A Cochrane review [Abstract] 1 included seven trials. Four trials with 403 patients compared an antibiotic with placebo or no intervention. Three trials compared at least one antibiotic regimen with another antibiotic regimen.
In four trials that compared antibiotics with placebo, there were no deaths in two of them. In the two other studies, the number of deaths were 16/200 (8.0%) in the antibiotic arm versus 11/203 (5.4%) in the placebo arm giving a fixed-effect OR 1.56 (95% CI 0.70 to 3.46), and random-effects OR 1.16 (95% CI 0.23 to 5.95). Only one trial (253 patients) reported days of hospitalisation. It compared parenteral penicillin to placebo without significant effect of therapy (8.9 versus 8.8 days; mean difference (MD) 0.10 days, 95% CI -0.83 to 1.03). The difference in days of clinical illness was reported in two of these trials (71 patients). While parenteral penicillin therapy conferred 4.7 to 5.6 days of clinical illness in contrast to 7.7 to 11.6 days in the placebo arm, the size of the estimate of effect increased but statistical significance was lost under the random-effect model (fixed-effect: MD -2.13 days, 95% CI -2.46 to -1.80; random-effects: MD -4.04, 95% CI -8.66 to 0.58). When duration of fever alone was assessed between antibiotics and placebo in a single trial (79 patients), no significant difference existed (6.9 versus 6.6 days; MD 0.30, 95% CI -1.26 to 1.86).
When one antibiotic was assessed against another antibiotic, there were no statistically significant results. For mortality in particular, these comparisons included cephalosporin versus penicillin (2 trials, 6/176 (3.4%) versus 9/175 (5.2%); fixed-effect: OR 0.65, 95% CI 0.23 to 1.87, I2= 16%), doxycycline versus penicillin (1 trial, 2/81 (2.5%) versus 4/89 (4.5); OR 0.54, 95% CI 0.10 to 3.02), cephalosporin versus doxycycline (1 trial, 1/88 (1.1%) versus 2/81 (2.5%); OR 0.45, 95% CI 0.04 to 5.10). There were no adverse events of therapy which reached statistical significance.
Comment: The quality of evidence is downgraded by imprecise results, heterogeneity of patients included and study limitations; inadequate concealment of allocation.
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