An ongoing dialogue on HIV/AIDS, infectious diseases,
October 21st, 2019
Amoxicillin for Chronic Low Back Pain? Are You Kidding Me? In Defense of a Controversial Clinical Trial
The BMJ just published a randomized trial comparing amoxicillin to placebo for people with chronic low back pain.
I kid you not.
The appearance of this trial elicited all kinds of snark from the medical community. Here, check this out, along with the responses:
Important RCT for anyone who’s been treating low back pain with <checks notes> amoxicillin https://t.co/RIxIVSr3kb
— David Juurlink (@DavidJuurlink) October 19, 2019
Dr. Juurlink, definite points for that <checks notes> stage direction! Love it.
But allow me to defend the people who did the study, and go even further — this is exactly the sort of practical, hypothesis-testing trial I wish we’d see more often.
Consider the problem — chronic low back pain. The bane of Western Civilization, it occurs in a quarter of the adult population. The misery from this condition results in millions of annual office visits a year, countless days out of work, and heavy economic losses.
Usually we don’t know the cause. And for severe sufferers, our medical treatments and surgeries offer inconsistent benefits.
Along comes the idea that a subset of back-pain patients — those with certain inflammatory changes on imaging, called “Modic” after the person who described them — might have a low-grade infection as the cause of this inflammation.
The theory is that a degenerating disc provides a suitable spot for this infection to settle, presumably after transient bacteremia. It would have to be a very indolent, slow-growing infection, as people with chronic low back pain don’t have fevers or other symptoms of acute infection, and also lack laboratory evidence of infection or inflammation.
Based on animal and human data, the leading candidate for this kind of infection is none other than our old friend Cutibacterium acnes, shown here again in a very good mood.
(Maybe it’s happy because, as I’ve written before, Cutibacterium acnes used to be Proprionobacterium acnes. The new name is a zillion times better, especially if it’s pronounced like a cute little puppy, and not like a paper cut, or like an old coot.)
We ID doctors are quite familiar with C. acnes as a relatively common cause of prosthetic joint infections, especially of the shoulder; dermatologists know it as one of the primary bacteria involved in <checks notes> acne.
C. acnes also sometimes pops up in blood cultures, usually as a contaminant — but maybe those aren’t contaminants after all!
(Cue dramatic music here.)
The idea that C. acnes could contribute to chronic low back pain has been supported by the occasional isolation of the organism during spine surgery, and animal models showing the bug could induce these Modic changes in rabbits. This information led to a controversial randomized clinical trial comparing amoxicillin-clavulanate to placebo in adults with chronic low back pain, showing significant improvement in the treatment arm.
A subsequent systematic review concluded:
… further work is needed to determine whether these organisms are a result of contamination or represent low grade infection of the spine which contributes to chronic low back pain.
All of which brings us back to the recent study, which enrolled 180 people with chronic low back pain and Modic changes (of two types) on imaging. They were randomized to receive oral treatment with either 750 mg amoxicillin or placebo three times daily for three months. The primary outcome was a validated disability score a year later. They set a difference of 4 points on the scale as being clinically meaningful.
The results showed that the amoxicillin group had significantly lower disability scores than the placebo group, but the difference did not meet the threshold for being clinically important (it was only 1.6 points). Plus, nearly twice as many in the amoxicillin arm experienced a drug-related adverse event.
I certainly agree with the authors’ conclusions that the “results do not support the use of antibiotic treatment for chronic low back pain”, especially if you consider the added potential problems of encouraging antibiotic resistance and alteration of the human microbiome.
But kudos to them for doing the research — even negative studies are important. It could have been an H. pylori and peptic ulcer disease, but was C. pneumoniae and CAD instead.
But just imagine if it worked!