Practice guidelines for the treatment of Lyme disease

Tick bites and prophylaxis. The best currently available method for preventing infection with Borrelia burgdorferi is to avoid vector tick exposure. If exposure to Ixodes scapularis or Ixodes pacificus ticks is unavoidable, measures recommended to reduce the risk of infection include using both protective clothing and tick repellents, checking the entire body for ticks daily, and promptly removing attached ticks, before transmission of B. burgdorferi can occur (A-III [see tables 1 and 2 for recommendation categories, indicated in parentheses throughout this text]). Routine use of either antimicrobial prophylaxis (E-I) or serological tests (D-III) after a tick bite is not recommended. Some experts recommend antibiotic therapy for patients bitten by I. scapularis ticks that are estimated to have been attached for >48 h (on the basis of the degree of engorgement of the tick with blood), in conjunction with epidemiological information regarding the prevalence of tick-transmitted infection (C-III). However, accurate determinations of species of tick and degree of engorgement are not routinely possible, and data are insufficient to demonstrate efficacy of antimicrobial therapy in this setting. Persons who remove attached ticks should be monitored closely for signs and symptoms of tick-borne diseases for up to 30 days and specifically for the occurrence of a skin lesion at the site of the tick bite (which may suggest Lyme disease) or a temperature >38°C (which may suggest human granulocytic ehrlichiosis [HGE] or babesiosis). Persons who develop a skin lesion or other illness within 1 month after removing an attached tick should promptly seek medical attention for assessment of the possibility of having acquired a tick-borne disease (A-II). Health care practitioners, particularly those in areas where Lyme disease is endemic, should become familiar with its clinical manifestations, recommended practices for testing for it, and therapy for the disease, as well as for HGE and babesiosis (A-III). Testing of ticks for tick-borne infectious organisms is not recommended, except in research studies (D-III). Prior vaccination with the recently licensed recombinant outer-surface protein A (OspA) vaccine preparation reduces the risk of developing Lyme disease associated with tick bites but should not alter the above recommendations (A-I). Early Lyme disease. Administration of doxycycline (100 mg twice daily) or amoxicillin (500 mg 3 times daily) for 14-21 days is recommended for treatment of early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of neurological involvement or third-degree atrioventricular heart block (A-I). In prospective studies, these agents have been shown to be effective in treating erythema migrans and associated symptoms. Doxycycline has the advantage of being efficacious for treatment of HGE, which may occur simultaneously with early Lyme disease. Doxycycline is relatively contraindicated during pregnancy or lactation and for children aged <8 years. Because of its higher cost, cefuroxime axetil (500 mg orally twice daily), which is as effective as doxycycline in the treatment of erythema migrans (A-I), should be reserved as an alternative agent for those patients who can take neither doxycycline nor amoxicillin. For children, we recommend amoxicillin at a dosage of 50 mg/kg/d, divided into 3 doses per day (maximum, 500 mg/dose), or doxycycline (for those aged ≥8 years) at a dosage of 1-2 mg/kg twice per day (maximum, 100 mg/dose) (B-II). Cefuroxime axetil, at a dosage of 30 mg/kg/d, divided into 2 doses daily (maximum, 500 mg/dose), is an acceptable alternative agent (B-III). Macrolide antibiotics are not recommended as first-line therapy for early Lyme disease (E-I). When used, they should be reserved for patients who are intolerant of amoxicillin, doxycycline, and cefuroxime axetil. Possible regimens for adults are as follows: azithromycin, 500 mg orally daily for 7-10 days; erythromycin, 500 mg orally 4 times daily for 14-21 days; and clarithromycin, 500 mg orally twice daily for 14-21 days. Possible dosages for children are the following: azithromycin, 10 mg/kg/d (maximum, 500 mg/d); erythromycin, 12.5 mg/kg 4 times daily (maximum, 500 mg/dose); and clarithromycin, 7.5 mg/kg twice daily (maximum, 500 mg/dose). Patients treated with macrolides should be closely followed. Ceftriaxone (2 g iv daily), although effective, is not superior to oral agents and is not recommended as a first-line agent for treatment of Lyme disease in the absence of neurological involvement or third-degree atrioventricular heart block (E-I). The use of ceftriaxone (2 g once daily iv for 14-28 days) in early Lyme disease is recommended for acute neurological disease manifested by meningitis or radiculopathy (B-II). Intravenous penicillin G at a dosage of 18-24 million units daily, divided into doses given every 4 h (for patients with normal renal function), may be a satisfactory alternative (B-II). Cefotaxime (2 g iv every 8 h) may also be a satisfactory alternative (B-II). For adult patients who are intolerant of both penicillin and cephalosporins, doxycycline (200-400 mg/d) in 2 divided doses given orally (or iv if the patient is unable to take oral medications) for 14-28 days may be adequate (B-II). For children, we recommend ceftriaxone (75-100 mg/kg/d) in a single daily iv dose (maximum, 2 g) (B-II) or cefotaxime (150-200 mg/kg/d) divided into 3 or 4 iv doses (maximum, 6 g/d) (B-III) for 14-28 days. An alternative is iv penicillin G (200,000-400,000 units/kg/d; maximum, 18-24 million units/d) divided into doses given every 4 h for those with normal renal function (B-II). Patients with first- or second-degree atrioventricular heart block associated with early Lyme disease should be treated with the same antimicrobial regimens as patients with erythema migrans without carditis (see paragraphs 1 and 2 of the recommendations in this section, above) (B-III). We recommend that patients with third-degree atrioventricular heart block be treated with parenteral antibiotics such as ceftriaxone (see paragraphs 5 and 6 of the recommendations in this section, above) in the hospital, although there are no clinical trials to support this recommendation (B-III). A temporary pacemaker may also be required. Although antibiotic treatment does not hasten the resolution of seventh-cranial-nerve palsy associated with B. burgdorferi infection, antibiotics should be given to prevent further sequelae (B-II). There was disagreement among panel members on the neurological evaluation of patients with seventh-cranial-nerve palsy. Some members perform a CSF examination on all patients with seventh-cranial-nerve palsy, whereas others reserve lumbar puncture for patients for whom there is strong clinical suspicion of CNS involvement (e.g., severe headache or nuchal rigidity). Patients whose CSF examinations yield normal findings may be treated with the same regimens used for patients with erythema migrans (B-III), whereas patients for whom there is clinical and laboratory evidence of CNS involvement should be treated with regimens effective against meningitis (see paragraphs 5 and 6 of the recommendations in this section, above) (B-II). Treatment for pregnant patients can be identical to that for nonpregnant patients with the same disease manifestation, except that tetracyclines should be avoided (B-III). Lyme arthritis. Lyme arthritis usually can be treated successfully with antimicrobial agents administered orally or intravenously. Administration of doxycycline (100 mg twice daily orally) or amoxicillin (500 mg 3 times daily), in each instance for 28 days, is recommended for patients without clinically evident neurological disease (B-II). For children, we recommend administration of doxycycline (1-2 mg/kg twice per day; maximum, 100 mg/dose), which can be given to patients aged ≥8 years, or amoxicillin (50 mg/kg/d, divided into 3 doses per day; maximum, 500 mg/dose) for 28 days (B-II). Oral therapy is easier to administer than iv antibiotics, is associated with fewer serious complications, and is considerably less expensive. Its disadvantage is that some patients treated with oral agents have subsequently manifested overt neuroborreliosis, which may require iv therapy for successful treatment. Further controlled trials are needed to compare oral with iv therapy. Neurological evaluation, including lumbar puncture, should be done for patients if there is a strong clinical suspicion of neurological involvement, Patients with both arthritis and objective evidence of neurological disease should receive iv ceftriaxone (2 g once daily for 14-28 days) (A-II). Alternative therapies include iv cefotaxime (2 g iv every 8 h) (B-III) or iv penicillin G (18-24 million units daily, divided into doses given every 4 h for patients with normal renal function) (B-lI). Because of low blood levels, the long-acting benzathine preparation of penicillin is not recommended (D-III). For children, we recommend administration of ceftriaxone (75-100 mg/kg/d in a single daily iv dose; maximum, 2 g) (B-III) or cefotaxime (150-200 mg/kg/d divided into 3 or 4 iv doses; maximum, 6 g/d) (B-III) for 14-28 days. An alternative is iv penicillin G (200,000-400,000 units/kg/d; maximum, 18-24 million units/d), divided into doses given every 4 h for those with normal renal function (B-III).