Abstract: We identified only one study for inclusion in this review. This study was a prospective, double-blind cross-over trial that compared the effect of systemic metronidazole with a placebo on odour in malignant wounds. Nine participants with a fungating wound and for whom the smell was troublesome were recruited and six of these completed both the intervention and control (placebo) stages of the trial. Each stage lasted fourteen days, with a fourteen day gap (washout period) between administration of the metronidazole and the placebo. The study, in comparing metronidazole and placebo, reported on two of this review's pre-specified primary outcomes (malodour and adverse effects of the treatment) and on none of the review's pre-specified secondary outcomes. Malodour The mean malodour (smell) scores for the metronidazole group was 1.17 (standard deviation (SD) 1.60) and the mean for the placebo group was 3.33 (SD 0.82). It is unclear if systemic antibiotics were associated with a difference in malodour (1 study with 6 participants; MD —2.16, 95% CI —3.6 to —0.72) as the quality of the evidence (GRADE) was very low for this outcome. The study was downgraded due to high risk of attrition bias (33% loss to follow-up) and very serious imprecision due to the small sample size. Adverse effects No adverse effects of the treatment were reported in either the intervention or control group by the trial authors. It is uncertain whether systemic metronidazole leads to a reduction in malodour in patients with malignant wounds. This is because we were only able to include a single study at high risk of bias with a very small sample size, which focused only on patients with breast cancer. More research is needed to substantiate these findings and to investigate the effects of systemic metronidazole and other antibiotics on quality of life, pain relief, exudate and tumour containment in patients with malignant wounds.

Plain-language summary: In March 2017 we searched for randomised controlled trials looking at the effects of systemic antibiotics on malignant wounds. We found only one trial, dating from 1984, which compared the effectiveness of the antibiotic metronidazole with a placebo (sugar pill) on six participants with malignant wounds resulting from breast cancer. The trial was a cross-over trial which means that participants receive both the treatment being tested and the comparison treatment, at different time-points, with a break between the treatments to ensure that the effects of the first treatment have worn off before the second treatment is taken. This is called the 'washout' period. In the one trial in this review, half the participants took the antibiotic first, for 14 days, and half took the placebo. Both groups then had 14 days with no medication before swapping over (cross-over) and trying the alternative treatment for 14 days. It is unclear if metronidazole reduces the smell of malignant wounds when taken orally (by mouth) in tablet form, without any side effects occurring. Its effectiveness in relation to other outcomes such as pain or quality of life was not measured in this trial. No change in the size or appearance of participants' tumours was reported. It is uncertain whether metronidazole reduces the smell of malignant wounds when taken orally in tablet form because the quality of the evidence is very low. This evidence came from a very small study with serious study design flaws, and more research is needed involving more people with different types of cancer. Trials looking at how antibiotics can affect other outcomes, such as quality of life, pain relief and reducing any bleeding or ooze from the wound are also needed. This plain language summary is up to date as of March 2017.