trimethoprim--sulfamethoxazole-drug-combination and Lyme-Disease

Lyme arthritis in children and adolescents due to infection with Borrelia burgdorferi responds well to intravenous and oral antibiotics, but nonresponders have been described with all antibiotic regimens tested and a standard therapy has not yet been established. We examined causes of the failure of antibiotic treatment in the presence of persistent organisms and autoimmune mechanisms.. A prospective multicenter study was carried out in 55 children and adolescents with Lyme arthritis.. There were significant differences between younger and older patients with pediatric Lyme arthritis. Younger patients were more likely to have fever at the onset of arthritis and to have acute or episodic arthritis. Older patients were more likely to have chronic arthritis, higher levels of IgG antibodies to B. burgdorferi (by ELISA and immunoblot), and a longer interval between antibiotic treatment and the disappearance of arthritis. Of 51 patients followed for at least 12 months after initiation of antibiotic treatment, 24% retained manifestations of the disease including arthritis (8 patients) and arthralgias (4 patients). These patients were predominantly female (9/12) and were significantly older than patients without residual symptoms. Patients who had received intraarticular steroids prior to antibiotic treatment required significantly more courses of antibiotic treatment and the time required for disappearance of the arthritis was longer.. Pediatric Lyme arthritis is more benign in younger children. Lyme arthritis should be excluded as a possible cause of arthritis prior to the administration of intraarticular steroids.

Topics: Acute Disease; Adolescent; Anti-Inflammatory Agents; Arthritis, Infectious; Borrelia burgdorferi Group; Ceftriaxone; Child; Child, Preschool; Doxycycline; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Injections, Intra-Articular; Knee Joint; Lyme Disease; Male; Roxithromycin; Steroids; Synovectomy; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

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.

Topics: Administration, Oral; Borrelia burgdorferi Group; Cell Movement; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Lyme Disease; Male; Microbial Sensitivity Tests; Pilot Projects; Prospective Studies; Roxithromycin; Trimethoprim, Sulfamethoxazole Drug Combination

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.

Topics: Administration, Oral; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Lyme Disease; Pilot Projects; Roxithromycin; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Arthritis, Infectious; Drug Administration Schedule; Drug Therapy, Combination; Humans; Lyme Disease; Male; Middle Aged; Roxithromycin; Time Factors; Trimethoprim, Sulfamethoxazole Drug Combination