Early diagnosis and treatment of meningitis and encephalitis is essential for reducing both their morbidity and mortality. The FilmArray® Meningitis/Encephalitis (FA-M/E) panel is a recently ...available molecular tool allowing the simultaneous detection of 14 pathogens in about one hour. We evaluated its routine use over a 13-month period at Nîmes University Hospital, France. Cerebrospinal fluid (CSF) specimens were prospectively analyzed, independently of cell count; results were retrospectively analyzed and positive results compared to clinical and microbiological data. Among the 708 patients included (734 CSF samples), 89 (12.6%) had a positive FA-M/E panel, 71 (80%) for a viral pathogen and 18 (20%) for a bacterial pathogen. Enterovirus and HHV-6 were the main detected pathogens. Mean time-to-results was 1h46mn. Four non-clinically relevant results were detected (3 HHV-6 and 1 Haemophilus influenzae) on the basis of inconsistent clinical and/or biological data, and/or after visualization of melting curves. No CSF pleocytosis was observed in 11% of the patients with a positive FA-M/E panel. For the 18 patients with a positive FA-M/E panel for a bacterial pathogen, five (28%) had CSF samples showing a positive Gram stain allowing an early diagnosis of bacterial infection and 67% had CSF displaying a positive culture. Altogether the panel detected 5 cases of bacterial M/E (29%) not diagnosed by culture. Despite undeniable advantages, mainly ease of use, quick result availability, and an extremely low rate of invalid results, measures should be implemented to limit false-positive results due to contamination and a careful interpretation based on the overall data for each patient is required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the context of a 3-month extended-spectrum beta-lactamase-producing
Klebsiella pneumonia
(ESBL-KP) outbreak in a neonatal care center (NCC), hygiene practices and hospital environment were ...investigated. ESBL-KP strains isolated from patients and environment were compared by molecular typing. The density of incidence of multi-drug-resistant bacteria (MDRB) was calculated from January 2014 to September 2016. The 3-month ESBL-KP outbreak involved 19 patients. Clinical strains from the 19 patients displayed the same molecular profile between them, and with a strain isolated from an incubator after cleaning. Furthermore, 52.4% of incubator mattresses were positive for diverse pathogens. Hygiene practices were acceptable except for external practitioners and parents. In addition to classical infection control (IC) measures, the replacement of mattresses and the improvement of incubators disinfection stopped the outbreak. The protocol of disinfection was revised and microbiological control was implemented. A significant decrease of MDRB incidence was concomitant (
p
value = 0.03219) but 3 months later, MDRB incidence increased again.
Conclusion
: This investigation highlighted incubators and mattresses as critical materials associated to infectious risk in NCC. NCC and IC teams should implement efficient protocol for incubators disinfection and monitoring.
What is Known:
•
Environment in neonatal intensive care units is often suspected as reservoir for Enterobacteriaceae outbreaks but is scarcely investigated
.
•
Incubators and mattresses offer wet and warm conditions suitable for pathogens multiplication
,
but microbiological survey is not performed routinely for assessing bacterial contamination
.
What is New:
•
Incubators and mattresses serve as reservoir for pathogens and relay in outbreak
.
•
An infection control protocol associating efficient disinfection and microbiology analysis is proposed
.
Background Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to ...both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients. Methods We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin-tazobactam, meropenem and trimethoprim-sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines. Results Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from less than or equal to 0.015 to 16 mg/L with MIC.sub.50/90 of less than or equal to 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains. Conclusions Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin. Keywords: Achromobacter, Opportunistic pathogen, Cystic fibrosis, Cefiderocol, Susceptibility
The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). ...From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female M/F ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range IQR, 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) (
< 10
). For CAPA, the presence of several mycological criteria was associated with death (
< 10
). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients (
= 0.001). Antimold treatment did not alter prognosis (
= 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses.
To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.
Sarcopenia involves a progressive loss of skeletal muscle force, quality and mass during ageing, which results in increased inability and death; however, no cure has been established thus far. Growth ...differentiation factor 5 (GDF5) has been described to modulate muscle mass maintenance in various contexts. For our proof of concept, we overexpressed GDF5 by AAV vector injection in Tibialis Anterior (TA) muscle of adult aged (20 months) mice and performed molecular and functional analysis of skeletal muscle. We analysed human Vastus Lateralis muscle biopsies from adult young (21-42 years) and aged (77-80 years) donors, quantifying the molecular markers modified by GDF5 overexpression (OE) in mouse muscle. We validated the major effects of GDF5 overexpression using human immortalized myotubes and Schwann Cells (SCs). We established a pre-clinical study by treating chronically (for 4 months) aged mice using recombinant GDF5 protein (rGDF5) in systemic administration and evaluated the long-term effect of this treatment on muscle mass and function. Here, we demonstrated that GDF5 OE in the old TAs promoted an increase of 16.5% of muscle weight (P = 0.0471) associated with a higher percentage of 5000-6000 µm2 large fibres (P = 0.0211), without the induction of muscle regeneration. Muscle mass gain was associated with an amelioration of 26.8% of rate of force generation (P = 0.0330) and a better neuromuscular connectivity (P = 0.0098). Moreover, GDF5 OE preserved neuromuscular junction (NMJ) morphology (38.5% of nerve terminal area increase, P < 0.0001) and stimulated the expression of re-innervation-related genes, in particular markers of SCs (fold change 3.19 for S100b gene expression, P = 0.0101). To further characterize the molecular events induced by GDF5 OE during ageing, we performed a genome-wide transcriptomic analysis of treated muscles and showed that this factor leads to a "rejuvenating" transcriptomic signature in aged mice, as 42% of the transcripts dysregulated by ageing reverted to youthful expression levels upon GDF5 OE (P < 0.05). Towards a pre-clinical approach, we performed a long-term systemic treatment using rGDF5 and showed its effectiveness in counteracting age-related muscle wasting, improving muscle function (17,8% of absolute maximal force increase, P = 0.0079), ensuring neuromuscular connectivity and preventing NMJ degeneration (7,96% of AchR area increase, P = 0.0125). In addition, in human muscle biopsies, we found the same age-related alterations than those observed in mice and improved by GDF5 and reproduced its major effects on human cells, suggesting this treatment as efficient in humans. Overall, these data provide a foundation to examine the curative potential of GDF5 drug in clinical trials for sarcopenia and, eventually, other neuromuscular diseases.
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