few days of symptoms and children whose symptoms are improving. However, this may not be sufficient. The most recent trial,10  which was powered to allow detection of treatment effect heterogeneity, reported that children who did not have S pneumoniae or H influenzae in their nasopharynx at the time of diagnosis did not benefit from antibiotic treatment as much as children with these pathogens. This suggests that, in addition to using stringent clinical criteria, testing for pathogens may represent an additional criterion that could be used to minimize the number of children with uncomplicated viral upper respiratory included in future studies.

In conclusion, antibiotics appear to be effective at reducing symptoms of children with clinically diagnosed acute sinusitis. However, given the favorable natural history of the condition, our results could also be viewed as supporting close observation without immediate antibiotic treatment. Our results underscore the importance of shared decision-making with parents of children with acute sinusitis.

Dr Shaikh is responsible for study concept and design, data acquisition, data analysis, data interpretation, drafting the manuscript, and statistical analysis, had full access to all data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis; Ms Conway and Ms Mueller are responsible for data acquisition, data analysis, interpretation of data, and drafting of the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2024-065732.

FUNDING: This study was supported by the National Institute of Allergy and Infectious Diseases (NIAID); U01AI118506.

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest to report.

AAP

American Academy of Pediatrics

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Supplementary data