Efficacy and toxicity of intravenous iron in a mouse model of critical care anemia

OBJECTIVE: Anemia is common in critically ill patients, due to inflammation and blood loss. Anemia can be associated with iron deficiency and low serum hepcidin levels. However, iron administration in this setting remains controversial because of its potential toxicity, including oxidative stress induction and sepsis facilitation. The objective of this work was to determine the efficacy and toxicity of iron administration using a mouse model mimicking critical care anemia as well as a model of acute septicemia. DESIGN: Prospective, randomized, open label controlled animal study. SETTING: University-based research laboratory. SUBJECTS: C57BL/6 and OF1 mice. INTERVENTIONS: Intraperitoneal injection of zymosan inducing generalized inflammation in C57BL/6 mice, followed in our full model by repeated phlebotomies. A dose equivalent to 15 mg/kg of ferric carboxymaltose was injected intravenously on day 5. To assess the toxicity of iron in a septicemia model, OF1 mice were simultaneously injected with iron and different Escherichia coli strains. MEASUREMENTS AND MAIN RESULTS: To investigate the effect of iron on oxidative stress, we measured reactive oxygen species production in the blood using luminol-amplified chemiluminescence and superoxide dismutase 2 messenger RNA levels in the liver. These markers of oxidative stress were increased after iron administration in control mice but not in zymosan-treated mice. Liver catalase messenger RNA levels decreased in iron-treated control mice. Iron administration was not associated with increased mortality in the septicemia model or in the generalized inflammation model. Iron increased hemoglobin levels in mice fed with a low iron diet and subjected to phlebotomies and zymosan 2 wks after treatment administration. CONCLUSIONS: Adverse effects of intravenous iron supplementation by ferric carboxymaltose seem to be minimal in our animal models. Furthermore, iron appears to be effective in correcting anemia, despite inflammation. Studies of efficacy and safety of iron in critically ill patients are warranted

Epidemiology of invasive candidiasis in a surgical intensive care unit: an observational study

Background: Invasive candidiasis (IC) is a frequent and life-threatening infection in critically ill patients. The aim of this study was to evaluate the epidemiology of IC and the antifungal susceptibility of etiological agents in patients admitted to our surgical intensive care unit (SICU) in Spain. Methods: We designed a prospective, observational, single center, population-based study in a SICU. We included all consecutive adult patients (≥18 years old) who had documented IC, either on admission or during their stay, between January 2012 and December 2013. Results: There were a total of 22 episodes of IC in the 1149 patients admitted during the 24-month study. The overall IC incidence was 19.1 cases per 1000 admissions. Thirteen cases of IC (59.1 %) were intra-abdominal candidiasis (IAC) and 9 (40.9 %) were candidemias. All cases of IAC were patients with secondary peritonitis and severe sepsis or septic shock. The overall crude mortality rate was 13.6 %; while, it was 33 % in patients with candidemia. All patients with IAC survived, including one patient with concomitant candidemia. The most common species causing IC was Candida albicans (13; 59.1 %) followed by Candida parapsilosis (5; 22.7 %), and Candida glabrata (2; 9.1 %). There was also one case each (4.5 %) of Candida krusei and Candida tropicalis. Thus, the ratio of non-C. albicans (9) to C. albicans (13) was 1:1.4. There was resistance to fluconazole and itraconazole in 13.6 % of cases. Resistance to other antifungals was uncommon. Conclusions: Candida parapsilosis was the second most common species after C. albicans, indicating the high prevalence of non-C. albicans species in the SICU. Resistance to azoles, particularly fluconazole, should be considered when starting an empirical treatment. Although IAC is a very frequent form of IC in critically ill surgical patients, prompt antifungal therapy and adequate source control appears to lead to a good outcome. However, our results are closely related to our ICU and any generalization must be taken with caution. Therefore, further investigations are needed. Keywords: Intensive care unit, Invasive candidiasis, Candidemia, Antifungal susceptibilit

Summary of the Standards, Options and Recommendations for the use of positron emission tomography with 2-[18F]fluoro-2-deoxy-D-glucose (FDP-PET scanning) in oncology (2002)

GuidelinePractice GuidelineResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Short-course antibiotic therapy for critically ill patients treated for postoperative intra-abdominal infection: the DURAPOP randomised clinical trial

PURPOSE: Shortening the duration of antibiotic therapy (ABT) is a key measure in antimicrobial stewardship. The optimal duration of ABT for treatment of postoperative intra-abdominal infections (PIAI) in critically ill patients is unknown. METHODS: A multicentre prospective randomised trial conducted in 21 French intensive care units (ICU) between May 2011 and February 2015 compared the efficacy and safety of 8-day versus 15-day antibiotic therapy in critically ill patients with PIAI. Among 410 eligible patients (adequate source control and ABT on day 0), 249 patients were randomly assigned on day 8 to either stop ABT immediately (n = 126) or to continue ABT until day 15 (n = 123). The primary endpoint was the number of antibiotic-free days between randomisation (day 8) and day 28. Secondary outcomes were death, ICU and hospital length of stay, emergence of multidrug-resistant (MDR) bacteria and reoperation rate, with 45-day follow-up. RESULTS: Patients treated for 8 days had a higher median number of antibiotic-free days than those treated for 15 days (15 [6-20] vs 12 [6-13] days, respectively; P < 0.0001) (Wilcoxon rank difference 4.99 days [95% CI 2.99-6.00; P < 0.0001). Equivalence was established in terms of 45-day mortality (rate difference 0.038, 95% CI - 0.013 to 0.061). Treatments did not differ in terms of ICU and hospital length of stay, emergence of MDR bacteria or reoperation rate, while subsequent drainages between day 8 and day 45 were observed following short-course ABT (P = 0.041). CONCLUSION: Short-course antibiotic therapy in critically ill ICU patients with PIAI reduces antibiotic exposure. Continuation of treatment until day 15 is not associated with any clinical benefit. CLINICALTRIALS. GOV IDENTIFIER: NCT01311765

Management of intra-abdominal infections : recommendations by the WSES 2016 consensus conference

This paper reports on the consensus conference on the management of intra-abdominal infections (IAIs) which was held on July 23, 2016, in Dublin, Ireland, as a part of the annual World Society of Emergency Surgery (WSES) meeting. This document covers all aspects of the management of IAIs. The Grading of Recommendations Assessment, Development and Evaluation recommendation is used, and this document represents the executive summary of the consensus conference findings.Peer reviewe

Intra-abdominal candidiasis: The importance of early source control and antifungal treatment

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, and identified risk factors for mortality. We performed a retrospective study of adults diagnosed with IAC at our center in 2012-2013. Risk factors for mortality were evaluated using multi-variable logistic regression. We identified 163 patients with IAC, compared to 161 with candidemia. Types of IAC were intra-abdominal abscesses (55%), secondary peritonitis (33%), primary peritonitis (5%), infected pancreatic necrosis (5%), and cholecystitis/cholangitis (3%). Eighty-three percent and 66% of secondary peritonitis and abscesses, respectively, stemmed from gastrointestinal (GI) tract sources. C. albicans (56%) and C. glabrata (24%) were the most common species. Bacterial co-infections and candidemia occurred in 67% and 6% of patients, respectively. Seventy-two percent of patients underwent an early source control intervention (within 5 days) and 72% received early antifungal treatment. 100-day mortality was 28%, and highest with primary (88%) or secondary (40%) peritonitis. Younger age, abscesses and early source control were independent predictors of survival. Younger age, abscesses and early antifungal treatment were independently associated with survival for IAC stemming from GI tract sources. Infectious diseases (ID) consultations were obtained in only 48% of patients. Consulted patients were significantly more likely to receive antifungal treatment. IAC is a common disease associated with heterogeneous manifestations, which result in poor outcomes. All patients should undergo source control interventions and receive antifungal treatment promptly. It is important for the ID community to become more engaged in treating IAC