Martian wrote:This is good news, isn't it?
Oral doxycycline is much more convenient, safer and cheaper than intravenous ceftriaxone.
The data that I am missing is the dosage. Since it's a case of neuroborreliosis I am guessing 400 mg per day.
I agree with you and velvetmagnetta that this is good news since oral doxycycline is indeed more convenient, safer, and far less expensive than intravenous ceftriaxone.
I wondered about the dosage too. There is compelling evidence by European researchers (that I have posted elsewhere and will try to find later *) that 400 mg of doxycycline is preferable to 200 mg in treating neuroborreliosis. Even the American Academy of Neurology allows for up to two doses of 200 mg of doxycycline per day in their treatment recommendations.
Neurology. 2007 Jul 3;69(1):91-102. Epub 2007 May 23.
Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.
Halperin JJ1, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, Krupp L, Gronseth G, Bever CT Jr; Quality Standards Subcommittee of the American Academy of Neurology.
1 Department of Neurosciences, Overlook Hospital, NYU School of Medicine, Summit, NJ, USA.
Neurology. 2008 Apr 1;70(14):1223.
To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed?
The authors analyzed published studies (1983-2003) using a structured review process to classify the evidence related to the questions posed.
The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis.
There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (> or =8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A).
Re: Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. [Neurology. 2008]
[PubMed - indexed for MEDLINE]
From the full article: http://www.neurology.org/content/69/1/91.full
Antimicrobial Regimens for the Treatment of Lyme Disease Neuroborreliosis
Doxycycline* (Vibramycin) 100 to 200 mg, twice per day
Children eight years or older: 4 to 8 mg per kg per day in two divided doses, maximum is 200 mg per dose
Although it is likely that US patients with the same manifestations of neuroborreliosis will similarly be doxycycline responsive, there are differences between the B burgdorferi strains and species prevalent in the United States and Europe; hence the data may not be fully applicable. However, European studies 38,39 assessing the susceptibility of different Borrelia strains to multiple antimicrobials, including doxycycline, have found no significant differences in minimal inhibitory concentrations among the different species. Minimal bactericidal concentrations (MBCs) have been more variable 39 but for doxycycline were comparable for all species. In light of these observations, treatment responses might be expected to be comparable in US and European patients; however, this remains untested.
Here are some European studies that indicate oral doxycycline is as effective as intravenous ceftriaxone -- at least in the majority of cases.
Scand J Infect Dis. 2005;37(6-7):449-54.
Intravenous ceftriaxone compared with oral doxycycline for the treatment of Lyme neuroborreliosis.
Borg R1, Dotevall L, Hagberg L, Maraspin V, Lotric-Furlan S, Cimperman J, Strle F.
1 Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden.
This prospective, open-label, non-randomized trial at the University Departments of Infectious Diseases in Ljubljana, Slovenia, and Göteborg, Sweden, was conducted to compare the kinetics of the cerebrospinal fluid (CSF) mononuclear cell count after 10-14 d of ceftriaxone or doxycycline for treatment of Lyme neuroborreliosis. 29 patients were treated with intravenous ceftriaxone 2 g daily in Ljubljana and 36 patients with oral doxycycline 400 mg daily in Göteborg. The study protocol included lumbar puncture before and 6-8 weeks after treatment initiation. There was a marked decrease (1.2 log10 x 10(6)/l) of the median CSF mononuclear cell count following treatment. With the assumption of a linear regression of the logarithmic mononuclear cell counts between the 2 lumbar punctures, no significant difference between the 2 antibiotic treatments could be found. All patients were clinically much improved after treatment. At 6 months follow-up 23 (79%) of the ceftriaxone- and 26 (72%) of the doxycycline-treated patients were completely recovered. Intravenous ceftriaxone or oral doxycycline was found to be effective, safe, and convenient for treatment of Lyme neuroborreliosis.
[PubMed - indexed for MEDLINE]
Lancet Neurol. 2008 Aug;7(8):690-5. doi: 10.1016/S1474-4422(08)70119-4. Epub 2008 Jun 21.
Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial.
Ljøstad U1, Skogvoll E, Eikeland R, Midgard R, Skarpaas T, Berg A, Mygland A.
1 Department of Neurology, Sørlandet Hospital HF, Kristiansand, Norway
Lancet Neurol. 2008 Aug;7(8):675.
Use of intravenous penicillin and ceftriaxone to treat Lyme neuroborreliosis is well documented, although oral doxycycline could be a cost-effective alternative. We aimed to compare the efficacy of oral doxycycline with intravenous ceftriaxone for the treatment of Lyme neuroborreliosis.
From April, 2004, to October, 2007, we recruited consecutive adult patients from nine hospitals in southern Norway into a non-inferiority trial. Inclusion criteria were neurological symptoms suggestive of Lyme neuroborreliosis without other obvious causes, and presence of any of the following: a CSF white-cell count of more than five per mL; intrathecal production of specific Borrelia burgdorferi antibodies; or acrodermatitis chronicum atrophicans. Patients were randomly allocated to receive 200 mg oral doxycycline or 2 g intravenous ceftriaxone once per day for 14 days, in a double-blind, double-dummy design. A composite clinical score (range 0 to 64, 0=best) was based on standardised interviews and clinical neurological examination. The primary outcome was reduction in clinical score at 4 months after the start of treatment. Analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT00138801.
Of 118 patients who underwent randomisation, 102 completed the study (mean clinical score at baseline 8.5 [SD 4.1]). 4 months after the start of treatment, mean score improvement in the doxycycline group (n=54) was 4.5 (95% CI 3.6 to 5.5) points and that in the ceftriaxone group (n=48) was 4.4 (3.4 to 5.4) points (95% CI for difference between groups -0.9 to 1.1; p=0.84). 26 (48%) patients in the doxycycline group and 16 (33%) in the ceftriaxone group had total recovery (95% CI for difference between groups -4% to 34%; p=0.13). Side-effects possibly related to treatment were reported in 21 (37%) and 26 (46%) patients in these groups, respectively (-28% to 9%; p=0.30). Three patients discontinued ceftriaxone treatment owing to adverse events.
Oral doxycycline is as efficient as intravenous ceftriaxone for the treatment of European adults with Lyme neuroborreliosis.
Oral doxycycline for neuroborreliosis. [Lancet Neurol. 2008]
[PubMed - indexed for MEDLINE]
Eur J Neurol. 2014 Sep;21(9):1162-7. doi: 10.1111/ene.12420. Epub 2014 Mar 29.
Oral doxycycline for Lyme neuroborreliosis with symptoms of encephalitis, myelitis, vasculitis or intracranial hypertension.
Bremell D1, Dotevall L.
1 Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
BACKGROUND AND PURPOSE:
The treatment recommendation for Lyme neuroborreliosis with central nervous system (CNS) symptoms is intravenous ceftriaxone, according to current American and European guidelines. For Lyme neuroborreliosis with peripheral nervous system (PNS) symptoms, treatment with intravenous ceftriaxone and oral doxycycline is considered equally effective. The purpose of this study was to evaluate the efficacy of oral doxycycline in the treatment of Lyme neuroborreliosis with CNS symptoms.
Patients with Lyme neuroborreliosis who had undergone cerebrospinal fluid (CSF) sampling before and after treatment at the Department of Infectious Diseases, Sahlgrenska University Hospital, during the period 1990-2012, were included in this retrospective study. The CSF mononuclear cell count was used as a surrogate marker of treatment outcome. Comparisons of CSF mononuclear cell counts were made between patients with CNS symptoms and patients with PNS symptoms before and after treatment with oral doxycycline.
Twenty-six patients classified as having CNS symptoms and 115 patients classified as having PNS symptoms were included. The decline in CSF mononuclear cell counts did not differ significantly between the two groups of patients. All patients with CNS disease showed a marked clinical improvement after treatment, even though 62% had remaining symptoms at the end of follow-up.
Treatment with oral doxycycline resulted in a similar decrease in CSF mononuclear cell counts in patients with Lyme neuroborreliosis with CNS symptoms compared with patients with Lyme neuroborreliosis with PNS symptoms. The results indicate that oral doxycycline is an effective treatment for Lyme neuroborreliosis irrespective of the severity of symptoms.
© 2014 The Author(s) European Journal of Neurology © 2014 EAN.
Lyme borreliosis; Lyme neuroborreliosis; central nervous system Lyme disease; doxycycline
Oral treatment of parenchymal central nervous system neuroborreliosis--are we there yet? [Eur J Neurol. 2014]
[PubMed - indexed for MEDLINE]
Edited to add:
* Here is one of the articles that I had in mind when it comes to treating neuroborreliosis with a total of 400 mg of doxycycline as opposed to 200 mg daily:
Antimicrob Agents Chemother. 1989 Jul;33(7):1078-80.
Penetration of doxycycline into cerebrospinal fluid in patients treated for suspected Lyme neuroborreliosis.
Dotevall L1, Hagberg L.
1 Department of Infectious Diseases, University of Göteborg, Sweden.
Twelve patients were treated orally with 100 mg of doxycycline twice a day (b.i.d.) and 10 patients were treated with 200 mg b.i.d. for suspected tick-borne neuroborreliosis (Lyme borreliosis). At 5 to 8 days after the start of therapy, the mean concentrations in serum were 4.7 micrograms/ml for the doxycycline dose of 100 mg b.i.d. and 7.5 micrograms/ml for 200 mg b.i.d., 2 to 3 h after the last drug administration. The corresponding levels for cerebrospinal fluid were 0.6 and 1.1 micrograms/ml. Since a doxycycline concentration in cerebrospinal fluid above the estimated MIC for Borrelia burgdorferi (0.6 to 0.7 microgram/ml) is wanted in patients treated for severe neuroborreliosis, the higher dose is preferable.
[PubMed - indexed for MEDLINE]
Free PMC Article