Correspondence

Treatment of Presumed Cerebral Toxoplasmosis with Azithromycin

N Engl J Med 1994; 330:575-576February 24, 1994

Article

To the Editor:

A 28-year-old man with AIDS was hospitalized because of nausea, vomiting, and dizziness. Human immunodeficiency virus (HIV) infection had been diagnosed in 1991. He had had several opportunistic infections, and a recent CD4 cell count was 27 per cubic millimeter. He had a new left-sided hemiataxia. Magnetic resonance imaging (MRI) with contrast medium revealed a 1-cm-by-1.5-cm ring-enhancing lesion in the left middle cerebellar peduncle, associated with moderate edema (Figure 1AFigure 1MRI Scans of a Cerebellar Lesion in a Patient with AIDS and Toxoplasmosis, at the Time of Hospitalization (Panel A) and after Six Weeks of Azithromycin Therapy (Panel B).). IgG serologic testing for toxoplasma had previously been reactive.

Because of a documented severe allergy to sulfa drugs, the patient was treated with clindamycin, pyrimethamine, and folinic acid for presumed cerebral toxoplasmosis. Corticosteroids were avoided, although infusions of mannitol were given. One week later, a severe maculopapular eruption prompted the discontinuation of therapy for toxoplasmosis, and the rash subsequently improved. After a loading dose of 1500 mg, oral monotherapy with azithromycin (1000 mg daily) was begun.

A second MRI after three weeks was markedly improved. After six weeks of therapy, a third MRI showed nearly complete resolution of the cerebellar lesion (Figure 1B). The patient was clinically much improved and began maintenance therapy at 500 mg of azithromycin daily. A final scan after six months of therapy showed no recurrence.

In vitro studies and studies in animals using azithromycin demonstrate activity against several stages of Toxoplasma gondii, including the cyst form1-3. Concentrations of the drug in brain tissue are nearly 10 times those in serum after oral dosing3. Oral administration of azithromycin protected 100 percent of mice against intraperitoneal infection with T. gondii and 80 percent against intracerebral infection2. Pyrimethamine or sulfadiazine appears to be synergistic with azithromycin in experimental murine toxoplasmosis4.

There are few reports of the treatment of cerebral toxoplasmosis with azithromycin5,6. One patient was treated successfully with the drug (150 mg daily) in conjunction with clindamycin and doxycycline,6 whereas in two others treatment with 500 mg per day of azithromycin alone was unsuccessful5. The AIDS Clinical Trials Group (ACTG) is currently evaluating a lactose-free preparation of azithromycin plus pyrimethamine as therapy for toxoplasmosis (ACTG protocol 156). Preliminary results indicate that generally favorable initial responses are followed by a high incidence of relapse, although some patients had sustained responses (Hafner R, National Institute of Allergy and Infectious Diseases: personal communication).

The substantial intolerance to conventional therapy for toxoplasmosis underscores the need for alternatives. Although it is potentially encouraging, the case we report may not represent the typical response of toxoplasmosis to macrolide therapy. If azithromycin is to have a role in the prevention or treatment of this disease, more studies are needed to determine the most appropriate patients, the best drug formulation, the optimal dosing regimen, and the usefulness of additional agents.

Eliot W. Godofsky, M.D.
Polyclinic Medical Center, Harrisburg, PA 17110

6 References

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   Huskinson-Mark J, Araujo FG, Remington JS. Evaluation of the effect of drugs on the cyst form of Toxoplasma gondii. J Infect Dis 1991;164:170-171
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   Araujo FG, Guptill DR, Remington JS. Azithromycin, a macrolide antibiotic with potent activity against Toxoplasma gondii. Antimicrob Agents Chemother 1988;32:755-757
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   Araujo FG, Shepard RM, Remington JS. In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii. Eur J Clin Microbiol Infect Dis 1991;10:519-524
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   Derouin F, Almadany R, Chau F, Rouveix B, Pocidalo JJ. Synergistic activity of azithromycin and pyrimethamine or sulfadiazine in acute experimental toxoplasmosis. Antimicrob Agents Chemother 1992;36:997-1001
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   Wynn RF, Leen CLS, Brettle RP. Azithromycin for cerebral toxoplasmosis in AIDS. Lancet 1993;341:243-244
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   Farthing C, Rendel M, Currie B, Seidlin M. Azithromycin for cerebral toxoplasmosis. Lancet 1992;339:437-438
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   Chunmei Jin, Suk-Yul Jung, Sung Yeon Kim, Hyun-Ok Song, Hyun Park. (2012) Simple and efficient model systems of screening anti- Toxoplasma drugs in vitro. Expert Opinion on Drug Discovery1-11
   CrossRef

2. 2

   Lindsay S. Alger. (1997) TOXOPLASMOSIS AND PARVOVIRUS B19. Infectious Disease Clinics of North America 11:1, 55-75
   CrossRef