Procalcitonin Algorithm Research Articles

A new procalcitonin cord-based algorithm in early-onset neonatal infection: for a change of paradigm

Diagnostic of early-onset neonatal infection (EONI) remains an emergency. Recent studies underline the potential benefit of using Procalcitonin (PCT) in early diagnosis of bacterial infections in neonates. The aim of this study was to evaluate the diagnostic value of an umbilical blood cord PCT based algorithm in newborns suspected of EONI. The diagnostic value of the PCT based algorithm was compared to the French one currently in use by analyzing an 18-months database of newborns suspected of EONI in University Hospital of Nantes from March 2011 to September 2012. Among the 2,408 (40.8 %) newborns suspected of infection during this period, 2,366 were included in the study. The incidence of EONI was 3.4‰ (n = 20). There was no significant difference between the sensibilities of the PCT based algorithm and the current algorithm (90 %, respectively, 95%CI 76.9-100 versus 85.4-100; p = 0.90) and between their specificities (respectively 91.7 % (90.6-92.8) versus 87.4 % (86-88.7); p = 0.25). The antibiotic treatment rate would be significantly reduced with the PCT based algorithm [211 i.e. 8.9 % (7.8-10) versus 314 i.e. 13.3 % (11.9-14.7) in the current algorithm; p < 0.005] and less biological analysis would be performed [301 i.e. 12.7 % (11.4-14) versus 937 i.e. 39.6 % (37.6-41.6); p < 0.005]. Blood cord PCT seems to be a new and efficient marker to guide neonatologists taking care of newborns suspected of EONI. The PCT algorithm seems to be a safe alternative in diagnosis of EONI, allowing detection of EONI significantly as well as the current algorithm, without resulting in a substantially higher number of missed infections. These results have to be confirmed by a multicentric validation study.

Capsule Commentary on Michaelidis et al., Cost-Effectiveness of Procalcitonin-Guided Antibiotic Therapy for Outpatient Management of Acute Respiratory Tract Infections in Adults

Antibiotic overuse in ambulatory settings is a major public health concern. Acute respiratory infections are often treated empirically and present challenges to judicious antimicrobial use. Procalcitonin has emerged as a biomarker to discriminate between viral and bacterial respiratory infections, and may add value to standard decision guides.1 Acute respiratory infections are costly, and innovations minimizing drug or utilization costs would hold interest, particularly if cost-effective. One study2 examining antibiotic decision making using procalcitonin algorithms in the ICU found procalcitonin cost-effective when daily antibiotics cost more than $149(CAN), while another reports procalcitonin protocols costing more than usual care, with physician non-adherence to procalcitonin algorithms influencing cost-effectiveness in community acquired pneumonia.3 Michaelidis et al. use a decision model with a health system perspective to estimate willingness-to-pay and costs per antibiotic prescription safely avoided for procalcitonin testing compared to usual care in adults with acute respiratory tract infections treated in outpatient settings.4 Overall, their results show that procalcitonin testing costs more than usual care, but reduces the number of antibiotic prescriptions. However, when including societal costs of antibiotic resistance and requirements for antimicrobial treatment, procalcitonin testing may be cost-effective. Decision makers need to evaluate how well innovations maximize health outcomes within budgetary constraints to allocate resources. Although debate continues about cost-effectiveness thresholds,5 knowledge diffusion, adoption and sustainable change management strategies may confound results when implementing innovative approaches such as procalcitonin testing. Michaelidis et al.’s decision model’s bias towards procalcitonin testing assumes strong uptake of this innovation, and may overestimate availability while also omitting the impact of physician adherence on costs or cost-effectiveness.3 The cost-effectiveness model uses two European clinical trials, which may diminish generalizability. Although this study includes important secondary costs associated with antibiotic resistance, future research could further delineate appropriate antibiotic prescribing, include costs associated with antibiotic-induced adverse events, or compare procalcitonin protocol costs to antibiotic stewardship programs.1 Michaelidis et al.’s study brings important cost-effectiveness information about outpatient procalcitonin testing in patients with acute respiratory infections, suggesting it is cost-effective when accounting for antibiotic resistance, although overestimating access to testing and underestimating physician non-adherence may diminish the benefit.

Biomarker-guided de-escalation of empirical therapy is associated with lower risk for adverse outcomes

Dear Editor, We would like to congratulate Dr. Garnacho-Montero and colleagues for their prospective study suggesting a mortality benefit for patients in whom antibiotic therapy was de-escalated early [1]. As acknowledged by the authors and due to the observational study design, causal inference remains somewhat unclear. Although the authors used a state-of-the-art statistical approach that includes multivariate regression and propensity score analysis, residual confounding cannot be excluded. Thus, a prospective randomized trial is warranted for ultimate proof. In line with these authors’ study, we have recently analyzed data from similar trials in which patients were treated according to a procalcitonin algorithm for antibiotic de-escalation and control patients were not treated with this approach [2, 3]. We included all published randomized controlled trial data in an individual patient data (IPD) meta-analysis. The main purpose of this analysis was to demonstrate the safety of using procalcitonin protocols. Surprisingly, as demonstrated in Fig. 1, there was a significantly lower risk for treatment failure in patients with communityacquired pneumonia and patients treated in the emergency department when procalcitonin protocols were used for antibiotic stewardship. In terms of the mortality endpoint, there were no significant differences. However, the point estimate of 0.84 for intensive care unit patients with systemic infections treated according to a procalcitonin protocol is reassuring and may prompt future randomized trials to de-escalate antibiotic therapy with the aim of reducing mortality and morbidity using a similar biomarker approach.

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections

Acute respiratory infections (ARIs) comprise a large and heterogeneous group of infections including bacterial, viral and other aetiologies. In recent years, procalcitonin - the prohormone of calcitonin - has emerged as a promising marker for the diagnosis of bacterial infections and for improving decisions about antibiotic therapy. Several randomised controlled trials (RCTs) have demonstrated the feasibility of using procalcitonin for starting and stopping antibiotics in different patient populations with acute respiratory infections and different settings ranging from primary care to emergency departments (EDs), hospital wards and intensive care units (ICUs). The aim of this systematic review based on individual patient data was to assess the safety and efficacy of using procalcitonin for starting or stopping antibiotics over a large range of patients with varying severity of ARIs and from different clinical settings. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 2) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to May 2011) and EMBASE (1974 to May 2011) to identify suitable trials. We included RCTs of adult participants with ARIs who received an antibiotic treatment either based on a procalcitonin algorithm or usual care/guidelines. Trials were excluded if they exclusively focused on paediatric patients or if they used procalcitonin for another purpose than to guide initiation and duration of antibiotic treatment. Two teams of review authors independently evaluated the methodology and extracted data from primary studies. The primary endpoints were all-cause mortality and treatment failure at 30 days. For the primary care setting, treatment failure was defined as death, hospitalisation, ARI-specific complications, recurrent or worsening infection, and patients reporting any symptoms of an ongoing respiratory infection at follow-up. For the ED setting, treatment failure was defined as death, ICU admission, re-hospitalisation after index hospital discharge, ARI-associated complications, and recurrent or worsening infection within 30 days of follow-up. For the ICU setting, treatment failure was defined as death within 30 days of follow-up. Secondary endpoints were antibiotic use (initiation of antibiotics, duration of antibiotics and total exposure to antibiotics (total amount of antibiotic days divided by total number of patients)), length of hospital stay for hospitalised patients, length of ICU stay for critically ill patients, and number of days with restricted activities within 14 days after randomisation for primary care patients. For the two co-primary endpoints of all-cause mortality and treatment failure, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable hierarchical logistic regression. The hierarchical regression model was adjusted for age and clinical diagnosis as fixed-effect. The different trials were added as random-effects into the model. We fitted corresponding linear regression models for antibiotic use. We conducted sensitivity analyses stratified by clinical setting and ARI diagnosis to assess the consistency of our results. We included 14 trials with 4221 participants. There were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared to 134 deaths in 2126 control patients (6.3%) (adjusted OR 0.94, 95% CI 0.71 to 1.23). Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting, or ARI diagnosis. These results proved robust in various sensitivity analyses. Total antibiotic exposure was significantly reduced overall (median (interquartile range) from 8 (5 to 12) to 4 (0 to 8) days; adjusted difference in days, -3.47, 95% CI -3.78 to -3.17, and across all the different clinical settings and diagnoses. 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.

Clinical Outcomes Associated With Procalcitonin Algorithms to Guide Antibiotic Therapy in Respiratory Tract Infections

In patients with respiratory tract infection, is measurement of procalcitonin to guide antibiotic prescriptions associated with reduced antibiotic exposure without increases in all-cause mortality or treatment failure? The measurement of procalcitonin to guide initiation and duration of antibiotic treatment in patients with respiratory tract infections of varying severity is associated with lower antibiotic exposure without increasing all-cause mortality or treatment failure.

Procalcitonin in Diagnosis of Post-Operative Bacterial Meningitis: A Promising but Limited Role

Procalcitonin in Diagnosis of Post-Operative Bacterial Meningitis: A Promising but Limited Role

Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis

IntroductionProcalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.MethodTwo reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org.Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.ResultsFinally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis.Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups.Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.ConclusionProcalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care.Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.

Influence of procalcitonin on decision to start antibiotic treatment in patients with a lower respiratory tract infection: insight from the observational multicentric ProREAL surveillance

Procalcitonin (PCT)-guided antibiotic stewardship is a successful strategy to decrease antibiotic use. We assessed if clinical judgement affected compliance with a PCT-algorithm for antibiotic prescribing in a multicenter surveillance of patients with lower respiratory tract infections (LRTI). Initiation and duration of antibiotic therapy, adherence to a PCT algorithm and outcome were monitored in consecutive adults with LRTI who were enrolled in a prospective observational quality control. We correlated initial clinical judgment of the treating physician with algorithm compliance and assessed the influence of PCT on the final decision to initiate antibiotic therapy. PCT levels correlated with physicians' estimates of the likelihood of bacterial infection (p for trend <0.02). PCT influenced the post-test probability of antibiotic initiation with a greater effect in patients with non-pneumonia LRTI (e.g., for bronchitis: -23 % if PCT ≤ 0.25 μg/L and +31 % if PCT > 0.25 μg/L), in European centers (e.g., in France -22 % if PCT ≤ 0.25 μg/L and +13 % if PCT > 0.25 μg/L) and in centers, which had previous experience with the PCT-algorithm (-16 % if PCT ≤ 0.25 μg/L and +19 % if PCT > 0.25 μg/L). Algorithm non-compliance, i.e. antibiotic prescribing despite low PCT-levels, was independently predicted by the likelihood of a bacterial infection as judged by the treating physician. Compliance was significantly associated with identification of a bacterial etiology (p = 0.01). Compliance with PCT-guided antibiotic stewardship was affected by geographically and culturally-influenced subjective clinical judgment. Initiation of antibiotic therapy was altered by PCT levels. Differential compliance with antibiotic stewardship efforts contributes to geographical differences in antibiotic prescribing habits and potentially influences antibiotic resistance rates.

Applying biomarkers to clinical practice: a guide for utilizing procalcitonin assays

Prudent use of antimicrobial therapies is an important component in decreasing bacterial resistance. Procalcitonin (PCT) is a novel biomarker proposed as both a diagnostic and prognostic agent for use in various severe infections. Elevated PCT levels have a high sensitivity and specificity for diagnosing infections. This biomarker has been studied as an aid to identify patients requiring antimicrobial initiation, stratify infections according to severity and guide therapy durations. Two commercially available tests are approved for use in the USA. Other biomarkers have been studied for similar indications, but are subject to elevation from chronic inflammatory conditions and medications. The advantage of PCT over other biomarkers is due to the limited disease states and drug therapies that may interfere with this assay. PCT has been studied extensively for use in patients with severe sepsis and septic shock, as well as in lower respiratory tract infections. Decreased antimicrobial utilization without an increase in patient morbidity and mortality has been illustrated through numerous studies using PCT algorithms. Determining the utility of PCT in practice requires a comprehensive evaluation of the impact this biomarker has on outcomes to the patient and healthcare system, as well as examining convenience and cost factors. PCT can be used to assist clinicians in initiating and guiding antimicrobial therapies for specific patient populations, as an adjunct to other diagnostic tools. Further studies examining long-term outcomes of PCT are needed to determine the effect of this intervention on resistance patterns and overall prescribing trends.

Biomarker-guided antibiotic therapy in adult critically ill patients: a critical review

Biomarkers of infection, namely C-reactive protein and procalcitonin (PCT), are potentially useful in the diagnosis of infection as well as in the assessment of its response to antibiotic therapy. C-reactive protein variations overtime appears to have a good performance for the diagnosis of infection. Procalcitonin shows a better correlation with clinical severity. In addition, to overcome the worldwide problem of antibiotic overuse as well as misuse, biomarker guidance of antibiotic stewardship represents a promising new approach. In several randomized, controlled trials, including adult critically ill patients, PCT guidance was repeatedly associated with a decrease in the duration of antibiotic therapy. However, these trials present several limitations, namely high rate of patients’ exclusion, high rate of algorithm overruling, long duration of antibiotic therapy in the control group, disregard the effect of renal failure on PCT level, and above all a possible higher mortality and higher late organ failure in the PCT arm. In addition, some infections (e.g., endocarditis) as well as frequent nosocomial bacteria (e.g., Pseudomonas aeruginosa) are not suitable to be assessed by PCT algorithms. Therefore, the true value of PCT-guided algorithm of antibiotic stewardship in assisting the clinical decision-making process at the bedside remains uncertain. Future studies should take into account the issues identified in the present review.

Effectiveness and Safety of Procalcitonin-Guided Antibiotic Therapy in Lower Respiratory Tract Infections in “Real Life”

In controlled studies, procalcitonin (PCT) has safely and effectively reduced antibiotic drug use for lower respiratory tract infections (LRTIs). However, controlled trial data may not reflect real life. We performed an observational quality surveillance in 14 centers in Switzerland, France, and the United States. Consecutive adults with LRTI presenting to emergency departments or outpatient offices were enrolled and registered on a website, which provided a previously published PCT algorithm for antibiotic guidance. The primary end point was duration of antibiotic therapy within 30 days. Of 1759 patients, 86.4% had a final diagnosis of LRTI (community-acquired pneumonia, 53.7%; acute exacerbation of chronic obstructive pulmonary disease, 17.1%; and bronchitis, 14.4%). Algorithm compliance overall was 68.2%, with differences between diagnoses (bronchitis, 81.0%; AECOPD, 70.1%; and community-acquired pneumonia, 63.7%; P < .001), outpatients (86.1%) and inpatients (65.9%) (P < .001), algorithm-experienced (82.5%) and algorithm-naive (60.1%) centers (P < .001), and countries (Switzerland, 75.8%; France, 73.5%; and the United States, 33.5%; P < .001). After multivariate adjustment, antibiotic therapy duration was significantly shorter if the PCT algorithm was followed compared with when it was overruled (5.9 vs 7.4 days; difference, -1.51 days; 95% CI, -2.04 to -0.98; P < .001). No increase was noted in the risk of the combined adverse outcome end point within 30 days of follow-up when the PCT algorithm was followed regarding withholding antibiotics on hospital admission (adjusted odds ratio, 0.83; 95% CI, 0.44 to 1.55; P = .56) and regarding early cessation of antibiotics (adjusted odds ratio, 0.61; 95% CI, 0.36 to 1.04; P = .07). This study validates previous results from controlled trials in real-life conditions and demonstrates that following a PCT algorithm effectively reduces antibiotic use without increasing the risk of complications. Preexisting differences in antibiotic prescribing affect compliance with antibiotic stewardship efforts. isrctn.org Identifier: ISRCTN40854211.

Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis.

Procalcitonin algorithms may reduce antibiotic use for acute respiratory tract infections (ARIs). We undertook an individual patient data meta-analysis to assess safety of this approach in different ARI diagnoses and different clinical settings. We identified clinical trials in which patients with ARI were assigned to receive antibiotics based on a procalcitonin algorithm or usual care by searching the Cochrane Register, MEDLINE, and EMBASE. Individual patient data from 4221 adults with ARIs in 14 trials were verified and reanalyzed to assess risk of mortality and treatment failure-overall and within different clinical settings and types of ARIs. Overall, there were 118 deaths in 2085 patients (5.7%) assigned to procalcitonin groups compared with 134 deaths in 2126 control patients (6.3%; adjusted odds ratio, 0.94; 95% confidence interval CI, .71-1.23)]. Treatment failure occurred in 398 procalcitonin group patients (19.1%) and in 466 control patients (21.9%; adjusted odds ratio, 0.82; 95% CI, .71-.97). Procalcitonin guidance was not associated with increased mortality or treatment failure in any clinical setting or ARI diagnosis. Total antibiotic exposure per patient was significantly reduced overall (median [interquartile range], from 8 [5-12] to 4 [0-8] days; adjusted difference in days, -3.47 [95% CI, -3.78 to -3.17]) and across all clinical settings and ARI diagnoses. Use of procalcitonin to guide initiation and duration of antibiotic treatment in patients with ARIs was effective in reducing antibiotic exposure across settings without an increase in the risk of mortality or treatment failure. Further high-quality trials are needed in critical-care patients.

Procalcitonin Algorithms for Antibiotic Therapy Decisions: A Systematic Review of Randomized Controlled Trials and Recommendations for Clinical Algorithms

Procalcitonin Algorithms for Antibiotic Therapy Decisions: A Systematic Review of Randomized Controlled Trials and Recommendations for Clinical Algorithms

Procalcitonin Algorithms for Antibiotic Therapy Decisions: A Systematic Review of Randomized Controlled Trials and Recommendations for Clinical Algorithms

Procalcitonin Algorithms for Antibiotic Therapy Decisions: A Systematic Review of Randomized Controlled Trials and Recommendations for Clinical Algorithms

Procalcitonin-Guided Antibiotic Therapy in Patients with Lower Respiratory Tract Infections

This article discusses data from a quality control survey [ISRCTN40854211] that monitored procalcitonin (PCT)-guided antibiotic therapy and algorithm adherence in simulated “real-life” conditions. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process by prescribing physicians [Schuetz P et al. Eur J Clin Microbiol Infect Dis 2010].

Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future

There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms.

Procalcitonin Algorithms for Antibiotic Therapy Decisions

Previous randomized controlled trials suggest that using clinical algorithms based on procalcitonin levels, a marker of bacterial infections, results in reduced antibiotic use without a deleterious effect on clinical outcomes. However, algorithms differed among trials and were embedded primarily within the European health care setting. Herein, we summarize the design, efficacy, and safety of previous randomized controlled trials and propose adapted algorithms for US settings. We performed a systematic search and included all 14 randomized controlled trials (N = 4467 patients) that investigated procalcitonin algorithms for antibiotic treatment decisions in adult patients with respiratory tract infections and sepsis from primary care, emergency department (ED), and intensive care unit settings. We found no significant difference in mortality between procalcitonin-treated and control patients overall (odds ratio, 0.91; 95% confidence interval, 0.73-1.14) or in primary care (0.13; 0-6.64), ED (0.95; 0.67-1.36), and intensive care unit (0.89; 0.66-1.20) settings individually. A consistent reduction was observed in antibiotic prescription and/or duration of therapy, mainly owing to lower prescribing rates in low-acuity primary care and ED patients, and shorter duration of therapy in moderate- and high-acuity ED and intensive care unit patients. Measurement of procalcitonin levels for antibiotic decisions in patients with respiratory tract infections and sepsis appears to reduce antibiotic exposure without worsening the mortality rate. We propose specific procalcitonin algorithms for low-, moderate-, and high-acuity patients as a basis for future trials aiming at reducing antibiotic overconsumption.

Procalcitonin-Based Guidelines and Lower Respiratory Tract Infections

To the Editor: In a randomized controlled trial, Dr Schuetz and colleagues studied the effect of a procalcitonin (PCT) algorithm in the antibiotic management of lower respiratory tract infections (LRTIs) in emergency departments of tertiary hospitals. Procalcitonin showed promise in helping to limit antibiotic therapy to those patients who are likely to benefit in inpatient settings where follow-up measurements are accessible and waiting time to obtain blood test results is short. In their discussion, the authors called for more widespread introduction of PCT measurement for milder LRTIs in outpatient physician offices. We think this conclusion is not justified because their study patients were managed in tertiary care settings. By focusing on the sickest patients with LRTI, the PCT test may have had better sensitivity in the study patients than it would have in less ill patients observed in primary care, a form of spectrum bias. Procalcitonin did not perform well in a prior study based in primary care. Despite a recent study showing efficacy and safety of a PCT approach to the restriction of activities of patients with LRTI in primary care, pragmatic evidence that the use of PCT for LRTI management in primary care leads to a reduction in antibiotic use is lacking. Explanatory trials evaluate efficacy in controlled conditions, and pragmatic trials evaluate effectiveness in usual care. How useful a trial is depends not only on the design but also on the similarity between the trial and the clinician’s context. It seems doubtful that introducing a costly test, not readily available as a near-patient test at present, will change physicians’ decision making. Moreover, such use runs a risk of defining a test result as a medical problem. In contrast, other less costly biomarkers, including C-reactive protein (CRP), have shown test characteristics similar to PCT when assessed in an outpatient population, and there is pragmatic evidence of the effectiveness of CRP testing when used at the point of care in a primary care setting. Before widespread use of PCT in primary care can be advocated, pragmatic evidence of the comparative and cost-effectiveness of different point-of-care strategies is needed.

Procalcitonin-Based Guidelines and Lower Respiratory Tract Infections

To the Editor: In a randomized controlled trial, Dr Schuetz and colleagues studied the effect of a procalcitonin (PCT) algorithm in the antibiotic management of lower respiratory tract infections (LRTIs) in emergency departments of tertiary hospitals. Procalcitonin showed promise in helping to limit antibiotic therapy to those patients who are likely to benefit in inpatient settings where follow-up measurements are accessible and waiting time to obtain blood test results is short. In their discussion, the authors called for more widespread introduction of PCT measurement for milder LRTIs in outpatient physician offices. We think this conclusion is not justified because their study patients were managed in tertiary care settings. By focusing on the sickest patients with LRTI, the PCT test may have had better sensitivity in the study patients than it would have in less ill patients observed in primary care, a form of spectrum bias. Procalcitonin did not perform well in a prior study based in primary care. Despite a recent study showing efficacy and safety of a PCT approach to the restriction of activities of patients with LRTI in primary care, pragmatic evidence that the use of PCT for LRTI management in primary care leads to a reduction in antibiotic use is lacking. Explanatory trials evaluate efficacy in controlled conditions, and pragmatic trials evaluate effectiveness in usual care. How useful a trial is depends not only on the design but also on the similarity between the trial and the clinician’s context. It seems doubtful that introducing a costly test, not readily available as a near-patient test at present, will change physicians’ decision making. Moreover, such use runs a risk of defining a test result as a medical problem. In contrast, other less costly biomarkers, including C-reactive protein (CRP), have shown test characteristics similar to PCT when assessed in an outpatient population, and there is pragmatic evidence of the effectiveness of CRP testing when used at the point of care in a primary care setting. Before widespread use of PCT in primary care can be advocated, pragmatic evidence of the comparative and cost-effectiveness of different point-of-care strategies is needed.

Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey

All published evidence on procalcitonin (PCT)-guided antibiotic therapy was obtained in trials where physicians knew that they were being monitored, possibly resulting in higher adherence to the PCT algorithm. This study investigates the effectiveness of PCT guidance in an observational quality control survey. We monitored antibiotic therapy and algorithm adherence in consecutive patients with respiratory tract infections admitted to the Kantonsspital Aarau, Switzerland, between May 2008 and February 2009. The results were compared to the site-specific results of the former ProHOSP study. Overall and more pronounced for patients with community-acquired pneumonia, the median duration of antibiotic treatment in this survey was shorter than the ProHOSP control patients (6 vs. 7 days, P = 0.048 and 7 vs. 9 days, P < 0.001). In 72.5% of patients, antibiotics were administered according to the prespecified PCT algorithm. No significant differences concerning adverse medical outcome could be detected. This study mirrors the use of PCT-guided antibiotic therapy in clinical practice, outside of trial conditions. If algorithm adherence is reinforced, antibiotic exposure can be markedly reduced with subsequent reduction of antibiotic-associated side effects and antibiotic resistance. The integration of the PCT algorithm into daily practice requires ongoing reinforcement and involves a learning process of the prescribing physicians.