Candida blood stream infections observed between 2011 and 2016 in a large Italian University Hospital: A time-based retrospective analysis on epidemiology, biofilm production, antifungal agents consumption and drug-susceptibility


Autoři: Grazia Brunetti aff001;  Anna Sara Navazio aff002;  Alessandro Giuliani aff003;  Alessandra Giordano aff001;  Enrica Maria Proli aff005;  Guido Antonelli aff002;  Giammarco Raponi aff001
Působiště autorů: Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy aff001;  Department of Molecular Medicine, Laboratory of Microbiology and Pasteur Institute-Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy aff002;  Department of Environment and Health, Istituto Superiore di Sanità, Rome, Italy aff003;  Microbiology and Virology Unit, Sapienza University Hospital Policlinico Umberto I, Rome, Italy aff004;  Hospital Pharmacy, University Hospital Policlinico Umberto I, Rome, Italy aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224678

Souhrn

Candida bloodstream infection (BSI) represents a growing infective problem frequently associated to biofilm production due to the utilization of intravascular devices. Candida species distribution (n = 612 strains), their biofilm production and hospital antifungal drug consumption were evaluated in different wards of a tertiary care academic hospital in Italy during the years 2011–2016. In the considered time window, an increasing number of Candida BSI (p = 0.005) and of biofilm producing strains were observed (p<0.0001). Although C. albicans was the species more frequently isolated in BSI with a major biofilm production, an increased involvement of non-albicans species was reported, particularly of C. parapsilosis that displayed a high frequency in catheter infections, and lower biofilm production compared to C. albicans. Although trends of biofilm production were substantially stable in time, a decreasing biofilm production by C. parapsilosis in the Intensive Care Unit (ICU) was observed (p = 0.0041). Principal component analysis displayed a change in antifungal drugs consumption driven by two mutually independent temporal trends, i.e. voriconazole use in the general medicine wards initially, and fluconazole use mainly in the ICU; these factors explain 68.9% and 25.7% of total variance respectively. Moreover, a significant trend (p = 0.003) in fluconazole use during the whole time period considered emerged, particularly in the ICU (p = 0.017), but also in the general medicine wards (p = 0.03). These trends paralleled with significant increase MIC90 of fluconazole (p = 0.05), particularly for C. parapsilosis in the ICU (p = 0.04), with a general and significant decreased trend of the MIC90 values of caspofungin (p = 0.04), and with significant increased MIC50 values for amphotericin B (p = 0.01) over the study period. In conclusion, drug utilization in our hospital turned out to be a putative influencing factor on the ecology of the species, on the increase in time of the biofilm producing strains and on the Candida antifungal susceptibility profile, thus influencing clinical management.

Klíčová slova:

Antifungals – Antimicrobial resistance – Biofilms – Candida – Candida albicans – Catheters – Intensive care units – Amphotericin


Zdroje

1. Yang ZT, Wu L, Liu XY, Zhou M, Li J, Wu JY, et al. 2014. Epidemiology, species distribution and outcome of nosocomial Candida spp. bloodstream infection in Shanghai. BMC Infect Dis 14:241. doi: 10.1186/1471-2334-14-241 24886130

2. Tumbarello M, Fiori B, Trecarichi EM, Posteraro P, Losito AR, De Luca A, et al. 2012. Risk factors and outcomes of candidemia caused by biofilm-forming isolates in a tertiary care hospital. PLoS One 7:e33705. doi: 10.1371/journal.pone.0033705 22479431

3. Leroy O, Gangneux JP, Montravers P, Mira JP, Gouin F, Sollet JP, et al. 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 37:1612–1618. doi: 10.1097/CCM.0b013e31819efac0 19325476

4. Bassetti M, Trecarichi EM, Righi E, Sanguinetti M, Bisio F, Posteraro B, et al. 2007. Incidence, risk factors, and predictors of outcome of candidemia. Survey in 2 Italian university hospitals. Diagn Microbiol Infect Dis 58:325–331. doi: 10.1016/j.diagmicrobio.2007.01.005 17350205

5. Pfaller MA, Diekema DJ. 2007. Epidemiology of invasive candidiasis: a persistent public health problem. Clin Microbiol Rev 20:133–163. doi: 10.1128/CMR.00029-06 17223626

6. Li WS, Chen YC, Kuo SF, Chen FJ, Lee CH. 2018. The impact of biofilm formation on the persistence of Candidemia. Front Microbiol 9:1196. doi: 10.3389/fmicb.2018.01196 29915571

7. Kang SJ, Kim SE, Kim UJ, Jang HC, Park KH, Shin JH, et al. 2017. Clinical characteristics and risk factors for mortality in adult patients with persistent candidemia. J Infect 75:246–253. doi: 10.1016/j.jinf.2017.05.019 28587831

8. Kojic EM, Darouiche RO. 2004. Candida infections of medical devices. Clin Microbiol Rev 17:255–267 doi: 10.1128/CMR.17.2.255-267.2004 15084500

9. Rajendran R, Sherry L, Nile CJ, Sherriff A, Johnson EM, Hanson MF, et al. 2016. Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012–2013. Clin Microbiol Infect 22:87–93. doi: 10.1016/j.cmi.2015.09.018 26432192

10. Sherry L, Rajendran R, Lappin DF, Borghi E, Perdoni F, Falleni M, et al. 2014. Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity. BMC Microbiol 14:182. doi: 10.1186/1471-2180-14-182 24996549

11. Lynch AS, Robertson GT. 2008. Bacterial and fungal biofilm infections. Annu Rev Med 59:415–428. doi: 10.1146/annurev.med.59.110106.132000 17937586

12. Muñoz P, Agnelli C, Guinea J, Vena A, Álvarez-Uría A, Marcos-Zambrano LJ, et al. 2018. Is biofilm production a prognostic marker in adults with Candidaemia? Clin Microbiol Infect 24:1010–1015. doi: 10.1016/j.cmi.2018.01.022 29408611

13. Tumbarello M, Posteraro B, Trecarichi EM, Fiori B, Rossi M, Porta R, et al. 2007. Biofilm production by Candida species and inadequate antifungal therapy as predictors of mortality for patients with candidemia. J Clin Microbiol 45:1843–1850. doi: 10.1128/JCM.00131-07 17460052

14. Shin JH, Kee SJ, Shin MG, Kim SH, Shin DH, Lee SK, et al. 2002. Biofilm production by isolates of Candida species recovered from nonneutropenic patients: comparison of bloodstream isolates with isolates from other sources. J Clin Microbiol 40:1244–1248. doi: 10.1128/JCM.40.4.1244-1248.2002 11923339

15. Pristov KE, Ghannoum MA. 2019. Resistance of Candida to azoles and echinocandins worldwide. Clin Microbiol Infect pii:S1198–743X(19)30149-1.

16. Marak MB, Dhanashree B. 2018. Antifungal Susceptibility and Biofilm Production of Candida spp. Isolated from Clinical Samples. Int J Microbiol 2018:7495218. doi: 10.1155/2018/7495218 30405717

17. Vandeputte P, Ferrari S, Coste AT. 2012. Antifungal resistance and new strategies to control fungal infections. Int J Microbiol 2012:713687. doi: 10.1155/2012/713687 22187560

18. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. 2016. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 62:e1–50. doi: 10.1093/cid/civ933 26679628

19. Milazzo L, Peri AM, Mazzali C, Grande R, Cazzani C, Ricaboni D, et al. 2014. Candidaemia observed at a university hospital in Milan (northern Italy) and review of published studies from 2010 to 2014. Mycopathologia 178:227–241. doi: 10.1007/s11046-014-9786-9 25056143

20. Cleveland AA, Farley MM, Harrison LH, Stein B, Hollick R, Lockhart SR, et al. 2012. Changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in Atlanta and Baltimore, 2008–2011. Clin Infect Dis 55:1352–1361. doi: 10.1093/cid/cis697 22893576

21. Playford EG, Nimmo GR, Tilse M, Sorrell TC. 2010. Increasing incidence of Candidaemia: long-term epidemiological trends, Queensland, Australia, 1999–2008. J Hosp Infect 76:46–51. doi: 10.1016/j.jhin.2010.01.022 20382444

22. Pfaller MA, Diekema DJ, Turnidge JD, Castanheira M, Jones RN. 2019. Twenty Years of the SENTRY Antifungal Surveillance Program: Results for Candida Species From 1997–2016. Open Forum Infect Dis 6(Suppl 1):S79–S94. doi: 10.1093/ofid/ofy358 30895218

23. Cleri DJ, Corrado ML, Seligman SJ. 1980. Quantitative culture of intravenous catheters and other intravascular inserts. J Infect Dis 141:781–786. doi: 10.1093/infdis/141.6.781 6993589

24. Ghezzi MC, Brunetti G, Visconti V, Giordano A, Raponi G. 2017. Candidaemia in a tertiary care academic hospital in Italy. The impact of C. parapsilosis complex on the species distribution and antifungal susceptibility. J Med Microbiol 66:990–998. doi: 10.1099/jmm.0.000505 28686553

25. Brunetti G, Visconti V, Ghezzi MC, Giordano A, Raponi G. 2017. The Correlation Between Biofilm Production and Catheter-Related Bloodstream Infections Sustained by Candida. A Case Control Study. Adv Exp Med Biol 973:89–98. doi: 10.1007/5584_2016_196 28213809

26. Ghosh AK, Paul S, Sood P, Rudramurthy SM, Rajbanshi A, Jillwin TJ, et al. 2015. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the rapid identification of yeasts causing bloodstream infections. Clin Microbiol Infect 21:372–378. doi: 10.1016/j.cmi.2014.11.009 25658527

27. Pinto A, Halliday C, Zahra M, van Hal S, Olma T, Maszewska K, et al. 2011. Matrix-assisted laser desorption ionization-time of flight mass spectrometry identification of yeasts is contingent on robust reference spectra. PLoS One 6:e25712. doi: 10.1371/journal.pone.0025712 22022438

28. Ramage G, Vandewalle K, Wickes BL, López-Ribot JL. 2001. Characteristics of biofilm formation by Candida albicans. Rev Iberoam Micol 18:163–170. 15496122

29. Sandini S, Stringaro A, Arancia S, Colone M, Mondello F, Murtas S, et al. 2011. The MP65 gene is required for cell wall integrity, adherence to epithelial cells and biofilm formation in Candida albicans. BMC Microbiol. May 16;11:106. doi: 10.1186/1471-2180-11-106 21575184

30. World Health Organization. 2019. Guidelines for ATC classification and DDD assignment. https://www.whocc.no/filearchive/publications/2019_guidelines_web.pdf

31. Retherford RD, Choe MK. 1993. Statistical models for causal analysis, p 119–150. John Wiley & Sons, New York, NY.

32. Giuliani A. 2017. The application of principal component analysis to drug discovery and biomedical data. Drug Discov Today 22:1069–1076. doi: 10.1016/j.drudis.2017.01.005 28111329

33. Jolicoeur P, Mosimann JE. 1960. Size and shape variation in the painted turtle. A principal component analysis. Growth 24:339–354. 13790416

34. Koehler P, Stecher M, Cornely OA, Koehler D, Vehreschild MJGT, Bohlius J, et al. 2019. Morbidity and mortality of Candidaemia in Europe: an epidemiologic meta-analysis. Clin Microbiol Infect pii:S1198–743X(19)30202-2.

35. Caggiano G, Coretti C, Bartolomeo N, Lovero G, De Giglio O, Montagna MT. 2015. Candida Bloodstream Infections in Italy: Changing Epidemiology during 16 Years of Surveillance. Biomed Res Int 2015:256580. doi: 10.1155/2015/256580 26064890

36. Chen PY, Chuang YC, Wang JT, Sheng WH, Yu CJ, Chu CC, et al. 2014. Comparison of epidemiology and treatment outcome of patients with candidemia at a teaching hospital in Northern Taiwan, in 2002 and 2010. J Microbiol Immunol Infect 47:95–103. doi: 10.1016/j.jmii.2012.08.025 23063082

37. Zhang XB, Yu SJ, Yu JX, Gong YL, Feng W, Sun FJ. 2012. Retrospective analysis of epidemiology and prognostic factors for candidemia at a hospital in China, 2000–2009. Jpn J Infect Dis 65:510–515. 23183203

38. Sakagami T, Kawano T, Yamashita K, Yamada E, Fujino N, Kaeriyama M, et al. 2019. Antifungal susceptibility trend and analysis of resistance mechanism for Candida species isolated from bloodstream at a Japanese university hospital. J Infect Chemother 25:34–40. doi: 10.1016/j.jiac.2018.10.007 30401513

39. Mencarini J, Mantengoli E, Tofani L, Riccobono E, Fornaini R, Bartalesi F, et al. 2018. Evaluation of candidemia and antifungal consumption in a large tertiary care Italian hospital over a 12-year period. Infection 46:469–476. doi: 10.1007/s15010-018-1139-z 29654496

40. Pfaller MA, Moet GJ, Messer SA, Jones RN, Castanheira M. 2011. Geographic variations in species distribution and echinocandin and azole antifungal resistance rates among Candida bloodstream infection isolates: report from the SENTRY Antimicrobial Surveillance Program (2008 to 2009). J Clin Microbiol 49:396–399. doi: 10.1128/JCM.01398-10 21068282

41. Hajjeh RA, Sofair AN, Harrison LH, Lyon GM, Arthington-Skaggs BA, Mirza SA, et al. 2004. Incidence of bloodstream infections due to Candida species and in vitro susceptibilities of isolates collected from 1998 to 2000 in a population-based active surveillance program. J Clin Microbiol 42:1519–1527. doi: 10.1128/JCM.42.4.1519-1527.2004 15070998

42. Soldini S, Posteraro B, Vella A, De Carolis E, Borghi E, Falleni M, et al. 2018. Microbiologic and clinical characteristics of biofilm-forming Candida parapsilosis isolates assciated with fungaemia and their impact on mortality. Clin Microbiol Infect 24:771–777. doi: 10.1016/j.cmi.2017.11.005 29133157

43. Silva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. 2011. Adherence and biofilm formation of non-Candida albicans Candida species. Trends Microbiol 19:241–247. doi: 10.1016/j.tim.2011.02.003 21411325

44. Nguyen MH, Peacock JE Jr, Morris AJ, Tanner DC, Nguyen ML, Snydman DR, et al. 1996. The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance. Am J Med 100:617–623. doi: 10.1016/s0002-9343(95)00010-0 8678081

45. 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 304:1192–1198. doi: 10.1016/j.ijmm.2014.08.012 25224357

46. Ramage G, Martínez JP, López-Ribot JL. 2006. Candida biofilms on implanted biomaterials: a clinically significant problem. FEMS Yeast Res 6:979–986. doi: 10.1111/j.1567-1364.2006.00117.x 17042747

47. Ramage G, Saville SP, Thomas DP, López-Ribot JL. 2005. Candida biofilms: an update. Eukaryot Cell 4:633–638. doi: 10.1128/EC.4.4.633-638.2005 15821123

48. Tóth R, Nosek J, Mora-Montes HM, Gabaldon T, Bliss JM, Nosanchuk JD et al. 2019. Candida parapsilosis: from Genes to the Bedside. Clin Microbiol Rev 32:pii:e00111–18. doi: 10.1128/CMR.00111-18 30814115

49. Bonassoli LA, Bertoli M, Svidzinski TI. 2005. High frequency of Candida parapsilosis on the hands of healthy hosts. J Hosp Infect 59:159–162. doi: 10.1016/j.jhin.2004.06.033 15620452

50. Clark TA, Slavinski SA, Morgan J, Lott T, Arthington-Skaggs BA, Brandt ME, et al. 2004. Epidemiologic and molecular characterization of an outbreak of Candida parapsilosis bloodstream infections in a community hospital. J Clin Microbiol 42:4468–4472. doi: 10.1128/JCM.42.10.4468-4472.2004 15472295

51. Bassetti M, Giacobbe DR, Vena A, Trucchi C, Ansaldi F, Antonelli M, et al. 2019. Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project. Crit Care. Jun 14;23(1):219. doi: 10.1186/s13054-019-2497-3 31200780

52. Lindberg E, Hammarström H, Ataollahy N, Kondori N. 2019. Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia. Sci Rep 9:3838. doi: 10.1038/s41598-019-40280-8 30846717

53. Bitew A, Abebaw Y. 2018. Vulvovaginal candidiasis: species distribution of Candida and their antifungal susceptibility pattern. BMC Womens Health 18:94. doi: 10.1186/s12905-018-0607-z 29902998

54. Monroy-Pérez E, Paniagua-Contreras GL, Rodríguez-Purata P, Vaca-Paniagua F, Vázquez-Villaseñor M, Díaz-Velásquez C, et al. 2016. High Virulence and Antifungal Resistance in Clinical Strains of Candida albicans. Can J Infect Dis Med Microbiol 2016:5930489. doi: 10.1155/2016/5930489 28058052

55. Cortegiani A., Misseri G., Chowdhary A. 2018. What’s new on emerging resistant Candida species. Intensive Care Medicine. Apr;45(4):512–515. doi: 10.1007/s00134-018-5363-x Epub 2018 Sep 6. 30191295


Článek vyšel v časopise

PLOS One


2019 Číslo 11