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Delaying the Empiric Treatment of Candida Bloodstream Infection until Positive Blood Culture Results Are Obtained: a Potential Risk Factor for Hospital Mortality
Open accessAbstract
Fungal bloodstream infections are associated with significant patient mortality and health care costs. Nevertheless, the relationship between a delay of the initial empiric antifungal treatment until blood culture results are known and the clinical outcome is not well established. A retrospective cohort analysis with automated patient medical records and the pharmacy database at Barnes-Jewish Hospital was conducted. One hundred fifty-seven patients with a Candida bloodstream infection were identified over a 4-year period (January 2001 through December 2004). Fifty (31.8%) patients died during hospitalization. One hundred thirty-four patients had empiric antifungal treatment begun after the results of fungal cultures were known. From the time that the first blood sample for culture that was positive was drawn, 9 (5.7%) patients received antifungal treatment within 12 h, 10 (6.4%) patients received antifungal treatment between 12 and 24 h, 86 (54.8%) patients received antifungal treatment between 24 and 48 h, and 52 (33.1%) patients received antifungal treatment after 48 h. Multiple logistic regression analysis identified Acute Physiology and Chronic Health Evaluation II scores (one-point increments) (adjusted odds ratio [AOR], 1.24; 95% confidence interval [CI], 1.18 to 1.31; P < 0.001), prior antibiotic treatment (AOR, 4.05; 95% CI, 2.14 to 7.65; P = 0.028), and administration of antifungal treatment 12 h after having the first positive blood sample for culture (AOR, 2.09; 95% CI, 1.53 to 2.84; P = 0.018) as independent determinants of hospital mortality. Administration of empiric antifungal treatment 12 h after a positive blood sample for culture is drawn is common among patients with Candida bloodstream infections and is associated with greater hospital mortality. Delayed treatment of Candida bloodstream infections could be minimized by the development of more rapid diagnostic techniques for the identification of Candida bloodstream infections. Alternatively, increased use of empiric antifungal treatment in selected patients at high risk for fungal bloodstream infection could also reduce delays in treatment.
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In the citing paper
“Finally, in a study of 10,811 patients treated in four Utah hospitals, each hour delay in time from ED arrival to administration of antimicrobials was associated with 1.16 increased odds of in-hospital and 1.10 increased odds of 1-year mortality (1.13 in patients with hypotension vs 1.09 in patients without hypotension) (111).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [111]
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In the citing paper
“Observational studies do, however, suggest that mortality may increase after intervals exceeding 3-5 hours from hospital arrival and/or sepsis recognition (98,111,119,120).”
From Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. (2021) · cites this paper as [111]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Attributable mortality from IC remains high and increases with delays in treatment.”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [136]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Blood cultures take an average of 2–3 days to grow Candida, or longer depending on the species.”
From Epidemiology of Invasive Candidiasis (2024) · cites this paper as [136]
Experimental — accuracy not yet measuredIn the citing paper
“Some observational studies suggested that prompt initiation of appropriate empiric antifungal therapy may be associated with a reduction in mortality, however these studies do not prove a causal relationship between antifungal therapy and outcome, nor do they clarify the role of timing of treatment, and some other studies have failed to show this association [167, 171–173].”
From Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021 (2021) · cites this paper as [173]
In the citing paper
“As mentioned previously, diagnosis of invasive candidiasis and candidemia remains a great challenge, since symptoms and signs are usually non-specific, microbiological cultures are difficult to analyze, and histological specimens require invasive procedures [29,30,46].”
From Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: part I. Epidemiology and diagnosis (2009) · cites this paper as [30]
In the citing paper
“Another single-center retrospective cohort of 157 consecutive patients with a Candida BSI showed a trend toward improved survival when appropriate antifungal therapy was administered within 12 hours of blood culture collection (mortality 11.1% vs 33.1%; P 5 .169).45”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [45]
In the citing paper
“In multivariate analysis the odds of death was 2-fold higher if adequate therapy was delayed more than 12 hours (P 5 .018).”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [45]
In the citing paper
“Invasive candidiasis occurs frequently in hospitalized patients, and is associated with high mortality rates due to delays in recognition and initiation of appropriate antifungals.”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [70]
In the citing paper
“There is extensive clinical evidence that delayed initiation of appropriate antifungal treatment is associated with increased mortality in patients with invasive candidiasis [70,71,72].”
From Treatment of Invasive Candidiasis: A Narrative Review (2018) · cites this paper as [70]
In the citing paper
“Mortality rates are estimated to be as high as 45% [16], probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies [17].”
From Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents (2013) · cites this paper as [17]
In the citing paper
“The Clinical and Laboratory Standards Institute (CLSI) Subcommittee for Antifungal Testing has developed standardized broth microdilution (BMD) (169) and disk diffusion (170) methods for in vitro susceptibility testing of Candida spp.”
From Epidemiology of Invasive Candidiasis: a Persistent Public Health Problem (2007) · cites this paper as [170]
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Stratman, R. C., Martin, C. A., Rapp, R. P., Berger, R., & Magnuson, B. L. (2010) · Nutrition in Clinical Practice · doi:10.1177/0884533610368704 · Cited by 16
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Mensa, J., de la Cámara, R., Carreras, E., Estrella, M. C., Rodríguez, J. Á. G., Gobernado, M., Picazo, J., Aguado, J. M., & Sanz, M. Á. (2009) · Medicina Clínica · doi:10.1016/j.medcli.2009.01.008 · Cited by 16
Defining standards of CARE for invasive fungal diseases in the ICU
Cuenca‐Estrella, M., Kett, D. H., & Wauters, J. (2019) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz038 · Cited by 16
Knabl, L., & Lass‐Flörl, C. (2020) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2020.1760841 · Cited by 17
Sensitive and rapid RT-qPCR quantification of pathogenic Candida species in human blood
Ogata, K., Matsuda, K., Tsuji, H., & Nomoto, K. (2015) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2015.07.021 · Cited by 16
Treatment options in candidaemia
Karthaus, M., & Cornely, O. A. (2007) · Mycoses · doi:10.1111/j.1439-0507.2007.01379.x · Cited by 15
Significant publications on infectious diseases pharmacotherapy in 2010
Hirsch, E. B., Cottreau, J. M., Ikwuagwu, J. O., Lusardi, K. T., Mohr, J., Rodriguez, S. M., Shah, D. N., & Tran, T. T. (2011) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp110125 · Cited by 16
Changing trends in the epidemiology of Candida blood stream infections: A matter for concern?*
Sobel, J. D. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181d16866 · Cited by 16
Andes, D. R., & Lepak, A. J. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cis446 · Cited by 16
Chen, C., Wang, Y., Wu, F., & Hong, W. (2023) · Analytical Chemistry · doi:10.1021/acs.analchem.3c02243 · Cited by 15
Zhou, Y., & Reynolds, T. B. (2024) · Journal of Fungi · doi:10.3390/jof10030171 · Cited by 18
Hoenigl, M., Enoch, D., Wichmann, D., Wyncoll, D. L. A., & Cortegiani, A. (2024) · Mycopathologia · doi:10.1007/s11046-024-00852-3 · Cited by 16
Bal, A. M., Pana, Z. D., Carlesse, F. A. D. M. C., Marek, A., Seidel, D., Mehler, K., Butzer, S., Sprute, R., Stemler, J., Ludwig-Bettin, D., et al. (2025) · Mycoses · doi:10.1111/myc.70041 · Cited by 15
Pappas, P. G., Kauffman, C. A., Andes, D. R., Benjamin, D. K., Calandra, T., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B. J., Ostrosky-Zeichner, L. L., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/598961 · Cited by 16
Pfaller, M. A. (2015) · Journal of Fungi · doi:10.3390/jof1020217 · Cited by 14
van der Geest, P. J., Rijnders, B. J. A., Vonk, A. G., & Groeneveld, A. B. J. (2015) · Mycoses · doi:10.1111/myc.12450 · Cited by 16
on behalf of GISA/FADOI Candida Study Group, Sozio, E., Pieralli, F., Azzini, A. M., Tintori, G., Demma, F., Furneri, G., Sbrana, F., Bertolino, G., Fortunato, S., et al. (2018) · Infection · doi:10.1007/s15010-018-1162-0 · Cited by 15
Candidemia in the patient with malignancy
Alves, J., Palma, P., Azevedo, D., & Rello, J. (2018) · Hospital Practice · doi:10.1080/21548331.2018.1508290 · Cited by 16
Castaño, P., Plaza, M., Molina, F., Hincapié, C., Maya, W., Cataño, J. C., González, J. M., León, A. L., & Jaimes, F. A. (2018) · Tropical Medicine & International Health · doi:10.1111/tmi.13186 · Cited by 16
Fidel, P. L., Yano, J., Esher, S. K., & Noverr, M. C. (2020) · Journal of Fungi · doi:10.3390/jof6010035 · Cited by 18
Singh, S., Singh, M., Verma, N., Sharma, M., Pradhan, P., Chauhan, A., Jaiswal, N., Chakrabarti, A., & Singh, M. (2020) · Medical Mycology · doi:10.1093/mmy/myaa038 · Cited by 16
Reichard, U., Buchheidt, D., Lass‐Flörl, C., Loeffler, J., Lugert, R., Ruhnke, M., Tintelnot, K., Weig, M., & Groß, U. (2012) · Mycoses · doi:10.1111/j.1439-0507.2011.02167.x · Cited by 15
Posteraro, B., Sanguinetti, M., Boccia, S., Feo, E. D., Sorda, M. L., Tana, M., Tirone, C., Aurilia, C., Vendettuoli, V., Fadda, G., et al. (2010) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3181da866d · Cited by 15
Lockhart, S. R., Bolden, C. B., Iqbal, N. J., & Kuykendall, R. J. (2011) · Journal of Clinical Microbiology · doi:10.1128/jcm.05479-11 · Cited by 15
Antifungal Susceptibility Testing: A Primer for Clinicians
Kuper, K. M., Coyle, E. A., & Wanger, A. R. (2012) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1146 · Cited by 16
Candidemia in Siriraj Hospital: epidemiology and factors associated with mortality.
Boonyasiri, A., Jearanaisilavong, J., & Assanasen, S. (2013) · PubMed · Cited by 15
The Black Yeasts: an Update on Species Identification and Diagnosis
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Evaluation of Candida bloodstream infection and antifungal utilization in a tertiary care hospital
Marins, T. A., Marra, A. R., Edmond, M. B., Martino, M. D. V., Yokota, P. K. O., Mafra, A. C. C. N., & Durão, M. S. (2018) · BMC Infectious Diseases · doi:10.1186/s12879-018-3094-9 · Cited by 15
Treatment of invasive candidiasis: between guidelines and daily clinical practice
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Nakada, N., Miyazaki, T., Ueda, T., Yamagishi, Y., Yamada, K., Kawamura, H., Kakeya, H., Mukae, H., Mikamo, H., Takesue, Y., et al. (2021) · Mycoses · doi:10.1111/myc.13380 · Cited by 14
Mayer, L. M., Strich, J. R., Kadri, S. S., Lionakis, M. S., Evans, N. G., Prevots, D. R., & Ricotta, E. (2022) · Open Forum Infectious Diseases · doi:10.1093/ofid/ofac401 · Cited by 14
Multi‐state evaluation of Candida infections in burn patients
Salimi, M., Javidnia, J., Abastabar, M., Mobayen, M., Moslemi, A., Rahimzadeh, G., Charati, J. Y., Tirabadi, N. M., Nouranibaladezaei, S., Asghari, H., et al. (2024) · Mycoses · doi:10.1111/myc.13788 · Cited by 16
Metadata
- Authors
- Morrell, M., Fraser, V. J., & Kollef, M. H.
- Affiliations
- Washington University in St. Louis (US)
- Pulmonary and Critical Care Division
- Corresponding author
- Kollef, Marin H.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2005-09
- Volume
- 49
- Issue
- 9
- Pages
- 3640-3645
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC1195428
- OpenAlex
- W2137575148
- Cited by
- 1,286
- References
- 47
- Citations by year
- 2026: 33 · 2025: 33 · 2024: 41 · 2023: 33 · 2022: 53 · 2021: 51 · 2020: 58 · 2019: 63 · 2018: 65 · 2017: 67 · 2016: 71 · 2015: 77 · 2014: 97 · 2013: 75 · 2012: 78
- FWCI
- 27.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Infective Endocarditis Diagnosis and Management
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Sepsis Diagnosis and Treatment
- Keywords
- candidemia, fungemia, empirical antifungal therapy, treatment delay, blood culture, in-hospital mortality, APACHE II score, prior antibiotic use, rapid diagnostic tests
- MeSH terms
- Adult, Aged, Aged, 80 and over, Candidiasis, Cross Infection, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Cohort Studies, Logistic Models, Fungemia, Treatment Outcome
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