Will late stage Lyme disease treatment include azlocillin?

Woman sleeping in car who needs late stage lyme disease treatment

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.

Study finds azlocillin may be a game-changer for the treatment of persistent Lyme disease symptoms. Click To Tweet

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]

References:
  1. 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.
  2. 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.
  3. 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.
  4. Wozel G, Blasum C. Dapsone in dermatology and beyond. Arch Dermatol Res. 2014;306(2):103-124.
  5. 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.
  6. Liegner KB. Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases. Antibiotics (Basel). 2019;8(2).
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1 Reply to "Will late stage Lyme disease treatment include azlocillin?"

  • Lori Barr
    06/27/2020 (9:12 pm)
    Reply

    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.


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