We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia.
Objectives
We prospectively monitored the epidemiology and antifungal susceptibility of Candida spp. from blood cultures and intra-abdominal samples in patients admitted to hospitals in the Madrid area.
Methods
Between 2019 and 2021, we prospectively collected incident isolates [one per species, patient and compartment (blood cultures versus intra-abdominal samples)] from patients admitted to any of 16 hospitals located in Madrid. We studied the antifungal susceptibilities to amphotericin B, triazoles, micafungin, anidulafungin and ibrexafungerp following the EUCAST E.Def 7.3.2 procedure.
Results
A total of 2107 Candida spp. isolates (1895 patients) from blood cultures (51.7%) and intra-abdominal samples were collected. Candida albicans, the Candida glabrata complex, the Candida parapsilosis complex, Candida tropicalis and Candida krusei accounted for 96.9% of the isolates; in contrast, Candida auris was undetected. Fluconazole resistance in Candida spp. was higher in blood cultures than in intra-abdominal samples (9.1% versus 8.2%; P > 0.05), especially for the C. parapsilosis complex (16.6% versus 3.6%, P < 0.05), whereas echinocandin resistance tended to be lower in blood cultures (0.5% versus 1.0%; P > 0.05). Resistance rates have risen, particularly for fluconazole in blood culture isolates, which increased sharply in 2021. Ibrexafungerp showed in vitro activity against most isolates. Species distributions and resistance rates varied among hospitals.
Conclusions
Whereas no C. auris isolates were detected, fluconazole-resistant C. parapsilosis isolates have been spreading across the region and this has pulled up the rate of fluconazole resistance. In contrast, the rate of echinocandin resistance continues to be low.
Background
Staphylococcus aureus is the leading cause of prosthetic joint infection (PJI). Beyond the antibiogram, little attention has been given to the influence of deep microbiological characteristics on patient’s prognosis. Our aim was to investigate whether microbiological genotypic and phenotypic features have a significant influence on infection pathogenesis and patient outcome.
Methods
prospective multicentre study was performed, including all S. aureus PJIs (2016-2017). Clinical data, phenotypic (agr functionality, β-hemolysis, biofilm formation) and genotypic characteristics of the strains were collected. Biofilm susceptibility to antimicrobials was investigated (MBEC assay).
Results
88 patients (39.8% men, age 74.7±14.1 years) were included. Forty-five had early post-operative (EPI), 21 chronic (CPI), and 19 hematogenous infections (HI). Twenty (22.7%) were caused by MRSA. High genotypic diversity was observed, including 16 clonal complexes (CC), CC5 being the most frequent (30.7%). agr activity was greater in EPI than CPI (55.6% vs 28.6%, p=0.041). Strains causing EPI were phenotypically and genotypically similar, regardless of symptom duration. Treatment failure (36.5%) occurred less frequently among cases treated with implant removal. In cases treated with debridement and implant retention, there were fewer failures among those who received combination therapy with rifampin. No genotypic or phenotypic characteristics predicted failure, except vancomycin MIC>=1.5 mg/L (23.1% failure vs 3.4%, p=0.044). MBEC50 was >128 mg/L for all antibiotics tested and showed no association with prognosis.
Conclusions
S. aureus with different genotypic backgrounds is capable of causing PJI, showing slight differences in clinical presentation and pathogenesis. No major microbiological characteristics were observed to influence the outcome, including MBEC.
High fluconazole MIC values did not negatively impact outcome of patients with candidaemia treated with fluconazole. No effect of PK/PD targets on the risk of clinical failure was found.
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