Reviews of antibiotic therapy for chronic pain conditions
| Study, Year | Study type | Conditions & populations | Results | Comments |
|---|---|---|---|---|
| Gilligan et al., 2021 [50] | Narrative review | 8 studies, 3 of which were placebo-controlled (controlled trials pertaining to chronic back pain and vertebral endplate signal changes). | 2 of 4 observational studies and 2 of 3 controlled trials were positive. Herniated and degenerated discs might contain bacteria at concentrations below detection thresholds. Nearly 50% of degenerated discs were infected (most commonly with Cutibacterium acnes). | 2 positive controlled studies assessed patients with Modic type 1 changes and used amoxicillin-clavulanic acid. The negative controlled study enrolled patients with Modic type 1 or type 2 changes and used amoxicillin (without clavulanic acid). All studies entailed a 100-day antibiotic course. Both positive controlled studies showed a statistically significant reduction in disability and pain, but more studies are necessary to determine which subpopulations would benefit most from antibiotics. |
| Anothaisintawee et al., 2011 [51] | Systematic review and meta-analysis | 3 studies, 226 patients with chronic prostatitis/pelvic pain syndrome | Reduction in pain compared to placebo: −4.4 (95% CI, −7.0 to −1.9) for antibiotics, −5.7 (95% CI, −7.8 to −3.6) for combination of α-blockers + antibiotics. | Based on a single study [90], the combination of antibiotics + α-blockers was more effective than other treatments. Duration of treatment was 6–12 weeks. Antibiotics included ciprofloxacin, levofloxacin, and tetracycline. |
| Franco et al., 2019 [52] | Systematic review and meta-analysis | 99 studies, 9,119 men with chronic prostatitis/pelvic pain syndrome; of these, 6 studies in 693 participants compared antibiotics to placebo | Antibiotics (fluoroquinolones) may reduce symptoms compared to placebo. Mean difference in National Institute of Health - Chronic Prostatitis Symptom Index score: –2.43 (95% CI, –4.72 to –0.15) from pooled data of 5 studies, 372 participants; low quality of evidence. Antibiotics do not significantly improve sexual dysfunction or quality of life, but are not associated with adverse events (moderate quality of evidence). | Because all included studies utilized fluoroquinolones (levofloxacin or ciprofloxacin), these results cannot be generalized to other antimicrobial classes. |
| Ford et al., 2018 [56] | Systematic review and meta-analysis | 9 studies, 2,845 patients with irritable bowel syndrome | All studies favored antibiotics compared to placebo. | 7 studies evaluated rifaximin, with 2 evaluating ciprofloxacin and neomycin, both of which were positive. When 4 rifaximin studies with low risk-of-bias were evaluated separately, results favored antibiotic treatment (RR = 0.87, 95% CI, 0.82–0.93). |
| Black et al., 2020 [57] | Systematic review and meta-analysis | 18 studies, 9,844 patients with irritable bowel syndrome | 5-hydroxytryptamine-3 receptor antagonists (e.g., alosetron, ramosetron) were the most effective medications, compared to eluxadoline (a mixed μ-opioid receptor agonist, δ-opioid receptor antagonist, and κ-opioid receptor agonist), rifaximin, and placebo. | Rifaximin conferred the lowest risk of adverse effects, including constipation, but did not demonstrate greater efficacy than placebo for improvement in global IBS symptoms (RR, 0.91, 95% CI, 0.77–1.07) or abdominal pain (RR, 0.95, 95% CI, 0.89–1.01). |
| Townsend et al., 2019 [64] | Systematic review and meta-analysis | 13 studies, 1,303 patients with Crohn’s disease | Patients who received antibiotics had a lower rate of failure to achieve remission compared to those who received placebo, within 6–10 weeks (RR, 0.86, 95% CI, 0.76 to 0.98; 7 studies, high certainty evidence) and 10–14 weeks (RR, 0.77, 95% CI, 0.64 to 0.93; 5 studies, moderate certainty evidence). | Antibiotics did not appear to reduce rates of relapse within 52 weeks compared to placebo (RR, 0.87, 95% CI, 0.52 to 1.47; 2 studies, low certainty evidence). |
| Norton et al., 2017 [65] | Systematic review | 15 studies, with only 1 randomized comparative- effectiveness study assessing antibiotics for inflammatory bowel disease (n = 29) [65] | In the randomized comparative-effectiveness study [65], either metronidazole or ciprofloxacin reduced abdominal symptoms (84% response rate for bloating, 47% for abdominal pain), without difference in efficacy between antibiotics. | Small bowel bacterial overgrowth was present in 29 of 145 patients with Crohn’s disease, with baseline abdominal pain present in 48%. There was no difference in outcomes between a 10-day course of either metronidazole or ciprofloxacin. Glucose breath tests normalized in most patients (27 of 29) after antibiotic treatment. |
| Du et al., 2016 [69] | Systematic review and meta-analysis | 25 studies, 5,555 patients with functional dyspepsia and Helicobacter pylori | Pooled RR was 1.23 (95% CI, 1.12–1.36, P < 0.0001) for symptom improvement after H. pylori eradication therapy. Symptoms improved at follow-up ≥ 1 year (RR = 1.24; 95% CI, 1.12–1.37, P < 0.0001) but not < 1 year (RR = 1.26; 95% CI, 0.83–1.92, P = 0.27). Seven studies showed no benefit on quality of life (SMD –0.01, 95% CI, –0.11 to 0.08, P = 0.80). | There was no short-term (< 1 year) symptomatic improvement, but there was significant long-term (≥ 1 year) improvement. This might be attributable to a greater likelihood of antibiotic-treated patients achieving histologic resolution of chronic gastritis (RR = 7.13; 95% CI, 3.68–13.81, P < 0.00001) and not developing peptic ulcer disease (RR = 0.35; 95% CI, 0.18–0.68, P = 0.002). |
| Kang et al., 2019 [70] | Systematic review and meta-analysis | 18 studies, 4,774 patients with functional dyspepsia and H. pylori | Eradication of H. pylori significantly improved dyspepsia symptoms (RR, 1.18; 95% CI, 1.07–1.30, P < 0.01) regardless of local prevalence. | In the subgroup analysis of RCTs conducted in Asia, there was no significant benefit from H. pylori eradication therapy (RR, 1.14; 95% CI, 0.99–1.33, P = 0.08). Due to differences in trial design (e.g., shorter duration of treatment regimens), smaller sample sizes, and conflicting results between the individual RCTs completed in Asia, this result should be interpreted with caution. |
| Ford et al., 2022 [71] | Systematic review and meta-analysis | 29 studies, 6,781 patients with functional dyspepsia and H. pylori | Eradication therapy was more likely than non-antibiotic therapies to result in symptom resolution (RR of non-cure = 0.91, 95% CI, 0.89 to 0.94; NNT = 14, 95% CI, 11 to 21) or symptomatic improvement (RR of no improvement = 0.84, 95% CI, 0.78 to 0.91; NNT =,9, 95% CI, 7 to 17). Subgroup analyses did not show a significant difference between different antibiotic regimens. | Authors concluded there is high-quality evidence supporting H. pylori eradication therapy in functional dyspepsia, but were unable to determine whether these benefits are directly due to the reduction of infectious burden or via indirect effects on gastrointestinal dysbiosis. The treatment effect size was larger in patients who had eradication of H. pylori (RR of non-cure = 0.74, 95% CI, 0.64 to 0.85; NNT = 6, 95% CI, 4 to 10). |
| Smith et al., 2015 [83] | Systematic review | Myalgic encephalomyelitis/ chronic fatigue syndrome | Four studies [83–86] assessed antimicrobial therapies. Two [83,84] assessed rintatolimod, one [85] assessed valganciclovir, and one [86] assessed intravenous immunoglobulin G. Improvements in physical function and cognition were reported, but two studies were small [85,86], and one study [86] showed no benefit. | Although nearly all patients reported pain symptoms (e.g., myalgia, headaches, arthralgia), changes in pain were not separately assessed in the included studies. Changes in inflammatory cytokines and immune cell counts were observed. |
CI: confidence interval, RR: risk ratio, SMD: standardized mean difference, IBS: irritable bowel syndrome, RCTs: randomized controlled trials.