Table 1:

Characteristics of included studies

Study	Treatment; no. of participants			Daily dose,^* mg or mg/kg	Period, d		Domain of care	Age group	Indication for antibiotic	Patient diary used	Patients asked about specific harms	Trial registration found^†	Usable harms data	No. of types of harms reported
Study	Amoxicillin	Amox– clav. acid	Placebo	Daily dose,^* mg or mg/kg	Treatment	Harms follow-up	Domain of care	Age group	Indication for antibiotic	Patient diary used	Patients asked about specific harms	Trial registration found^†	Usable harms data	No. of types of harms reported
Treatment of respiratory or ENT infection
Burke et al.7	114	NA	118	375	7	21	Primary	Child	Acute otitis media	Yes	Yes	No	Yes	3
Gottfarb et al.8	NA	26	26	20/kg	7	14	Referral	Child	Persistent cough	No	?	No	Yes	1
Heikkinen et al.9	NA	57	58	40/kg	7	7	Referral	Child	Prevention of acute otitis media	No	?	No	No	0
Hoberman et al.10	NA	144	147	90/kg	10	10	Referral	Child	Acute otitis media	Yes	?	Yes	Yes	5
Jørgensen et al.11	133	NA	137	1500	7	8	Primary	Adult	Acute exacerbation of chronic bronchitis	No	No	No	Yes	5
Kaiser et al.12	NA	146	142	1125	5	7	Primary	Adult	Common cold	Yes	Yes	No	Yes	1
Leach et al.13	52	NA	51	50/kg	168	NR	Primary	Child	Prevention of high-risk otitis media	No	?	Yes	No	0
Little et al.14	1038	NA	1023	3000	7	28	Primary	Adult	Acute lower respiratory tract infection	Yes	Yes	Yes	No	5
Mandel et al.15	83	NA	81	1000	14	28	Referral	Child	Otitis media with effusion (glue ear)	No	No	No	Yes	1
Mandel et al.16	57	NA	54	40/kg	14	NR	Referral	Child	Prophylaxis for recurrent otitis media	No	?	No	No	0
Marchant et al.17	NA	25	25	20/kg	14	28	Referral	Child	Chronic wet cough	Yes	No	Yes	Yes	2
Meltzer et al.18	251	NA	252	45/kg	14	29	Primary	Adult	Acute rhinosinusitis	No	?	No	Yes	7
Merenstein et al.19	67	NA	68	1500	10	14	Primary	Adult	Acute rhinosinusitis	No	?	No	Yes	10
Nduba et al.20	330	NA	330	2000	7	14	Primary	Adult	Acute bronchitis in a high-prevalence HIV-positive population	No	Yes	No	Yes	5
Ruohola et al.21	NA	39	40	45/kg	7	7	Primary	Child	Ear discharge from tympanostomy tube for glue ear	No	?	No	No	0
Rwalah et al.22	NA	50	46	40/kg	7	NR	Referral	Child	Prevention of otitis media in otitis-prone children with new acute respiratory infection	No	?	No	No	0
Taylor et al.23	56	NA	66	375	5	8	Primary	Child	Presumed viral acute respiratory infection	Yes	Yes	No	Yes	4
Wald et al.24	41	44	48	40/kg	10	10	Primary or referral	Child	Acute rhinosinusitis	No	?	No	Yes	2
Williamson et al.25	60	NA	63	1500	7	42	Primary	Adult	Acute rhinosinusitis	No	?	Yes	Yes	0
Treatment of other infections
Glupczynski et al.26	22	NA	23	2000	8	NR	Referral	Adult	Campylobacter gastritis	No	?	No	No	0
Huizinga et al.27	NA	51	22	750	5	5	Referral	Adult	Infected skin wounds (surgical and nonsurgical)	No	?	No	Yes	0
Nelson et al.28	15	NA	15	100/kg	5	6	Primary	Child	Salmonella gastroenteritis	Yes	No	No	Yes	5
Sclafani et al.29	NA	86	81	40/kg	30	30	Referral	Child	Chronic adenotonsillar hypertrophy	No	?	No	Yes	2
Prevention or prophylaxis against infection
Albu et al.30	NA	50	50	1250	14	NR	Referral	Adult	Postoperative prophylaxis (endoscopic sinus surgery)	No	?	No	No	0
Baecher et al.31	16	NA	16	1000	5	7	Referral	Adult	Prophylaxis for obstetric Streptococcus colonization	No	?	No	Yes	1
Balme et al.32	39	NA	35	Not stated	5	NR	Referral	Child	Prophylaxis for kerosene-associated pneumonitis	No	?	Yes	No	0
Brakenbury et al.33	NA	88	97	375–750	5	— ^‡	Referral	Child, adult	Prophylaxis for animal bites	No	?	No	Yes	2
Duff et al.34	54	NA	54	1500	14	14	Referral	Adult	Bacterial vaginosis in pregnancy	Yes	No	No	No	1
Kumana et al.35	38	NA	12	3000	1	NR	Dental	Adult	Pharmacokinetics (antibiotic levels) in prophylaxis against endocarditis	No	?	No	No	0
Liang et al.36	39	NA	34	750	28	NR	Referral	Adult	Postoperative prophylaxis (endoscopic sinus surgery)	No	?	No	No	0
Shapiro et al.37	205	NA	182	750	10	7	Primary	Child, adult	Prophylaxis for Lyme disease after tick bite	No	?	No	Yes	1
Yip et al.38	NA	65	65	375	1	NR	Referral	Adult	Prevention of UTI after urodynamic study	No	?	No	No	0
Dental treatment or prophylaxis
Arteagoitia et al.39	NA	16	17	4000	5	NR	Dental	Adult	Prophylaxis for dental extraction	No	?	Yes	No	0
Bulut et al.40	15	NA	15	1500	5	NR	Dental	Adult	Prophylaxis for dental extraction	No	?	No	No	0
Esposito et al.41	165	NA	165	2000	1	7	Dental	Adult	Prophylaxis for dental implant	No	?	No	Yes	3
Esposito et al.42	254	NA	255	2000	1	7	Dental	Adult	Prophylaxis for dental implant	No	?	No	Yes	0
Hafferjee et al.43	NA	10	11	750	30	NR	Dental	Adult	Periodontal infection	No	?	No	No	0
Lockhart et al.44	96	NA	96	2000	1	NR	Dental	Adult	Preoperative prophylaxis for tooth extraction or toothbrushing	No	?	Yes	No	0
Rooney et al.45	16	NA	15	750	7	180	Dental	Adult	Periodontal disease	No	?	No	Yes	0
Winkel et al.46	NA	10	11	1500	10	24	Dental	Adult	Periodontal disease	No	No	No	Yes	1
Obstetric or gynecologic treatment or prophylaxis
Almeida et al.47	50	NA	56	2250	1	NR	Referral	Adult	Prophylaxis for premature rupture of membranes	No	?	No	No	0
Peters et al.48	NA	76	73	1500	7 or 14	— ^‡	Referral	Adult	Prophylaxis for preterm delivery of twins	No	?	No	No	2
Other
Chantelau et al.49	NA	22	22	1500	3–20	20	Referral	Adult	Foot ulcers in diabetic neuropathy	No	?	No	Yes	1
Khin et al.50	22	NA	78	25/kg	180	NR	Primary	Child	Malabsorption and growth	No	?	No	No	0
Trehan et al.51	952	NA	959	80–90/kg	5	14	Primary	Child	Severe acute malnutrition	No	Yes	Yes	Yes	6
Total no. of studies	28	18	45	NA	NA	NA	20 referral, 15 primary, 9 dental, 1 primary or referral	26 adult, 17 child, 2 child and adult	20 preventive or prophylaxis	8 Yes	6 Yes, 6 No, 33 uncertain	NA	25 Yes, 20 No	NA
Median or mean						Median 14								Mean 2.7^§
Total no. of participants	4280	1005	5234

Note: amox–clav. acid = amoxicillin–clavulanic acid; ENT = ear, nose, throat; NA = not applicable; NR = harms data not reported; UTI = urinary tract infection; ? = not clear from trial report.
↵* The most commonly prescribed dose if there was a loading dose.
↵† At www.clinicaltrialsregister.eu, www.clinicaltrials.gov, www.controlled-trials.com or www.anzctr.org.au.
↵‡ Harms data were reported, but the follow-up period was not specified and was likely variable.
↵§ Calculated only for studies with usable harms data (“Yes” in preceding column).