Antimicrobial agents for the treatment of tick-borne relapsing fever

	Antimicrobial agent	Duration	Comment
Patients without known CNS disease
Preferred regimen	Adults: Penicillin G (5 million units IV every six hours) or ceftriaxone (2 g IV daily or 1 g IV twice daily) Children: Penicillin G (50,000 to 100,000 units/kg IV every six hours, up to a maximum per dose of 5 million units) or ceftriaxone (50 to 75 mg/kg IV in a single dose, up to a maximum daily dose of 2 g)	10 days It is reasonable to switch to oral therapy when the patient is clinically stable*^¶	There is more clinical experience with penicillin compared with ceftriaxone. However, ceftriaxone may be preferable for empiric therapy, if other infections (eg, meningococcal infection) are being considered, or for ease of administration.
Alternative regimen	Doxycycline PO/IV twice daily^¶ A macrolide can be used for patients who cannot take a beta-lactam or doxycycline^Δ	10 days
Patients with CNS disease (eg, meningoencephalitis)^◊
Preferred regimen	Penicillin G or ceftriaxone intravenously at the doses described above	10 to 14 days IV therapy with a penicillin or ceftriaxone should be continued for the entire duration	Refer to comments above about choice of penicillin or ceftriaxone.
Alternative regimen	All efforts should be made to administer penicillin or ceftriaxone If the patient is unable to tolerate a penicillin or ceftriaxone, a tetracycline (eg, doxycycline) is preferred, since tetracyclines have good CNS penetration^¶	10 to 14 days
Patients with isolated Bell's palsy
Preferred regimen	Penicillin G or ceftriaxone intravenously at the doses described above	10 to 14 days It is reasonable to switch to an oral tetracycline (eg, doxycycline) when the patient is clinically stable^¶
Alternative regimen	Doxycycline PO/IV twice daily^¶	10 to 14 days
Pregnant women
Preferred regimen	Penicillin G or ceftriaxone intravenously at the doses described above	10 to 14 days IV therapy with a beta-lactam antibiotic should be continued for the entire duration	IV penicillin or ceftriaxone should be continued regardless of the presence of CNS disease, given the greater risk of mortality for the mother and fetus or neonate.
Alternative regimen	All efforts should be made to administer a beta-lactam antibiotic If the patient is unable to tolerate a beta-lactam, the choice of an alternative agent depends upon the risks of therapy^§	10 to 14 days

All patients being treated for TBRF should be observed for a Jarisch-Herxheimer reaction, which typically occurs within several hours of the first dose.

CNS: central nervous system; JHR: Jarisch-Herxheimer reaction; PO: orally; IV: intravenous; TBRF: tick-borne relapsing fever.
* If possible, we prefer to switch the patient to an oral tetracycline (eg, doxycycline), as oral tetracyclines have good CNS penetration. However, if there are contraindications to tetracyclines, an oral beta-lactam, such as penicillin or a third generation cephalosporin, can be used. We avoid amoxicillin due to conflicting data about the efficacy of this agent.
¶ The dose of doxycycline for adults is 100 mg twice daily. For children <45 kg, the dose of doxycycline is 2.2 mg/kg/dose (maximum dose: 100 mg/dose) every 12 hours. If doxycycline is not available, tetracycline (eg, 500 mg four times daily PO for adults) can be used for many nonpregnant patients. However, for nursing mothers and children <8 years old, a macrolide, such as erythromycin or azithromycin, may be preferred if doxycycline cannot be used. Although the risk of dental staining is very low for children when a short course of doxycycline is administered, the risk of toxicity appears greater if other tetracyclines are used, and the choice of agent must be determined on a case-by-case basis. Refer to the topic that discusses the management of relapsing fever for additional information on the treatment of children.
Δ There is most experience with erythromycin base (500 mg PO every six hours for adults; 12.5 mg/kg [maximum dose 500 mg] PO every six hours for children) as an alternative to tetracyclines; however, this agent is likely to produce adverse drug effects. A macrolide such as azithromycin is better tolerated and is likely to be as effective at doses used to treat other Borrelia infections (eg, 500 mg daily for adults; 10 mg/kg [maximum dose 500 mg per day] daily for children).
◊ Refer to the topic that discusses the clinical manifestations of relapsing fever for more information on neurologic signs and symptoms.
§ For pregnant women who are unable to tolerate a beta-lactam, the choice of an alternative agent depends upon the risks of therapy. Available data suggest that doxycycline has not been associated with serious adverse events. However, the risk appears greater if other tetracyclines are used, and if doxycycline is not available, a macrolide may be preferred, particularly in those without evidence of CNS disease. Refer to the topic that discusses management of relapsing fever for additional information on the treatment of pregnant women.

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Antimicrobial agents for the treatment of tick-borne relapsing fever