•Data regarding the use of isavuconazole in non-neutropenic IFI patients is scarce.•Our study positions isavuconazole as a safe treatment for these patients.•Isavuconazole could be used in patients ...with QT elongation.•Mortality and clinical response are comparable to other antifungals.•Isavuconazole could replace other triazoles as reference treatment.
Information is scarce on clinical experiences with non-neutropenic patients with invasive fungal infection (IFI) receiving isavuconazole. We aimed to report the safety and effectiveness of this drug as a first-line treatment or rescue in real life.
A retrospective, observational multicentric study of non-neutropenic patients who received isavuconazole as an IFI treatment at 12 different university hospitals (January 2018-2022). All patients met criteria for proven, probable or possible IFI according to EORTC-MSG.
A total of 238 IFIs were treated with isavuconazole during the study period. Combination therapy was administered in 27.7% of cases. The primary IFI was aspergillosis (217, 91.2%). Other IFIs treated with isavuconazole were candidemia (n = 10), mucormycosis (n = 8), histoplasmosis (n = 2), cryptococcosis (n = 2), and others (n = 4). Median time of isavuconazole treatment was 29 days. Only 5.9% (n = 14) of cases developed toxicity, mainly hepatic-related (10 patients, 4.2%). Nine patients (3.8%) had treatment withdrawn. Successful clinical response at 12 weeks was documented in 50.5% of patients.
Isavuconazole is an adequate treatment for non-neutropenic patients with IFIs. Toxicity rates were low and its effectiveness was comparable to other antifungal therapies previously reported.
Display omitted
The objectives of this study were to gain further insight on
genotype distribution and percentage of clustered isolates between hospitals and to identify potential clusters involving different ...hospitals and cities. We aim to genotype
spp. isolates causing candidemia in patients admitted to 16 hospitals in Spain, Italy, Denmark, and Brazil. Eight hundred and eighty-four isolates (
= 534;
= 282; and
= 68) were genotyped using species-specific microsatellite markers. CDC3, EF3, HIS3, CAI, CAIII, and CAVI were used for
, Ctrm1, Ctrm10, Ctrm12, Ctrm21, Ctrm24, and Ctrm28 for
, and CP1, CP4a, CP6, and B for
. Genotypes were classified as singletons (genotype only found once) or clusters (same genotype infecting two or more patients). Clusters were defined as intra-hospital (involving patients admitted to a single hospital), intra-ward (involving patients admitted to the same hospital ward) or widespread (involving patients admitted to different hospitals). The percentage of clusters and the proportion of patients involved in clusters among species, genotypic diversity and distribution of genetic diversity were assessed. Seven hundred and twenty-three genotypes were detected, 78 (11%) being clusters, most of which (57.7%;
= 45/78) were intra-hospital clusters including intra-ward ones (42.2%;
= 19/45). The proportion of clusters was not statistically different between species, but the percentage of patients in clusters varied among hospitals. A number of genotypes (7.2%; 52/723) were widespread (found at different hospitals), comprising 66.7% (52/78) of clusters, and involved patients at hospitals in the same city (
= 21) or in different cities (
= 31). Only one
cluster was a widespread genotype found in all four countries. Around 11% of
and
isolates causing candidemia are clusters that may result from patient-to-patient transmission, widespread genotypes commonly found in unrelated patients, or insufficient microsatellite typing genetic discrimination.
Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis.
The aim of this study was to assess the
...activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of
.
Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163
, 108
, 60
, 40
, 29
, 20
, 6
, 2
, 2
, and 1 isolate each of
,
, and
. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22
from different clinical specimens were evaluated.
Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for
(geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for
(geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC
s (mg/L) against
spp. were 0.125/0.06 for
, 0.5/0.5 for
, 0.25/0.25 for
, 0.5/0.5 for
, 1/1 for
, 4/2 for
, and 0.5/0.5 for
. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%)
, 4 (5%)
, and 1 (2.5%)
.
Ibrexafungerp showed a potent
activity against
.
The SARS-CoV-2 can be excreted in feces and can reach sewage systems. Determining the presence of infective viral particles in feces and sewage is necessary to take adequate control measures and to ...elucidate new routes of transmission. Here, we have developed a sample concentration methodology that allows us to maintain viral infectivity. Feces of COVID-19 patients and wastewater samples have been analyzed both by molecular methods and cell culture. Our results show no evidence of infective viral particles, suggesting that fecal–oral transmission is not a primary route. However, larger-scale efforts are needed, especially with the emergence of new viral variants.
Pneumocystis pneumonia (PcP) is a disease produced by the opportunistic infection of the fungus
. As delayed or unsuitable treatments increase the risk of mortality, the development of rapid and ...accurate diagnostic tools for PcP are of great importance. Unfortunately, current standard methods present severe limitations and are far from adequate. In this work, a time-competitive, sensitive and selective biosensor based on DNA-gated nanomaterials for the identification of
is presented. The biosensor consists of a nanoporous anodic alumina (NAA) scaffold which pores are filled with a dye reporter and capped with specific DNA oligonucleotides. In the presence of
genomic DNA, the gated biosensor is open, and the cargo is delivered to the solution where it is monitored through fluorescence spectroscopy. The use of capping oligonucleotides able to form duplex or triplex with
DNA is studied. The final diagnostic tool shows a limit of detection (LOD) of 1 nM of target complementary DNA and does not require previous amplification steps. The method was applied to identify DNA from
in unmodified bronchoalveolar lavage, nasopharyngeal aspirates, and sputum samples in 60 min. This is a promising alternative method for the routinely diagnosis of Pneumocystis pneumonia.
Statins have immunomodulatory properties and hinder Candida growth. However, it is unknown whether they may improve prognosis in patients with candidemia. We sought to determine the effect of prior ...statin use on the clinical outcomes of patients suffering candidemia.
Multicenter cohort study of hospitalized adults with candidemia between 2005 and 2011 in six hospitals in Spain, Brazil and Argentina. Of 326 candidemias, 44 (13.5%) occurred in statin users and 282 (86.5%) in statin non-users. The median value of APACHE II at candidemia diagnosis was similar between groups (18 vs. 16; p=.36). Candida albicans was the most commonly isolated species, followed by C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei. There were no differences regarding appropriate empirical antifungal treatment. Statin users had a lower early (5 d) case-fatality rate than non-users (4.5 vs. 17%; p=.031). This effect was not observed with other cardiovascular drugs (aspirin, beta blockers and ACE inhibitors). Independent factor related to early case-fatality rate was APACHE II score (AOR, 1.08; 95% CI, 1.03-1.14; p=.002). An appropriate empirical antifungal therapy (AOR, 0.11; 95% CI, 0.04-0.26; p=<.001) and prior statin use were independently associated with lower early case-fatality (AOR, 0.17; 95% CI, 0.03-0.93; p=.041). Fourteen days (14d) and overall (30d) case-fatality rates were similar between groups (27% vs. 29%; p=0.77 and 40% vs. 44%; p=.66).
The use of statins might have a beneficial effect on outcomes of patients with candidemia. This hypothesis deserves further evaluation in randomized trials.
PDF
