Making sense of antibiotics for chronic low back pain with Modic changes

Abstract

This post discusses a new preprint analysing published studies of antibiotics in chronic low back pain with Modic changes through an exposure-response framework. Rather than treating the literature as irreconcilably inconsistent, the analysis asks whether differences in antibiotic exposure at the disc can explain variation in clinical outcomes. Using study-level meta-regression together with pharmacokinetic/pharmacodynamic modelling and probability of target attainment, the work concludes that higher estimated intradiscal antibiotic exposure was associated with greater 12-month improvement in pain and disability. The relationship remained significant when oral and intradiscal studies were considered together, suggesting that apparently conflicting findings may be interpretable within a common pharmacological framework. Intradiscal linezolid was highlighted as achieving the highest estimated intradiscal exposure and the largest observed improvements. The broader implication is that future studies should pay closer attention to antibiotic selection, dose, route, tissue penetration, and PK/PD when evaluating antibiotics for this condition.

Exposure-response blog

I wanted to share a new analysis of published antibiotic studies in chronic low back pain with Modic changes.

We have posted a new preprint “Higher exposure to antibiotics is associated with greater clinical improvement of chronic low back pain with Modic changes” by Czaplewski et al., that explains diverse literature conclusions.

Preprint: Higher exposure to antibiotics is associated with greater clinical improvement of chronic low back pain with Modic changes

Rather than treating the studies reaching different conclusions on the efficacy of antibiotics to treat cLBP with Modic changes as irreconcilable, we looked at them through an exposure-response lens. The analysis suggests the apparently conflicting findings can be understood within a coherent pharmacological framework and may help explain why outcomes differed across studies.

The work extends an earlier high level estimate of intradiscal antibiotic exposure (Czaplewski et al., 2023) and investigates whether between-study differences in outcome can be explained by differences in intradiscal antibiotic exposure, using study-level meta-regression together with pharmacokinetic/pharmacodynamic modelling and probability of target attainment (PTA).

The main finding is that higher antibiotic exposure at the disc, whether assessed by nominal oral dose or modelled intradiscal PTA, was associated with greater 12-month improvement in pain and disability. When oral and intradiscal studies were considered together, the exposure-outcome relationship remained significant, supporting the view that these published studies can be interpreted within a common exposure-response framework rather than as genuinely conflicting results. Intradiscal linezolid achieved the highest estimated intradiscal exposure and was associated with the largest improvements in pain and disability.

More broadly, we think this offers a constructive case for continued research and development of antibiotics to teat cLBP with Modic changes.

If you work in this area, I’d be very interested in your thoughts.

Czaplewski L, Gilligan C, McHale D. Higher exposure to antibiotics is associated with greater clinical improvement of chronic low back pain with Modic changes. 2026; published online Sept DOI:https://doi.org/10.21203/rs.3.rs-10748663/v1.

Czaplewski LG, Zeitlinger M, Standing JF. Intradiscal pharmacokinetics of oral antibiotics to treat Chronic Lower Back Pain. npj Antimicrob Resist 2023; 1: 1–9.

Albert HB, Sorensen JS, Christensen BS, Manniche C. Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy. Eur Spine J 2013; 22: 697–707.

Albert HB. Antibiotic treatment of patients with chronic low back pain and Modic changes. Schmerzmed 2017; 33: 49–52.

Bråten LCH, Rolfsen MP, Espeland A, et al. Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial. BMJ 2019; 367: l5654.

Lassen M, Scarborough M, Gilchrist N, Tripathi S, Price C. Intradiscal linezolid (PP353) treatment for chronic Low Back Pain associated with Modic Change type 1: a first-in-human, randomised, sham procedure-controlled, double-blinded, international phase 1b clinical trial. eClinicalMedicine 2026; published online Feb 2. DOI:10.1016/j.eclinm.2026.103764.

FAQs Exposure-response analysis

What did the exposure-response analysis examine?

This analysis looked at published clinical studies of oral and intradiscal antibiotics in people with chronic low back pain (cLBP) and Modic changes.

The aim was to test whether differences in antibiotic exposure at the disc could help explain why prior studies have reported different outcomes.

What did the analysis find?

It found that higher antibiotic exposure was associated with greater 12-month improvement in pain and disability.

Exposure was assessed using either:

• nominal oral dose, or

• modelled intradiscal probability of target attainment (PTA)

When oral and intradiscal studies were considered together using the PTA framework, the association remained significant.

What does that mean in simple terms?

A fair reading of the literature may not be that antibiotic results are simply "variable" or that antibiotics "do not work."

A more accurate interpretation may be that clinical outcomes depend in part on how much active antibiotic exposure is achieved at the disc. If different studies delivered very different local exposure, different outcomes would be expected.

Did one treatment stand out?

Yes. Intradiscal linezolid achieved the highest estimated intradiscal exposure and was associated with the largest improvements in pain and disability.

Does this mean all antibiotics work?

No.

This analysis does not say that all antibiotics work, that all patients with chronic low back pain are affected by bacteria, or that antibiotic treatment should be interpreted in a simple yes/no way.

The more specific conclusion is that within the published literature, higher estimated intradiscal antibiotic exposure was associated with better clinical outcomes.

Why have clinical studies appeared inconsistent?

One likely explanation is differences in antibiotic exposure.

If one study achieved relatively low antibiotic exposure at the disc and another achieved much higher local exposure, then different clinical outcomes would be expected. That provides a pharmacological explanation for why the literature may have looked heterogeneous.

What is the fairest summary of this clinical literature?

A fair summary may be:

Published antibiotic studies in cLBP with Modic changes may fit a shared exposure-response pattern, with higher estimated intradiscal antibiotic exposure associated with greater clinical improvement.

Why does this matter for future clinical research?

Future studies should pay much closer attention to:

• antibiotic selection

• dose

• route of administration

• tissue penetration

• pharmacokinetics/pharmacodynamics

• probability of target attainment

Headline comparisons between studies may be misleading if those factors are not taken into account.

Lloyd Czaplewski is Chief Scientific Officer at Persica Pharmaceuticals