New Antimicrobial Combination for Patients with Babesiosis
Symptoms of Acute Illness in Subjects with Babesia Microti Infection*
Atovaquone plus azithromycin Clindamycin plus quinine Symptoms at start of therapy Percentage of subjects (N=40) Percentage of subjects (N=18) Fever 92 94 Fatigue 92 89 Sweats 80 89 Muscle aches 80 83 Headache 78 83 Chills 75 89 Anorexia 75 83 Neck stiffness 52 44 Emotional lability 52 44 Cough 50 50 Nausea 45 61 Joint pain 45 61 Sore throat 38 17 Vomiting 20 22 Conjunctivitis 12 6 Joint swelling 10 11 Splenomegaly 2 6
*--The mean (one standard deviation) number of symptoms at the start of therapy was 8.9 ± 3.2 in the atovaquone-plus-azithromycin group and 9.3 ± 2.8 in the clindamycin-plus-quinine group. The mean number of symptoms during therapy was 1.0 ± 0 in the atovaquone-plus-azithromycin group and 1.5 ± 0.8 in the clindamycin-plus-quinine group. Adapted with permission from Krause PJ, Lepore T, Sikand VK, Gadbaw J Jr, Burke G, Telford SR 3d, et al. Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med 2000;343:1456.
Babesiosis is a tick-borne illness caused by Babesia microti. The organism is transmitted by the same tick (Ixodes dammini, also known as Ixodes scapularis) that is the vector for Lyme disease and human granulocytic ehrlichiosis. Clinically, babesiosis is manifested by malaria-like symptoms including fever, fatigue, sweats, myalgias and headache (see accompanying table). The illness is enzootic in southern New England, southern New York, Wisconsin and Minnesota but has been reported in other parts of North America, Europe and Asia. The standard treatment regimen for babesiosis is clindamycin and quinine. Although effective, this treatment causes significant adverse reactions including gastroenteritis and tinnitus. Azithromycin and atovaquone represent an alternative combination that has been found effective in animal models of babesial infection. Krause and colleagues performed a prospective, nonblinded, randomized trial to compare the safety and efficacy of these two-drug regimens in adults with babesiosis.
Subjects with symptoms suggestive of babesiosis were enrolled at several clinical sites in New England. The diagnosis was confirmed by a variety of laboratory techniques, including microscopic examination of Giemsa-stained thin blood smears for the organism; attempted amplification of B. microti DNA by polymerase chain reaction (PCR) technique; and serologic testing for antibodies against B. microti. Serologic testing for Borrelia burgdorferi and Ehrlichia equi was also performed.
Research subjects who had positive serologic reactivity against B. microti antigen (at least a fourfold elevation in titers or a single antibody titer of greater than 1:1,024) plus a positive thin blood smear or positive PCR testing for babesia were randomized into the trial. Excluded were those with life-threatening complications of the disease such as shock, renal failure, congestive heart failure or disseminated intravascular coagulation. One treatment arm received atovaquone in a dosage of 750 mg every 12 hours plus azithromycin in a dosage of 500 mg on day 1 and then 250 mg daily. The second treatment arm received 650 mg of quinine plus 600 mg of clindamycin every eight hours. All treatment medications were given orally for seven days. Follow-up visits were at one and two weeks, and at months 1, 3 and 6 after completion of therapy. All subjects were then seen monthly until there was clinical and laboratory evidence of disease resolution.
Fifty-eight subjects were enrolled in the study; 40 received atovaquone and azithromycin, and 18 were treated with quinine and clindamycin. There were an almost equal number of men and women in the study, and the median age of participants was 55 years. Twenty-two percent receiving atovaquone and azithromycin and 17 percent receiving quinine and clindamycin were concurrently diagnosed with Lyme disease. By the end of three months, symptoms of babesiosis had fully resolved in 65 percent of participants in the atovaquone and azithromycin group and in 73 percent in the quinine and clindamycin group. There was no evidence of parasitemia in any participant by thin blood smear examination. However, 13 of 18 subjects (72 percent) in the quinine and clindamycin group reported symptoms of decreased hearing, vertigo, tinnitus and diarrhea. Six required discontinuation of treatment. In the atovaquone and azithromycin group, only six of 40 (15 percent) reported any adverse events that primarily included diarrhea and rash, with only one subject requiring discontinuation of therapy. Four of the 18 subjects in the quinine and clindamycin group required hospitalization because of worsening of symptoms, compared with no subjects in the azithromycin and atovaquone group.
The authors conclude that azithromycin with atovaquone is an effective and well-tolerated regimen for the treatment of babesiosis. Although it is more expensive than therapy with quinine and clindamycin, this combination should be considered the first-line choice for treatment of nonlife-threatening cases of babesiosis in adults because of its lower incidence of systemic side effects.
JEFFREY T. KIRCHNER, D.O.
Krause PJ, et al. Atovaquone and azithromycin for the treatment of babesiosis. N Engl J Med November 16, 2000;343:1454-8.
Copyright © 2001 by the American Academy of Family Physicians.
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