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Cited by 20Antifungal resistance and susceptibilityFungal Infections and StudiesCancer, Lipids, and Metabolism

Effect of Statin Use on Outcomes of Adults with Candidemia

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Cuervo, Guillermo, Garcia-Vidal, Carolina, Nucci, Marcio, Puchades, Francesc, Fernández-Ruiz, Mario, Mykietiuk, Analía, Manzur, Adriana, Gudiol, Carlota +4 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0077317PMC PMC3796506
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Abstract

BACKGROUND: Statins have immunomodulatory properties and hinder Candida growth. However, it is unknown whether they may improve prognosis in patients with candidemia. We sought to determine the effect of prior statin use on the clinical outcomes of patients suffering candidemia. METHODS AND FINDINGS: Multicenter cohort study of hospitalized adults with candidemia between 2005 and 2011 in six hospitals in Spain, Brazil and Argentina. Of 326 candidemias, 44 (13.5%) occurred in statin users and 282 (86.5%) in statin non-users. The median value of APACHE II at candidemia diagnosis was similar between groups (18 vs. 16; p=.36). Candida albicans was the most commonly isolated species, followed by C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei. There were no differences regarding appropriate empirical antifungal treatment. Statin users had a lower early (5 d) case-fatality rate than non-users (4.5 vs. 17%; p=.031). This effect was not observed with other cardiovascular drugs (aspirin, beta blockers and ACE inhibitors). Independent factor related to early case-fatality rate was APACHE II score (AOR, 1.08; 95% CI, 1.03-1.14; p=.002). An appropriate empirical antifungal therapy (AOR, 0.11; 95% CI, 0.04-0.26; p=<.001) and prior statin use were independently associated with lower early case-fatality (AOR, 0.17; 95% CI, 0.03-0.93; p=.041). Fourteen days (14d) and overall (30d) case-fatality rates were similar between groups (27% vs. 29%; p=0.77 and 40% vs. 44%; p=.66). CONCLUSIONS: The use of statins might have a beneficial effect on outcomes of patients with candidemia. This hypothesis deserves further evaluation in randomized trials.

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  • Pravastatin enhanced survival and led to a decreased fungal burden in C3H/HeN mice infected with C. albicans.

    “other work has demonstrated that pravastatin enhanced survival and led to a decreased fungal burden in C3H/HeN mice infected with C. albicans and the potential benefits of statins in the clinic against Candida have been described [10, 40-42].”

    From Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans. (2019) · cites this paper as [41]

    The Results and Discussion (page unavailable) concern statin use in hospitalized adults with candidemia, not pravastatin-treated mice. Searches for pravastatin, C3H/HeN mice, and fungal burden found no passage addressing the quoted mouse finding. The paper does support the citing sentence’s separate point about potential clinical benefits of statins. (LLM, conf=0.76)

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References 40 · Cited by 20

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  1. [1]Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF et al. (2009) Guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48: 503– 535. doi: 10.1086/596757. PubMed: 19191635. 19191635 PMC7294538 · DOI · Paper page
  2. [2]Flückiger U, Marchetti O, Bille J, Eggimann P, Zimmerli S et al. (2006) Treatment options of invasive fungal infections in adults. Swiss Med Wkly 136: 447– 463. PubMed: 16937323. 16937323
  3. [3]Horn DL, Neofytos D, Anaissie EJ, Fishman JA, Steinbach WJ et al. (2009) Epidemiology and Outcomes of Candidemia in 2019 Patients: Data from the Prospective Antifungal Therapy Alliance Registry. Clin Infect Dis 48: 1695– 1703. doi: 10.1086/599039. PubMed: 19441981. 19441981 · DOI · Paper page
  4. [6]Liao JK, Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45: 89– 118. doi: 10.1146/annurev.pharmtox.45.120403.095748. PubMed: 15822172. 15822172 PMC2694580 · DOI · Paper page
  5. [7]Viasus D, Garcia-Vidal C, Gudiol F, Carratalà J (2010) Statins for community-acquired pneumonia: current state of the science. Eur J Clin Microbiol Infect Dis 29: 143– 152. doi: 10.1007/s10096-009-0835-0. PubMed: 19943074. 19943074 · DOI
  6. [9]Novack V, Eisinger M, Frenkel A, Terblanche M, Adhikari NK et al. (2009) The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized doubleblind placebo controlled clinical trial. Intensive Care Med 35: 1255- 1260. doi: 10.1007/s00134-009-1429-0. PubMed: 19205663. 19205663 · DOI
  7. [10]Almog Y, Shefer A, Novack V, Maimon N, Barski L et al. (2004) Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation 110: 880- 885. doi: 10.1161/01.CIR.0000138932.17956.F1. PubMed: 15289367. 15289367 · DOI
  8. [11]Ma Y, Wen X, Peng J, Lu Y, Guo Z et al. (2012) Systematic Review and Meta-Analysis on the Association between Outpatient Statins Use and Infectious Disease-Related Mortality. PLOS ONE 7(12): e51548. doi: 10.1371/journal.pone.0051548. PubMed: 23284711. 23284711 PMC3524177 · DOI
  9. [12]Liappis AP, Kan VL, Rochester CG, Simon GL (2001) The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 33: 1352– 1357. doi: 10.1086/323334. PubMed: 11565076. 11565076 · DOI
  10. [13]Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP et al. (2008) Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients. Arch Intern Med 168: 2081- 2087. doi: 10.1001/archinte.168.19.2081. PubMed: 18955636. 18955636 · DOI
  11. [14]Khan AR, Riaz M, Bin Abdulhak AA, Al-Tannir MA, Garbati MA et al. (2013) The role of statins in prevention and treatment of community acquired pneumonia: a systematic review and meta-analysis. PLOS ONE 8(1): e52929. doi: 10.1371/journal.pone.0052929. PubMed: 23349694. 23349694 PMC3538683 · DOI
  12. [15]Bearman GM, Shankaran S, Elam K (2010) Treatment of Severe Cases of Pandemic (H1N1) 2009 Influenza: Review of Antivirals and Adjuvant Therapy. Recent Pat Antiinfect Drugs Discov 5: 152- 156. doi: 10.2174/157489110791233513. PubMed: 20334616. 20334616 · DOI
  13. [16]Kwong JC, Li P, Redelmeier DA (2009) Influenza morbidity and mortality in elderly patients receiving statins: a cohort study. PLOS ONE 4(11): e8087. doi: 10.1371/journal.pone.0008087. PubMed: 19956645. 19956645 PMC2778952 · DOI
  14. [17]Westermeyer C, Macreadie IG (2007) Simvastatin reduces ergosterol levels, inhibits growth and causes loss of mtDNA in Candida glabrata. FEMS Yeast Res 7: 436- 441. doi: 10.1111/j.1567-1364.2006.00194.x. PubMed: 17257373. 17257373 · DOI · Paper page
  15. [18]Pittet D, Wenzel RP (1995) Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths. Arch Intern Med 155: 1177- 1184. doi: 10.1001/archinte.1995.00430110089009. PubMed: 7763123. 7763123 · DOI · Paper page
  16. [19]Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL et al. (2002) Health care associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 137: 791– 797. doi: 10.7326/0003-4819-137-10-200211190-00007. PubMed: 12435215. 12435215 · DOI
  17. [20]Garcia-Vidal C, Ardanuy C, Tubau F, Viasus D, Dorca J et al. (2010) Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes. Thorax 65: 77- 81. doi: 10.1136/thx.2010.150961.1. PubMed: 19996337. 19996337 · DOI
  18. [22]Almirante B, Rodríguez D, Park BJ, Cuenca-Estrella M, Planes AM et al. (2005) Epidemiology and Predictors of Mortality in Cases of Candida Bloodstream Infection: Results from Population-Based Surveillance, Barcelona, Spain, from 2002 to 2003. J Clin Microbiol 43: 1829– 1835. doi: 10.1128/JCM.43.4.1829-1835.2005. PubMed: 15815004. 15815004 PMC1081396 · DOI
  19. [23]Pemán J, Cantón E, Gobernado M (2005) Epidemiology and antifungal susceptibility of Candida species isolated from blood: results of a 2-year multicentre study in Spain. Eur J Clin Microbiol Infect Dis 24: 23– 30. doi: 10.1007/s10096-004-1267-5. PubMed: 15619060. 15619060 · DOI
  20. [24]Nace HL, Horn D, Neofytos D (2009) Epidemiology and outcome of multiple-species candidemia at a tertiary care center between 2004 and 2007. Diagn Microbiol Infect Dis 64: 289– 294. doi: 10.1016/j.diagmicrobio.2009.03.010. PubMed: 19376670. 19376670 · DOI
  21. [25]Pappas PG, Rex JH, Lee J, Hamill RJ, Larsen RA et al. (2003) A Prospective Observational Study of candidemia: epidemiology, therapy, and influences on mortality in hospitalized adult and pediatric patients. Clin Infect Dis 37: 634– 643. doi: 10.1086/376906. PubMed: 12942393. 12942393 · DOI
  22. [26]Gudlaugsson O, Gillespie S, Lee K, Vande Berg J, Hu J et al. (2003) Attributable mortality of nosocomial candidemia, revisited. Clin Infect Dis 37: 1172– 1177. doi: 10.1086/378745. PubMed: 14557960. 14557960 · DOI · Paper page
  23. [28]Welch ML, Liappis AP, Kan VL (2013) Candidemia outcomes not improved with statin use. Med Mycol 51: 219- 222. doi: 10.3109/13693786.2012.692490. PubMed: 22662759. 22662759 · DOI
  24. [29]Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG (2007) Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis 7: 358- 368. doi: 10.1016/S1473-3099(07)70111-1. PubMed: 17448939. 17448939 · DOI
  25. [30]Subramani J, Kathirvel K, Leo MD, Kuntamallappanavar G, Uttam Singh T et al. (2009) Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis. J Cardiovasc Pharmacol 54: 526- 534. doi: 10.1097/FJC.0b013e3181bfafd6. PubMed: 19755915. 19755915 · DOI
  26. [31]Alvarez de Sotomayor M, Vega S, Mingorance C, Marhuenda E, Herrera MD (2008) Effects of HMG-CoA reductase inhibition by simvastatin on vascular dysfunction induced by lipopolysaccharide in rats. Pharmacologist 82: 89- 96. PubMed: 18509252. 18509252
  27. [32]McGown CC, Brookes ZLS (2007) Beneficial effects of statins on the microcirculation during sepsis: the role of nitric oxide. Br J Anaesth 98: 163– 175. doi: 10.1093/bja/ael358. PubMed: 17251210. 17251210 · DOI
  28. [34]AUSTRIAN R, GOLD JAustrian R. Gold J (1964) Pneumococcal bacteremia with especial reference to bacteremic pneumococcal pneumonia. Ann Intern Med 60: 759- 770. doi: 10.7326/0003-4819-60-5-759. PubMed: 14156606. 14156606 · DOI
  29. [35]Garcia-Vidal C, Fernández-Sabé N, Carratalà J et al. (2008) Early mortality in patients with community acquired pneumonia: causes and risk factors. Eur Respir J 32: 733– 739. doi: 10.1183/09031936.00128107. PubMed: 18508820. 18508820 · DOI
  30. [36]Wiersinga WJ (2011) Current insights in sepsis: from pathogenesis to new treatment targets. Curr Opin Crit Care 5: 480- 486. PubMed: 21900767. 21900767
  31. [38]Cornely OA, Bassetti M, Calandra T, Garbino J, Kullberg BJ et al. (2012) ESCMID guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients. Clin Microbiol Infect; 18 (7): 19– 37. 23137135

Authors
Cuervo, G., Garcia-Vidal, C., Nucci, M., Puchades, F., Fernández-Ruiz, M., Mykietiuk, A., Manzur, A., Gudiol, C., Pemán, J., Viasus, D., Ayats, J., & Carratalà, J.
Affiliations
  • Bellvitge University Hospital (ES)
  • Hospital Universitari i Politècnic La Fe (ES)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-10-14
Volume
8
Issue
10
Pages
e77317
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0077317
PMC
PMC3796506
OpenAlex
W2068967993
Cited by
20
References
40
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 2
FWCI
0.73
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by)
  • RECERCAT (Consorci de Serveis Universitaris de Catalunya) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Greater South Information System
Funders
  • Ministerio de Ciencia e Innovación (REIPI RD06/0008)
  • Instituto de Salud Carlos III (RD06/0008, REIPI RD06/0008, FIS 10/01318)
  • European Regional Development Fund
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
statins, candidemia, case fatality rate, Candida albicans, Candida parapsilosis, APACHE II score, empirical antifungal therapy, immunomodulation, hospitalized adults, cardiovascular drugs
MeSH terms
Adult, Aged, Candida, Female, Humans, Male, Middle Aged, Multivariate Analysis, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Candidemia

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