Monday, November 28, 2022

Antibiotic Therapy For Lyme Disease

Prevention Of Disease Spreading

Clinical Trial of Xenodiagnosis After Antibiotic Treatment for Lyme Disease

In addition to the paucity of data for a preventive effect of antibiotics, epidemiological studies show a discrepancy between the extent of seropositivity and clinical disease manifestations in Europe. The incidence of manifest borreliosis for rural inhabitants in a given area does not appear to be higher than for city dwellers. Even though up to 80% of forest workers report tick bites and up to 50% show immunoreactivity to Borrelia spp,, the incidence of clinical disease in this population is around 8/1000 irrespective of whether only seropositive or all forest workers are analysed. Of 16 subjects with seroconversion, only two developed clinical disease. A high frequency of tick bites and a high rate of transmission of the bacterium is contrasted by the comparatively low rate of clinical disease., This suggests that European borrelial infection may often be self limiting. We do not know which patients might be at risk for the development of late stage disease.

Has Niaid Looked At The Potential Benefits Of Long

Yes. NIAID has funded three placebo-controlled clinical trials on the efficacy of prolonged antibiotic therapy for treating PTLDS. The published results were subjected to rigorous statistical, editorial, and scientific peer review.

These trials were designed to ensure that several key parameters were addressed:

  • The susceptibility of B.burgdorferi to the antibiotics used
  • The ability of the antibiotics to both cross the blood-brain barrier and access the central nervous system and to persist at effective levels throughout the course of therapy
  • The ability of the antibiotics to kill bacteria living both outside and inside mammalian cells
  • The safety and welfare of patients enrolled in the trials

The first clinical trial, which included two multicenter studies, provided no evidence that extended antibiotic treatment is beneficial. In those studies, physicians examined long-term antibiotic therapy in patients with a well-documented history of previous Lyme disease but who reported persistent pain, fatigue, impaired cognitive function, or unexplained numbness. Those symptoms are common among people reporting PTLDS. Patients were treated with 30 days of an intravenous antibiotic followed by 60 days of an oral antibiotic.

In 2016, a clinical trial conducted in the Netherlands also concluded that in patients with persistent symptoms attributed to Lyme disease, longer term treatment with antibiotics did not provide additional benefits compared with shorter term regimens.

Lyme Disease Antibiotics Overview

The following are four general rules I use to develop a Lyme disease antibiotic regimen.

  • Rule 1. Combine antibiotics to treat all forms of the germ.
  • Rule 2. Combine antibiotics to treat Lyme living outside and inside of cells.
  • Rule 3. Combine antibiotics that work in different ways to attack the germ from different angles.
  • Rule 4. Treat all growth phases of Lyme at the same time – this means treatments should include antimicrobials that address persisters in addition to the growth phase of the term.

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Iv Antibiotic Regimen: Cephalosporin Plus Azole Plus Liposomal Cinnamon Clove And Oregano

  • ceftriaxone 2 gm IV 2 times a day for 4 days on and 3 days off
  • tinidazole 500 mg taken orally 1 pill 2-3 times a day for 4 days on and 3 days off in 7-day cycles
  • liposomal cinnamon, clove, and oregano capsules 1 pill 2 times a day

Key Points:

  • Various antibiotics can be used as IV. I use this one most commonly because it is the easiest to administer and one of the lowest cost IV regimens. The ceftriaxone is given in a syringe and injected over 10 minutes. This is also a pulse dose regimen . Ceftriaxone could be given daily instead as 2 gm IV 1 time a day.
  • I have found various pulse dose regimens of tinidazole to work. These include 2 weeks on and 2 weeks off or in the regimen seen here.

Treatment For Erythema Migrans

LYME DISEASE TREATMENT: PROPHYLAXIS, EARLY LYME, ...

People treated with appropriate antibiotics in the early stages of Lyme disease usually recover rapidly and completely. Early diagnosis and proper antibiotic treatment of Lyme disease can help prevent late Lyme disease.

Treatment regimens listed in the following table are for the erythema migrans rash, the most common manifestation of early Lyme disease. These regimens may need to be adjusted depending on a persons age, medical history, underlying health conditions, pregnancy status, or allergies. Consult an infectious disease specialist regarding individual patient treatment decisions.

Treatment regimens for localized Lyme disease.

Age Category
100 mg, twice per day orally N/A
500 mg, three times per day orally N/A
500 mg, twice per day orally N/A
4.4 mg/kg per day orally, divided into 2 doses 100 mg per dose
50 mg/kg per day orally, divided into 3 doses 500 mg per dose
30 mg/kg per day orally, divided into 2 doses 500 mg per dose

*When different durations of antibiotics are shown to be effective for the treatment of Lyme disease, the shorter duration is preferred to minimize unnecessary antibiotics that might result in adverse effects, including infectious diarrhea and antimicrobial resistance.

NOTE: For people intolerant of amoxicillin, doxycycline, and cefuroxime, the macrolide azithromycin may be used, although it is less effective. People treated with azithromycin should be closely monitored to ensure that symptoms resolve.

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Biofilms And Cysts Respond To Lyme Pulse Antibiotics

Lyme lives in two different forms, inside and outside of cells, and in biofilms. The two forms are spirochete and microscopic cyst form also sometimes called a round body or an L-form. When Lyme spirochetes are exposed to antibiotics they can morph into cyst forms or move into biofilm communities. Once antibiotics are stopped, Lyme comes out of biofilms where it is easier to treat. And cysts turn back into spirochetes, which are also easier to treat. So in a Lyme pulse antibiotic regimen, during the off periods Lyme can move back into a state which is easier to treat with antibiotics.

Description Of The Intervention

People with the characteristic skin lesion of Lyme disease, erythema migrans, followed by manifestations of infection of the nervous system, referred to as LNB, were successfully treated with antibiotics as early as 1948 . Treatment with antibiotics capable of crossing the bloodbrain barrier is now the standard of care for people diagnosed with LNB. However, no placebocontrolled trials have ever been performed, and the antibiotic of choice, route of administration, dose, and length of treatment for LNB remain controversial.

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Xenodiagnosis After Antibiotic Treatment For Lyme Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
First Posted : May 18, 2015Last Update Posted : October 29, 2021
  • Study Details

Background:

The most common tick-borne illness in the United States, Lyme disease is caused by Borrelia burgdorferi bacteria that are transmitted to people by Ixodes scapularis ticks. Most cases of Lyme disease are cured by antibiotics, but some patients continue to experience symptoms despite the absence of detectable Lyme bacteria. Xenodiagnosis uses a vector to detect the presence of a disease-causing microbe.. Researchers will use live, laboratory-bred ticks to see if Lyme disease bacteria can be detected in people after completing antibiotic therapy and if that is more common in people who continue to experience symptoms such as fatigue and joint pain.

Objectives:

– To see if ticks can be used to detect B. burgdorferi in people who have had Lyme disease and received antibiotic therapy and if it correlates with persistent symptoms.

Eligibility:

Condition or disease
Procedure: Skin biopsyProcedure: Blood drawDevice: Xenodiagnosis Phase 1Phase 2

Oral Antibiotics For Early Treatment Of Lyme

IV antibiotics for neurologic Lyme disease – Video abstract: 23829

The bacteria involved in spreading Lyme disease throughout the body are intelligent. They find ways to hide in the bloodstream along the lining, making it hard for antibiotics to find and attack. The bacteria are also robust. They can move and replicate even when traveling against the flow of blood.

Plus, to eliminate Lyme bacteria, Borrelia burgdorferi, the bacterias antibodies must be present at the time of antibiotic treatment. This means that if your doctor prescribes antibiotics for two weeks, the bacteria are in hibernation during those two weeks, and they can remain after the treatment ends.

Timing is everything when using oral antibiotics. This becomes even more true for patients who have had Lyme disease for a long time. Oral antibiotics are not as successful when treating late or chronic Lyme disease, plus they can have side effects.

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Macrolide Plus Grapefruit Seed Extract Plus Cryptolepis

  • clarithromycin 500 mg 1 pill 2 times a day
  • grapefruit seed extract 250 mg 1 pill 2 times a day.
  • cryptolepis 5 ml 3 times a day

Key Points:

  • Grapefruit seed extract is better tolerated than both tinidazole and metronidazole and supports killing of Lyme cysts.
  • Cryptolepis can treat persister and growing Lyme. If a person also has Babesia, cryptolepis can treat this too.

Key Points For Healthcare Providers

  • In patients with facial palsy who are unable to close one or both eyes, eye drops or an eye patch may be needed to prevent dry eyes.
  • Neurologic symptoms do not necessarily indicate central nervous system infection in a patient with Lyme disease.
  • Two-step serologic testing for Lyme disease is the recommended diagnostic test for neurologic Lyme disease.
  • Cerebral spinal fluid analysis is not necessary to diagnose Lyme meningitis, but can help exclude other causes of illness, such as bacterial meningitis.
  • Consider Lyme radiculoneuritis in patients who report severe limb or truncal radicular pain without preceding trauma who live in or who have traveled to Lyme-endemic areas.
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    Chronic Lyme Disease Or Postlyme Disease Syndrome

    Following an episode of Lyme disease that is treated appropriately, some persons have a variety of subjective complaints . Some of these patients have been classified as having chronic Lyme disease or postLyme disease syndrome, which are poorly defined entities. These patients appear to be a heterogeneous group. Although European patients rarely have been reported to have residual infection with B. burgdorferi , this has yet to be substantiated either in a large series of appropriately treated European patients or in a study of North American patients. Residual subjective symptoms that last weeks or months also may persist after other medical diseases . It has also been recognized that the prevalence of fatigue and/or arthralgias in the general population is > 10% .

    In areas of endemicity, coinfection with B. microti or the Ehrlichia species that causes HGE may explain persistent symptoms for a small number of these patients . Randomized controlled studies of treatment of patients who remain unwell after standard courses of antibiotic therapy for Lyme disease are in progress. To date, there are no convincing published data showing that repeated or prolonged courses of oral or iv antimicrobial therapy are effective for such patients. The consensus of the IDSA expert-panel members is that there is insufficient evidence to regard chronic Lyme disease as a separate diagnostic entity.

    Stages Of Lyme Disease

    Developing New Guidelines on Lyme Disease

    There are three stages of Lyme disease. Early localized Lyme disease is defined as being diagnosed soon after a tick has bitten you. You may have seen the tick, removed it, and noticed a rash. You may even be starting to feel like you have the flu or coping with headaches.

    This is the best time to treat Lyme disease. This is, for many, the only stage in which oral antibiotics are successful. Once the disease begins to move to other places in the body, as it does in the Early Dissemination stage, oral antibiotics may not be strong enough to fight infection.

    In the third stage, Late Lyme, it is unlikely oral antibiotics alone can rid you of the bacterial infection. This is when doctors and patients start to look at alternative methods of treatment.

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    What Is Chronic Lyme Disease

    Lyme disease is an infection caused by the bacterium Borrelia burgdorferi. In the majority of cases, it is successfully treated with oral antibiotics. In some patients, symptoms, such as fatigue, pain and joint and muscle aches, persist even after treatment, a condition termed Post Treatment Lyme Disease Syndrome .

    The term chronic Lyme disease has been used to describe people with different illnesses. While the term is sometimes used to describe illness in patients with Lyme disease, it has also been used to describe symptoms in people who have no clinical or diagnostic evidence of a current or past infection with B. burgdorferi . Because of the confusion in how the term CLD is employed, and the lack of a clearly defined clinical definition, many experts in this field do not support its use.

    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:

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    All Antibiotics Are Not Good To Pulse

    The Northeastern experiments showed in a lab persister cells require 24 hours before they wake up out of hibernation. In the experiment they literally washed the existing antibiotics off of the petri dish. In humans, we cannot just wash antibiotics out. It takes time for antibiotics to build up to an effective dose and time for the same antibiotic to get out of the body.

    In pharmacy science each medicine has an elimination half-life. An elimination half-life is the time it takes to get half of a medicine out. Physicians use the elimination half-life for a drug to determine how long it takes to completely remove a drug or how long it takes to get the drug to a maximum level in the blood.

    It takes 4 elimination half-lives to remove a medicine completely. It takes 4 elimination half-lives for a medicine to reach the highest drug level in the blood.

    Long-half life medicines should not be pulsed. One of these antitibiotics is azithromycin . It has an elimination half-life of 68 hours. This means it takes 272 hours to completely eliminate this medicine from the body once it is stopped. Of the current antibiotics most Lyme Literate Medical Doctors use, azithromycin is the only one that should not be pulsed.

    Read more about Lyme antibiotic regimens in A Lyme Disease Antibiotic Guide.

    Why This Is Important

    Lyme Disease: The Latest Guidelines on Testing, Prophylaxis, and Treatment

    The use and duration of antibiotics for chronic Lyme disease treatment is controversial because there is no biomarker that can determine whether the Lyme bacteria has been eradicated in CLD patients. Patients are often told that either chronic Lyme disease does not exist or that it is incurable. If this were true, we would not expect more well and substantially improved patients to be taking antibiotics. Instead, we might have expected the percentage of people using antibiotics to be roughly the same among the patient subgroups.

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    How Is It Treated

    Facial palsy is treated with oral antibiotics and Lyme meningitis/radiculoneuritis can either be treated with oral or intravenous antibiotics, depending on severity . Most people with Lyme disease respond well to antibiotics and fully recover. Varying degrees of permanent nervous system damage may develop in people who do not receive treatment in the early stages of illness and who develop late-stage Lyme disease.

    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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