REKOMMENDATIONER FOR BEHANDLING AF BORRELIOSE
i DK, sml. med EUROPA (EUCALB) og USA....

Danmark 1999 - Lægeforeningens medicinfortegnelse 1999
Erythema migrans
Tabl. phenoxymethylpenicillin. Voksne: 1,5 MIE 3 x dgl. i 10 dage. Børn: 0,15 MIE/kg/døgn fordelt på 3 doser i 10 dage.
Alternativ Ved penicillinallergi. Voksne: Tabl. tetracyclin 250mg 4 x dgl. i 10 dage. Børn: Tabl. erythromycin 50 mg/kg/døgn fordelt på 4 doser i 10 dage
Meningo-radikulitis
lnj. benzylpenicillin. Voksne: 5 MIE i.v. 4xdgl. i 10 dage. Børn: 0,4 MIE/kg/døgn i.v. fordelt på 4 doser i 10 dage.
Alternativ Inj. ceftriaxon. Voksne: 2 g i.v. lxdgl. i 10 dage. Børn: 50 mg/kg/døgn i.v. 1xdgl. i 10 dage.
Kommentar Ved andre manifestationer af Borrelia-lnfektion, kontakt klinisk mikrobiolog. Der er ikke indikation for profylaktlsk behandling efter bid af skovflåt.

Danmark 2000 - Lægeforeningens medicinfortegnelse 2000 og 2003 (uændret)
Erythema migrans
Tabl. phenoxymethylpenicillin. Voksne: 1,5 MIE 3 x dgl. i 10 dage. Børn: 0,15 MIE/kg/døgn fordelt på 3 doser i 10 dage.
Alternativ Ved penicillinallergi. Voksne: Tabl. doxycyclin 100 mg 2xdgl.i 1døgn, herefter 100 mg 1xdgl. til i alt 10 dages behandling. Børn: Tabl. erythromycin 50 mg/kg/døgn fordelt på 4 doser i 10 dage.
Neuro-borreliose
Ved udtalte smerter og påvirket almentilstand samt ved kronisk neuroborreliose anbefales parentetal behandling.
lnj. benzylpenicillin. Voksne: 5 MIE i.v. 4xdgl. i 10 dage. Børn: 0,4 MIE/kg/døgn i.v. fordelt på 4 doser i 10 dage.
Alternativ Inj. ceftriaxon. Voksne: 2 g i.v. lxdgl. i 10 dage. Børn: 50 mg/kg/døgn i.v. 1xdgl. i 10 dage.
Ved moderate smerter og upåvirket almentilstand kan peroral behandling anvendes.
Voksne: Tabl. doxycyclin 200 mg 2xdgl. i et døgn, herefter 100mg x2 til i alt 14 dages behandling.
Kommentar Ved andre manifestationer af Borrelia-lnfektion, kontakt klinisk mikrobiolog. Der er ikke indikation for profylaktlsk behandling efter bid af skovflåt. En positiv titer uden kliniske tegn på borreliose bør ikke medføre antibiotisk behandling.

NB! Tilføjelser/ændringer i forh. til 1999 udgaven er fremhævet med rødt

Til sammenligning hermed bringes uddrag fra Klaus Hansen's artikel 'Borreliose',
Maanedskr Prakt Laege 1994; 74:791-806 ……….. side 804

Erythema migrans
Penicillin V 1,5 mio. E x 3 dagl. i 10 dage
(børn 0,15 mio. E/kg/døgn i 10 dage)
Doxycyclin 200mg x 1 1.dag, 100 mg x 1 2.-l0. dag
Tetracyclin 250 mg x 4 dgl. i 10 dage
Ved penicillinallergi hos børn <12 år:
Erythromycin 50 mg/kg/døgn i 10 dage
Multiple Erythema migrans
Doxycyclin 100 mg x 2 dgl. i 10 dage
Borrelia lymfocytom (LABC)
præparat og dosis som ved erythema migrans [<> tegn manglede er tilføjet af mig]
LABC-varighed [<] 2 mdr. behandles i 10 dage
LABC-varighed [>] 2 mdr. behandles i 21 dage
Acrodermatitis chronica athrophicans
Penicillin V 1,5 mio.E x 3 dgl. i 21 dage
Doxycyclin 100 mg x 2 dgl. i 21 dage
Neuroborreliose (stadie 2)
Penicillin G i.v. 20 mio. E dgl. fordelt på 3-4 doser i 10 dage
(børn 0,4 mio. E/kg/døgn)
Ceftriaxon i.v. 2 g x 1 dgl. i 10 dage (børn 50 mg/kg/døgn)
Ved penicillin- og cefalosporinallergi:
Doxycyclin p.o. 200 mg x 2 i 14 dage
Kronisk neuroborreliose
som ved stadie 2 neuroborreliose dog bør behandling vare mindst 14 dage
Borrelia-myokardit
som ved stadie 2 neuroborreliose
Borrelia-artrit
Penicillin V 1,5 mio. E x 3 dgl. i 21 dage
Doxycyclin 100 mg x 2 dgl. i 21 dage

Europa - EUCALB 2000
http://www.dis.strath.ac.uk/vie/LymeEU/treatment_in-europe.html
Erythema migrans
Amoxicillin 3x500 mg or 2x1000 mg oral 14-21 days
Doxycycline 2x100 mg or 1x200 mg oral 14-21 days
Penicillin V 3x1000 mg oral 14-21 days
Cefuroximeaxetil 2x500 mg oral 14-21 days
Neuro-borreliosis (acute)
Ceftriaxone 1x2000 mg i.v. 14-21 days
Cefotaxime 3x2000 mg i.v. 14-21 days
Penicillin G 3x3000 mg i.v. 14-21 days
Doxycycline 2x1-200 mg oral 14-28 days
Treatment for chronic neuroborreliosis similar, but i.v. only and for 28 days
Arthritis
Amoxicillin 4x500 mg or 2x1000 mg oral 21-28 days
Doxycycline 1x200 mg or 2x100 mg Oral 21-28 days
Ceftriaxone 1x2000 mg i.v. 14-21 days
Cefotaxime 3x2000 mg i.v. 14-21 days
ACA
Amoxicillin 4x500 mg or 2x1000 mg Oral 21-28 days
Doxycycline 2x100 mg or 1x200 mg Oral 21-28 days
Ceftriaxone 1x2000 mg i.v. 14-21 days
Cefotaxime 3x2000 mg i.v. 14-21 days
Penicillin G 3x3000 mg i.v. 14-21 days
Carditis
Ceftriaxone 1x2000 mg i.v. 14 days
Cefotaxime 3x2000 mg i.v. 14 days
Penicillin G 3x3000 mg i.v. 14 days

Children
Tetracyclines (doxycycline) are contra-indicated to children less than 8 years old (12 in some countries). Other treatments are based on recommendations for adults, but doses should be reduced by weight. In the case of penicillin allergy, azithromycin may be given for erythema migrans (in most countries 2x500 mg on d1, then 1x500 mg for days 2-5), however data on efficacy of this drug is scarce.

Pregnancy
Tetracyclines are contra-indicated in pregnancy and breast feeding. Ceftriaxone and cefuroxime should be used with caution in the first trimester of pregnancy because of lack of data in this respect. Amoxicillin and penicillin are still the drugs of choice.

EUCALB nyeste retningslinier for behandling af Borreliose i Europa:

Doser og varighed synes ved hurtig gennemlæsning nogenlunde samme som i 2000, fraset at 28 dage er rettet til 30 dg.

USA - Steere 1997 (konservativ) Med Clin North Am 1997 Jan; 81(1): 179-94

Oral doxycycline or amoxicillin for 30 to 60 days
Arthritis and neuroborreliosis: ceftriaxone 2 g i.v. once a day for 30d.
Persistent arthritis after more than 2 mo of antibiotics and PCR negative: NSAID, intra-articular steroid injection, arthroscopic synovectomy.

USA - Burrascano 2000 - 13. ed.

ORAL THERAPY
Always check blood levels when using agents marked with an *, and adjust dose to achieve a peak level in the mid- teens and a trough greater than five. Because of this, the doses listed below may have to be raised. Consider Doxycycline first due to concern for Ehrlichia.
*Amoxicillin- Adults: 1g q8h plus probenecid 500mg q8h; doses up to 6 grams daily are often needed. Pregnancy: 1g q6h and adjust. Children: 50 mg/kg/day divided into q8h doses.
*Doxycycline- Adults: 100 mg qid with food; doses of up to 600 mg daily are often needed, as doxycycline is only effective at high blood levels. Not for children or in pregnancy. If levels are too low at tolerated doses, give parenterally.
*Cefuroxime axetil- Oral alternative that may be effective in amoxicillin and doxycycline failures. Useful in EM rashes co-infected with common skin pathogens. Adults and pregnancy: 1g q12h and adjust. Children: 125 to 500 mg q12h based on weight.
Tetracycline- Adults only, and not in pregnancy. 500 mg tid to qid
Erythromycin- Poor response and not recommended.
Azithromycin- Adults: 500 to 1200 mg/d. Adolescents: 250 to 500 mg/d add hydroxychloroquine, 200-400 mg/d, or amantadine 100-200 mg/d. Cannot be used in pregnancy or in younger children.
Clarithromycin- Adults: 250 to 500 mg q6h plus hydroxychloroquine, 200-400 mg/d, or amantadine 100-200 mg/d. Cannot be used in pregnancy or in younger children.
Augmentin- Cannot exceed three tablets daily due to the clavulanate, thus is given with amoxicillin.
Chloramphenicol- Not recommended as not proven and potentially toxic.
Metronidazole (see later section): 500 to 1500 mg daily in divided doses. Adults only.

PARENTERAL THERAPY
Ceftriaxone- Risk of biliary sludging can be minimized with intermittent breaks in therapy (ie: infuse five days in a row per week). Adults and pregnancy: 2g q24h. For large body habitus or more severe illness: up to 4g daily. Children: 75 mg/kg/day up to 2g/day
Cefotaxime- Comparable efficacy to ceftriaxone; no biliary complications. Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Suggest a continuous infusion. Children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to exceed 12 g daily.
*Doxycycline- Requires central line as is caustic. Surprisingly effective, probably because blood levels are higher when given parenterally. Always measure blood levels. Adults: 400 mg q24h and adjust based on levels. Cannot be used in pregnancy or in younger children.
Azithromycin- Requires central line as is caustic. Dose: 500 to 1000 mg daily in adolescents and adults.
Penicillin G- IV penicillin G is minimally effective and not recommended.
Benzathine penicillin- Surprisingly effective IM alternative to oral therapy. May need to begin at lower doses as strong, prolonged (6 or more week) Herxheimer-like reactions have been observed. Adults: 1.2 million U once to twice weekly. Adolescents: 300,000 to 1.2 million U weekly. Should not be used in pregnancy. Poorly studied but anecdotally effective
Vancomycin- observed to be one of the best drugs in treating Lyme, but potential toxicity limits its use. It is a perfect candidate for pulse therapy to minimize these concerns. Use standard doses and confirm levels.
Imipenim and Unisyn- similar in efficacy to cefotaxime, but often works when cephalosporins have failed. Must be given q6 to q8 hours.
Cefuroxime- useful but not demonstrably better than ceftriaxone or cefotaxime.
Ampicillin IV- more effective than penicillin G. Must be given q6 hours.

Duration of treatment:

EARLY LOCALIZED - Single erythema migrans with no constitutional symptoms:
1) Adults: oral therapy for 6 weeks.
2) Pregnancy: 1st and 2nd trimesters: I.V. X 21 days then oral X 6 weeks 3rd trimester: Oral therapy X 6 weeks. Any trimester- test for Babesia and Ehrlichia
3) Children: oral therapy for 6 weeks.

EARLY DISSEMINATED: Milder symptoms present for less than one year and not complicated by immune deficiency or prior steroid treatment:
1) Adults: oral therapy until no active disease for 4 weeks (4-6 months typical)
2) Pregnancy: As in localized disease, but duration as above. Some experienced clinicians treat throughout pregnancy.
3) Children: Oral therapy with duration based upon clinical response.

LATE DISSEMINATED: present greater than one year, more severely ill patients, and those with prior significant steroid therapy or any other cause of impaired immunity:
1) Adults and pregnancy: extended I.V. therapy (6 to 10 or more weeks), then oral or IM, if effective, to same endpoint.
2) Children: IV therapy for 6 or more weeks, then oral or IM follow up as above.

Aktuel ILADS / Burrascano (14. ed.) behandlings-rekommendation:

Ved stikprøve tjek har jeg ikke fundet afvigelser fra 2000 udgaven …

Marie Kroun
Læge
Dec. 2003