Dataset Information

Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis.

ABSTRACT:

Objectives

Invasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety.

Methods

We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candidiasis among predominantly adult populations. We performed a meta-analysis and then conducted a Bayesian mixed treatment comparison to differentiate treatment effectiveness. Sensitivity analyses included dosage forms of amphotericin B and fluconazole compared to other azoles.

Results

Our analysis included 11 studies enrolling a total of 965 patients. For our primary analysis of global response rates, we pooled 7 trials comparing azoles to amphotericin B, Relative Risk [RR] 0.87 (95% Confidence Interval [CI], 0.78-0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI, 0.99-1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded a RR of 1.26 (95% CI, 1.06-1.51) in favor of anidulafungin. We pooled 7 trials assessing azoles versus amphotericin B for all-cause mortality, resulting in a pooled RR of 0.88 (95% CI, 0.74-1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR of 1.01 (95% CI, 0.84-1.20, P = 0.93). Anidulafungin versus fluconazole resulted in a RR of 0.73 (95% CI, 0.48-1.10, P = 0.34). Our mixed treatment comparison analysis found similar within-class effects across all interventions. Adverse event profiles differed, with amphotericin B exhibiting larger adverse event effects.

Conclusion

Treatment options appear to offer preferential effects on response rates and mortality. When mycologic data are available, therapy should be tailored.

SUBMITTER: Mills EJ

PROVIDER: S-EPMC2713200 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Publications

Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis.

Mills Edward J EJ Perri Dan D Cooper Curtis C Nachega Jean B JB Wu Ping P Tleyjeh Imad I Phillips Peter P

Annals of clinical microbiology and antimicrobials 20090626

<h4>Objectives</h4>Invasive fungal infections are a major cause of mortality among patients at risk. Treatment guidelines vary on optimal treatment strategies. We aimed to determine the effects of different antifungal therapies on global response rates, mortality and safety.<h4>Methods</h4>We searched independently and in duplicate 10 electronic databases from inception to May 2009. We selected any randomized trial assessing established antifungal therapies for confirmed cases of invasive candid ...[more]

PMID: 19558681

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Project description:BackgroundCandida albicans is a fungal pathogen causing human infections. Here we investigated differential gene expression patterns and functional enrichment in C. albicans strains grown under different conditions.MethodsA systematic GEO database search identified 239 "Candida albicans" datasets, of which 14 were selected after rigorous criteria application. Retrieval of raw sequencing data from the ENA database was accompanied by essential metadata extraction from dataset descriptions and original articles. Pre-processing via the tailored nf-core pipeline for C. albicans involved alignment, gene/transcript quantification, and diverse quality control measures. Quality assessment via PCA and DESeq2 identified significant genes (FDR < = 0.05, log2-fold change > = 1 or <= -1), while topGO conducted GO term enrichment analysis. Exclusions were made based on data quality and strain relevance, resulting in the selection of seven datasets from the SC5314 strain background for in-depth investigation.ResultsThe meta-analysis of seven selected studies unveiled a substantial number of genes exhibiting significant up-regulation (24,689) and down-regulation (18,074). These differentially expressed genes were further categorized into 2,497 significantly up-regulated and 2,573 significantly down-regulated Gene Ontology (GO) IDs. GO term enrichment analysis clustered these terms into distinct groups, providing insights into the functional implications. Three target gene lists were compiled based on previous studies, focusing on central metabolism, ion homeostasis, and pathogenicity. Frequency analysis revealed genes with higher occurrence within the identified GO clusters, suggesting their potential as antifungal targets. Notably, the genes TPS2, TPS1, RIM21, PRA1, SAP4, and SAP6 exhibited higher frequencies within the clusters. Through frequency analysis within the GO clusters, several key genes emerged as potential targets for antifungal therapies. These include RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101 which exhibited higher occurrence within the identified clusters.ConclusionThis comprehensive study significantly advances our understanding of the dynamic nature of gene expression in C. albicans. The identification of genes with enhanced potential as antifungal drug targets underpins their value for future interventions. The highlighted genes, including TPS2, TPS1, RIM21, PRA1, SAP4, SAP6, RSP5, GLC7, SOD2, SOD5, SOD1, SOD6, SOD4, SOD3, and RIM101, hold promise for the development of targeted antifungal therapies.

Project description:ContextCandida-related infections are nowadays a serious Public Health Problem emerging multidrug-resistant strains. Candida biofilm also leads bloodstream infections to invasive systemic infections.ObjectiveThe present meta-analysis aimed to analyze Candida biofilm rate, type, and antifungal resistance among hospitalized patients between 1995 and 2020.Data sourcesWeb of Science, Scopus, PubMed, and Google Scholar databases were searched for English papers using the following medical subject heading terms (MESH): "invasive candidiasis"; "bloodstream infections"; "biofilm formation"; "biofilm-related infections"; "mortality"; and "prevalence".Study selectionThe major inclusion criteria included reporting the rate of biofilm formation and the prevalence of biofilm-related to Candida species, including observational studies (more exactly, cohort, retrospective, and case-control studies). Furthermore, data regarding the mortality rate, the geographical location of the study set, and the use of anti-fungal agents in clinical isolates were also extracted from the studies.Data extractionIndependent extraction of articles by 2 authors using predefined data fields, including study quality indicators.Data synthesisA total of 31 studies from publicly available databases met our inclusion criteria. The biofilm formation in the data set varied greatly from 16 to 100% in blood samples. Most of the studies belonged to Europe (17/31) and Asia (9/31). Forest plot showed a pooled rate of biofilm formation of 80.0% (CI: 67-90), with high heterogeneity (Q = 2567.45, I2 = 98.83, τ2 = 0.150) in random effects model (p < 0.001). The funnel plot and Egger's linear regression test failed to find publication bias (p = 0.896). The mortality rate in Candida-related bloodstream infections was 37.9% of which 70.0% were from biofilm-associated infections. Furthermore, Candida isolates were also characterized in low, intermediate, or high biofilm formers through their level of biofilm mass (crystal violet staining or XTT assays) after a 24h growth. When comparing between countries, statistical differences were obtained (p = 0.0074), showing the lower and higher biofilm prevalence values in Italy and Spain, respectively. The prevalence of low, intermediate, and high biofilms were 36.2, 18.9, and 35.0% (p < 0.0001), respectively. C. tropicalis was the prevalent species in high biofilm formation (67.5%) showing statistically significant differences when compared to other Candida species, except for C. krusei and C. glabrata. Finally, the rates of antifungal resistance to fluconazole, voriconazole, and caspofungin related to biofilm were 70.5, 67.9 and 72.8% (p < 0.001), respectively.ConclusionsEarly detection of biofilms and a better characterization of Candida spp. bloodstream infections should be considered, which eventually will help preserve public health resources and ultimately diminish mortality among patients.

Dataset Information

Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis.

Objectives

Methods

Results

Conclusion

Publications

Antifungal treatment for invasive Candida infections: a mixed treatment comparison meta-analysis.

Similar Datasets

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