In this issue of Pediatrics, Conway and colleagues report a systematic review and meta-analysis of randomized clinical trials comparing antibiotic treatment to placebo for acute sinusitis in children.1  With nearly 5 million antibiotics dispensed to children diagnosed with acute sinusitis in the United States annually, quantifying the incremental benefit of antibiotic treatment is essential.2  Conway and colleagues included 6 randomized clinical trials in their meta-analysis, 4 of which were referenced in the American Academy of Pediatrics’ (AAP’s) clinical practice guidelines, and thus present an updated analysis to inform clinical practice.

The 6 studies included 956 children; 5 studies had low risk of bias and 3 adhered to the AAP diagnostic criteria for acute bacterial sinusitis.3  The 6 included studies defined treatment failure as either (1) worsening at any time or (2) lack of substantial improvement (either while on therapy, by day 10, on day 12–18, or on/by day 14). Treatment failure was assessed by either validated scale (1 study),4  unvalidated scale (4 studies),5 8  or overall clinical status (1 study).9  In their primary analysis, they found that antibiotic treatment (with either amoxicillin, amoxicillin/clavulanate, or cefuroxime) reduced the risk of treatment failure by 41% (relative risk [RR] 0.59; 95% confidence interval [CI] 0.49–0.72) compared with placebo (absolute risk 23% in antibiotic-treated group, 40.8% in placebo group). Notably, 59.2% of patients in the placebo group did not experience treatment failure. Although studies have demonstrated bacterial recovery in 68% to 72% of patients with acute sinusitis, this meta-analysis suggests that nonbacterial causes of sinusitis (eg, viruses) may be commonplace.4 ,10  After excluding the study with a high risk of bias, the benefit of antibiotics was attenuated somewhat: RR 0.64 (95% CI 0.53–0.79), and an analysis restricted to the 3 studies employing the AAP diagnostic criteria found similar results: RR 0.66 (95% CI 0.54–0.82). Among the 3 studies that reported the risk of diarrhea, there was a 62% increased risk of diarrhea among those treated with antibiotics (RR 1.62, 95% CI 1.04–2.51), although this finding was driven by a single study comparing amoxicillin-clavulanate to placebo.4 ,7 ,9 

Establishing a diagnosis of acute bacterial sinusitis in clinical practice remains challenging. The AAP clinical diagnostic criteria have not been validated against a gold standard diagnostic approach, such as sinus puncture with bacterial culture, but remain the current best attempt at identifying patients most likely to benefit from antibiotics. Conway and colleagues demonstrate that, when using these criteria, 6 children need to be treated with antibiotics to prevent 1 treatment failure. In general, this would be a favorable number needed to treat. However, the nature of treatment failure is difficult to elucidate fully: Are we treating 6 children with antibiotics to prevent 1 child from experiencing a few more days of congestion? Or are we treating 6 children with antibiotics to prevent 1 from deteriorating and requiring the emergency department? Fortunately, treatment failure resulting in an emergency department or inpatient encounter is very rare for children with ambulatory acute sinusitis. No patients in the included studies experienced this outcome, and a recent large study comparing amoxicillin/clavulanate to amoxicillin found the risk to be 0.05%.11  Though the benefit of antibiotics may lie primarily in symptom alleviation, this relief may make a considerable difference to the patient and family, allowing some children to experience some irritability rather than “an extreme amount” of irritability.4  Although we all may agree this is a tangible benefit, we remain challenged to determine which children are most likely to benefit from antibiotics.

The randomized controlled trial by Shaikh et al included in the meta-analysis attempted to elucidate this very question. The authors performed nasopharyngeal bacterial culture and recovered bacteria in 72% of cases meeting the AAP diagnostic criteria.4  They found that, among patients with sterile cultures, antibiotics provided no benefit. This finding is an enticing first hint that rapid tests with a high negative predictive value and specificity may allow clinicians to discriminate patients with sinusitis who could benefit from antibiotics from those unlikely to benefit. Until such a cheap, accurate, and rapid test is widely available, however, clinicians must weigh the potential benefits of improved symptom duration with antibiotic treatment among patients meeting the AAP diagnostic criteria against the increased risk of diarrhea and the potential (but unmeasured) microbiome disruption among treated patients.

Ultimately, this meta-analysis reminds us that antibiotics have a role in the management of acute sinusitis in children. But questions of how to optimize this treatment through using the narrowest spectrum agent and shortest effective treatment duration remain. We agree with Conway and colleagues that, although high-dose amoxicillin-clavulanate demonstrated the greatest benefit over placebo, high-dose amoxicillin may have been equally effective, a conclusion supported by a recent study of >300 000 children comparing these 2 antibiotics.11  Similarly, determining whether 5 to 7 days of treatment, as recommended in the current RedBook, has equal effectiveness to 10 days as recommended in guidelines will be essential.12 ,13 

Drs Savage and Kronman drafted the commentary and reviewed it critically for important intellectual content; and both 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.2023-064244.

FUNDING: Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (T32HD040128 and K08HD110600 [both to Dr Savage]). Dr Kronman received no additional funding. The funder had no role in the design or conduct of this study.

CONFLICT OF INTEREST DISCLOSURES: Dr Savage reports a grant to his institution (investigator) from UCB outside the submitted work. Dr Kronman has indicated he has no conflicts of interest relevant to this article to disclose.

AAP

American Academy of Pediatrics

CI

confidence interval

RR

relative risk

1
Conway
SJ
,
Mueller
GD
,
Shaikh
N
.
Antibiotics for acute sinusitis in children: a meta-analysis
.
Pediatrics
.
2024
;
153
(
5
):
e2023064244
2
Fleming-Dutra
KE
,
Hersh
AL
,
Shapiro
DJ
, et al
.
Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010–2011
.
JAMA
.
2016
;
315
(
17
):
1864
1873
3
Wald
ER
,
Applegate
KE
,
Bordley
C
, et al
.
American Academy of Pediatrics
.
Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years
.
Pediatrics
.
2013
;
132
(
1
):
e262
e280
4
Shaikh
N
,
Hoberman
A
,
Shope
TR
, et al
.
Identifying children likely to benefit from antibiotics for acute sinusitis: a randomized clinical trial
.
JAMA
.
2023
;
330
(
4
):
349
358
5
Wald
ER
,
Chiponis
D
,
Ledesma-Medina
J
.
Comparative effectiveness of amoxicillin and amoxicillin-clavulanate potassium in acute paranasal sinus infections in children: a double-blind, placebo-controlled trial
.
Pediatrics
.
1986
;
77
(
6
):
795
800
6
Wald
ER
,
Nash
D
,
Eickhoff
J
.
Effectiveness of amoxicillin/clavulanate potassium in the treatment of acute bacterial sinusitis in children
.
Pediatrics
.
2009
;
124
(
1
):
9
15
7
Garbutt
JM
,
Goldstein
M
,
Gellman
E
,
Shannon
W
,
Littenberg
B
.
A randomized, placebo-controlled trial of antimicrobial treatment for children with clinically diagnosed acute sinusitis
.
Pediatrics
.
2001
;
107
(
4
):
619
625
8
Wan
KS
,
Wu
WF
,
Chen
TC
,
Wu
CS
,
Hung
CW
,
Chang
YS
.
Comparison of amoxicillin + clavulanate with or without intranasal fluticasone for the treatment of uncomplicated acute rhinosinusitis in children
.
Minerva Pediatr
.
2015
;
67
(
6
):
489
494
9
Kristo
A
,
Uhari
M
,
Luotonen
J
,
Ilkko
E
,
Koivunen
P
,
Alho
OP
.
Cefuroxime axetil versus placebo for children with acute respiratory infection and imaging evidence of sinusitis: a randomized, controlled trial
.
Acta Paediatr
.
2005
;
94
(
9
):
1208
1213
10
Sawada
S
,
Matsubara
S
.
Microbiology of acute maxillary sinusitis in children
.
Laryngoscope
.
2021
;
131
(
10
):
E2705
E2711
11
Savage
TJ
,
Kronman
MP
,
Sreedhara
SK
,
Lee
SB
,
Oduol
T
,
Huybrechts
KF
.
Treatment failure and adverse events after amoxicillin-clavulanate versus amoxicillin for pediatric acute sinusitis
.
JAMA
.
2023
;
330
(
11
):
1064
1073
12
Savage
TJ
,
Kronman
MP
,
Sreedhara
SK
, et al
.
Trends in the antibiotic treatment of acute sinusitis: 2003–2020
.
Pediatrics
.
2023
;
151
(
4
):
e2022060685
13
Kimberlin
D
,
Barnett
E
,
Lynfield
R
,
Sawyer
M
.
Committee on Infectious Diseases–American Academy of Pediatrics
.
Red Book: 2021–2024 Report of the Committee on Infectious Diseases
, 32nd ed.
2021