Legionnaires' disease at a Dutch flower show: prognostic factors and impact of therapy - Research

Emerging Infectious Diseases, Dec, 2002 by Kamilla D. Lettinga, Annelies Verbon, Gerrit-Jan Weverling, Joop F.P. Schellekens, Jeroen W. Den Boer, Ed P.F. Yzerman, Jacobus Prins, Wim G. Boersma, Ruud J. van Ketel, Jan M. Prins, Peter Speelman

Of the 70 patients admitted before the nationwide alert on March 12, 44 (63%) were treated with adequate antibiotics with a median delay of 1.5 days (range 0-14 days). After the alert, antibiotics were changed to a macrolide or a fluoroquinolone for 21 patients, and 5 patients were never treated with adequate antibiotics (three of them died). All patients admitted after the alert received adequate therapy within a median of 0 days (range 0-3 days). Next, we studied the influence of immediate start of adequate treatment compared with delayed treatment on the outcome. Initiation of adequate therapy within 24 hours after admission resulted in a higher ICU-free survival rate compared with initiation after 24 hours: 78% versus 54% (Figure 2; log rank: p= 0.005). The difference in ICU-free survival was not explained by differences in severity of pneumonia in the two groups, since the percentage of patients with severe pneumonia in the group treated within 24 hours (31% severe Legionnaires' disease) did not significantly differ from the percentage in the group adequately treated after 24 hours (36% severe Legionnaires' disease; chi square: p=0.5).

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A Binax Now urinary antigen test with positive results can provide a diagnosis of Legionella pneumonia within 1 hour. This test was positive in 86/141 (61%), negative in 51/141 (36%) and not done in 4/141 (3%) of the patients. Table 3 shows the results of other diagnostic tests of patients with positive and negative urinary antigen test results. In 16 patients with negative urinary antigen test results, no other test had positive results, although the clinical and epidemiologic features strongly suggested Legionnaires' disease. Two of these patients were admitted to the ICU. Patients with negative urinary antigen test results had a higher ICU-free survival rate than patients with positive test results: 90% ICU-free survival compared with 58% of those with positive test results (Figure 3A; log rank: p=0.0001). No effect on outcome was found when initiation of adequate therapy was delayed in patients with a negative urinary antigen test (Figure 3B, 92% vs. 84% ICU-free survival; log rank: p= 0.46). In contrast, patients with positive urinary antigen test results in whom adequate therapy was started within 24 hours after admission had a higher ICU-free survival rate compared with patients in whom therapy was initiated after 24 hours (67% vs. 48%, Figure 3C; log rank: p= 0.09), resulting in a relative risk reduction of 38%. The proportion of patients with severe pneumonia was comparable for both groups of patients with a positive urinary antigen test (within 24 hours: 39%, after 24 hours, 45% severe Legionnaires' disease, chi square: p= 0.58).

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In addition, 36 (38%) of 95 patients with nonsevere Legionnaires' disease were treated with adequate antibiotic therapy >24 hours after admission; 13 of those patients (36%) had a poor outcome. In 10 (77%) of these patients, the urinary antigen test was positive for L. pneumophila, indicating that these patients should have been identified as high risk on admission.