Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease

Dournon, E; Mayaud, C; Wolff, Michel; Schlemmer, Benoı̂t; Samuel, Didier; Sollet, Jean-Pierre; Levasseur-Rajagopalan, P.

doi:10.1093/jac/26.suppl_b.129

Cited by 46 publications

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“…In the third, or cidal, group are some fluoroquinolone antimicrobial agents, such as pefloxacin or sparfloxacin, and azithromycin. There is solid data from experimental studies in animals and some less solid clinical evidence (only for pefloxacin) that these cidal drugs are more effective than those drugs in the strictly inhibitory group (2,3,12,14,24). There are no good data regarding the meaning of quantitative differences within these categories.…”

Section: Discussionmentioning

confidence: 99%

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species

Edelstein

1994

Antimicrob Agents Chemother

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The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90%o of strains tested were 2 and 1 ,ug/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 ,ug/ml, respectively, for the two LegioneUla pneumophila strains tested with piperacillin and were 0.25 and 0.5 ,ug/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 ,ug/ml), piperacillin (32 ,ug/ml), tazobactam alone (16 ,Ig/ml), clavulanate alone (2 ,ig/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 ,ug/ml) or piperacillin (32/4 ,ig/ml). Erythromycin (1 ,ug/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with f-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.Contrary to expectations, the ,-lactamase inhibitor clavulanic acid has been shown to be active against extracellular and intracellular Legionella pneumophila and in murine models of L. pneumophila infection (28, 33-36, 38, 39). This has led to the evaluation of the activities of other P-lactamase inhibitors against L. pneumophila. Recently, Collins and colleagues (1) reported that tazobactam, with or without piperacillin, is active against extracellular Legionella species. We tested tazobactam alone and in combination with either ceftriaxone or piperacillin to confirm the findings of Collins and colleagues and to determine whether these antimicrobial agents were active against intracellular L. pneumophila. The activity of clavulanic acid alone was also determined. We demonstrate that both tazobactam and clavulanic acid are active against extracellular, but not intracellular, L. pneumophila. MATERIALS AND METHODSBacteria and growth media. All legionellae studied were clinical isolates. These strains were identical to those used in prior studies and comprised 2 strains each of Legionella dumoffli, Legionella longbeachae, Legionella micdadei, 1 strain of Legionella bozemanii, and 15 strains of L. pneumophila (9,12

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Section: Discussionmentioning

confidence: 99%

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species

Edelstein

1994

Antimicrob Agents Chemother

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“…Two to fifteen percent of all hospitalizations for community-acquired pneumonias in Europe and North America are caused by Legionella and recent studies suggest that rates of legionellosis may be increasing [2]. The optimal antibiotic treatment of legionellosis has never been investigated in a randomized clinical trial, but most clinicians use either macrolides or fluoroquinolones [3,4] alone or combined with rifampicin [5]. …”

Section: Introductionmentioning

confidence: 99%

Clinical features and predictors of mortality in admitted patients with community- and hospital-acquired legionellosis: A Danish historical cohort study

et al. 2010

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BackgroundLegionella is a common cause of bacterial pneumonia. Community-acquired [CAL] and hospital-acquired legionellosis [HAL] may have different presentations and outcome. We aimed to compare clinical characteristics and examine predictors of mortality for CAL and HAL.MethodsWe identified hospitalized cases of legionellosis in 4 Danish counties from January 1995 to December 2005 using the Danish national surveillance system and databases at departments of clinical microbiology. Clinical and laboratory data were retrieved from medical records; vital status was obtained from the Danish Civil Registration System. We calculated 30- and 90-day case fatality rates and identified independent predictors of mortality using logistic regression analyses.ResultsWe included 272 cases of CAL and 60 cases of HAL. Signs and symptoms of HAL were less pronounced than for CAL and time from in-hospital symptoms to legionellosis diagnosis was shorter for CAL than for HAL (5.5 days vs. 12 days p < 0.001). Thirty-day case fatality was 12.9% for CAL and 33.3% for HAL; similarly 90-day case fatalities in the two groups were 15.8% and 55.0%, respectively. In a logistic regression analysis (excluding symptoms and laboratory tests) age >65 years (OR = 2.6, 95% CI: 1.1-5.9) and Charlson comorbidty index ≥2 (OR = 2.7, 95% CI: 1.1-6.5) were associated with an increased risk of death in CAL. We identified no statistically significant predictors of 30-day mortality in HAL.ConclusionsSigns and symptoms were less pronounced in HAL compared to CAL. Conversely, 30-day case fatality was almost 3 times higher. Clinical awareness is important for the timely diagnosis and treatment especially of HAL. There is a need for further studies of prognostic factors in order to improve the therapeutic approach to legionellosis and potentially reduce mortality.

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“…Dournon et al [6] retrospectively compared the efficacy of three antibiotic regimens in 60 patients with severe Legionella pneumonia, including nosocomial cases. The highest mortality rate (50%; 10/20) was reported with erythromycin and the lowest rate (28.6%; 2/7) was reported with pefloxacin.…”

Section: Discussionmentioning

confidence: 99%

Impact of rifampicin addition to clarithromycin in Legionella pneumophila pneumonia

Grau

Antonio

Ribes

et al. 2006

International Journal of Antimicrobial Agents

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Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease

Cited by 46 publications

References 0 publications

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species

Clinical features and predictors of mortality in admitted patients with community- and hospital-acquired legionellosis: A Danish historical cohort study

Impact of rifampicin addition to clarithromycin in Legionella pneumophila pneumonia

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