Impact of systemic antifungal therapy on the detection of Candida species in blood cultures in clinical cases of candidemia

  • S. Bailly
  • C. Garnaud
  • M. Cornet
  • P. Pavese
  • R. Hamidfar-Roy
  • L. Foroni
  • S. Boisset
  • J.-F. Timsit
  • D. Maubon
Original Article


The diagnosis and follow-up of candidemia still rely on blood cultures (BCs). In vitro studies show that antifungals can significantly modify the result of blood culture not containing adsorbing agents. We aimed to evaluate, under clinical conditions, the impact on BC yeast detection of systemic antifungal therapy (SAT). Patients (n = 125) experiencing candidemia at Grenoble University Hospital (France) were included in a 4-year retrospective study. The Plus Aerobic/F (Aerobic) and Plus Anaerobic/F (Anaerobic) bottles, which both contain adsorbing resins and the non-resin selective Mycosis IC/F (Mycosis) bottles, were compared using multivariate hierarchical models adjusted for clinical characteristics. The positivity rate (PR) is decreased in patients with SAT (p < 0.01), abdominal surgery (p = 0.01), and hemodialysis (p = 0.02). In all bottles, SAT reduces PR by a factor of 0.16 (95 % CI: [0.08; 0.32]) and increases the time to positivity (TTP) by a factor of 1.76 ([1.30; 2.40]; p < 0.01). In the presence of SAT, TTP is higher in non-resin bottles (Mycosis) than in resin bottles (RR = 1.76, [1.30; 2.40]); however, the TTP in nonresin and resin bottles remains comparable. Although discordant results are observed with and without SAT (37 and 58 % respectively), we showed that the presence of SAT decreases significantly the agreement rate by a factor of 0.29 (CI: [0.12; 0.68]). The combination of Anaerobic and Mycosis bottles allowed a 100 % positivity rate for C. glabrata. SAT significantly affects BC results. Because they provide additional and complementary results, this study supports the concomitant use of resin and selective bottles, especially in patients receiving SAT.


Candida Species Agreement Rate Adsorb Resin Systemic Antifungal Therapy Anaerobic Bottle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors are grateful to Lucie Le Pennec for the collection of the clinical and pharmacological data and to Jean Iwaz (Hospices Civils de Lyon) for the revision of the final drafts.

Compliance with ethical standards



Conflicts of interest

During the past 5 years, CG received travel grants from Pfizer and MSD, MC has received money for lectures from Pfizer and travel expenses from Pfizer, Gilead, and MSD. JFT has given lectures for symposiums set up by Astellas, Pfizer, MSD, 3 M, Novartis, and Gilead; has benefited from unrestricted research grants to his research unit from 3 M, MSD, and Astellas; and has been a consultant involved in scientific boards for MSD, 3 M, and Bayer. SB, PP, RHR, LF, and DM have no conflicts of interest.

Ethical approval/informed consent

As this was a retrospective study based on anonymized data, there was no need for ethical approval or informed consent.

Supplementary material

10096_2016_2633_MOESM1_ESM.docx (399 kb)
Esm 1 (DOCX 399 kb)


  1. 1.
    Enoch DA, Ludlam HA, Brown NM (2006) Invasive fungal infections: a review of epidemiology and management options. J Med Microbiol 55(Pt 7):809–818CrossRefPubMedGoogle Scholar
  2. 2.
    Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39(3):309–317CrossRefPubMedGoogle Scholar
  3. 3.
    Morrell M, Fraser VJ, Kollef MH (2005) Delaying the empiric treatment of candida bloodstream infection until positive blood culture results are obtained: a potential risk factor for hospital mortality. Antimicrob Agents Chemother 49(9):3640–3645CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Garey KW, Rege M, Pai MP, Mingo DE, Suda KJ, Turpin RS, Bearden DT (2006) Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study. Clin Infect Dis 43(1):25–31CrossRefPubMedGoogle Scholar
  5. 5.
    Bassetti M, Righi E, Ansaldi F, Merelli M, Cecilia T, De Pascale G, Diaz-Martin A, Luzzati R, Rosin C, Lagunes L, Trecarichi EM, Sanguinetti M, Posteraro B, Garnacho-Montero J, Sartor A, Rello J, Rocca GD, Antonelli M, Tumbarello M (2014) A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality. Intensive Care Med 40(6):839–845CrossRefPubMedGoogle Scholar
  6. 6.
    Cuenca-Estrella M, Verweij PE, Arendrup MC, Arikan-Akdagli S, Bille J, Donnelly JP, Jensen HE, Lass-Flörl C, Richardson MD, Akova M, Bassetti M, Calandra T, Castagnola E, Cornely OA, Garbino J, Groll AH, Herbrecht R, Hope WW, Kullberg BJ, Lortholary O, Meersseman W, Petrikkos G, Roilides E, Viscoli C, Ullmann AJ, EFISG (2012) ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures. Clin Microbiol Infect 18:9–18CrossRefPubMedGoogle Scholar
  7. 7.
    Marchetti O, Lamoth F, Mikulska M, Viscoli C, Verweij P, Bretagne S (2012) ECIL recommendations for the use of biological markers for the diagnosis of invasive fungal diseases in leukemic patients and hematopoietic SCT recipients. Bone Marrow Transplant 47(6):846–854CrossRefPubMedGoogle Scholar
  8. 8.
    Pappas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky‐Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48(5):503–535Google Scholar
  9. 9.
    Meyer MH, Letscher-Bru V, Jaulhac B, Waller J, Candolfi E (2004) Comparison of Mycosis IC/F and plus Aerobic/F media for diagnosis of fungemia by the bactec 9240 system. J Clin Microbiol 42(2):773–777CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Arendrup MC, Bruun B, Christensen JJ, Fuursted K, Johansen HK, Kjaeldgaard P, Knudsen JD, Kristensen L, Møller J, Nielsen L, Rosenvinge FS, Røder B, Schønheyder HC, Thomsen MK, Truberg K (2011) National surveillance of fungemia in Denmark (2004 to 2009). J Clin Microbiol 49(1):325–334CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ericson E-L, Klingspor L, Ullberg M, Ozenci V (2012) Clinical comparison of the Bactec Mycosis IC/F, BacT/Alert FA, and BacT/Alert FN blood culture vials for the detection of candidemia. Diagn Microbiol Infect Dis 73(2):153–156CrossRefPubMedGoogle Scholar
  12. 12.
    George BJ, Horvath LL, Hospenthal DR (2005) Effect of inoculum size on detection of Candida growth by the BACTEC 9240 automated blood culture system using aerobic and anaerobic media. J Clin Microbiol 43(1):433–435CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Jekarl DW, Lee S-Y, Lee S, Park Y-J, Lee J, Baek SM, An YJ, Ock SM, Lee M-K (2012) Comparison of the Bactec Fx Plus, Mycosis IC/F, Mycosis/F Lytic blood culture media and the BacT/Alert 3D FA media for detection of Candida species in seeded blood culture specimens containing therapeutic peak levels of fluconazole. J Clin Lab Anal 26(6):412–419CrossRefPubMedGoogle Scholar
  14. 14.
    Kock R, Eissing LC, Boschin MG, Ellger B, Horn D, Idelevich EA, Becker K (2013) Evaluation of bactec mycosis IC/F and Plus Aerobic/F blood culture bottles for detection of Candida in the presence of antifungal agents. J Clin Microbiol 51(11):3683–3687CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Fricker-Hidalgo H, Lebeau B, Pelloux H, Grillot R (2004) Use of the BACTEC 9240 System with Mycosis-IC/F blood culture bottles for detection of fungemia. J Clin Microbiol 42(4):1855–1856CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Bosshard PP (2011) Incubation of fungal cultures: how long is long enough? Mycoses 54(5):e539–e545CrossRefPubMedGoogle Scholar
  17. 17.
    Takesue Y, Ueda T, Mikamo H, Oda S, Takakura S, Kitagawa Y, Kohno S (2015) Management bundles for candidaemia: the impact of compliance on clinical outcomes. J Antimicrob Chemother 70(2):587–593CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Bailly S, Bouadma L, Azoulay E, Orgeas MG, Adrie C, Souweine B, Schwebel C, Maubon D, Hamidfar-Roy R, Darmon M, Wolff M, Cornet M, Timsit J-F (2015) Failure of empirical systemic antifungal therapy in mechanically ventilated critically ill patients. Am J Respir Crit Care Med 191(10):1139–1146CrossRefPubMedGoogle Scholar
  19. 19.
    Azoulay E, Dupont H, Tabah A, Lortholary O, Stahl J-P, Francais A, Martin C, Guidet B, Timsit J-F (2012) Systemic antifungal therapy in critically ill patients without invasive fungal infection*. Crit Care Med 40(3):813–822CrossRefPubMedGoogle Scholar
  20. 20.
    Flayhart D, Borek AP, Wakefield T, Dick J, Carroll KC (2007) Comparison of BACTEC PLUS blood culture media to BacT/Alert FA blood culture media for detection of bacterial pathogens in samples containing therapeutic levels of antibiotics. J Clin Microbiol 45(3):816–821CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Horvath LL, George BJ, Murray CK, Harrison LS, Hospenthal DR (2004) Direct comparison of the BACTEC 9240 and BacT/ALERT 3D automated blood culture systems for Candida growth detection. J Clin Microbiol 42(1):115–118CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Horvath LL, George BJ, Hospenthal DR (2007) Detection of fifteen species of Candida in an automated blood culture system. J Clin Microbiol 45(9):3062–3064CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Riedel S, Eisinger SW, Dam L, Stamper PD, Carroll KC (2011)Comparison of BD Bactec Plus Aerobic/F medium to VersaTREK Redox 1 blood culture medium for detection of Candida spp. in seeded blood culture specimens containing therapeutic levels of antifungal agents. J Clin Microbiol 49(4):1524–1529CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Klingspor L, Muhammed SA, Ozenci V (2012) Comparison of the two blood culture systems, Bactec 9240 and BacT/Alert 3D, in the detection of Candida spp. and bacteria with polymicrobial sepsis. Eur J Clin Microbiol Infect Dis 31(11):2983–2987CrossRefPubMedGoogle Scholar
  25. 25.
    Taur Y, Cohen N, Dubnow S, Paskovaty A, Seo SK (2010) Effect of antifungal therapy timing on mortality in cancer patients with candidemia. Antimicrob Agents Chemother 54(1):184–190CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Huang L, Zhang YY, Sun LY (2013) Time to positivity of blood culture can predict different Candida species instead of pathogen concentration in candidemia. Eur J Clin Microbiol Infect Dis 32(7):917–922CrossRefPubMedGoogle Scholar
  27. 27.
    Cobos-Trigueros N, Morata L, Torres J, Zboromyrska Y, Soriano A, Pitart C, Calle CDL, Marco F, Hernandez C, Almela M, Mensa J, Martinez JA (2013) Usefulness of time-to-positivity in aerobic and anaerobic vials to predict the presence of Candida glabrata in patients with candidaemia. J Antimicrob Chemother 68(12):2839–2841CrossRefPubMedGoogle Scholar
  28. 28.
    Nunes CZ, Marra AR, Edmond MB, Victor ES, Pereira CAP (2013) Time to blood culture positivity as a predictor of clinical outcome in patients with Candida albicans bloodstream infection. BMC Infect Dis 13(1):486CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kim S-H, Yoon YK, Kim MJ, Sohn JW (2013) Clinical impact of time to positivity for Candida species on mortality in patients with candidaemia. J Antimicrob Chemother 68(12):2890–2897CrossRefPubMedGoogle Scholar
  30. 30.
    Fricker-Hidalgo H, Chazot F, Lebeau B, Pelloux H, Ambroise-Thomas P, Grillot R (1998) Use of simulated blood cultures to compare a specific fungal medium with a standard microorganism medium for yeast detection. Eur J Clin Microbiol Infect Dis 17(2):113–116CrossRefPubMedGoogle Scholar
  31. 31.
    Patel R, Vetter EA, Harmsen WS, Schleck CD, Fadel HJ, Cockerill FR (2011) Optimized pathogen detection with 30- compared to 20-milliliter blood culture draws. J Clin Microbiol 49(12):4047–4051CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Martinez JA, Pozo L, Almela M, Marco F, Soriano A, López F, Balasso V, Aguilar J, Mensa J (2007) Microbial and clinical determinants of time-to-positivity in patients with bacteraemia. Clin Microbiol Infect 13(7):709–716CrossRefPubMedGoogle Scholar
  33. 33.
    Chow JK, Golan Y, Ruthazer R, Karchmer AW, Carmeli Y, Lichtenberg DA, Chawla V, Young JA, Hadley S (2008) Risk factors for albicans and non-albicans candidemia in the intensive care unit. Crit Care Med 36(7):1993–1998CrossRefPubMedGoogle Scholar
  34. 34.
    Chang J, Park JS, Park S, Choi B, Yoon NS, Sung H, Kim M-N (2015) Impact of monitoring blood volume in the BD BACTEC™ FX blood culture system: virtual volume versus actual volume. Diagn Microbiol Infect Dis 81(2):89–93CrossRefPubMedGoogle Scholar
  35. 35.
    Lortholary O, Renaudat C, Sitbon K, Madec Y, Denoeud-Ndam L, Wolff M, Fontanet A, Bretagne S, Dromer F (2014) Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002–2010). Intensive Care Med 40(9):1303–1312CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Laboratoire de Parasitologie-Mycologie, Institut de Biologie et de PathologieCHU de GrenobleGrenobleFrance
  2. 2.U823Université Grenoble AlpesSaint-Martin-d’HèresFrance
  3. 3.UMR 1137—IAME Team 5—DeSCID, Inserm/Paris DiderotSorbonne Paris Cité UniversityParisFrance
  4. 4.Laboratoire TIMC—TheREx, UMR 5525 CNRS-UJFUniversité Grenoble AlpesSaint-Martin-d’HèresFrance
  5. 5.Département des maladies infectieusesCHU GrenobleGrenobleFrance
  6. 6.Réanimation médicaleCHU GrenobleGrenobleFrance
  7. 7.Pharmacie hospitalièreCHU GrenobleGrenobleFrance
  8. 8.Laboratoire de Bactériologie-Hygiène, Institut de Biologie et de PathologieCHU GrenobleGrenobleFrance
  9. 9.Réanimation Médicale et des Maladies InfectieusesHôpital BichatParisFrance

Personalised recommendations