According to FAIR Health, Lyme disease diagnoses have increased significantly in the U.S from 2016 to 2021, reporting a 60% increase within rural areas and 19% increase within urban areas. If a patient seeks medical care for a suspected tickborne disease, treatment with antibiotics should be initiated as soon as possible. For patients with early localized disease, the treatment is Doxycycline 100mg tablets twice a day for 10 days. However, depending on symptoms and days after exposure, prophylactic treatment with Doxycycline 200mg x 1 dose may be initiated if the tick had been attached for more than 36 hours and it has been less than 72 hours since removal. 

In this 2014 experimental study, researchers sought out to determine if prophylactic application of Azithromycin cream would have similar efficacy to a topical Doxycycline cream. They also wanted to determine if the timing of applying the cream post-removal of the tick influenced the drug’s efficacy and if the cream will have both a systemic and transdermal effect. This study was performed in the lab setting with female Nymphal I. Scapularis ticks collected from New Jersey and Connecticut. The mice used were 4 weeks of age and bought from the Charles River Laboratories in Massachusetts. The Nymphal I. Scapularis ticks were infected with a strain of B.burgdorferi, and then the ticks were allowed to feed on the mice for about 72 hours before being removed. A PCR assay was used to confirm positively infected ticks; any PCR-negative ticks were removed from the study. Borrelia culturing and Xenodiagnoses were used to determine infection patterns in the mice. 

There was a total of 4 groups being studied: mice treated with 4% Azithromycin cream vs cream without an antibiotic, and mice treated with 4% Doxycycline cream vs cream without an antibiotic. The experiment was conducted in 2 phases. In the first phase, the researchers wanted to directly compare the protective effect of Azithromycin cream compared to Doxycycline cream. Either Azithromycin, Doxycycline, or a no antibiotic containing cream was immediately applied after the tick was removed. The second phase of the experiment was dedicated to determining if Azithromycin cream would only be effective if applied directly onto the site of the tick bite or if it had any benefit if applied to a distal site, as well as if ingestion of the cream provided any protection.

Results of phase 1 showed that none of the 12 mice (100% protection) who received Azithromycin cream developed spirochetal infection, compared to the 11/12 mice (8% protection) who developed spirochetal infection with the Doxycycline cream and 11/11 mice who were in the control group. The researchers also found that Azithromycin cream provided the mouse with 100% protection up until 3 days after first noticing the tick and removing it. Protection dropped to 74% after 3 days but remained at that efficacy at 2 weeks. 

Results of the second phase showed that among the mice that were allowed to groom themselves (ingesting some of the cream), no spirochetes were found whether the cream was placed at the tick bite site or at a distal site. Among the mice who couldn’t groom themselves (not ingesting any of the cream), 1/18 tested spirochete-positive when the cream was applied at the bite site (92% protection) and 0/12 mice test spirochete-positive when the cream was applied to a distal site (100% protective). None of the mice who were protected against spirochete infection seroconvert, which was confirmed through xenodiagnoses on the 10^th day post-tick removal. 

Overall, the study found that Azithromycin has the potential to be an effective prophylaxis against Lyme disease spirochete infection in the cream form. Results showed that it provides 100% protection if applied in the first 3 days following tick removal, and then 74% in the following 2 weeks. This can be very beneficial among individuals who cannot tolerate oral antibiotics and among residents who live in regions where Lyme disease incidence is high, and they may not have immediate access to a provider to get a prescription for Doxycycline. Residents will be able to self-apply a small amount of this cream immediately after removing a tick. Future experimental studies need to be performed on larger hosts to determine if the transdermal effects will be adequate for protection.  

Sources:

• Piesman, Joseph et al. “Efficacy of an experimental azithromycin cream for prophylaxis of tick-transmitted lyme disease spirochete infection in a murine model.” Antimicrobial agents and chemotherapy vol. 58,1 (2014): 348-51. doi:10.1128/AAC.01932-13
• https://www.cdc.gov/lyme/resources/FS-Guidance-for-Clinicians-Patients-after-TickBite-508.pdf
• https://s3.amazonaws.com/media2.fairhealth.org/infographic/asset/Lyme%20Disease%20Infographic%20-%20Final.pdf
• https://www.fda.gov/consumers/consumer-updates/ticks-and-lyme-disease-symptoms-treatment-and-prevention