Table 3. Complications and Adverse Events According to Study Group and Treatment Received at the Time of Occurrence*.
| Adverse Event | Amoxicillin–Clavulanate Group (N = 144) | Placebo Group (N = 147) | ||||
|---|---|---|---|---|---|---|
| During Receipt of Amoxicillin–Clavulanate |
During Receipt of Rescue Therapy |
Total | During Receipt of Placebo |
During Receipt of Rescue Therapy |
Total | |
|
number of children (percent) |
||||||
| Mastoiditis† | 0 | 0 | 0 | 1 (1) | 0 | 1 (1) |
| Perforation of tympanic membrane | 1 (1) | 0 | 1 (1) | 6 (4) | 1 (1) | 7 (5) |
| Protocol-defined diarrhea‡ | 34 (24) | 2 (1) | 36 (25) | 11 (7) | 11 (7) | 22 (15)§ |
| Diaper-area dermatitis | 67 (47) | 6 (4) | 73 (51) | 24 (16) | 27 (18) | 51 (35)¶ |
| Oral thrush | 7 (5) | 0 | 7 (5) | 0 | 1 (1) | 1 (1) |
| Vomiting‖ | 12 (8) | 0 | 12 (8) | 11 (7) | 1 (1) | 12 (8) |
| Rash** | 1 (1) | 0 | 1 (1) | 1 (1) | 1 (1) | 2 (1) |
In each study group, one child was not followed beyond enrollment. Comparisons were adjusted for study site, history or no history of recurrent acute otitis media, and exposure or no exposure to other children.
Mastoiditis developed on day 5 in an 11-month-old child with unilateral acute otitis media and a score on the Acute Otitis Media Severity of Symptoms (AOM-SOS) scale of 14 at entry and of 7 on day 5. A culture of middle-ear aspirate yielded serotype 19A Streptococcus pneumoniae with a penicillin minimum inhibitory concentration of 2 μg per milliliter. The child was hospitalized for 41 hours and treated initially with parenteral antibiotics and subsequently with oral antibiotics; he recovered uneventfully.
Diarrhea was defined in the protocol as three or more watery stools in 1 day or two watery stools daily for at least 2 days. Treatment was discontinued because of diarrhea in six children in the amoxicillin–clavulanate group and one child in the placebo group, in whom Clostridium difficile enteritis developed.
P = 0.05 for the difference between the amoxicillin–clavulanate group and the placebo group.
P = 0.008 for the difference between the amoxicillin–clavulanate group and the placebo group.
In the amoxicillin–clavulanate group, treatment was discontinued in one child because of vomiting.
In each group, treatment was discontinued in one child because of rash.