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 Post subject: Pubmed medical abstracts regarding LD & Meds
PostPosted: Mon Feb 18, 2008 3:24 pm 
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Many medical abstract regarding Lyme Disease and the co-infections can be found by searching: http://www.pubmed.com

Lyme disease is a complex multisystem disorder recognized on three continents, which is epidemic in some regions during spring, summer, and fall seasons. It primarily affects skin, nervous system, heart, and joints. It is an infectious disease caused by a spirochete Borellia burgdorferi, which is transmitted chiefly by Ixodes dammini and pacificus ticks in the United States and Ixodes ricinus in Europe. Diagnosis is based on patient contact with an endemic area, one or more characteristic clinical features, particularly erythema migrans rash, and a positive serologic test for B. burgdorferi infection in the majority of cases. Although infection is the primary cause of the disease, immune mechanisms may play a synergistic role in some manifestations. Prompt diagnosis and treatment are important for full recovery. Treatment with oral tetracycline or penicillin is effective in the earliest stages but late complications require high doses of intravenous penicillin and sometimes corticosteroids. Some late complications are refractory to antibiotic therapy. Antibody appears to be protective in human and experimental studies. http://www.ncbi.nlm.nih.gov/pubmed/3332 ... d_RVDocSum
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To compare the efficacy of oral doxycycline and IV penicillin G for the treatment of neuroborreliosis, we randomized consecutive patients with Lyme neuroborreliosis to receive either IV penicillin G (3 g q 6 h) or oral deoxycycline (200 mg q 24 h) for 14 days. All patients had antibodies against Borrelia burgdorferi in serum, CSF, or both, or had a positive CSF culture. Twenty-three patients randomized to penicillin G and 31 patients to doxycycline were included in the study. All patients improved during treatment, and there were no significant differences between the two treatment groups in patient scoring, CSF analysis, or serologic and clinical follow-up during 1 year. There were no treatment failures, although one patient in each treatment group was re-treated because of residual symptoms. In conclusion, oral doxycycline is an adequate and cost-effective alternative to IV penicillin for the treatment of Lyme neuroborreliosis.
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Ultrastructure of Borrelia burgdorferi after exposure to benzylpenicillin.
The aim of this study was to investigate the morphological changes of Borrelia burgdorferi associated with penicillin treatment. An isolate of B. burgdorferi from an erythema migrans lesion was cultivated in BSK II medium and exposed to increasing concentrations (0.0625 mg/l-2 mg/l) of penicillin G for 5 days. The in vitro minimal inhibitory concentration (MIC) was determined to be 0.5 mg/l by broth dilution method. The morphological structures of untreated spirochetes, as well as their characteristic ultrastructural changes when exposed to penicillin, were observed by electron microscopy. The following alterations were discovered: (i) Numerous outer sheath blebs at a penicillin concentration of 0.0625 mg/l. (ii) A characteristic irregular waveform of the borrelial cells and complete loss of the outer sheath at a penicillin concentration of 0.125 mg/l. (iii) The presence of "spheroplasts" at the same concentration. (iv) Structural changes of the protoplasmic cylinder complex which showed an irregular pattern at a penicillin concentration of 0.125 mg/l. (v) Disruption of the protoplasmic cylinder complex into several parts at penicillin concentrations of 0.25 mg/l and 0.5 mg/l. (vi) Severe cytolysis at penicillin concentrations of 1 mg/l and 2 mg/l.

PMID: 7698837 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/7698 ... d_RVDocSum
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Changes in the expression pattern of structural proteins after exposure of Borrelia burgdorferi to penicillin G and doxycycline.
The numerous genes and proteins encoded in the borrelial genome have been shown to undergo differential expression in response to environmental cues. To gain a better understanding of possible interactions between antimicrobial agents and Borrelia, we investigated here the effects of increasing concentrations of penicillin G and doxycycline on the protein expression of the Borrelia burgdorferi s.s. isolate LW2 after 24 and 48h of incubation. For 14 protein spots in Borrelia exposed to penicillin G at 0.25 and 0.5mug/ml and for 5 protein spots in Borrelia exposed to doxycycline at 0.5 and 1mug/ml, differences in spot intensity were identified by use of high resolution two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). At concentrations of both antimicrobial agents around the median minimal inhibitory concentration (0.5mug/ml), all but one of the detected spots showed a considerable down-regulation as revealed by a 50% decrease of spot intensity in comparison to untreated controls. Most of the spots identified thus far belong to proteins that are encoded by genes localized on the borrelial chromosome and are known to be involved in the different pathways of bacterial cell metabolism. Interestingly, one spot, identified as triosephosphate isomerase, was clearly up-regulated in the presence of doxycycline. Our data provide for the first time scientific evidence that B. burgdorferi s.l., although it possesses a small genome and extremely limited biosynthetic capabilities, shows a variable but distinct physiological response to exposure with penicillin G and doxycycline.

PMID: 18249152 [PubMed - as supplied by publisher] http://www.ncbi.nlm.nih.gov/pubmed/1824 ... d_RVDocSum
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Macrolide therapy of chronic Lyme Disease
BACKGROUND: Macrolide antibiotics are highly active in vitro against B.burgdorferi, but have limited efficacy in the treatment of patients with Lyme Disease. As macrolides are less active at a low pH, their poor clinical activity might be due to localization of borrelia to an acidic endosome, and their activity improved by alkalinization of that compartment with hydroxychloroquine. MATERIAL/METHODS: 235 patients with a multi-symptom complex typical of chronic Lyme disease, ie fatigue, musculoskeletal pain, and neurocognitive dysfunction and with serologic reactivity against B.burgdorferi were treated with a macrolide antibiotic (eg clarithromycin) and hydroxychloroquine. RESULTS: Eighty % of patients had self-reported improvement of 50% or more at the end of 3 months. After 2 months of treatment, 20% of patients felt markedly improved (75-100% of normal); after 3 months of treatment, 45% were markedly improved. Improvement frequently did not begin until after several weeks of therapy. There were no differences among the three macrolide antibiotics used. Patients who had been on hydroxychloroquine or macrolide antibiotic alone had experienced little or no improvement. Compared to patients ill for less than 3 years, the onset of improvement was slower, and the failure rate higher in patients who were ill for longer time periods. CONCLUSIONS: These results support the hypothesis that the Lyme borrelia reside in an acidic endosome and that the use of a lysosomotropic agent augments the clinical activity of macrolide antibiotics in the treatment of patients with chronic Lyme Disease. In contrast, the efficacy of tetracycline in such patients is not affected by hydroxychloroquine.

PMID: 14586290 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1458 ... d_RVDocSum
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Clarithromycin in treatment of early Lyme disease: a pilot study.
Dattwyler RJ, Grunwaldt E, Luft BJ.
Lyme Disease Center, State University of New York at Stony Brook 11794-8161, USA.

Forty-one patients with erythema migrans were enrolled in an open-labelled pilot study of oral clarithromycin, 500 mg twice daily for 21 days, for the treatment of early Lyme disease. Immediately posttherapy, pretreatment signs and symptoms resolved among 91% of the 33 evaluable patients. At 6 months, all 28 of the evaluable patients were well. Clarithromycin shows promise as an effective agent for the treatment of early Lyme disease and warrants further study.

PMID: 8834900 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/8834 ... d_RVDocSum
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Efficacy of clarithromycin for treatment of experimental Lyme disease in vivo.
Clarithromycin provided effective therapy against arthritis induced by Borrelia burgdorferi infection in the hamster. In vitro, clarithromycin was at least 1 log more potent than tetracycline against two isolates of B. burgdorferi from human sources, as measured by MICs and 50% inhibitory concentrations. Clarithromycin was effective in preventing the onset of B. burgdorferi-induced arthritis, as determined by several parameters of paw swelling. When administered after the onset of arthritis, clarithromycin therapy reduced the degree of swelling and decreased recovery time. These results suggest that clarithromycin has potential as an effective therapy for Lyme disease.

PMID: 8328782 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/8328 ... d_RVDocSum
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Comparative antimicrobial activity of the new macrolides against Borrelia burgdorferi.
Preac-Mursic V, Wilske B, Schierz G, Süss E, Gross B.
Max von Pettenkofer Institute for Hygiene and Medical Microbiology, University of Munich, FRG.

The in vitro and in vivo activity of the new macrolides azithromycin, clarithromycin and roxythromycin was compared with that of erythromycin against Borrelia burgdorferi. In in vitro tests using ten clinical isolates all macrolides were highly active against Borrelia burgdorferi (MIC90 0.015-0.06 micrograms/ml). Azithromycin was more potent than the other macrolides in experimental animal infection, eradicating the organism in all animals tested at a dosage of 8 mg/kg.

PMID: 2550233 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/2550 ... d_RVDocSum
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Tetracycline therapy for chronic Lyme disease.
Donta ST.
Boston University Medical Center and Boston Veterans Affairs Medical Center, Massachusetts 02118, USA.

Two hundred seventy-seven patients with chronic Lyme disease were treated with tetracycline for 1 to 11 months (mean, 4 months); the outcomes for these patients were generally good. Overall, 20% of the patients were cured; 70% of the patients' conditions improved, and treatment failed for 10% of the patients. Improvement frequently did not take place for several weeks; after 2 months of treatment, 33% of the patients' conditions were significantly improved (degree of improvement, 75%-100%), and after 3 months of treatment, 61% of the patients' conditions were significantly improved. Treatment outcomes for seronegative patients (20% of all patients) were similar to those for seropositive patients. Western immunoblotting showed reactions to one or more Borrelia burgdorferi-specific proteins for 65% of the patients for whom enzyme-linked immunosorbent assays were negative. Whereas age, sex, and prior erythema migrans were not correlated with better or worse treatment outcomes, a history of longer duration of symptoms or antibiotic treatment was associated with longer treatment times to achieve improvement and cure. These results support the use of longer courses of treatment in the management of patients with chronic Lyme disease. Controlled trials need to be conducted to validate these observations.

PMID: 9233665 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/9233 ... d_RVDocSum
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Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with lyme disease.
Stricker RB.
International Lyme and Associated Diseases Society, Bethesda, MD, USA. rstricker@usmamed.com

BACKGROUND: Controversy exists regarding the diagnosis and treatment of Lyme disease. Patients with persistent symptoms after standard (2-4-week) antibiotic therapy for this tickborne illness have been denied further antibiotic treatment as a result of the perception that long-term infection with the Lyme spirochete, Borrelia burgdorferi, and associated tickborne pathogens is rare or nonexistent. METHODS: I review the pathophysiology of B. burgdorferi infection and the peer-reviewed literature on diagnostic Lyme disease testing, standard treatment results, and coinfection with tickborne agents, such as Babesia, Anaplasma, Ehrlichia, and Bartonella species. I also examine uncontrolled and controlled trials of prolonged antibiotic therapy in patients with persistent symptoms of Lyme disease. RESULTS: The complex "stealth" pathology of B. burgdorferi allows the spirochete to invade diverse tissues, elude the immune response, and establish long-term infection. Commercial testing for Lyme disease is highly specific but relatively insensitive, especially during the later stages of disease. Numerous studies have documented the failure of standard antibiotic therapy in patients with Lyme disease. Previous uncontrolled trials and recent placebo-controlled trials suggest that prolonged antibiotic therapy (duration, >4 weeks) may be beneficial for patients with persistent Lyme disease symptoms. Tickborne coinfections may increase the severity and duration of infection with B. burgdorferi. CONCLUSIONS: Prolonged antibiotic therapy may be useful and justifiable in patients with persistent symptoms of Lyme disease and coinfection with tickborne agents.

PMID: 17578772 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1757 ... d_RVDocSum

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Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role of RpoS.
Murgia R, Piazzetta C, Cinco M.
Dipartimento di Scienze Biomediche, sez. Microbiologia, Università degli Studi di Trieste, Trieste, Italy. rmurgia@dsbmail.units.it

It has been demonstrated recently that cells of Borrelia burgdorferi sensu lato, the etiological agent of Lyme disease, transform from mobile spirochetes into nonmotile cystic forms in the presence of certain unfavourable conditions, and that cystic forms are able to reconvert to vegetative spirochetes in vitro and in vivo. The purpose of this study was to investigate the kinetics of conversion of borreliae to cysts in different stress conditions such as starvation media or the presence of different antibiotics. Using the same experimental conditions we also investigated the possible role in cyst formation of RpoS, an alternative sigma factor that controls a regulon in response to starvation and transition to stationary phase. We observed that beta-lactams penicillin G and ceftriaxone, the antibiotics of choice in Lyme borreliosis treatment, favoured the production of cysts when used with serum-depleted BSK medium. In contrast, we observed a low level of cyst formation in the presence of macrolides and tetracyclines. In order to elucidate the role of the rpoS gene in cyst formation we analyzed the reaction of the rpoS mutant strain in comparison with its wild-type in different conditions. Under the same stimuli, both the wild-type borrelia and the rpoS knock-out isogenic strain produced cystic forms with similar kinetics, thus excluding the participation of the gene in this phenomenon. Our findings suggest that cyst formation is mainly due to a physical-chemical rearrangement of the outer membrane of Borrelia burgdorferi sensu lato leading to membrane fusion and controlled by different regulation mechanisms.
pubmed: search words: borrelia cystic from penicillin g

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