Abstract
Background: Candida bloodstream infection is associated with high mortality. Infectious disease consultation improves outcomes in several infections, including Staphylococcus aureus and cryptococcosis, as well as multidrug-resistant organisms. We aimed to examine the association between infectious disease consultation and differences in management with mortality in candida bloodstream infections. Methods: In this retrospective, single-centre cohort study, we reviewed the medical charts of all patients admitted to Barnes-Jewish Hospital (St Louis, MO, USA), a tertiary referral centre, aged 18 years or older with candida bloodstream infection from 2002 to 2015. We collected data for demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation to assess 90-day all-cause mortality between individuals with and without an infectious disease consultation. For the survival analysis we used Cox proportional hazards model with inverse weighting by propensity score to assess the effects of infectious disease consultation on mortality and differences in management. Findings: Between Jan 1, 2002, and Dec 31, 2015, of 1794 patients assessed for eligibility, we analysed 1691 patients with candida bloodstream infection; 776 (45·9%) who had an infectious disease consultation and 915 (54·1%) who did not have an infectious disease consultation. All 1691 patients were included in the analysis. None were missing data. Most underlying comorbidities were evenly distributed between groups. 90-day mortality was lower in the infectious disease consultation group than in patients who did not receive an infectious disease consultation (29% [222/776] vs 51% [468/915]; p<0·0001). In the model with inverse weighting by the propensity score, infectious disease consultation was associated with a hazard ratio of 0·81 (95% CI 0·73–0·91; p<0·0001) for mortality. In the consultation group, median duration of antifungal therapy was longer (18 [IQR 14–35] vs 14 [6–20] days; p<0·0001) and central-line removal (587 [76%] of 776 vs 538 [59%] of 915; p<0·0001), echocardiography use (442 [57%] of 776 vs 305 [33%] of 915; p<0·0001), and ophthalmological examination (412 [53%] of 776 vs 160 [17%] of 915; p<0·0001) were more frequently done. Fewer patients in the infectious disease consultation group were not treated (13 [2%] of 776 vs 128 [14%] of 915; p<0·0001). Interpretation: Patients with candida bloodstream infection receiving an infectious disease consultation have lower mortality. This finding might be attributable to these individuals receiving a higher number of non-pharmacological, evidence-based interventions and lower amounts of non-treatment. These data suggest that an infectious disease consultation should be an integral part of clinical care of patients with candida bloodstream infection. Funding: Astellas Global Development Pharma, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.
| Original language | English |
|---|---|
| Pages (from-to) | 1336-1344 |
| Number of pages | 9 |
| Journal | The Lancet Infectious Diseases |
| Volume | 19 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2019 |
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In: The Lancet Infectious Diseases, Vol. 19, No. 12, 12.2019, p. 1336-1344.
Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Effect of infectious disease consultation on mortality and treatment of patients with candida bloodstream infections
T2 - a retrospective, cohort study
AU - Mejia-Chew, Carlos
AU - O'Halloran, Jane A.
AU - Olsen, Margaret A.
AU - Stwalley, Dustin
AU - Kronen, Ryan
AU - Lin, Charlotte
AU - Salazar, Ana S.
AU - Larson, Lindsey
AU - Hsueh, Kevin
AU - Powderly, William G.
AU - Spec, Andrej
N1 - Funding Information: In patients with candida bloodstream infection, infectious disease consultation was associated with an adjusted HR of 0·81 for mortality, translating to a 19% survival benefit. Previous studies have shown that patients with serious and complex infections that have diverse presentations and outcomes have decreased mortality or improvements in other quality-of-care metrics when managed with the assistance of an infectious disease consultation. 6,7 To our knowledge, this is the largest cohort of patients with candida bloodstream infection in which the association between infectious disease consultation and mortality has been examined. In keeping with our findings, previous studies with a smaller number of patients with candidaemia have also found improved survival associated with having an infectious disease consultation. 5,8,9,21 However, this is the first study that included an extensive number of known risk factors to account for confounding by indication through the use of propensity score modelling and to extensively document the differences in management. Furthermore, this particular cohort was constructed specifically to study outcomes in patients with Candida spp infections and has been previously used to address other research questions related to candida. 16,22 Clinical practice guidelines from the Infectious Disease Society of America and the European Society of Clinical Microbiology and Infectious Diseases provide evidence-based recommendations for the management of patients with candida bloodstream infection. 23,24 Treatment of candida bloodstream infection can be complex given the need for timely interventions that improve patient outcomes, such as indwelling device and catheter removal, 25 prompt initiation of antifungal treatment 26 of adequate duration, 23 need for medical and surgical specialty interventions, 27 as well as consideration of Candida spp and host specific factors. 28 Appropriate management of these factors seem to yield better outcomes. 5 A scoring system developed in 2018, the EQUAL Candida Score, summarises and weighs the recommendations for the optimal management of candida bloodstream infection, providing a tool that could be used to measure guideline adherence, facilitate clinical decision making, and improve quality of care. 29 Candidaemia is associated with up to 71% mortality, an alarming rate that can be decreased by almost half when appropriate therapy is given. 3 In our study, when an infectious disease consultation was done, blood cultures were much less frequently ignored and therefore fewer patients in this group went untreated. The most common causes of not treating patients in the infectious disease consultation group were physician unawareness of a positive culture and the patient leaving against medical advice. Previous studies have shown higher rates of appropriate empirical antimicrobial therapy in patients with bloodstream infections caused by other types of microorganisms who had an infectious disease consultation. 6 Inadequate initial empirical antifungal therapy is associated with increased mortality in patients with candida bloodstream infection. 30 Although in our study initial selection of antifungals was not dissimilar between groups, patients seen by an infectious disease physician received a significantly longer treatment course (18 vs 14 days). Longer duration of treatment could be attributed to the increased number of candida bloodstream infection complications seen in the infectious disease consultation group or because documented negative blood culture was established as the first day of the prescribed treatment course received, as recommended per current treatment guidelines. 23 Central lines are a well known predisposing factor for candida bloodstream infection. 31 Central-line removal is an intervention that is associated with faster blood culture clearance and shown to be a prognostic factor of mortality. 25,31 However, based on the absence of randomised controlled trials to evaluate the effect of central-line removal, a 2016 meta-analysis found no evidence to support catheter removal in patients with candida bloodstream infection. 32 In our study, removal of the central line was associated with lower 90-day mortality in patients with candida bloodstream infection; an intervention that was more frequently done when infectious disease physicians were involved in the patient's care. In our study, patients in the infectious disease consultation group were more often assessed for complications of candidaemia. Not identifying patients with a higher burden of disease could also explain the higher mortality seen in the group who did not have an infectious disease consultation. Use of echocardiography and subsequent diagnosis of infective endocarditis were both more common in patients who received an infectious disease consultation, similar to the increased use of such diagnostic tools in patients with Staphylococcus aureus bacteraemia who were seen by an infectious disease physician. 33 In the infectious disease consultation group, the incidence of endocarditis in patients with candida bloodstream infection was 3·9% (30 patients), similar to that seen in a 2015 retrospective study (4·2%). 34 The prevalence of haematogenous endophthalmitis can vary between 2·2% to 20·1% in patients with candida bloodstream infection. 35 Given that ocular candidiasis can be clinically silent in up to 50% of cases, 36 and that many patients with candida bloodstream infection are too ill to communicate their symptoms, current treatment guidelines recommend that all patients with candidaemia should have a funduscopic examination. 23 In our study, ophthalmological examination was more frequently done when patients had an infectious disease consultation and therefore detection of endophthalmitis was also more common in this group. The increased frequency of these interventions, not ignoring positive blood cultures and a longer duration of antifungal therapy, might have been responsible for the decreased mortality seen in the infectious disease consultation group. This finding is in keeping with the mortality benefit of a consultation in patients with S aureus bacteraemia, in which it has been shown that the effect is derived from better adherence to these quality-of-care standards. 33 However, our study has several limitations. First, it is a single centre, retrospective study subject to potential unmeasured confounding. However, to date, it is the largest cohort of patients with candida bloodstream infection and included a very extensive list of established prognostic comorbidities, 15 as well as known specific predisposing factors for development of candida bloodstream infection. 37 The beneficial effect of receiving an infectious disease consultation appears to be a universal phenomenon across institutions, as seen in much smaller studies. 5,8,9 Notably, this study was done in the USA where clinical microbiologists rarely advise physicians on direct patient management. It would be interesting to examine the effect of an infectious disease physician consultation on outcomes in a setting with different clinical practice models. Second, even in a large centre, the number of patients with some of the important predisposing factors were small. However, this distribution is likely to be reflective of the patient case mixes seen in other tertiary referral centres. Finally, selection bias could have occurred as some patient populations were under-represented in each group. However, we adjusted these differences between groups with inverse weighting by propensity score and used Cox proportional hazards regression analysis. In the primary analysis, we included only infectious disease consultation in the model, and in secondary analysis, other variables independently associated with 90-day mortality. In conclusion, in our study, using a conservative analysis method, patients with candida bloodstream infection who received an infectious disease consultation were significantly less likely to die than patients without an infectious disease consultation. The patients in the infectious disease consultation group more often had investigations and treatment consistent with evidence-based practices. The disease was less often left untreated by infectious disease physicians. The protective effect of obtaining an infectious disease consultation on mortality in patients with candida bloodstream infection suggests that this consultation should be an integral part of the clinical care of patients with candidaemia. Contributors All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. AS, CM-C, MAO, KH, and JO'H were responsible for study concept and design. CM-C, JO'H, MAO, DS, ASS, RK, CL, KH, GP, and AS were responsible for acquisition, analysis, or interpretation of data. AS, CM-C, MAO, and JO'H were responsible for drafting of the manuscript. MAO and DS were responsible for statistical analysis. AS obtained funding. Declaration of interests AS reports grants and personal fees from Astellas Global Development Pharma and Mayne Pharma; grants from Scynexis, Cidara, MiraVista, and IMMY; and personal fees from Viamet, during the conduct of the study. WGP reports grants and personal fees from Merck and Co, and Gilead Sciences, outside the submitted work. DS reports personal stock ownership in AbbVie and Bristol-Myers Squibb. MAO reports grants and personal fees from Pfizer; and grants from Merck and Sanofi. All other authors declare no competing interests. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health or Astellas Global Development Pharma. Acknowledgments This study was funded by Astellas Global Development Pharma , through an investigator-sponsored grant ( MYCA-15L03 ) to the hosting institution. In addition, research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health, and grant number R24 HS19455 through the Agency for Healthcare Research and Quality. Publisher Copyright: © 2019 Elsevier Ltd
PY - 2019/12
Y1 - 2019/12
N2 - Background: Candida bloodstream infection is associated with high mortality. Infectious disease consultation improves outcomes in several infections, including Staphylococcus aureus and cryptococcosis, as well as multidrug-resistant organisms. We aimed to examine the association between infectious disease consultation and differences in management with mortality in candida bloodstream infections. Methods: In this retrospective, single-centre cohort study, we reviewed the medical charts of all patients admitted to Barnes-Jewish Hospital (St Louis, MO, USA), a tertiary referral centre, aged 18 years or older with candida bloodstream infection from 2002 to 2015. We collected data for demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation to assess 90-day all-cause mortality between individuals with and without an infectious disease consultation. For the survival analysis we used Cox proportional hazards model with inverse weighting by propensity score to assess the effects of infectious disease consultation on mortality and differences in management. Findings: Between Jan 1, 2002, and Dec 31, 2015, of 1794 patients assessed for eligibility, we analysed 1691 patients with candida bloodstream infection; 776 (45·9%) who had an infectious disease consultation and 915 (54·1%) who did not have an infectious disease consultation. All 1691 patients were included in the analysis. None were missing data. Most underlying comorbidities were evenly distributed between groups. 90-day mortality was lower in the infectious disease consultation group than in patients who did not receive an infectious disease consultation (29% [222/776] vs 51% [468/915]; p<0·0001). In the model with inverse weighting by the propensity score, infectious disease consultation was associated with a hazard ratio of 0·81 (95% CI 0·73–0·91; p<0·0001) for mortality. In the consultation group, median duration of antifungal therapy was longer (18 [IQR 14–35] vs 14 [6–20] days; p<0·0001) and central-line removal (587 [76%] of 776 vs 538 [59%] of 915; p<0·0001), echocardiography use (442 [57%] of 776 vs 305 [33%] of 915; p<0·0001), and ophthalmological examination (412 [53%] of 776 vs 160 [17%] of 915; p<0·0001) were more frequently done. Fewer patients in the infectious disease consultation group were not treated (13 [2%] of 776 vs 128 [14%] of 915; p<0·0001). Interpretation: Patients with candida bloodstream infection receiving an infectious disease consultation have lower mortality. This finding might be attributable to these individuals receiving a higher number of non-pharmacological, evidence-based interventions and lower amounts of non-treatment. These data suggest that an infectious disease consultation should be an integral part of clinical care of patients with candida bloodstream infection. Funding: Astellas Global Development Pharma, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.
AB - Background: Candida bloodstream infection is associated with high mortality. Infectious disease consultation improves outcomes in several infections, including Staphylococcus aureus and cryptococcosis, as well as multidrug-resistant organisms. We aimed to examine the association between infectious disease consultation and differences in management with mortality in candida bloodstream infections. Methods: In this retrospective, single-centre cohort study, we reviewed the medical charts of all patients admitted to Barnes-Jewish Hospital (St Louis, MO, USA), a tertiary referral centre, aged 18 years or older with candida bloodstream infection from 2002 to 2015. We collected data for demographics, comorbidities, predisposing factors, all-cause mortality, antifungal use, central-line removal, and ophthalmological and echocardiographic evaluation to assess 90-day all-cause mortality between individuals with and without an infectious disease consultation. For the survival analysis we used Cox proportional hazards model with inverse weighting by propensity score to assess the effects of infectious disease consultation on mortality and differences in management. Findings: Between Jan 1, 2002, and Dec 31, 2015, of 1794 patients assessed for eligibility, we analysed 1691 patients with candida bloodstream infection; 776 (45·9%) who had an infectious disease consultation and 915 (54·1%) who did not have an infectious disease consultation. All 1691 patients were included in the analysis. None were missing data. Most underlying comorbidities were evenly distributed between groups. 90-day mortality was lower in the infectious disease consultation group than in patients who did not receive an infectious disease consultation (29% [222/776] vs 51% [468/915]; p<0·0001). In the model with inverse weighting by the propensity score, infectious disease consultation was associated with a hazard ratio of 0·81 (95% CI 0·73–0·91; p<0·0001) for mortality. In the consultation group, median duration of antifungal therapy was longer (18 [IQR 14–35] vs 14 [6–20] days; p<0·0001) and central-line removal (587 [76%] of 776 vs 538 [59%] of 915; p<0·0001), echocardiography use (442 [57%] of 776 vs 305 [33%] of 915; p<0·0001), and ophthalmological examination (412 [53%] of 776 vs 160 [17%] of 915; p<0·0001) were more frequently done. Fewer patients in the infectious disease consultation group were not treated (13 [2%] of 776 vs 128 [14%] of 915; p<0·0001). Interpretation: Patients with candida bloodstream infection receiving an infectious disease consultation have lower mortality. This finding might be attributable to these individuals receiving a higher number of non-pharmacological, evidence-based interventions and lower amounts of non-treatment. These data suggest that an infectious disease consultation should be an integral part of clinical care of patients with candida bloodstream infection. Funding: Astellas Global Development Pharma, Washington University Institute of Clinical and Translational Sciences, and the Agency for Healthcare Research and Quality.
UR - http://www.scopus.com/inward/record.url?scp=85075472563&partnerID=8YFLogxK
U2 - 10.1016/S1473-3099(19)30405-0
DO - 10.1016/S1473-3099(19)30405-0
M3 - Article
C2 - 31562024
AN - SCOPUS:85075472563
SN - 1473-3099
VL - 19
SP - 1336
EP - 1344
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 12
ER -