Abstract
The aim of this study was to systematically evaluate the predictive value of time to positivity (TTP) in candidemia. All first episodes of candidemic patients admitted to our hospital between January 2008 and July 2012 were recorded retrospectively. We analyzed the relationship between TTP, identification of Candida species, antifungal agent susceptibility, and patients’ clinical characteristics (30-day mortality, underlying diseases, and associated risk factors). TTP of simulated blood culture with equal inoculum amounts of different Candida species was determined. We included 87 patients during the study period, with a mean TTP of 43.47 ± 19.51 h. TTP of C. glabrata was significantly longer (p < 0.001) and TTP of C. tropicalis was significantly shorter (p < 0.001) than that of other Candida species. Receiver operating characteristic (ROC) curve analysis showed that TTP can predict C. glabrata (with the cut-off value of >45.17 h) and C. tropicalis (with the cut-off value of ≤33.17 h) in candidemia with good sensitivity and specificity. No statistically significant relationship was found between TTP, antifungal agent susceptibility, and patients’ clinical characteristics (p > 0.05). TTP was not a risk factor associated with mortality (p > 0.05). The TTP result in simulated blood culture was in accordance with that of the included patients. TTP has been demonstrated to be helpful to differentiate C. glabrata and C. tropicalis from other Candida species in candidemia, and it is not associated with antifungal agent susceptibility and patients’ clinical characteristics. TTP cannot predict pathogen concentration in the blood of candidemic patients.
Similar content being viewed by others
References
Pfaller MA, Diekema DJ (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20(1):133–163. doi:10.1128/CMR.00029-06
Leroy O, Gangneux JP, Montravers P, Mira JP, Gouin F, Sollet JP, Carlet J, Reynes J, Rosenheim M, Regnier B, Lortholary O; AmarCand Study Group (2009) Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005–2006). Crit Care Med 37(5):1612–1618. doi:10.1097/CCM.0b013e31819efac0
Morgan J, Meltzer MI, Plikaytis BD, Sofair AN, Huie-White S, Wilcox S, Harrison LH, Seaberg EC, Hajjeh RA, Teutsch SM (2005) Excess mortality, hospital stay, and cost due to candidemia: a case–control study using data from population-based candidemia surveillance. Infect Control Hosp Epidemiol 26(6):540–547. doi:10.1086/502581
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):309–317. doi:10.1086/421946
Ruan SY, Hsueh PR (2009) Invasive candidiasis: an overview from Taiwan. J Formos Med Assoc 108(6):443–451. doi:10.1016/S0929-6646(09)60091-7
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):25–31
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):184–190
Pfaller MA, Diekema DJ, Messer SA, Hollis RJ, Jones RN (2003) In vitro activities of caspofungin compared with those of fluconazole and itraconazole against 3,959 clinical isolates of Candida spp., including 157 fluconazole-resistant isolates. Antimicrob Agents Chemother 47(3):1068–1071
Massonet C, Van Eldere J, Vaneechoutte M, De Baere T, Verhaegen J, Lagrou K (2004) Comparison of VITEK 2 with ITS2-fragment length polymorphism analysis for identification of yeast species. J Clin Microbiol 42(5):2209–2211
Coignard C, Hurst SF, Benjamin LE, Brandt ME, Warnock DW, Morrison CJ (2004) Resolution of discrepant results for Candida species identification by using DNA probes. J Clin Microbiol 42(2):858–861
Louie RF, Tang Z, Albertson TE, Cohen S, Tran NK, Kost GJ (2008) Multiplex polymerase chain reaction detection enhancement of bacteremia and fungemia. Crit Care Med 36(5):1487–1492. doi:10.1097/CCM.0b013e31816f487c
Gherna M, Merz WG (2009) Identification of Candida albicans and Candida glabrata within 1.5 hours directly from positive blood culture bottles with a shortened peptide nucleic acid fluorescence in situ hybridization protocol. J Clin Microbiol 47(1):247–248. doi:10.1128/JCM.01241-08
Hsiue HC, Huang YT, Kuo YL, Liao CH, Chang TC, Hsueh PR (2010) Rapid identification of fungal pathogens in positive blood cultures using oligonucleotide array hybridization. Clin Microbiol Infect 16(5):493–500. doi:10.1111/j.1469-0691.2009.02828.x
Haimi-Cohen Y, Vellozzi EM, Rubin LG (2002) Initial concentration of Staphylococcus epidermidis in simulated pediatric blood cultures correlates with time to positive results with the automated, continuously monitored BACTEC blood culture system. J Clin Microbiol 40(3):898–901
Lai CC, Wang CY, Liu WL, Hou CC, Huang YT, Hsueh PR (2011) Time to blood culture positivity as a predictor of methicillin resistance in Staphylococcus aureus bacteremia. J Infect 62(2):190–191. doi:10.1016/j.jinf.2010.11.006
Lai CC, Wang CY, Liu WL, Cheng A, Lee YC, Huang YT, Hsueh PR (2011) Time to blood culture positivity as a predictor of drug resistance in Acinetobacter baumannii complex bacteremia. J Infect 63(1):96–98. doi:10.1016/j.jinf.2011.05.009
Álvarez R, Viñas-Castillo L, Lepe-Jiménez JA, García-Cabrera E, Cisneros-Herreros JM (2012) Time to positivity of blood culture association with clinical presentation, prognosis and ESBL-production in Escherichia coli bacteremia. Eur J Clin Microbiol Infect Dis 31(9):2191–2195. doi:10.1007/s10096-012-1554-5
Kim J, Gregson DB, Ross T, Laupland KB (2010) Time to blood culture positivity in Staphylococcus aureus bacteremia: association with 30-day mortality. J Infect 61(3):197–204
Lai CC, Wang CY, Liu WL, Huang YT, Hsueh PR (2012) Time to positivity of blood cultures of different Candida species causing fungaemia. J Med Microbiol 61(Pt 5):701–704
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):115–118
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):2983–2987. doi:10.1007/s10096-012-1650-6
Bone RC, Sprung CL, Sibbald WJ (1992) Definitions for sepsis and organ failure. Crit Care Med 20(6):724–726
Huang AH, Yan JJ, Wu JJ (1998) Comparison of five days versus seven days of incubation for detection of positive blood cultures by the Bactec 9240 system. Eur J Clin Microbiol Infect Dis 17(9):637–641
Leaw SN, Chang HC, Sun HF, Barton R, Bouchara JP, Chang TC (2006) Identification of medically important yeast species by sequence analysis of the internal transcribed spacer regions. J Clin Microbiol 44(3):693–699. doi:10.1128/JCM.44.3.693-699.2006
National Committee for Clinical Laboratory Standards (NCCLS) (1997) Reference method for broth dilution antifungal susceptibility testing of yeasts; Approved standard—second edition. NCCLS document M27-A. NCCLS, Wayne, PA
Ben-Ami R, Weinberger M, Orni-Wasserlauff R, Schwartz D, Itzhaki A, Lazarovitch T, Bash E, Aharoni Y, Moroz I, Giladi M (2008) Time to blood culture positivity as a marker for catheter-related candidemia. J Clin Microbiol 46(7):2222–2226. doi:10.1128/JCM.00214-08
Peralta G, Roiz MP, Sánchez MB, Garrido JC, Ceballos B, Rodríguez-Lera MJ, Mateos F, De Benito I (2007) Time-to-positivity in patients with Escherichia coli bacteraemia. Clin Microbiol Infect 13(11):1077–1082
Acknowledgment
The authors would like to thank the clinical microbiology staff of our hospital for the initial processing of the included isolates.
Author contributions
Conceived and designed the experiments: L.H. Performed the experiments and collected the data: L.H., Y.Y.Z., and L.Y.S. Analyzed the data: L.H. Y.Y.Z., and L.Y.S. Wrote the manuscript: L.H.
Funding
This study was partially supported by the National Natural Science Foundation of China to Lei Huang (grant no. 81201338).
Conflict of interest
The authors declare no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Huang, L., Zhang, Y.Y. & Sun, L.Y. Time to positivity of blood culture can predict different Candida species instead of pathogen concentration in candidemia. Eur J Clin Microbiol Infect Dis 32, 917–922 (2013). https://doi.org/10.1007/s10096-013-1826-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10096-013-1826-8