Lyme borreliosis. Treatment. 
TREATMENT OF LYME BORRELIOSIS 
V. Maraspin-Čarman, F. Strle, J. Cimperman and S. Lotrič-Furlan 
SUMMARY 
Lyme borreliosis is a multi system disease, which is caused by the spirochete Borrelia burgdorferi and 
transmitted by Ixodes ticks. In this article treatment with antibiotics in patients with Lyme borreliosis at the 
University Department of Infectious Diseases in Ljubljana is presented. 
In the early localized disease, which is characterized by erythema migrans and often associated with flu-like 
symptoms, patients are treated orally with doxycycline, tetracycline, amoxycillin, azithromycin, phenoxymethylpenicillin 
or erythromycin. The treatment lasts two weeks, with the exception of azithromycin, which is prescribed for 
five days. 
For the manifestations of Lyme borreliosis in the second stage (cardiac, neurologic and joint involvement) 
and third stage ( acrodermatitis chronica atrophicans, neuroborreliosis, arthritis) intravenous treatment with 
antibiotics, currently with ceftriaxone or benzylpenicillin, is used. The exception are patients with mild cardiac 
involvement (first degree A-V block) who are treated with oral antibiotics. 
Patients with Bell's palsy and pregnant women with erythema migrans are treated with intravenous 
antibiotics. Prophylactic treatment after tick bites is not recomended. 
KEY WORDS 
Lyme borreliosis, antibiotics, treatment. 
INTRODUCTION 
Lyme borreliosis is the most common tick-borne 
illness in Europe and the United States (1, 2, 3). 
The infection is caused by the spirochete Borrelia 
burgdorferi ( 4,5), which is transmitted by Ixodes 
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species ticks. The disease may affect many organic 
systems. Because of different clinical manifestatiems 
and long-standing evolution it has been divided into 
three stages (6). Recently, similar to syphilis, early 
127 
Lyme borreliosis. Treatment. 
localized, early disseminated and late manifestations 
are recognized (7,8). Treatment with antibiotics has 
been shown to be effective during early and also 
late stages of the disease (9), but it has not yet 
been established, which antibiotic is the most efficacious 
(10-14) . 
Penicillin was the first antibiotic used in Europe 
and it remained the only one for many years. After 
discovery of Borrelia burgdorferi, in vitro studies to 
determine antibiotic sensitivities of the causative 
agent were performed as well as studies on 
experimental animals (15-18). In 1983, Steere et al. 
reported that phenoxymethylpenicillin, tetracycline 
and erythromycin are effective drugs for resolving 
erythema migrans and preventing the development 
of the later manifestations of the disease (10) . It 
was found out that tetracycline appeared to be the 
most effective drug, followed by penicillin and finally 
erythromycin (8, 19). Amoxycillin and amoxycillin 
plus probenecid (20) as well as cefuroxime axetil 
(21) and ceftriaxone (22) are also effective in the 
treatment of early stage of Lyme borreliosis . Recently 
studies to determine the in vitro effectiveness of 
some other cephalosporins ( ceftizoxime, FK 037), 
and of severa! new macrolides (clarithromycin, 14-
OH clarithromycin, dirithromycin) were published 
(23,24). Clinical efficacy of these agents has not 
been evaluated. Studies on azithromycin demonstrate 
that it represents a suitable agent for treatment of 
erythema migrans (25-27). 
For the majority of the manifestations of Lyme 
borreliosis in the second and third stage, intravenous 
treatment with antibiotics is indicated. Third generation 
cephalosporins ( cefotaxime, ceftriaxone) and benzyl-
penicillin, which are currently used, have been shown 
to be effective (8,19,28-31). 
Since failures or relapses have been reported with 
ali regimens, the optimal antibiotic, the optimal 
dosage and optimal duration of antibiotic therapy 
have to be determined (14,27,29,32,33). 
The treatment of patients with Lyme borreliosis 
at the Department of lnfectious Diseases of the 
University Medica! Centre in Ljubljana is · reported. 
TREATMENT OF THE FIRST 
STAGE OF LYME BORRELIOSIS 
(EARL Y LOCALIZED INFECTION) 
The pathognomonic skin lesion at this stage is 
erythema migrans which usually appears within one 
128 
month after a tick bite. It may be accompanied by 
nonspecific symptoms such as fatigue, malaise, lethargy, 
headache, myalgias, arthralgias, regional or generalized 
lymphoadenopathy. Some patients are totally asym-
ptomatic (6,8,11,13) . Although erythema migrans can 
disappear spontaneously, treatment with antibiotics 
in this stage is important because it reduces the 
duration of the cutaneous lesion and associated 
symptoms and prevents later manifestations of the 
illness (8,10,13,21,25-27). 
At the Department of Infectious Diseases in 
Ljubljana adult patients are treated with doxycycline 
(100 mg orally twice daily), tetracycline (250 mg 
orally four times daily), amoxycillin (500 mg orally 
three times daily) or phenoxymethylpenicillin (1 rnillion 
units orally three times daily) for two weeks. Treatment 
with azithromycin for five days (500 mg twice daily 
for the first day, followed by 500 mg once daily for 
four days) is also used. 
For children with erythema migrans we use 
phenoxymethylpenicillin (30000-50000 units/kg/day) or 
amoxycillin ( 40 mg/kg/day). In case of allergy to 
penicillin erythromycin (30 mg/kg/day) is used. A 
study of the use of azithromycin in children is 
currently in course at our department. 
The same antibiotics are in use also for the 
treatment of borrelial lymphocytoma, a rare mani-
festation of Lyme borreliosis described in Europe 
(3,7,34,35). 
TREATMENT OF THE SECOND 
STAGE OF LYME BORRELIOSIS 
(EARLY DISSEMINATED INFECTION) 
Symptoms in this stage begin usually 2 to 3 
months after the onset of erythema migrans, sometimes 
as late as 9-10 months after the beginning of 
infection (8). 
A minority of patients with erythema migrans in 
Europe develop multiple skin lesions as a result of 
hematogenous dissemination of Borrelia burgdorferi 
(11,13). 
In patients with neurologic involvement may develop 
a classical Bannwarth's syndrome, often associated 
with certain neurological manifestations such as 
meningitis, encephalomyelitis, neuritis of the cranial 
nerves ( especially of the facial nerve ), radiculoneuritis, 
and peripheraf neuritis (6,8,36-38). Heart involvement 
(myocarditis, endocarditis and/or pericarditis) is ·usually 
asymptomatic. Carditis typically manifests with various 
degrees of atrioventricular conduction defects, 
acta derrnatovenerologica A.P A. Vol 3, 94, No 1/2 
Lyme bo"eliosis. Treatment. 
sometimes with tachyarrhythmias, ECG signs of 
myo(peri)carditis and rarely with mild congestive 
heart failure (6,8,39). 
Other manifestations in this stage of Lyme borreliosis 
are also migratory pains in joints, muscles, tendons 
and bones and recurrent attacks of large joints' 
arthritis ( 6;8). 
In all these patients we use intravenous therapy 
with ceftriaxone (for adults 2 g once daily and for 
children 50-80 mg/kg/day) or benzylpenicillin (for 
adults 20 million units daily, for children 0.25-0.40 
million units/kg/day) for two weeks. 
Since patients with clinically isolated Bell's palsy 
frequently have asymptomatic meningitis, we treat 
them with an intravenous antibiotic. 
Only patients with mild cardiac involvement, such 
as first degree atrioventricular block with P-R interval 
less than 0.30 second, are treated orally with above 
mentioned antibiotics for treatment of early localized 
infection. 
TREATMENT OF THE THIRD 
STAGE OF LYME BORRELIOSIS 
(LATE INFECTION) 
The chronic stage occurs a year or more after the 
onset of infection with Borrelia burgdorferi, usually 
following a latent period (6,8) . 
The typical cutaneous lesion is acrodermatitis 
chronica atrophicans, occurring predominantly on 
the lower arms and legs (6,7,13,40,41). Neurological 
involvement of this stage, the so-called late neuro-
borreliosis, is manifested as progressive ence-
phalomyelopathy, peripheral neuritis, and as mental 
and/or psychiatric disorders (6,8). Patients can display 
symptoms of chronic arthritis, which typically affects 
knees (6,8) . 
In the patients with late Lyme borreliosis we use 
intravenous ceftriaxone or benzylpenicillin in the 
same doses as in the second stage, but for a longer 
period (usually three weeks). 
TREATMENT OF LYME 
BORRELIOSIS IN PREGNANCY 
Because of the possibility of fetal anomalies or 
death ( 42-44), pregnant women with erythema migrans 
are treated with ceftriaxone (2 g daily i.v.) or 
benzylpenicillin (20 million units daily i.v.) for two 
weeks. 
PREVENTION 
OF L YME BORRELIOSIS 
Although Lyme borreliosis in Slovenia is endemic, 
we don't recommend prophylactic therapy with 
antibiotics in persons which experienced tick bites, 
because the risk to develop the disease is probably 
very low (45). We recommend wearing proper clothing 
and eventual use of repellents, and stress the 
importance of early tick removal (preferable within 
the first 24 hours). 
CONCLUSIONS 
Treatment with 'antibiotics is reasonable in any 
stage of Lyme borreliosis. However it is much more 
effective in the early localized and early disseminated 
infection than in chronic disease. The response r:pay 
be delayed especially in patients with long-lasting 
illness. There is also a correlation between the 
severity of the early stage of disease and/or the 
presence of multiple erythema migrans lesions and 
progression to later stages (8). However, even the 
mildest or unapparent cases of Lyme borreliosis in 
early stage may progress (8,46). To prevent further 
manifestations of the disease it is important to start 
treatment promptly with an adequate antibiotic 
regimen. In view of the described failures of antibiotic 
treatment in Lyme borreliosis, further studies are 
needed to determine the optimal drug for various 
clinical manifestation, its dosage as well as duration 
of therapy. 
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AUTHORS' ADDRESSES 
Vera Maraspin-Čarman, MD, University Medica! Centre 
Department of lnfectious Diseases, Japljeva 2, 61000 Ljubljana, Slovenia 
F. Strle, MD, PhD, professor of infectious diseases, same address 
J. Cimperman, MD, same address 
S. Lotrič-Furlan, MD, same address 
acta dermatovenerologica A.P.A. Vol 3, 94, No 1/2 131