Statin Use and the Risk of C. Difficile
Statin Use and the Risk of C. Difficile
Objectives To estimate the possible relationship between statin use and the risk of healthcare facility onset Clostridium difficile.
Methods Patients over 18 years of age admitted to hospitals contributing data to the University HealthSystem Consortium between 2002 and 2009 were eligible. Patients with the ICD-9-CM code 008.45 who received a minimum 3-day course of either metronidazole or oral vancomycin on/after day 5 of admission were considered incident cases of C difficile infection. 31 472 incident cases of C difficile infection were identified and matched to five controls, on hospital, year/quarter of admission date, and age ±10 years (N=78 096). Patients who were administered one drug in the statin class (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) before the index date were considered to be exposed. Conditional logistic regression modelling provided adjusted odds ratios and 95% CI.
Results Compared with non-users, users of any drug within the statin class were 0.78 times less likely to develop C difficile infection in the hospital (95% CI 0.75 to 0.81) adjusting for potential confounders. Differences in estimates for specific statins were minimal. Niacin, fibrates and selective cholesterol absorption inhibitors showed no association with the risk of C difficile infection.
Conclusions Our data were consistent with a growing body of literature demonstrating a reduced risk of infections with statin use. Statins' pleiotropic properties may provide protection against C difficile infection.
Clostridium difficile is a spore-forming, anaerobic, Gram-positive bacterium that is thought to be responsible for approximately 20% of cases of hospital-acquired diarrhoea. Recent estimates indicate more than 250 000 hospitalisations associated with C difficile infection, which appears to be increasing. In the USA, mortality rates due to C difficile infection have also increased, very likely caused by a new more virulent strain of C difficile. The cost of managing C difficile infection is not trivial, exceeding US$3.2 billion.
In addition to age and disease severity, risk factors for C difficile infection include the use of antibiotics and gastric acid suppressants. The relationship between statin use and healthcare facility (HCF) onset C difficile infection has previously been hypothesised; however, this relationship has not previously been explored. In general, statins have been associated with a reduced risk of infections. The prophylactic nature of statins in these infections is possibly due to the myriad of pleiotropic effects of these drugs. There is a biological basis for belief in these effects, stemming from mechanisms involving immunomodulatory and cell signalling pathways. Briefly, statins are hypothesised to reduce inflammation in endothelial cells. The reduced inflammation could either reduce the risk of acquiring C difficile infection, or reduce the severity of C difficile infection. Other epidemiological studies have previously found a reduced risk of C difficile infection in patients taking statins.
In the USA, statin use has increased significantly, with 24 million Americans (35.9% of those with high low-density lipoprotein cholesterol levels) taking statins in 2003–4 compared with 12.5 million (19.6% of those with high low-density lipoprotein cholesterol levels) taking statins in 1999–2000. As a result of the increase in the prevalence of statin use, it is especially important to understand what other effects may be perpetuated beyond their intended cholesterol-lowering purpose. The extent and magnitude of the pleiotropic nature of statins in infections is just beginning to come into focus. Therefore, evaluating the indirect effects of statins in conjunction with specific infections, such as C difficile infection, is warranted.
The purpose of this study was to determine the extent to which statin use was associated with a decreased risk of HCF-onset C difficile infection.
Abstract and Introduction
Abstract
Objectives To estimate the possible relationship between statin use and the risk of healthcare facility onset Clostridium difficile.
Methods Patients over 18 years of age admitted to hospitals contributing data to the University HealthSystem Consortium between 2002 and 2009 were eligible. Patients with the ICD-9-CM code 008.45 who received a minimum 3-day course of either metronidazole or oral vancomycin on/after day 5 of admission were considered incident cases of C difficile infection. 31 472 incident cases of C difficile infection were identified and matched to five controls, on hospital, year/quarter of admission date, and age ±10 years (N=78 096). Patients who were administered one drug in the statin class (atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin or simvastatin) before the index date were considered to be exposed. Conditional logistic regression modelling provided adjusted odds ratios and 95% CI.
Results Compared with non-users, users of any drug within the statin class were 0.78 times less likely to develop C difficile infection in the hospital (95% CI 0.75 to 0.81) adjusting for potential confounders. Differences in estimates for specific statins were minimal. Niacin, fibrates and selective cholesterol absorption inhibitors showed no association with the risk of C difficile infection.
Conclusions Our data were consistent with a growing body of literature demonstrating a reduced risk of infections with statin use. Statins' pleiotropic properties may provide protection against C difficile infection.
Introduction
Clostridium difficile is a spore-forming, anaerobic, Gram-positive bacterium that is thought to be responsible for approximately 20% of cases of hospital-acquired diarrhoea. Recent estimates indicate more than 250 000 hospitalisations associated with C difficile infection, which appears to be increasing. In the USA, mortality rates due to C difficile infection have also increased, very likely caused by a new more virulent strain of C difficile. The cost of managing C difficile infection is not trivial, exceeding US$3.2 billion.
In addition to age and disease severity, risk factors for C difficile infection include the use of antibiotics and gastric acid suppressants. The relationship between statin use and healthcare facility (HCF) onset C difficile infection has previously been hypothesised; however, this relationship has not previously been explored. In general, statins have been associated with a reduced risk of infections. The prophylactic nature of statins in these infections is possibly due to the myriad of pleiotropic effects of these drugs. There is a biological basis for belief in these effects, stemming from mechanisms involving immunomodulatory and cell signalling pathways. Briefly, statins are hypothesised to reduce inflammation in endothelial cells. The reduced inflammation could either reduce the risk of acquiring C difficile infection, or reduce the severity of C difficile infection. Other epidemiological studies have previously found a reduced risk of C difficile infection in patients taking statins.
In the USA, statin use has increased significantly, with 24 million Americans (35.9% of those with high low-density lipoprotein cholesterol levels) taking statins in 2003–4 compared with 12.5 million (19.6% of those with high low-density lipoprotein cholesterol levels) taking statins in 1999–2000. As a result of the increase in the prevalence of statin use, it is especially important to understand what other effects may be perpetuated beyond their intended cholesterol-lowering purpose. The extent and magnitude of the pleiotropic nature of statins in infections is just beginning to come into focus. Therefore, evaluating the indirect effects of statins in conjunction with specific infections, such as C difficile infection, is warranted.
The purpose of this study was to determine the extent to which statin use was associated with a decreased risk of HCF-onset C difficile infection.
