Cochrane Database Syst Rev. 2026 Apr 07. 4
CD014221
Chang Liu,
Christina Abdel Shaheed,
Lars Christian Braten,
Mark J Hancock,
Martin Underwood,
Jeffrey G Jarvik,
Julian Elliott,
Christopher G Maher,
Siya Zhao,
Meng Lyu,
Renea V Johnston,
Rachelle Buchbinder,
Chung-Wei Christine Lin.
RATIONALE: Low back pain is the leading cause of disability worldwide. Research has associated Modic changes (signal changes in the vertebral endplate on magnetic resonance imaging (MRI)) with low back pain. Some hypothesise that Modic type 1 changes (oedema) may have an infective cause, and that antibiotics could serve as targeted treatment.
OBJECTIVES: To assess the benefits and harms of antibiotic therapy, compared with placebo or another treatment, in people with low back pain, radicular pain, or both.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trials registries up to 26 August 2025, with no restrictions related to language or date of publication.
ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that assessed antibiotics versus placebo (primary comparison) or other treatments. We assessed the evidence separately for four populations of adults with low back pain, radicular pain, or both: those with 1) Modic type 1 changes and evidence of disc herniation, 2) other Modic changes and evidence of disc herniation, 3) any Modic changes but no evidence of disc herniation, and 4) evidence of disc herniation without any Modic changes.
OUTCOMES: Critical outcomes were pain intensity and disability or function up to 12 to 14 weeks, and the number of participants with any adverse events and serious adverse events at the end of the trial period.
RISK OF BIAS: Two review authors independently evaluated the risk of bias using the Cochrane risk of bias tool RoB 1.
SYNTHESIS METHODS: Two review authors independently screened studies and extracted data. We synthesised results for each outcome using random-effects meta-analysis. Where this was not possible due to the nature of the data, we reported the results descriptively. We used GRADE to assess the certainty of evidence. The primary comparison was antibiotics versus placebo in people with low back pain, radicular pain, or both, and Modic type 1 changes with evidence of disc herniation (population 1) up to 12 to 14 weeks.
INCLUDED STUDIES: We included three trials, conducted in Denmark, Belgium, and Norway, with a total of 402 participants (mean ages ranged from 44.7 years to 51.0 years). Two trials recruited people with chronic (> 6 months) moderate-to-severe low back pain (with or without radicular pain), Modic changes, and disc herniation. One trial included people with Modic type 1 changes only (population 1) and compared oral amoxicillin-clavulanate 500 mg/125 mg to placebo (for both treatments, 1 or 2 tablets 3 times daily for 100 days). The second trial included people with either Modic type 1 changes (population 1) or Modic type 2 changes (population 2) and compared oral amoxicillin 750 mg to placebo (for both treatments, 3 times daily for 100 days). Follow-up was 12 months in both trials. The third trial recruited people with lumbar radicular pain (with or without low back pain) and disc herniation. Modic changes was not an inclusion criterion (population 4). This trial evaluated minocycline 100 mg versus amitriptyline 25 mg versus placebo and followed participants for 14 days (treatment duration). There were no trials with population 3.
SYNTHESIS OF RESULTS: All three trials were at low risk of selection, performance, and detection bias. We rated one trial at high risk of attrition bias and unclear risk of reporting and other bias. The overall certainty of evidence is low to very low, primarily due to imprecision and indirectness. In people with low back pain, Modic type 1 changes, and disc herniation, the antibiotic oral amoxicillin (with or without clavulanate) may improve pain slightly and may result in a small to moderate improvement in disability at 12 to 14 weeks compared with placebo (low-certainty evidence, downgraded for imprecision and indirectness). At this time point, the mean back pain score was 50.6/100 (where a lower score indicates less pain) in the amoxicillin group versus 59/100 in the placebo group (mean difference (MD) -8.42 points, 95% CI -16.18 to -0.67; I² = 35%; 2 trials, 255 participants), and the mean disability score was 45.2/100 (where a lower score indicates less disability) in the amoxicillin group versus 55.7/100 in the placebo group (MD -10.52 points, 95% CI -15.94 to -5.09; I² = 0%; 2 trials, 255 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting adverse events (very low-certainty evidence, downgraded for imprecision, inconsistency, and indirectness). Adverse events were reported in 76 of every 100 people taking amoxicillin compared with 49 of every 100 people taking placebo (risk ratio (RR) 1.79, 95% CI 0.54 to 5.94; I² = 96%; 2 trials, 262 participants). We are unsure if amoxicillin (with or without clavulanate) results in more people reporting serious adverse events (very low-certainty evidence, downgraded for imprecision and indirectness). Serious adverse events were reported in three of every 100 people taking amoxicillin (with or without clavulanate) compared with two of every 100 people taking placebo (RR 1.43, 95% CI 0.11 to 18.35; I² = 45%; 2 trials, 262 participants). We are unsure of the effects of amoxicillin compared to placebo in people with low back pain, Modic type 2 change, and disc herniation. Similarly, we are unsure of the effects of minocycline compared to placebo or amitriptyline in people with low back pain, disc herniation, and no Modic changes.
AUTHORS' CONCLUSIONS: In people with low back pain, Modic type 1 changes, and evidence of disc herniation, the antibiotic amoxicillin (with or without clavulanate) may provide slight to small benefits in reducing back pain and small to moderate benefits in improving disability compared to placebo at 12 to 14 weeks. The evidence on the risk of adverse events, including serious adverse events, with amoxicillin (with or without clavulanate) is very uncertain. Further research is likely to change our confidence in the estimates.
FUNDING: This review had no dedicated funding.
REGISTRATION: Protocol (2021): DOI 10.1002/14651858.CD014221.