Antibiotic treatm.ent rl Lyme borreliosis 
Antibwtic treatment oj Lyme borrelios"is: 
• our expenerices 
F. Strle 
S UM M ARY 
Treatment with antibiotics is indicated in all stages of Lyme borreliosis and for ali clinical manifestations. 
It has been, however, most effective in the early course of illness. The choice of antibiotic depends on 
many factors, including the efficacy, pharmacokinetics, side effects, expected compliance, and price. 
Far the majority of manifestations, the most effective antibiotic, the optimal dosage, and the most ap-
propriate duration of treatment have not been exactly determined. 
Basic principles of antibiotic therapy of Lyme borreliosis and recommendations for treatment of this 
disease as used in Slovenia are presented. 
The objective of this repo rt is to summarize the prin-
ci ples of antibiotic therapy of Lyme borreliosis ancl to 
outline the treatment approach as used in Slovenia. 
Basic principles ojtreatment 
Clinical signs and symptoms are essential for the 
correct diagnosis oflyme borreliosis (LB). Only a reli-
able c!iagnosis enables rational treatment. The fact is 
that in Lyme borreliosis with its insufficient clinical speci-
ficity and the lack of stanclardized serological tests, a 
reliable diagnosis is usually not an easy goal to achieve. 
Solicl knowleclge of clinical manifestations is a prereq-
uisite for rational treatment (1). 
Treatment with antibiotics is inclicated in ali stages 
of LB anc! for ali clinical manifestations, it is however 
most effective in the early course of the illness (2). The 
efficacy of treatment clepencls on clinical manifestations 
(severity, duration, ancl involvement of a particular or-
gan/ organ system) and the choice of an effective anti-
biotic that should be given in an optimal closage ancl 
for an appropriate tirne, ancl on the compliance of the 
patient. Selection of an antibiotic implicates many fac-
tors including the efficacy, pharmacokinetics , sicle ef-
fects, expected compliance, and price. 
The aim of antibiotic therapy isto eraclicate bacteria 
causing infection. Eraclication of pathogenic bacteria is 
a precondition, but unfortunately nota guarantee for 
cure , nor for exclusion of eventual sequelae. Healing 
of the injured tissue (caused by bacteria or associated 
inflammation) may take much longer than the effective 
eradication. In such cases some clinical features may 
Treatm.ent 
E y 
:WORDS 
Lyrne 
borreliosis, 
treatrnent, 
antibiotics, 
Slovenia 
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Treatment Antibiotic treatment of" Lyme borreliosis 
Table l. Recommendations for treatment of early Lyme borreliosis with antibiotics in Slovenia. 
Eiythema amoxicillin oral 3x500-1000 mg 20-50 mg/ kg 14 (10-30) allergy 
migrans, or 
Lymphocytoma azithromycin oral 2x500 mg 20 mg/kg 1st day allergy 
or lx500 mg 10 mg/kg 4 days 
cefuroxime oral 2x500 mg 30-40 mg/kg 14 (10-30) allergy 
or 
doxycycline oral 2xl00 mg 14 (10-30) children, pregnancy 
or lactation, allergy 
phenoxy- oral 3x0.5-1.0 0.1-0.15 14 (10-30) allergy 
methylpenicillin MIU MIU/kg 
e1ythromycin" oral 4x250 mg 30 mg/kg 14 (10-30) allergy 
ceftriaxonei, i.v. 2g 50-100 mg/kg 14 allergy 
or (up to 2 g/day) 
penicillin Gh i.v. 20MIU 0.25-0.5 MIU/kg 14 allergy 
LEGEND 
MIU = million international units 
" e1ythromycin only for patients allergic to penicillin and/or tetracyclines 
h ceftriaxone and penicillin G are used for treatment of e1ythema migrans only in specific situations 
persist in spite of successful antibiotic therapy. Thus, in 
certain infectious diseases including LB, persistence of 
signs or symptoms shoulcl not necessarily leacl to of an-
tibiotic treatment until the complete disappearance of 
ali signs and symptoms. 
The most effective antibiotic, the optimal dosage and 
the appropriate duration of treatment have not been 
exactly established for any of the many clinical mani-
festations of LB. Some physicians would treat only pa-
tients who fulfil all the rigorous criteria for LB, while 
others treat patients with poorly defined symptoms of 
chronic LB with repeated or prolonged courses of anti-
biotics. Sometimes even antibiotics are used to which 
Bon-eliaeare in vitro resistant. Current shortcomings of 
therapy should be a stimulus for well designed investi-
gations to study the unresolved problems (1). 
In the last few years a trend of prolongation of treat-
ment of Lyme borreliosis has been observed. Reasons 
for this prolongation have been predominantly based 
on disappointments with the results of treatment per-
formed according to current recommendations. These 
are often based on reports or personal experiences of 
individual treatment failures, and not on the results of 
controlled studies. It is however possible that such stud-
ies would show that a prolonged treatment is superior 
to a shorter one. Anyway, it is reasonable to expect that 
the recommendations for treatment (1-1 O) will be chang-
ing in future. 
Because of different pathogenesis of LB in North 
America and Europe, differences in clinical presenta-
tion ofthe disease (11-13), and paucity of data compar-
ing the outcome of the illness on either side of the At-
lantic, it may be prndent to consider the existing infor-
mation with caution. 
Antibiotic treatment oj Lyme 
borreliosis as used in Slovenia 
Recommendations for treatment ofLyme borreliosis 
as used in Slovenia are shown in Tables 1, 2 and 3. 
Early localized Lyme borreliosis 
Recommendations for treatment of the early local-
izecl clisease (Table 1) were introduced in our country 
in 1992, ancl have not changed substantially. Patients 
with solita1y erythema migrans and borrelial lympho-
cytoma are treated with amoxicillin, azithromycin, doxy-
cycline, cefuroxime-axetil, or phenoxymethylpenicillin 
(the last one predominantly in chilclren). With the ex-
ception of azithromycin the usual duration of treatment 
Acta Dermatoven APA Vol 10, 2001, No 4 ------------------------ ----------163 
Antibiotic treatment 11f' Lyme borreliosis 
Table 2. Approaches in a case of treatment failure in e1ythema migrans as used in Slovenia. 
Persistence of skin lesion 
(> 4 w eeks) 
Check cliagnosis 
Re-treatment with an alternative" (oral) antibiotic 
Reappearance of skin lesion Check diagnosis 
Re-treatment with an alternative " (oral) antibiotic 
Persistence of Borreliae in skin Re-treatment with an alternative" (oral) antibiotic 
Appearance of rninor rnanifestations 
of Lyme borreliosis 
Wait and watch; check cliagnosis 
Eventual antibiotic treatment (ceftriaxone i.v.?) 
Appearance of major manifestations 
of Lyme borreliosis 
Treatment with ceftriaxone i.v. 
LEGEND 
" beta-lactam antibiotics (amoxicillin or cefu roxime axetyl) are replacecl by tetracyclines (cloxycycline) 
or macrolicles (azithromycin) ancl vice versa . 
is 14 clays. The efficacy is similar but there are cliffer-
ences in dosage (from one tirne to 3 times daily), side 
effects (relatively frequent with cloxycycline) as well as 
the price (the most expensive is cefuroxime axetil while 
the cheapest is doxycycline) . 
Parenteral therapy with ceftriaxone or penicillin G is 
used only exceptionally in p atients with erythema 
migrans . It is limitecl to: 
i) patients w ith multiple skin lesions; an article from the 
USA demonstrating that therapy of multiple erythema 
migrans with doxycycline was as effective as treatment 
with ceftriaxone was publishecl recently (14); 
ii ) patients with e1ythema rnigrans and concomitant other 
manifestations of LB (e.g. neurological involvement); 
iii) e1ytherna migrans in pregnancy (15); and 
iv) parenteral antibiotic treatrnent might be indicatecl 
also for immuno deficient p atients w ith erytherna 
rnigrans; however, there are not enough clata to sup-
port this• decision (16). 
In case of a treatrnent failure in e1ythema rnigrans 
we use approaches as shown in Table 2. 
Early disseminated and late Lyme 
borreliosis 
Recomrnendations for treatment of early dissemi-
natecl ancl late LB in Slovenia are shown in Table 3. 
Nervous system involvement and severe Lyrne carclitis 
are as a rule treated w ith ceftriaxone or penicillin G for 
2 to 3 weeks and only exceptionally orally with doxy-
cycline or arnoxicillin (Table 3). 
For therapy of acroderrnatitis chronica atrophicans 
and arthritis , ceftriaxone, penicillin G, doxycycline or 
amoxicillin are recornrnended. Parenteral therapy is 
used because of the possible involvement of the cen-
tral nervous system. Duration of intravenous treatment 
is as a rule 3 weeks for acroclermatitis chronica atro-
phicans ancl 2 weeks for arthritis, while the cluration of 
oral therapy is 4 weeks (Table 3). 
Asymptomatic persons with a positive 
borrelial antibody titre, persons with a 
recent tick bite 
No reliable data support the use of antibiotics in 
asymptornatic persons with a positive borrelial serologic 
test. Decision to treat a patient w ith an antibiotic should 
always be based on the presence of at least suggestive 
clinical signs ancl symptorns . Tl1ti°s, our general ap-
proach in the case of an asyrnptomatic person with 
positive borrelial antibody serum titres is to wait and 
watch (1). As a rule we use a sirnilar approach in an 
asyrnptomatic person reporting a recent tick bite (1 ,17) . 
Reasons far antibiotic treatment 
jailure 
There are severa! reasons for antibiotic treatment 
failure in LB. One p ossibility is the persistence of 
Borreliae in tissues. There are convincing clinical and 
Treatment 
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Treatment Antibiotic treatment o( Lyme borreliosis 
Table 3. Recommendations for treatment of late Lyme borreliosis with antibiotics in Slovenia. 
CNS 
involvement 
(early or late) 
ceftriaxone 
or 
penicillin G 
Hea1t involvement 
doxycycline 
Possible 
exceptions" 
or 
amoxicillin 
i.v. 2g 
i.v. 20MIU 
oral 2x200 mg 
oral 3x0.5-1 g 
50-100 mg/kg 14 (10-30) allergy 
0.25-0.5 MIU/kg 14 (10-30) allergy 
20-50 mg/kg 
28 (14-30) children, pregnancy 
lactation, allergy 
28 (14-30) allergy 
Arthritis 
(intermittent 
or chronic) 
doxycycline 
or 
amoxicillin 
oral 2x100-200 mg - 14 (10-30)1' children, pregnancy 
lactation, allergy 
Acroclermatitis ceftriaxone 
chronica 
atrophicans" 
LEGEND 
or 
penicillin G 
CNS = central nervous system 
oral 3x0.5-1 g 
i.v. 2 g 
i.v . 20 MIU 
20-50 mg/ kg 
50-100 mg/kg 
14 (10-30)h allergy 
14 (10-30)1' allergy 
0.25-0.5 MIU/ kg 14 (10-30)" allergy 
" Possible exceptions: - peripheral facial palsy alone (normal cerebrospinal fluid examination result~) 
- atrio-ventricular block of first degree (P - Q < 0.30 s) 
"Treatment of acrodermatitis chronica atrophicans is asa rule longer than 14 days (ceftriaxone 21 days, doxycy-
cline 28 clays) 
experimental data, predominantly in the European lit-
erature, showing tl1at after so callecl adequate (recom-
mendecl) treatment Borreliae can persist in tissue (18-
20), it is however clifficult to assess the significanse of 
this problem. 
In some cases a possible explanation for treatment 
failure could be an irreversible tissue clamage causecl 
cluring active borrelial infection or inflammation or the 
induction of auto-immune mechanisms; in such cases 
treatment with an antibiotic can be ineffective (1,3). 
An important and probably a common cause for 
treatment failure is wrong cliagnosis. It is quite possible 
that treating a patient with, for example, arthralgias and 
myalgias and a positive borrelial antibody titre in se-
rnm, is nota treatment of LB but "therapy" of serologi-
cal tests Cl,3,8,9) . 
Conclusion 
A well-established principle in medicine says that a 
reliable diagnosis is the basis for rational treatment. 
However, in LB with its lack of clinical specificity ancl 
Jack of standarclizecl serological tests, a reliable cliagno-
sis is usually not an easy goal to achieve. Antibiotic 
therapy is indicated in ali stages of LB and for ali clini-
cal manifestations, however, it is more effective in the 
early stage of the illness. 
l. Strle F. Principles of diagnosis and antibiotic treatment of Lyme borreliosis. Wien Klin Wochenschr 
1999; 111: 911-5. 
2. Steere AC. Lyme disease. N Eng!J Med 1989; 321: 586-96. 
3. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet 1998; 352: 557-65. 
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Antibiotic treatment o{ Lyme borreliosis 
AUTHOR'S 
ADDRESS 
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Franc Strle, MD, PhD, profess01; Department of Jnfectious Diseases, 
University Medical Centre, Japljeva 2, 1525 Ljubljana, Slovenia 
Treatment 
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