clarithromycin vs. roxithromycin?

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Huck
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clarithromycin vs. roxithromycin?

Post by Huck » Fri 3 Aug 2007 14:17

I have been trying to start clarithromycin but I get really bad anxiety symptoms from it. I dont really know if its a herx or a side effect. I have read on the net that chlarithromycin can have psychiatric side effects (see Biaxin on askapatient.com) I was wondering if roxithromycin would be better in this regard? Any experiences? Thanks

Martian
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Re: clarithromycin vs. roxithromycin?

Post by Martian » Mon 6 Aug 2007 14:48

Huck wrote:I have read on the net that chlarithromycin can have psychiatric side effects (see Biaxin on askapatient.com) I was wondering if roxithromycin would be better in this regard?
I don't know, and I hardly hear of people who take roxithromycin, and those who do often use a combination of roxithromycin and co-trimoxazole ((trimethoprim & sulphamethoxazole). This treatment has been studied by Gasser and is known as the Gasser protocol:

====================

Acta Med Austriaca. 1996;23(3):99-101.

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]

====================

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 Universitätsklinik 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.

PMID: 7782115 [PubMed - indexed for MEDLINE]

====================

Lancet. 1990 Nov 10;336(8724):1189-90.

Comment in:
Lancet. 1990 Dec 15;336(8729):1514.
Lancet. 1991 Jan 26;337(8735):241.

Oral treatment of late borreliosis with roxithromycin plus co-trimoxazole.

Gasser R, Dusleag J.

PMID: 1978043 [PubMed - indexed for MEDLINE]

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Yvonne
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Re: clarithromycin vs. roxithromycin?

Post by Yvonne » Tue 14 Aug 2007 14:01

Huck wrote:I have been trying to start clarithromycin but I get really bad anxiety symptoms from it. I dont really know if its a herx or a side effect. I have read on the net that chlarithromycin can have psychiatric side effects (see Biaxin on askapatient.com) I was wondering if roxithromycin would be better in this regard? Any experiences? Thanks
Roxythromycin also can give side effects like anxiety, confusion, depression, sleep disorder and hallucination

http://www.medsafe.govt.nz/profs/datash ... cintab.htm

I have read several times that it is the only macrolide antibiotic that crosses the blood brain barrier .Is that really so ?

http://www.anapsid.org/lyme/matthewgoss/drugs.html

On the German lyme forum there are some people take only Roxythromycin but there more people who did/do the Gasser protocol.
Listen to all,
plucking a feather from every passing goose,
but follow no one absolutely

Martian
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Re: clarithromycin vs. roxithromycin?

Post by Martian » Tue 14 Aug 2007 14:55

Yvonne wrote:I have read several times that it is the only macrolide antibiotic that crosses the blood brain barrier .Is that really so ?

http://www.anapsid.org/lyme/matthewgoss/drugs.html
I don't know. Unfortunately, Matthew Goss doesn't provide references. I think he a making a very explicit declaration about roxithromycin: "This is the only macrolide antibiotic that crosses the blood brain barrier (BBB)".

I think that in order to tell if a drug crosses the BBB it needs to be studied (unless you are certain it can't), and AFAIK there are very few, if any, studies of the different macrolides and the BBB. There is a study about azithromycin that seems to indicate that it crosses the BBB well, but I have not seen a study that confirms this study. Furthermore, Joe Ham pointed out that the BBB of the subjects may have been compromised.

Huck
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Re: clarithromycin vs. roxithromycin?

Post by Huck » Wed 29 Aug 2007 17:53

Well I have been trying roxithromycin for some days now and it seems to cause even worse anxiety than clarithromycin though I have been taking minimal doses. So I guess it might cross the bbb better than clarithromycin. The problem is, this anxiety is just too much to take and I think I wont be able to continue with this treatment. Plus this roxi is giving me strange heart symptoms that I havent had before... :(

Martian
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Re: clarithromycin vs. roxithromycin?

Post by Martian » Thu 30 Aug 2007 16:15

Huck wrote:Well I have been trying roxithromycin for some days now and it seems to cause even worse anxiety than clarithromycin though I have been taking minimal doses. So I guess it might cross the bbb better than clarithromycin. The problem is, this anxiety is just too much to take and I think I wont be able to continue with this treatment. Plus this roxi is giving me strange heart symptoms that I havent had before... :(
Too bad you get these symptoms. Perhaps you should try a tetracycline class of drug like doxycycline.

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stf
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Re: clarithromycin vs. roxithromycin?

Post by stf » Wed 13 Aug 2008 19:51

Martian wrote:
Yvonne wrote:I have read several times that it is the only macrolide antibiotic that crosses the blood brain barrier .Is that really so ?

http://www.anapsid.org/lyme/matthewgoss/drugs.html
I don't know. Unfortunately, Matthew Goss doesn't provide references. I think he a making a very explicit declaration about roxithromycin: "This is the only macrolide antibiotic that crosses the blood brain barrier (BBB)".

I think that in order to tell if a drug crosses the BBB it needs to be studied (unless you are certain it can't), and AFAIK there are very few, if any, studies of the different macrolides and the BBB. There is a study about azithromycin that seems to indicate that it crosses the BBB well, but I have not seen a study that confirms this study. Furthermore, Joe Ham pointed out that the BBB of the subjects may have been compromised.
It's been almost a year now. Do you know anything more about that?

STF

cave76
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Re: clarithromycin vs. roxithromycin?

Post by cave76 » Wed 13 Aug 2008 20:22

Doxycycline:

Relative molecular mass. 512.9

http://www.who.int/medicines/publicatio ... oNov07.pdf

Tetracycline:

Molecular weight: 444.44

http://www.chm.bris.ac.uk/motm/tetracycline/phys.htm

Azithromycin:

molecular weight is 749.00

Roxithromycin:

Mol. mass 837.047 g/mol

http://www.bionity.com/lexikon/e/Roxithromycin

http://www.rxlist.com/cgi/generic/zithromaxsusp.htm

Clarithromycin:

molecular weight is 747.96.

http://pubchem.ncbi.nlm.nih.gov/summary ... ?cid=84029

Ceftin:

molecular weight of 510.48

http://www.rxlist.com/cgi/generic/cefurox.htm

rlstanley
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Re: clarithromycin vs. roxithromycin?

Post by rlstanley » Thu 14 Aug 2008 4:19

From thread: http://www.lymeneteurope.org/forum/view ... 84&p=11059

If you check the literature, distribution of azithromycin in CSF as in serum is low, but brain levels are high in animal models & in humans with inflammed meninges. There is rapid distribution into cells of the drug.

BTW one can only work on human brain tissue in diseased states, obviously.
Pharmacokinetics of azithromycin after single oral dosing of experimental animals

D. Davila 1 *, Lidija Kolany-babi 1, F. Plavi 2
1Pliva Research Institute, Laboratory of Experimental Medicine, IL Ribara 89, 41000 Zagreb, Yugoslavia
2Rebro Clinical Hospital, Department of Clinical Pharmacology, Zagreb, Yugoslavia

*Correspondence to D. Davila, Pliva Research Institute, Laboratory of Experimental Medicine, IL Ribara 89, 41000 Zagreb, Yugoslavia

Keywords
Azithromycin • Erythromycin • Pharmacokinetics • Tissue levels

Abstract
Azithromycin, a macrolide antibiotic with an enhanced antimicrobial spectrum, was found to have a longer half-life than erythromycin, with marked tissue penetration. The pharmacokinetics of azithromycin after oral administration were compared with those of erythromycin in rats (200 mg kg-1) and rabbits (80 mg kg-1).

Concentrations of azithromycin in liver, lung, kidney, ileum, and brain were higher than serum concentrations.

The slow decline in tissue concentrations was evident from the biphasic elimination profile. Thus, advantageous pharmacokinetic properties and the broader antimicrobial spectrum of azithromycin relative to erythromycin appear to further support its therapeutic potential.
In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin againstToxoplasma gondii

F. G. Araujo1, R. M. Shepard2 and J. S. Remington1, 3

(1) Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, 94301 Palo Alto, California, USA
(2) Pfizer Inc., Central Research Division, Eastern Point Road, 06340 Groton, Connecticut, USA
(3) Division of Infectious Diseases, Stanford University School of Medicine, 94305 Stanford, California, USA


Abstract The macrolide antibiotics azithromycin, roxithromycin and spiramycin were examined in parallel for in vivo activity againstToxoplasma gondii. Azithromycin was considerably more active in protecting mice against death due to acute toxoplasmosis even when the other two antibiotics were used at twice its dose. The higher activity of azithromycin prompted a further examination of its activity against five different strains ofToxoplasma gondii, including two isolated from patients with AIDS. Although variable degrees of protection against death were noted, treatment with 200 mg/kg/day for ten days was sufficient to promote survival of 100 % of mice infected with inocula as high as 1 × 105 tachyzoites ofToxoplasma gondii. 90 % of mice inoculated with 1 × 105 tachyzoites of strain MO, isolated from an AIDS patient, and treated orally with 200 mg/kg/day for ten days survived the infection whereas only 40 % of mice infected with the same inoculum of the SOU strain, also isolated from an AIDS patient, survived. Tissue concentrations of azithromycin were examined in treated infected and non-infected mice. In both groups of mice azithromycin attained high concentrations in liver, spleen and heart, which exceeded concurrent serum levels by 25- to 200-fold. The concentrations in the brain were almost tenfold higher than the concentrations in serum after treatment with 200 mg/kg/day for ten days. Moreover, the concentrations in brains of infected mice were approximately two-fold higher than in brains of non-infected mice.
Distribution:

Rapidly and widely distributed throughout the body. Concentrates intracellularly, resulting in tissue concentrations 10 to 100 times higher than those found in plasma or serum {05}. Azithromycin is highly concentrated in phagocytes and fibroblasts. Phagocytes transport the drug to the site of infection and inflammation. Release of azithromycin from phagocytes is gradual, but it is enhanced by exposure to the cell membrane of bacteria {06}. Release of azithromycin from fibroblasts is not enhanced by bacteria, but fibroblasts may act as reservoirs of the antibiotic, releasing azithromycin to phagocytes {06}. Very low concentrations (< 0.01 mcg per mL [mcg/mL]) have been detected in the cerebrospinal fluid of human subjects with noninflamed meninges {01}; however, higher concentrations were found in brain tissue in animal studies {16}.

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Yvonne
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Re: clarithromycin vs. roxithromycin?

Post by Yvonne » Thu 14 Aug 2008 10:31

In a study presented at the October 1988 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), roxithromycin was found to reach very high concentrations in the human brain (Manuel and others, 1988). Researchers in France and Switzerland, noting that roxithromycin had been effective in treating toxoplasmosis in mice, gave the antibiotic to volunteers who were scheduled to undergo brain surgery, so that levels in brain tissue could be determined. (These volunteers did not have toxoplasmosis or AIDS.) The four patients for whom concentra- tions were measured had much higher roxithromycin concentrations in brain tissue than in blood plasma; two had brain concentrations seven times as high, the other two had fifty times or more roxithromycin in brain tissue than in blood. These measurements were taken 12 hours after the last roxithromycin dose; since blood levels are known to remain high for 12 hours or more, the comparison is a fair one

This study suggests that roxithromycin is extremely effective in crossing the blood-brain barrier. No other macrolides are known to behave similarly

In comparable tests in rats, roxithromycin was found not to penetrate well into brain tissue--suggesting that the drug may be even more effective in humans than it was in the mouse studies cited above. The potential value for humans might have been missed

http://www.aids.org/atn/a-075-07.html


Roxithromycin: review of its antimicrobial activity

Borrelia spp. Lyme disease is the most commonly reported
tick-borne disease in Europe and the USA. In-vitro and
in-vivo studies have been carried out to assess the efficacy
of roxithromycin in the treatment of the disease and have
shown that isolates of Borrelia burgdorferi are highly
susceptible to the new macrolides (MIC ' 0.03
mg/L).149–153 Sambri et al.149 tested roxithromycin and
other antibacterial agents against six clinical isolates of B.
burgdorferi and one of Borrelia hermsii. MBCs of roxithromycin
for all isolates were 0.125 mg/L. Gasser et al.153
found a roxithromycin MIC of 0.031 mg/L for B.
burgdorferi ATCC 35210. Hansen et al.151 showed that all
strains of B. burgdorferi were highly susceptible to roxithromycin
in vitro, with a median MBC of 0.12 mg/L. In an
animal (gerbil) model systemic B. burgdorferi infection
was eradicated within 10 days’ treatment with roxithromycin
at doses of .25 mg/kg/day. Preac-Mursic et al.
tested the antibacterial activity of roxithromycin, erythromycin
A, clarithromycin and azithromycin against B.
burgdorferi in vitro and in vivo. In vitro, all macrolides
displayed excellent activity (roxithromycin MIC50 5 0.015,
MIC90 = 0.03 mg/L). However, roxithromycin was not
effective in the gerbil model.
Early investigations revealed relative homogeneity of
protein profiles and antigenic reactions among American
isolates of B. burgdorferi and heterogeneity among
European isolates.154 B. burgdorferi sensu lato has been
subdivided into three genospecies:155 B. burgdorferi sensu
stricto, Borrelia garinii and Borrelia afzelii. Recent
findings suggest that the genospecies are associated with
different clinical manifestations (arthritis, neurological
symptoms and acrodermatitis chronica atrophicans,
respectively).156 Péter & Bretz152 investigated the in-vitro
activity of seven antibacterial agents, including roxithromycin,
against these three subspecies. MICs of roxithromycin
were 0.062 mg/L, 0.015 mg/L and 0.125–0.062 mg/L,
respectively, and roxithromycin was bacteriostatic for
most isolates. Roxithromycin was more effective against
B. burgdorferi sensu stricto and B. garinii than B. afzelii. In
another study the combination of roxithromycin and
minocycline was synergic against all three B. burgdorferi genospecies

http://jac.oxfordjournals.org/cgi/repri ... pl_2/1.pdf
Listen to all,
plucking a feather from every passing goose,
but follow no one absolutely

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