Summary of findings 1. Systemic antibiotics compared to no treatment/placebo.

Systemic antibiotics compared to no treatment/placebo
Patient or population: children with CSOM Setting: tertiary hospital, Israel Intervention: systemic antibiotics (mezlocillin or ceftazidime) Comparison: placebo
Outcomes	Relative effect (95% CI)	Number of participants (studies)	Anticipated absolute effects* (95% CI)			Certainty of the evidence (GRADE)	What happens
			Without systemic antibiotics	With systemic antibiotics	Difference
Resolution of ear discharge ‐ measured at 1 to 2 weeks Assessed with: unclear if otoscopically confirmed	RR 8.47 (1.88 to 38.21)	33 (1 RCT)	Study population			⊕⊝⊝⊝ VERY LOW 1,2,3	The evidence is very uncertain about the effect of systemic antibiotics (mezlocillin or ceftazidime) on the resolution of ear discharge at one to two weeks, as compared to placebo.
			8.3%	70.6% (15.7 to 100)	62.3% more (7.3 more to 310.1 more)
Resolution of ear discharge ‐ measured after 4 weeks	No study reported this outcome at this time point.					—	—
Health‐related quality of life	No study reported this outcome.					—	—
Ear pain (otalgia) or discomfort or local irritation	No study reported this outcome.					—	—
Hearing Assessed with: air conduction and bone conduction	—	33 (1 RCT)	Fliss 1990 reported measuring air conduction thresholds at 0.25 kHz, 0.5 kHz, 1 kHz, 2 kHz, 4 kHz and 8 kHz, and bone conduction thresholds at 0.5 kHz, 1 kHz and 2 kHz. The time at which these were performed is not described. The authors state that "audiometric tests did not show any worsening of the hearing during or after the antimicrobial treatment".			⊕⊝⊝⊝ VERY LOW 1,3,4	The evidence is very uncertain about the effect of systemic antibiotics (mezlocillin or ceftazidime) on hearing.
Serious complications ‐ during 6 months of follow‐up Assessed with: unclear	—	33 (1 RCT)	Fliss 1990 reported that no intracranial complications occurred during the study or during the follow‐up period.			⊕⊝⊝⊝ VERY LOW 1,2,3	The evidence is very uncertain about the effect of systemic antibiotics (mezlocillin or ceftazidime) on serious complications.
Suspected ototoxicity	No study reported this outcome.					—	—
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

¹Downgraded by two levels due to risk of bias (unclear methods for randomisation, allocation concealment or blinding, and placebo arm of the trial discontinued early due to lack of effect).

²Downgraded by two levels due to imprecision (very small study with only 33 participants resulting in wide confidence intervals).

³Downgraded by one level for indirectness (single study including children who were hospitalised, who did not respond to an intensive aural toileting regimen. This study involves inpatient use of mezlocillin and ceftazidime, which are broad‐spectrum antibiotics only administered parenterally (intramuscular or intravenous). It is unclear if this finding is applicable to other more commonly available antibiotics).

⁴Downgraded by two levels due to imprecision (very small study and numerical results were not reported for this outcome).