Azlocillin Comes Out On Top
The drug, which is not on the market, was tested in mouse models of Lyme disease at seven-day, 14-day and 21-day intervals and found to eliminate the infection. For the first time, azlocillin was also shown to be effective in killing drug-tolerant forms of B. burgdorferi in lab dishes, indicating that it may work as a therapy for lingering symptoms of Lyme disease.
Pothineni and Rajadas have patented the compound for the treatment of Lyme disease and are working with a company to develop an oral form of the drug. Researchers plan to conduct a clinical trial.
Rajadas is also a professor of bioengineering and therapeutic sciences at the University of California-San Francisco.
Other Stanford co-authors are Hari-Hara S. K. Potula, PhD, senior research scientist postdoctoral scholars Aditya Ambati, PhD, and Venkata Mallajosyula, PhD senior research scientist Mohammed Inayathullah, PhD and intern Mohamed Sohail Ahmed.
A researcher at Loyola College in India also contributed to the work.
The study was funded by the Bay Area Lyme Foundation and Laurel STEM Fund.
How Effective Is Cefuroxime Against Lyme Disease
Cefuroxime is a good choice for Lyme disease because it is effective against most strains of Borrelia burgdorferi, the bacteria responsible for Lyme disease.
Cefuroxime has also been effective in treating some infections caused by other species of Borrelia and different types of bacterial pathogens.
Features Associated With Improved Treatment Outcomes
As noted above, the companion machine learning study analyzed 215 features from the MyLymeData patient registry and identified key predictive features . Most of the 30 features identified related to treatment, which is the focus of this section. More specifically, we focus on treatment approach, treatment duration, and clinical focus of the treating clinician.
The use of antibiotics and the duration of antibiotic treatment for CLD is controversial . This is because there is no biomarker that can determine whether Borrelia burgdorferi has been eradicated in CLD patients. In addition, CLD is an under-funded disease that has not attracted pharmaceutical interest in treatment improvement. Only three grants have been funded by the NIH to assess treatment response in Lyme patients who remain ill after a short course of antibioticsthe last was funded over 20 years ago. These trials yielded conflicting results, relied on average treatment effects, employed small samples , and excluded over 89% of patients who sought to enroll .
It is against this backdrop that this study was conducted. To our knowledge, it is the largest observational study of patients using real-world data to analyze the response of CLD patients to treatment.
4.3.1. The Use of Antibiotics Is Associated with Improved Treatment Outcomes
4.3.2. Longer Treatment Durations Associated with Greater Treatment Response
4.3.3. Clinical Focus of Treating Practitioner
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How Do You Know If Its A Herx And Not An Adverse Drug Reaction
It is important to distinguish between a herx and an adverse drug reaction . The onset of a Herxheimer reaction is somewhat diagnostic of a spirochetal infection. So, if youre being treated for Lyme based on a clinical diagnosis, the herx can actually be a good sign that you are killing the right bacteria.
Ive talked to patients whove had Herxheimer reactions and almost all of them tell me it is a very intense experience. One patient described it as an altered state. Said one: Every cell in my body feels like its being crippled. Its mentally overwhelming and physically exhausting. I usually have a pulsing feeling in my body which distinguishes it from a medication side effect.
Adverse drug reactions, on the other hand, can range from mild to severe and can be mistaken for a herx. So how do you tell the difference?
Another patient distinguishes the two reactions as follows: Herxes for me seem to be more all over and include psych symptoms. Drug reactions seem to be more in line with what is described in the drug manufacturers papers. With antimicrobials, you can have both simultaneously, of course.
Mild ADRs will typically resolve shortly after the medication is stopped. On the other hand, a severe allergic reaction, called anaphylaxis, causes swelling of the airways, and can be fatal if not treated immediately .
Defining Patient Subgroups: Post
Patients with persistent symptoms related to Lyme disease likely represent a heterogeneous population, which includes previously untreated patients, as well as those treated patients who remain symptomatic. As a result, some will manifest primarily patient-reported symptoms while others will present with symptoms in conjunction with objective, physical findings. This heterogeneity is further complicated by variation in terminology and the definitions used by different groups in the field.
Figure 3. A schematic of clinical- and research-defined patient subgroups among those with persistent symptoms associated with Lyme disease . The size of each patient subgroup is not meant to represent actual population frequency, as prevalence data is extremely limited. IDSA, Infectious Diseases Society of America ILADS, International Lyme and Associated Diseases Society CLD-PT, Chronic Lyme Disease-Previously Treated CLD-U, Chronic Lyme Disease-Untreated IgG, Immunoglobulin G CFS, Chronic Fatigue Syndrome FM, Fibromyalgia.
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Symptoms Of Late Stage Lyme Disease
The CDC reports that late stage Lyme disease may appear days to months after the initial tick bite and may include but are not limited to:
- Severe headaches and neck stiffness
- Additional EM rashes in new places on the body
- Facial palsy, also known as Bells palsy paralysis of one side of the face
- Arthritis or joint pain and swelling, especially of large joints
- Intermittent tendon, muscle, joint, nerve, or bone pain
- Heart palpitations or arrhythmia
- Dizziness or shortness of breath
- Inflammation of the brain or spinal cord
- Shooting pains, numbness, or tingling in the hands or feet
As mentioned above, late stage Lyme may also be characterized by the recurrence of early stage symptoms, such as fatigue.
Symptoms Check Out? Get Tested. Get Answers.
Treatment For Chronic Lyme Disease
Sometimes, people go through treatment for Lyme disease but their symptoms donât go away. If this lasts over 6 months, itâs known as chronic Lyme disease or âpost-treatment Lyme disease syndromeâ .
Doctors still arenât sure why some people get PTLDS. Some believe that getting Lyme disease may cause damage to your tissues or immune system. Others believe itâs because the bacteria that causes Lyme hasnât completely gone away.
There is little evidence that taking more antibiotics at this stage will help. They may actually be harmful. Instead, your doctor will focus on treating the symptoms youâre still having. This will be different for everyone. Some people could benefit from a medicine that relieves fatigue, while others may need a drug that can help with headaches or very sensitive skin.
Your doctor could also have you try a treatment that helps people with chronic fatigue syndrome or fibromyalgia.
More research is needed to figure out how best to treat PTLDS. Itâs something that can be frustrating. Just remember: Many people who have this condition do start feeling like their old selves after a few months.
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Early Detection Is Key
Lyme disease is easiest to treat at the early or acute stage, within the first 30 days of exposure. This is why its so important to take precautions to prevent tick bites, both during and outside of tick season. Protect yourself when near potential tick habitats, always perform tick checks after outdoor activity , and dont delay seeking medical attention if you notice any symptoms that might be related to tick-borne illness. Its important to get tested as soon as possible for the best chances of recovery.
I Took All The Right Meds For Lyme So Why Didn’t I Get Better
In the autumn of 2010, I was a newly minted PhD living in North Carolina and trying to find employment on the elusive tenure track. I juggled my search for a medical sociology position with postdoctoral research, adjunct teaching and a lively social life. My days were full but fulfilling. The first two weeks of November, however, brought leaden fatigue, and I blamed my busy schedule. Seeking respite, I booked an inexpensive silent retreat at a nearby spiritual center.
I lucked into an unusually warm weekend and spent my time strolling well-worn woodland paths and sitting in quiet meditation in a nearby grassy field. Back home after three days, I peeled off my clothes for a shower. Reflected in the bathroom mirror was a rash the shape of a bulls-eye, blooming bright red on my left hip. After dinner I developed a fever that alternately froze and scalded me. My joints turned to piercing shards of glass, and pain stabbed my left temple. My vision blurred and my eyes became so sensitive that I flinched when my husband, Kevin, turned on an overhead light.
A few minutes on Google confirmed that the bulls-eye rash was a clear sign of Lyme disease. I read that antibiotics, administered early, could zap the corkscrew-shaped bacteria and prevent their wreaking long-term havoc on a persons brain, muscles and joints.
Youve been sick for months, he reminded me.
At my first visit, Dr. 2 suggested two months of antibiotics, double my prior dosage.
Good, I said. I guess.
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Antibiotics For Lyme Disease
How long to treat patients with Lyme remains an issue of controversy. With traditional antibiotic therapy, lasting 2-4 weeks, 10-20% of patients will have ongoing symptoms including fatigue, joint pain, insomnia and complaints of brain fog. Indefinite long-term treatment is advocated by ILADS , based on a patients symptoms. In contrast, IDSA only recommends 2-4 weeks’ treatment. The two groups are bitter adversaries.
A new study supports short-course treatmentbut is not entirely above criticism.
This study from the Netherlands, reported in the New England Journal of Medicine, was well designed, being randomized and double blind, and with a quasi-placebo group .
The upshot: There were no differences in the outcomes of the three treatment groupsbut some lingering questions remain. Notably, a large percentage of patients had side effects from the antibiotics, some quite serious.
Why is this important?
Lyme has been increasing, especially in the northeastern and upper Midwest portions of the U.S. The CDC now estimates there are about 300,000 cases of Lyme each year, with 30,000 reported cases.
But Lyme can be difficult to diagnose, and the assays miss a lot of patients . So if 20% of patients are left with persistent symptoms, that means that 60,000 people per year are being left with untreated problems that we just dont know what to do with. This study, along with others before it, suggests that longer antibiotics are not the answer.
The fine print:
Study Findings:
How Long Does Lyme Disease Last If Not Treated
Lyme borreliosis is a bacterial infection typically caused by the bacteria Borrelia burgdorferi.
It spreads to humans through the bite of an infected tick, which can be challenging to spot because its often so small.
Its best to prevent tick bites because symptoms can include fatigue, fever, and headaches once youve been bitten. Left untreated, it can lead to long-term problems such as arthritis or heart complications.
Since this disease is not easily diagnosed by blood tests alone , many infected people dont get adequately treated unless they have a doctor who understands this illness.
If left untreated for too long sometimes years permanent damage may result from chronic inflammation caused by Lyme spirochetes remaining in your body despite antibiotic therapy.
Some researchers believe that chronic Lyme disease affects up to 20 % of all people who contract it!
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What Is Lyme Arthritis
Lyme arthritis occurs when Lyme disease bacteria enter joint tissue and cause inflammation. If left untreated, permanent damage to the joint can occur. Lyme arthritis accounts for approximately one out of every four Lyme disease cases reported to CDC. Because of reporting practices, this statistic may overstate the frequency of arthritis among patients seen in routine clinical practice.
Chronic Lyme Disease Vs Ptlds
The terms chronic Lyme disease and Post-Treatment Lyme Disease Syndrome are sometimes used interchangeably. However, PTLDS is slightly more restrictive, referring to patients who have received treatment for Lyme disease but go on to experience Lyme disease symptoms. It does not include those who received a misdiagnosis or delayed diagnosis and have developed chronic symptoms of Lyme disease before receiving any kind of treatment.
The CDC defines PTLDS as generalized and/or recurring pain, fatigue, and cognitive difficulties that last for more than 6 months after treatment. These mirror symptoms associated with chronic Lyme disease, with or without treatment.
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Stage : Late Disseminated Lyme Disease
Stage 3 or late disseminated Lyme disease is the final stage of the disease. A person may enter this stage if they did not receive treatment for Lyme disease in the early stages, or if their symptoms persisted despite treatment. As such, doctors sometimes refer to this stage as chronic or post-treatment Lyme disease .
Stage 3 Lyme disease can occur after an infected tick bites a person.
A person with stage 3 Lyme disease may experience additional symptoms, including:
- severe joint pain and swelling, known as chronic Lyme arthritis
- heart palpitations or irregular heartbeat, due to Lyme carditis
- inflammation of the brain and spinal cord
- mental fogginess
How Is Lyme Disease Diagnosed
It can be hard for doctors to diagnose Lyme disease because:
- The tick bites and rash might not be noticed.
- Many early symptoms seem like the flu or other illnesses.
- Blood tests are not always accurate, especially early in the illness.
Doctors can diagnose early Lyme disease if they see a tick bite and rash. Blood tests usually arent helpful in the first month of Lyme disease.
To diagnose late Lyme disease, doctors:
- Ask about symptoms.
- Do blood tests that look for signs of Lyme disease.
Depending on the symptoms, doctors might order other tests, such as a spinal tap, which looks at the fluid around the brain and spinal cord.
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Potential Treatment For Lyme Disease Kills Bacteria That May Cause Lingering Symptoms Study Finds
Screening thousands of drugs, Stanford scientists determined that in mice, azlocillin, an antibiotic approved by the Food and Drug Administration, eliminated the bacteria that causes Lyme disease.
Deer ticks are vectors of Borrelia burgdorferi, the bacteria that causes Lyme disease.Scott Bauer/USDA Agricultural Research Service
For decades, the routine treatment for Lyme disease has been standard antibiotics, which usually kill off the infection. But for up to 20% of people with the tick-borne illness, the antibiotics dont work, and lingering symptoms of muscle pain, fatigue and cognitive impairment can continue for years sometimes indefinitely.
A new Stanford Medicine study in lab dishes and mice provides evidence that the drug azlocillin completely kills off the disease-causing bacteria Borrelia burgdorferi at the onset of the illness. The study suggests it could also be effective for treating patients infected with drug-tolerant bacteria that may cause lingering symptoms.
This compound is just amazing, said Jayakumar Rajadas, PhD, assistant professor of medicine and director of the Biomaterials and Advanced Drug Delivery Laboratory at the Stanford School of Medicine. It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease. Rajadas is the senior author of the study, which was published online March 2 in Scientific Reports. The lead author is research associate Venkata Raveendra Pothineni, PhD.
Lyme Disease Frequently Asked Questions
If you have not done so already, remove the tick with fine-tipped tweezers.
The chances that you might get Lyme disease from a single tick bite depend on the type of tick, where you acquired it, and how long it was attached to you. Many types of ticks bite people in the U.S., but only blacklegged ticks transmit the bacteria that cause Lyme disease. Furthermore, only blacklegged ticks in thehighly endemic areas of the northeastern and north central U.S. are commonly infected. Finally, blacklegged ticks need to be attached for at least 24 hours before they can transmit Lyme disease. This is why its so important to remove them promptly and to check your body daily for ticks if you live in an endemic area.
If you develop illness within a few weeks of a tick bite, see your health care provider right away. Common symptoms of Lyme disease include a rash, fever, body aches, facial paralysis, and arthritis. Ticks can also transmit other diseases, so its important to be alert for any illness that follows a tick bite.
References:
Moody KD, Barthold SW, 1991. Relative infectivity of Borrelia burgdorferi in Lewis rats by various routes of inoculation.Am J Trop Med Hyg 44: 135-9.
There are no reports of Lyme disease being spread to infants through breast milk. If you are diagnosed with Lyme disease and are also breastfeeding, make sure that your doctor knows this so that he or she can prescribe an antibiotic thats safe for use when breastfeeding.
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How Long Does It Take To Get Better On Antibiotics For Lyme
If you take doxycycline or minocycline, your symptoms will probably disappear within two weeks. If youre taking amoxicillin or cefuroxime axetil , your symptoms should go away within three weeks.
However, keep in mind that antibiotics may not cure everyone. This is because some people dont respond well to drugs, and others have other conditions contributing to their illness.
Pathophysiology Of Lyme Disease
B. burgdorferi is a fascinating bacterium . It has < 1500 gene sequences with at least 132 functioning genes. In contrast, Treponema pallidum, the spirochetal agent of syphilis, has only 22 functioning genes. The genetic makeup of B. burgdorferi is quite unusual. It has a linear chromosome and 21 plasmids, which are extrachromosomal strands of DNA. This is 3 times more plasmids than any other known bacteria . Plasmids are thought to give bacteria a kind of rapid response system that allows them to adapt very rapidly to changes in the environment, and the complex genetic structure of B. burgdorferi suggests that this is a highly adaptable organism .
In addition to its complex genetic makeup, B. burgdorferi engages in so-called stealth pathology to evade the human immune response . Stealth pathology involves 4 basic strategies: immunosuppression genetic, phase, and antigenic variation physical seclusion and secreted factors . These strategies are outlined below.
Stealth pathology of Borrelia burgdorferi.
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