The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials ...investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection.
For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the "procalcitonin-guided" group) or the current standard of care (the "controls"). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay.
Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p < 0.001).
Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.
Oxidative stress is a modifiable risk-factor in infection causing damage to human cells. As an adaptive response, cells catabolize Tyrosine to 3-Nitrotyrosine (Tyr-NO2) by nitrosylation. We ...investigated whether a more efficient reduction in oxidative stress, mirrored by a lowering of Tyrosine, and an increase in Tyr-NO2 and the Tyrosine/Tyr-NO2 ratio was associated with better clinical outcomes in patients with community-acquired pneumonia (CAP).
We measured Tyrosine and Tyr-NO2 in CAP patients from a previous randomized Swiss multicenter trial. The primary endpoint was adverse outcome defined as death or ICU admission within 30-days; the secondary endpoint was 6-year mortality.
Of 278 included CAP patients, 10.4% experienced an adverse outcome within 30 days and 45.0% died within 6 years. After adjusting for the pneumonia Severity Index PSI, BMI and comorbidities, Tyrosine nitrosylation was associated with a lower risk for short-term adverse outcome and an adjusted OR of 0.44 (95% CI 0.20 to 0.96, p = 0.039) for Tyr-NO2 and 0.98 (95% CI 0.98 to 0.99, p = 0.043) for the Tyrosine/Tyr-NO2 ratio. There were no significant associations for long-term mortality over six-years for Tyr-NO2 levels (adjusted hazard ratio 0.81, 95% CI 0.60 to 1.11, p = 0.181) and Tyrosine/Tyr-NO2 ratio (adjusted hazard ratio 1.00, 95% CI 0.99 to 1.00, p = 0.216).
Tyrosine nitrosylation in our cohort was associated with better clinical outcomes of CAP patients at short-term, but not at long term. Whether therapeutic modulation of the Tyrosine/Tyr-NO2 pathway has beneficial effects should be evaluated in future studies.
ISRCTN95122877. Registered 31 July 2006.
Is the use of procalcitonin for guiding antibiotic decisions in patients with acute upper and lower respiratory tract infections associated with improved clinical outcomes compared with usual care?
...Among patients with varying types and severity of acute respiratory infection, using procalcitonin to guide decisions about antibiotics is associated with lower rates of antibiotic exposure, antibiotic-related adverse effects, and mortality.
...the non-significant result in the subgroups is due to the small sample size and low statistical power (with large confidence intervals). Instead of limiting the analysis to trials mainly with ...patients with respiratory infections, as done by Aarati Keshary and Robert Badgett, we did an individual patient data meta-analysis extracting all individual patients with proven respiratory infection from the various included trials. All other authors delcare no competing interests. 1 P Schuetz, Y Wirz, R Sager, Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis, Lancet Infect Dis, Vol. 18, 2018, 95-107 2 P Schuetz, D Aujesky, C Muller, B Muller, Swiss Med Wkly, Vol. 145, 2015, w14079 3 P Schuetz, V Chiappa, M Briel, JL Greenwald, Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms, Arch Int Med, Vol. 171, 2011, 1322-1331 4 F Muller, M Christ-Crain, T Bregenzer, Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial, Chest, Vol. 138, 2010, 121-129 5 SF Mitsuma, MK Mansour, JP Dekker, Promising new assays and technologies for the diagnosis and management of infectious diseases, Clin Infect Dis, Vol. 56, 2013, 996-1002
Procalcitonin (PCT), an inflammatory blood biomarker, is well studied in infectious diseases. Its prognostic value in unselected emergency department (ED) patients remains yet undefined. Herein, we ...investigated association of admission PCT levels and mortality in a large, international-multicenter ED patient cohort.
We prospectively enrolled 6970 unselected, consecutive, adult, medical patients seeking ED care in three tertiary-care hospitals in Switzerland, France and the USA. We used multivariable logistic regression models to examine association of admission PCT levels (as a continuous predictor and across cut-offs) and 30-day mortality. We also investigated subgroup effects by main diagnosis, comorbidities and clinical features at presentation.
During the 30-day follow-up, 328 (4.7%) participants died. Mortality increased stepwise within higher PCT cut-offs (0.05, 0.1, 0.25, 0.5 ng/mL) from 1%, 3%, 7%, 13% to 15%, respectively. This association was also confirmed in a fully-adjusted model including age, gender, main symptom, main diagnosis and vital parameters on admission. Receiver operating characteristic (ROC) curve analysis showed that PCT differentiated well between survivors and non-survivors in the overall cohort (area under ROC curve AUC 0.75) with best results for patient with metabolic (AUC: 0.85) and cardiovascular disease (AUC: 0.82). Addition of PCT also improved the prognostic accuracy of the quick sequential organ failure assessment (qSOFA) score from an AUC of from 0.61 to 0.76 (p<0.001). Results were similar for other secondary endpoints including intensive care unit (ICU) admission and hospital readmission.
In this large and heterogenous medical ED patient cohort, admission PCT was a strong and independent outcome predictor for 30-day mortality across different medical diagnoses independent of underlying infection. PCT may help to improve risk stratification in unselected medical ED patients.
Whether procalcitonin (PCT)-guided antibiotic management in patients with positive blood cultures is safe remains understudied. We performed a patient-level meta-analysis to investigate effects of ...PCT-guided antibiotic management in patients with bacteremia.
We extracted and analyzed individual data of 523 patients with positive blood cultures included in 13 trials, in which patients were randomly assigned to receive antibiotics based on PCT levels (PCT group) or a control group. The main efficacy endpoint was duration of antibiotic treatment. The main safety endpoint was mortality within 30 days.
Mean duration of antibiotic therapy was significantly shorter for 253 patients who received PCT-guided treatment than for 270 control patients (-2.86 days 95% confidence interval CI, -4.88 to -.84; P = .006). Mortality was similar in both arms (16.6% vs 20.0%; P = .263). In subgroup analyses by type of pathogen, we noted a trend of shorter mean antibiotic durations in the PCT arm for patients infected with gram-positive organisms or Escherichia coli and significantly shorter treatment for subjects with pneumococcal bacteremia. In analysis by site of infection, antibiotic exposure was shortened in PCT subjects with Streptococcus pneumoniae respiratory infection and those with E. coli urogenital infections.
This meta-analysis of patients with bacteremia receiving PCT-guided antibiotic management demonstrates lower antibiotic exposure without an apparent increase in mortality. Few differences were demonstrated in subgroup analysis stratified by type or site of infection but notable for decreased exposure in patients with pneumococcal pneumonia and E. coli urogenital infections.
Due to overlap of clinical findings and low sensitivity of bacterial diagnostic tests, differentiation between bacterial and viral respiratory tract infections remains challenging, ultimately leading ...to antibiotic overuse in this population of patients. Addition of procalcitonin, a blood biomarker expressed by epithelial cells in response to bacterial infections, to the clinical assessment leads to a reduction in inappropriate antibiotic initiation. Procalcitonin also provides prognostic information about the resolution of illness, and significant decreases over time are a strong signal for the discontinuation of antibiotics. Current evidence from randomized trials indicates that procalcitonin-guided antibiotic stewardship results in a reduction in antibiotic use and antibiotic side effects, which importantly translates into improved survival of patients with respiratory infections. Inclusion of procalcitonin into antibiotic stewardship algorithms thus improves the diagnostic and therapeutic management of patients presenting with respiratory illnesses and holds great promise to mitigate the global bacterial resistance crisis.
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