ANALYSIS OF RISK FACTORS FOR MORTALITY IN METHICILLIN SENSITIVE STAPHYLOCOCCUS AUREUS BACTERAEMIA: CEFAZOLIN IS ASSOCIATED WITH BETTER OUTCOME

Abstract

Objective: Methicillin-sensitive Staphylococcus aureus (MSSA) is frequent cause of bacteraemias and associated with substantial mortality. We defined risk factors for mortality among patients with either community-acquired (CA) or healthcare-associated (HCA) MSSA bacteraemia with special emphasis on treatment options including cefazolin and other antimicrobials (mainly ampicillin-sulbactam). Material and Method: All adult patients who were hospitalized and whose blood cultures were positive for MSSA between 2009 and 2014 were included. Patients with CA and HCA MSSA bacteraemia were compared. Results: 83% of the 127 patients with MSSA bacteraemia had HCA. The mortality rate of patients was 20.5% and this did not differ between patients with either CA or HCA MSSA bacteraemia. In the multivariate analysis, higher comorbidity index (HR 1.557), presence of metastatic foci (HR 2.883), and requirement for ICU support (HR 16.239) were found as independent risk factors for mortality, and cefazolin use was found to be protective against mortality (HR 0.178). Conclusion: Patients with MSSA bacteraemia should be treated with cefazolin instead of other antimicrobial options, especially in countries where anti-staphylococcal penicillins are not available or in patients who cannot tolerate anti-staphylococcal penicillins, as cefazolin was found to be protective against mortality

Keywords

• Methicillin-sensitive Staphylococcus aureus,healthcare associated bacteraemia,cefazolin

STAPHYLOCOCCUS AUREUS BAKTERİYEMİLERİNDE MORTALİTE RİSK FAKTÖRLERİNİN ANALİZİ: SEFAZOLİN DAHA İYİ SONUÇLA İLİŞKİLİ

Abstract

Amaç: Metisiline duyarlı Staphylococcus aureus (MSSA), önemli bir bakteriyemi etkeni olup, hastalarda ciddi mortaliteye neden olur. Bu çalışmada, toplum kaynaklı (TK) veya sağlık bakımı (SB)’yla ilişkili MSSA bakteriyemilerinde mortaliteye etki eden risk faktörlerinin belirlenmesi amaçlanmıştır. Ayrıca MSSA bakteriyemilerinin tedavi seçeneklerinden sefazolin ve özellikle ampisilin-sulbaktam olmak üzere diğer antimikrobiklerin tedavideki yeterlikleri karşılaştıırlmıştır. Gereç ve Yöntem: 2009-2014 yılları arasında hastanemizde yatarak tedavi edilen ve MSSA bakteriyemisi tanısı konulan erişkin hastalar çalışmaya dahil edildi. TK veya SB ilişkili MSSA bakteriyemisi olan hastalar karşılaştırıldı. Bulgular: Toplam 127 MSSA bakteriyemili hastanın %83’ü SB ile ilişkiliydi. Mortalite oranı %20,5 olup, TK ve SB MSSA bakteriyemili hastalar arasında fark yoktu. Çok değişkenli analizde yüksek komorbidite indeksi (HR 1,557), metastatik infeksiyon odağı varlığı (HR 2,883) ve yoğun bakım desteğine ihtiyacın olması (HR 16,239) mortalite için bağımsız risk faktörleri, tedavide sefazolin kullanımı ise mortaliteyi azaltan bir faktör olarak saptandı (HR 0,178). Sonuç: Diğer antimikrobiyallerle karşılaştırıldığında sefazolinle tedavi edilen MSSA bakteriyemilerinde klinik sonuçlar daha iyi belirlendiği için, özellikle antistafilokoksik penisilinlerin bulunmadığı yerlerde veya bu ajanları tolere edemeyen hastalarda diğer antimikrobiklerin yerine sefazolin tercih edilmelidir.

Keywords

• Metisiline duyarlı Staphylococcus aureus,sağlık bakımı ile ilişkili bakteriyemi,sefazolin

References

1. 1. Que Y, Moreillon P. Staphylococcus aureus (Including Staphylococcal Toxic Shock Syndrome). In: Bennett JE, Dolin R, Blaser M, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 8th ed. Philadelphia: Elsevier Saunders 2015: 2237-71.
2. 2. Deodhar D, Varghese G, Balaji V, John J, Rebekah G, Janardhanan J, et al. Prevalence of toxin genes among the clinical isolates of Staphylococcus aureus and its clinical impact. J Glob Infect Dis 2015;7(3):97-102.
3. 3. Chang FY, MacDonald BB, Peacock JE Jr, Musher DM, Triplett P, Mylotte JM, et al. A prospective multicenter study of Staphylococcus aureus bacteremia incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Medicine 2003;82(5):322-32.
4. 4. Aguado JM, San-Juan R, Lalueza, A, Sanz F, Rodriguez-Otero J, Gómez-Gonzalez C, et al. High vancomycin MIC and complicated methicillin-susceptible Staphylococcus aureus bacteremia. Emerg Infect Dis 2011;17(6):1099-102.
5. 5. Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O’Sullivan MVN, et al. Antibiotic choice may not explain poorer outcomes in patients with Staphylococcus aureus bacteremia and high vancomycin minimum inhibitory concentrations. J Infect Dis 2011;204(3):340-7.
6. 6. Topeli A, Ünal S, Akalın HE. Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish university hospital. Int J Antimicrob Agents 2000;14(1):5763.
7. 7. Melzer M, Welch C. Thirty-day mortality in UK patients with community-onset and hospital-acquired meticillinsusceptible Staphylococcus aureus bacteraemia. J Hosp Infect 2013;84(2):143-50.
8. 8. Lyytikäinen O, Ruotsalainen E, Järvinen A, Valtonen V, Ruutu P. Trends and outcome of nosocomial and communityacquired bloodstream infections due to Staphylococcus aureus in Finland, 1995-2001. Eur J Clin Microbiol Infect Dis 2005;24(6):399-404.

9. 9. Yılmaz M, Elaldi N, Balkan İİ, Arslan F, Batırel AA, Bakıcı MZ, et al. Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study. Ann Clin Microbiol Antimicrob 2016;15:7.
10. 10. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 1987;40(5):373-84.
11. 11. Friedman ND, Kaye KS, Stout JE, McGarry SA, Trivette SL, Briggs JP, et al. Health care-associated blood-stream infections in adults: a reason to change the accepted definition of community-acquired infections. Ann Intern Med 2002;137(10):791-7.
12. 12. Paul M, Zemer-Wassercug N, Talker O, Lishtzinsky Y, Lev B, Samra Z, et al. Are all beta-lactams similarly effective in the treatment of methicillin-sensitive Staphylococcus aureus bacteraemia? Clin Microbiol Infect 2011;17(10):1581-6.
13. 13. Horino T, Sato F, Hosaka Y, Hoshina T, Tamura K, Nakaharai K, et al. Predictive factor for metastatic infection in patients with bacteremia caused by methicillin-sensitive Staphylococcus aureus. Am J Med Sci 2015;349(1):24-8.
14. 14. Forsblom E, Ruotsalainen E, Mölkänen T, Ollgren J, Lyytikäinen O, Järvinen A. Predisposing factors, disease progression and outcome in 430 prospectively followed patients of healtcare and community-associated Staphylococcus aureus bacteraemia. J Hosp Infect 2011;78(2):102-7.
15. 15. Shorr AF, Tabak YP, Killian AD, Gupta V, Liu LZ, Kollef MH. Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database. Crit Care Med 2006;34(10):2588-95.
16. 16. van Hal SJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus bacteremia. Clin Microbiol Rev 2012;25(2):362-86.
17. 17. Holland T L, Arnold C, Fowler VG Jr. Clinical management of Staphylococcus aureus bacteremia: a review. JAMA 2014;312(13):1330-41.
18. 18. Kok J, O’Sullivan MV, Gilbert GL. Feedback to clinicians on preventable factors can reduce hospital onset Staphylococcus aureus bacteraemia rates. J Hosp Infect 2011;79(2):108-14.
19. 19. Lesens O, Hansmann Y, Brannigan E, Remy V, Hopkins S, Martinot M, et al. Positive surveillence blood culture is a predictive factor for secondary metastatic infection in patients with Staphylococcus aureus bacteraemia. J Infect 2004;48(3):245-52.
20. 20. Jensen AG, Wachmann CH, Espersen F, Scheibel J, Skinhoj P, Frimodt-Moller N. Treatment and outcome of Staphylococcus aureus bacteremia. Arch Intern Med 2002;162(1):25-32.
21. 21. Kaech C, Elzi L, Sendi P, Frei R, Laifer G, Bassetti S, et al. Course and outcome of Staphylococcus aureus bacteraemia: a retrospective analysis of 308 episodes in a Swiss tertiary-care centre. Clin Microb Infect 2006;12(4):34552.
22. 22. Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Török ME, et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis 2011;11(3):208-22.
23. 23. Palraj BR, Baddour LM, Hess EP, Steckelberg JM, Wilson WR, Lahr BD, et al. Predicting risk of endocarditis using a clinical tool (PREDICT): scoring system to guide use of echocardiography in the management of Staphylococcus aureus bacteremia. Clin Infect Dis 2015;61(1):18-28.
24. 24. Li J, Echevarria KL, Traugott KA. Beta-lactam therapy for methicillin-susceptible Staphylococcus aureus bacteremia: A comparative review of cefazolin versus antistaphylococcal penicillins. Pharmacotherapy 2017;37(3):346-60.
25. 25. Davis JS, Turnidge J, Tong S. A large retrospective cohort study of cefazolin compared with flucloxacillin for methicillin-susceptible Staphylococcus aureus bacteraemia. Int J Antimicrob Agents 2018;52(2):297-300.
26. 26. Pollett S, Baxi SM, Rutherford GW, Doernberg SB, Bacchetti P, Chambers HF. Cefazolin versus nafcillin for methicillinsensitive Staphylococcus aureus bloodstream infection in a California Tertiary Medical Center. Antimicrob Agents Chemother 2016;60(8):4684-89.
27. 27. Lee S, Song KH, Jung SI, Park WB, Lee SH, Kim YS, et al. Comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective multicentre cohort study in Korea. Clin Microbiol Infect 2017;24(2):152-8.
28. 28. Loubet P, Burdet C, Vindrios W, Grall N, Wolff M, Yazdanpanah Y, et al. Cefazolin versus anti-staphylococcal penicillins for treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a narrative review. Clin Microbiol Infect 2018;24(2):125-32.
29. 29. McDanel JS, Roghmann MC, Perencevich EN, Ohl ME, Goto M, Livorsi DJ, et al. Comparative effectiveness of cefazolin versus nafcillin or oxacillin for treatment of methicillinsusceptible Staphylococcus aureus infections complicated by bacteremia: A nationwide cohort study. Clin Infect Dis 2017;65(1):100-6.
30. 30. Blumenthal KG, Parker RA, Shenoy ES, Walensky RP. Improving clinical outcomes in patients with methicillinsensitive Staphylococcus aureus bacteremia and reposted penicilin allergy. Clin Infect Dis 2015;61(5):741-9.