Early Biomarker-Guided Prediction of Bloodstream Infection in Critically Ill Patients: C-Reactive Protein, Procalcitonin, and Leukocytes.

Background: Bloodstream infections (BSIs) often lead to critical illness and death. The primary aim of this study was to determine the diagnostic accuracy of the biomarkers C-reactive protein (CRP), procalcitonin (PCT), and leukocyte count for the diagnosis of BSI in critically ill patients. Methods: This was a nested case-control study based on the Procalcitonin And Survival Study (PASS) trial (n = 1200). Patients who were admitted to the intensive care unit (ICU) <24 hours, and not expected to die within <24 hours, were recruited. For the current study, we included patients with a BSI within ±3 days of ICU admission and matched controls without a BSI in a 1:2 ratio. Diagnostic accuracy for BSI for the biomarkers on days 1, 2, and 3 of ICU admission was assessed. Sensitivity, specificity, and negative and positive predictive values were calculated for prespecified thresholds and for a data-driven cutoff. Results: In total, there were 525 patients (n = 175 cases, 350 controls). The fixed low threshold for all 3 biomarkers (CRP = 20 mg/L; leucocytes = 10 × 109/L; PCT = 0.4 ng/mL) resulted in negative predictive values on day 1: CRP = 0.91; 95% CI, 0.75-1.00; leukocyte = 0.75; 95% CI, 0.68-0.81; PCT = 0.91; 95% CI, 0.84-0.96). Combining the 3 biomarkers yielded similar results as PCT alone (P = .5). Conclusions: CRP and PCT could in most cases rule out BSI in critically ill patients. As almost no patients had low CRP and ∼20% had low PCT, a low PCT could be used, along with other information, to guide clinical decisions.

Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial.

OBJECTIVES: To explore whether a strategy of more intensive antibiotic therapy leads to emergence or prolongation of renal failure in intensive care patients. DESIGN: Secondary 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. SETTING: Nine mixed surgical/medical intensive care units across Denmark. PARTICIPANTS: 1200 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. INTERVENTIONS: Patients 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 MEASURES: Primary end point: estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). 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. RESULTS: 28-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 m(2), 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 m(2)/24 h while exposed to this drug (95% CI 0.7 to 1.3 ml/min/1.73 m(2)/24 h) vs meropenem: 2.9 ml/min/1.73 m(2)/24 h (2.5 to 3.3 ml/min/1.73 m(2)/24 h)); after discontinuing piperacillin/tazobactam, the renal recovery rate increased: 2.7 ml/min/1.73 m(2)/24 h (2.3 to 3.1 ml/min/1.73 m(2) /24 h)). eGFR <60 ml/min/1.73 m(2) in the two groups at entry and at last day of follow-up was 57% versus 55% and 41% versus 39%, respectively. CONCLUSIONS: Piperacillin/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 REGISTRATION: ClinicalTrials.gov identifier: NCT00271752.

A three year population based survey of paediatric mechanical ventilation in east Denmark.

BACKGROUND: East Denmark has a population of 396,000 children 0-14 years and a yearly birth rate of 30,000, but at present no paediatric intensive care unit (PICU). OBJECTIVE: To perform a population based survey of paediatric mechanical ventilation with the purpose of providing the background for discussions for or against centralization of paediatric intensive care. METHODS: Case records of children 0-14 years treated with mechanical ventilation from January 1996 to December 1998 were retrospectively reviewed and the following data were obtained: Whether or not the child was settled in East Denmark, date of admission, gender, age, underlying chronic condition(s), acute condition(s) leading to mechanical ventilation, duration of positive pressure ventilation, duration of endotracheal intubation, length of stay in ICU, and outcome. Children undergoing mechanical ventilation because of neonatal problems, cardiac surgery or neurosurgery were excluded. RESULTS: Data were obtained from 197 children of which 123 were boys (p < 0.001 for boys vs girls). Median age at admission to ICU was 30 months. Boys were younger than girls (median age 22 vs 41 months, p = 0.01), but as determined by mortality, duration of positive pressure ventilation, intubation and stay in ICU there were no differences between boys and girls with respect to disease course (p > 0.28). Totally, 86 (44%) had at least one underlying chronic condition. The incidence of disease leading to mechanical ventilation in children in East Denmark was estimated to 1.6/10,000/year. An average of 1.1 child was intubated each day. Taking into account the seasonal variation two beds would be required to give coverage for 85% of ICU days needed for paediatric mechanical ventilation while three beds would cover 98%. Children admitted to referral hospital RH more often had underlying chronic conditions and had more severe courses of disease than children admitted to other hospitals (p < 0.001). Mortality did not differ (p = 0.66). CONCLUSION: The number of children requiring mechanical ventilation in East Denmark is too low to provide the background for establishing an independent PICU. However, since paediatric intensive care is a rare and complicated event further centralization of children undergoing mechanical ventilation in East Denmark should be considered.