Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Procalcitonin guidance for reduction of antibiotic use in low-risk outpatients with community-acquired pneumonia. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. [The value of serum procalcitonin in treatment of community acquired pneumonia in outpatient]. Procalcitonin to guide duration of antibiotic therapy in intensive care patients: a randomized prospective controlled trial. Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Antibiotic treatment interruption of suspected lower respiratory tract infections based on a single procalcitonin measurement at hospital admission--a randomized trial.
Therapy with antibiotics influences recovery only in selected cases of COPD exacerbations. We evaluated the efficacy and safety of procalcitonin guidance compared to standard therapy with antibiotic prescriptions in patients experiencing exacerbations of COPD.
                A total of 208 consecutive patients requiring hospitalization for COPD exacerbation were randomized at the index exacerbation to procalcitonin-guided or standard antibiotic therapy. Patients receiving procalcitonin-guided therapy were treated with antibiotics according to serum procalcitonin levels; standard-therapy patients received antibiotics according to the attending physician. The primary outcome was the antibiotic exposure at the index exacerbation and the subsequent antibiotic requirement for COPD exacerbation within 6 months. Secondary outcomes were clinical recovery, symptom scores, length of hospitalization, ICU stay, death, lung function, exacerbation rate, and time to next exacerbation.
                At the index exacerbation, procalcitonin guidance reduced antibiotic prescription (40% vs 72%, respectively; p < 0.0001) and antibiotic exposure (relative risk [RR], 0.56; 95% confidence interval [CI], 0.43 to 0.73; p < 0.0001) compared to standard therapy. Moreover, procalcitonin guidance at the index exacerbation allowed a significant sustained reduction in total antibiotic exposure for up to 6 months (RR, 0.76; 95% CI, 0.64 to 0.92; p = 0.004). Clinical outcome and improvement in FEV(1) at 14 days and 6 months did not differ between groups. Within 6 months, the exacerbation rate (0.62 vs 0.64, respectively), the rehospitalization rate (0.21 vs 0.24, respectively), and mean (+/- SD) time to the next exacerbation (70.0 +/- 46.1 vs 70.4 +/- 51.9 days, respectively; p = 0.523) were similar in both groups.
                Procalcitonin guidance for exacerbations of COPD offers a sustained advantage over standard therapy in reducing antibiotic use for up to 6 months with a number-needed-to-treat of 3. Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.
                In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly 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, randomisation. 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 ClinicalTrials.gov, number NCT00472667.
                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).
                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.
                Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.
                Copyright 2010 Elsevier Ltd. All rights reserved. In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications.
                To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia.
                In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25 microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome.
                At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%.
                Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications. Acute respiratory tract infections are the most common reason for antibiotic therapy in primary care despite their mainly viral etiology. A laboratory test measuring procalcitonin levels in blood specimens was suggested as a tool to reduce unnecessary prescribing of antibiotics. We consider whether antibiotic therapy guided by procalcitonin reduces the use of antibiotics without increasing the restrictions experienced by patients by more than 1 day.
                Fifty-three primary care physicians recruited 458 patients, each patient with an acute respiratory tract infection and, in the physician's opinion, in need of antibiotics. Patients were centrally randomized to either a procalcitonin-guided approach to antibiotic therapy or to a standard approach. For patients randomized to procalcitonin-guided therapy, the use of antibiotics was more or less strongly discouraged (procalcitonin level, < or =0.1 or < or =0.25 microg/L, respectively) or recommended (procalcitonin level, >0.25 microg/L). Follow-up data were collected at 7 days by treating physicians and at 14 and 28 days by blinded interviewers.
                Adjusted for baseline characteristics, the mean increase at 14 days in days in which activities were restricted was 0.14 with procalcitonin-guided therapy (95% confidence interval [CI], -0.53 to 0.81 days), which met our criterion of an increase in days in which activities were restricted by no more than 1 day. With procalcitonin-guided therapy, the antibiotic prescription rate was 72% lower (95% CI, 66%-78%) than with standard therapy. Both approaches led to a similar proportion of patients reporting symptoms of ongoing or relapsing infection at 28 days (adjusted odds ratio, 1.0 [95% CI, 0.7-1.5]).
                As an adjunct to guidelines, procalcitonin-guided therapy markedly reduces antibiotic use for acute respiratory tract infections in primary care without compromising patient outcome. In practice, this could be achieved with 1 to 2 procalcitonin measurements in patients for whom the physician intends to prescribe antibiotics. Lower respiratory tract infections are often treated with antibiotics without evidence of clinically relevant bacterial disease. Serum calcitonin precursor concentrations, including procalcitonin, are raised in bacterial infections. We aimed to assess a procalcitonin-based therapeutic strategy to reduce antibiotic use in lower respiratory tract infections with a new rapid and sensitive assay.
                243 patients admitted with suspected lower respiratory tract infections were randomly assigned standard care (standard group; n=119) or procalcitonin-guided treatment (procalcitonin group; n=124). On the basis of serum procalcitonin concentrations, use of antibiotics was more or less discouraged (<0.1 microg/L or <0.25 microg/L) or encouraged (> or =0.5 microg/L or > or =0.25 microg/L), respectively. Re-evaluation was possible after 6-24 h in both groups. Primary endpoint was use of antibiotics and analysis was by intention to treat.
                Final diagnoses were pneumonia (n=87; 36%), acute exacerbation of chronic obstructive pulmonary disease (60; 25%), acute bronchitis (59; 24%), asthma (13; 5%), and other respiratory affections (24; 10%). Serological evidence of viral infection was recorded in 141 of 175 tested patients (81%). Bacterial cultures were positive from sputum in 51 (21%) and from blood in 16 (7%). In the procalcitonin group, the adjusted relative risk of antibiotic exposure was 0.49 (95% CI 0.44-0.55; p<0.0001) compared with the standard group. Antibiotic use was significantly reduced in all diagnostic subgroups. Clinical and laboratory outcome was similar in both groups and favourable in 235 (97%).
                Procalcitonin guidance substantially reduced antibiotic use in lower respiratory tract infections. Withholding antimicrobial treatment did not compromise outcome. In view of the current overuse of antimicrobial therapy in often self-limiting acute respiratory tract infections, treatment based on procalcitonin measurement could have important clinical and financial implications. Use of antibiotics in outpatients with community-acquired pneumonia (CAP) is empirical, which may lead to overuse and selection pressure for resistance. Procalcitonin (PCT) levels may predict the severity of CAP and may be used to guide antibiotic use in hospitalized patients. This study evaluated the value of PCT measurements for guiding antibiotic use in low-risk outpatients with CAP.
                This was a randomized intervention trial conducted between February 2005 and December 2008 that included 172 consecutive patients with suspected CAP, of whom 156 completed the study. The control group received antibiotics according to current guidelines. In the PCT group, antibiotic treatment was based on PCT levels as follows: <0.1 µg/L, strongly discouraged; ≤0.25 µg/L, discouraged; >0.25 µg/L, encouraged. The primary end-points were total antibiotic use and duration of antibiotic treatment; laboratory and clinical outcomes were measured.
                Prescription of antibiotics on admission (84.4% vs 97.5%; P = 0.004), total antibiotic exposure (relative risk 0.55, 95% CI: 0.51-0.60; P = 0.003) and duration of antibiotic treatment (median 5 days vs 7 days; P < 0.001) were reduced in the PCT guidance group, compared with patients treated according to current guidelines. At 4-week follow up, all patients had survived and laboratory and clinical outcomes were similar in the two groups.
                Under PCT guidance, antibiotic use was reduced and duration of antibiotic treatment was shortened in low-risk outpatients with CAP, without apparent harm.
                © 2011 The Authors; Respirology © 2011 Asian Pacific Society of Respirology. In patients with ventilator-associated pneumonia (VAP), guidelines recommend antibiotic therapy adjustment according to microbiology results after 72 h. Circulating procalcitonin levels may provide evidence that facilitates the reduction of antibiotic therapy. In a multicentre, randomised, controlled trial, 101 patients with VAP were assigned to an antibiotic discontinuation strategy according to guidelines (control group) or to serum procalcitonin concentrations (procalcitonin group) with an antibiotic regimen selected by the treating physician. The primary end-point was antibiotic-free days alive assessed 28 days after VAP onset and analysed on an intent-to-treat basis. Procalcitonin determination significantly increased the number of antibiotic free-days alive 28 days after VAP onset (13 (2-21) days versus 9.5 (1.5-17) days). This translated into a reduction in the overall duration of antibiotic therapy of 27% in the procalcitonin group (p = 0.038). After adjustment for age, microbiology and centre effect, the rate of antibiotic discontinuation on day 28 remained higher in the procalcitonin group compared with patients treated according to guidelines (hazard rate 1.6, 95% CI 1.02-2.71). The number of mechanical ventilation-free days alive, intensive care unit-free days alive, length of hospital stay and mortality rate on day 28 for the two groups were similar. Serum procalcitonin reduces antibiotic therapy exposure in patients with ventilator associated pneumonia. Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL(-1). Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73-0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%. In previous smaller trials, a procalcitonin (PCT) algorithm reduced antibiotic use in patients with lower respiratory tract infections (LRTIs).
                To examine whether a PCT algorithm can reduce antibiotic exposure without increasing the risk for serious adverse outcomes.
                A multicenter, noninferiority, randomized controlled trial in emergency departments of 6 tertiary care hospitals in Switzerland with an open intervention of 1359 patients with mostly severe LRTIs randomized between October 2006 and March 2008.
                Patients were randomized to administration of antibiotics based on a PCT algorithm with predefined cutoff ranges for initiating or stopping antibiotics (PCT group) or according to standard guidelines (control group). Serum PCT was measured locally in each hospital and instructions were Web-based.
                Noninferiority of the composite adverse outcomes of death, intensive care unit admission, disease-specific complications, or recurrent infection requiring antibiotic treatment within 30 days, with a predefined noninferiority boundary of 7.5%; and antibiotic exposure and adverse effects from antibiotics.
                The rate of overall adverse outcomes was similar in the PCT and control groups (15.4% [n = 103] vs 18.9% [n = 130]; difference, -3.5%; 95% CI, -7.6% to 0.4%). The mean duration of antibiotics exposure in the PCT vs control groups was lower in all patients (5.7 vs 8.7 days; relative change, -34.8%; 95% CI, -40.3% to -28.7%) and in the subgroups of patients with community-acquired pneumonia (n = 925, 7.2 vs 10.7 days; -32.4%; 95% CI, -37.6% to -26.9%), exacerbation of chronic obstructive pulmonary disease (n = 228, 2.5 vs 5.1 days; -50.4%; 95% CI, -64.0% to -34.0%), and acute bronchitis (n = 151, 1.0 vs 2.8 days; -65.0%; 95% CI, -84.7% to -37.5%). Antibiotic-associated adverse effects were less frequent in the PCT group (19.8% [n = 133] vs 28.1% [n = 193]; difference, -8.2%; 95% CI, -12.7% to -3.7%).
                In patients with LRTIs, a strategy of PCT guidance compared with standard guidelines resulted in similar rates of adverse outcomes, as well as lower rates of antibiotic exposure and antibiotic-associated adverse effects.
                isrctn.org Identifier: ISRCTN95122877. The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.
                To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.
                In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.
                Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).
                Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm. To evaluate the value of serum procalcitonin (PCT) on antibiotic use in treatment of community acquired pneumonia (CAP) in outpatient.
                From November 2006 to February 2008, a total of 127 patients with CAP in outpatient were randomly assigned into two groups: PCT group (n = 63) and control group (n = 64). PCT levels of all patients were measured after study admission. On the base of similarly normal treatment, the control group received antibiotics according to the attending physicians and the PCT group were treated with antibiotics according to serum PCT levels: antibiotic treatment was applied with PCT level > or = 0.25 microg/L and was discouraged with PCT level < 0.25 microg/L. Clinical efficacy, rate of antibiotics use, duration courses and costs of antibiotics were observed.
                Clinical efficacy of the PCT group was similar with the control group (92.1% vs 87.5%, P > 0.05); rate and costs of antibiotics use was lower, antibiotic duration of the PCT group was shorter than that of the control group (P < 0.05, P < 0.001, P < 0.001).
                PCT could be used in treatment of CAP for antibiotic use in outpatient, which may reduce antibiotic use, shorten antibiotic duration and lower costs of antibiotic. 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 aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients.
                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 randomly assigned to either a PCT-guided (study group) or a standard (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 standard regimen over eight days.
                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 standardized 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.
                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).
                ISRCTN10288268. Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis.
                Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules.
                The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome.
                Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine. Recent studies have suggested that procalcitonin (PCT) is a safe marker for the discrimination between bacterial and viral infection, and that PCT-guided treatment may lead to substantial reductions in antibiotic use. The present objective was to evaluate the effect of a single PCT measurement on antibiotic use in suspected lower respiratory tract infections (LRTIs) in a Danish hospital setting. In a randomized, controlled intervention study, 223 adult patients admitted to the hospital because of suspicion of LRTI were included with 210 patients available for analysis. Patients were randomized to either PCT-guided treatment or standard treatment. Antibiotic treatment duration in the PCT group was based on the serum PCT value at admission. The cut-off point for recommending antibiotic treatment was PCT > or =0.25 microg/L. Physicians could overrule treatment guidelines. The mean duration of hospital stay was 5.9 days in the PCT group vs. 6.7 days in the control group (p 0.22). The mean duration of antibiotic treatment during hospitalization in the PCT group was 5.1 days on average, as compared to 6.8 days in the control group (p 0.007). In a subgroup analysis of chronic obstructive pulmonary disease patients, the mean length of stay was reduced from 7.1 days in the control group to 4.8 days in the PCT group (p 0.009). It was concluded that the determination of a single PCT value at admission in patients with suspected LRTIs can lead to a reduction in the duration of antibiotic treatment by 25% without compromising outcome. No effect on the length of hospital stay was found.
Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARI was not associated with higher mortality rates or treatment failure. Antibiotic consumption was significantly reduced across different clinical settings and ARI diagnoses. Further high-quality research is needed to confirm the safety of this approach for non-European countries and patients in intensive care. Moreover, future studies should also establish cost-effectiveness by considering country-specific costs of procalcitonin measurement and potential savings in consumption of antibiotics and other healthcare resources, as well as secondary cost savings due to lower risk of side effects and reduced antimicrobial resistance.