Candida biofilm. José Garnacho Montero Hospital Universitario Virgen del Rocío Sevilla. Spain

Transcription

1 Candida biofilm José Garnacho Montero Hospital Universitario Virgen del Rocío Sevilla. Spain

2 Introduction Candidemia is frequently associated with the biofilm growth of Candida organisms on medical devices (venous catheter or urinary catheter). This infection is greatly serious because all antifungal agents do not have in vitro efficacy against Candida biofilms. Organisms in biofilms behave differently from freely suspended cells with respect to antimicrobial resistance

3 Introduction The mechanism of antifungal resistance of Candida species has not been fully elucidated. One possibility is that the exopolymeric matrix forms a barrier to antifungals. Under these conditions, Candida cells overexpress efflux pumps, which may enhance antifungal resistance.

4 Factors that contribute to the formation of Candida biofilms Conditioning films Characteristics of the contact surface Candida morphogenesis Candida strain Bacterial competition/cooperation Location of the implanted medical device

5 Effect of hydrophobicity and roughness of several biomaterials on Candida biofilms formation

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7 Mechanisms of biofilm resistance Limited penetration of drugs through the matrix. Slow growth of organisms in biofilms Changes in cell surface composition Unique biofilm-associated patterns of gene expression

8 Biofilm production: Influence of the species of Candida and the infection site Biofilm production by C. albicans was significantly less frequent (8%) than that by non-albicans Candida species (61%; P < ). Biofilm production was detected in 58 (57%) of 101 bloodstream isolates, and 83 (32%) of 259 isolates from other sites (P<0.0001). J Clin Microbiol 2002; 40:

9 AAC 2011; 55: MICs for different Candida species isolates under planktonic or biofilm growth conditions Fluconazole and voriconazole were ineffective against biofilms of all five Candida species

10 AAC 2011; 55: MICs for different Candida species isolates under planktonic or biofilm growth conditions Fluconazole and voriconazole were ineffective against biofilms of all five Candida species Amphotericin B

11 AAC 2011; 55: MICs for different Candida species isolates under planktonic or biofilm growth conditions Anidulafungin and Caspofungin

12 AAC 2013; 57: * Liposomal amphotericin kills C. albicans biofilms rapidly (12 h) and effectively (>90%) in a dose-dependent manner * Caspofungin displays an inverse concentration-dependent effect. Liposomal Amphotericin B Caspofungin

13 AAC 2013; 57: Voriconazole was highly ineffective, with no notable activity Voriconazole

14 Activity of echinocandins against biofilms of Candida spp Candida albicans Simitsopoulou. AAC 2013; 57:

15 Activity of echinocandins against biofilms of Candida spp Simitsopoulou. AAC 2013; 57: Candida parapsilosis

16 Regrowth of the cells forming the biofilm was reduced by more than 80% at micafungin serum concentrations of 4 μg/ml. Micafungin concentrations of 2 μg/ml may be sufficiently high to eradicate Candida biofilms. Antimicrob Agents Chemother. 2014; 58:

17 Biofilm Production in Patients with Candidemia 294 patients with Candida BSIs Fungal isolates were tested for biofilm formation capacity Biofilm-positive Biofilm-negative C glabrata 6 20 C parapsilosis C tropicalis 8 20 C albicans 38 J Clin Microbiol 2007; 45:

18 Biofilm Production as Predictors of Mortality for Patients with Candidemia 30 day mortality rate: 52.3% Mortality rate in patients with BSIs due to biofilmpositive isolates was significantly higher than in patients with BSIs due to biofilm negative isolates (70% [56 of 80] versus 45.7% [98 of 214]; P < 0.001). Risk factor Biofilm-forming forming Candida APACHE II Inadequate therapy Odds ratio (95% CI) 2.33 ( ) 1.03 ( ) 1.15) 2.35 ( ) p-value < J Clin Microbiol 2007; 45:

19 Risk Factors of Mortality in Candidemia Caused by Biofilm-Forming Strains 207 episodes of candidemia (84 biofilmforming strains) Patients with biofilm-forming CBSI were compared to those with non-biofilm-forming CBSI. Patients with biofilm-forming CBSI were matched to patients with non-biofilm-forming CBSI for the following factors: age (±10 years), sex, APACHE III score (±3) Receipt of adequate antifungal therapy Tumbarello M. PLoS One. 2012;7(3):e33705.

20 Risk Factors of Mortality in Candidemia Caused by Biofilm-Forming Strains Importance of treatment with highly active antibiofilm agents (echinocandins) vs non-highly active antibiofilm agents (fluconazole) 207 episodes of candidemia (84 biofilm-forming strains) Tumbarello M. PLoS One. 2012;7(3):e33705.

21 Risk Factors of Mortality in Candidemia Caused by Biofilm-Forming Strains Importance of treatment with highly active antibiofilm agents (echinocandins) vs non-highly active antibiofilm agents (fluconazole) 207 episodes of candidemia (84 biofilm-forming strains) Tumbarello M. PLoS One. 2012;7(3):e33705.

22 Hospital length of stay following the CBSI All patients: White box-plots Surviving patients: Grey box-plots Tumbarello M. PLoS One. 2012;7(3):e33705.

23 Biofilm production does not impact on mortality 467 episodes of candidemia. In 160 episodes: 77 high-biofilm-forming isolates 83 low-biofilm-forming isolates No difference in the crude mortality rate was observed according to biofilmforming ability in C. albicans or nonalbicans Candida Infection (2013) 41:

24 Biofilm production does not impact on mortality No difference in mortality between patients infected by biofilm-producing isolates and treated with lipid-based amphotericin B or echinocandins (17 patients) and patients treated with drugs not active against biofilms (fluconazole and voriconazole; 59 patients). Infection (2013) 41:

25 Biofilm production is not a predictor of catheter-related candidemia 45/54 (83.3%) were capable of forming biofilms: C. albicans 97% C. parapsilosis 70.6% C. glabrata 25% No difference in the mortality of candidemia patients infected by biofilmforming isolates and those with infection caused by nonbiofilm-forming species Medical Mycology, 2014, 52,

26 Biofilm production is neither a predictor of catheter-related candidemia nor associated with mortality Medical Mycology, 2014, 52,

27 Biofilm production is neither a predictor of catheter-related candidemia nor associated with mortality Medical Mycology, 2014, 52,

28 Take-Home Messages Candidemia is frequently associated with the biofilm growth of Candida organisms on medical devices (mainly venous catheter). This infection is greatly serious because biofilms are thought to be recalcitrant to antifungal (e.g., fluconazole and voriconazole) therapy, and only two classes of agents (liposomal amphotericin B and echinocandins) appear to have in vitro efficacy against Candida biofilms.

29 Take-Home Messages However, the impact on mortality of biofilm-forming strains and the use of antifungals with efficacy against Candida biofilm is still a matter of debate In the meanwhile, the use of agents with activity against Candida biofilms seems reasonable.