Correspondence

Legionnaires' Disease

N Engl J Med 1998; 338:200-201January 15, 1998

Article

To the Editor:

In their review of legionnaires' disease (Sept. 4 issue),1 Stout and Yu list imipenem as efficacious, citing a review that I wrote. In my review I stated that there is evidence that this drug is not effective for the treatment of experimental Legionella pneumophila pneumonia in guinea pigs and that there is no reason to expect it to be effective in the treatment of human disease.2 The occasional apparent success of this therapy for legionnaires' disease may be fortuitous; imipenem should not be used to treat this disease. I also take exception to their suggested practice of doubling the first dose of azithromycin and levofloxacin. Data in humans show that both drugs appear to be effective for the treatment of legionnaires' disease without doubling the first dose.3-5 Lastly, the finding of a single antibody titer of 1:256 is nonspecific, and single antibody titers should be used only in epidemiologic studies, when serum samples from the acute phase of illness are unavailable.6

Paul H. Edelstein, M.D.
University of Pennsylvania Medical Center, Philadelphia, PA 19104-4283

6 References

1. 1

   Stout JE, Yu VL. Legionellosis. N Engl J Med 1997;337:682-687
   Full Text | Web of Science | Medline

2. 2

   Edelstein PH. Antimicrobial chemotherapy for legionnaires' disease: a review. Clin Infect Dis 1995;21:Suppl 3:S265-S276
   CrossRef | Web of Science | Medline

3. 3

   Kuzman I, Soldo I, Schonwald S, Culig J. Azithromycin for treatment of community acquired pneumonia caused by Legionella pneumophila: a retrospective study. Scand J Infect Dis 1995;27:503-505
   CrossRef | Web of Science | Medline

4. 4

   Myburgh J, Nagel GJ, Petschel E. The efficacy and tolerance of a three-day course of azithromycin in the treatment of community-acquired pneumonia. J Antimicrob Chemother 1993;31:Suppl E:163-169
   Web of Science | Medline

5. 5

   File TM Jr, Segreti J, Dunbar L, et al. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother 1997;41:1965-1972
   Web of Science | Medline

6. 6

   Plouffe JF, File TM Jr, Breiman RF, et al. Reevaluation of the definition of Legionnaires' disease: use of the urinary antigen assay. Clin Infect Dis 1995;20:1286-1291
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Dr. Edelstein claims that we listed imipenem as efficacious in the treatment of legionnaires' disease, but we did not list imipenem in our recommendations for antibiotic therapy, given in Table 2 of our article. Imipenem and several other antibiotics that were mentioned have been reported as efficacious in isolated cases. Since imipenem is often used empirically for severe infection, it is important for clinicians to know that legionnaires' disease cannot be ruled out because of a patient's response to imipenem. We did not list the numerous references on the efficacy of imipenem or the lack of it. We have seen one case of successful therapy with imipenem and one failure.

Dr. Edelstein disagrees with our suggestion of doubling the first dose of azithromycin and levofloxacin, antimicrobial agents that will be used not only for legionnaires' disease but also as empirical therapy for community-acquired pneumonia. Both drugs are effective at their recommended doses, and we have had success with both these antibiotics for legionnaires' disease. However, relatively few patients with severe pneumonia have been treated with these newer agents. We fear that in selected patients with unusually severe pneumonia, the once-daily dose of azithromycin and levofloxacin may be suboptimal, and there will be failures. It was the many failures with erythromycin in patients with legionnaires' disease that led us to recommend doubling the dose of erythromycin to 4 g daily, which most authorities have adopted. Given the safety of azithromycin and levofloxacin, doubling only the first dose should not lead to a notable increase in toxicity, and it may maximize efficacy early in the course of the disease, when therapy is most crucial.

Dr. Edelstein claims that a single antibody titer of 1:256 is nonspecific. This is incorrect: Dr. Edelstein confuses specificity and sensitivity with predictive value. As knowledge about legionnaires' disease has become more widespread, application of these criteria to a wider population has decreased the predictive value (not the specificity) of the test. When sputum samples are not available and empirical antibiotic therapy is initiated, elevated antibody titers have often been the only objective evidence of the presence of legionnaires' disease. In a prospective study, 27 percent of patients with legionnaires' disease had single elevated titers as high as 1:128.1 With respect to patients with pneumonia, our statement that a titer of 1:256 or greater may be suggestive of legionellosis is an understatement.

Victor L. Yu, M.D.
Janet E. Stout, Ph.D.
Veterans Affairs Medical Center, Pittsburgh, PA 15240

1 References

1. 1

   Zuravleff JJ, Yu VL, Shonnard JW, Davis BK, Rihs JD. Diagnosis of Legionnaires' disease: an update of laboratory methods with new emphasis on isolation by culture. JAMA 1983;250:1981-1985
   CrossRef | Web of Science | Medline

Citing Articles (2)

Citing Articles

1. 1

   K. Fragou, P. Kokkinos, C. Gogos, Y. Alamanos, A. Vantarakis. (2011) Prevalence of Legionella spp. in water systems of hospitals and hotels in South Western Greece. International Journal of Environmental Health Research1-15
   CrossRef

2. 2

   Christine Campese, Dounia Bitar, Sophie Jarraud, Catherine Maine, Françoise Forey, Jerome Etienne, Jean Claude Desenclos, Christine Saura, Didier Che. (2011) Progress in the surveillance and control of Legionella infection in France, 1998–2008. International Journal of Infectious Diseases 15:1, e30-e37
   CrossRef