The impact of prior long-term versus short-term statin use on the mortality of bacteraemic patients

Nseir, William; Mograbi, Julnar; Abu-Elheja, O.; Bishara, Jihad; Assy, Nimer

doi:10.1007/s15010-011-0190-9

Cited by 29 publications

(42 citation statements)

References 34 publications

(32 reference statements)

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“…These reviews included studies on infections such as bacteremia, pneumonia, sepsis, and some acute infections, and the patient populations received several different statins. For instance, two single-center retrospective studies showed that patients with bacteremia who had undergone prior statin treatment have significantly decreased risks of in-hospital mortality of 6% versus 28% (P ϭ 0.002) and 13% versus 24% (P ϭ 0.001), respectively (14,15). The latter study also showed that there was an inverse correlation between the duration of statin treatment and the risk of mortality in comparisons of statin use Ն12 and Ͻ12 weeks prior to infection (11% versus 14%, P ϭ 0.04) (15).…”

Section: Clinical Evidence That Statins Influence Morbidity and Mortamentioning

confidence: 99%

“…For instance, two single-center retrospective studies showed that patients with bacteremia who had undergone prior statin treatment have significantly decreased risks of in-hospital mortality of 6% versus 28% (P ϭ 0.002) and 13% versus 24% (P ϭ 0.001), respectively (14,15). The latter study also showed that there was an inverse correlation between the duration of statin treatment and the risk of mortality in comparisons of statin use Ն12 and Ͻ12 weeks prior to infection (11% versus 14%, P ϭ 0.04) (15). A meta-analysis of available published data found that the use of statins was specifically associated with a reduced risk of morbidity and mortality resulting from pneumonia (12).…”

Section: Clinical Evidence That Statins Influence Morbidity and Mortamentioning

confidence: 99%

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Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

104

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bStatins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents. O ne of the major undisputed clinical breakthroughs of the 20th century was the discovery of the statin family of drugs. These compounds are renowned for their ability to lower cholesterol levels and are used to treat approximately 40 million individuals with high cholesterol levels worldwide. Since the discovery of mevastatin as a metabolic product of Penicillium citrinum in 1976 (1, 2), a total of nine statins have been characterized, seven of which are approved by the FDA to treat patients with high cholesterol. Structurally, statins are characterized by the presence of a conserved lactone ring (3). This structure is present as a hydrolyzed (active) form in all statins except for mevastatin, lovastatin, and simvastatin; in those statins, the lactone ring is hydrolyzed in the liver (4). Statins can be divided into two broad classes (Fig. 1). Type 1 statins are lipophilic and possess a butyryl side chain-they are said to structurally resemble mevastatin (3). Lovastatin, pravastatin, and simvastatin are type 1 statins. Type 2 statins are classically lipophobic and are distinguished from type 1 by the replacement of the butyryl side chain with a fluorophenol group and typically possess larger side chains than type 1 statins (3). Atorvastatin, cerivastatin, fluvastatin, pitavastatin, and rosuvastatin are type 2 statins.Statins exert their cholesterol-lowering effect by binding to the active site of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR), a rate-limiting enzyme involved in cholesterol biosynthesis (3). HMGR is an integral part of the mevalonate pathway, which not only is essential for cholesterol biosynthesis but also contributes to the production of isoprenoids, lipid compounds that are essential for cell signaling and structure. As well as inhibition of cholesterol, statins have also been found to have a number of cholesterol-independent, socalled "pleiotropic" effects. Statins have been reported to confer anti-inflammatory, immunomodulatory, and anticancer effects on host cells, and these effects are well characterized (5-9). Furthermore, several studies have explored the pleiotropic effects of statins in combating multisystem microbial infections, such as sepsis and pneumonia, and a growing number of studies are demonstrating that statins can directly influence the growth and virulence of bacterial pathogens. With the global increase in antibiotic resistance to existing antib...

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Section: Clinical Evidence That Statins Influence Morbidity and Mortamentioning

confidence: 99%

Section: Clinical Evidence That Statins Influence Morbidity and Mortamentioning

confidence: 99%

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

104

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“…Alguns estudos descrevem prováveis efeitos positivos da terapia com estatinas no quadro inflamatório da sepse [27][28][29][30][31] . O efeito das estatinas na progressão da sepse com administração imediata e contínua somente após a internação foi investigado em dois estudos 27,30 , nos quais foram selecionados pacientes sép-ticos para receber o medicamento durante o período de internação e seus efeitos foram comparados ao do grupo placebo.…”

Section: Resultsunclassified

“…Desta forma, a relevância da redução dos níveis de citocinas exercendo um efeito protetor na sepse e apresentando um possível benefício clínico ainda permanece inconclusivo. Esses ensaios clínicos controlados se basearam em evidências advindas de estudos retrospectivos e prospectivos observacionais anteriores, demonstrando que pacientes em tratamento com estatina pré e pós-hospitalização tiveram melhores resultados nas taxas de progressão da sepse e sobrevida quando comparados a outros grupos 29,31 . Donnino et al 31 , em estudo retrospectivo, investigaram a associação entre a terapia com estatinas e a taxa de mortalidade em pacientes internados com suspeita de infecção.…”

Section: Resultsunclassified

“…Os resultados positivos encontrados nos estudos com relação ao uso contínuo ou não da estatina pré e pós-internação, incentivaram Nseir et al 29 a irem mais além e investigarem se haveria diferenças significativas relacionadas ao tempo prévio de uso do medicamento. Assim, realizaram estudo clínico e epidemiológi-co com objetivo de avaliar a taxa de mortalidade entre pacientes sépticos em tratamento com estatina em longo e em curto prazo antes da hospitalização.…”

Section: Resultsunclassified

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Efeitos pleiotrópicos das estatinas na sepse

et al. 2014

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Artigo DE rEViSÃo rESumoO objetivo do presente estudo foi revisar os efeitos da terapia com estatinas em pacientes com quadro de sepse. Foi realizada uma busca bibliográfica de artigos na base de dados MEDLINE/PubMed, SciELO e LILACS, no período de publicação delimitado entre 2009 e 2013. Foram incluídos artigos referentes a ensaios clínicos randomizados controlados e estudos de coorte observacionais clínicos. Foram encontrados diversos estudos clínicos e observacionais que investigaram o efeito do uso de estatinas em infecções e em sepse, tanto de uso contínuo pré-hospitalar (com ou sem interrupção durante internação) ou com início imediato pós-internação. Alguns estudos descrevem prováveis efeitos positivos e benéficos da terapia com estatinas no quadro de sepse, dentre eles a melhora dos parâmetros inflamatórios e da taxa de mortalidade, porém, esses resultados não se sustentam quando são aplicados métodos estatísticos que levam em conta diferentes variáveis, tais como idade, sexo, comorbidades e gravidade da doença. Até o momento nenhum estudo demonstrou evidências sólidas e significativas quanto à redução de mortalidade e morbidade no quadro séptico associado ao uso de estatinas, indicando que seu efeito benéfico e protetor ainda não foi plenamente delimitado, sendo necessários mais estudos que confirmem os resultados até agora encontrados.Palavras-chave: sepse; anticolesterolemiantes; choque séptico; hidroximetilglutaril CoA redutases; inflamação. AbStrActThe objective of this study was to review the effects of statin therapy in patients with signs of sepsis. A bibliographic search of articles published between 2009-2013 was performed in the MEDLINE/PubMed, SciELO and LILACS databases. Randomized controlled trials and observational clinical cohort studies were included. The results show that several clinical and observational studies have investigated the effect of statin in infection and sepsis, both pre-hospital continuous use (with or without interruption during hospitalization) or starting immediately post-hospitalization. Some studies describe positive and beneficial effects of statin therapy in the context of sepsis, including improvement on inflammatory parameters and mortality rates. However, these results do not hold on when statistic methods, which take into account different variables such as age, sex, comorbidities and severity disease, are applied. To date, no study has demonstrated strong and significant evidence regarding the reduction of morbidity and mortality in sepsis associated with the use of statin. This indicates that beneficial and protective effects have not been fully defined yet. More researches are required to confirm the results found so far.

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The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients

Atamna

Yahav

Eliakim‐Raz

et al. 2016

Eur J Clin Microbiol Infect Dis

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• Clostridium difficile is the most common cause of infectious nosocomial diarrhea among hospitalized adult patients in the developed countries. • There is an increasing morbidity and mortality of CDI patients due to the emergence of new strains of high virulence. • Recent studies demonstrated that prior statin use has protective and ameliorating effects on morbidity and mortality among CDI patients. • Our study showed that concomitant statin use has no significant impact on short-term mortality, CDI severity and its complications.

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The impact of prior long-term versus short-term statin use on the mortality of bacteraemic patients

Abstract: Statins reduce the 30-day in-hospital all-cause mortality of bacteraemic patients. Long-term statin use prior to the bacteraemia improves the survival of bacteraemic patients more than short-term statin use.

Cited by 29 publications

References 34 publications

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Efeitos pleiotrópicos das estatinas na sepse

The effect of statins on the outcome of Clostridium difficile infection in hospitalized patients

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