http://cid.oxfordjournals.org/content/30/1/237.2.long
Clin Infect Dis. 2000 Jan;30(1):237-8.
Minocycline versus doxycycline in the treatment of Lyme neuroborreliosis.
Cunha BA.
Comment in
Possibility of the use of oral long-acting tetracyclines in the treatment of Lyme neuroborreliosis. [Clin Infect Dis. 2000]
Adverse effects of minocycline versus doxycycline in the treatment of Lyme neuroborreliosis. [Clin Infect Dis. 2000]
Comment on
Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis. [Clin Infect Dis. 1999]
PMID: 10619782 [PubMed - indexed for MEDLINE]
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SIR—Dotevall and Hagberg [1] from Göteborg University (Göteborg, Sweden) deserve praise for their well-done study on oral doxycycline treatment of Lyme disease—associated facial palsy and meningitis. This study confirms that oral doxycycline is equivalent to parenteral ceftriaxone in the treatment of Lyme disease—associated palsy and/or meningitis. Experience indicates 21 days of oral doxycycline therapy is equivalent to 14 days of ceftriaxone therapy [3], and Swedish investigators have demonstrated that equivalent results are achieved with doxycycline therapy for ≤2 weeks (median, 10.8 days).
Dotevall and Hagberg correctly point out that there has been some reluctance to use oral antibiotics in the treatment of Lyme neuroborreliosis because of fear of inadequate CSF and/or CNS penetration [2, 3]. Doxycycline is preferred over conventional tetracycline for this purpose because of its lipid solubility characteristics [4–6], as stated by Dotevall and Hagberg.
Doxycycline is 5 times more lipid soluble than conventional tetracycline, which is an important determinant of permeability of the blood-brain barrier [7, 8]. Dotevall and Hagberg showed that most patients had highly elevated CSF protein levels, which is the best index of antibiotic permeability of the blood-brain barrier. Aside from emphasizing a shorter duration of therapy, these researchers stressed the use of high dosages of doxycycline (e.g., 400 mg/d) for treatment of Lyme neuroborreliosis.
It is not commonly appreciated that ill patients treated with doxycycline (e.g., patients with legionnaires' disease) should be given a loading regimen of 200 mg iv q12h for the first 72 h, because of doxycycline's lipid solubility characteristics and long half-life. Since 5 serum half-lives are usually required to achieve steady-state serum concentrations, and early therapeutic effect, a loding regimen rather than a loading dose permits rapid saturation of the serum. If doxycycline is administered in the usual dosage of 100 mg q12h, then it takes 4–5 days to achieve steady-state kinetics and an observable therapeutic response. In Lyme neuroborreliosis, rapid saturation of the CNS compartment is key to the efficacy of short-course regimens (≤14 days). Doxy-cycline is usually given in dosages of 100 mg q12h, which means that the first week of treatment is virtually lost in achieving steady-state equilibrium, and equilibrium results require 3 weeks [7–10]. Dotevall and Hagberg correctly used 400 mg of doxycycline daily and decreased treatment time to ∼10.8 days.
Because of its pharmacokinetic characteristics, doxycycline may be given at a dosage of 200 mg q12h or may be given as a single daily dose of 400 mg. Gastrointestinal upset is minimal if the tablet form of the formulation is used and taken with meals. CSF concentrations achieved with high doses of doxycycline are approximately twice those achieved with conventional dosing and are achieved more rapidly. There is no toxic liability associated with the high-dose doxycycline regimen [9, 10]. Use of 400 mg of doxycycline daily assures clinicians that CNS concentrations of doxycycline are predictably and rapidly achieved above the MIC90 for Borrelia burgdorferi [1, 6].
snip
I read this article and the refs cited in it, right after figuring out that my family's mystery illness was late neurological Lyme, and started treatment with oral 400 mg doxycycline/day. I agree that oral 200 mg/day is not enough to expect to kill Bb in the brain, though you'd slow them down some (and yes, probably enhance cyst/round body/non-dividing spiral formation).
I doubt the part about reducing duration of treatment, though. Granted, they're not treating late encephalopathy, but facial palsy. Still, you're still only reliably exceeding the MIC (minimum inhibitory concentration), not the MBC (minumum bacteriocidal concentration). But since even IV ceftriaxone doesn't reliably effect a permanent cure in late Lyme encephalopathy, might as well go with long-term orals, at least in ambulatory patients, at a high enough dose to get into the CSF reliably. IMHO, of course.
Here's the article Cunha was responding to:
Clin Infect Dis. 1999 Mar;28(3):569-74.
Successful oral doxycycline treatment of Lyme disease-associated facial palsy and meningitis.
Dotevall L, Hagberg L.
Source
Department of Infectious Diseases, Institute of Internal Medicine, Göteborg University, Sweden.
leif.dotevall@medfak.gu.se
Abstract
Twenty-nine patients, aged 11-79 years (mean, 50 years), with Lyme neuroborreliosis, facial nerve palsy, and meningitis were treated with oral doxycycline (daily dose, 200-400 mg) for 9-17 days in a prospective, nonrandomized study. Facial paresis was bilateral in eight (28%) of the 29 patients. Twenty-six patients (90%) recovered without sequelae within 6 months, while three of the patients with bilateral facial palsy at admission had remaining paresis at follow-up. In five patients, contralateral facial paresis developed 1-12 days after initiation of therapy, and two patients were retreated with antibiotics. Posttreatment examinations of cerebrospinal fluid showed a marked decrease of inflammatory cells and protein concentrations compared with pretreatment levels in all followed up patients. The favorable clinical outcome agrees with findings of other reports on intravenous antibiotic therapy for Lyme disease-associated meningitis with facial palsy. Our conclusion is that oral doxycycline is an effective and convenient therapy for Lyme disease-associated facial palsy.
Comment in
Possibility of the use of oral long-acting tetracyclines in the treatment of Lyme neuroborreliosis. [Clin Infect Dis. 2000]
Minocycline versus doxycycline in the treatment of Lyme neuroborreliosis. [Clin Infect Dis. 2000]
PMID: 10194080 [PubMed - indexed for MEDLINE]
Free full text
Thanks to Dotevall and Hagberg from Sweden for alerting us all to this dosing issue!
Calling things "woo" is a "discerning critique"?