***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units . We aim ed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting . METHODS In this multicentre , prospect i ve , parallel-group , open-label trial , we used an independent , computer-generated r and omisation sequence to r and omly assign patients in a 1:1 ratio to procalcitonin ( n=311 patients ) or control ( n=319 ) groups ; investigators were masked to assignment before , but not after , r and omisation . For the procalcitonin group , antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations ; the control group received antibiotics according to present guidelines . Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician . Patients were expected to stay in the intensive care unit for more than 3 days , had suspected bacterial infections , and were aged 18 years or older . Primary endpoints were mortality at days 28 and 60 ( non-inferiority analysis ) , and number of days without antibiotics by day 28 ( superiority analysis ) . Analyses were by intention to treat . The margin of non-inferiority was 10 % . This trial is registered with Clinical Trials.gov , number NCT00472667 . FINDINGS Nine patients were excluded from the study ; 307 patients in the procalcitonin group and 314 in the control group were included in analyses .  Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 ( 21.2 % [ 65/307 ] vs 20.4 % [ 64/314 ] ; absolute difference 0.8 % , 90 % CI -4.6 to 6.2 ) and day 60 ( 30.0 % [ 92/307 ] vs 26.1 % [ 82/314 ] ; 3.8 % , -2.1 to 9.7 ) . Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group ( 14.3 days [ SD 9.1 ] vs 11.6 days [ SD 8.2 ] ; absolute difference 2.7 days , 95 % CI 1.4 to 4.1 , p<0.0001 ) . INTERPRETATION A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes . FUNDING Assistance Publique-Hôpitaux de Paris , France , and Brahms , Germany Objective : For patients in intensive care units , sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis . The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation , guided by daily measurements of the biomarker procalcitonin , could reduce the time to appropriate therapy , thus improving survival . Design : R and omized controlled open-label trial . Setting : Nine multidisciplinary intensive care units across Denmark . Patients : A total of 1,200 critically ill patients were included after meeting the following eligibility requirements : expected intensive care unit stay of ≥24 hrs , nonpregnant , judged to not be harmed by blood sampling , bilirubin < 40 mg/dL , and triglycerides < 1000 mg/dL ( not suspensive ) . Interventions : Patients were r and omized either to the “ st and ard-of-care-only arm , ” receiving treatment according to the current international guidelines and blinded to procalcitonin levels , or to the “ procalcitonin arm , ” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements . Measurements and Main Results : The primary end point was death from any cause at day 28 ; this occurred for 31.5 % ( 190 of 604 ) patients in the procalcitonin arm and for 32.0 % ( 191 of 596 ) patients in the st and ard-of-care-only arm ( absolute risk reduction , 0.6 % ; 95 % confidence interval [ CI ] −4.7 % to 5.9 % ) . Length of stay in the intensive care unit was increased by one day ( p = .004 ) in the procalcitonin arm , the rate of mechanical ventilation per day in the intensive care unit increased 4.9 % ( 95 % CI , 3.0–6.7 % ) , and the relative risk of days with estimated glomerular filtration rate < 60 mL/min/1.73 m2 was 1.21 ( 95 % CI , 1.15–1.27 ) . Conclusions : 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 can not be recommended IMPORTANCE High-dose intravenous administration of sodium selenite has been proposed to improve outcome in sepsis by attenuating oxidative stress . Procalcitonin-guided antimicrobial therapy may hasten the diagnosis of sepsis , but effect on outcome is unclear . OBJECTIVE To determine whether high-dose intravenous sodium selenite treatment and procalcitonin-guided anti-infectious therapy in patients with severe sepsis affect mortality . DESIGN , SETTING , AND PARTICIPANTS The Placebo-Controlled Trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis ( SISPCT ) , a multicenter , r and omized , clinical , 2 × 2 factorial trial performed in 33 intensive care units in Germany , was conducted from November 6 , 2009 , to June 6 , 2013 , including a 90-day follow-up period . INTERVENTIONS Patients were r and omly assigned to receive an initial intravenous loading dose of sodium selenite , 1000 µg , followed by a continuous intravenous infusion of sodium selenite , 1000 µg , daily until discharge from the intensive care unit , but not longer than 21 days , or placebo . Patients also were r and omized to receive anti-infectious therapy guided by a procalcitonin algorithm or without procalcitonin guidance . MAIN OUTCOMES AND MEASURES The primary end point was 28-day mortality . Secondary outcomes included 90-day all-cause mortality , intervention-free days , antimicrobial costs , antimicrobial-free days , and secondary infections . RESULTS Of 8174 eligible patients , 1089 patients ( 13.3 % ) with severe sepsis or septic shock were included in an intention-to-treat analysis comparing sodium selenite ( 543 patients [ 49.9 % ] ) with placebo ( 546 [ 50.1 % ] ) and procalcitonin guidance ( 552 [ 50.7 % ] ) vs no procalcitonin guidance ( 537 [ 49.3 % ] ) . The 28-day mortality rate was 28.3 % ( 95 % CI , 24.5%-32.3 % ) in the sodium selenite group and 25.5 % ( 95 % CI , 21.8%-29.4 % ) ( P = .30 ) in the placebo group . There was no significant difference in 28-day mortality between patients assigned to procalcitonin guidance ( 25.6 % [ 95 % CI , 22.0%-29.5 % ] ) vs no procalcitonin guidance ( 28.2 % [ 95 % CI , 24.4%-32.2 % ] ) ( P = .34 ) . Procalcitonin guidance did not affect frequency of diagnostic or therapeutic procedures but did result in a 4.5 % reduction of antimicrobial exposure . CONCLUSIONS AND RELEVANCE Neither high-dose intravenous administration of sodium selenite nor anti-infectious therapy guided by a procalcitonin algorithm was associated with an improved outcome in patients with severe sepsis . These findings do not support administration of high-dose sodium selenite in these patients ; the application of a procalcitonin-guided algorithm needs further evaluation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00832039 Introduction The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment . Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting . Until recently , no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction ; however , over the past years , procalcitonin ( PCT ) is the first among a large array of inflammatory variables that offers this possibility . The present study aim ed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients . Methods All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible . Patients were r and omly assigned to either a PCT-guided ( study group ) or a st and ard ( control group ) antibiotic regimen . Antibiotic therapy in the PCT-guided group was discontinued , if clinical signs and symptoms of infection improved and PCT decreased to < 1 ng/ml or the PCT value was > 1 ng/ml , but had dropped to 25 to 35 % of the initial value over three days . In the control group antibiotic treatment was applied as st and ard regimen over eight days . Results A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high- grade suspected infections were enrolled in this study . In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly . The control group comprised 53 patients with a st and ardized duration of antibiotic therapy over eight days . Demographic and clinical data were comparable in both groups . However , in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls ( 5.9 + /- 1.7 versus 7.9 + /- 0.5 days , P < 0.001 ) without negative effects on clinical outcome . Conclusions Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients . This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine . Annotation Results were previously published in German in Anaesthesist 2008 ; 57 : 571–577 ( PMID : 18463831).Trial registration IS RCT Objective : We sought to evaluate whether procalcitonin was superior to C-reactive protein in guiding antibiotic therapy in intensive care patients with sepsis . Design : R and omized open clinical trial . Setting : Two university hospitals in Brazil . Patients : Patients with severe sepsis or septic shock . Interventions : Patients were r and omized in two groups : the procalcitonin group and the C-reactive protein group . Antibiotic therapy was discontinued following a protocol based on serum levels of these markers , according to the allocation group . The procalcitonin group was considered superior if the duration of antibiotic therapy was at least 25 % shorter than in the C-reactive protein group . For both groups , at least seven full-days of antibiotic therapy were ensured in patients with Sequential Organ Failure Assessment greater than 10 and /or bacteremia at inclusion , and patients with evident resolution of the infectious process had antibiotics stopped after 7 days , despite biomarkers levels . Measurements and Main Results : Ninety-four patients were r and omized : 49 patients to the procalcitonin group and 45 patients to the C-reactive protein group . The mean age was 59.8 ( SD , 16.8 ) years . The median duration of antibiotic therapy for the first episode of infection was 7.0 ( Q1–Q3 , 6.0–8.5 ) days in the procalcitonin group and 6.0 ( Q1–Q3 , 5.0–7.0 ) days in the C-reactive protein group ( p = 0.13 ) , with a hazard ratio of 1.206 ( 95 % CI , 0.774–1.3 ; p = 0.13 ) . Overall , protocol overruling occurred in only 13 ( 13.8 % ) patients . Twenty-one patients died in each group ( p = 0.836 ) . Conclusions : C-reactive protein was as useful as procalcitonin in reducing antibiotic use in a predominantly medical population of septic patients , causing no apparent Objective Some patients with the phenotype of severe sepsis may have no overt source of infection or identified pathogen . We investigated whether a procalcitonin-based algorithm influenced antibiotic use in patients with non-microbiologically proven apparent severe sepsis . Design This multicentre , r and omised , controlled , single-blind trial was performed in two parallel groups . Setting E 
    Output:
    
Conclusion : When evaluating all studies of procalcitonin-guided antibiotics management in critically ill patients , no difference in short-term mortality was observed .
However , when only examining procalcitonin-guided cessation of antibiotics , lower mortality was detected .