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NIHR Signal Several antibiotics appear effective against early-stage Lyme disease

Published on 29 January 2019

doi: 10.3310/signal-000719

Most cases of Lyme disease, which is an infection carried by ticks, can be easily managed if treated early using antibiotics, with choice of antibiotic agent having little bearing on success.

This network meta-analysis suggests that when symptoms of the disease are confined to a localised skin infection, treatment failures are relatively infrequent, only 2% at 12 months. Effective antibiotics include penicillin V, doxycycline, azithromycin, cefuroxime, amoxicillin and ceftriaxone plus doxycycline.

The research has significant limitations, but choice, dose and duration of antibiotics appear to have little impact on outcomes. This research does not suggest that guidelines need to be reviewed.

  •   Infections, Medicines, Skin conditions, Primary care
Several antibiotics appear effective against early-stage Lyme disease

Why was this study needed?

Lyme disease affects around 2,000 to 3,000 people a year in England and Wales. Although still uncommon, cases have risen in recent years, with warmer winters likely to be a contributing factor. It is caused by an infection with the bacteria Borrelia burgdorferi, spread through infected ticks.

Early symptoms are usually mild. Many people experience a rash that starts around the bite area (erythema migrans) and may have flu-like symptoms. If left untreated, more serious complications can occur such as nerve pain and heart problems. 

Antibiotics are the standard treatment, with doxycycline being the first line antibiotic recommended by NICE. Whilst it is clear they work, the evidence supporting the choice of antibiotic agent is not conclusive. Additionally, the researchers wanted to see if the data pointed to a best treatment regimen and whether dose and treatment length are important.

What did this study do?

This network meta-analysis included 19 randomised controlled trials involving 2,532 people with erythema migrans due to Lyme disease. No trials were based in the UK; most were from the United States or Europe.

Each trial compared two or three antibiotics. Doxycycline was the most frequently used antibiotic. A number of doses and treatment durations were represented. For example, treatment length for doxycycline ranged from 10 to 21 days. For the main analyses, doxycycline was used as the reference treatment.

Both direct and indirect data were extracted from the studies. This approach is helpful when there is a shortage of head to head research, but this, and the overall low quality of included studies means that results need to be treated with some caution.

What did it find?

  • Compared to doxycycline, there was no difference between the following antibiotics for treatment response by 12 months: penicillin V (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.12 to 2.55), azithromycin (OR 1.01, 95% CI 0.19 to 5.42), cefuroxime axetil (OR 1.17, 95% CI 0.66 to 2.09), amoxicillin (OR 1.26, 95% CI 0.41 to 3.87) or ceftriaxone plus doxycycline (OR 1.56, 95% CI 0.83 to 2.93).
  • More than 80% of patients showed a treatment response, 84% at two or fewer months after starting treatment and 80% at 12 or more months following treatment initiation. There was no available data on outcomes for around 15%.
  • There were few treatment failures in those people who were followed up – 4% by two months and 2% by 12 months.
  • Treatment-related adverse effects occurred in around 31% of people and included vomiting and diarrhoea as well as a Herxheimer-like reaction (a systemic reaction to endotoxin-like products released by the death of the bacteria). Only 1% experienced haematologic adverse events, such as low platelet counts.

What does current guidance say on this issue?

NICE guidance on Lyme disease states that those without focal symptoms (such as nervous system involvement) should receive 100mg oral doxycycline twice a day or 200mg once per day for 21 days. The first alternative to this is oral amoxicillin, 1g three times per day for 21 days and the second alternative is oral azithromycin, 500mg daily for 17 days.

What are the implications?

Most people with erythema migrans respond well to antibiotics, and there is no evidence from this study to change the guidelines about antibiotic use.

Citation and Funding

Torbahn G, Hofmann H, Rücker G et al. Efficacy and safety of antibiotic therapy in early cutaneous lyme borreliosis: a network meta-analysis. JAMA Dermatol. 2018;154(11):1292–1303.

This study was supported in part by funding from the German Dermatological Society and the German Paul- Ehrlich-Society to Drs Torbahn and Hofmann and from the German Society for Pediatric Infectious Diseases to Dr Torbahn.

Bibliography

NICE. Lyme disease. NG95. London: National Institute for Health and Care Excellence; 2018.

Public Health England. Lyme disease: resources and guidance. London: GOV.UK; updated 2018.

Expert commentary

Lyme disease generates much patient anxiety and consequently, pressure, on those managing such patients. Studies are required to develop evidence-based clinical guidelines to reduce inappropriate antibiotic use.

This comprehensive analysis examined data from studies on antibiotic therapy for erythema migrans, the most common and only clinically diagnostic sign of early Lyme disease.

Reassuringly, short duration treatments of first-line antibiotics (doxycycline/amoxicillin) were comparably effective for the vast majority of patients with little adverse reaction. High quality, large-scale clinical studies are still needed to identify smaller differences in treatment regimens and exclude drug-related safety issues.

Dr Sally Mavin & Dr Roger Evans, Scottish Lyme Disease and Tick-borne Infections Reference Laboratory (SLDTRL)

The commentators declare no conflicting interests