Statin Use and Risk of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Case-Control Study

doi:10.1016/j.mayocp.2017.07.008

Mayo Clinic Proceedings

Volume 92, Issue 10, October 2017, Pages 1469-1478

https://doi.org/10.1016/j.mayocp.2017.07.008 Get rights and content

Abstract

Objective

To ascertain whether persons treated with statins experience a decreased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB) as compared with nonusers.

Patients and Methods

Using population-based medical registries, we conducted a case-control study including all adults with first-time CA-SAB and population controls matched on age, sex, and residence in Northern Denmark from January 1, 2000, through December 31, 2011. Statin users were categorized as current users (new or long-term use), former users, and nonusers. We used conditional logistic regression to compute odds ratios (ORs) for CA-SAB according to statin exposure, overall and stratified by intensity (<20, 20-39, ≥40 mg/d) and duration of use (<365, 365-1094, ≥1095 days).

Results

We identified 2638 patients with first-time CA-SAB and 26,379 matched population controls. Compared with nonusers, current statin users experienced markedly decreased risk of CA-SAB (adjusted OR, 0.73; 95% CI, 0.63-0.84). The adjusted OR was 0.96 (95% CI, 0.60-1.51) for new users, 0.71 (95% CI, 0.62-0.82) for long-term users, and 1.12 (95% CI, 0.94-1.32) for former users as compared with nonusers. The CA-SAB risk decreased with increasing intensity of statin use; thus, compared with nonusers, the adjusted OR was 0.84 (95% CI, 0.68-1.04) for current users with daily dosages of less than 20 mg/d, 0.71 (95% CI, 0.58-0.87) for 20 to 39 mg/d, and 0.63 (95% CI, 0.49-0.81) for 40 mg/d or more. Conversely, we observed no differences in the risk of CA-SAB with successive increases in the duration of statin use.

Conclusion

Statin use was associated with a decreased risk of CA-SAB, particularly in long-term users.

Section snippets

Setting

This case-control study was conducted in the North and Central Regions of Denmark (catchment population ∼1.8 million inhabitants) between January 1, 2000, and December 31, 2011, using routinely recorded data from population-based medical registries. During the study period, a reform of local government merged 4 counties into 2 health regions: Central Denmark Region and North Denmark Region, collectively referred to as Northern Denmark. Denmark has a tax-supported health care system providing

Descriptive Data

Table 1 presents characteristics of cases and controls. During the study period, we identified 2638 patients with CA-SAB and 26,379 population controls, of which 368 (14.0%) and 3221 (12.2%), respectively, were current users of statins. Among current statin users, 81.4% (4283) received simvastatin, 9.8% (514) atorvastatin, and 8.9% (467) other statins. Among patients with CA-SAB, 42.2% (1115) had recently been in contact with the health care system before admission (health care–associated SAB).

Discussion

In this population-based case-control study, the use of statins was associated with a decreased risk of CA-SAB, which appeared to be driven primarily by long-term use. Compared with nonusers, the risk of CA-SAB decreased with increasing intensity of statin use whereas successive increases in the duration of statin use did not markedly influence the CA-SAB risk. The association between statin use and decreased risk of CA-SAB remained consistent across strata of age, sex, comorbidity level, and

Conclusion

Current users of statins experienced an almost 30% decreased risk of CA-SAB as compared with nonusers. The risk decreased gradually with increasing intensity of use, revealing a distinct dose-response relation, and the association was most pronounced in patients with concomitant chronic kidney disease and patients with diabetes. Statins may have a place in the prevention of CA-SAB, particularly in patients with these common chronic diseases and in other persons at high risk of CA-SAB.

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To investigate for potential protective effects of statin use among patients with infective endocarditis (IE) with consideration for underlying diseases and bacterial culture — variables which have prognostic implications and show considerable geographic variation yet are unappreciated in previous pharmacoepidemiological studies.
Patients diagnosed with IE between January 1, 1996, and December 31, 2019, were identified. We estimated the effect on mortality of pre-admission statin use (≥90 cumulative days of use before index date) and in-hospital use (use beginning within 2 days of admission), compared with nonusers and discontinued users, respectively, through propensity score analytics.
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Citation Excerpt :
Preventive measures for healthcare-associated SAB includes typical infection control actions and decolonisation of patients undergoing high-risk procedures. Curiously, statin use was associated with a dose-dependent lower risk of developing community-acquired SAB in a large Danish population-based study, with adjusted odds ratios (OR) of 0.84 (95% confidence interval [CI], 0.68–1.04) for current users using <20 mg/day, 0.71 (95% CI, 0.58–0.87) for 20–39 mg/day, and 0.63 (95% CI, 0.49–0.81) for ≥40 mg/day.3 The pathophysiological bases of this association are not clear, so these results should be reproduced before any recommendation can be done.
Staphylococcus aureus bacteremia (SAB) is still a daily challenge for clinicians. Despite all efforts, the associated mortality and morbidity has not significantly improved in the last 20 years. The available evidence suggests that adherence to some quality-of-care indicators with regard to clinical management is important in improving the outcome of patients, but it is lower than desired in many hospitals; as such, management of patients with SAB by infectious diseases specialists has been demonstrated to contribute in the reduction of the mortality rate of these patients. In this article, the most relevant clinical studies published over the last few years evaluating the efficacy and safety of alternative drugs for the treatment of SAB are reviewed. However, classic drugs are still used in a high proportion of patients because the promising results obtained from in vivo and in vivo studies with these alternative drugs have not translated as frequently as expected into evident superiority in clinical studies. Nevertheless, some data suggest that certain alternatives may offer advantages in specific situations. Overall, an individualised and expert approach is needed in order to decide the best treatment according to the source, severity, complications, patients’ features and microbiological data.
La bacteriemia por Staphylococcus aureus continúa siendo un reto diario para los clínicos. A pesar de todos los esfuerzos realizados, su mortalidad y morbilidad asociadas no han descendido de forma significativa en los últimos 20 años. Existe evidencia de que la adherencia a los indicadores de calidad para su manejo clínico es importante para mejorar el pronóstico de los pacientes, aunque su cumplimiento sigue siendo menor de lo deseado en muchos hospitales; en este sentido, la asistencia por especialistas en enfermedades infecciosas ha demostrado contribuir a reducir la mortalidad de estos pacientes. En este artículo se revisan los estudios clínicos más relevantes realizados en los últimos años con objeto de evaluar la eficacia y la seguridad de los fármacos alternativos a los clásicos. Sin embargo, estos siguen siendo utilizados en un alto porcentaje de pacientes, ya que los prometedores resultados obtenidos por esos fármacos alternativos y determinadas combinaciones en estudios in vitro y modelos animales no se han traducido en una evidente superioridad en los estudios clínicos con la frecuencia que se hubiera esperado. Dicho esto, existen datos que sugieren que determinadas alternativas pueden ofrecer ventajas en situaciones concretas. En general, es necesario un manejo individualizado y experto de los pacientes para decidir la mejor terapia en base al foco, la gravedad y las complicaciones, las características de los pacientes y los datos microbiológicos.
Statin Use Associated With a Decreased Risk of Community-Acquired Staphylococcus aureus Bacteremia
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Beyond Vasoprotection: Statins and Risk Reduction for Community-Acquired Staphylococcus aureus Bacteremia
2017, Mayo Clinic Proceedings
Protective efficacy of statins in patients with Klebsiella pneumoniae bloodstream infection
2023, Frontiers in Cellular and Infection Microbiology

View all citing articles on Scopus

: For editorial comment, see page 1463

: Grant Support: The work was supported by research grants from the Heinrich Kopp, Hertha Christensen, and North Denmark Health Sciences Research foundations. Dr López-Cortés and Dr Rodríguez-Bãno received research funding from the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, co-financed by the European Development Regional Fund “A way to achieve Europe” (ERDF), Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015).

: Potential Competing Interests: Dr López-Cortés has received payments from Merck Sharp & Dohme and Angelini. Dr Nielsen serves on the advisory board of Gilead. Dr Rodríguez-Bãno has received honoraria from AstraZeneca and Merck.

View full text

Original articleStatin Use and Risk of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Case-Control Study

Abstract

Objective

Patients and Methods

Results

Conclusion

Section snippets

Setting

Descriptive Data

Discussion

Conclusion

J Infect

J Am Coll Cardiol

Cell Host Microbe

J Infect

J Chronic Dis

Int J Cardiol

Lancet

Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management

Clin Microbiol Rev

Predictors for mortality in Staphylococcus aureus bacteremia

Clin Microbiol Rev

Simvastatin inhibits Staphylococcus aureus host cell invasion through modulation of isoprenoid intermediates

J Pharmacol Exp Ther

Statins and antimicrobial effects: simvastatin as a potential drug against Staphylococcus aureus biofilm

PLoS One

Unexpected antimicrobial effect of statins

J Antimicrob Chemother

The Danish Civil Registration System as a tool in epidemiology

Eur J Epidemiol

Classification of healthcare-associated Staphylococcus aureus bacteremia: influence of different definitions on prevalence, patient characteristics, and outcome

Infect Control Hosp Epidemiol

The Danish National Patient Registry: a review of content, data quality, and research potential

Clin Epidemiol

Original article
Statin Use and Risk of Community-Acquired Staphylococcus aureus Bacteremia: A Population-Based Case-Control Study