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| − | The Legionellaceae family includes over 40 acknowledged variety, but significantly less than half these cause disease in humans. The most generally pathogenic species is Legionella pneumophila, of which you will find 14 serogroups. L. pneumophilaaccounts for 3 months (and serogroups 1- 6 for 85%) of attacks. Other essential species include Legionella micdadei, Legionella bozemanii, Legionella dumoffii and Legionella longbeachae.The principal medical illness is pneumonia (Legionnairesa condition), even though L. pneumophila in addition has been implicated in instances of endocarditis and myocarditis, and in haemodialysis infections.
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| − | Treatment recommendations for Legionnairesa disease are largely centered on clinical experience of the first recognized outbreak in Philadelphia in 1976; in a review, patients treated with erythromycin or tetracycline had a 50% lower death rate compared with patients treated with I-lactams.1 Subsequently, erythromycin turned the treatment ofchoice. Now, a number of new antimicrobial brokers have appeared, but previously assessing their comparative effectiveness in therapy has proved difficult. No prospective controlled studies of treatment have now been done.
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| − | Review of the effectiveness and potential utility of antimicrobials against Legionellaspp. Is dependant on four methods. First, in-vitro susceptibility testing can be performed to display for active agents. Legionella spp. may be grown in either buffered yeast extract (BYE) broth or buffered charcoal- yeast extract (BCYE) agar, both supplemented with I -ketoglutarate. The MICs of an antibiotic may differ between these growth media. Several antimicrobials, including I-lactams, are extremely effective in vitro. But I -lactams don't penetrate the intracellular compartment and as legionellae are intracellular pathogens in vitro, extracellular susceptibility does not always correspond to in-vivo activity.
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| − | 2nd, M. pneumophila has been developed in vitroin lots of cell lines in order to measure the intracellular action of antimicrobials. The cells used have involved guinea pig alveolar macrophages, human monocytes or macrophages, HeLa and HL-60 cells. A good correlation is generally given by results obtained with this method with animal studies. One exception is gentamicin, that is active against bacteria grown in cell lines but inactive in animal models and human disease. A problem of the technique is that it's frustrating and expensive, while better programs are now being produced. 2
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| − | Next, guinea pigs produce severe pneumonia when L. pneumophilais introduced into their lower respiratory system by aerosol and so they may be used as an animal model to evaluate antimicrobials. Some studies also have used intraperitoneal disease in guinea pigs. Clinical efficacy in humans has corresponded to efficacy in the respiratory tract model.
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| − | Eventually, clinical studies have been tried but these have generally been case series and retrospective analyses. They suffer from being small studies, generally not controlling for severity of illness and usually concentrating on extreme hospitalized cases. This helps it be difficult to gauge the results with regard to mild, community-acquired cases. It has been determined that around 900 circumstances would be needed in each treatment arm of a test on community-acquired pneumonia to show a 50% reduction in mortality by use of an antimicrobial agent. 3 But, Legionnairesa disease isn't common, with c. 200 proved cases annually in England and Wales, 4 and there is usually a delay for making the diagnosis until after scientific treatment is finished. For these reasons a big, prospective controlled trial hasn't been performed and is unlikely to take place.
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| − | On the cornerstone of studies using these four practices the effectiveness of important classes of antimicrobials is reviewed below. Many studies have concentrated on L. pneumophila, but there's evidence that other Legionella spp. are equally vulnerable.
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| − | Between the macrolides most experience has been received with erythromycin. But, by in-vitro extracellular, assessment it's less active than clarithromycin, azithromycin and roxithromycin, though more active than dirithromycin and josamycin (Table). In certain comparative studies clarithromycin has been more active than azithromycin 5,,6 but generally azithromycin has been shown to be the more active. Within HL-60 cells azithromycin achieves the maximum inhibition of growth of L. pneumophila, followed so as of activity by erythromycin, roxithromycin, dirithromycin and clarithromycin. 7 Within guinea pig alveolar macrophages azithromycin prevents development of L. pneumophila better than erythromycin. 8 Azithromycin also exerts a effect in these alveolar macrophages: after azithromycin in high levels (5 mg/L) is beaten up, regrowth of M. pneumophila is restricted for an additional 5 days. In this model azithromycin is also bactericidal, although erythromycin is bacteriostatic.
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| − | In the guinea pig style of pneumonia mg/L is reached 13.4 by azithromycin concentrations in infected lung. 9 After 48 h of therapy the concentration of azithromycin within alveolar macrophages is 582 times the extracellular concentration and this is fivefold greater than the concentration of erythromycin. In M. pneumophila-infected guinea pigs the use of azithromycin, 3.6 mg/kg, leads to 100% survival although none survive with exactly the same dose of clarithromycin, a dosage of 28.8 mg/kg being required for clarithromycin to achieve 100% survival.10
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| − | Traditionally erythromycin, 2a'4 g/day, has been used to treat patients with Legionnairesa pneumonia. With these amounts, gastrointestinal unwanted effects are common and ototoxicity sometimes appears at the bigger amount in in regards to a quarter of patients. 11 Macrolides other than erythromycin aren't from the same frequency of negative effects. Short courses of erythromycin have been related to relapse and, therefore, 10a'14 days of treatment is preferred. Clinical studies evaluating erythromycin with other macrolides are few. Failed treatment was described by a single case report of a patient with severe Legionnairesa disease with erythromycin plus rifampicin and recovery only after intravenous azithromycin. 12 When azithromycin is employed from the outset in treating community-acquired legionellosis cure has been observed with a complete dose of 1.5 g given more than 3 or 5 days. 13 Other macrolides have proven clinically effective. 3
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| − | On the foundation of the available data, azithromycin would appear to function as the best macrolide, with good intracellular penetration, bactericidal activity, established clinical efficacy, short durations of treatment and a good safety profile. Moreover, the 15-membered lactone ring of azithromycin does not interact with cytochrome P450 3A isoenzymes, unlike the other, 14-membered macrolides. This reduces the possibility of drug interactions. Currently, antimicrobial resistance to azithroymcin, or indeed any macrolide, has not been a problem in clinical isolates of L. pneumophila.
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| − | When treating Legionnairesa condition, the option is first between macrolides and quinolones, and then between available, certified examples in each group, on the foundation of the above mentioned data. As time goes by other antimicrobials, such as streptogramins and ketolides, may be worthy of consideration.
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| − | Quinolones and macrolides have been compared in in and vitro vivo. Ciprofloxacin was more active than azithromycin, clarithromycin and erythromycin in some studies evaluating extracellular susceptibility 5,,6,8 however in another was less active than clarithromycin, while being more active than erythromycin and azithromycin. 29 In other reports levofloxacin and moxifloxacin were more active than erythromycin and roxithromycin, 32 and grepafloxacin and ofloxacin were much like clarithromycin. 31 Trovafloxacin 17 and levofloxacin 19 reduce bacterial counts of M. pneumophila within guinea pig alveolar macrophages more effectively than erythromycin. In HL-60 cells erythromycin was less effective at suppressing M. pneumophila growth than levofloxacin, ciprofloxacin and ofloxacin. 20
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| − | In a retrospective report on matched, extreme cases of Legionnairesa illness, requiring admission to intensive care, nothing of seven patients treated with pefloxacin alone died, although seven of 20 patients treated with erythromycin alone did. 25 Other clinical evaluations of quinolones and macrolides are derived from group of community-acquired pneumonia, within which some cases proved to be because of Legionella spp. The variety of people with legionella illness have already been modest, and drawing conclusions on relative effectiveness is difficult.
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| − | The overall picture to emerge from the above mentioned studies is that quinolones tend to be more active than macrolides. Nevertheless, if one specifically talks about newer quinolones, the best of the accessible macrolides, and azithromycin (ciprofloxacin, grepafloxacin, levofloxacin and ofloxacin are licensed in britain) there are no direct comparative studies. [http://www.xfire.com/blog/mdnacurnc/4612290 legionella management]
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