Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions. (Funded by the Danish Strategic Research Council and others; TRISS ClinicalTrials.gov number, NCT01485315.).

Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.

Caspofungin is used for the treatment of acute invasive candidiasis and as salvage treatment for invasive aspergillosis. We report characteristics of isolates of Candida albicans and Aspergillus fumigatus detected in a patient with breakthrough infection complicating severe gastrointestinal surgery and evaluate the capability of susceptibility methods to identify candin resistance. The susceptibility of C. albicans to caspofungin and anidulafungin was investigated by Etest, microdilution (European Committee on Antibiotic Susceptibility Testing [EUCAST] and CLSI), disk diffusion, agar dilution, and FKS1 sequencing and in a mouse model. Tissue was examined by immunohistochemistry, PCR, and sequencing for the presence of A. fumigatus and resistance mutations. The MICs for the C. albicans isolate were as follows: >32 g/ml caspofungin and 0.5 g/ml anidulafungin by Etest, 2 g/ml caspofungin and 0.125 g/ml anidulafungin by EUCAST methods, and 1 g/ml caspofungin and 0.5 g/ml anidulafungin by CLSI methods. Sequencing of the FKS1 gene revealed a mutation leading to an S645P substitution. Caspofungin and anidulafungin failed to reduce kidney CFU counts in animals inoculated with this isolate (P > 0.05 compared to untreated control animals), while both candins completely sterilized the kidneys in animals infected with a control isolate. Disk diffusion and agar dilution methods clearly separated the two isolates. Immunohistochemistry and sequencing confirmed the presence of A. fumigatus without FSK1 resistance mutations in liver and lung tissues. Breakthrough disseminated aspergillosis and candidiasis developed despite an absence of characteristic FKS1 resistance mutations in the Aspergillus isolates. EUCAST and CLSI methodology did not separate the candin-resistant clinical isolate from the sensitive control isolate as well as did the Etest and agar methods.

ObjectivesTo explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients.DesignSecondary analysis from a randomised antibiotic strategy trial (the Procalcitonin And Survival Study). The randomised arms were conserved from the primary trial for the main analysis.SettingNine mixed surgical/medical intensive care units across Denmark.Participants1200 adult intensive care patients, 18+ years, expected to stay +24 h. Exclusion criteria: bilirubin >40 mg/dl, triglycerides >1000 mg/dl, increased risk from blood sampling, pregnant/breast feeding and psychiatric patients.InterventionsPatients were randomised to guideline-based therapy (‘standard-exposure’ arm) or to guideline-based therapy supplemented with antibiotic escalation whenever procalcitonin increased on daily measurements (‘high-exposure’ arm).Main outcome measuresPrimary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Secondary end points: (1) delta eGFR after starting/stopping a drug and (2) RIFLE criterion Risk ‘R’, Injury ‘I’ and Failure ‘F’. Analysis was by intention to treat.Results28-day mortality was 31.8% and comparable (Jensen et al, Crit Care Med 2011). A total of 3672/7634 (48.1%) study days during follow-up in the high-exposure versus 3016/6949 (43.4%) in the ‘standard-exposure arm were spent with eGFR <60 ml/min/1.73 m2, p<0.001. In a multiple effects model, 3 piperacillin/tazobactam was identified as causing the lowest rate of renal recovery of all antibiotics used: 1.0 ml/min/1.73 m2/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m2/24 h) vs meropenem: 2.9 ml/min/1.73 m2/24 h (2.5 to 3.3 ml/min/1.73 m2/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m2/24 h (2.3 to 3.1 ml/min/1.73 m2 /24 h)). eGFR <60 ml/min/1.73 m2 in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively.ConclusionsPiperacillin/tazobactam was identified as a cause of delayed renal recovery in critically ill patients. This nephrotoxicity was not observed when using other beta-lactam antibiotics.Trial registrationClinicalTrials.gov identifier: NCT00271752.

Background Invasive candidiasis (IC) comprises candidemia and deep-seated candidiasis. Blood culture (BC) is the gold standard test, but sensitivity is low. T2Candida is a new diagnostic test. We investigated the performance of T2Candida, BC, and Candida mannan antigen (MAg) for detection of IC in a high-risk intensive care unit (ICU) population. Methods One-hundred twenty-six ICU patients at high risk of IC with sepsis despite 3 days of broad-spectrum antibiotics were included. Paired BC, T2Candida, and MAg were obtained twice weekly (334 sets). Patients were classified into proven, likely, possible, or unlikely IC based on patient record review. Results At enrollment, 92 (77%) patients were receiving antifungal therapy (mainly fluconazole 66%). Fifteen (11.9%) patients were positive by BC (n = 4), T2Candida (n = 11), or MAg (n = 10). The T2Candida species distribution at inclusion (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]) was supported by the identification of BC or colonizing isolates in 10/11 cases. Patients were classified with proven (11), likely (6), possible (11), and unlikely (98) IC. Defining IC as proven/proven&likely/proven&likely&possible, respectively, the sensitivity was as follows: T2Candida (55%/59%/39%), BC (45%/29%/ 8%), and MAg (36%/41%/32%). The negative predictive value was similar across the tests for proven vs others and proven/likely vs others (94%–96% and 90%–95%, respectively). For test combinations including T2Candida, the sensitivity increased to 64%–65%, without hampering the positive predictive value. Conclusions In conclusion, although the diagnostic performance was modest for all the tests, the combination of T2Candida and BC seemed to have the best diagnostic performance, and thus implementation of T2Candida may improve the diagnosis of IC.

BackgroundTransfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients.Methods/DesignThe Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point.DiscussionThe TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.Trial registrationClinicalTrials.gov: NCT01485315. Registration date 30 November 2011. First patient was randomised 3 December 2011.

BackgroundThe use of systemic antifungal agents has increased in most tertiary care centers. However, antifungal stewardship has deserved very little attention. Our objective was to assess the knowledge of European prescribing physicians as a first step of an international program of antifungal stewardship.MethodsStaff physicians and residents of 4 European countries were invited to complete a 20-point questionnaire that was based on current guidelines of invasive candidiasis and invasive aspergillosis.Results121 physicians (44.6% staff, 55.4% residents) from Spain 53.7%, Italy 17.4%, Denmark 16.5% and Germany 12.4% completed the survey. Hospital departments involved were: medical 51.2%, ICUs 43%, surgical 3.3% and pharmaceutical 2.5%. The mean score of adequate responses (± SD) was 5.8 ± 1.7 points, with statistically significant differences between study site and type of physicians. Regarding candidiasis, 69% of the physicians clearly distinguished colonization from infection and the local rate of fluconazole resistance was known by 24%. The accepted indications of antifungal prophylaxis were known by 38%. Regarding aspergillosis, 52% of responders could differentiate colonization from infection and 42% knew the diagnostic value of galactomannan. Radiological features of invasive aspergillosis were well recognized by 58% of physicians and 57% of them were aware of the antifungal considered as first line treatment. However, only 37% knew the recommended length of therapy.ConclusionsThis simple, easily completed questionnaire enabled us to identify some weakness in the knowledge of invasive fungal infection management among European physicians. This survey could serve as a guide to design a future tailored European training program.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0809-z) contains supplementary material, which is available to authorized users.

A 48-year-old man was admitted to department of emergency medicine at a tertiary referral hospital due to dizziness and fatigue. Clinical features on admission were non-pitting oedema, dry skin, very sparse hair, a hoarse voice, hypothermia (rectal temperature 28.7°C), macroglossia, sinus bradycardia and slow cerebration. Blood tests revealed severe hypothyroidism. During admission, the patient developed respiratory failure, renal failure, bleeding symptoms and diffuse colitis. The patient was treated with hydrocortisone and levothyroxine and he survived miraculously. This case describes a patient with myxoedema coma with severe hypothermia and cardiac involvement with development of multiorgan dysfunction all linked to the severe depletion of triiodothyronine.