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ntroductiontroduction

e European Union Concerted Action on Lyme Borreliosis (EUCALB) initiative,

ded initially by the EU, continues to promote research and evidence-based clinical

ctice through European multi-disciplinary collaboration and a highly-regarded andquently updated website. Its clinical case definitions for Lyme borreliosis were

blished in 1997. An updated version has been published (Clin Microbiol Infect

10 doi:10.1111/j.1469-0691.2010.03175.x). EUCALBs work programme also

ludes a review of currently recommended treatments in Europe and the evidence

which they are based.

ce the publication of the Infectious Diseases Society of North Americas updated

delines for Lyme borreliosis in 2006 there has been considerable public dispute inUSA and elsewhere regarding choice of antibiotic agents and duration of

ibiotic treatment for Lyme borreliosis, particularly for patients who have persistent

mptoms following standard treatment. Some patient support groups and a minority

physicians have been very active in promoting prolonged or multiple courses of

ibiotics for patients with persistent symptoms in North America and in Europe.

ere has also been criticism about the use of the IDSA guidelines for patients in

rope, prompting this evaluation of European guidelines and recommendations and

omparison with American recommendations.

Recommendations for diagnosis and treatment of LymeRecommendations for diagnosis and treatment of Lyme borreliosisborreliosis::

guidelines and consensus papers from specialist societies and exguidelines and consensus papers from specialist societies and expert groups inpert groups in

Europe and North AmericaEurope and North AmericaSue O'Connell, Health Protection Agency LymeSue O'Connell, Health Protection Agency Lyme BorreliosisBorreliosis Unit, HPA Microbiology Laboratory,Unit, HPA Microbiology Laboratory,

Southampton University Hospitals Trust, Southampton SO16 6YDSouthampton University Hospitals Trust, Southampton SO16 6YD

ethodsethods

CALB participants collated diagnostic and treatment guidelines prepared

ependently by specialist societies and expert groups in various Europeanuntries and in North America. National and/or specialist society guidelines and

ommendations of experts from the Czech Republic, Denmark, Finland, France,

rmany, the Netherlands, Norway, Poland, Slovenia, Sweden and Switzerland have

en evaluated and compared with regard to clinical and laboratory diagnostic and

atment recommendations (including antibiotic agents, dosages and durations) for

thema migrans, neuroborreliosis and Lyme arthritis. They have also been

mpared to those of the IDSA and the American Academy of Neurology.

e first-line treatment recommendations of the various European and Northmerican guidelines are presented in tabular form to permit easy comparison.

indingsndings

e majority of guidelines and reviews listed here give explicit details about quality of

dence and strength of recommendations. They list references of published

domised controlled treatment trials and numerous other peer-reviewed papers on

gnosis and management of Lyme borreliosis in the international literature.

guidelines give recommendations for clinical diagnosis and for the application of

oratory tests. There is overall agreement regarding the clinical features of Lyme

rreliosis and on the requirement for supporting laboratory evidence of a clinical

gnosis of later-stage infection. Two-tier serological testing, with immunoblot as a

cond-stage test, is currently recommended in most guidelines and reviews, . No

deline or review recommends serological testing in support of a diagnosis of

thema migrans.

erall there are great similarities of antibiotic choice between the various treatment

delines and reviews, with some minor differences in dosing and duration.

e most commonly recommended first-line treatments for different stages of

me borreliosis in non-pregnant, non-breastfeeding adults in Europe are:

ythema migrans:

Doxycycline 100mg bd (10-21days)

Amoxicillin 500mg 1g tid (14-21 days)

rly neuroborreliosis:

Ceftriaxone 2g daily (14 days)

Doxycycline 100mg-200mg bd (14-21 days)

te neuroborreliosis:

Ceftriaxone 2g daily (14-28 days)

me arthritis:

Doxycycline 100mg bd (28 days)

Amoxicllin 500mg tid (28 days)

ese recommendations, independently developed by a wide range of European

perts in infectious diseases and other specialities, are similar to those of the IDSA.

1. Refs cited: Number of references cited in the guideli ne.2. NRVPMT = No recommendation for very prolonged or multiple courses of treatment3. Netherlands references are for the treatment section only. (38)4. Norwegian references are for the summary only. (50)5. IDSA references are for the complete guideline, including diagnosis, treatment and prevention of Lyme borreliosis,anaplasmosisand babesiosis(405)

CommentsCommentsThere are only minor differences in antibiotic treatment recommendations, with twoScandinavian countries favouring the use of high dose penicillin V over amoxicillin asfirst-choice B-lactam agent for erythema migrans, and slightly shorter treatmentcourses.

Doxycycline is widely recommended for treatment of all stages of Lyme borreliosisother than late neuroborreliosis.

Ceftriaxone is the antibiotic most widely recommended for parenteral use.

The most recently prepared guidelines have stronger recommendations for the use ofdoxycycline in neuroborreliosis without encephalitic or myelitic features, followingpublication in 2008 of a Norwegian double-blind randomised controlled trial whichshowed non-inferiority of oral doxycycline 200mg daily versus intravenous ceftriaxone2g daily for 14 days. (Ljostad U et al. Lancet Neurology 2008;7:690-95)

No evidence-based European or North American guideline recommends prolonged ormultiple courses of antibiotics for persistent symptoms following previously treatedLyme disease.

AcknowledgementsAcknowledgements

I am most grateful to Drs Ram Dessau, Volker Fingerle, Lise Gern, John Halperin, Joppe Hovius, Janusz Janiec, Benoit

Jaulhac, Wolfgang Kristoferitsch, Satu Kurkela, Marjorie Monnickendam, Dag Nyman, Katharina Ornstein, Tone Skarpaas,

Robert Smith, Gary Wormser, Mrs Anne Southwell, Miss Nicki Daughtrey and Mr Derek Nudd for their support in the

development of this work. I thank the staff at SUHT Learning Media for skilled help in poster preparation.

We should be most grateful for notification of other evidence-based guidelines to EUCALB for collation.

or

or

or

European and AmericanEuropean and American LymeLyme BorreliosisBorreliosis Diagnostic / Treatment GuidelinesDiagnostic / Treatment Guidelines

First line treatment recommendations for nonFirst line treatment recommendations for non --pregnant, nonpregnant, non--breastfeeding adultsbreastfeeding adults See individual guidelines for further detailsSee individual guidelines for further details

Diagnostic / Treatment Guideline Diagnosticcriteria

specified?

E ry t hema m igrans E ar ly d is seminat ed

(non-nervous system)

Neuroborreliosis Lyme arthritis Refs

cited(1)Comment

Czech Republic

VanousovaD, HercegovaJ. Lymeborreliosistreatment. DermatolTher2008;21:101-9.

Y es Do xy cy cl in e 10 0m g bd or

Amoxicillin1g tid

(14-21 days)

Ceftriaxone2g daily or

Penicillin G 5MIUqid

(14-21 days) or

Doxycycline100-200mgbd(14-28 days)



(14-21 days) or

Doxycycline100-200mgbd(14-28 days)

Doxycycline100mgbd or

Amoxicillin500mg-1gtid

(21-28 days) or

Ceftriaxone2g daily(14-21 days)

40 NRVPMT(4)

Denmark

DanskSelskab for KliniskMikrobiologi, DanskSelskabfor Infektionsmedicinog DanskNeuroliskSelskab 2006 35pp.

Dessau R, BangsborgJM, EjlertsenTP et al.UgeshrLaeger2006:1682805-7(summary)

Yes Pen ic il l in V 1. 5M IU tid or

Doxycycline200mgstat then100mgdaily or

Cefuroximeaxetil 500mgbd

(10 days)


Penicillin V 1.5MIU tid

(10 days)


(10 days) or

Doxycycline200mgbd on day1, then 100mg bd

(14 days) or

Ceftriaxone2g daily orCefotaxime2g tid

(10 days)

Agentsgiven for14 daysfor late NB

Penicillin V 1.5MIU tid or

Doxycycline100mgbd

(21 days)

175 NRVPMT(4)

Finland

OksiJ, SeppalaIJ, HytonenJ. Lymenborrelioosindiagnostiikkaja hoito. Duodecim2008;124:1483-91

Yes Amoxici l li n500mg-1g tid or

Doxycycline100mgbd

(14 days)

Carditis:

Ceftriaxone2g daily

(14-21 days)

Ceftriaxone2g daily

(14 -21days) or

Doxycycline100mgbd

(1-3 months)

Ceftriaxone2g daily

(14-21 days) or

Amoxicillin500mgtid orDoxycycline100mgbd

(1-2 months)

13 NRVPMT(4)

France

Societede Pathologie InfectieusedeLangueFrancaise. Lymeborreliosis: diagnostic,therapeutic andpreventive approaches. MedMal Infect 2007; 37(S3), 8153-74.


AmoxicillinIg tid

(14-21 days)


Amoxicillin1g tid

(21-28 days)

Carditis:

Ceftriaxone2g od(21-28days)


Penicillin G 18-24MIU daily

(21-28 days) or

Doxycycline200mgdaily (isolatedfacial palsy [14-21days] orif otheragents contraindicated[21-28days])

Doxycycline200mgdaily or

Amoxicillin1g tid

(21-28 days, extended upto 90daysif persistent) or

Ceftriaxone2g daily(14-21 days)

160 NRVPMT(4)

Germany

Leitliniender DeutschenGesellschaftfurNeurologie 2008

http://leitlinien.net/AWMF Leitlinien-RegisterNr 030/071

Yes Not applicable Not applicable Doxycycline 100mg bd or tid

Ceftriaxone2g daily orCefotaxime2g tid or

Penicillin G 18-24MIU daily

(Acuteneuroborreliosis:14 days)

(Late NB: iv first line: 14-21days)

Not applicable 60 NRVPMT(4)

Germany

Leitliniender DeutschenDermatologischenGesellschaft2009 http://leitlinien.net/AWMFLeitlinien-Register Nr 013/044

Yes Doxycycline100mgbd or

Amoxicillin500mg1gtid or

Cefuroxime500mgbd

(14-21 days) or

Azithromycin250mg bd

(5-10 days)


Amoxicillin500mg-1gtid

(21-30 days)

Not applicable Not applicable 64 NRVPMT(2)

Netherlands

CBO RichtlijnLyme Borreliose2004ISBN: 90-76906-89-0

SpeelmanP, de JonghBM, Wolfs TF,Wittenberg; CBO. NedTijdschr Geneeskd

2004;148:659-63. (summary)

Y es Do xy cy cl in e 10 0m g bd

(10 days) or

Amoxiillin500mg tid

(14 days)

Doxycycline100mgbd

(21 days) or

Ceftriaxone2g daily (carditis)

(14 days)


Penicillin G 2-3 MIU 4hourly

(Acuteneuroborreliosis:14 days; lateNB: 30days) or

Doxycycline200mgbd

(Acuteneuroborreliosis:21 days; lateNB: 30days)

Doxycycline100mgbd (30days)or

Amoxicillin500mgtid (30 days)or

Ceftriaxone2g daily (14days)

38(3) NRVPMT(2)

Norway

LjostadU, MyglandA.Lyme-borreliosehosvoksne.TidsskrNor Legeforen2008; 128:11758.

Norsklegemiddelhndbokfor helsepersonell

(www.legemiddelhandboka.no)

Yes D ox yc yc line200mgdai l yor

Amoxicillin500mgtid

(14 days)

Doxycycline200mgdaily

(14 days)

(Alternatively forcarditis:

Ceftriaxone2g daily for 14 days)


Cefotaxime2g tid or

Penicillin G 5MIUqid or


(14-28 days)


(20-30 days)

50(4)

Poland

FlisiakR, PancewiczS. Diagnosis andtreatment of Lymeborreliosis:recommendationsof the Polish Society ofEpidemiology and InfectiousDiseases. PrzeglEpidemiol2008;62:193-199.


Amoxicillin500mgtid orCefuroximeaxetil 500mgbd

(14-21 days)


Amoxicillin500mg-1gtid or


(14-28 days)


Cefotaxime2g tid or

Penicillin G 3-4 MIU four-hourly

(14-28 days)




Penicillin G 3-4MIUfour-hourly

(14-28 days)

Not stated NRVPMT(2)

Slovenia

StrleF. Principles of the diagnosis andantibiotic treatment of Lymeborreliosis. WienKlinWochenschr1999;111:911-915


Amoxicillin500mg 1gtid or

Cefuroxime500mgbd or

Penicillin V 0.5-2MIU tid

(14 days; range10-30) or

Azithromycin1g onday 1;500mgdaily for 4days.

Doxycycline100mg-200mgbdor


Cefuroxime500mgbd

(14 days; range10-21)


Penicillin G 20 MIU daily


Doxycycline200mgbd


Doxycycline100mg-200mg bd or

Amoxicillin0.5-1gtid or

Ceftriaxone2g daily

or

Penicillin G 20MIU daily


30 NRVPMT(2)

Sweden

Lakemedelsbehandlingav borreliainfektion- nyrecommendati on. Information franLakemedesverket4:2009:12-17

Y es P en ic il li n V 1g ti dor

Doxycycline100mgbd

(10 days)

Doxycycline100mgbd (10days)

Alternativeforcarditis:

Doxycycline100mgbd orCeftriaxone2g daily (14 days)

Doxycycline200mgdaily (14 days) or

200mgbd (10 days) or


Doxycycline200mgdaily or

Ceftriaxone2g daily

(14 days)


Switzerland

EvisonJ, Aebi C, FrancioliP et al. Borreliosede Lyme. Diagnostic et traitement delaborreliosede Lymechez ladulte et lenfant:recommandationsde la SocieteSuissedInfectiologie. RevMed Suisse 2006; 2, 19-40.


(10 days) or

Amoxicillin500mgtid

(14-21 days)


Amoxicillin500mgtid

(14-21 days)

Carditiswith AV III block

Ceftriaxone2g daily (28 days)

Ceftriaxone2g daily orPenicillin G 3-4MIUx 6/day

(28 days)

Isolated facial palsy:

Doxycycline100mgbd orceftriaxone2 g daily

(14-21days)


Amoxicillin500mgtid

(30-60 days)

135 NRVPMT(2)

(SeealsoBull

OFSP

2008;24:424-7)

European Federation of Neurological

Societies

MyglandA, LjostadU, FingerleV et al.European Federation of Neurological Societiesguidelines on thediagnosis and managementof EuropeanLymeneuroborreliosis EurJNeurol2010;17:8-16

Yes Not applicable Not applicable Early NB without encephalitis, myelitisor vasculitis:

Doxycycline200mgdaily or Ceftriaxone2g daily

(14 days)

Early encephalitisor myelitis:


Late encephalomyelitis orvasculitis:


ACA andperipheral neuropathy:

Doxycycline200mgdaily or Ceftriaxone2g daily(21d)


EUCALB website

European UnionConcertedAction on LymeBorreliosis

http://meduni09.edis.at/eucalb/cms/index.php

(Accessed 8th September2010)



Penicillin V 1-1.5MIU tid orCefuroximeaxetil 500mgbd


Doxycycline100 mg bd or


Penicillin V 1g tid or

Ceftriaxone2g daily


Ceftriaxone2g daily orCefotaxime2g tid or

Penicillin G 20MIU daily


Doxycycline100-200mg bd


Doxycycline100mgbd) or


Ceftriaxone2g daily

(21 days; range14-30 days)


USA

WormserGP, DattwylerDJ, Shapiro ED et al.The clinical assessment, treatment andprevention of Lymedisease, humangranulocytic anaplasmosisandbabesiosis.Clinical Practice Guidelines by the InfectiousDiseases Society of America. ClinInfect Dis2006; 43, 1089-1134. (Upheldby the LymeDisease Guideline Review Panel of IDSA,2010: LantosPM et al. CID 2010;51:1-5)



Amoxicillin500mgtid or







Carditis:Asabove orstart withCeftriaxone2g daily (see g/ls)


Cefotaxime2 g tid or

Penicillin G 3-4MIUx 6/day


Doxycycline100-200mgbd




Cefuroximeaxetil 500 mg bd

(28 days)

405(5) NRVPMT(2)

USA

HalperinJJ, Shapiro ED, LogigianEet al.PracticeParameter: Treatment of nervoussystemLymedisease (an evidence-basedreview) Report of the Quality StandardsSubcommittee of the AmericanAcademy ofNeurology. Neurology 2007;69:1-12.

Yes Not applicable Not applicable Ceftriaxone 2g daily or

Cefotaxime2g tid or

Penicillin G 3-4 MIU x 6/day or

Doxycycline100-200mg bd



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