Outcomes assessed
Recurrence
Wiksten et al 2016  conducted a double-blind, adequately powered RCT involving 200 patients.15 With the primary outcome measured being  recurrence within 56 days of follow up, they found that there was no significant difference in the recurrence rates between the two groups (penicillin and placebo vs penicillin and metronidazole). Furthermore, no significant difference was found in the time to recurrence or the baseline characteristics of these patients including age, gender, smoking status or prior antibiotic use. Similar findings were identified by Tuner et al 1986 in which all patients in both the penicillin and placebo and the penicillin and metronidazole group were deemed fully recovered after 10 days of treatment.20 Every patient was treated with needle aspiration or incision and drainage daily for the 10 days or until no pus was drained, and the main conclusion drawn was that daily incision and debridement along with antibiotics is the treatment of choice.
Symptoms
Wiksten et al 2016 assessed symptom duration with patient questionnaires. The follow up of the questionnaires fell well below the number required for statistical power, however intention to treat analysis was used. The mean duration of throat-related symptoms (difficult mouth opening, sore throat, painful swallowing) was 5.3 days in the penicillin and metronidazole group and 5.6 days in the penicillin and placebo group; this was not statistically significant. The patients also reported on their general physical condition and presence of pyrexia, and these findings were not statistically different between the two groups.
Yilmaz et al 1998  conducted a double blind RCT comparing a 10-day course procaine-penicillin alone vs sulbactam-ampicillin.21 There were 42 patients in total, randomly assigned however the co-morbidities or initial clinical symptoms on presentation were not described. Both treatments were given intramuscularly on an outpatient basis. The main resistance mechanism of some anaerobic bacteria to beta-lactams is beta-lactamase production. Therefore the addition of a beta-lactamase inhibitor, sulbactam, to the ampicillin group in this instance broadens the spectrum of antibiotic activity.22 The duration of throat pain and the time to resumption of normal eating in both groups as measured by patient report of symptoms was not significantly different. Axillary temperature did also not differ significantly between the groups. Turner et al 1986 broadly described the clinical outcomes of the penicillin and placebo vs penicillin and metronidazole as very similar between groups.
Wiksten et al 2016 also asked patients to report on symptoms associated with adverse antibiotic effects. The study found a significant increase in the association of nausea and diarrhoea with the penicillin and metronidazole group compared with the penicillin and placebo group, advocating the use of penicillin alone for the desired clinical outcome with minimal treatment harm. Although many of the other papers included discuss the harms of unnecessary additional treatment Wiksten et al 2016 were the only group to formally assess the increased risk of side effects.