In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.
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The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections. (+info)
Azithromycin in the treatment of Legionella pneumonia requiring hospitalization.
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Azithromycin is highly active against Legionella pneumophila and has been shown to be efficacious in animal models and in clinical studies of patients with legionnaires disease. This open, prospective, multicenter trial evaluated azithromycin for the treatment of legionnaires disease. Twenty-five hospitalized patients with community-acquired pneumonia and a positive result of a L. pneumophila serogroup 1 urinary antigen assay received monotherapy with intravenous azithromycin (500 mg/day) for 2-7 days, followed by oral azithromycin (1500 mg administered over the course of 3 or 5 days). The mean total duration of intravenous plus oral therapy was 7.92 days. The overall cure rate among clinically evaluable patients was 95% (20 of 21 patients) at 10-14 days after therapy and 96% (22 of 23 patients) at 4-6 weeks after therapy. The results of this study support previously reported data demonstrating that azithromycin is both safe and efficacious for the treatment of hospitalized patients with legionnaires disease. (+info)
Clinical and environmental distributions of Legionella strains in France are different.
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In France, the clinical distribution of Legionella species and serogroups does not correspond to their environmental distribution. Legionella pneumophila serogroup 1 is more prevalent among clinical isolates (95.4%) than in the environment (28.2%), whereas L. anisa is more frequent in the environment (13.8%) than in the clinical setting (0.8%). (+info)
In vitro activity of Ro 23-9424 against clinical isolates of Legionella species.
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Agar and broth microdilution MICs of Ro 23-9424 that inhibited 90% of 22 Legionella clinical isolates tested were 0.64 and 0.08 micrograms/ml, respectively; respective erythromycin values were 1.0 and 0.12 micrograms/ml. Ro 23-9424 (1 microgram/ml) was slightly more active than the same erythromycin concentration in a macrophage system, for both Legionella pneumophila strains studied. (+info)
A 3-year follow-up study of anti-Legionella antibodies in users of Japanese 24-hour hot water baths.
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Although it has been found that legionellae can exist in a 24-h hot water bath (24HHWB), which has been used recently in Japan, whether longer use of the 24HHWB causes legionellosis is unclear. The present longitudinal study was conducted in 2000 to investigate the 3-yr change in antibody titers in association with the continuous use, non-use, or canceling the use of the 24HHWB, and possible factors relating to the antibody changes. Ninety-two subjects (85 males and 7 females), who had had their anti-Legionella pneumophila (Lp) serum antibody titers measured in our initial study in 1997 and consented to blood sampling 3 yr later, were selected as subjects. There were no clinical cases who had experienced Legionnaires' disease or Pontiac fever during the 3 yr. The continuous users showed no significant changes in antibody titers within 3 yr, whereas the continuous non-users had a significant increase in antibody titers against the Lp serogroup (SG) 5 and 6. Eleven ex-users of the 24HHWB showed a significant decrease in antibody titers against Lp SG 6. The changes in the 24HHWB use, job sector, stress coping strategies, and alcohol-drinking habit were associated with the changes in antibody titers against Lp SG 1, 5 or 6. The anti-Lp antibodies were considered to be IgM dominant. In conclusion, this study indicates that 24HHWB use by healthy subjects does not tend to result in a higher onset risk of legionellosis, even if it is continuously used for 3 yr, although 24HHWB use is likely to induce production of antibodies against legionellae. (+info)
Legionella micdadei infection presenting as severe secretory diarrhea and a solitary pulmonary mass.
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Sixty percent of infections with non-pneumophila species of Legionella are caused by Legionella micdadei. Although diarrhea is a common symptom of legionellosis, including that due to L. micdadei infection, severe, life-threatening diarrhea is rare. We describe a patient with profound secretory diarrhea (secretion rate, up to 8 L/day) that was secondary to culture-proven L. micdadei pneumonia. In addition, a 3-cm pulmonary nodule was detected, which completely resolved after proper treatment for Legionella infection. Resolving pulmonary nodules have been previously reported in association with treatment of L. micdadei infections. (+info)
Legionella shakespearei sp. nov., isolated from cooling tower water.
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A Legionella-like organism (strain 214T [T = type strain]) was isolated from a cooling tower in Stratford-upon-Avon, England. This strain required L-cysteine and contained cellular branched-chain fatty acids that are typical of the genus Legionella. Strain 214T produced pink colonies on buffered charcoal-yeast extract agar. Ubiquinone Q-12 was the major quinone. Strain 214T was serologically distinct from other legionellae as determined by a slide agglutination test. The results of DNA hybridization studies showed that strain 214T (= ATCC 49655T) is a member of a new Legionella species, Legionella shakespearei. (+info)
Legionella infection risk from domestic hot water.
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We investigated Legionella and Pseudomonas contamination of hot water in a cross-sectional multicentric survey in Italy. Chemical parameters (hardness, free chlorine, and trace elements) were determined. Legionella spp. were detected in 33 (22.6%) and Pseudomonas spp. in 56 (38.4%) of 146 samples. Some factors associated with Legionella contamination were heater type, tank distance and capacity, water plant age, and mineral content. Pseudomonas presence was influenced by water source, hardness, free chlorine, and temperature. Legionella contamination was associated with a centralized heater, distance from the heater point >10 m, and a water plant >10 years old. Furthermore, zinc levels of <100 microg/L and copper levels of >50 microg/L appeared to be protective against Legionella colonization [corrected]. Legionella species and serogroups were differently distributed according to heater type, water temperature, and free chlorine, suggesting that Legionella strains may have a different sensibility and resistance to environmental factors and different ecologic niches. (+info)