Unexpected antimicrobial effect of statins

Jerwood, S.; Cohen, Jonathan

doi:10.1093/jac/dkm496

Cited by 158 publications

(136 citation statements)

References 6 publications

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“…Taken together, the data suggest that the antibacterial activity of statins may be statin specific and/or strain/species specific or both. Simvastatin and atorvastatin generally appear to be more effective against S. aureus, S. pneumoniae, and enterococci than other statins (37)(38)(39)43), while three distinct simvastatin MICs were reported against S. aureus clinical isolates from the United Kingdom and Jordan as well as against typed reference strains (Table 1) (37,38,41,42). It is also noteworthy that, while the MICs of statins varied according to the statin and pathogen tested, the in vitro MICs ranged from circa 15 to 400 mg/liter, far exceeding the range of typical peak plasma concentrations of patients on oral statins, which generally range from circa 10 to 300 g/liter.…”

Section: Effects Of Statins On In Vitro Bacterial Growthmentioning

confidence: 95%

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: Effects Of Statins On In Vitro Bacterial Growthmentioning

confidence: 95%

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Hennessy

Adams

Reen

et al. 2016

Antimicrob Agents Chemother

104

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“…A laboratory study demonstrated a significant reduction of leukocyte counts in septic mice treated with atorvastatin compared to other statins and placebo. 12 Another laboratory study, on blood culture, showed an antimicrobial effect for simvastatin, 13 but not for fluvastatin, with a possible explanation related to the difference in origin of these two statins: fungal fermentation and chemical synthesis respectively.…”

Section: Introductionmentioning

confidence: 99%

Risk of pneumonia in patients taking statins: population-based nested case-control study

Vinogradova¹,

Coupland²,

Hippisley‐Cox³

2011

Br J Gen Pract

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“…Of note, aspirin does not have growth inhibitory or bactericidal activity at pharmacologically relevant concentrations and thus may be less likely to promote bacterial resistance as traditional antimicrobials do (Eisen et al, 2009). The same might apply for statins as well (Jerwood & Cohen, 2008). However, retrospective and observational studies are prone to multiple sources of bias that are unquantifiable and of indeterminate direction.…”

Section: Resultsmentioning

confidence: 99%

“…(Endo A., 1992). The antimicrobial effects of statins were rediscovered at a later time and it was noted that the minimum inhibitory concentration of simvastatin for S.aureus was much higher than the serum levels that can be achieved during routine treatment at recommended doses (Jerwood S. & Cohen J., 2008). Direct antimicrobial effects with potential clinical relevance have been postulated for HIV, CMV, HCV, Salmonella and yeast (Gupta et al, 2007) but are perhaps less relevant for dialysis catheter associated infection.…”

Section: Statinsmentioning

confidence: 99%

Nontraditional Anti - Infectious Agents in Hemodialysis

Sedlacek¹

2011

Progress in Hemodialysis - From Emergent Biotechnology to Clinical Practice

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Unexpected antimicrobial effect of statins

Cited by 158 publications

References 6 publications

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Risk of pneumonia in patients taking statins: population-based nested case-control study

Nontraditional Anti - Infectious Agents in Hemodialysis

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