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Impact of an Evidence-Based BundleIntervention in the Quality-of-Care Managementand Outcome of Staphylococcus aureusBacteremia Luis E. López-Cortés,1,a Maria Dolores del Toro,1,2 Juan Gálvez-Acebal,1,2 Elena Bereciartua-Bastarrica,3María Carmen Fariñas,4 Mercedes Sanz-Franco,5 Clara Natera,6 Juan E. Corzo,7 José Manuel Lomas,8 Juan Pasquau,9Alfonso del Arco,10 María Paz Martínez,11 Alberto Romero,12 Miguel A. Muniain,1,2,14 Marina de Cueto,1,2 Álvaro Pascual,1,2,13 and Jesús Rodríguez-Baño;1,2,14 for the REIPI/SAB groupb 1Unidad Clínica de Enfermedades Infecciosas y Microbiología, Hospital Universitario Virgen Macarena, Sevilla; 2Spanish Network for Research inInfectious Diseases, Instituto de Salud Carlos III, Madrid; 3Unidad de Enfermedades Infecciosas, Hospital de Cruces, Baracaldo; 4Unidad deEnfermedades Infecciosas, Hospital Universitairo Marqués de Valdecilla, Universidad de Cantabria–IFIMAV, Santander, Cantabria; 5Unidad deEnfermedades Infecciosas, Hospital de San Pedro, La Rioja; 6Unidad de Enfermedades Infecciosas, Hospital Universitario Reina Sofía, Córdoba;7 Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Hospital Virgen de Valme, Sevilla; 8Unidad de Enfermedades Infecciosas, Hospital Juan Ramón Jiménez, Huelva; 9Unidad de Enfermedades Infecciosas y Microbiología Clínica, Hospital Virgen de las Nieves, Granada;10Unidad de Enfermedades Infecciosas, Hospital Costa del Sol, Málaga; 11Unidad de Enfermedades Infecciosas, Hospital de Torrecárdenas, Almería;12Unidad de Enfermedades Infecciosas, Hospital Universitario de Puerto Real, Cádiz; and 13Departamento de Microbiología and 14Departamento deMedicina, Universidad de Sevilla, Spain (See the Editorial Commentary by Liu on pages 1234–6.) Background. Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality.
Several aspects of clinical management have been shown to have significant impact on prognosis. The objective of the study was to identify evidence-based quality-of-care indicators (QCIs) for the management of SAB, and toevaluate the impact of a QCI-based bundle on the management and prognosis of SAB.
Methods. A systematic review of the literature to identify QCIs in the management of SAB was performed. Then, the impact of a bundle including selected QCIs was evaluated in a quasi-experimental study in 12 tertiary Spanish hos-pitals. The main and secondary outcome variables were adherence to QCIs and mortality. Specific structured individu-alized written recommendations on 6 selected evidence-based QCIs for the management of SAB were provided.
Results. A total of 287 and 221 patients were included in the preintervention and intervention periods, respective- ly. After controlling for potential confounders, the intervention was independently associated with improved adher-ence to follow-up blood cultures (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.78–4.49), early source control(OR, 4.56; 95% CI, 2.12–9.79), early intravenous cloxacillin for methicillin-susceptible isolates (OR, 1.79; 95% CI,1.15–2.78), and appropriate duration of therapy (OR, 2.13; 95% CI, 1.24–3.64). The intervention was independently as-sociated with a decrease in 14-day and 30-day mortality (OR, 0.47; 95% CI, .26–.85 and OR, 0.56; 95% CI, .34–.93, re-spectively).
Conclusions. A bundle orientated to improving adherence to evidence-based QCIs improved the management of patients with SAB and was associated with reduced mortality.
Keywords. Staphylococcus aureus; intervention; bacteremia; bloodstream infections; clinical management.
Received 14 March 2013; accepted 17 June 2013; electronically published 8 August 2013.
aPresent affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen del Rocío, Sevilla, Spain.
Clinical Infectious Diseases bOther authors from the REIPI/SAB group are listed in the Acknowledgments.
The Author 2013. Published by Oxford University Press on behalf of the Infectious Correspondence: Jesús Rodríguez-Baño, PhD, MD, Unidad Clínica de Enferme- Diseases Society of America. All rights reserved. For Permissions, please e-mail: dades Infecciosas y Microbiología, Avda Dr Fedriani 3, 41009 Sevilla, Spain DOI: 10.1093/cid/cit499 Evidence-Based Bundle on SAB • CID 2013:57 (1 November) • 1225 Staphylococcus aureus is an important human pathogen and At present, many tertiary hospitals develop active "bactere- one of the leading causes of both nosocomial and community- mia programs," in which infectious diseases specialists and onset bloodstream infections worldwide ]. Staphylococcus clinical microbiologists provide early unsolicited advice for the aureus bacteremia (SAB) causes significant morbidity, mortali- management of patients with bacteremia. Despite this, the spe- ty, and healthcare costs; complications are frequent, and mor- cific difficulties inherent to management of SAB may need ad- tality ranges from 20% to 40% [Importantly, some aspects ditional interventions. The objectives of this study were (1) to of clinical management have been associated with better out- identify evidence-based quality-of-care indicators (QCIs) for comes [Thus, previous studies showed that adherence to the management of SAB; and (2) to evaluate the impact of an specialized advice is associated with improved management intervention based on a bundle of selected QCIs aimed at im- and, in some of them, even reduced mortality [In these proving the management and outcome of patients with SAB.
studies, the management and outcomes of patients with SABwho were treated following the recommendations of infectious diseases specialists were compared with those of patients forwhom specialized consultation was not sought or where the Identification of Quality-of-Care Indicators for the Management recommendations provided were not followed. The recommen- dations provided by specialists in these studies were not struc- A systematic review of the literature was performed to identify tured and/or had not been prioritized in accordance with an the best evidence on aspects related to the clinical management of SAB that had a significant influence in prognosis. Studieswere retrieved from the PubMed database using the followingsearch terms: Staphylococcus aureus OR S. aureus, AND bacter-emia OR bloodstream infection OR sepsis, AND outcome OR Preintervention and Intervention Activities Performed on Patients With Staphylococcus aureus Bacteremia in the Partic- complication OR mortality OR death OR recurrence. Observa- ipating Hospitals tional and randomized studies were selected if the 2 followingcriteria were fulfilled: the predictors or risk factors for outcome determinants (including rates of clinical cure, microbiological Early report (verbal or written) of Gram stain cure, mortality, complications or recurrence) were studied, and results was provided for all patients with accepted methods for control of confounding were used in the positive blood cultures by clinicalmicrobiologists in 6 of the 12 participating case of observational studies (including multivariate or strati- centers. Seven centers had an active fied analysis or matching). The studies were reviewed by 2 in- "bacteremia program" in which unsolicitedconsultation for all SAB cases of BSI were vestigators (L.E.L.-C. and J.R.-B.). The variables independently provided by infectious diseases subspecialists; and consistently (eg, they were found in at least 2 studies) neither the recommendations provided nor the related to outcome and amenable to clinical intervention were follow-up procedures were structured, but weredone at the discretion of the infectious diseases selected as QCIs; for each of them a formula to measure the subspecialist. Adherence to recommendations level of adherence to the indicator was defined.
was not prospectively measured.
1. The intervention was explained to the different services in specific educational sessions. An Intervention: Study Design and Setting informative letter was also sent to all heads of The intervention study was performed in 12 tertiary hospitals services before the intervention period started.
in Spain; 8 of them are teaching hospitals, and 10 have >500 2. Specific recommendations, based on the 6 selected quality-of-care indicators, were beds. There are infectious diseases services or units in all 12, specifically provided at least 3 days per week by and active transplantation programs in 4. A quasi-experimental an infectious diseases specialists from the day design, before (from January through June 2010) and during S. aureus was identified from blood culture untilthe patient was discharged or died. The the implementation of the intervention (from July to December recommendations were discussed with the 2010), was used; in one hospital where the intervention was attending physician and were also provided in astructured form which was added to the charts piloted, the preintervention and intervention periods were and signed by the from March 2008 to August 2009, and from September 2009 to infectious diseases specialist at each visit.
Adherence to the recommendations was at the May 2011, respectively. All episodes of SAB involving admitted discretion of attending physician.
patients >17 years of age were considered eligible. Patients were 3. The form also included a summary of the detected through daily review of microbiology reports. Only 1 rationale for the intervention, which served aseducational material.
episode per patient (the first) was included, unless a laterepisode was separated from the previous one by an interval of Abbreviations: BSI, bloodstream infection; SAB, Staphylococcus aureusbacteremia.
>3 months without evidence of recurrence from a deep-seated 1226 • CID 2013:57 (1 November) • López-Cortés et al Definitions of Quality-of-Care Indicators for Staphylococcus aureus Bacteremia Selected After Systematic Review of the Follow-up blood cultures Performance of control blood cultures 48–96 h Patients in whom follow-up blood cultures [9–11] [14] [15] [21] after antimicrobial therapy was started were collected ×100/patients alive regardless of clinical evolution Early source control Removal of nonpermanent vascular catheter Patients in which the amenable source whenever the catheter was suspected or was removed in <72 h ×100/patients confirmed as the source of SAB, or drainage with source amenable of removal/ of an abscess in <72 h Echocardiography in Performance of echocardiography in patients Patients with echocardiography ×100/ [9] [10] [12–15] patients with clinical with complicated bacteremia (see definition patients with complicated bacteremia or in Methods) or predisposing conditions for predisposing condition for endocarditis, alive at least 96 h Early use of intravenous Definitive therapy with intravenous cloxacillin Definitive therapy with intravenous [9] [13] [79] [81] cloxacillin for MSSA as (at least 2 g every 6 h or adjusted based on cloxacillin ×100/nonallergic patients with definitive therapy renal function in renal failure) in cases of methicillin-susceptible strains (allergicpatients excluded). Treatment should bestarted within the first 24 h after methicillinsensitivity was available. For hemodialysispatients, cefazolin 2 g after eachhemodialysis session was acceptable Adjustment of vancomycin Measurement of trough levels of vancomycin Patients with trough level of vancomycin [24] [59] [76–80] dose according to trough in patients treated for at least 3 d with this determined and dose adjusted ×100/ antibiotic and adjustment of dose in order to patients treated with vancomycin for at achieve plasma trough levels between 15 and 20 mg/L in survivors Treatment duration Duration of antimicrobial therapy of at least 14 Patients with appropriate duration of [10] [12–14] [21] d for uncomplicated bacteremia and 28 d for therapy ×100/patients alive at 14 or 28 d complexity of infection complicated bacteremia. Sequential oral in cases of uncomplicated or treatment with fluoroquinolone plus complicated bacteremia, respectively rifampin, trimethoprim-sulfamethoxazole, orlinezolid was considered accepted in Abbreviations: MSSA, methicillin-susceptible Staphylococcus aureus; SAB, Staphylococcus aureus bacteremia.
infection. Patients who died in the first 48 hours (who were not Variables and Definitions subject to intervention) and those patients receiving palliative The main outcome variable of the quasi-experimental study care for terminal conditions were excluded.
was adherence to the 6 QCIs selected, measured as the propor- The intervention and the activities performed during the tion of cases in which the recommended action was performed.
preintervention period are summarized in Table The inter- As secondary outcome variables, 14- and 30-day all-cause mor- vention consisted of a set of written recommendations accord- tality and the 90-day recurrence rate were considered. Explana- ing to the 6 aspects selected as QCIs provided in a structured tory variables included demographics, type and severity of form by an infectious diseases specialist at each hospital. All pa- underlying conditions, acquisition type of SAB, source of infec- tients were followed until discharge or death and were assessed tion, severity of systemic inflammatory response syndrome at for survival and recurrence on days 30 and 90 during a visit to presentation ], susceptibility to methicillin, antimicrobial the outpatient clinic or by phone call. Patient data were collect- therapy, support therapy, and outcome [We used the ed by a nonblinded investigator in each of the participating Charlson comorbidity index to measure the severity of chronic underlying conditions [validated as predictive of mortality The study was approved by the ethics committee of the Hos- among patients with SAB Acute severity of illness was as- pital Universitario Virgen Macarena, which waived the need to sessed using the Pitt bacteremia score, measured retrospectively obtain written informed consent from the patients on the un- on the day before SAB was diagnosed, which has also been vali- derstanding that the intervention was aimed at improving dated as a predictor for mortality in SAB ]. Type of acquisition quality of care according to evidence-based standard of care.
was classified as community-associated, healthcare-associated, or Evidence-Based Bundle on SAB • CID 2013:57 (1 November) • 1227

Microbiological Studies The recommendations of the Spanish Society of Infectious Dis-eases and Clinical Microbiology were followed for performing,processing, and interpreting the blood cultures ]. Sus-ceptibility testing was performed using accepted methods ateach hospital.
Statistical Analysis Crude comparisons were performed using the χ2 or Fisherexact tests for percentages, as appropriate, and the Mann-Whitney Flow chart of patients included in the multicenter quasi- U test for continuous variables. Relative risks with experimental study.
95% confidence intervals (Cis) were calculated for the crudeanalysis of adherence to the indicators in the preinterventionand intervention periods. Multivariate analyses were performedusing logistic regression. Variables were selected using the nosocomial, following Friedman criteria [Primary sources of backward stepwise procedure; P values <.2 and <.1 were used as SAB were defined according to the Centers for Disease Control cutoffs for including and deleting variables in the models, re- and Prevention [], and evaluated in consensus by 2 investiga- spectively. The predictive ability of the models was studied by tors in each on the participant centers. Sources of SAB associated the area under the receiver operating characteristic curves.
with high mortality in previous studies were classified as high-risk Effect modifications between the exposure of interest and other sources; these included endocarditis, endovascular infections other variables were investigated. The software used for the analysis than catheter-related, central nervous system infections, intra- was the SPSS v17.0 package.
abdominal infections, and respiratory tract infections [, We considered empirical antibiotic treatment as appropriate if at least 1 active drug according to in vitro susceptibility resultshad been initiated in the first 12 hours after the blood culture Systematic Review and Definition of Quality-of-Care Indicators was obtained. Persistent SAB was defined as the isolation of S.
The search strategy retrieved 2828 articles. After reviewing the aureus in blood cultures obtained from peripheral veins for ≥3 abstracts, 184 articles were fully reviewed and 81 were selected days despite active antimicrobial therapy according to suscepti- according to the preestablished criteria (see references in bility testing. For the purpose of clinical decisions, SAB was Six aspects of clinical management from 16 considered as complicated if any of the following criteria were articles showing an impact on outcome were selected as QCIs present: persistent bacteremia; development of endocarditis or (Table performance of follow-up blood cultures; early metastatic foci; presence of Janeway lesions, Osler nodes, or source control; performance of echocardiography in patients other cutaneous or mucosal lesions suggestive of acute systemic with specific criteria; early use of intravenous cloxacillin in infection (including petechiae, vasculitis, infarcts, ecchymoses, cases of methicillin-susceptible S. aureus (MSSA) (or cefazolin pustules, Roth spots, or conjunctival hemorrhage) in the in patients under hemodialysis) as definitive therapy in nonal- absence of a firm alternate explanation [presence of any per- lergic patients; adjustment of vancomycin dose according to manent prosthetic device; any device-related infection where trough levels; and provision of an appropriate duration of the device could not be removed in the first 3 days; and SAB in therapy according to the complexity of infection. The defini- patients under chronic hemodialysis [, ]. We included tions of QCIs and the formulas used to measure them are the variable "unfavorable clinical course" to reflect the clinical shown in Table .
situation in the same day the intervention was started (typically,48 hours after the blood cultures were taken); it was defined Analysis of the Impact of Intervention as worsening or lack of evident improvement in the signs of During the study period, 536 episodes of SAB were diagnosed sepsis [with regard to the situation the day the blood cul- in adult patients admitted to the participating hospitals and tures were taken. Cure was defined as the absence of all signs were considered eligible for the study; 28 cases were excluded and symptoms of infection and a negative blood culture at the (Figure so that 287 episodes were finally included in the pre- end of antibiotic therapy []. Recurrence was defined as the intervention period and 221 in the intervention period. The isolation of S. aureus with the same susceptibility pattern from baseline demographics and clinical characteristics of the pa- blood cultures or from a deep-seated focus in the following 3 tients in both periods are shown in Table . The proportion of months after clinical cure had been reached.
vascular catheter–related episodes was higher in the intervention 1228 • CID 2013:57 (1 November) • López-Cortés et al Features of the Patients With Staphylococcus aureus Bacteremia All Patients (n = 508) Preintervention (n = 287) Intervention (n = 221) Median age, y, (IQR) Diabetes mellitus Chronic pulmonary disease Chronic liver disease Intravenous drug abuse Charlson index ≥2 Source of bacteremia Vascular catheter Skin and/or soft tissue Respiratory tract High-risk sourcea Complicated bacteremia Endocarditis (primary and secondary)b Appropriate empirical therapy Severe sepsis or septic shock Unfavorable coursec Data are expressed as No. (%) unless otherwise indicated.
Abbreviations: IQR, interquartile range; MRSA, methicillin-resistant Staphylococcus aureus.
a High-risk source: endocarditis, nervous central system, abdominal, and respiratory.
b Considered only among patients for whom echocardiography was performed.
c Considered the day the blood culture results were reported as defined in the Methods.
period, whereas those related to a skin and soft tissue infection intervention was independently associated with improved ad- were less frequent.
herence to follow-up blood cultures (from 61.2% to 80.3% in The crude comparison of adherence to QCIs between the the different hospitals), source control (from 70.2% to 90.3%), preintervention and intervention periods is shown in Table echocardiography in patients with complicated bacteremia Adherence significantly improved during the intervention (from 52.8% to 73.3%), early cloxacillin in MSSA (from 56.9% period for all QCIs except for adjustment of vancomycin dose to 76.3%), and appropriate duration of treatment depending on according to trough levels. All centers increased the adherence clinical complexity (from 72.9% to 85.2%).
to at least 4 QCIs; a statistically significant improvement (eg, Crude analysis showed a higher 14-day mortality rate in the P < .05) to at least 2 QCIs was seen in 9 participant centers (it preintervention period than in the intervention period (51/287 should be noted that the number of cases was low in some [17.8%] vs 25/221 [11.3%], P = .04), whereas the difference for centers). The median percentage of improvement for each QCI 30-day mortality was not statistically significant (64/287 and interquartile range is shown in Table To control the [22.3%] vs 37/221 [16.7%], P = .12). Recurrence of SAB at 90 effect of potential confounders on the effect of the intervention, days showed no significant differences (3/287 [1%] vs 2/221 we carried out multivariate analyses (Table . In summary, the [0.9%]; RR = 0.86; 95% CI, .14–5.13; P = .87). Ninety-day Evidence-Based Bundle on SAB • CID 2013:57 (1 November) • 1229 Adherence to Quality-of-Care Indicators Median Improvement in Relative Risk for Intervention Percentage of Adherence to 1.31 (1.15–1.49) 2.83 (1.78–4.49)b 1.29 (1.13–1.49) 4.56 (2.12–9.79)c 1.38 (1.13–1.68) 2.50 (1.42–4.41)d Early cloxacillin in 1.25 (1.07–1.45) 1.79 (1.15–2.78)e Vancomycin dosing 1.18 (.80–1.73) 1.42 (.65–3.10)f Treatment duration 1.16 (1.05–1.29) 2.13 (1.24–3.64)g Data are expressed as No. (%) of patients except otherwise indicated.
Abbreviations: CI, confidence interval; IQR, interquartile range; MSSA, methicillin-susceptible Staphylococcus aureus; OR, odds ratio; QCI, quality-of-care indicator.
a Adjusted ORs were calculated by multivariate analyses.
The variables included in final models were: bUnfavorable clinical course and catheter source; cType of acquisition; dCatheter source and Charlson index; eCathetersource, Charlson index and type of acquisition; fCatheter source; gComplicated bacteremia, Charlson index, and catheter source.
mortality was higher in the preintervention group, although time to first administration of an active drug and to produce without statistical significance (97/287 [33.8%] vs 59/162 better clinical management of sepsis [, ]. In the specific [26.7%]; relative risk [RR] = 0.78; 95% CI, .60–1.03; P = .08).
case of SAB, some previous studies showed that infectious dis- We then performed specific analyses to evaluate the impact of eases specialists' consultation was associated with better man- the intervention on 14-day and 30-day mortality. First, we per- agement and, in some studies, with a better prognosis ]. A formed univariate analyses of the association of different vari- summary of the adherence to the 6 QCIs used in this study as ables with mortality and ). The variables age ≥60 reported in previous studies is shown in years, source other than catheter, Pitt score >2, and interven- tion period were associated with 14- and 30 day mortality. Mul- The use of QCIs is useful for evaluating and monitoring dif- tivariate analyses are shown in Table ; the clinical intervention ferent aspects of healthcare procedures. Indicators are quantita- was independently associated with a decrease in 14-day and 30- tive measures that should be sufficiently sensitive, specific, day mortality after controlling for potential confounders in the valid, and reliable to evaluate those aspects of care that influ- multivariate analysis. The results did not significantly change ence appropriately defined outcomes, and they should be when the variable source was considered as polychotomous (eg, ideally evidence based [, Management of SAB is clinical- all the sources were included) instead of the dichotomized low/ ly challenging and has been demonstrated as importantly influ- high-risk sources. Including the variable "preintervention bac- encing outcome, making it a suitable process for defining QCIs.
teremia program" was not associated with mortality and did To our knowledge, QCIs for SAB management had not previ- not influence the impact of the intervention.
ously been established using an appropriate methodology; byusing a systematic review of the literature we were able to iden- tify key aspects for SAB management that were amenable fordesigning an intervention.
Our study shows that a bundle intervention aimed at improving During the intervention period, adherence to CQI was sig- the adherence to selected evidence-based QCI indicators in the nificantly and independently improved except for adjustment management of SAB was effective and associated with reduced of vancomycin dose according to trough levels, probably due to the lower number of patients in this subset. These results dem- The management of patients with bacteremia is complex.
onstrate that it is possible to improve the clinical management Widely recognized important aspects of management includes of SAB with an intervention based on quality-of-care indica- providing early adequate support and antimicrobial therapy, tors. We think that the use of a structured form for making rec- identifying potential foci which should be properly and timely ommendations, which could then be included in the medical controlled, and active workup and follow-up to promptly records, was crucial to achieving these results; apart from pro- detect complications [Advice from infectious diseases spe- viding clear and structured recommendations, the form was cialists has been shown to reduce inappropriate treatment and also useful for reminding the infectious diseases specialists of 1230 • CID 2013:57 (1 November) • López-Cortés et al Univariate Analysis of Variables Associated With 14- Univariate Analysis of Variables Associated With 30- 2.26 (1.30–3.92) 2.52 (1.55–4.11) 1.34 (.66–2.72) 1.41 (.75–2.63) 2.20 (1.40–3.44) 1.76 (1.10–2.82) 1.02 (.58–1.81) 0.09 (.58–1.12) 2.09 (1.22–3.59) 4.37 (2.28–8.39) 1.52 (.99–2.34) 1.44 (.63–3.27) 3.67 (2.27–5.93) 0.86 (.40–1.86) 3.63 (2.28–5.78) 2.13 (1.48–3.04) 1.65 (.84–3.10) Complicated bacteremia 0.86 (.54–1.36) Complicated bacteremia 1.02 (.67–1.54) Empirical treatment 1.11 (.78–1.57) Empirical treatment 1.05 (.58–1.89) 1.14 (.72–1.80) Hospital with "bacteremia program" 0.81 (.52–1.25) Hospital with "bacteremia program" 1.05 (.71–1.54) Intervention period Intervention period 0.46 (.29–0.72) Abbreviations: CI, confidence interval; ICU, intensive care unit; MRSA, 0.75 (.42–1.08) methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; RR, relative risk.
Abbreviations: CI, confidence interval; ICU, intensive care unit; MRSA,methicillin-resistant Staphylococcus aureus; MSSA, methicillin-susceptible Staphylococcus aureus; RR, relative risk.
all the key aspects to consider for the management of patientswith SAB in a convenient and timely manner.
control for the effect of source, this variable was included in the The intervention was also associated with lower mortality.
multivariate models both as a polychotomous (all the sources) The crude association found might be influenced by the different and as a dichotomous variable (low- and high-risk sources); the proportion of some variables potentially affecting outcome results were similar and showed that mortality was lower during (confounders), such as the source of SAB. In relation with the the intervention period. However, it is possible that it was not the source of bacteremia, catheter-related SAB was more frequent specific way that intervention was performed that caused the in the intervention period; catheter-related bacteremia is reduction in mortality; unmeasured aspects of improved man- usually associated with lower mortality, whereas others such as agement of the patients may have also had an impact on these respiratory tract infections have a higher mortality rate To results. Whatever the reason, implementing the intervention Evidence-Based Bundle on SAB • CID 2013:57 (1 November) • 1231 Multivariate Analyses of Variables Associated With 14- and 30-Day Mortality Among Patients With Staphylococcus Other REIPI/SAB group authors.
Carmen Velasco and Francisco aureus Bacteremia Javier Caballero (Departamento de Microbiología, Universidad de Sevilla);Miguel Montejo and Jorge Calvo (Unidad de Enfermedades Infecciosas, Hospital de Cruces, Baracaldo); Marta Aller-Fernández (Unidad de Enfer-medades Infecciosas, Hospital Universitario Marqués de Valdecilla, Univer- sidad de Cantabria); Luis Martínez, María Dolores Rojo, and Victoria 2.97 (1.51–5.87) Manzano-Gamero (Unidad de Enfermedades Infecciosas y Microbiología, 3.04 (1.74–5.33) Hospital Virgen de Valme, Sevilla).
High-risk sourcea 2.80 (1.32–5.92) J. R.-B. and L. E. L.-C. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: J. R.-B., J. G.-A., A. P., M. A. M., and L. E. L.- C. Intervention activities: J. G.-A., M. D. dT., 3.48 (1.89–6.41) M. A. M., J. R.-B., E. B. B., M. C. F., M. S.-F., C. N., J. E. C., J. M. L., J. P., 2.34 (1.40–3.92) A. dA., M. P. M., A. R., M. M., J. C., M. A.-F., L. M. Process and interpreta- High-risk sourcea 3.11 (1.54–6.26) tion of microbiological isolates: C. V., F. J. C., M. dC., M. D. R., V. M.-G.
Analysis and interpretation of data: J. R.-B., M. D. dT., M. dC., and L. E. L.- C. Drafting of the manuscript: L. E. L.-C. Critical revision of the manuscript Abbreviations: CI, confidence interval; OR, odds ratio.
for important intellectual content: J. G.-A., M. D. dT., C. V., M. dC., aHigh-risk source includes endovascular sources different than catheter, M. A. M., and A. P. Statistical analysis: L. E. L.-C. and J. R.-B. Study supervi- endocarditis, nervous central system infections, intra-abdominal infections, sion: J. R.-B.
and respiratory tract infection.
Financial support.
This study was supported by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, co-financed bythe European Development Regional Fund "A Way to Achieve Europe"; theSpanish Network for the Research in Infectious Diseases (REIPI RD12/ had a positive impact. As in all bundle interventions, it is diffi- 0015); the Consejería de Salud, Junta de Andalucía (PI-0185–2010); and the Fundación Progreso y Salud, Junta de Andalucía.
cult to identify the impact of individual measures; we hypothe- The funding institutions had no role in the design, perfor- size that all or several measures act synergistically, although mance of the study, analysis, writing, or decision to publish.
more studies would be needed to identify the essential compo- Potential conflicts of interest. J. R.-B. has served as consultant and nents of the intervention.
speaker for Pfizer, Roche, Astellas, Novartis, and Merck. A. P. has been aconsultant for Pfizer; has served as speaker for Wyeth, and Pfizer; and has Some of the limitations of previous studies include their retro- received research support from Pfizer, Wyeth, and Novartis. All other spective nature [; that the way the recommendations were authors report no potential conflicts.
provided were not structured or were unspecified All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the and that they were performed in one center.
content of the manuscript have been disclosed.
Our study has limitations that should be taken into account.
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6. Liu C, Bayer A, Cosgrove SE, Daum RS, et al. Clinical practice guide- are available at Clinical Infectious Diseases online lines by the Infectious Diseases Society of America for the treatment of ). Supplementary materials consist of data methicillin-resistant Staphylococcus aureus infections in adults and provided by the author that are published to benefit the reader. The posted children. Clin Infect Dis 2011; 52:285–92.
materials are not copyedited. The contents of all supplementary data are the 7. Gudiol F, Aguado JM, Pascual A, et al. Consensus document for the sole responsibility of the authors. Questions or messages regarding errors treatment of bacteremia and endocarditis caused by methicillin- should be addressed to the author.
resistant Staphylococcus aureus. Sociedad Española de Enfermedades 1232 • CID 2013:57 (1 November) • López-Cortés et al Infecciosas y Microbiología Clínica. Enferm Infecc Microbiol Clin 24. Fowler VG, Justice A, Moore C, et al. Risk factors for hematogenous 2009; 27:105–15.
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Evidence-Based Bundle on SAB • CID 2013:57 (1 November) • 1233 Figure S1. Form used to provide recommendations during the intervention period (English translation). The form was adapted at each participating center for electronic or paper charts. S References.
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Table S1. Summary of adherence fo the 6 quality-of-care indicators used in this study as found in previous reports evaluating the impact of infectious disease specialist consultation on the management of S. aureus bacteraemia. Data are expressed as percentage of patients in the intervention / non-intervention groups except where specified. Prospective cohort / Routine IDCa Before-after / Retrospective cohort / Prospective cohort / Retrospective cohort / Retrospective cohort / Before-after, multicenter / MRSA: methicil in-resistant S. aureus. IDC: Infectious diseases consultation. aData means adherence / non adherence to infectious diseases recommendations. bTransesophageal echocardiography

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