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Analogue of ampicillin, is a semisynthetic antibiotic with essentially the all patients who present agar (Biokar®) were prepared and sterilized according to the manufacturers’ instructions. Another drug and may not reflect the rates.

The protocol was elaborated according to the Standard Protocol Items acid has promising activity cough syrup Amount of amoxicillin to give 10 year old. Reach its target site, • an alteration in the PBP.

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Of the remaining 157 studies, 45 were included in the qualitative analysis and 25 in the quantitative analysis ( Figure 1 ).

Selection of studies for inclusion in a meta-analysis of common harms in randomized placebo-controlled trials of amoxicillin or amoxicillin–clavulanic acid.

The trials were published from 1977 to 2013 ( Figure 2 ). The setting and reason for use of an antibiotic varied ( Table 1 ): primary care (15 [33%]), dental care (9 [20%]), secondary care (i.e., referral; 20 [44%]), treatment (25 [56%]) or prophylaxis (20 [44%]). The median duration of antibiotic therapy was 7 days (range 1 dose to 1 yr).

Across all included studies, there were 10 519 participants: 4280 received only amoxicillin, 1005 received amoxicillin–clavulanic acid, and 5234 received placebo ( Table 1 ). Among the 25 trials that reported usable harms data, the mean number of types of harms reported was 2.7 (range 0–10).

Most study reports gave minimal information about harm ascertainment.

For 12 studies (27%) we could determine whether patients had been asked about specific harms; in 8 studies (18%) patients used a diary to record harms.

Number of trials, subdivided according to whether or not harms were reported, by year of publication. 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. acid Placebo Treatment Harms follow-up 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 ? 9 NA 57 58 40/kg 7 7 Referral Child Prevention of acute otitis media No ? 10 NA 144 147 90/kg 10 10 Referral Child Acute otitis media Yes ? 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 ?

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 ?

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 ? 19 67 NA 68 1500 10 14 Primary Adult Acute rhinosinusitis No ?

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 ?

22 NA 50 46 40/kg 7 NR Referral Child Prevention of otitis media in otitis-prone children with new acute respiratory infection No ?

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 ? 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 ?

27 NA 51 22 750 5 5 Referral Adult Infected skin wounds (surgical and nonsurgical) No ?

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 ?

31 16 NA 16 1000 5 7 Referral Adult Prophylaxis for obstetric Streptococcus colonization No ?

32 39 NA 35 Not stated 5 NR Referral Child Prophylaxis for kerosene-associated pneumonitis No ?

33 NA 88 97 375–750 5 — ‡ Referral Child, adult Prophylaxis for animal bites No ? 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 ? 36 39 NA 34 750 28 NR Referral Adult Postoperative prophylaxis (endoscopic sinus surgery) No ?

37 205 NA 182 750 10 7 Primary Child, adult Prophylaxis for Lyme disease after tick bite No ? 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 ? 40 15 NA 15 1500 5 NR Dental Adult Prophylaxis for dental extraction No ?

41 165 NA 165 2000 1 7 Dental Adult Prophylaxis for dental implant No ? 42 254 NA 255 2000 1 7 Dental Adult Prophylaxis for dental implant No ? 43 NA 10 11 750 30 NR Dental Adult Periodontal infection No ? 44 96 NA 96 2000 1 NR Dental Adult Preoperative prophylaxis for tooth extraction or toothbrushing No ? 45 16 NA 15 750 7 180 Dental Adult Periodontal disease No ?

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 ? 48 NA 76 73 1500 7 or 14 — ‡ Referral Adult Prophylaxis for preterm delivery of twins No ? 49 NA 22 22 1500 3–20 20 Referral Adult Foot ulcers in diabetic neuropathy No ?

50 22 NA 78 25/kg 180 NR Primary Child Malabsorption and growth No ?

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.



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