High silver concentrations in biological samples following different exposures: Two case reports.

BACKGROUND: Silver is used in various industrial applications, but also in confectioneries and for therapeutic use due to its antibiotic properties. Its toxicity is not well documented and most often only in the context of professional exposure. AIM: Here we report two cases of high silver concentrations in biological samples in two women: the first patient presented grey marks around her cuticles, probably due to her consumption of silvered sweets and the second patient presented agranulocytosis and thrombocytopenia occurring within 24 h after the topical application of a cream containing sulfadiazine and silver to burns over a large surface area. METHODS: Silver concentrations were determined in blood and urine samples and sweets using inductively coupled plasma- mass spectrometry (ICP-MS). RESULTS: The silver concentrations were elevated compared to population reference values and confirmed the hypotheses for the patients: the significant consumption of sweets coated with silver nanoparticles and the topical application of a cream containing silver to burns over a large area. DISCUSSION-CONCLUSION: After initial questioning by the dermatologist, Patient 1 explained that she consumed more than 30 bags of the sweets per year. She decreased her consumption of the sweets and the control performed one year later showed a plasma silver concentration of 1.5 µg/L. For Patient 2, the absorption of silver through burns over a large area appeared relatively significant, whereas it is very low through undamaged skin. The haematological cells counts returned to normal levels quickly and no other major effects were highlighted. To apply these findings to a larger population, further investigation to determine sulfadiazine and silver concentrations in plasma and urine have been initiated in a cohort of patients with burns over a large area.

Recipient Selection for Optimal Utilization of Discarded Grafts in Liver Transplantation.

BACKGROUND: In France, liver grafts that have been refused by at least 5 teams are considered for rescue allocation (RA), with the choice of the recipient being at the team's discretion. Although this system permits the use of otherwise discarded grafts in a context of organ shortage, outcomes and potential benefits need to be assessed. METHODS: Between 2011 and 2015, outcomes of RA grafts (n = 33) were compared with SA grafts (n = 321) at a single French center. RESULTS: Liver grafts in the RA group were older (63 ± 17 years vs 54 ± 18 years, P = 0.007) and had a higher DRI (1.86 ± 0.45 vs 1.61 ± 0.47, P = 0.010). Recipients in this group had a lower Model for End-Stage Liver Disease score (14 ± 5 vs 22 ± 10, P < 0.001) and had mostly hepatocellular carcinoma (67.0% vs 40.4%, P = 0.010). The balance of risk score was significantly lower in the RA group (5.5 ± 2.9 vs 9.2 ± 5.5, P < 0.001). There were higher rates of early and delayed hepatic artery thrombosis (15.2% vs 3.1%, P = 0.001) and retransplantation (18.2% vs 4.7%, P = 0.002) in the RA group. Patient survival was not different between groups, but graft survival was impaired (95% vs 82% at 1 year and 94% vs 74% at 3 years, P = 0.001). CONCLUSION: Our results show that discarded liver grafts can be used provided that there is a strict recipient selection process, although hepatic artery thrombosis and retransplantation are more frequent. This strategy enables utilization of otherwise discarded grafts in the context of organ shortage.

Epidemiological Outbreaks of Pneumocystis jirovecii Pneumonia Are Not Limited to Kidney Transplant Recipients: Genotyping Confirms Common Source of Transmission in a Liver Transplantation Unit.

Over a 5-month period, four liver transplant patients at a single hospital were diagnosed with Pneumocystis jirovecii pneumonia (PCP). This unusually high incidence was investigated using molecular genotyping. Bronchoalveolar lavage fluids (BALF) obtained from the four liver recipients diagnosed with PCP were processed for multilocus sequence typing (MLST) at three loci (SOD, mt26s, and CYB). Twenty-four other BALF samples, which were positive for P. jirovecii and collected from 24 epidemiologically unrelated patients with clinical signs of PCP, were studied in parallel by use of the same method. Pneumocystis jirovecii isolates from the four liver recipients all had the same genotype, which was different from those of the isolates from all the epidemiologically unrelated individuals studied. These findings supported the hypothesis of a common source of contamination or even cross-transmission of a single P. jirovecii clone between the four liver recipients. Hospitalization mapping showed several possible encounters between these four patients, including outpatient consultations on one particular date when they all possibly met. This study demonstrates the value of molecular genotyping of P. jirovecii isolated from clinical samples for epidemiological investigation of PCP outbreaks. It is also the first description of a common source of exposure to a single P. jirovecii clone between liver transplant recipients and highlights the importance of prophylaxis in such a population.

Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature.

BACKGROUND: Clostridium difficile infection (CDI) is a common cause of nosocomial diarrhoea. People in the general community are not usually considered to be at risk of CDI. CDI is associated with a high risk of morbidity and mortality. The risk of severity is defined by the Clostridium Severity Index (CSI). METHODS: The cases of 136 adult patients with CDI treated at the University Hospital of Tours, France between 2008 and 2012 are described. This was a retrospective study. RESULTS: Among the 136 patients included, 62 were men and 74 were women. Their median age was 64.4 years (range 18-97 years). Twenty-six of the 136 (19%) cases were community-acquired (CA) and 110 (81%) were healthcare-acquired (HCA). The major risk factors for both groups were long-term treatment with proton pump inhibitors (54% of CA, 53% of HCA patients) and antibiotic treatment within the 2.5 months preceding the CDI (50% of CA, 91% of HCA). The CSI was higher in the CA-CDI group (1.56) than in the HCA-CDI group (1.39). Intensive care was required for 8% of CA-CDI and 16.5% of HCA-CDI patients. CONCLUSIONS: CDI can cause community-acquired diarrhoea, and CA-CDI may be more severe than HCA-CDI. Prospective studies of CDI involving people from the general community without risk factors are required to confirm this observation.

Etomidate increases susceptibility to pneumonia in trauma patients.

PURPOSE: To investigate the impact of etomidate on the rate of hospital-acquired pneumonia (HAP) in trauma patients and the effects of hydrocortisone in etomidate-treated patients. METHODS: This was a sub-study of the HYPOLYTE multi-centre, randomized, double-blind, placebo-controlled trial of hydrocortisone in trauma patients (NCT00563303). Inclusion criterion was trauma patient with mechanical ventilation (MV) of ≥48 h. The use of etomidate was prospectively collected. Endpoints were the results of the cosyntropin test and rate of HAP on day 28 of follow-up. RESULTS: Of the 149 patients enrolled in the study, 95 (64 %) received etomidate within 36 h prior to inclusion. 79 (83 %) of 95 patients receiving etomidate and 34 of the 54 (63 %) not receiving etomidate had corticosteroid insufficiency (p = 0.006). The administration of etomidate did not alter basal cortisolemia (p = 0.73), but it did decrease the delta of cortisolemia at 60 min (p = 0.007). There was a correlation between time from etomidate injection to inclusion in the study and sensitivity to corticotropin (R (2) = 0.19; p = 0.001). Forty-nine (51.6 %) patients with etomidate and 16 (29.6 %) patients without etomidate developed HAP by day 28 (p = 0.009). Etomidate was associated with HAP on day 28 in the multivariate analysis (hazard ratio 2.48; 95 % confidence interval 1.19-5.18; p = 0.016). Duration of MV with or without etomidate was not significantly different (p = 0.278). Among etomidate-exposed patients, 18 (40 %) treated with hydrocortisone developed HAP compared with 31 (62 %) treated with placebo (p = 0.032). Etomidate-exposed patients treated with hydrocortisone had fewer ventilator days (p < 0.001). CONCLUSIONS: Among the patients enrolled in the study, etomidate did not alter basal cortisolemia, but it did decrease reactivity to corticotropin. We suggest that in trauma patients, etomidate is an independent risk factor for HAP and that the administration of hydrocortisone should be considered after etomidate use.

Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study.

CONTEXT: The role of stress-dose hydrocortisone in the management of trauma patients is currently unknown. OBJECTIVE: To test the efficacy of hydrocortisone therapy in trauma patients. DESIGN, SETTING, AND PATIENTS: Multicenter, randomized, double-blind, placebo-controlled HYPOLYTE (Hydrocortisone Polytraumatise) study. From November 2006 to August 2009, 150 patients with severe trauma were included in 7 intensive care units in France. INTERVENTION: Patients were randomly assigned to a continuous intravenous infusion of either hydrocortisone (200 mg/d for 5 days, followed by 100 mg on day 6 and 50 mg on day 7) or placebo. The treatment was stopped if patients had an appropriate adrenal response. MAIN OUTCOME MEASURE: Hospital-acquired pneumonia within 28 days. Secondary outcomes included the duration of mechanical ventilation, hyponatremia, and death. RESULTS: One patient withdrew consent. An intention-to-treat (ITT) analysis included the 149 patients, a modified ITT analysis included 113 patients with corticosteroid insufficiency. In the ITT analysis, 26 of 73 patients (35.6%) treated with hydrocortisone and 39 of 76 patients (51.3%) receiving placebo developed hospital-acquired pneumonia by day 28 (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.30-0.83; P = .007). In the modified ITT analysis, 20 of 56 patients (35.7%) in the hydrocortisone group and 31 of 57 patients (54.4%) in the placebo group developed hospital-acquired pneumonia by day 28 (HR, 0.47; 95% CI, 0.25-0.86; P = .01). Mechanical ventilation-free days increased with hydrocortisone by 4 days (95% CI, 2-7; P = .001) in the ITT analysis and 6 days (95% CI, 2-11; P < .001) in the modified ITT analysis. Hyponatremia was observed in 7 of 76 (9.2%) in the placebo group vs none in the hydrocortisone group (absolute difference, -9%; 95% CI, -16% to -3%; P = .01). Four of 76 patients (5.3%) in the placebo group and 6 of 73 (8.2%) in the hydrocortisone group died (absolute difference, 3%; 95% CI, -5% to 11%; P = .44). CONCLUSION: In intubated trauma patients, the use of an intravenous stress-dose of hydrocortisone, compared with placebo, resulted in a decreased risk of hospital-acquired pneumonia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00563303.