THE LANCET, VOL. 336, (NOV 10, 1990) p. 1189f. Oral treatment of late borreliosis with roxithromycin plus co-trimoxazole SIR, - Early, but not late, Lyme borreliosis has been successfully treated with oral antibiotics such as penicillins, erythromycin, and tetracycline. The possibility of an oral treatement is desirable, especially in view of the great difficulties that arise with long-lasting intravenous treatment in third-world countries.(1, 2) Various workers have shown relapses and failure of treatment in late Lyme borreliosis(adrodermatitits chronica atrophicans, arthritis, neuroborreliosis) even with high doses of intravenous penicillin or ceftriaxone. (2, 3) Treatment that is both orally applicable and effective is certainly needed.(2) Co-trimoxazole is a powerful antibiotic combination to which many microorganisms respond, including the spirochaete Treponema pallidum. Furthermore, it has been show that the new macrolides(such as roxithromycin) show a remarkable antimicrobial activity angaint B burgdorferi.(4,5) It is noteworthy that the blood/brain barrier is highly permeable to roxithromycin. A 30-year-old man infected with B burgdorferi 7 years ago was successfully treated with a combination of roxithromycin(300 mg twice daily) and trimethoprim/sulphamethoxazole(320 mg/1600 mg twice daily) after both intraveous penicillin(20 million IU daily ober 3 weeks) and later ceftriaxone 2 g twice daily for 3 weeks) had failed (figure {not included} ). Both intravenous penicillin and ceftriaxone reduced the symptoms transiently, while IgG remained positive. However, shortly after a 3-week course of roxithromycin/co-trimoxazole all symptoms disappeared and a recent assessment of IgG revealed a negative titre. The recovery of the patient's neurological disorders was strikingly rapid, possibly because of the high permeability of the blood/brain barrier to roxithromycin. Thus, albeit in only 1 patient, we have shown successful oral treatment of late Lyme borreliosis with a combination of roxithromycin and co-trimoxazole. Robert Gasser, University Laboratory of Physiology, Osford OX1 3 PT, UK Johann Dusleag, University Medical Clinic, Graz, Austria 1. Steere AC, Malawista SE, Newman J, Spieler PN, Bartenhagen HN. Antibiotic therapy in Lyme disease. Ann Intern Med 1990;93:1-8. 2. Weber, K, Preac-Mursic V, Neubert V, et al. Antibiotic therapy of early European Lyme borreliosis and acrodermatitis chronica athrophicans. Ann NY Acad Sci 1988; 325-45 3.Dattwyler RJ, Halperin JJ, Volkman DJ, Luft BJ. Treatment of later Lyme borreliosis - randomisesd comparison of ceftriaxone and penicillin. Lancet 1988: i: 1191-94 4. Preac-Mursic V, Gross B, Suiss E, Wilske B, Schierz G. Comparative antimicrobial activity of the new macrolides against Borrelia burgdorferi. Eur J Clinical Microbiol Inf Dis 1989; 8: 651-53 5. Steere AC, Grodzicki RL, Kornblatt AN, et al. The spirochaetal etiology of Lyme disease. N Engl J Med 1983; 308: 733-40. _________________________ [note from poster] In response to this article a few weeks later there was an article from two physicians of the University Hospital of Frederiksberg, Denmark (Departement of Rheumatology and Clinical Microbiology) entitled with: Late treatment of chronic Lyme arthritis. They discussed a similar case and also tried this combination treatment of Gasser and Dueslag. They also were successful and came to the conclusion that, "combined therapie with roxithromycin and co-trimoxazole may prove effectiv in chronic Lyme arthritis where conventional antibiotics have failed." (THE LANCET, VOL. 337, JAN 26, 1991, page 241) ----------------------- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7782115&dopt=Abstract Infection 1995;23 Suppl 1:S39-43 Roxithromycin in the treatment of Lyme disease--update and perspectives. Gasser R, Wendelin I, Reisinger E, Bergloff J, Feigl B, Schafhalter I, Eber B, Grisold M, Klein W. Klinische Physiologie, Medizinische Universitatsklinik Graz, Austria. Spirochaetal infections have been successfully treated with penicillin; more recently, erythromycin has been used in cases with known penicillin allergy. The discovery of the spirochaete Borrelia burgdorferi and the elaboration of a new generation of macrolides with properties that differ from older macrolides have led to new ways of treating spirochaetal disease with these compounds. This paper presents data on the in vitro and in vivo efficacy of a combination of roxithromycin and co-trimoxazole against B. burgdorferi. In vitro (checkerboard technique; B. burgdorferi strain B31; modified BSK II medium) it was found that while roxithromycin showed excellent efficacy against B. burgdorferi (MIC 0.031 mg/l), co-trimoxazole had no effect. However, the combination of both chemotherapeutics led to a minor synergistic effect, decreasing the MIC for roxithromycin by one dilution step at concentrations of co-trimoxazole from 256 to 8 mg/l. In addition, a clearly reduced growth of microorganisms was seen at concentrations of roxithromycin as low as 0.015 mg/l in combination with 256 to 4 mg/l co-trimoxazole, when compared to the positive controls. Most interestingly, however, the motility of B. burgdorferi was markedly reduced even when the two drugs were combined at very low concentrations. In an in vivo, non-randomised, open, prospective pilot study it was found that of 17 patients with confirmed late Lyme borreliosis (stage II/III), treated with combined roxithromycin (300 mg b.i.d.) and co-trimoxazole for 5 weeks, 13 (76%) recovered completely by the end of treatment, and four continued to have symptoms on follow-up at 6 and 12 months. This success rate is similar to that seen with i.v. penicillin and ceftriaxone. It appears that the reduced motility of B. burgdorferi makes the pathogen more accessible to the immune system. Publication Types: Clinical Trial PMID: 7782115 [PubMed - indexed for MEDLINE] --------------------- : Acta Med Austriaca 1996;23(3):99-101 Related Articles, Links Oral treatment of late Lyme borreliosis with a combination of roxithromycin and co-trimoxazole--a pilot study on 18 patients. Gasser R, Reisinger E, Sedaj B, Horvarth R, Seinost G, Keplinger A, Wendelin I, Klein W. Department of Internal Medicine, University Graz. In this pilot trial, 18 patients participated in an investigation in which the combined therapy of co-trimoxazole and roxithromycin in late Lyme borreliosis was tested. The study has been performed as a result of earlier case reports in "The Lancet" where this combination has been used successfully in order to thwart late Lyme disease. The authors show that 76% of the patients recovered completely. In 2 patients, symptoms could be resolved with i.v. penicillin and 2 did not respond to any antibiotic therapy. These results show that oral therapy of co-trimoxazole and roxithromycin in combination provides similar results as i.v. antibiotics in earlier studies. PMID: 8798283 [PubMed - indexed for MEDLINE] ---------------------- Title: Cases of Lyme borreliosis resistant to conventional treatment: improved symptoms with cephalosporin plus specific beta-lactamase inhibition. Authors: Gasser R, Reisinger E, Eber B, Pokan R, Seinost G, Bergloff J, Horwarth R, Sedaj B, Klein W Source: Microb Drug Resist 1995 Winter;1(4):341-4 Organization: Department of Medicine, University of Graz, Austria. Abstract: We present four cases of verified late Lyme borreliosis with persistent symptoms and positive serology despite repeated courses of high-dose intravenous penicillin G and/or cephalosporins (including cefoperazone). The patients were now treated with cefoperazone 2 g plus sulbactam 1 g bid iv for 14 days. At the end of treatment, patients were symptom free and have remained so for the following 12 months. By then, IgG against Borrelia burgdorferi had decreased. It is concluded that the addition of beta-lactamase inhibitors to intravenous treatment could be beneficial in Lyme disease refractory to conventional treatment. ------- Fwom:Steve McLain (see_end@post.com) Subject:Re: Augmentin View this article only Newsgwoups:sci.med.diseases.lyme Date:2001-02-28 05:55:17 PST I've attached one more paper on Bb and betalactam antibiotic resistance. Gasser appears to be the main researcher who has studied this. I've read his papers and they are case studies that sound quite convincing. The patients he described had Bb infections that apparently developed resistance to betalactam antibiotics after they had received multiple treatments of short or moderate length. They were then treated succesfully by adding betalactamase inhibitors to the treatment. However, to my knowledge no one has ever isolated and cultured a Bb strain that is resistant to betalactam drugs like Rocephin. Thus the idea of Bb developing antibiotic resistance remains controversial and detractors can legitimitely claim that it has not been rigorously proven. Gasser's work suggests that resistance to betalactam antibiotics develops in individual patients due to inadequate treatment length. I've seen no published evidence that Bb develops resistance to betalactam antibiotics in its natural hosts. That would be unlikely since Bb has no antibiotic pressure in its natural transmission cycle, and a human patient with resistant Bb is very unlikely to transmit it. This idea of Bb developing resistance to betalactam antibiotics after inadequate treatment is the rationale behind using Primaxin (a 4th generation cephalasporin) in patients who have had treatment failure on 3rd generation cephalasporins such as Rocephin and Claforan. Primaxin is not the treatment used by Gasser, but it is being used by some LLMD's ---------------- sci.med.diseases.lyme Augmentin is amoxicillin with an "augmentor" called clauvanate potassium. The later is a beta-lactamase inhibitor which the basic importance of this is that the B-lactamases are often partly responsible for antibiotic resistance to penicillins and cephalosporins on bacteria. In respect to Lyme Disease I am "guessing" that the European results will be better (vs. US) for the strain of B.burgdoferi that exists there I believe is heavily associated with B-lactamase producing strains of Staphyloccus infections of the skin, which Augmentin is effective for. Regardless,(and unfortunately) I think it still leaves a patient at square one, given the variable response to certain antibiotics. Of note at normal doses Amoxicillian or Augmentin does not diffuse into the brain and CSF. If you have CNS symptoms it may not be the drug of choice. Though some have had success on high doses of Amoxicillian on CNS infection. ------------------------------------- The Lyme Disease Network Medical / Scientific Abstract Title: Cases of Lyme borreliosis resistant to conventional treatment: improved symptoms with cephalosporin plus specific beta-lactamase inhibition. Authors: Gasser R, Reisinger E, Eber B, Pokan R, Seinost G, Bergloff J, Horwarth R, Sedaj B, Klein W Source: Microb Drug Resist 1995 Winter;1(4):341-4 Organization: Department of Medicine, University of Graz, Austria. Abstract: We present four cases of verified late Lyme borreliosis with persistent symptoms and positive serology despite repeated courses of high-dose intravenous penicillin G and/or cephalosporins (including cefoperazone). The patients were now treated with cefoperazone 2 g plus sulbactam 1 g bid iv for 14 days. At the end of treatment, patients were symptom free and have remained so for the following 12 months. By then, IgG against Borrelia burgdorferi had decreased. It is concluded that the addition of beta-lactamase inhibitors to intravenous treatment could be beneficial in Lyme disease refractory to conventional treatment. Keywords: beta-Lactamases, ANTAGONISTS & INHIB, Antibiotics, Combined, ADMINISTRATION & DOSAGE, THERAPEUTIC USE, Case Report, Cefoperazone, ADMINISTRATION & DOSAGE, THERAPEUTIC USE, Cephalosporins, ADMINISTRATION & DOSAGE, THERAPEUTIC USE, Drug Resistance, Microbial, Enzyme Inhibitors, ADMINISTRATION & DOSAGE, THERAPEUTIC USE, Female, Human, Infusions, Intravenous, Lyme Disease, DRUG THERAPY, MICROBIOLOGY, PHYSIOPATHOLOGY, Male, Middle Age, Sulbactam, ADMINISTRATION & DOSAGE, THERAPEUTIC USE Language: Eng Unique ID: 97302560 ------------------------------- The Lyme Disease Network Medical / Scientific Abstract Title: First description of recurrent pericardial effusion associated with borrelia burgdorferi infection. Authors: Gasser R, Horn S, Reisinger E, Fischer L, Pokan R, Wendelin I, Klein W Source: Int J Cardiol 1998 May 15;64(3):309-10 Organization: The Borreliosis Study Group, Department of Medicine, University of Graz, Austria. Abstract: Lyme disease is well known for affecting the myocardium in the form of carditis and dilated cardiomyopathy. Pericardial effusion associated with Lyme disease has not been described as yet. This article demonstrates a case of a female patient, 54 years of age, with Borrelia burgdorferi infection and associated pericardial effusion. Recurrent pericardiocenteses as well as conventional treatment of the condition were without success. Diagnosis of Borrelia infection and subsequent treatment with ceftriaxone led to permanent restitution of the pericardial effusion. Keywords: Borrelia burgdorferi, Case Report, Echocardiography, Female, Human, Lyme Disease, COMPLICATIONS, DIAGNOSIS, DRUG THERAPY, Middle Age, Pericardial Effusion, MICROBIOLOGY Language: Eng Unique ID: 98336159 ----------------------- The Lyme Disease Network Medical / Scientific Abstract Title: [Cardiac manifestations of Lyme borreliosis with special reference to contractile dysfunction] Authors: Seinost G, Gasser R, Reisinger E, Rigler MY, Fischer L, Keplinger A, Dattwyler RJ, Dunn JJ, Klein W Source: Acta Med Austriaca 1998;25(2):44-50 Organization: Klinischen Abteilung fur Kardiologie, Medizinischen Universitatsklinik Graz, Osterreich. gseinost@mail.som.sunysb.edu Abstract: Borrelia burgdorferi infection (BBI) is suggested to be associated with dilated cardiomyopathy (IDC). Stanek et al. were able to cultivate Borrelia burgdorferi (BB) from myocardial biopsy tissue of a patient with longstanding dilated cardiomyopathy. Here we present a study in which we examined the effect of standard antibiotic treatment on the left ventricular ejection fraction (LV-EF) in patients with dilated cardiomyopathy associated with BBI. In this study we assessed the serum (IgG, IgM ELISA; Western Blot) and the history of 46 IDC-patients with specific respect spect to BBI (mean LV-EF: 30.4 +/- 1.3%; measured by cardiac catheterisation and echocardiography--length-area-volume method). All 46 patients received standard treatment for dilated cardiomyopathy: ACE-inhibitors, digitalis and diuretics. 11 (24%) patients showed positive serology and a history of BBI; 9 of these also had a typical history of tick bite and erythema chronicum migrans (ECM) and/or other organ involvement, 2 had no recollection of tick bite or EMC, but showed other BB-associated disorders (neuropathy, oligoarthritis). These 11 patients with BBI received standard antibiotic treatment with intravenous ceftriaxone 2 g bid for 14 days. 6 (55%) recovered completely and showed a normal LV-EF after 6 months, 3 (27%) improved their LV-EF and 2 (18%) did not improve at all. This amounts to 9 (82%) recovery/improvement in the BB-group. The 35 patients who did not show positive serology or a history of BBI did not receive antibiotic treatment. In this group without BBI 12 (26%) showed recovery/improvement following the standard treatment of dilated cardiomyopathy (see above). Our results indicate that BBI could play a decisive role in the development of dilated cardiomyopathy, especially in a geographical region as Graz, where BB is endemic. While aware of the small number of BB-patients in this study, we nevertheless conclude that, in a remarkable number of patients with signs of BBI, dilated cardiomyopathy could be reversed and LV-EF improved upon standard antibiotic treatment. Keywords: Adolescence, Adult, Aged, Cardiomyopathy, Congestive, DIAGNOSIS, DRUG THERAPY, PHYSIOPATHOLOGY, Cardiovascular Agents, THERAPEUTIC USE, Ceftriaxone, ADMINISTRATION & DOSAGE, Drug Therapy, Combination, Echocardiography, English Abstract, Female, Heart Catheterization, Human, Infusions, Intravenous, Lyme Disease, DIAGNOSIS, DRUG THERAPY, PHYSIOPATHOLOGY, Male, Middle Age, Myocardial Contraction, DRUG EFFECTS, PHYSIOLOGY, Stroke Volume, DRUG EFFECTS, PHYSIOLOGY, Treatment Outcome, Ventricular Function, Left, DRUG EFFECTS, PHYSIOLOGY Language: Ger Unique ID: 98346019