Printer Friendly

ANALYSIS OF RISK FACTORS FOR MORTALITY IN METHICILLIN-SENSITIVE STAPHYLOCOCCUS AUREUS BACTERAEMIA: CEFAZOLIN IS ASSOCIATED WITH BETTER OUTCOME/ STAPHYLOCOCCUS AUREUS BAKTERIYEMILERINDE MORTALITE RISK FAKTORLERININ ANALIZI: SEFAZOLIN DAHA IYI SONUCLA ILISKILI.

INTRODUCTION

Methicillin-sensitive Staphylococcus aureus (MSSA) is one of the most frequently isolated causative agents of both healthcare-associated (HCA) and community-acquired (CA) bacteraemia. Mortality related to S. aureus bacteraemia is high, ranging from 20% to 30%, and varies as a function of underlying comorbid conditions, presence or absence of metastatic foci, and some features of the microorganism itself, such as a higher vancomycin minimum inhibitory concentration (MIC) level (1-6). Some studies reported an increased risk of mortality among patients with CA MSSA bacteraemia, but there are also reports with conflicting results (7, 8). Although cefazolin is the first choice in most of the current guidelines for the treatment of MSSA bacteraemia in the case of unavailability of anti-staphylococcal penicillins (ASP) like being in our country, other beta-lactams including ampicillin-sulbactam or other cephalosporins, glycopeptides and daptomycin are also used frequently (9). In this study, we analysed the risk factors for mortality among patients with MSSA bacteraemia with special emphasis on CA or HCA infections, and treatment with cefazolin and other antimicrobial treatment options.

MATERIALS AND METHODS

All adult (aged >18 years) patients who were hospitalized in our hospital and whose 2 blood cultures were positive for MSSA in the microbiology laboratory between January 2009 and December 2014 were included in the study. Patients with polymicrobial bacteraemia and those who died without antimicrobial therapy were excluded from the study.

Patients with positive blood cultures for MSSA and clinical and laboratory characteristics of them were retrospectively obtained from the laboratory and hospital databases. The following variables were recorded on previously prepared forms: age, sex, hospital ward (surgical or internal), requirement for intensive care unit (ICU) support, comorbid conditions (cancer, diabetes mellitus, cardiac valve disease, chronic renal failure, haemodialysis, cirrhosis, cerebrovascular accident), Charlson comorbidity index (CCI) (10), presence of echocardiographic examination and metastatic foci, laboratory values such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, C-reactive protein (CRP) levels and white blood cell counts at the time of diagnosis of the infection, type of the antibacterial used for the treatment, outcome (mortality), and duration of hospitalization from the blood culture positivity until discharge from hospital or death.

MSSA bacteraemia was defined as the isolation of MSSA from at least two or more bottles of blood cultures with associated symptoms and signs of systemic infection.

Cases of S. aureus bacteraemia were classified as HCA or CA. CA bacteraemia was defined as a positive blood culture result obtained at the time of hospital admission or within 48 hours of hospital admission. HCA bacteraemia was defined either nosocomial, (as positive blood culture result obtained from patients who had been hospitalized for [greater than or equal to]48 hours), or non-nosocomial (as a positive blood culture result obtained from a patient within 48 hours of admission if the patient (a) had intravenous medical therapy in the previous 30 days; (b) attended a hospital or haemodialysis clinic or received intravenous chemotherapy in the previous 30 days; (c) was hospitalised in an acute care hospital for 2 days in the previous 90 days; or (d) resided in a nursing home or long-term care facility) (11).

A BacT/ALERT 3D (bioMerieux, Marcy l'Etoile, France) automatic blood culture system was used for blood cultures. Classic methods (Gram-staining, catalase, coagulase, DNAse and cefoxitine susceptibility tests) were used for the identification of MSSA.

Statistical Analysis

Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) for Windows version 16.0 (SPSS Inc., Chicago, IL, USA). For analysis of risk factors for mortality and comparison of patients with CA and HA MSSA bacteraemia, [chi square] and Student's t-test were used for the univariate analysis of categorical and continuous variables of patients' characteristics, respectively. The univariate effect of the type of antimicrobial treatment on patient survival was investigated using log-rank test. Kaplan-Meier survival estimates were calculated. Cox regression analysis with backward selection was used to determine independent predictors of mortality. Variables found to be significant (p<0.05) in the univariate analysis or reported to be risk factors for mortality in the literature were included in the Cox regression analyses. Among correlated factors with similar effects on survival, only those with clinical significance were included. The proportional hazards assumption and model fit were assessed by means of residual (Schoenfeld and Martingale) analysis.

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethic Review Board of Hospital.

RESULTS

A total of 147 adult patients with clinically significant MSSA bacteraemia were identified between January 2009 and December 2014 from the database of the microbiology laboratory. Twenty patients were excluded from the study; 16 were excluded because they received outpatient management, and 4 patients died without receiving antimicrobial treatment. A total of 127 patients were included in the final analysis. Eighty-two (64.6%) patients were men and the median age was 54.4[+ or -]17.0 years. One hundred five of the 127 (82.7%) patients had HCA MSSA, and 22 (17.3%) had CA MSSA. The comparison of patients with HCA MSSA and CA MSSA is shown in Table 1.

Presence of intravenous catheters (52.4% vs 0%, p<0.001), chronic renal failure (30.5% vs 4.5%, p=0.014) and higher CCI (Charlson comorbidity index) (4.83 vs 3.04, p=0.001) were more frequently seen in patients with HCA MSSA than patients with CA-MSSA. Patients with CA-MSSA underwent more frequent echocardiographic investigations (68% vs 40%, p=0.016), were more likely to have heart valve disease (40.9% vs 17.1%, p=0.013), infective endocarditis (36% vs 3%, p<0.001), bone and joint infection (22.7% vs 0.9%, p=0.001), metastatic focus (59% vs 10%, p<0.001) and had higher WBC count (15.459 vs 11.831, p=0.019) than patients with HCA-MSSA. The mean mortality rate of patients was 20.5% and did not differ between patients with either CA or HCA MSSA (p=0.77). The comparison of patients' characteristics with and without mortality is shown in Table 2.

Vancomycin alone was used for 5 patients because of empiric choice and allergies against beta-lactam in 3 and 2 patients, respectively. Combined vancomycin and beta-lactam treatment were given empirically to the patients with either health-care (16 patients) or community acquired (2 patients) sepsis. Daptomycin was given to 3 patients with health-care associated infections empirically.

Durations of treatment were not found to be different among patients treated with different types of antimicrobials (p>0.005). Mean durations (+SD) of treatment were found to be 25[+ or -]24 and 18[+ or -]18 days for patients treated with cefazolin and other antimicrobials, respectively (p=0.073); 19[+ or -]18 and 20[+ or -]20 days for patients treated with ampicilllin-sulbactam and other antimicrobials, respectively (p=0.935); and 22[+ or -]19 and 19[+ or -]19 days for patients treated with vancomycin + other beta-lactams and other antimicrobials, respectively (p=0.483).

In the univariate analysis, the requirement for ICU support (p<0.001), higher CCI (p=0.001), AST level (p=0.003) and treatment with antimicrobials other than cefazolin (p=0.038) or other beta-lactams (including piperacillin-tazobactam, ceftriaxone, imipenem, meropenem) (p=0.022) were determined as risk factors for mortality among patients with MSSA.

In the analysis of the univariate effect of types of antimicrobial treatment on survival, it was found that cefazolin was associated with improved survival (log-rank test p=0.023).

In the subgroup analysis of patients treated with either cefazolin (n=30) or ampicillin-sulbactam (n=47), it was found that the mortality rate of patients treated with cefazolin (2/30, 6.6%) was lower than in patients treated with ampicillin-sulbactam (9/47, 19%); however, it did not reach statistical significance (log-rank p=0.082) (Figure 1).

In the multivariate analysis, higher CCI (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 among patients with MSSA, and cefazolin use was found to protect against mortality (HR 0.178).

DISCUSSION

In our study, MSSA bacteraemias mainly resulted from HCA infections, 82.7% of the cases had either nosocomial (acquired during hospitalization) or non-nosocomial (acquired in other type of health-care centers like haemodialysis units, nursing home or long-term care facility, etc). The reported rate of HCA infections among MSSA bacteraemia cases is wide ranging, between 27 and 81%, because the increasing numbers of individuals who are treated in outpatient programs make CA and HCA infections progres-sively overlapped (6, 12-14). Especially after the definition of non-nosocomial HCA infections, it was noticed that like MRSA bacteraemia, MSSA bacteraemia also originated mainly from healthcare-associated infections (15). It is especially important to be aware of preventable risk factors that predispose patients to MSSA bacteraemia because the mortality rate of MSSA bacteraemia is still very high, 20% in our study, which is in accordance with the other reports (16, 17) and healthcare associated infections can be prevented. In a study from Australia, at least one preventable risk factor was defined among 33% of MSSA blood stream infections, and feedback about preventable factors was associated with a reduction in HCA S. aureus bacteraemia rates (18). In our study, 43% and 10% of MSSA bacteraemias resulted from IV catheter or surgical site infections, respectively. As a result, nearly 50% of cases had at least one preventable factor of this blood stream infection. Fourteen percent of our patients had undergone haemodialysis and this finding once again highlights the increased risk of this group of patients for MSSA bacteraemia (1). Patients with HCA MSSA had higher CCI and more frequent catheter-related infections and surgical unit hospitalization (p<0.05) than patients with CA MSSA, and patients with CA MSSA were more frequently associated with IE, bone and joint infections, metastatic foci, and underwent more echocardiographic evaluations and cefazolin treatment (p<0.05) than those with HCA MSSA. The mortality rate of HCA and CA MSSA bacteraemia did not differ significantly in our study (p=0.77). The increased risk of mortality reported among patients with HCA S. aureus bacteraemia could be attributed to the inclusion of patients with MRSA, confusion of community-onset HCA with community-onset CA infections, or increased risk of comorbidities among HCA infections (1, 7-9). After eliminating all of these confounding factors through the inclusion of only MSSA bacteraemia, using up-to-date definitions for HCA and CA bacteraemia, and analysing independent risk factors, the mortality rate of MSSA bacteraemia was found the same between HCA and CA MSSA bacteraemia in our study. There are also some reports of increased risk of mortality among CA MSSA bacteraemia related to increased complications, especially metastatic foci due to delayed diagnosis and treatment of disease (19). The diagnosis of HCA MSSA bacteraemia could be more rapid than the diagnosis of CA MSSA, which probably contributed to the increased risk of complication and death among patients with CA MSSA reported in some studies (20, 21). In accordance with some published studies (4), the higher CCI of patients with HCA MSSA and higher incidence of metastatic foci among patients with CA MSSA probably contributed to the lack of difference in mortality rates between patients with HCA or CA MSSA in our study.

The presence of metastatic foci was found to be an independent risk factor for mortality in our study and confirms results of other studies (20). It has been clearly described that risk of metastatic foci is significantly increased with prolonged duration of bacteraemia (19). Since the tendency of S. aureus for metastatic infection is well known, it is especially important to search with a clinical scoring system, TEE or PET/CT, to find and treat properly metastatic foci in order to decrease the risk of mortality in patients with MSSA bacteraemia (20, 22, 23). Comorbid conditions defined as increased CCI and severity of infection documented as a need to ICU support were found to increase mortality significantly in our study, which have already been demonstrated in several other studies (9, 22).

Cefazolin was found as an independent protective factor against mortality in our study. Although cefazolin has been shown to be effective equally with anti-staphylococcal penicillins (24-28) or have a mortality benefit (29) for treatment of MSSA bacteremia, there have not been studies comparing the effectivenes of cefazolin and other beta-lactams for this indication in situations where ASPs are not availible. In accordance with our study, in a retrospective cohort study of 498 patients with MSSA bacteraemia, treatment with cefazolin was not significantly different from treatment with cloxacillin, whereas treatment with other beta-lactams, including beta-lactam/beta-lactamase inhibitors, second- and third-generation cephalosporins, were associated with higher mortality (12). In a recent study of patients with MSSA bacteraemia and penicillin allergy, cefazolin was found superior to vancomycin for the treatment of MSSA bacteraemia, with significant difference in mortality rates between patients treated with either cefazolin or vancomycin (19.6% vs 5.9%) (30). It is common practice to use either cefazolin or ampicillin-sulbactam for the treatment of infections caused by MSSA in our country because ASPs are not available. Therefore, we performed a subgroup analysis of patients treated with either cefazolin or ampicillin-sulbactam and found that the mortality rate of patients treated with cefazolin was lower than in patients treated with ampicillin-sulbactam (6.6 % versus 19.1%), although it did not reach statistical significance because of the lower number of patients. Additonal studies are needed to compare the effectiveness of cefazolin and specific beta-lactam agents including ampicillin-sulbactam in the treatment of MSSA bacteraemia.

Our study has some limitations. Although the first choice of S. aureus bacteremia is anti-staphylococcal penicillins (ASP) at the moment, we were unable to use them because of the unavailability of this agents in our country. As well as vancomycin and daptomycin are not recommended treatments for MSSA bacteremia, some of our patients were given either vancomycin combined with other beta-lactams or daptomycin because of severe health-care associated sepsis. Some of the variables that could have an effect on the mortality rate such as the duration of blood culture positivity could not be obtained because of retrospective design of the study. Also, metastatic foci could not be investigated properly with TEE or PET/CT in most patients.

Either HAC or CA, MSSA bacteraemia is associated with a high mortality rate, reaching 20%. Like MRSA bacteraemia, the proportion of nosocomial and non-nosocomial HCA infections is quite high, also in MSSA bacteraemia. Consequently, preventive measures are of vital importance. Patients with MSSA bacteraemia should be treated with cefazolin instead of other options including other beta-lactams, glycopeptides and daptomycin because of the associated lower mortality rate with cefazolin, especially in countries where anti-staphylococcal penicillins are not available or in patients who cannot tolerate anti-staphylococcal penicillins.

Ethics Committee Approval: Ethics committee approval was received for this study from the local ethics committee.

Informed Consent: Informed consent was not received due to the retrospective nature of the study.

Peer Review: Externally peer-reviewed.

Author Contributions: Conception/Design of Study S.B., S.S.Y., A.C., A.O.; Data Acquisition- B.S.C, A.Y.; Data Analysis/Interpretation-S.B., S.S.Y., H.O., H.E.; Drafting Manuscript- S.B., S.S.Y., B.S.C., A.Y.; Critical Revision of Manuscript- A.C., O.O., H.O., H.E.; Final Approval and Accountability- S.B., S.S.Y., B.S.C., A.Y., A.C., O.O., H.O., H.E.; Technical or Material Support- S.B., S.S.Y., B.S.C., A.Y.; Supervision- A.C., O.O., H.O., H.E.

Conflict of Interest: Authors declared no conflict of interest.

Financial Disclosure: Authors declared no financial support.

Etik Komite Onayi: Etik komite onayi bu calisma icin, yerel etik komiteden alinmistir.

Bilgilendirilmis Onam: Retrospektif bir calisma oldugundan bilgilendirilmis onam alinmamistir.

Hakem Degerlendirmesi: Dis bagimsiz.

Yazar Katkilari: Calisma Konsepti/Tasarim- S.B., S.S.Y., A.C., A.O.; Veri Toplama- B.S.C, A.Y.; Veri Analizi/Yorumlama- S.B., S.S.Y., H.O., H.E.; Yazi Taslagi- S.B., S.S.Y., B.S.C., A.Y.; Icerigin Elestirel Incelemesi- A.C., O.O., H.O., H.E.; Son Onay ve Sorumluluk-S.B., S.S.Y., B.S.C., A.Y., A.C., O.O., H.O., H.E.; Malzeme ve Teknik Destek- S.B., S.S.Y., B.S.C., A.Y.; Supervizyon- A.C., O.O., H.O., H.E..

Cikar Catismasi: Yazarlar cikar catismasi beyan etmemislerdir.

Finansal Destek: Yazarlar finansal destek beyan etmemislerdir.

REFERENCES

(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.) 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. [CrossRef]

(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. [CrossRef]

(4.) Aguado JM, San-Juan R, Lalueza, A, Sanz F, Rodriguez-Otero J, Gomez-Gonzalez C, et al. High vancomycin MIC and complicated methicillin-susceptible Staphylococcus aureus bacteremia. Emerg Infect Dis 2011;17(6):1099-102. [CrossRef]

(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. [CrossRef]

(6.) Topeli A, Unal S, Akalin HE. Risk factors influencing clinical outcome in Staphylococcus aureus bacteraemia in a Turkish university hospital. Int J Antimicrob Agents 2000;14(1):57-63. [CrossRef]

(7.) Melzer M, Welch C. Thirty-day mortality in UK patients with community-onset and hospital-acquired meticillin-susceptible Staphylococcus aureus bacteraemia. J Hosp Infect 2013;84(2):143-50. [CrossRef]

(8.) Lyytikainen O, Ruotsalainen E, Jarvinen A, Valtonen V, Ruutu P. Trends and outcome of nosocomial and community-acquired bloodstream infections due to Staphylococcus aureus in Finland, 1995-2001. Eur J Clin Microbiol Infect Dis 2005;24(6):399-404. [CrossRef]

(9.) Yilmaz M, Elaldi N, Balkan II, Arslan F, Batirel AA, Bakici MZ, et al. Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study. Ann Clin Microbiol Antimicrob 2016;15:7. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(14.) Forsblom E, Ruotsalainen E, Molkanen T, Ollgren J, Lyytikainen O, Jarvinen 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. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(17.) Holland T L, Arnold C, Fowler VG Jr. Clinical management of Staphylococcus aureus bacteremia: a review. JAMA 2014;312(13):1330-41. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(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):345-52. [CrossRef]

(22.) Thwaites GE, Edgeworth JD, Gkrania-Klotsas E, Kirby A, Tilley R, Torok ME, et al. Clinical management of Staphylococcus aureus bacteraemia. Lancet Infect Dis 2011;11(3):208-22. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(26.) Pollett S, Baxi SM, Rutherford GW, Doernberg SB, Bacchetti P, Chambers HF. Cefazolin versus nafcillin for methicillin-sensitive Staphylococcus aureus bloodstream infection in a California Tertiary Medical Center. Antimicrob Agents Chemother 2016;60(8):4684-89. [CrossRef]

(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. [CrossRef]

(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. [CrossRef]

(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 methicillin-susceptible Staphylococcus aureus infections complicated by bacteremia: A nationwide cohort study. Clin Infect Dis 2017;65(1):100-6. [CrossRef]

(30.) Blumenthal KG, Parker RA, Shenoy ES, Walensky RP. Improving clinical outcomes in patients with methicillin-sensitive Staphylococcus aureus bacteremia and reposted penicilin allergy. Clin Infect Dis 2015;61(5):741-9. [CrossRef]

Seniha BASARAN (1) [iD], Serap SIMSEK YAVUZ (1) [iD], Betul SADIC COPUR (1) [iD], Asiye YIR (1) [iD], Atahan CAGATAY (1) [iD], Oral ONCUL (1) [iD], Halit OZSUT (1) [iD], Haluk ERAKSOY (1) [iD]

(1) Istanbul University, Istanbul Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Istanbul, Turkey

ORCID IDs of the authors: S.B. 0000-0002-3402-2510; S.S.Y. 0000-0002-4675-169X; B.S.C. 0000-0001-5534-1388; A.Y. 0000-0001-9473-5099; A.C. 0000-0002-3051-8199; O.O. 0000-0002-1681-1866; H.O. 0000-0002-5222-9320; H.E. 0000-0002-5790-0806

Cite this article as: Basaran S, Simsek-Yavuz S, Sadic-Copur B, Yir A, Cagatay A, Oncul O, Ozsut H, Eraksoy H. Analysis of risk factors for mortality in methicillin-sensitive staphylococcus aureus bacteraemia: cefazolin is associated with better outcome. J Ist Faculty Med 2019;82(3):131-8. doi: 10.26650/IUITFD.2019.0009

Corresponding author/Iletisim kurulacak yazar: senihabasaran@yahoo.com

Submitted/Basvuru: 22.01.2019 * Accepted/Kabul: 26.03.2019 * Published Online/Online Yayin: 29.04.2019

DOI: 10.26650/IUITFD.2019.0009
Table 1. Comparison of patients with community acquired
methicillin-sensitive Staphylococcus aureus bacteraemia and health-care
associated methicillin-sensitive Staphylococcus aureus bacteraemia.

Characteristics               All patients         Community-acquired
                                (n=127)             MSSA bacteraemia
                                                         (n=22)

Sex (male), n (%)            82 (64.6)              17 (77.3)
Age (mean[+ or -]SD)         54.38[+ or -]16.98     49.91[+ or -]16.41
Hospital service             87 (68.5)              21 (95.5)
(medical), n (%)
Duration of hospital         20.10[+ or -]19.82     25.64[+ or -]19.39
stay, (mean[+ or -]SD)
Need for ICU                 33 (26.0)               6 (27.3)
support, n (%)
Charlson comorbidity          4.52[+ or -]2.41       3.04[+ or -]1.61
index (mean[+ or -]SD)
Echocardiographic            57 (44.9)              15 (68.2)
investigation, n (%)
Presence of                  24 (18.9)              13 (59.1)
metastatic foci, n (%)
WBC, (mean[+ or -]SD)     12459[+ or -]8348      15459[+ or -]7265
Serum CRP level             209[+ or -]138         208[+ or -]108
(mean[+ or -]SD)
Serum ALT level              61[+ or -]120          54[+ or -]62
(mean[+ or -]SD)
Serum AST level              60[+ or -]123          60[+ or -]104
(mean[+ or -]SD)
Serum creatinine level        1.95[+ or -]2.01       1.22[+ or -]0.79
(mean[+ or -]SD)
Mortality, n (%)             26 (20.5)               5 (22.7)
Comorbid conditions
Malignity, n (%)             44 (34.6)               4 (18.2)
Diabetes mellitus, n (%)     27 (21.3)               4 (18.2)
Chronic renal                33 (26.0)               1 (4.5)
failure, n (%)
Heart valve                  27 (21.3)               9 (40.9)
disease, n (%)
Cerebrovascular               9 (7.1)                0
accident, n (%)
Cirrhosis, n (%)              4 (3.1)                0
Immunosuppressive            13 (10.2)               1 (4.5)
treatment, n (%)
None, n (%)                  18 (14.2)               5 (22.7)
Source of bacteraemia
Intravenous                  55 (43.3)               0
catheter, n (%)
Primary, n (%)               16 (12.6)               4 (18.2)
Pneumonia, n (%)             15 (11.8)               3 (13.6)
Surgical site                13 (10.2)               0
infection, n (%)
Skin and soft tissue         11 (8.7)                2 (9.1)
infection, n (%)
Infective                    11 (8.7)                8 (36.4)
endocarditis, n (%)
Bone and joint                6 (4.7)                5 (22.7)
infection, n (%)
Antimicrobial treatment
Ampicillin-sulbactam,        47 (37.0)               7 (31.8)
n (%)
Cefazolin, n (%)             30 (23.6)               9 (40.9)
Other                        24 (18.9)               2 (9.1)
beta-lactams (1), n (%)
Vancomycin, n (%)             5 (3.9)                2 (9.1)
Vancomycin plus              18 (14.2)               2 (9.1)
beta-lactam, n (%)
Daptomycin, n (%)             3 (2.4)                0

Characteristics           Healthcare-associated     p
                             MSSA bacteraemia
                                 (n=105)

Sex (male), n (%)            65 (61.9)            0.171
Age (mean[+ or -]SD)         55.31[+ or -]17.03   0.116
Hospital service             66 (62.9)            0.002
(medical), n (%)
Duration of hospital         18.94[+ or -]19.80   0.092
stay, (mean[+ or -]SD)
Need for ICU                 27 (25.7)            0.880
support, n (%)
Charlson comorbidity          4.83[+ or -]2.44    0.001
index (mean[+ or -]SD)
Echocardiographic            42 (40.0)            0.016
investigation, n (%)
Presence of                  11 (10.5)           <0.001
metastatic foci, n (%)
WBC, (mean[+ or -]SD)     11831[+ or -]8454       0.019
Serum CRP level             209[+ or -]144        0.731
(mean[+ or -]SD)
Serum ALT level              62[+ or -]129        0.443
(mean[+ or -]SD)
Serum AST level              60[+ or -]127        0.426
(mean[+ or -]SD)
Serum creatinine level        2.10[+ or -]2.14    0.475
(mean[+ or -]SD)
Mortality, n (%)             21 (20.0)            0.773
Comorbid conditions
Malignity, n (%)             40 (38.1)            0.088
Diabetes mellitus, n (%)     23 (21.9)            1.000
Chronic renal                32 (30.5)            0.014
failure, n (%)
Heart valve                  18 (17.1)            0.013
disease, n (%)
Cerebrovascular               9 (8.6)             0.357
accident, n (%)
Cirrhosis, n (%)              4 (3.8)             1.000
Immunosuppressive            12 (11.4)            0.464
treatment, n (%)
None, n (%)                  13 (12.4)            0.206
Source of bacteraemia
Intravenous                  55 (52.4)           <0.001
catheter, n (%)
Primary, n (%)               12 (11.4)            0.477
Pneumonia, n (%)             12 (11.4)            0.724
Surgical site                13 (12.4)            0.123
infection, n (%)
Skin and soft tissue          9 (8.6)             1.000
infection, n (%)
Infective                     3 (2.9)            <0.001
endocarditis, n (%)
Bone and joint                1 (0.9)             0.001
infection, n (%)
Antimicrobial treatment
Ampicillin-sulbactam,        40 (38.1)            0.579
n (%)
Cefazolin, n (%)             21 (20.0)            0.036
Other                        22 (21.0)            0.245
beta-lactams (1), n (%)
Vancomycin, n (%)             3 (2.9)             0.207
Vancomycin plus              16 (15.1)            0.737
beta-lactam, n (%)
Daptomycin, n (%)             3 (2.9)             1.000

MSSA: methicillin-sensitive Staphylococcus aureus; ICU: intensive care
unit; WBC: white blood cell, CRP: C-reactive protein; ALT: alanine
aminotransferase; AST: aspartate aminotransferase
(1) Other beta-lactams (number of patients): Piperacillin-tazobactam
(16), ceftriaxone (4), imipenem (2), meropenem (2).

Table 2. Comparison of methicillin-sensitive Staphylococcus aureus
bacteraemia patients with and without mortality.

Characteristics             Patients               Patients
                            without                  with
                            mortality              mortality
                            (n=101)                 (n=26)

Age, year                 53.55[+ or -]16.76     57.58[+ or -]17.80
(mean[+ or -]SD)
Sex (male), n (%)         62 (61.4)              20 (76.9)
Hospital service          70 (69.3)              17 (65.4)
(medical), n (%)
Community acquired        17 (16.8)               5 (19.2)
infection, n (%)
Duration of hospital      23.04[+ or -]20.28      8.69[+ or -]12.8
stay,
(mean[+ or -]SD)
Need for ICU              12 (11.9)              21 (80.8)
support, n (%)
Presence of               17 (16.8)               7 (26.9)
metastatic foci,
n (%)
Echocardiographic         49 (48.5)               8 (30.8)
investigation, n (%)
WBC, (mean[+ or -]SD)  12491[+ or -]8394      12336[+ or -]8332
Serum CRP level          197.9[+ or -]127.8     253.7[+ or -]171.1
(mean[+ or -]SD)
Serum ALT level           43.7[+ or -]58.0      132.1[+ or -]229.9
(mean[+ or -]SD)
Serum AST level           38.0[+ or -]50.50     149[+ or -]238.4
(mean[+ or -]SD)
Serum creatinine           1.94[+ or -]2.12       1.97[+ or -]1.52
level
(mean[+ or -]SD)
Charlson comorbidity       2.98[+ or -]1.75       4.15[+ or -]1.59
index
(mean[+ or -]SD)
Comorbid conditions
Malignity, n (%)          34 (33.6)              10 (38.5)
Diabetes                  22 (21.8)               5 (19.2)
mellitus, n (%)
Chronic renal             25 (24.7)               8 (30.8)
failure, n (%)
Heart valve               19 (18.8)               8 (30.8)
disease, n (%)
Cerebrovascular            7 (6.9)                2 (7.7)
accident, n (%)
Cirrhosis, n (%)           2 (1.9)                2 (7.7)
Immunosuppressive         12 (11.9)               1 (3.8)
treatment, n (%)
Hemodialysis, n (%)       15 (14.9)               3 (11.5)
None, n (%)               17 (16.8)               1 (3.8)
Source of
bacteraemia
Intravenous               47 (46.5)               8 (30.8)
catheter, n (%)
Primary, n (%)            11 (10.9)               5 (19.2)
Pneumonia, n (%)           9 (8.9)                6 (23.1)
Surgical site              9 (8.9)                4 (15.4)
infection, n (%)
Skin and soft             11 (10.9)               0
tissue infection,
n (%)
Infective                  8 (7.9)                3 (11.5)
endocarditis, n (%)
Bone and joint             6 (5.9)                0
infection, n (%)
Antimicrobial
treatment
Ampicillin-sulbactam,     38 (37.6)               9 (34.6)
n (%)
Cefazolin, n (%)          28 (27.7)               2 (7.7)
Other                     15 (13.5)               9 (34.6)
beta-lactams (1),
n (%)
Vancomycin, n (%)          3 (3.0)                2 (7.7)
Vancomycin plus           15 (14.8)               3 (11.5)
beta-lactam, n (%)
Daptomycin, n (%)          2 (2.0)                1 (3.8)

Characteristics             p            p           HR      %95 CI
                       (univariate  (multivariate
                       analysis)    analysis)

Age, year               0.286
(mean[+ or -]SD)
Sex (male), n (%)       0.140
Hospital service        0.701
(medical), n (%)
Community acquired      0.773
infection, n (%)
Duration of hospital   <0.001
stay,
(mean[+ or -]SD)
Need for ICU           <0.001       <0.001         16.239  6.021-43.799
support, n (%)
Presence of             0.241        0.047          2.883  1.013-8.210
metastatic foci,
n (%)
Echocardiographic       0.105
investigation, n (%)
WBC, (mean[+ or -]SD)   0.903
Serum CRP level         0.158
(mean[+ or -]SD)
Serum ALT level         0.065
(mean[+ or -]SD)
Serum AST level         0.003
(mean[+ or -]SD)
Serum creatinine        0.423
level
(mean[+ or -]SD)
Charlson comorbidity    0.001       <0.001          1.557  1.234-1.964
index
(mean[+ or -]SD)
Comorbid conditions
Malignity, n (%)        0.647
Diabetes                0.772
mellitus, n (%)
Chronic renal           0.533
failure, n (%)
Heart valve             0.184
disease, n (%)
Cerebrovascular         1.000
accident, n (%)
Cirrhosis, n (%)        0.186
Immunosuppressive       0.302
treatment, n (%)
Hemodialysis, n (%)     1.000
None, n (%)             0.119
Source of
bacteraemia
Intravenous             0.148
catheter, n (%)
Primary, n (%)          0.253
Pneumonia, n (%)        0.046
Surgical site           0.466
infection, n (%)
Skin and soft           0.118
tissue infection,
n (%)
Infective               0.695
endocarditis, n (%)
Bone and joint          0.346
infection, n (%)
Antimicrobial
treatment
Ampicillin-sulbactam,   0.824
n (%)
Cefazolin, n (%)        0.038        0.037          0.178  0.035-0.904
Other                   0.022
beta-lactams (1),
n (%)
Vancomycin, n (%)       0.271
Vancomycin plus         1.000
beta-lactam, n (%)
Daptomycin, n (%)       0.500

ICU: intensive care unit; WBC: white blood cell, CRP: C-reactive
protein; ALT: alanine aminotransferase; AST: aspartate aminotransferase
(1) Other beta-lactams (number of patients): Piperacillin-tazobactam
(16), ceftriaxone (4), imipenem (2), meropenem (2).
COPYRIGHT 2019 AVES
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2019 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:ARASTIRMA / RESEARCH
Author:Basaran, Seniha; Yavuz, Serap SImsek; Copur, Betul Sadic; YIr, Asiye; Cagatay, Atahan; Oncul, Oral;
Publication:Journal of Istanbul Faculty of Medicine
Date:Sep 1, 2019
Words:5371
Previous Article:EVALUATING THE CAUSES FOR REJECTION OF POTENTIAL LIVE-RENAL DONORS: SINGLE CENTER EXPERIENCE/ POTANSIYEL CANLI BOBREK VERICILERININ REDDEDILME...
Next Article:UCUNCU BASAMAK BIR MERKEZDEKI OPERATIF VAJINAL DOGUM SIKLIGININ DEKATLAR ARASINDAKI DEGISIMININ RETROSPEKTIF OLARAK INCELENMESI/ RETROSPECTIVE...
Topics:

Terms of use | Privacy policy | Copyright © 2022 Farlex, Inc. | Feedback | For webmasters |