Research

Rapid multiplex molecular syndromic panels (RMMSP) (3 or more pathogens and time-to-results < 6 h) allow simultaneous detection of multiple pathogens and genotypic resistance markers. Their implementation has revolutionized the clinical landscape by significantly enhancing diagnostic accuracy and reducing time-to-results in different critical conditions. The current revision is a comprehensive but not systematic review of the literature. We conducted electronic searches of the PubMed, Medline, Embase, and Google Scholar databases to identify studies assessing the clinical performance of RMMSP in critically ill patients until July 30, 2024. A multidisciplinary group of 11 Spanish specialists developed clinical questions pertaining to the indications and limitations of these diagnostic tools in daily practice in different clinical scenarios. The topics covered included pneumonia, sepsis/septic shock, candidemia, meningitis/encephalitis, and off-label uses of these RMMSP. These tools reduced the time-to-diagnosis (and therefore the time-to-appropriate treatment), reduced inappropriate empiric treatment and the length of antibiotic therapy (which has a positive impact on antimicrobial stewardship and might be associated with lower in-hospital mortality), may reduce the length of hospital stay, which could potentially lead to cost savings. Despite their advantages, these RMMSP have limitations that should be known, including limited availability, missed diagnoses if the causative agent or resistance determinants are not included in the panel, false positives, and codetections. Overall, the implementation of RMMSP represents a significant advancement in infectious disease diagnostics, enabling more precise and timely interventions. This document addresses relevant issues related to the use of RMMSP on different critically ill patient profiles, to standardize procedures, assist in making management decisions and help specialists to obtain optimal outcomes.

Purpose To assess the risk factors and outcomes associated with fungemia caused by the six most commonly occurring Candida species in patients with and without malignancies. Methods Analysis of the episodes of fungemia due to common Candida species in adults, based on an active hospital-based surveillance program (Paris area, France, 2002 to 2014). Results Of the 3417 patients (3666 isolates), 1164 (34.1%) had a solid tumor (45.7% digestive tract) and 586 (17.1%) a hematological malignancy (41.8% lymphoma, 33.5% acute leukemia). The hematology patients were significantly younger, more often pre-exposed to antifungals, more often infected by C. tropicalis, C. krusei, or C. kefyr, and more often treated in the first instance with an echinocandin. Compared with inpatients who were not in ICU at the time of fungemia, those in ICU were less frequently infected by C. parapsilosis (p < 0.02), had more recent surgery (p < 0.03), and died more frequently before day 8 and day 30 (p < 0.0001). An increase in crude mortality over time in ICU was observed only in oncology patients (p < 0.04). For all patients, lack of prescription of antifungals despite knowledge of positive blood culture increased the risk of death. The odds of being infected by a given Candida species compared with C. albicans were uneven regarding age, gender, type of malignancy, hospitalization in ICU, central venous catheter, HIV status, intravenous drug addiction, and previous exposure to antifungal drugs. Compared with C. albicans, C. glabrata (OR = 0.69 [0.54–0.89]) and C. parapsilosis (OR = 0.49 [0.35–0.67]) were associated with a decreased risk of death by day 8 and day 30. Conclusion The clinical context of underlying malignancy and hospitalization in ICU may be relevant to the initial management of candidemia.

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Abstract. Introduction: Being elderly is a well-known risk factor for candidemia, but few data are available on the prognostic impact of candidemia in the very old (VO) subjects, as defined as people aged ≥75 years. Objective: The aim of this study was to assess risk factors for nosocomial candidemia in two groups of candidemia patients, consisting of VO patients (≥75 years) and adult and old (AO) patients (18–74 years). In addition, risk factors for death (30-day mortality) were analysed separately in the two groups. Methods: We included all consecutive candidemia episodes from January 2011 to December 2013 occurring in six referral hospitals in north-eastern Italy. Results: A total of 683 nosocomial candidemia episodes occurred. Of those, 293 (42.9%) episodes were in VO and 390 (57.1%) in AO patients. Hospitalization in medical wards, chronic renal failure, urinary catheter, and peripheral parenteral nutrition (PPN) were more common in VO than in AO patients. In the former patient group, adequate antifungal therapy (73.2%) and central venous catheter (CVC) removal (67.6%) occurred less frequently than in AO patients (82.5 and 80%, p < 0.002 and p < 0.004, respectively). Thirty-day mortality was higher in VO compared to AO patients (47.8 vs. 23.6%, p < 0.0001). In AO patients, independent risk factors for death were age (OR 1.04, 95% CI 1.00–1.09, p = 0.038), recent history of chemotherapy (OR 22.01, 95% CI 3.12–155.20, p = 0.002), and severity of sepsis (OR 40.68, 95% CI 7.42–223.10, p < 0.001); CVC removal was associated with higher probability of survival (OR 0.10, 95% CI 0.03–0.33, p < 0.001). In VO patients, independent risk factors for death were PPN (OR 3.5, 95% CI 1.17–10.47, p = 0.025) and hospitalization in medical wards (OR 2.58, 95% CI 1.02–6.53, p = 0.046), while CVC removal was associated with improved survival (OR 0.40, 95% CI 0.16–1.00, p = 0.050). Conclusion: Thirty-day mortality was high among VO patients and was associated with inadequate management of candidemia, especially in medical wards.

This study aimed to evaluate the effectiveness of fluconazole and echinocandins in the treatment of candidemia caused by both fluconazole- and echinocandin-susceptible common Candida species. A retrospective study which enrolled adult candidemia patients ≥19 years diagnosed at a tertiary care hospital in the Republic of Korea from 2013 to 2018 was conducted. Common Candida species were defined as C. albicans, C. tropicalis, and C. parapsilosis. Cases of candidemia were excluded based on the following exclusion criteria: (1) candidemia showed resistance to either fluconazole or echinocandins, or (2) candidemia was caused by other Candida species than common Candida species. In order to compare the mortality rates between patients who receive fluconazole or echinocandins, the propensity scores on variables of baseline characteristics using the multivariate logistic regression analysis were employed to balance the antifungal treatment groups, and a Kaplan–Meier survival analysis was performed. Fluconazole and echinocandins were used in 40 patients and in 87 patients, respectively. The propensity score matching included 40 patients in each treatment group. After matching, the rates of 60-day mortality after candidemia were 30% in the fluconazole group and 42.5% in the echinocandins group, and a Kaplan–Meier survival analysis showed no significant difference between antifungal treatment groups, p = 0.187. A multivariable analysis demonstrated that septic shock was significantly associated with the 60-day mortality, whereas fluconazole antifungal treatment was not associated with an excess 60-day mortality. In conclusion, our study results suggest that fluconazole use in the treatment of candidemia caused by susceptible common Candida species may be not associated with increased 60-day mortality compared to echinocandins.

2019

Presents letters written by children to King, praising and questioning his role in the Civil Rights movement

Dr. Martin Luther King, Jr.’s 1967 speech at the National Conference on New Politics in Chicago. Here, he speaks about what he calls the Triple Evils: War, R...

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