Skip to main content
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 3/2019

24.01.2019 | Original Article

Persistent Candidemia in adults: underlying causes and clinical significance in the antifungal stewardship era

verfasst von: Caroline Agnelli, Maricela Valerio, Emilio Bouza, Antonio Vena, Jesús Guinea, María del Carmen Martínez-Jiménez, Laura Judith Marcos-Zambrano, Pilar Escribano, Patricia Muñoz, on behalf of the COMIC Study Group (Collaborative Group on Mycosis)

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 3/2019

Einloggen, um Zugang zu erhalten

Abstract

To investigate the causes and the clinical significance of persistent candidemia (PC) in adults diagnosed in a tertiary hospital with an active antifungal stewardship program. Retrospective cohort including all adults with candidemia from 2010 to 2018. PC was defined as any positive follow-up blood culture (BC) obtained ≥ 5 days from the first BCs yielding the same Candida species. PC was detected in 35/255 (13.7%) patients. There were no differences regarding antifungal adequacy in PC vs. non-PC (94.3% vs. 82.3%, p = 0.084) and primary source control (63.3% vs. 76.4%, p = 0.172) at the time of the follow-up BCs. The average time until source control (2 [0–37] vs. 2 days [0–44], p = 0.311) or adequate antifungal treatment (2 [0–26] vs. 2 days [− 2–10], p = 0.748) was similar. Patients with PC had more non-ocular complications (31.4% vs. 10.5%, p = 0.002). No impact on 30-day mortality was observed (31.4% vs. 22.3%, p = 0.238). The only independent factor associated with PC was to have a previously undetected site of infection [OR 4.28, 95%CI (1.77–10.34), p = 0.001]. Persistent candidemia was not associated with inadequate or delayed therapeutic management, nor higher 30-day mortality rates. Timely screening and control of unexpected infection sources are encouraged to shorten hospitalization and improve patient care.
Literatur
1.
Zurück zum Zitat Noyola DE, Fernandez M, Moylett EH, Baker CJ (2001) Ophthalmologic, visceral, and cardiac involvement in neonates with candidemia. Clin Infect Dis 32(7):1018–1023CrossRefPubMed Noyola DE, Fernandez M, Moylett EH, Baker CJ (2001) Ophthalmologic, visceral, and cardiac involvement in neonates with candidemia. Clin Infect Dis 32(7):1018–1023CrossRefPubMed
2.
Zurück zum Zitat Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC (1992) Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 15(3):414–421CrossRefPubMed Fraser VJ, Jones M, Dunkel J, Storfer S, Medoff G, Dunagan WC (1992) Candidemia in a tertiary care hospital: epidemiology, risk factors, and predictors of mortality. Clin Infect Dis 15(3):414–421CrossRefPubMed
3.
Zurück zum Zitat Luzzati R, Amalfitano G, Lazzarini L et al (2000) Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital. Eur J Clin Microbiol Infect Dis 19(8):602–607CrossRefPubMed Luzzati R, Amalfitano G, Lazzarini L et al (2000) Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital. Eur J Clin Microbiol Infect Dis 19(8):602–607CrossRefPubMed
4.
Zurück zum Zitat Zaoutis TE, Greves HM, Lautenbach E, Bilker WB, Coffin SE (2004) Risk factors for disseminated candidiasis in children with candidemia. Pediatr Infect Dis J 23(7):635–641CrossRefPubMed Zaoutis TE, Greves HM, Lautenbach E, Bilker WB, Coffin SE (2004) Risk factors for disseminated candidiasis in children with candidemia. Pediatr Infect Dis J 23(7):635–641CrossRefPubMed
5.
Zurück zum Zitat Nucci M (2011) Persistent candidemia: causes and investigations. Curr Fungal Infect Rep 5(1):3–11CrossRef Nucci M (2011) Persistent candidemia: causes and investigations. Curr Fungal Infect Rep 5(1):3–11CrossRef
6.
Zurück zum Zitat Kang SJ, Kim SE, Kim UJ et al (2017) Clinical characteristics and risk factors for mortality in adult patients with persistent candidemia. J Infect Elsevier 75(3):246–253CrossRef Kang SJ, Kim SE, Kim UJ et al (2017) Clinical characteristics and risk factors for mortality in adult patients with persistent candidemia. J Infect Elsevier 75(3):246–253CrossRef
7.
Zurück zum Zitat Vena A, Munoz P, Corisco R, et al. Efficacy of a “check-list” intervention bundle on the clinical evolution of patients with Candida bloodstream infections. 27th ECCMID. 2017. p. 24–25 Vena A, Munoz P, Corisco R, et al. Efficacy of a “check-list” intervention bundle on the clinical evolution of patients with Candida bloodstream infections. 27th ECCMID. 2017. p. 24–25
8.
Zurück zum Zitat Valerio M, Muñoz P, Rodríguez CG et al (2015) Antifungal stewardship in a tertiary-care institution: a bedside intervention. Clin Microbiol Infect 21(5):492.e1–492.e9CrossRef Valerio M, Muñoz P, Rodríguez CG et al (2015) Antifungal stewardship in a tertiary-care institution: a bedside intervention. Clin Microbiol Infect 21(5):492.e1–492.e9CrossRef
9.
Zurück zum Zitat Muñoz P, Valerio M, Vena A, Bouza E (2015) Antifungal stewardship in daily practice and health economic implications. Mycoses 58:14–25CrossRefPubMed Muñoz P, Valerio M, Vena A, Bouza E (2015) Antifungal stewardship in daily practice and health economic implications. Mycoses 58:14–25CrossRefPubMed
10.
Zurück zum Zitat Vena A, Bouza E, Valerio M et al (2017) Candidemia in non-ICU surgical wards: comparison with medical wards. PLoS One Public Libr Sci 12(10):e0185339CrossRef Vena A, Bouza E, Valerio M et al (2017) Candidemia in non-ICU surgical wards: comparison with medical wards. PLoS One Public Libr Sci 12(10):e0185339CrossRef
11.
Zurück zum Zitat Mermel LA, Allon M, Bouza E et al (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49(1):1–45CrossRefPubMed Mermel LA, Allon M, Bouza E et al (2009) Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 49(1):1–45CrossRefPubMed
12.
Zurück zum Zitat Pappas PG, Kauffman CA, Andes DR et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis Oxford Univ Press 62(4):e1–e50 Pappas PG, Kauffman CA, Andes DR et al (2016) Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis Oxford Univ Press 62(4):e1–e50
13.
Zurück zum Zitat Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope W (2012) EUCAST-AFST. EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST)*. Clin Microbiol Infect 18(7):E246–E247CrossRefPubMed Arendrup MC, Cuenca-Estrella M, Lass-Flörl C, Hope W (2012) EUCAST-AFST. EUCAST technical note on the EUCAST definitive document EDef 7.2: method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for yeasts EDef 7.2 (EUCAST-AFST)*. Clin Microbiol Infect 18(7):E246–E247CrossRefPubMed
14.
Zurück zum Zitat Marcos-Zambrano LJ, Escribano P, Bouza E, Guinea J (2014) Production of biofilm by Candida and non-Candida spp. isolates causing fungemia: comparison of biomass production and metabolic activity and development of cut-off points. Int J Med Microbiol 304(8):1192–1198CrossRefPubMed Marcos-Zambrano LJ, Escribano P, Bouza E, Guinea J (2014) Production of biofilm by Candida and non-Candida spp. isolates causing fungemia: comparison of biomass production and metabolic activity and development of cut-off points. Int J Med Microbiol 304(8):1192–1198CrossRefPubMed
15.
Zurück zum Zitat Marcos-Zambrano LJ, Gómez-Perosanz M, Escribano P, Zaragoza O, Bouza E, Guinea J (2016) Biofilm production and antibiofilm activity of echinocandins and liposomal amphotericin B in echinocandin-resistant yeast species. Antimicrob Agents Chemother 60(6):3579–3586CrossRefPubMedPubMedCentral Marcos-Zambrano LJ, Gómez-Perosanz M, Escribano P, Zaragoza O, Bouza E, Guinea J (2016) Biofilm production and antibiofilm activity of echinocandins and liposomal amphotericin B in echinocandin-resistant yeast species. Antimicrob Agents Chemother 60(6):3579–3586CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Nucci M, Perfect JR (2008) When primary antifungal therapy fails. Clin Infect Dis 46(9):1426–1433CrossRefPubMed Nucci M, Perfect JR (2008) When primary antifungal therapy fails. Clin Infect Dis 46(9):1426–1433CrossRefPubMed
17.
Zurück zum Zitat Baden LR, Bensinger W, Angarone M et al (2012) Prevention and treatment of cancer-related infections. J Natl Compr Cancer Netw 10(11):1412–1445CrossRef Baden LR, Bensinger W, Angarone M et al (2012) Prevention and treatment of cancer-related infections. J Natl Compr Cancer Netw 10(11):1412–1445CrossRef
18.
Zurück zum Zitat Ruhnke M, Schwartz S (2016) Recent developments in the management of invasive fungal infections in patients with oncohematological diseases. Ther Adv Hematol SAGE Publ 7(6):345–359CrossRef Ruhnke M, Schwartz S (2016) Recent developments in the management of invasive fungal infections in patients with oncohematological diseases. Ther Adv Hematol SAGE Publ 7(6):345–359CrossRef
19.
Zurück zum Zitat Clancy CJ, Nguyen MH (2013) Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 56(9):1284–1292CrossRefPubMed Clancy CJ, Nguyen MH (2013) Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 56(9):1284–1292CrossRefPubMed
20.
21.
Zurück zum Zitat Monfredini PM, Souza ACR, Cavalheiro RP, Siqueira RA, Colombo AL (2017) Clinical impact of Candida spp. biofilm production in a cohort of patients with candidemia. Med Mycol 56(7):803–808CrossRef Monfredini PM, Souza ACR, Cavalheiro RP, Siqueira RA, Colombo AL (2017) Clinical impact of Candida spp. biofilm production in a cohort of patients with candidemia. Med Mycol 56(7):803–808CrossRef
22.
Zurück zum Zitat Lin K-Y, Chen P-Y, Chuang Y-C et al (2018) Effectiveness of echinocandins versus fluconazole for treatment of persistent candidemia: a time-dependent analysis. J Inf Secur 77(3):242–248 Lin K-Y, Chen P-Y, Chuang Y-C et al (2018) Effectiveness of echinocandins versus fluconazole for treatment of persistent candidemia: a time-dependent analysis. J Inf Secur 77(3):242–248
23.
Zurück zum Zitat Muñoz P, Agnelli C, Guinea J et al (2018) Is biofilm production a prognostic marker in adults with candidaemia? Clin Microbiol Infect 24(9):1010–1015CrossRefPubMed Muñoz P, Agnelli C, Guinea J et al (2018) Is biofilm production a prognostic marker in adults with candidaemia? Clin Microbiol Infect 24(9):1010–1015CrossRefPubMed
24.
Zurück zum Zitat Hamdy RF, Zaoutis TE, Seo SK (2017) Antifungal stewardship considerations for adults and pediatrics. Virulence 8(6):658–672CrossRefPubMed Hamdy RF, Zaoutis TE, Seo SK (2017) Antifungal stewardship considerations for adults and pediatrics. Virulence 8(6):658–672CrossRefPubMed
25.
Zurück zum Zitat Nucci M, Anaissie E, Betts RFF et al (2010) Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin Infect Dis 51(3):295–303CrossRefPubMed Nucci M, Anaissie E, Betts RFF et al (2010) Early removal of central venous catheter in patients with candidemia does not improve outcome: analysis of 842 patients from 2 randomized clinical trials. Clin Infect Dis 51(3):295–303CrossRefPubMed
26.
Zurück zum Zitat Garnacho-Montero J, Diaz-Martin A, Garcia-Cabrera E, Ruiz Perez de Pipaon M, Hernandez-Caballero C, Lepe-Jimenez JA (2013) Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother 68(1):206–213CrossRefPubMed Garnacho-Montero J, Diaz-Martin A, Garcia-Cabrera E, Ruiz Perez de Pipaon M, Hernandez-Caballero C, Lepe-Jimenez JA (2013) Impact on hospital mortality of catheter removal and adequate antifungal therapy in Candida spp. bloodstream infections. J Antimicrob Chemother 68(1):206–213CrossRefPubMed
27.
Zurück zum Zitat Caccese R, Carfagna P, Pistilli N, Massetti AP, Falcone M, Venditti M (2012) Candidal thrombophlebitis of central veins: case report and review. Med Mycol 50(3):299–304CrossRefPubMed Caccese R, Carfagna P, Pistilli N, Massetti AP, Falcone M, Venditti M (2012) Candidal thrombophlebitis of central veins: case report and review. Med Mycol 50(3):299–304CrossRefPubMed
29.
Zurück zum Zitat Sharma P, Mukherjee A, Karunanithi S, Bal C, Kumar R (2014) Potential role of 18 F-FDG PET/CT in patients with fungal infections. Am J Roentgenol American Roentgen Ray Society 203(1):180–189CrossRef Sharma P, Mukherjee A, Karunanithi S, Bal C, Kumar R (2014) Potential role of 18 F-FDG PET/CT in patients with fungal infections. Am J Roentgenol American Roentgen Ray Society 203(1):180–189CrossRef
30.
Zurück zum Zitat Kauffman C (2015) Complications of candidemia in ICU patients: endophthalmitis, osteomyelitis, endocarditis. Semin Respir Crit Care Med. Thieme Medical Publishers 36(05):641–649CrossRefPubMed Kauffman C (2015) Complications of candidemia in ICU patients: endophthalmitis, osteomyelitis, endocarditis. Semin Respir Crit Care Med. Thieme Medical Publishers 36(05):641–649CrossRefPubMed
31.
Zurück zum Zitat Fernández-Cruz A, Cruz Menárguez M, Muñoz P et al (2015) The search for endocarditis in patients with candidemia: a systematic recommendation for echocardiography? A prospective cohort. Eur J Clin Microbiol Infect Dis 34(8):1543–1549CrossRefPubMed Fernández-Cruz A, Cruz Menárguez M, Muñoz P et al (2015) The search for endocarditis in patients with candidemia: a systematic recommendation for echocardiography? A prospective cohort. Eur J Clin Microbiol Infect Dis 34(8):1543–1549CrossRefPubMed
32.
Zurück zum Zitat Safdar A, Bannister TW, Safdar Z (2004) The predictors of outcome in immunocompetent patients with hematogenous candidasis. Int J Infect Dis 8(3):180–186CrossRefPubMed Safdar A, Bannister TW, Safdar Z (2004) The predictors of outcome in immunocompetent patients with hematogenous candidasis. Int J Infect Dis 8(3):180–186CrossRefPubMed
33.
Zurück zum Zitat Velasco E, Bigni R (2008) A prospective cohort study evaluating the prognostic impact of clinical characteristics and comorbid conditions of hospitalized adult and pediatric cancer patients with candidemia. Eur J Clin Microbiol Infect Dis 27(11):1071–1078CrossRefPubMed Velasco E, Bigni R (2008) A prospective cohort study evaluating the prognostic impact of clinical characteristics and comorbid conditions of hospitalized adult and pediatric cancer patients with candidemia. Eur J Clin Microbiol Infect Dis 27(11):1071–1078CrossRefPubMed
34.
Zurück zum Zitat Phillips P, Shafran S, Garber G et al (1997) Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis 16(5):337–345CrossRefPubMed Phillips P, Shafran S, Garber G et al (1997) Multicenter randomized trial of fluconazole versus amphotericin B for treatment of candidemia in non-neutropenic patients. Canadian Candidemia Study Group. Eur J Clin Microbiol Infect Dis 16(5):337–345CrossRefPubMed
35.
Zurück zum Zitat Chen C-Y, Huang S-Y, Tsay W et al (2012) Clinical characteristics of candidaemia in adults with haematological malignancy, and antimicrobial susceptibilities of the isolates at a medical centre in Taiwan, 2001–2010. Int J Antimicrob Agents 40(6):533–538CrossRefPubMed Chen C-Y, Huang S-Y, Tsay W et al (2012) Clinical characteristics of candidaemia in adults with haematological malignancy, and antimicrobial susceptibilities of the isolates at a medical centre in Taiwan, 2001–2010. Int J Antimicrob Agents 40(6):533–538CrossRefPubMed
36.
Zurück zum Zitat Bassetti M, Righi E, Montravers P, Cornely OA (2018) What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother 73(suppl_1):i14–i25CrossRefPubMedPubMedCentral Bassetti M, Righi E, Montravers P, Cornely OA (2018) What has changed in the treatment of invasive candidiasis? A look at the past 10 years and ahead. J Antimicrob Chemother 73(suppl_1):i14–i25CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Puig-Asensio M, Padilla B, Garnacho-Montero J et al (2014) Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect 20(4):O245–O254CrossRefPubMed Puig-Asensio M, Padilla B, Garnacho-Montero J et al (2014) Epidemiology and predictive factors for early and late mortality in Candida bloodstream infections: a population-based surveillance in Spain. Clin Microbiol Infect 20(4):O245–O254CrossRefPubMed
Metadaten
Titel
Persistent Candidemia in adults: underlying causes and clinical significance in the antifungal stewardship era
verfasst von
Caroline Agnelli
Maricela Valerio
Emilio Bouza
Antonio Vena
Jesús Guinea
María del Carmen Martínez-Jiménez
Laura Judith Marcos-Zambrano
Pilar Escribano
Patricia Muñoz
on behalf of the COMIC Study Group (Collaborative Group on Mycosis)
Publikationsdatum
24.01.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 3/2019
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-019-03477-3

Weitere Artikel der Ausgabe 3/2019

European Journal of Clinical Microbiology & Infectious Diseases 3/2019 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.