Chronic Low Back Pain, Bacterial Infection, and Antibiotic Treatment

Chronic low back pain (CLBP) is a leading cause of disability globally, affecting millions and posing significant challenges to healthcare systems due to its complex aetiology and limited effective treatments (Gilligan et al., 2021). Recent research has sparked debate by suggesting that low-grade bacterial infections, particularly involving Cutibacterium acnes (C. acnes), may contribute to CLBP in a subset of patients, especially those with disc herniation and Modic Type 1 changes (bone oedema visible on MRI). This hypothesis, if validated, could revolutionise treatment by introducing antibiotics as an alternative to conventional therapies or invasive procedures like spinal surgery. However, the evidence remains controversial, with concerns about contamination, antibiotic efficacy, and stewardship. The following summary synthesises findings from key studies, highlighting microbiology evidence, clinical trial outcomes, and ongoing research challenges.

Microbiology Evidence: Bacterial Presence in Herniated Discs

Several studies have investigated whether bacteria, particularly C. acnes, are present in herniated disc tissue and contribute to CLBP. Gilligan et al. (2021) reviewed five well-designed microbiology studies that confirmed bacteria in disc samples, suggesting infection rather than contamination. These studies found C. acnes, a low-virulence anaerobic bacterium commonly associated with acne, in herniated disc tissue, particularly in patients with Modic Type 1 changes. However, the bacterial burden was low, potentially below detection limits in some studies, which may explain conflicting results where bacteria were absent or attributed to surgical contamination (Gilligan et al., 2021).

Astur et al. (2023) conducted a prospective cohort study to identify bacteria in herniated intervertebral discs, reporting C. acnes in a significant proportion of samples. Their stringent aseptic protocols minimised contamination risks, supporting the infection hypothesis. Similarly, Urquhart et al. (2015) conducted a systematic review and found moderate evidence that low-virulence bacteria are present in spinal disc material, particularly in patients with disc herniation and Modic Type 1 changes. They applied Bradford Hill’s criteria to assess causation, concluding modest evidence for a causal link but noting the need for further research to distinguish infection from contamination (Urquhart et al., 2015).

In contrast, Monge-García et al. (2024) explored whether bacterial presence in disc cultures represents true infection or contamination. Their study suggested that while C. acnes was frequently detected, contamination during surgical procedures could not be ruled out, particularly given the bacterium’s ubiquity on skin and in hair follicles. This raises a critical question: are bacteria in disc tissue causative agents of CLBP or incidental findings due to procedural artefacts? The conflicting findings underscore the need for standardised microbiological methods and larger sample sizes to clarify the role of C. acnes (Monge-García et al., 2024).

Clinical Evidence: Antibiotic Efficacy in CLBP

Clinical trials have tested whether antibiotics can reduce pain and disability in CLBP patients with suspected bacterial infections. Two randomised controlled trials (RCTs) reviewed by Gilligan et al. (2021) demonstrated significant pain and disability reductions in patients with CLBP and Modic Type 1 changes treated with oral antibiotics, typically amoxicillin-clavulanate, for up to 100 days. These patients, often unresponsive to conventional treatments like physiotherapy or analgesics, showed clinically meaningful improvements, suggesting antibiotics as a potential alternative to surgery for those facing disc replacement or fusion (Gilligan et al., 2021).

A landmark RCT by Albert et al. (2013), cited across multiple articles, found that 100 days of amoxicillin-clavulanate significantly reduced pain and disability in patients with CLBP post-disc herniation and Modic Type 1 changes compared to placebo. At one-year follow-up, the antibiotic group reported a median Roland Morris Disability Questionnaire (RMDQ) score reduction from 15 to 7, compared to 15 to 14 in the placebo group (p=0.0001). Pain scores and constant pain prevalence also improved significantly (Urquhart et al., 2015; Gilligan et al., 2021). However, the trial reported high rates of adverse events, particularly gastrointestinal issues like diarrhoea, in 65% of the antibiotic group versus 23% in the placebo group, raising concerns about tolerability (Urquhart et al., 2015).

Despite these promising results, not all studies support antibiotic efficacy. Some trials reported modest or non-significant effects, potentially due to underdosing or variable bacterial susceptibility. A review by Czaplewski et al. (2023) highlighted that oral amoxicillin doses (500–1000 mg, two or three times daily) may not achieve adequate intradiscal concentrations to target C. acnes effectively, with only 6.5% of serum concentrations reaching herniated disc tissue. Higher doses (e.g., 1000 mg three times daily) may be needed to reach efficacy targets for 90% of C. acnes strains, suggesting that previous studies may have been underdosed (Czaplewski et al., 2023).

Modic Changes and Infection Hypothesis

Modic Type 1 changes, characterised by vertebral bone oedema, are six times more prevalent in CLBP patients than the general population and are strongly associated with the infection hypothesis. Aebi (2013) noted that 80% of discs infected with C. acnes in surgical samples developed Modic Type 1 changes, suggesting that bacterial infection may trigger inflammation and oedema in adjacent vertebrae (Aebi, 2013). The neovascularisation following disc herniation is thought to allow C. acnes to enter the disc during transient bacteraemia, such as during tooth brushing, leading to chronic low-grade infection (Urquhart et al., 2015).

However, Modic changes may also result from mechanical stress or degeneration, complicating the attribution to infection alone. Lings (2013) and Rolfsen et al. (2024) emphasised that Modic Type 1 and Type 2 changes might represent different stages of a common degenerative process, questioning the specificity of infection as a cause. Rolfsen et al. (2024) proposed a multicentre case-control biopsy study to further investigate bacterial growth in CLBP patients with Modic changes, aiming to use advanced microbiological techniques like PCR to detect low-burden infections and control for contamination (Rolfsen et al., 2024).

Controversies and Challenges

The hypothesis that bacterial infection causes CLBP faces several challenges. First, the presence of C. acnes in disc tissue may reflect contamination rather than infection, given its prevalence on skin and difficulty in culturing due to its anaerobic nature (Monge-García et al., 2024). Second, the clinical significance of antibiotic benefits is debated, with some studies showing only modest effects and high adverse event rates (Gilligan et al., 2021). Third, long-term antibiotic use raises concerns about antimicrobial resistance and secondary infections like Clostridium difficile (Urquhart et al., 2015).

Antibiotic stewardship is a critical issue. The prolonged regimens (up to 100 days) used in trials contrast with typical short-course antibiotic treatments, increasing risks of resistance and side effects. Aebi (2013) and Lings (2013) cautioned against widespread antibiotic use without robust evidence, drawing parallels with the paradigm shift in peptic ulcer treatment following Helicobacter pylori discovery but urging caution until confirmatory studies are conducted.

Future Directions

The reviewed studies advocate for further research to refine patient selection, optimise antibiotic regimens, and address stewardship concerns. Rolfsen et al. (2024) and Czaplewski et al. (2023) emphasised the need for studies incorporating advanced diagnostics (e.g., quantitative microbiology, proteomics) and pharmacokinetic/pharmacodynamic evaluations to ensure adequate intradiscal antibiotic concentrations. Identifying biomarkers, such as cytokine patterns or genetic predispositions, could help select patients most likely to benefit from antibiotics (Gilligan et al., 2021).

Moreover, alternative delivery methods, such as intradiscal antibiotic injections (e.g., PP353, a novel treatment combining linezolid and a thermosensitive gel), are being explored to minimise systemic side effects and improve efficacy (Tripathi et al., 2025, cited in The Guardian). These approaches could offer targeted treatment for infection-related CLBP, reducing the need for prolonged oral antibiotics.

Conclusion

The hypothesis that low-grade bacterial infections contribute to CLBP, particularly in patients with disc herniation and Modic Type 1 changes, is supported by microbiological evidence and some clinical trials demonstrating antibiotic efficacy. However, controversies persist regarding contamination, variable clinical outcomes, and antibiotic stewardship. While antibiotics offer a potential alternative to surgery for a subset of CLBP patients, widespread adoption requires further validation through rigorous, multicentre studies. Future research should focus on optimising diagnostics, treatment regimens, and patient selection to balance efficacy with safety, potentially transforming the management of this debilitating condition.

Antibiotics For Low Back Pain?

Persica Pharmaceuticals has developed PP353, an intradiscal injection designed to treat chronic low back pain linked to bacterial infections, particularly cases associated with Modic changes (pathological alterations in vertebrae seen on MRI). PP353 combines:

• Linezolid (antibiotic) – targets bacterial infection
• Iohexol (contrast agent) – aids imaging and distribution
• Thermosensitive gel – ensures controlled release

Recent Study & Findings

• Conducted on 44 patients
• Patients received two injections four days apart
• 60% reported significant pain and disability reduction
• Study supports infectious origins in some chronic back pain cases

Potential Impact

• Could benefit the 25% of chronic low back pain cases linked to bacterial infection
• Offers a minimally invasive alternative to surgery or long-term medication
• Further clinical trials required before widespread use

Can Antibiotics Cure Low Back Pain?

Last week I picked up a copy of Metro and came across an article entitled “Back pain ‘cured with a £114 dose of antibiotics'”. The story has also been covered by theguardian, The Times and the NHS. It’s based on the results of 2 studies published in the European Spine Journal by Hanne B Albert et al. from the University of Southern Denmark. It appears that oedema (swelling) of the vertebrae is observed in 6% of the general population and in 35-40% of people with low back pain. In their first study, Albert et al. examined 61 patients that had MRI-confirmed disc herniation and were undergoing surgery to address this. The disc material was analysed and it turned out that anaerobic bacteria were present in 43% of patients. Of those with anaerobic bacterial infections, 80% presented with oedema of the vertebrae next to the disc prolapse. Whereas only 44% of patients with negative cultures had bone oedema of adjacent vertebrae. The association between anaerobic bacterial presence and bone swelling was highly statistically significant. It’s thought that bacteria reach the inside of intervertebral discs via newly formed blood vessels that penetrate the damaged discs. The flow chart below shows how the process takes place.

 

In their second study, Albert et al. conducted a double-blind randomised controlled trial with 162 patients whose only known illness was chronic low back pain of greater than 6 months duration occurring after a previous disc herniation. They also had bone edema in the vertebrae next to the previous herniation. The patients were split into 2 groups. One group was given antibiotics for 100 days and the other group was given a placebo for 100 days. The patients were evaluated at the start of treatment, at the end of treatment and 1 year after the end of treatment. The patients given antibiotics improved on all measures; they had less low back pain, less leg pain and better function and the changes were highly statistically significant.

Although these results are extremely encouraging, they should be confirmed with larger groups. Additionally, it’s worth bearing in mind that this form of treatment only applies to a subgroup of people with low back pain and that the indiscriminate use of antibiotics for low back pain should be discouraged as it could lead to decreased efficacy of antibiotics through the spread of drug-resistant bacteria.