Is a 5 day course of azithromycin enough for infections caused by Legionella pneumophila?

A. J. Matute, C. A. M. Schurink and I. M. Hoepelman*

Division of Infectious Diseases and AIDS, Department of Internal Medicine, University Hospital Utrecht, The Netherlands

Sir,

In a recent editorial,1 5 day treatment with azithromycin was recommended for inpatients with legionnaires' disease. However, clinical experience with short-course therapy with azithromycin is limited.2 We describe here a patient with legionella infection who failed on a 5 day course of azithromycin. The patient, a 60-year-old woman, was hospitalized in May 1999 with a 2 day history of fever with neutropenia. The patient had had breast cancer diagnosed 10 years previously and had received radiotherapy after surgery, and chemotherapy with taxotere 10 days before admission. The patient had stayed in a French hotel for 1 week, until 2 days before admission.

On admission, the patient was acutely sick, with a temperature of 39°C, a pulse rate of 130 beats per min, respiration rate of 30 per min, and blood pressure of 90/70 mmHg. Examination of the lungs showed decreased breath sounds and decreased excursions of the lower part of the right side of the chest. Percussion showed dullness with absent tactile fremitus over the same area. The heart beat was fast and irregular but there were no murmurs. Laboratory findings included a haemoglobin of 6.7 g/dL and a white blood cell count of 0.7 x 109/L, with 4% band forms, 8% neutrophils, 32% monocytes and 4% basophils. Analysis of arterial blood gases revealed a pH of 7.45, PaCO2 of 24 mmHg and PaO2 of 60 mmHg. A chest X-ray showed a right pleural effusion and a left superior lobe infiltrate. An echocardiogram on the next day showed no pericardial effusion and a moderate decrease in left ventricular function. Severe community-acquired pneumonia was diagnosed.

Cultures of blood, sputum and pleural effusion were negative. A Binax legionella urinary antigen test was positive on the second day and a 10-fold increase in serum titre of IgG was found.

Therapy with ceftriaxone and erythromycin was started; 24 h after admission, iv erythromycin was stopped and the patient was switched to oral azithromycin tablets qd for 5 days (azithromycin iv is not available in The Netherlands). Ceftriaxone was discontinued on the fifth hospital day. The patient returned 10 days after receiving the last azithromycin tablet, with a recurrence of fever and dyspnoea but a normal peripheral white blood cell count and signs of pericarditis (confirmed by an echocardiogram). A presumptive diagnosis of relapse of legionella infection was made, urinary antigen was still positive and clarithromycin 500 mg bid was started and continued for 2 weeks. Within 72 h the patient was afebrile, sputum culture remained negative and no recurrence of symptoms was seen during 6 months' follow up.

Azithromycin is the first member of the azalide class of antimicrobial agents. It is now widely available for the treatment of infections in adults and children.3 We have shown that a 3 day course of azithromycin is efficacious for acute exacerbation of chronic bronchitis and lower respiratory bacterial infections.3,4 Infections caused by Legionella pneumophila are treated either with a quinolone or with a 2–3 week course of a macrolide, with or without rifampicin. Shorter treatment regimens have been recommended for azithromycin although experience is limited.1,2,5

In conclusion, we have described a case of a patient with severe community-acquired pneumonia due to a complicated form of legionnaires' disease which failed (relapsed) on a 5 day course of azithromycin (after 1 day of erythromycin iv), but was cured on a subsequent 14 day course of clarithromycin. It may be prudent, therefore, to prescribe azithromycin for longer (10 days) in complicated cases or in immunosuppressed patients, as has been recommended5 and also performed in a recent sponsored study.6

Notes

J Antimicrob Chemother 2000; 45: 930–931

* Correspondence address. Division of Infectious Diseases and AIDS, Room F.02.126, Department of Internal Medicine, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. Tel: +31-30-2506228; Fax: +31-30-2523741. Back

References

1 . Edelstein, P. H. (1998). Antimicrobial chemotherapy for Legionnaires' disease: Time for a change. Annals of Internal Medicine 129, 328–30.[Free Full Text]

2 . Hoepelman, I. M. (1996). Diagnosis of chemotherapy of Legionnaires' disease. Netherlands Journal of Medicine 49, 185–8.[ISI][Medline]

3 . Hoepelman, I. M. & Schneider, M. M. E. (1995). Azithromycin; the first of the tissue-selective azalides. International Journal of Antimicrobial Agents 5, 145–67.[ISI]

4 . Hoepelman, I. M., Mollers, M. J., van Schie, M. H., Greefhorst, A. P., Schlosser, N. J., Sinninghe, E. J. et al. (1997). A short (3-day) course of azithromycin tablets versus a 10-day course of amoxycillin–clavulanic acid (co-amoxiclav) in the treatment of adults with lower respiratory tract infections and effects on long-term outcome. International Journal of Antimicrobial Agents 9, 141–6.[ISI][Medline]

5 . Yu, V. L. & Vergis, E. N. (1998). New macrolides or new quinolones as monotherapy for patients with community-acquired pneumonia: our cup runneth over? Chest 5, 1158–9.

6 . Plouffe, J., Fields, B., Nicolle, L., Herbert, M., Sherman, B. & Inverso, J. (1999). Azithromycin (IV/PO) for treatment of Legionnaires disease. Thirty-Seventh Clinical Infectious Diseases 29, 986 (Abstract 141).