Incidence of pneumococcal disease has increased worldwide in recent years. Response to pneumococcal vaccine is usually measured using the multiserotype enzyme-linked immunosorbent assay (ELISA) ...pneumococcal test. However, this approach presents several limitations. Therefore, the introduction of new and more robust analytical approaches able to provide information on the efficacy of the pneumococcal vaccine would be very beneficial for the clinical management of patients. Surface plasmon resonance (SPR) has been shown to offer a valuable understanding of vaccines' properties over the last years. The aim of this study is to evaluate the reliability of SPR for the anti-pneumococcal capsular polysaccharides (anti-PnPs) IgGs quantification in vaccinated. Fast protein liquid chromatography (FPLC) was used for the isolation of total IgGs from serum samples of vaccinated patients. Binding-SPR assays were performed to study the interaction between anti-PnPs IgGs and PCV13. A robust correlation was found between serum levels of anti-PnPs IgGs, measured by ELISA, and the SPR signal. Moreover, it was possible to correctly classify patients into "non-responder", "responder" and "high-responder" groups according to their specific SPR PCV13 response profiles. SPR technology provides a valuable tool for reliably characterize the interaction between anti-PnPs IgGs and PCV13 in a very short experimental time.
For the specialist, the management of invasive candidiasis infections, from diagnosis to selection of the therapeutic protocol, is often a challenge. Although early diagnosis and treatment are ...associated with a better prognosis, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, relying on many different factors, clinical and laboratory findings but there is certainly a need for the specific markers in this disease. Recently, new serodiagnostic assays as Candida albicans germ-tube antibodies or (1,3)-β- d-glucan detection and molecular techniques for the detection of fungal-specific DNA have been developed with controversial results in critical care setting. One of the main features in diagnosis is the evaluation of risk factor for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. For these reasons, an approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the new prediction rules and its application situations has been made. Currently, the combination of prediction rules and non-culture microbiological tools could be the clue for improving the diagnosis and prognosis of invasive fungal infections in critically ill patients.
Objective: The evaluation of the Sensititre YeastOne and Etest methods for determining susceptibility to amphotericin B and itraconazole by comparing the MICs obtained by these methods at different ...times of reading with those of the M38-A broth microdilution method. Methods: Sixty-three clinical isolates of Aspergillus spp. (23 Aspergillus flavus, 24 Aspergillus fumigatus, nine Aspergillus niger, three Aspergillus glaucus, two Aspergillus terreus and two Aspergillus flavipes) were assayed. Two itraconazole-resistant strains (NCPF7100 and 7099) were also included. Results: Itraconazole MICs for the two resistant strains were >4 mg/L by the three methods. The overall agreement (±2 log2) between M38-A (48 h) and colorimetric (48 h) method was 93.4% for amphotericin B and 90.2% for itraconazole. By the Etest, the best agreement with M38-A was obtained when readings were made at 24 h: 88.5% for amphotericin B and 67.2% for itraconazole. Etest MICs were higher for all species except A. niger. Conclusions: The colorimetric method appears to be a suitable alternative procedure for antifungal susceptibility testing of Aspergillus spp. and is able to detect resistance to itraconazole. The range of MICs for amphotericin B by Etest is wider and for some strains is >16 mg/L, suggesting that this method could be useful for detecting resistant strains as occur in yeasts.
Abstract
Background
Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians.
Main body
This opinion paper ...discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by
Candida glabrata
. Other situations and alternatives, such as new compounds or combination therapy, are also analysed.
Conclusion
There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance.
Candida auris is an emerging, multidrug-resistant yeast causing hospital outbreaks. This study describes the first 24 months of the ongoing C. auris outbreak in our hospital and analyzes predisposing ...factors to C. auris candidemia/colonization.
A 12-month prospective, case-controlled study was performed including a total of 228 patients (114 colonized/candidemia and 114 controls). Data from the first 79 candidemia episodes and 738 environmental samples were also analyzed. Definitive C. auris identification was performed by ITS sequencing. Antifungal susceptibility was carried out by EUCAST methodology.
Polytrauma (32%), cardiovascular disease (25%), and cancer (17%) were the most common underlying condition in colonized/candidemia patients. Indwelling CVC (odds ratio {OR}, 13.48), parenteral nutrition (OR, 3.49), and mechanical ventilation (OR, 2.43) remained significant predictors of C. auris colonization/candidemia. C. auris was most often isolated on sphygmomanometer cuffs (25%) patient tables (10.2%), keyboards (10.2%), and infusion pumps (8.2%). All isolates were fully resistant to fluconazole (MICs >64 mg/L) and had significantly reduced susceptibility to voriconazole (GM, 1.8 mg/L).
Predictor conditions to C. auris colonization/candidemia are similar to other Candida species. C. auris colonizes multiple patient's environment surfaces. All isolates are resistant to fluconazole and had significant reduced susceptibility to voriconazole.
Critically ill COVID-19 patients have higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4, IL-10) cytokine levels, less CD
interferon-gamma expression, and ...fewer CD
and CD
cells. This severe clinical situation increases the risk of serious fungal infections, such as invasive pulmonary aspergillosis, invasive candidiasis or Pneumocystis jirovecii pneumonia. However, few studies have investigated fungal coinfections in this population. We describe an update on published reports on fungal coinfections and our personal experience in three Spanish hospitals. We can conclude that despite the serious disease caused by SARS-CoV-2 in many patients, the scarcity of invasive mycoses is probably due to the few bronchoscopies and necropsies performed in these patients because of the high risk in aerosol generation. However, the presence of fungal markers in clinically relevant specimens, with the exception of bronchopulmonary colonization by Candida, should make it advisable to early implement antifungal therapy.
The high morbidity, mortality, and health care costs associated with invasive fungal infections, especially in the critical care setting and immunocompromised host, have made it an excellent target ...for prophylactic, empiric, and preemptive therapy interventions principally based on early identification of risk factors. Early diagnosis and treatment are associated with a better prognosis. In the last years there have been important developments in antifungal pharmacotherapy. An approach to the new diagnosis tools in the clinical mycology laboratory and an analysis of the use new antifungal agents and its application in different clinical situations has been made. Furthermore, an attempt of developing a state of the art in each clinical scenario (critically ill, hematological, and solid organ transplant patients) has been performed, trying to choose the best strategy for each clinical situation (prophylaxis, pre-emptive, empirical, or targeted therapy). The high mortality rates in these settings make mandatory the application of early de-escalation therapy in critically ill patients with fungal infection. In addition, the possibility of antifungal combination therapy might be considered in solid organ transplant and hematological patients.
Minimum fungicidal concentrations (MFCs) of amphotericin B were obtained for 165 bloodstream isolates (104
Candida parapsilosis, 14
C.glabrata, 13
C.tropicalis, 15
C.krusei, and 19
C.albicans) and 36
...C.dubliniensis from oropharyngeal infections. Minimum inhibitory concentrations (MICs) were determined by the M27-A microdilution method. MFCs (≥99.9% killing) were obtained following MIC determination (inoculum size, 10
4 CFU/ml) by seeding the entire volume of all clear wells. The best fungicidal activity was for
C. albicans, (MFC
90 1 μg/ml) and the lowest for
C.parapsilosis, C.tropicalis and
C.glabrata (MFC
90 16 μg/ml). Although MFCs were ≥16× MIC for some isolates, including
C. glabrata, the overall MFCs were ≥2× MICs. However, major differences between MICs and MFCs were observed for
C.parapsilosis and
C.dubliniensis (3.8% and 8.9%, respectively, were tolerant: MFC ≥32MIC). MFCs for
C.tropicalis and
C. glabrata were ≥2 μg/ml. By this more stringent method we found substantial differences from those previously reported between amphotericin B MIC and MFCs for
Candida spp.
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