Pectin beads encapsulating Cwp84 provide partial protection against
C. difficile after oral vaccination.
We have designed an oral vaccine against
Clostridium difficile infection. The virulent factor ...Cwp84, that is a cystein protease highly immunogenic in patients with
C. difficile-associated disease, was entrapped within pectin beads. Beads encapsulating Cwp84 were shown to be stable in the simulated intestinal medium and to release the cystein protease once in the simulated colonic medium. Three groups of hamsters were immunized, the first receiving pectin beads encapsulating Cwp84, the second unloaded beads and the third one free Cwp84. After three immunizations by the intragastric route, all groups received clindamycine. Post-challenge survival with a strain of
C. difficile showed that 2
days after infection, all hamsters treated with unloaded beads and all hamsters treated with free Cwp84 have deceased after 7
days, whereas about 40% of hamsters administered with Cwp84-loaded beads survived 10
days after challenge, proving that oral vaccination provides partial protection. These first data obtained with an oral vaccine against
C. difficile appear promising for preventing this infection.
Urinary tract infection diagnosis and management generally involves a 48-h microbiological delay to obtain the antibiotic susceptibility test (AST) results. In the context of multidrug resistance, ...reducing the time to obtain AST results is an essential factor, allowing for more timely appropriate treatment. We conducted a single-centre prospective study on urinary samples meeting two criteria: significant leukocyturia > 50/mm
3
and exclusive presence of Gram-negative bacilli on direct examination. AST were performed by direct inoculation on Mueller-Hinton Rapid-SIR (MHR-SIR) agar. We evaluated the time to antibiotic adaptation by the antimicrobial stewardship team according to rapid AST results. Patients were subsequently excluded from the study if asymptomatic bacteria were confirmed, or in the absence of clinical data. Seventy patients were included. Mean age of patients was 68.8 years (± 21.3). Empirical antibiotic treatment were mainly based on third generation cephalosporins (
n
= 33), fluoroquinolones (
n
= 15), beta-lactamin/beta-lactamase inhibitors (
n
= 7), fosfomycin and nitrofurantoin (
n
= 5, each). The average time to obtain results was 7.2 h (± 1.6 h). Adaptation of therapy following MHR-SIR was performed for 29 patients (41%) with early switch to oral antibiotics, de-escalation or escalation in respectively 72.3%, 30%, and 11% of cases. Time saving of MHR-SIR compared with the standard technique was 42.6 (± 16.7) h. This study showed that rapid antibiotic susceptibility test results, using MHR-SIR method directly from urine, can be obtained 40 h earlier than conventional AST. The study also demonstrated significant clinical impact on the selection and reduction of the antibiotic therapy spectrum.
Overconsumption of antibiotics in hospitals has led to policy implementation, including the control of antibiotic prescriptions. The impact of these policies on the evolution of antimicrobial ...resistance remains uncertain. In this work, we review the possible limits of such policies and focus on the need for a more efficient approach. Establishing a causal relationship between the introduction of new antibiotics and the emergence of new resistance mechanisms is difficult. Several studies have demonstrated that many resistance mechanisms existed before the discovery of antibiotics. Overconsumption of antibiotics has worsened the phenomenon of resistance. Antibiotics are responsible for intestinal dysbiosis, which is suspected of being the source of bacterial resistance. The complexity of the intestinal microbiota composition, the impact of the pharmacokinetic properties of antibiotics, and the multiplicity of other factors involved in the acquisition and emergence of multidrug-resistant organisms, lead us to think that de-escalation, in the absence of studies proving its effectiveness, is not the solution to limiting the spread of multidrug-resistant organisms. More studies are needed to clarify the ecological risk caused by different antibiotic classes. In the meantime, we need to concentrate our efforts on limiting antibiotic prescriptions to patients who really need it, and work on reducing the duration of these treatments.
Abstract
Syndromic respiratory panels are increasingly used worldwide. Their performance for detection of Bordetella pertussis needs to be evaluated. We found that the FilmArray Respiratory Panel ...2plus (RP2+) assay, which uses the pertussis toxin promoter target for B. pertussis, can only detect highly charged samples. Negative RP2+ results should not be interpreted as an absence of B. pertussis in clinical samples.
The β LACTA™ test (BLT) is a chromogenic test detecting resistance to third-generation cephalosporins on bacterial colonies. Some studies have shown that this test can be used directly in urine ...samples. The aim of this study was to determine the optimal conditions of use of this test in order to detect the ESBL-producing bacteria directly in urine samples. During a 4-months period, a total of 365 consecutive urine samples were tested with the BLT using the recommendation of the manufacturer. We isolated 56 ESBL-producing bacteria and 17 AmpC-overproducing bacteria. ESBL- and/or AmpC β-lactamase-producing bacteria isolates were systematically characterized by disc diffusion antibiotic susceptibility testing interpreted according to the guidelines of EUCAST. The sensitivity and the specificity for 3GC-resistance detection, regardless the mechanism of resistance, were, respectively, 60.3% and 100%, whereas for ESBL detection, it was, respectively, 75.4% and 99.7%. We applied then modification of the initial protocol considering urines with a bacteriuria >1000/μL, a reading time at 30 min and considering any change of the initial colour as positive. The overall sensitivity was 81% and the sensitivity for ESBL-detection raised to 95.7%.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Information regarding coronavirus disease 2019 (COVID-19) in haemodialysis (HD) patients is limited and early studies suggest a poor outcome. We aimed to identify clinical and ...biological markers associated with severe forms of COVID-19 in HD patients.
Methods
We conducted a prospective, observational and multicentric study. Sixty-two consecutive adult HD patients with confirmed COVID-19 from four dialysis facilities in Paris, France, from 19 March to 19 May 2020 were included.
Blood tests were performed before diagnosis and at Days 7 and 14 after diagnosis. Severe forms of COVID-19 were defined as requiring oxygen therapy, admission in an intensive care unit or death. Cox regression models were used to compute adjusted hazard ratios (aHRs). Kaplan–Meier curves and log-rank tests were used for survival analysis.
Results
Twenty-eight patients (45%) displayed severe forms of COVID-19. Compared with non-severe forms, these patients had more fever (93% versus 56%, P < 0.01), cough (71% versus 38%, P = 0.02) and dyspnoea (43% versus 6%, P < 0.01) at diagnosis. At Day 7 post-diagnosis, neutrophil counts, neutrophil:lymphocyte (N:L) ratio, C-reactive protein, ferritin, fibrinogen and lactate dehydrogenase levels were significantly higher in severe COVID-19 patients. Multivariate analysis revealed an N:L ratio >3.7 was the major marker associated with severe forms, with an aHR of 4.28 (95% confidence interval 1.52–12.0; P = 0.006). After a median follow-up time of 48 days (range 27–61), six patients with severe forms died (10%).
Conclusions
HD patients are at increased risk of severe forms of COVID-19. An elevated N:L ratio at Day 7 was highly associated with the severe forms. Assessing the N:L ratio could inform clinicians for early treatment decisions.
As data from Clostridium difficile infection (CDI) in intensive care unit (ICU) are still scarce, our objectives were to assess the morbidity and mortality of ICU-acquired CDI.
We compared patients ...with ICU-acquired CDI (watery or unformed stools occurring ≥ 72 hours after ICU admission with a stool sample positive for C. difficile toxin A or B) with two groups of controls hospitalized at the same time in the same unit. The first control group comprised patients with ICU-acquired diarrhea occurring ≥ 72 hours after ICU admission with a stool sample negative for C. difficile and for toxin A or B. The second group comprised patients without any diarrhea.
Among 5,260 patients, 512 patients developed one episode of diarrhea. Among them, 69 (13.5%) had a CDI; 10 (14.5%) of them were community-acquired, contrasting with 12 (17.4%) that were hospital-acquired and 47 (68%) that were ICU-acquired. A pseudomembranous colitis was associated in 24/47 (51%) ICU patients. The median delay between diagnosis and metronidazole administration was one day (25th Quartile; 75th Quartile (0; 2) days). The case-fatality rate for patients with ICU-acquired CDI was 10/47 (21.5%), as compared to 112/443 (25.3%) for patients with negative tests. Neither the crude mortality (cause specific hazard ratio; CSHR = 0.70, 95% confidence interval; CI 0.36 to 1.35, P = 0.3) nor the adjusted mortality to confounding variables (CSHR = 0.81, 95% CI 0.4 to 1.64, P = 0.6) were significantly different between CDI patients and diarrheic patients without CDI. Compared to the general ICU population, neither the crude mortality (SHR = 0.64, 95% CI 0.34 to 1.21, P = 0.17), nor the mortality adjusted to confounding variables (CSHR = 0.71, 95% confidence interval (CI) 0.38 to 1.35, P = 0.3), were significantly different between the two groups. The estimated increase in the duration of stay due to CDI was 8.0 days ± 9.3 days, (P = 0.4) in comparison to the diarrheic population, and 6.3 days ± 4.3 (P = 0.14) in comparison to the general ICU population.
If treated early, ICU-acquired CDI is not independently associated with an increased mortality and impacts marginally the ICU length of stay.
To investigate the predictors and burden of hospital readmission with recurrent
Clostridioides difficile
infection (rCDI) in a large European healthcare system with a low prevalence of hyper-virulent
...C. difficile
clones. We conducted an inception cohort study based on an exhaustive health insurance database and including all survivors of a first hospital stay with CDI over a one-year period (2015) in France. Readmissions with rCDI were defined as a novel hospital stay with CDI within 12 weeks following discharge of the index hospitalization. Risk factors for readmission with rCDI were investigated through multivariate logistic regression analyses. Among the 14,739 survivors of the index hospital stay (females, 57.3%; median age, 74 58–84 years), 2135 (14.5%) required at least one readmission with rCDI. Independent predictors of readmission were age ≥ 65 years (adjusted odds ratio (aOR), 1.34, 95% confidence interval (CI), 1.21–1.49,
P
< 0.0001), immunosuppression (aOR, 1.27, 95% CI, 1.15–1.41,
P
< 0.0001), chronic renal failure (aOR, 1.29, 95% CI, 1.14–1.46,
P
< 0.0001), and a previous history of CDI (aOR, 2.05, 95% CI, 1.55–2.71,
P
< 0.0001). The cumulative number of risk factors was independently associated with the hazard of readmission. Mean acute care costs attributable to rCDI were 5619 ± 3594 Euros for readmissions with rCDI as primary diagnosis (mean length of stay, 11.3 ± 10.2 days) and 4851 ± 445 Euros for those with rCDI as secondary diagnosis (mean length of stay, 16.8 ± 18.2 days), for an estimated annual nation-wide cost of 14,946,632 Euros. Hospital readmissions with rCDI are common after an index episode and drive major healthcare expenditures with substantial bed occupancy, strengthening the need for efficient secondary prevention strategies in high-risk patients.
Clostridium difficile infection (CDI) is associated with a substantial Quality of life impact on patients that has not been so far measured with a generic validated instrument.
A prospective study ...was performed in 7 French acute-care settings in patients presenting with a bacteriologically-confirmed CDI. The EQ-5D-3 L was filled in by patients at 7 ± 2 days after CDI diagnosis to describe their state of health at that date as well as their state of health immediately before the CDI episode (baseline). Individual utility decrement was obtained by subtracting the corresponding utilities. The Quality Adjusted Life Year (QALY) loss was calculated by multiplying the days spent from baseline to the date of the interview, by the decrement of utility. A multivariate analysis of variance of the utility decrement according to CDI and patients characteristics was performed.
Eighty patients were enrolled (mean age: 69.4 years, 55% females). The utility scores dropped from a mean 0.542 (SD: 0.391) at baseline to 0.050 (SD: 0.404) during the CDI episode with a mean adjusted utility decrement of 0.492 (SD: 0.398) point. This decrement increased significantly with CDI severity (Zar score ≥ 3) (p = 0.001), in patients with a positive baseline utility (p = 0.032), in women as compared to men (p = 0.041) and in patients aged more than 65 years (p = 0.041). No association with the Charlson index was found. The associated QALY loss not integrating the excess mortality was 0.028 (SD: 0.053).
The impact on quality of life of CDI episodes is major and translates in a substantial QALY loss despite their short duration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The major virulence factors of
(
) are enterotoxins A (TcdA) and B (TcdB). The study of toxins is a crucial step in exploring the virulence of this pathogen. Currently, the toxin purification process ...is either laborious and time-consuming in
or performed in heterologous hosts. Therefore, we propose a streamlined method to obtain functional toxins in
. Two
strains were generated, each harboring a sequence encoding a His-tag at the 3' end of
630∆
or
genes. Each toxin gene is expressed using the P
promoter, which is inducible by anhydro-tetracycline. The obtained purification yields were 0.28 mg and 0.1 mg per liter for rTcdA and rTcdB, respectively. In this study, we successfully developed a simple routine method that allows the production and purification of biologically active rTcdA and rTcdB toxins with similar activities compared to native toxins.
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