***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Sepsis is considered to induce immune suppression , leading to increased susceptibility to secondary infections with associated late mortality . OBJECTIVE To determine the clinical and host genomic characteristics , incidence , and attributable mortality of intensive care unit (ICU)-acquired infections in patients admitted to the ICU with or without sepsis . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve observational study comprising consecutive admissions of more than 48 hours in 2 ICUs in the Netherl and s from January 2011 to July 2013 stratified according to admission diagnosis ( sepsis or noninfectious ) . MAIN OUTCOMES AND MEASURES The primary outcome was ICU-acquired infection ( onset > 48 hours ) . Attributable mortality risk ( fraction of mortality that can be prevented by elimination of the risk factor , acquired infection ) was determined using time-to-event models accounting for competing risk . In a subset of sepsis admissions ( n = 461 ) , blood gene expression ( whole-genome transcriptome in leukocytes ) was analyzed at baseline and at onset of ICU-acquired infectious ( n = 19 ) and noninfectious ( n = 9 ) events . RESULTS The primary cohort included 1719 sepsis admissions ( 1504 patients ; median age , 62 years ; interquartile range [ IQR ] , 51 - 71 years ] ; 924 men [ 61.4 % ] ) . A comparative cohort included 1921 admissions ( 1825 patients , median age , 62 years ; IQR , 49 - 71 years ; 1128 men [ 61.8 % ] in whom infection was not present in the first 48 hours .  Intensive care unit-acquired infections occurred in 13.5 % of sepsis ICU admissions ( n = 232 ) and 15.1 % of nonsepsis ICU admissions ( n = 291 ) . Patients with sepsis who developed an ICU-acquired infection had higher disease severity scores on admission than patients with sepsis who did not develop an ICU-acquired infection ( Acute Physiology and Chronic Health Evaluation IV [ APACHE IV ] median score , 90 [ IQR , 72 - 107 ] vs 79 [ IQR , 62 - 98 ] ; P < .001 ) and throughout their ICU stay but did not have differences in baseline gene expression . The population attributable mortality fraction of ICU-acquired infections in patients with sepsis was 10.9 % ( 95 % CI , 0.9%-20.6 % ) by day 60 ; the estimated difference between mortality in all patients with a sepsis admission diagnosis and mortality in those without ICU-acquired infection was 2.0 % ( 95 % CI , 0.2%-3.8 % ; P = .03 ) by day 60 . Among nonsepsis ICU admissions , ICU-acquired infections had a population attributable mortality fraction of 21.1 % ( 95 % CI , 0.6%-41.7 % ) by day 60 . Compared with baseline , blood gene expression at the onset of ICU-acquired infections showed reduced expression of genes involved in gluconeogenesis and glycolysis . CONCLUSIONS AND RELEVANCE Intensive care unit-acquired infections occurred more commonly in patients with sepsis with higher disease severity , but such infections contributed only modestly to overall mortality . The genomic response of patients with sepsis was consistent with immune suppression at the onset of secondary infection Purpose The optimal treatment duration for ventilator-associated pneumonia is based on one study dealing with late-onset of the condition . Shortening the length of antibiotic treatment remains a major prevention factor for the emergence of multiresistant bacteria . Objective To demonstrate that 2 different antibiotic treatment duration s ( 8 versus 15 days ) are equivalent in terms of clinical cure for early-onset ventilator-associated pneumonia . Methods R and omized , prospect i ve , open , multicenter trial carried out from 1998 to 2002 . Measurements The primary endpoint was the clinical cure rate at day 21 . The mortality rate was evaluated on days 21 and 90 . Results 225 patients were included in 13 centers . 191 ( 84.9 % ) patients were cured : 92 out of 109 ( 84.4 % ) in the 15 day cohort and 99 out of 116 ( 85.3 % ) in the 8 day cohort ( difference = 0.9 % , odds ratio = 0.929 ) . 95 % two-sided confidence intervals for difference and odds ratio were [ −8.4 % to 10.3 % ] and [ 0.448 to 1.928 ] respectively . Taking into account the limits of equivalence ( 10 % for difference and 2.25 for odds ratio ) , the objective of demonstrative equivalence between the 2 treatment duration s was fulfilled . Although the rate of secondary infection was greater in the 8 day than the 15 day cohort , the number of days of antibiotic treatment remained lower in the 8 day cohort . There was no difference in mortality rate between the 2 groups on days 21 and 90 . Conclusion Our results suggest that an 8-day course of antibiotic therapy is safe for early-onset ventilator-associated pneumonia in intubated patients . Trial Registration Clinical Trials.gov Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 Eight intensive care units in France . Participants Adults with the phenotype of severe sepsis and no overt source of infection , negative microbial cultures from multiple matrices and no antibiotic exposure shortly before intensive care unit admission . Intervention The initiation and duration of antibiotic therapy was based on procalcitonin levels in the experimental arm and on the intensive care unit physicians ’ clinical judgement without reference to procalcitonin values in the control arm . Main outcome measure The primary outcome was the proportion of patients on antibiotics on day 5 postr and omisation . Results Over a 3-year period 
    Output:
    
Conclusions : Although the duration of antibiotic therapy is reduced with procalcitonin-guided therapy or prespecified limited duration , meta- analysis and trial sequential analyses are inconclusive for mortality benefit .