The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.
Empirical Fluconazole versus Placebo for Intensive Care Unit Patients: A Randomized Trial
Abstract
BACKGROUND: Invasive infection with Candida species is an important cause of morbidity and mortality in intensive care unit (ICU) patients. Optimal preventive strategies have not been clearly defined. OBJECTIVE: To see whether empirical fluconazole improves clinical outcomes more than placebo in adult ICU patients at high risk for invasive candidiasis. DESIGN: Double-blind, placebo-controlled, randomized trial conducted from 1995 to 2000. SETTING: 26 ICUs in the United States. PATIENTS: 270 adult ICU patients with fever despite administration of broad-spectrum antibiotics. All had central venous catheters and an Acute Physiology and Chronic Health Evaluation II score greater than 16. INTERVENTION: Patients were randomly assigned to either intravenous fluconazole, 800 mg daily, or placebo for 2 weeks and were followed for 4 weeks thereafter. Two hundred forty-nine participants were available for outcome assessment. MEASUREMENTS: A composite primary outcome that defined success as all 4 of the following: resolution of fever; absence of invasive fungal infection; no discontinuation because of toxicity; and no need for a nonstudy, systemic antifungal medication (as assessed by a blinded oversight committee). RESULTS: Only 44 of 122 (36%) fluconazole recipients and 48 of 127 (38%) placebo recipients had a successful outcome (relative risk, 0.95 [95% CI, 0.69 to 1.32; P = 0.78]). The main reason for failure was lack of resolution of fever (51% for fluconazole and 57% for placebo). Documented invasive candidiasis occurred in 5% of fluconazole recipients and 9% of placebo recipients (relative risk, 0.57 [CI, 0.22 to 1.49]). Seven (5%) fluconazole recipients and 10 (7%) placebo recipients had adverse events resulting in discontinuation of the study drug. Discontinuation because of abnormal liver test results occurred in 3 (2%) fluconazole recipients and 5 (4%) placebo recipients. LIMITATIONS: Twenty-one randomly assigned patients were not included in the analysis because they either did not meet entry criteria or did not have postbaseline assessments. Fewer fungal infections than anticipated occurred in the control group. Confidence bounds were wide and did not exclude potentially important differences in outcomes between groups. CONCLUSION: In critically ill adults with risk factors for invasive candidiasis, empirical fluconazole did not clearly improve a composite outcome more than placebo.
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“A recent study examining non-neutropenic Fungal Sepsis patients did not find a benefit for the preemptive addition of fluconazole to persistently febrile patients in the ICU.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [193]
Citations
Cites
The Prevalence of Nosocomial Infection in Intensive Care Units in Europe
Vincent, J. (1995) · JAMA · doi:10.1001/jama.274.8.639 · Cited by 2,592
Rex, J. H., Bennett, J. E., Sugar, A. M., Pappas, P. G., van der Horst, C. M., Edwards, J. E., Washburn, R. G., Scheld, W. M., Karchmer, A. W., Dine, A. P., et al. (1994) · New England Journal of Medicine · doi:10.1056/nejm199411173312001 · Cited by 1,039
Self-citationWingard, J. R., Merz, W. G., Rinaldi, M. G., Johnson, T. R., Karp, J. E., & Saral, R. (1991) · New England Journal of Medicine · doi:10.1056/nejm199110313251803 · Cited by 937
Resistance of Candida species to fluconazole
Rex, J. H., Rinaldi, M. G., & Pfaller, M. A. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.1.1 · Cited by 880
Self-citationHospital-Acquired Candidemia: The Attributable Mortality and Excess Length of Stay
Wey, S. B. (1988) · Archives of Internal Medicine · doi:10.1001/archinte.1988.00380120094019 · Cited by 831
Management of Fever in Patients with Cancer and Treatment-Induced Neutropenia
Wood, A. J. J., & Pizzo, P. A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305063281808 · Cited by 831
Candida Colonization and Subsequent Infections in Critically III Surgical Patients
Pittet, D., Monod, M., Suter, P. M., Frenk, E., & Auckenthaler, R. (1994) · Annals of Surgery · doi:10.1097/00000658-199412000-00008 · Cited by 798
Zaoutis, T. E., Argon, J., Chu, J., Berlin, J. A., Walsh, T. J., & Feudtner, C. (2005) · Clinical Infectious Diseases · doi:10.1086/496922 · Cited by 784
The Epidemiology of Hematogenous Candidiasis Caused by Different Candida Species
Abi‐Said, D., Anaissie, E., Uzun, O., Raad, I., Pinzcowski, H., & Vartivarian, S. (1997) · Clinical Infectious Diseases · doi:10.1086/513663 · Cited by 755
1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever
Hughes, W. T., Armstrong, D., Bodey, G. P., Brown, A. E., Edwards, J. E., Feld, R. D., Pizzo, P. A., Rolston, K. V. I., Shenep, J. L., & Young, L. S. (1997) · Clinical Infectious Diseases · doi:10.1086/513764 · Cited by 664
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- 10.1001/jama.1995.03530080055041 · DOI
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Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., Reboli, A. C., Schuster, M. G., Vazquez, J. A., Walsh, T. J., et al. (2016) · Clinical Infectious Diseases · doi:10.1093/cid/civ933 · Cited by 4,200
Self-citationPappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191
Self-citationPappas, P. G., Lionakis, M. S., Arendrup, M. C., Ostrosky-Zeichner, L., & Kullberg, B. J. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.26 · Cited by 1,636
Cornely, O. A., Bassetti, M., Calandra, T., Garbino, J., Kullberg, B. J., Lortholary, O., Meersseman, W., Akova, M., Arendrup, M. C., Arikan-Akdagli, S., et al. (2012) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12039 · Cited by 1,217
Candida Infections of the Genitourinary Tract
Achkar, J. M., & Fries, B. C. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00076-09 · Cited by 736
Metadata
- Authors
- Schuster, M. G., Edwards, J. E., Sobel, J. D., Darouiche, R. O., Karchmer, A. W., Hadley, S., Slotman, G., Panzer, H., Biswas, P., & Rex, J. H.
- Affiliations
- Tufts Medical Center (US)
- Tufts University (US)
- AstraZeneca (United Kingdom) (GB)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2008-07-15
- Volume
- 149
- Issue
- 2
- Pages
- 83-90
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2041927838
- Semantic Scholar
- 7f6c28e24e62a031b9fbd07664f827cb67f8e714
- Cited by
- 210
- References
- 28
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 3 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 14 · 2018: 7 · 2017: 15 · 2016: 12 · 2015: 14 · 2014: 20 · 2013: 11 · 2012: 16
- FWCI
- 14.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Nosocomial Infections in ICU
- Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
- Keywords
- invasive candidiasis, fluconazole, intensive care unit patients, critically ill adults, central venous catheters, APACHE II score, antifungal toxicity, liver function tests, composite endpoints, treatment discontinuation, ICU length of stay, cost-effectiveness
- MeSH terms
- Adult, Aged, Antifungal Agents, Candidiasis, Critical Care, Cross Infection, Double-Blind Method, Female, Follow-Up Studies, Humans, Intensive Care Units, Male, Middle Aged, Risk Factors, Fluconazole, Fungemia
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