Late stage Lyme disease treatment might include azlocillin in the future.
A study by Stanford Medicine indicates that a drug called azlocillin “completely kills off the disease-causing bacteria Borrelia burgdorferi at the onset of the illness.” [1] In addition, the authors say, azlocillin “could be effective for treating [Lyme disease] patients infected with drug-tolerant bacteria that may cause lingering symptoms.”
Researchers identified azlocillin after screening nearly 8,000 drug compounds. They found that in the test tube and in mice, azlocillin was effective against drug-tolerant Borrelia burgdorferi s.s., the pathogen causing Lyme disease. But will late stage Lyme disease treatment soon include azlocillin, an FDA-approved drug that is often used to treat infections such as Pseudomonas aeruginosa and Escherichia coli? Stanford researchers say that is what they are working towards.
“This compound is just amazing,” says Rajadas, senior author of the study. “It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease.”
Chronic Lyme disease
Unfortunately, treatment fails for too many patients with late stage Lyme disease. Multiple studies have shown that as many as 34% to 62% of patients have Lyme disease symptoms that persist long term despite treatment.
In fact, one study found that at their six-month follow-up visit, “36% of patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties.”
When late stage Lyme disease treatment fails, chronic symptoms may be due, in part, to what scientists call ‘persisters,’ bacterial cells that are resistant to antibiotics.
“This compound is just amazing,” says Rajadas, senior author of the study. “It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease.”
“These studies reveal that a small subpopulation of dormant B. burgdorferi persisters still survives with current Lyme therapy antibiotics,” says Pothineni and colleagues in the article, “Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto.” [1]
“The probable mechanisms as evidenced by scientific literature are the persister formation, evading the immune system by hiding in the privileged sites, surface lipoproteins modifications to avoid antigenic responses, biofilm formation, and immunomodulation,” explains Pothineni.
Azlocillin in mice
The authors inoculated mice with high doses of Borrelia burgdorferi (Bb) to test the effectiveness of each of the antibiotics. Doxycycline cleared the infection on Day 7 but did not clear the Borrelia bacteria at Days 14 and 21. Cefotaxime alone failed to eradicate the B. burgdorferi infection completely in mice who had been infected for 7 and 14 days.
Meanwhile, azlocillin completely cleared the infection in all mice but some B. burgdorferi DNA remained.
“Though the azlocillin eliminated B. burgdorferi infection completely in all the mice infected for 21 days, still 2 of 8 mice infected for 14 days had some B. burgdorferi DNA in ear tissues,” says Pothineni.
[bctt tweet=”Study finds azlocillin may be a game-changer for the treatment of persistent Lyme disease symptoms. ” username=”DrDanielCameron”]
The authors points out, “the drug combinations of 40 μg/ml azlocillin and 80 μg/ml cefotaxime is much more effective in killing persisters than using azlocillin alone.”
Treatment for patients
Unfortunately, treatments that are successful in the test tube and in mice, may not work in humans.
Azlocillin is a semisynthetic β-lactam drug that cannot be used in patients who are allergic to penicillin. Currently, it is only available intravenously and the dosage, duration, efficacy, and side effects in B. burgdorferi-infected patients has not been studied.
For now, there are a number of antibiotics that are better understood including oral doxycycline, amoxicillin, cefuroxime, cefdinir, azithromycin, and clarithromycin, as well as intravenous ceftriaxone and cefotaxime. And specific drugs are available to target tick-borne co-infections, such as atovaquone and azithromycin for the treatment of Babesia.
Lastly, medications, which have recently been studied in the laboratory or in mice are now being considered as late-stage Lyme disease treatment options. These include dapsone [2], a combination of daptomycin, ceftriaxone, and doxycycline [3-5], and disulfiram. [6]
Related Articles:
Case report: Persistent pain and fatigue after treatment for Lyme disease
Could ketamine help manage pain for post-treatment Lyme disease syndrome?
References:
- Pothineni VR, Potula HSK, Ambati A, et al. Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31. Sci Rep. 2020;10(1):3798.
- Horowitz RI, Freeman PR. Precision medicine: retrospective chart review and data analysis of 200 patients on dapsone combination therapy for chronic Lyme disease/post-treatment Lyme disease syndrome: part 1. Int J Gen Med. 2019;12:101-119.
- Feng J, Li T, Yee R, et al. Stationary phase persister/biofilm microcolony of Borrelia burgdorferi causes more severe disease in a mouse model of Lyme arthritis: implications for understanding persistence, Post-treatment Lyme Disease Syndrome (PTLDS), and treatment failure. Discov Med. 2019;27(148):125-138.
- Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch Dermatol Res. 2014;306(2):103-124.
- Gonzalez-Ruiz A, Seaton RA, Hamed K. Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections. Infect Drug Resist. 2016;9:47-58.
- Liegner KB. Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases. Antibiotics (Basel). 2019;8(2).
Fred J Scholl
08/24/2021 (8:58 am)
Are there any study’s taking place for volunteers? I have been battling Lyme’s for 8 years now and just can’t beat it.
Dr. Daniel Cameron
08/24/2021 (10:45 am)
I have not heard of any study taking volunteers. I would encourage you to take my Lyme disease and COVID-19 survey to understand the virus or vaccine. You can participate even if you have not had the illness or taken the vaccine. https://danielcameronmd.com/lyme-disease-covid-survey/
donald w baxley
09/08/2021 (7:56 pm)
I’ve had chronic lymes for 32+ yrs and would be very happy to be part study and very greatful
Dr. Daniel Cameron
09/09/2021 (7:46 pm)
I have not seen a azlocillin trial, yet.
Greg
10/30/2022 (9:42 pm)
As a LONG TIME Late Stage Lyme sufferer who had multiple bullseye rashes on my stomach in 1986 , I had never heard of Lyme Disease in the 80’s so I didn’t go to a Doctor until 10 years later because my then 34 year old body felt like it was 140 , I would try just about ANYTHING right about now 😏😏😏😏
Jim habash
01/03/2023 (2:13 pm)
Greg. Do you have any eyesight problems. Retinal detachment, PVD s vitreal detachments. (strands of retina coming loose). For example I have the Octopus floater arms, but I have colored spots that never move in the periphery of both my eyes. They are visible when I blink, but do not obstruct vision. I have Lyme A + Ehrlichia since 1989. Never treated but tolerated well unknowingly, until penicillin shot then hard PTLD that has never for almost 16 years. Now eye problems.
Terry
04/04/2023 (7:45 am)
Greg, can you tell me more about your PVD. I may have the same.
Fred
04/05/2023 (3:05 pm)
Eye problems can be caused by infection(s) with Borrelia (Lyme), Bartonella or both. If you want significant improvements you should start treating with antibiotics, Doxy + Rifampin for 4 weeks and everything will be OK.
Christine
09/14/2023 (6:29 am)
Azlocillin has been discontinued
Dr. Daniel Cameron
09/14/2023 (8:01 am)
Yes. I am hoping for new treatments for my patients that are struggling to get better.
Jenna
09/16/2023 (2:35 pm)
Hi Dr. Cameron,
I’ve been looking around online and can’t find any new information about Azlocillin. The Stanford researchers were showing such amazing results against Lyme, but what happened? It doesn’t look like anything came of this treatment. I don’t see any new information over the last two to three years. Have you heard any updates? Or did a better treatment come along that they’re trying to get out? Thank you!
Dr. Daniel Cameron
09/17/2023 (8:03 am)
I don’t have any new information on Azlocillin. I had also been waiting for a breakthrough
Camille Ross
03/14/2021 (5:08 pm)
When does he plan to start human clinical trials?
Susan
01/05/2021 (7:03 pm)
Is there any update on the efficacy of Azlocillin in humans? If this drug was already FDA approved for one illness, will it have to be re-approved for Lyme? Any chance there will be clinical trials in NY?
Dr. Daniel Cameron
01/06/2021 (8:12 am)
I have not seem any humans. The authors of the first study did not include people. The authors suggested the need for a pill version.
Doug Hilgers
03/19/2022 (9:16 pm)
Dear Susan( and Others) I am with You all and would be over the moon if Azlocillin were available in the US. I have found ( as per usual) it is already being used in the UK but to treat a different organism and in combination with another antibiotic , likely both IV. – It is available in bulk ( salt ) form for research purposes only. I do however want to point out a very promising study already concluded and demonstrating superb results of a quite old med used for an entirely different purpose: ANTATBUSE( disulfiram) that I have not hesitated to take advantage of due to its general safety ( WITH SAFE GUARDS- See YOUR PHYSICIAN) As of 2019 , in LymesDisease.Org , Dr.Dan Kinderleher has been treating up to 60 patients just in His case load .
Google or look to That site or contact Your Provider to follow .Doug H. ( Retired R.N and long standing Lymes sufferer )- Bless You All , Brothers and Sisters!
Dr. Daniel Cameron
03/23/2022 (7:13 am)
Disulfiram was identified as a potential drug for tick borne diseases based on research in the test tube. Dr. Ken Liegner described his use of disulfiram in the following research paper. https://pubmed.ncbi.nlm.nih.gov/31151194/
James S. West
10/01/2020 (5:58 pm)
In 1984 I was walking through a meadow in the county of Mendocino to avoid the manzanita because of all the ticks. All at once I felt an extreme itching on my left ankle so I sat down, pulled my pantleg up and my sock down and there were two tiny little ticks stuck on my ankle about 2 inches apart. I said well I’ll be darned, I’m not safe anywhere from these things. There was a red rash and for over 6 months after starting out with the flue like symptoms I was nauseated. It went from nausea to pain in the joints and vision trouble…tunnel-vision and temporary loss of vision in one eye. After surviving and getting somewhat better but not completely free of symptoms, while living in Hawaii, I went to a neurologist. He said they didn’t have Lyme disease in Hawaii. I tried to explain about airplanes and timeframes but he was convinced that Lyme disease was not there and it was rare anywhere else. At this point in my life I have had two Western Blot tests and one other kind. Both kinds showed negative. I have a feeling that I’m going to die with this disease. What is the best test for chronic Lyme and what is the best treatment?
Dr. Daniel Cameron
10/01/2020 (6:55 pm)
Some of my patients never test positive for a tick-borne illness. There are a number of treatments. I also arrange for consultations to look for other illnesses.
Jim habash
01/03/2023 (2:25 pm)
Drop alcohol, sugar, and breads. Take vitamin c , zinc. Avoid stress. Stay in the sun. Wish I could. I tolerated 1989 Ehrlichia infection well without knowing I had Lyme. Got an unrelated penicillin shot in 2005, the herx and inflammation have never let up. Tried treating with heavy oral antibiotics off and on without any results. I think they made me worse. Even iodine based x ray dye for CT scan sends me into massive herx. Amazing. Retinal eye issues with dry eye and virus Epstein barr are doing well in me. Retinal specialist says eyes are fine. Have vitreal detachments and colored permanent artifacts always in the same spots of both eyes now. Since antibiotics have never helped in any way, I’m just trying to keep health in check. Dropped beef for ehrlichia after juicy red steak caused ganglion cysts appearing hours after eating a juicy red steak. After dropping beef the cysts all disappeared. But dropping all red meat for a year hasn’t helped given that I’ve had ehrlichia since 1989. Will be doing some hiking this spring while I still have my eyesight. Maybe get my bucket list rounded out while I still can.
Lori Barr
06/27/2020 (9:12 pm)
So happy that people in and out of the medical field have finally admitted Lyme is not cured after IV antibiotics. My poor husband has suffered from chronic Lyme for 10 yrs. and has been subjected to cruel and unnecessary criticism from many doctors, often being told to go and see a psychiatrist, it was all in his head, well considering it took a year to arrive at a diagnosis, at which time it had traveled to his CNS and has caused cognitive impairment, you might say it is in his head. 30 days of IV did not eradicate the damage.
Kathleen Rhodes
11/18/2021 (10:43 am)
I’m told same thing. Doctors tell me it’s all in my head
5 years so far for me. My symptoms are mostly neurological
Fred
03/07/2022 (3:29 pm)
Doctors tell that it is in your head, because they do not know what is the problem. Many MDs are not educated how to detect and treat Lyme and co-infections. You have to be your own doctor, otherwise it is very nasty and deadly disease.
Jim habash
01/03/2023 (2:27 pm)
I agree, never had iv but any antibiotics have never helped. Only made worse.