Association between statin use and clinical course, microbiologic characteristics, and long-term outcome of early Lyme borreliosis. A post hoc analysis of prospective clinical trials of adult patients with erythema migrans.

BACKGROUND: Statins were shown to inhibit borrelial growth in vitro and promote clearance of spirochetes in a murine model of Lyme borreliosis (LB). We investigated the impact of statin use in patients with early LB. METHODS: In this post-hoc analysis, the association between statin use and clinical and microbiologic characteristics was investigated in 1520 adult patients with early LB manifesting as erythema migrans (EM), enrolled prospectively in several clinical trials between June 2006 and October 2019 at a single-center university hospital. Patients were assessed at enrollment and followed for 12 months. RESULTS: Statin users were older than patients not using statins, but statin use was not associated with Borrelia seropositivity rate, Borrelia skin culture positivity rate, or disease severity as assessed by erythema size or the presence of LB-associated symptoms. The time to resolution of EM was comparable in both groups. The odds for incomplete recovery decreased with time from enrollment, were higher in women, in patients with multiple EM, and in those reporting LB-associated symptoms at enrollment, but were unaffected by statin use. CONCLUSION: Statin use was not associated with clinical and microbiologic characteristics or long-term outcome in early LB.

Forty Years of Evidence on the Efficacy and Safety of Oral and Injectable Antibiotics for Treating Lyme Disease of Adults and Children: A Network Meta-Analysis.

Lyme disease (LD) is a heavy public health burden. The most common manifestations of LD include erythema migrans (EM), Lyme neuroborreliosis (LNB), and Lyme arthritis (LA). The efficacy and safety of antibiotics for treating LD is still controversial. Thus, we performed a network meta-analysis (NMA) to obtain more data and tried to solve this problem. We searched studies in the databases of Embase and PubMed from the date of their establishments until 22 April 2021. Odds ratios (ORs) were used to assess dichotomous outcomes. A total of 31 randomized controlled trials (RCTs) involving 2,748 patients and 11 antibiotics were included. Oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD (range of ORs, 1.02 to 1,610.43). Cefuroxime and penicillin were safe for treating LD (range of ORs, 0.027 to 0.98). Amoxicillin was effective for treating EM (range of ORs, 1.18 to 25.66). Based on the results, we thought oral amoxicillin (1.5 g/day), oral azithromycin (0.5 g/day), injectable ceftriaxone, and injectable cefotaxime were effective for treating LD. Cefuroxime and penicillin were safe for treating LD. Amoxicillin was effective for treating EM. We did not observe evidence proving the advantage of doxycycline in efficacy and safety for treating LD, LA, LNB, and EM of children or adults. We did not have sufficient data to prove the significant difference of efficacy for treating LA and LNB in adults and LD in children, the significant difference of safety of oral drugs for treating LD, and the significant difference of safety of drugs for treating EM. IMPORTANCE Some previous studies investigated the efficacy and safety of antibiotics for treating Lyme disease (LD). However, due to technical limitations, several questions regarding the routes of drug administration and the dosages of drug are still unclear, which might be causing problems for clinicians. Hence, we performed network meta-analysis (NMA) to quantitatively analyze the clinical data published during the last 40 years. Here, we demonstrate the evidence regarding the efficacy and safety of antibiotics commonly used for treating LD in adults and children. We found that amoxicillin, azithromycin, ceftriaxone, and cefotaxime were effective for treating LD, but we did not observe significant efficacy and safety of doxycycline for treating LD.

Impact of four local anaesthetics on growth and viability of in vitro cultured Borrelia burgdorferi sensu stricto, Borrelia bavariensis and Borrelia afzelii.

Many local anaesthetics, including lidocaine, procaine and ropivacaine inhibit bacterial growth. This study investigates potential effects of these local anaesthetics on growth of Borrelia burgdorferi sensu stricto (Bbss), Borrelia bavariensis (Bbav) and Borrelia afzelii (Ba). For this purpose, Borrelia spp. organisms were either continuously or temporarily exposed to one of four local anaesthetics preparations: 20 mg/ml procaine hydrochloride (P); 10 mg/ml ropivacaine hydrochloride (R); 20 mg/ml lidocaine hydrochloride (L1, L2). L2 also contained the preservatives methyl-benzoate and propyl-benzoate, whereas P, R and L1 did not. All four local anaesthetic preparations inhibited in vitro growth of Borrelia spp. depending on concentration and exposure time. There are differences in sensitivity among the Borrelia spp. with Bbav being more susceptible to growth inhibition than Bbss and Ba. When comparing the different local anaesthetic preparations with their regard to inhibition of growth of Borrelia spp. organisms, P showed the lowest impact. It cannot be completely excluded that preservatives present in L2, methyl-benzoate and propyl-benzoate, may be a reason for further inhibition of Borrelia spp. organisms. Concentrations of local anaesthetics used in these experiments may also be present in the skin of patients during regular medical procedures. These are preliminary findings and further experiments, preferably in vivo, are necessary. To minimize the risk to produce false negative results with cultures, we recommend using procaine in a preparation without preservatives for local anaesthesia prior to skin sampling.

A combined transcriptomic approach to identify candidates for an anti-tick vaccine blocking B. afzelii transmission.

Ixodes ricinus is the vector for Borrelia afzelii, the predominant cause of Lyme borreliosis in Europe, whereas Ixodes scapularis is the vector for Borrelia burgdorferi in the USA. Transcription of several I. scapularis genes changes in the presence of B. burgdorferi and contributes to successful infection. To what extend B. afzelii influences gene expression in I. ricinus salivary glands is largely unknown. Therefore, we measured expression of uninfected vs. infected tick salivary gland genes during tick feeding using Massive Analysis of cDNA Ends (MACE) and RNAseq, quantifying 26.179 unique transcripts. While tick feeding was the main differentiator, B. afzelii infection significantly affected expression of hundreds of transcripts, including 465 transcripts after 24 h of tick feeding. Validation of the top-20 B. afzelii-upregulated transcripts at 24 h of tick feeding in ten biological genetic distinct replicates showed that expression varied extensively. Three transcripts could be validated, a basic tail protein, a lipocalin and an ixodegrin, and might be involved in B. afzelii transmission. However, vaccination with recombinant forms of these proteins only marginally altered B. afzelii infection in I. ricinus-challenged mice for one of the proteins. Collectively, our data show that identification of tick salivary genes upregulated in the presence of pathogens could serve to identify potential pathogen-blocking vaccine candidates.

Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials.

Lyme borreliosis is the most prevalent vector-borne disease in northern hemisphere. Borrelia burgdorferi sensu lato spirochetes are transmitted by Ixodes species ticks. During a blood meal, these spirochetes are inoculated into the skin where they multiply and often spread to various target organs: disseminated skin sites, the central nervous system, the heart and large joints. The usual diagnosis of this disease relies on serological tests. However, in patients presenting persistent clinical manifestations, this indirect diagnosis is not capable of detecting an active infection. If the serological tests are positive, it only proves that exposure of an individual to Lyme spirochetes had occurred. Although culture and quantitative PCR detect active infection, currently used tests are not sensitive enough for wide-ranging applications. Animal models have shown that B. burgdorferi persists in the skin. We present here our targeted proteomics results using infected mouse skin biopsies that facilitate detection of this pathogen. We have employed several novel approaches in this study. First, the effect of lidocaine, a local anesthetic used for human skin biopsy, on B. burgdorferi presence was measured. We further determined the impact of topical corticosteroids to reactivate Borrelia locally in the skin. This local immunosuppressive compound helps follow-up detection of spirochetes by proteomic analysis of Borrelia present in the skin. This approach could be developed as a novel diagnostic test for active Lyme borreliosis in patients presenting disseminated persistent infection. Although our results using topical corticosteroids in mice are highly promising for recovery of spirochetes, further optimization will be needed to translate this strategy for diagnosis of Lyme disease in patients.

Metamorphoses of Lyme disease spirochetes: phenomenon of Borrelia persisters.

The survival of spirochetes from the Borrelia burgdorferi (sensu lato) complex in a hostile environment is achieved by the regulation of differential gene expression in response to changes in temperature, salts, nutrient content, acidity fluctuation, multiple host or vector dependent factors, and leads to the formation of dormant subpopulations of cells. From the other side, alterations in the level of gene expression in response to antibiotic pressure leads to the establishment of a persisters subpopulation. Both subpopulations represent the cells in different physiological states. "Dormancy" and "persistence" do share some similarities, e.g. both represent cells with low metabolic activity that can exist for extended periods without replication, both constitute populations with different gene expression profiles and both differ significantly from replicating forms of spirochetes. Persisters are elusive, present in low numbers, morphologically heterogeneous, multi-drug-tolerant cells that can change with the environment. The definition of "persisters" substituted the originally-used term "survivors", referring to the small bacterial population of Staphylococcus that survived killing by penicillin. The phenomenon of persisters is present in almost all bacterial species; however, the reasons why Borrelia persisters form are poorly understood. Persisters can adopt varying sizes and shapes, changing from well-known forms to altered morphologies. They are capable of forming round bodies, L-form bacteria, microcolonies or biofilms-like aggregates, which remarkably change the response of Borrelia to hostile environments. Persisters remain viable despite aggressive antibiotic challenge and are able to reversibly convert into motile forms in a favorable growth environment. Persisters are present in significant numbers in biofilms, which has led to the explanation of biofilm tolerance to antibiotics. Considering that biofilms are associated with numerous chronic diseases through their resilient presence in the human body, it is not surprising that interest in persisting cells has consequently accelerated. Certain diseases caused by pathogenic bacteria (e.g. tuberculosis, syphilis or leprosy) are commonly chronic in nature and often recur despite antibiotic treatment. Three decades of basic and clinical research have not yet provided a definite answer to the question: is there a connection between persisting spirochetes and recurrence of Lyme disease in patients?

[Bilateral diaphragmatic palsy due to Lyme neuroborreliosis]. / Une paralysie diaphragmatique bilatérale révélant une neuroborréliose de Lyme.

INTRODUCTION: Lyme disease is not uncommon and can sometimes progress to neurological complications. We report here an unusual case of bilateral diaphragmatic paralysis secondary to Lyme neuroborreliosis. CASE REPORT: A 79-year-old man was admitted to the intensive care unit for acute respiratory distress requiring intubation and the long-term use of nocturnal non-invasive ventilation. Three months beforehand he had been bitten by a tick and developed erythema migrans which was treated with Doxycycline for 10 days. This clinical presentation became complicated a few days later by the progressive onset of severe dyspnoea. At admission, chest radiography revealed bilateral elevation of the diaphragm. Pulmonary function tests revealed a severe restrictive disorder aggravated by decubitus. A diaphragmatic electromyogram showed bilateral axonal polyneuropathy of the phrenic nerves. IgG and IgM antibodies to Borrelia burgdorferi were detectable in serum and cerebrospinal fluid, leading to the diagnosis of Lyme disease. He was treated with intravenous ceftriaxone 2g per day for 21 days, leading to a substantial improvement in symptoms. CONCLUSION: In the presence of unilateral or bilateral diaphragmatic paralysis of undetermined aetiology, it seems relevant to perform Lyme serology in the blood and, in positive cases, to follow up with a lumbar puncture in order to detect intrathecal IgG synthesis.

Clinical spectrum of Lyme disease.

Lyme disease (borreliosis) is one of the most common vector-borne diseases worldwide. Its incidence and geographic expansion has been steadily increasing in the last decades. Lyme disease is caused by Borrelia burgdorferi sensu lato, a heterogeneous group of which three genospecies have been systematically associated to Lyme disease: B. burgdorferi sensu stricto Borrelia afzelii and Borrelia garinii. Geographical distribution and clinical manifestations vary according to the species involved. Lyme disease clinical manifestations may be divided into three stages. Early localized stage is characterized by erythema migrans in the tick bite site. Early disseminated stage may present multiple erythema migrans lesions, borrelial lymphocytoma, lyme neuroborreliosis, carditis, or arthritis. The late disseminated stage manifests with acordermatitis chronica atrophicans, lyme arthritis, and neurological symptoms. Diagnosis is challenging due to the varied clinical manifestations it may present and usually involves a two-step serological approach. In the current review, we present a thorough revision of the clinical manifestations Lyme disease may present. Additionally, history, microbiology, diagnosis, post-treatment Lyme disease syndrome, treatment, and prognosis are discussed.

Genomic and phenotypic characterization of Borrelia afzelii BO23 and Borrelia garinii CIP 103362.

In recent years, the number of Lyme disease or borreliosis cases in Eurasia has been dramatically increasing. This tick-borne disease is caused by Borrelia burgdorferi sensu lato, which includes B. burgdorferi sensu stricto, the main species found in North America, and B. afzelii and B. garinii, which are primarily responsible for the disease in Eurasia. Currently, research on Lyme disease has focused mainly on B. burgdorferi while B. afzelii and B. garinii, which cause disease with distinctly different symptoms, are less studied. The purpose of this study is to evaluate B. afzelii BO23 and B. garinii CIP 103362 as model organisms to study Eurasian Lyme disease. To begin our analyses, we sequenced, annotated the chromosomes of both species and compared them to B. burgdorferi strain B31. We also assayed shuttle vector, pBSV2, for transformation efficacy and demonstrated that these strains can be cultured on solid media. In addition, we characterized how physicochemical parameters (e.g., oxygen, osmolarity, oxidative stress) affect both growth and motility of the bacteria. Finally, we describe each strain's antibiotic susceptibility and accessed their ability to infect mice. In conclusion, B. afzelii BO23 was more practical for in vitro and in vivo studies than B. garinii CIP 103362.

Cooperation of Doxycycline with Phytochemicals and Micronutrients Against Active and Persistent Forms of Borrelia sp.

Phytochemicals and micronutrients represent a growing theme in antimicrobial defense; however, little is known about their anti-borreliae effects of reciprocal cooperation with antibiotics. A better understanding of this aspect could advance our knowledge and help improve the efficacy of current approaches towards Borrelia sp. In this study, phytochemicals and micronutrients such as baicalein, luteolin, 10-HAD, iodine, rosmarinic acid, and monolaurin, as well as, vitamins D3 and C were tested in a combinations with doxycycline for their in vitro effectiveness against vegetative (spirochetes) and latent (rounded bodies, biofilm) forms of Borrelia burgdorferi and Borrelia garinii. Anti-borreliae effects were evaluated according to checkerboard assays and supported by statistical analysis. The results showed that combination of doxycycline with flavones such as baicalein and luteolin exhibited additive effects against all morphological forms of studied Borrelia sp. Doxycycline combined with iodine demonstrated additive effects against spirochetes and biofilm, whereas with fatty acids such as monolaurin and 10-HAD it produced FICIs of indifference. Additive anti-spirochetal effects were also observed when doxycycline was used with rosmarinic acid and both vitamins D3 and C. Antagonism was not observed in any of the cases. This data revealed the intrinsic anti-borreliae activity of doxycycline with tested phytochemicals and micronutrients indicating that their addition may enhance efficacy of this antibiotic in combating Borrelia sp. Especially the addition of flavones balcalein and luteolin to a doxycycline regimen could be explored further in defining more effective treatments against these bacteria.

In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii.

AIMS: Little is known about the effects of phytochemicals against Borrelia sp. causing Lyme disease. Current therapeutic approach to this disease is limited to antibiotics. This study examined the anti-borreliae efficacy of several plant-derived compounds and micronutrients. METHODS AND RESULTS: We tested the efficacy of 15 phytochemicals and micronutrients against three morphological forms of Borrelia burgdoferi and Borrelia garinii: spirochetes, latent rounded forms and biofilm. The results showed that the most potent substances against the spirochete and rounded forms of B. burgdorferi and B. garinii were cis-2-decenoic acid, baicalein, monolaurin and kelp (iodine); whereas, only baicalein and monolaurin revealed significant activity against the biofilm. Moreover, cis-2-decenoic acid, baicalein and monolaurin did not cause statistically significant cytotoxicity to human HepG2 cells up to 125 µg ml(-1) and kelp up to 20 µg ml(-1) . CONCLUSIONS: The most effective antimicrobial compounds against all morphological forms of the two tested Borrelia sp. were baicalein and monolaurin. This might indicate that the presence of fatty acid and phenyl groups is important for comprehensive antibacterial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reveals the potential of phytochemicals as an important tool in the fight against the species of Borrelia causing Lyme disease.

Defensin from the ornate sheep tick Dermacentor marginatus and its effect on Lyme borreliosis spirochetes.

Expression of the previously reported defensin of the tick Dermacentor marginatus (defDM) was analysed in different organs by RT-PCR. mRNA of the defDM gene was detected in the hemolymph, midgut and salivary glands. Moreover defDM was isolated from the tick hemolymph using RP-HPLC and its sequence was determined by mass spectrometry and Edman degradation. Synthetic peptide was used for determining biological activities. The results showed an anti-Gram-positive bacterial role for the defensin. As D. marginatus ticks appear not to be vectors of the Lyme disease agent of the complex Borrelia burgdorferi sensu lato, we tested the influence of defDM on Borrelia afzelii. There is a very clear borrelicidal activity of the defensin, which is concentration dependent and suggests a possible role in the clearing of Borrelia ingested by D. marginatus ticks.

Protective value of prophylactic antibiotic treatment of tick bite for Lyme disease prevention: an animal model.

Clinical studies have demonstrated that prophylactic antibiotic treatment of tick bites by Ixodes scapularis in Lyme disease hyperendemic regions in the northeastern United States can be effective in preventing infection with Borrelia burgdorferi sensu stricto, the Lyme disease spirochete. A large clinical trial in Westchester County, NY (USA), demonstrated that treatment of tick bite with 200mg of oral doxycycline was 87% effective in preventing Lyme disease in tick-bite victims (Nadelman, R.B., Nowakowski, J., Fish, D., Falco, R.C., Freeman, K., McKenna, D., Welch, P., Marcus, R., Agúero-Rosenfeld, M.E., Dennis, D.T., Wormser, G.P., 2001. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N. Engl. J. Med. 345, 79-84.). Although this excellent clinical trial provided much needed information, the authors enrolled subjects if the tick bite occurred within 3 days of their clinical visit, but did not analyze the data based on the exact time between tick removal and delivery of prophylaxis. An animal model allows for controlled experiments designed to determine the point in time after tick bite when delivery of oral antibiotics would be too late to prevent infection with B. burgdorferi. Accordingly, we developed a tick-bite prophylaxis model in mice that gave a level of prophylactic protection similar to what had been observed in clinical trials and then varied the time post tick bite of antibiotic delivery. We found that two treatments of doxycycline delivered by oral gavage to mice on the day of removal of a single potentially infectious nymphal I. scapularis protected 74% of test mice compared to controls. When treatment was delayed until 24 h after tick removal, only 47% of mice were protected; prophylactic treatment was totally ineffective when delivered ≥2 days after tick removal. Although the dynamics of antibiotic treatment in mice may differ from humans, and translation of animal studies to patient management must be approached with caution, we believe our results emphasize the point that antibiotic prophylactic treatment of tick bite to prevent Lyme disease is more likely to be efficacious if delivered promptly after potentially infectious ticks are removed from patients. There is only a very narrow window for prophylactic treatment to be effective post tick removal.

Treatment of infection caused by Borrelia burgdorferi sensu lato.

Borrelia burgdorferi sensu lato (Bbsl) infections, which are transmitted by Ixodes ticks, cause a wide variety of clinical manifestations and are of public health importance in parts of North America, Europe and Asia. A literature review of pertinent articles published up untill July 6th 2010 was performed on the use of antimicrobials in the treatment and prevention of Bbsl infections. The clinical outcome with 10-28 days of antibiotic treatment is generally excellent, but in view of the experience with other infections, future studies might address whether the duration of antibiotic therapy could be shortened.

Growth, cysts and kinetics of Borrelia garinii (Spirochaetales: Spirochaetacea) in different culture media.

The aim of the present paper was to evaluate cyst formation and growth parameters of Borrelia garinii in a range of media differing in formulation and cost. A qualitative assessment of morphology and motility of B. garinii was conducted. All media were prepared aseptically and used in test tubes or Petri dishes. For each medium, the initial spirochete concentration was standardized to 10(3) spirochets/mL. The following culture media were suitable to grow B. garinii: Barbour-Stoenner-Kelly, brain heart infusion and PMR. Growth was minimal at six weeks post-inoculation and maximum spirochete density was observed between 9-12 weeks. Often, the cultures developed cysts of different sizes, isolated or in groups, with a spiraled portion of variable sizes, mainly in unfavorable culture media. Brazilian Lyme disease-like illness, also known as Baggio-Yoshinari syndrome (BYS), is a new and interesting emerging tick-borne disease, caused by Borrelia burgdorferi sensu lato spirochetes, only during its cystic forms. It has been assumed that the peculiar clinical and laboratory features of BYS are consequential to the absence of a human sucker Ixodes ricinus complex tick at risk areas in Brazil, supporting the concept that the borrelia phenotypic expression pattern is modified as it is transmitted through the host.

In vitro activity of tigecycline against multiple strains of Borrelia burgdorferi.

OBJECTIVES: To compare the antimicrobial activity of tigecycline and doxycycline against multiple isolates of Borrelia burgdorferi. METHODS: In vitro antimicrobial assays were carried out using a microdilution assay. The time needed to inhibit, immobilize and kill the B31 strain of B. burgdorferi was determined. The MIC, MBC and concentration needed to immobilize the organism were determined for each antimicrobial for various strains of B. burgdorferi. RESULTS: Tigecycline inhibited the growth of and killed the organism more rapidly than doxycycline. Tigecycline was able to kill B. burgdorferi within 24 h at clinically achievable concentrations (<1 mg/L). In contrast, doxycycline was bacteriostatic and required 48-72 h to achieve its maximal inhibitory effect. The anti-Borrelia activity of the antibiotics was tested against 20 different isolates from three species. Tigecycline was 16- to 1000-fold more active than doxycycline at immobilizing Borrelia for the 20 isolates tested. CONCLUSIONS: We demonstrate that the in vitro activity of tigecycline against B. burgdorferi is superior to that of doxycycline. Tigecycline acted more rapidly and was bactericidal, whereas doxycycline was bacteriostatic and required a more prolonged co-incubation to achieve its maximal inhibitory effect.

Antimicrobial activity of three tick defensins and four mammalian cathelicidin-derived synthetic peptides against Lyme disease spirochetes and bacteria isolated from the midgut.

In this study, chemically synthesized tick defensins and cathelicidin-derived mammalian peptides were used to investigate the activity spectrum against Borrelia garinii and symbiotic Stenotrophomonas maltophila. Synthetic tick defensins showed antimicrobial activity against Staphylococcus aureus but not B. garinii and S. maltophila. Mammalian peptides which have cationic property similar to tick defensins, showed antimicrobial activity similar to tick defensins. The antimicrobial peptides in ticks and mammalian hosts have common characteristics against microbial invasion in the innate immune system.

The tick salivary protein Salp15 inhibits the killing of serum-sensitive Borrelia burgdorferi sensu lato isolates.

Borrelia burgdorferi, the agent of Lyme disease, is transmitted by ticks. During transmission from the tick to the host, spirochetes are delivered with tick saliva, which contains the salivary protein Salp15. Salp15 has been shown to protect spirochetes against B. burgdorferi-specific antibodies. We now show that Salp15 from both Ixodes ricinus and Ixodes scapularis protects serum-sensitive isolates of Borrelia burgdorferi sensu lato against complement-mediated killing. I. ricinus Salp15 showed strong protective effects compared to those of I. scapularis Salp15. Deposition of terminal C5b to C9 (one molecule each of C5b, C6, C7, and C8 and one or more molecules of C9) complement complexes, part of the membrane attack complex, on the surface of B. burgdorferi was inhibited in the presence of Salp15. In the presence of normal human serum, serum-sensitive Borrelia burgdorferi requires protection against complement-mediated killing, which is provided, at least in part, by the binding to the tick salivary protein Salp15.

[Microbiological and pharmacological data useful for the treatment of Lyme disease. Treatment and follow up of early Lyme disease (erythema migrans)]. / Bases microbiologiques et pharmacologiques du traitement de la borréliose de Lyme. Traitement et suivi de la phase aiguë (érythème migrant).

The aim of this review was first to analyze the microbiological and pharmacological criteria used to choose a treatment for Lyme disease. The determination of Borrelia burgdorferi sensu lato susceptibility to antibiotics is difficult, especially because of the lack of standardization in the methods used. In vitro data is helpful to determine Lyme treatment but discrepancies between in vitro and in vivo results highlight the need to confirm this data by clinical trials. The second part is an analysis of the literature made to evaluate the current strategies of treatment and follow up of early Lyme disease characterized by erythema migrans (EM). beta-lactams (penicillin G and V, amoxicillin, cefuroxime axetil, ceftriaxone), tetracyclines (doxycycline), and macrolides (mainly azithromycin) are the drugs most frequently used during clinical trials. The comparison between treatments is difficult because of the lack of reliable clinical and biological criteria to identify complete recovery. However the prognosis of treated EM is good in most trials. If a clinical follow-up remains necessary after the treatment of an EM, prolonged antibody production among asymptomatic patients reduces the interest of a serological follow-up.