Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication of cirrhosis, contributing to considerable morbidity and mortality.

A cross-sectional derivation study was conducted to assess the diagnostic accuracy of two sepsis-related calcitonin peptide family biomarkers, mid-regional pro-adrenomedullin (MR-pro-ADM) and procalcitonin, in ascitic fluid for identifying bacteriologically confirmed SBP (BC-SBP). In a subsequent validation study, the diagnostic performance of the 'SBP score' was evaluated in an independent patient cohort using an absolute polymorphonuclear (PMN) leukocyte count threshold of ≥250 cells/mm3 as the diagnostic benchmark for diagnosing SBP.

In the derivation study, the concentration of MR-pro-ADM in ascitic fluid was significantly higher in patients with BC-SBP compared to those without BC-SBP (3.14 nmol/L [IQR, 2.39-6.74] vs. 1.91 nmol/L [IQR, 1.33-2.80]; p = .0002). Bayesian ANOVA indicated that MR-pro-ADM was highly discriminative for diagnosing BC-SBP, with a substantial Bayes factor (BFM = 2505), whereas procalcitonin exhibited poor discriminatory performance. Receiver-operating characteristic (ROC) analysis identified an optimal MR-pro-ADM cut-off of ≥2.50 nmol/L for diagnosing BC-SBP, with an area under the ROC curve (AUROC) of 0.746 (95% CI, 0.685-0.801; p < .0001). Multivariable logistic regression identified three independent predictors of BC-SBP, which were subsequently incorporated into the 'SBP score' (MR-pro-ADM ≥2.5 nmol/L, absolute PMN count ≥250 cells/mm3 and Child-Pugh score). In the validation study, the 'SBP score' demonstrated an AUROC of 0.993 (95% CI, 0.929-1.000; p < .0001) for diagnosing SBP.

MR-pro-ADM in ascitic fluid emerges as a promising biomarker for SBP diagnosis. Combining MR-pro-ADM with absolute PMN count and Child-Pugh score in the 'SBP score' greatly improves the diagnostic accuracy of SBP.

Procalcitonin (PCT) is recognized as an inflammatory biomarker, often elevated in COVID-19 pneumonia alongside other biomarkers. Understanding its association with severe outcomes and comparing its predictive ability with other biomarkers is crucial for clinical management.

This retrospective multicenter observational study aimed to investigate the association between PCT levels and adverse outcomes in hospitalized COVID-19 patients. Additionally, it sought to compare the predictive performance of various biomarkers.

The study analyzed data from the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry, comprising COVID-19 patients hospitalized across multiple Mayo Clinic sites between March 2020 and June 2022.

A total of 7851 adult COVID-19 patients were included. Patients were categorized into 6 groups based on the worst WHO ordinal scale. Multivariate models were constructed using peak biomarker levels within 72 hours of admission, adjusted for confounders.

Elevated PCT levels were independently associated with increased odds of adverse outcomes, including ICU admission (adjusted odds ratio [aOR] 1.32, 95%CI 1.27-1.38), IMV requirement (aOR 1.35, 95%CI: 1.28-1.42), and in-hospital mortality (aOR 1.30, 95%CI: 1.22-1.37). A 3.48-fold increase in IMV requirement and 3.55 times increase in in-hospital mortality were noted with peak PCT ⩾ 0.25 ng/ml. Similar associations were observed with other biomarkers like NLR (AUC 0.730), CRP, IL-6, LDH (AUC 0.800), and D-dimer (AUC 0.719). Models incorporating NLR, LDH, D-dimer, and PCT demonstrated the highest predictive accuracy, with a combined model exhibiting an area under the curve (AUC) of 0.826 (95%CI 0.803-0.849).

Higher PCT levels were significantly linked to worse outcomes in COVID-19 patients, emphasizing its potential as a prognostic marker. Biomarker-based predictive models, particularly those including PCT, showed promising utility for risk assessment and clinical decision-making. Further prospective studies are warranted to validate these findings on a larger scale.

The aim of the study was to develop and validate an algorithm based on procalcitonin (PCT) monitoring to predict the prognosis of patients with sepsis.

The design was a retrospective and observational prospective study.

The study was set in intensive care units (ICUs) in 2 different hospitals in Spain.

Patients in the study included 101 patients with sepsis aged ≥18 years.

In the retrospective study, PCT results from patients admitted to the ICU in 2011-2012 were collected. In the prospective study, PCT was determined at specific time points as indicated by the algorithm from March 2018 to April 2019. The primary outcome measure, 28-day mortality, was the main variable of interest.

The study developed an algorithm based on early PCT monitoring for predicting the prognosis of patients with sepsis. The algorithm was initially developed retrospectively in 1 cohort and subsequently validated prospectively in another cohort.

The developed algorithm provides information on the prognosis of patients with sepsis, distinguishing between those with a good prognosis and those with a poor prognosis (defined as mortality).

Antibiotic de-escalation (ADE) is important to help optimize antibiotic use and balance the positive and negative effects of antimicrobial therapy. ADE should be performed promptly, and infections should be treated with the shortest course of antimicrobials as clinically feasible to avoid unnecessary use of broad-spectrum antimicrobials. Several tools have been developed to increase efficient ADE, including rapid diagnostic tests (ex. multiplex PCR), MRSA nasal PCR/culture, and biomarkers. Multiplex PCR and MRSA nasal PCR/culture have been associated with reductions in inappropriate antibiotic use. Procalcitonin, a biomarker, has been associated with shorter antimicrobial durations in some studies; however, widespread use may be limited by lack of specificity for bacterial infections, cost, and lack of set cut-off points. Additional biomarkers such as IL-6, HMGB1, presepsin, sTREM-1, CD64, PSP, proadrenomedullin, and pentraxin-3 are currently being studied. As technology improves, additional tools may be leveraged to better optimize ADE even better, such as antimicrobial spectrum scoring tools and artificial intelligence (AI). Spectrum scores, which quantify antibiotic activity using specific numeric values, could be incorporated into electronic health records to identify patients on unnecessarily broad antibiotics. AI modeling has the potential to predict personal antibiograms or provide the probability that an empiric regimen may cover a particular infection, among other potential applications. This review will discuss the literature associated with ADE in the ICU, selected tools to help guide ADE, and perspectives on how to implement ADE into clinical practice.

Biomarkers are objectively measurable parameters that provide clinicians with timely information to guide diagnosis and patient management beyond that which can be obtained from routinely available data. The literature contains thousands of articles on biomarkers in veterinary medicine. Specifically reviewed are the acute kidney injury markers neutrophil gelatinase-associated lipocalin, cystatin, clusterin, and kidney-injury molecule-1; the cardiac troponins and natriuretic peptides as biomarkers of heart disease; the acute phase protein C-reactive protein; procalcitonin; inflammatory cytokines; the markers of neutrophil extracellular trap formation cell-free DNA and nucleosomes; and markers of injury to the endothelium and endothelial glycocalyx including hyaluronan.

Severe pneumonia is a leading cause of mortality and morbidity worldwide. Being a complex condition caused by a variety of microorganisms including bacteria, viruses, and fungi, it requires intensive care. A combination of early initiation of antimicrobial therapy and adjunctive nonantimicrobial interventions improve patient outcomes. This article reviews the most recent data on the epidemiology, microbiology, diagnosis, and management of severe pneumonia.

Procalcitonin is a 14.5 kDa protein used clinically as a marker of sepsis and therapeutic response to antibiotic therapy. However, its utility in critically ill patients with either acute kidney injury (AKI) or end-stage kidney disease (ESKD) who require continuous kidney replacement therapy (CKRT) is unknown. The aim of this study was to determine if plasma levels of procalcitonin could reliably distinguish septic from nonseptic status in patients with AKI or ESKD prior to or during CKRT.

Procalcitonin concentrations were measured in plasma of 41 critically ill septic or non-septic subjects with AKI or ESKD prior to CKRT (pre-CKRT) and on days 1, 2, and 3 of CKRT in this retrospective cohort study (n = 111 total plasma measurements). Continuous venovenous hemodialysis was the modality of CKRT in these patients. Sepsis status was stringently defined based on culture results. Effluent procalcitonin levels were ascertained on days 1, 2, and 3 of CKRT to assess the clearance of procalcitonin and effects on plasma levels.

92% (66/72) of the plasma procalcitonin measurements among nonseptic patients with either AKI or ESKD were ≥ 0.5 ng/mL (the diagnostic threshold beyond which bacterial infection is very likely). Prior to CKRT initiation, procalcitonin levels were (median (IQR), ng/mL) 5.6 (1.5-18.9) in nonseptic AKI and 58.1 (6.9-195.5) in septic AKI (P = 0.03) and were 3.3 (1.2-8.3) in nonseptic ESKD and 3.7 (1.4-209.8) in septic ESKD (P = 0.79). However, despite being significantly elevated in septic patients with AKI, substantial overlap among procalcitonin levels was present and ROC curve analysis found no cut point that could reliably separate septic from nonseptic patients. Effluent procalcitonin levels were consistently ~ 20% of plasma levels throughout the course of CKRT (i.e., sieving coefficient was 0.2) suggesting that clearance occurs during therapy. However, plasma procalcitonin levels did not significantly decline during CKRT in either AKI or ESKD.

Procalcitonin levels are markedly elevated in nonseptic critically ill patients with either AKI or ESKD and do not effectively distinguish sepsis from nonseptic status prior to or during CKRT. We conclude that procalcitonin testing should be avoided in critically ill patients with kidney failure since results are nonspecific in this population.

Critical care medicine is a highly complex field where diagnosing diseases and selecting effective therapies pose daily challenges for clinicians. In critically ill patients, biomarkers can play a crucial role in identifying and addressing clinical problems. Selecting the right biomarkers and utilizing them effectively can lead to more informed decisions, ultimately impacting patient outcomes. However, each biomarker has its strengths and limitations, making a thorough understanding essential for accurate diagnosis and treatment management. For instance, neuron-specific enolase (NSE) is commonly used to predict outcomes in out-of-hospital cardiac arrest (OHCA), procalcitonin (PCT) levels strongly correlate with bacterial infections, and NT-proBNP serves as a reliable indicator of cardiac stress. Additionally, serum creatinine (SCr) remains fundamental in renal diagnostics, while prealbumin helps differentiate catabolic and anabolic phases in critically ill patients. This narrative review highlights a carefully selected set of biomarkers known for their clinical utility and reliability in guiding critical care decisions. Further refining the application of biomarkers-especially by integrating them into a multimodal approach-will enhance clinicians' ability to navigate the challenges of critical care, always striving to improve patient outcomes.

The PROGRESS randomised trial (ClinicalTrials.gov: NCT03333304) showed that early stopof antibiotics guided by procalcitonin (PCT) decreased the incidence of infections by multidrug-resistant organisms and/or Clostridioides difficile and was associated with survival benefit. This study was conducted to investigate whether this survival benefit is associated with microbiome dysbiosis. Patients with sepsis due to lung infection, acute pyelonephritis or primary bacteraemia were randomised to standard-of-care (SoC) duration of antibiotics or early stop using PCT. Faecal samples were collected before, and 7 and 28 days after randomisation and analysed using 16S rRNA Nanopore sequencing. Calprotectin was measured using an enzyme immunoassay. Median (Q1-Q3) antimicrobial duration was 5 (5-7.5) days in the PCT arm and 11 (8-15) days in the SoC arm (P < 0.001). Faecal calprotectin levels were similar in the two treatment arms at baseline. By day 7, the levels of faecal calprotectin were significantly increased in the SoC arm (P = 0.002) but were unchanged in the PCT arm. Microbiome α- and β-diversity was similar at baseline in the PCT (n=81) and SoC (n=76) treatment arms. Shannon's index was significantly lower in the SoC arm on day 7 compared with baseline (median [Q1-Q3], 2.88 [2.37-3.39] at day 1 vs. 2.24 [1.52-3.08] at day 7; Pt-test = 0.0013). This was not the case for the PCT arm (median [Q1-Q3], 2.73 [2.26-3.4] at day 1 vs. 2.43 [1.81-3.21] at day 7; Pt-test = 0.037, Bonferroni corrected α = 0.0125). The relative abundance of Actinomycetota and Pseudomonadota was decreased in the PCT arm by day 7 and that of Bacillota was increased. Early PCT-guided stop of antibiotics contributes to decreased microbiome dysbiosis by day 7.

 Nosocomial pneumonia, encompassing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), remains a major cause of morbidity and mortality in hospitalized adults. In response to evolving pathogen profiles and emerging resistance patterns, this updated S3 guideline (AWMF Register No. 020-013) provides an evidence-based framework to enhance the diagnosis, risk stratification, and treatment of nosocomial pneumonia.

 The guideline update was developed by a multidisciplinary panel representing key German professional societies. A systematic literature review was conducted with subsequent critical appraisal using the GRADE methodology. Structured consensus conferences and external reviews ensured that the recommendations were clinically relevant, methodologically sound, and aligned with current antimicrobial stewardship principles.

 For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to non-bronchoscopic sampling in terms of main outcomes. Combination antibiotic therapy is now reserved for patients in septic shock and high risk for multidrug-resistant pathogens, while select patients may be managed with monotherapy (e. g., meropenem). In clinically stabilized patients, antibiotic therapy should be de-escalated and focused, as well as duration shortened to 7-8 days. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid.

 This updated S3 guideline offers a comprehensive, multidisciplinary approach to the management of nosocomial pneumonia in adults. By integrating novel diagnostic modalities and refined therapeutic strategies, it aims to standardize care, improve patient outcomes, and enhance antimicrobial stewardship to curb the emergence of resistant pathogens.

Respiratory infection may account for 30% of acute chest syndrome (ACS) aetiologies. However, antimicrobials are routinely prescribed, and de-escalation and/or discontinuation are challenging. Multiplex Polymerase Chain Reaction (mPCR) with an enlarged respiratory panel might support antimicrobial stewardship, and procalcitonin (PCT) measurements help reduce duration of antibiotic therapy. We hypothesized that a strategy combining the use of mPCR with repeated PCT measurements would reduce antibiotic exposure during ACS.

We conducted a randomised, controlled, parallel group, open-label study in two French hospitals. Consecutive adult patients with ACS were randomly assigned to the conventional or interventional strategy, where antibiotic therapy was targeted on the results of mPCR performed on lower respiratory tract secretions (LRTS) samples, and antibiotic discontinuation based on PCT values and kinetics at Day 1 (D1), D3 and D7. The primary outcome was the number of days of antibiotic exposure at D28 after randomisation. This trial was registered on ClinicalTrial.gov (NCT03919266) and is closed to recruitment.

From June 2020 to September 2022, 72 patients were assigned to the interventional (n = 37) or conventional strategy (n = 35). Despite a higher rate of microbiological documentation with the intervention (n = 25; 67.6% versus n = 13; 37.1%; difference, 30.4%; 95% CI 6.7%-51.5%), antibiotic exposure at D28 was similar between the two strategies (6 days [4.0-8.0] versus 6 days [5.0-9.0], respectively; difference, 0.0 day; 95% CI, -2.1 to 2.1). The time to clinical stability, and ICU and hospital lengths of stay did not differ.

As compared with conventional tests, an enlarged respiratory panel mPCR combined with a PCT-guided algorithm did not reduce antibiotic exposure at D28 in adults with ACS.

Assistance Publique-Hôpitaux de Paris, AP-HP (CRC180159). A financial support for the multiplex PCR kits used in this study was partially provided by bioMérieux.

To determine the impact of procalcitonin-guided antibiotic stewardship protocol (PCT-ASP) in children admitted with sepsis and lower respiratory tract infection on the duration of antibiotic therapy and clinical outcome.

This was a single-center study involving children with infections treated with antibiotic therapy according to the PCT-ASP as the study group. The control group consisted of children with same age and diagnosis who were treated with antibiotics according to individual unit protocol before the implementation of PCT-ASP. The primary outcome was median duration of antibiotic therapy and hospital stay.

Among 127 patients, 66 were enrolled in the study and 61 in the control group respectively. The median (IQR) PCT values at admission, day 4 and day 6 of antibiotic therapy were 5.59 (61.3), 2.57 (47.35), and 0.35 (0.47) ng/ml respectively, and showed a decreasing trend. All the children in the control group received antibiotics at admission while 12% of children in the study group were not initiated on antibiotics. In the study group, 53% of the children received antibiotics only for three days in the absence of treatment failure. The duration of antibiotics (p = 0.001) and hospital stay (p = 0.03) were less in the study group when compared to the control group.

PCT-ASP reduces the duration of antibiotics and duration of hospital stay without increasing morbidity and mortality.

Optimal duration of therapy in SSTIs - a heterogeneous group of infections - remains unknown. The advances in knowledge of antibiotic duration of treatment in selected SSTIs that can impact clinical practice and published in the last 18 months are reviewed.

Recent evidence indicates that few patients receive guideline concordant empiric antibiotics and appropriate duration in the United States, although this likely can be extrapolated to other countries. One of the most commonly identified opportunities to improve antibiotic stewardship is duration of therapy more than 10 days. The long-standing debate regarding the significance of abscess size and its impact on clinical response to antibiotics, following proper drainage, is increasingly shifting towards the conclusion that abscess size is not directly associated with cure.In obese patients with SSTI, there is no benefit to longer antibiotic durations for SSTIs in patients with obesity, and it appears that longer antibiotic duration of therapy was associated with increased treatment failure. In diabetic foot infections (DFO), two randomized studies suggest that in the presence of osteomyelitis, the total duration of antibiotic therapy for patients treated nonsurgically does not need to be more than 6 weeks. In a prospective, randomized, noninferiority, pilot trial, patients with DFO who underwent surgical debridement and received either a 3-week or 6-week course of antibiotic therapy had similar outcomes and antibiotic-related adverse events. In patients with necrotizing soft tissue infections, successive observational studies clearly suggest that short duration of antibiotic treatment after NSTI source control is as well tolerated and effective as a longer course. It appears that 48 h would be enough. The possibility of fixed versus individualized approaches to therapy for common bacterial infections, including SSTIs merits to be considered seriously. Fully individualized therapy may be an ideal approach to maximize the benefits and minimize the harms of antimicrobials. Much more work is needed before this strategy becomes feasible.

There is increasing evidence that shorter duration of treatment is better in different types of SSTIs. Paradoxically, evaluation of real-life clinical practice indicates that long treatments continue to be commonly given to this population.

Evidence behind antibiotic duration while treating ventilator-associated pneumonia (VAP) remains unclear. There is a need to balance minimizing the development of antimicrobial resistance without compromising clinical outcomes given the high mortality.

Recent studies have suggested that shorter antibiotic courses, when individualized to clinical response, may be adequate for treating VAP without increasing the incidence of mortality or recurrence, regardless of pathogens. Moreover, shortening duration may reduce the risk of adverse events, including acute kidney injury.

Shortening the duration of antibiotic treatment for VAP, in the setting of appropriate clinical response, is a reasonable strategy to reduce costs and selective pressure driving antimicrobial resistance. This was demonstrated in the latest REGARD-VAP study, even among VAP patients with nonfermenting Gram-negative bacilli or carbapenem-resistant pathogens. Given the challenges in diagnosing VAP, such pragmatic approaches would be essential as part of overall antibiotic stewardship programmes. Further refinement to the criteria for antibiotic cessation may be possible.

We sought to delineate the mortality outcome time frames reported in septic shock randomized control trials (RCTs).

Systematic review of PubMed, EMBASE, and the Cochrane Database of Systematic Reviews.

Intensive care units.

Studies that included adult patients with septic shock.

Any type of intervention.

Information about the study, specific patient population, type of study intervention, specific intervention, and number of patients. Mortality time frames were analyzed for geographical differences and changes over time.

The search yielded 2660 unique citations. After screening, 132 eligible studies were identified. A total of 234 mortality time frames were collected from the included studies, of which 15 timeframes were unique. The most frequently reported time frame was 28-day mortality (n = 98, 74% of trials), followed by hospital mortality (n = 35, 27%), ICU mortality (n = 30, 23%), and 90-day mortality (n = 29, 22%). The most reported mortality time frame was 28 days in studies from every continent except Africa. The studies published between 2008 and 2013 (25%) more frequently reported hospital and ICU mortality combination than studies published between 2014 and 2019 (11.4%) (P = 0.043).

There was considerable variability in the mortality time frames reported in ICU-based septic shock trials. This variability may lead to under or overestimation of the problem, overlooking the effectiveness of the interventions studied, and further limiting the application of trials and their pooling in meta-analyses. A consensus regarding time frame reporting in septic shock trials is long overdue.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.

In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days. Antibiotic selection, dosing, and route were at the discretion of the treating team. We excluded patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding Staphylococcus aureus. The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points.

Across 74 hospitals in seven countries, 3608 patients underwent randomization and were included in the intention-to-treat analysis; 1814 patients were assigned to 7 days of antibiotic treatment, and 1794 to 14 days. At enrollment, 55.0% of patients were in the ICU and 45.0% were on hospital wards. Infections were acquired in the community (75.4%), hospital wards (13.4%) and ICUs (11.2%). Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died (difference, -1.6 percentage points [95.7% confidence interval {CI}, -4.0 to 0.8]), which showed the noninferiority of the shorter treatment duration. Patients were treated for longer than the assigned duration in 23.1% of the patients in the 7-day group and in 10.7% of the patients in the 14-day group. A per-protocol analysis also showed noninferiority (difference, -2.0 percentage points [95% CI, -4.5 to 0.6]). These findings were generally consistent across secondary clinical outcomes and across prespecified subgroups defined according to patient, pathogen, and syndrome characteristics.

Among hospitalized patients with bloodstream infection, antibiotic treatment for 7 days was noninferior to treatment for 14 days. (Funded by the Canadian Institutes of Health Research and others; BALANCE ClinicalTrials.gov number, NCT03005145.).

Procalcitonin (PCT) is a precursor of calcitonin, and its determination is used in daily clinical practice. It is a good marker for bacterial infection and can help diagnose sepsis. In this review, we summarize recent findings on the utility of PCT serum concentration measurement in noninfectious conditions. We found that elevated PCT levels may help in diagnosing or monitoring the course of cancer or inflammatory diseases. An increase was observed in emergency care such as acute renal failure or injuries, which may be promising in estimating the risk of complications. PCT has the potential to become a useful and clinically relevant marker beyond the assessment of bacterial infection. Due to its limited specificity, therapeutic decisions should be based on an individual evaluation of each clinical case.

To retrospectively observe procalcitonin (PCT) and antibiotic ordering practices in patients hospitalized with community-acquired pneumonia (CAP).

Retrospective, exact matched, multicenter cohort study from October 1, 2018 - March 31, 2023.

All hospitals across the Mayo Clinic Enterprise.

Adult patients with CAP, identified using pneumonia diagnosis codes and receipt of systemic antibiotics with an indication of "respiratory tract infection" within 48 hours of hospitalization.

PCT testing within the first 7 days of hospitalization was compared to non-PCT care (nPCT). The primary outcomes were treatment duration, antibiotic days of therapy (DOT), and length of stay (LOS).

15364 patients met inclusion criteria. PCT testing occurred in 42.4% (6515/15364) of encounters, totaling 8214 PCT results. 12880 unique patient encounters were matched 1:1, 6440 in each group. Treatment duration was longer in the PCT group compared to the nPCT group (5.1 vs 4.6 days, respectively, P < 0.001). Patients in the PCT group also received more DOT (8.6 vs 7.6 DOT, P < 0.001) and had a longer LOS (6.8 vs 5.9 days, P < 0.001), respectively. There was no difference in 30-day all-cause mortality or C. difficile infection between groups. In a sensitivity analysis of nPCT patients compared to those with a peak value <0.25 ng/mL (i.e. normal result) there was no difference in treatment duration (4.6 days nPCT vs 4.7 days normal PCT, P = 0.104) or LOS (5.9 days nPCT vs 6.0 days normal PCT, P = 0.134).

PCT testing in patients hospitalized with CAP was not associated with reduced antimicrobial utilization, LOS, or 30-day all-cause mortality.

Fever in cancer patients can occur for reasons other than bacterial infections. Without practical tools to distinguish actual infections, treatment delays may occur, reducing effectiveness and increasing antibiotic resistance. This study aimed to identify clinical features and procalcitonin (PCT) levels as indicators of bacterial infection in fevers among cancer patients.

This retrospective study enrolled 225 patients with cancer and fever at the Maharat Nakhon Ratchasima Hospital. Data on the clinical characteristics, laboratory results, and bacterial cultures were collected. Associations were analyzed using logistic regression, and the appropriate PCT cutoff point was determined using ROC analysis.

Of 225 cancer patients with fever, 54 (24%) had positive bacterial cultures, with Klebsiella pneumoniae being the most common pathogen. Significant clinical features included age (OR 1.06, 95% CI 1.01-1.12), increased heart rate (OR 1.05, 95% CI 1.02-1.08), and localizing symptoms (OR 7.62, 95% CI 2.49-22.70). Key laboratory findings were absolute neutrophil count (OR 1.15, 95% CI 1.03-1.28) and PCT level (OR 1.39, 95% CI 1.07-1.80). Appropriate PCT cutoff points for predicting bacterial infection were analyzed using various methods, resulting in values of 1.045, 0.546, 0.546, and 0.4025 ng/ml. The concordance probability and closest to the point (0,1) methods suggested a rounded cutoff point of 0.5 ng/ml, which provided a sensitivity of 61% and a specificity of 78%. The AUC for PCT was 0.731, indicating moderate accuracy.

Procalcitonin, in conjunction with clinical features, may be used to classify the cause of fever in cancer patients. Therefore, a clinically predictive model would be useful.

Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales. Children aged 72 h to 18 years who were admitted to hospital and were being treated with intravenous antibiotics for suspected or confirmed bacterial infection and who were expected to remain on intravenous antibiotics for more than 48 h were enrolled. Participants were randomly assigned (1:1) to receive either current clinical management alone (usual care group) or clinical management with the addition of a procalcitonin test guided algorithm (procalcitonin group). Participants were randomly assigned by minimisation, with site and age group (0-6 months, 6 months to 2 years, 2-5 years, and older than 5 years) as minimisation factors and a random element to reduce predictability. Participants were randomly assigned remotely using a secure 24 h web-based randomisation programme. The coprimary outcomes were duration of intravenous antibiotic use, assessed for superiority, and a composite safety measure, assessed for non-inferiority (non-inferiority margin 5%). The primary analysis sample for each coprimary endpoint included all randomly assigned participants with available outcome data. This trial is registered with the International Standard Randomised Controlled Trial Number registry, ISRCTN11369832.

Between June 11, 2018, and Oct 12, 2022, 15 282 children were screened for eligibility, 1949 of whom were randomly assigned to receive procalcitonin-guided antibiotic therapy (n=977) or usual care (n=972). The median intravenous antibiotic duration was 96·0 h (IQR 59·5-155·5) in the procalcitonin group and 99·7 h (61·2-153·8) in the usual care group (hazard ratio 0·96 [95% CI 0·87-1·05]). 78 (9%) of 917 participants in the procalcitonin group and 85 (9%) of 904 participants in the usual care group had at least one event covered by the composite safety outcome measure (estimated adjusted risk difference -0·81% [95% CI upper bound 1·11]).

In children with suspected or confirmed bacterial infection admitted to hospitals in England and Wales for intravenous antibiotic treatment of at least 48 h, the introduction of a procalcitonin-guided algorithm did not reduce duration of intravenous antibiotics treatment and is non-inferior to usual care for safety outcomes. Therefore, evidence does not support the use of procalcitonin-guided algorithms where robust effective paediatric antibiotic stewardship programmes are established.

National Institute for Health and Care Research.

The escalating resistance of microorganisms to antimicrobials poses a significant public health threat. Strategies that use biomarkers to guide antimicrobial therapy-most notably Procalcitonin (PCT) and C-reactive protein (CRP)-show promise in safely reducing patient antibiotic exposure. While CRP is less studied, it offers advantages such as lower cost and broader availability compared with PCT.

This randomised clinical trial aims to evaluate a novel algorithm for non-critically ill adult patients. The algorithm incorporates key clinical variables and CRP behaviour. It will be applied through a mobile application as a digital clinical decision support system. The primary goal will be to assess the algorithm's effectiveness in reducing treatment duration compared with standard care based on current guidelines, while ensuring patient safety by monitoring the occurrence of adverse events.

Only patients who agree to participate in the study after reading the informed consent form will be included. This project was submitted for consideration to the Research Ethics Committee of the Federal University of Minas Gerais (COEP-UFMG) and received approval (Approval Number: 5.905.290). Collection of clinical and laboratory data from 200 patients is expected, extracted from electronic medical records and laboratory systems, along with serum samples stored for potential future analyses. Data will be preserved using the Research Electronic Data Capture platform, and serum samples will be stored in a regulated biorepository at UFMG. Access will be controlled via credentials, with privacy protections and anonymisation prior to sharing, which will occur during scientific publications.

This trial was registered on ClinicalTrials.gov (NCT05841875) and was last updated on 5 December 2024 at 12:49.

Introduction: Nosocomial lower respiratory tract infections (nLRTIs), including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), remain significant challenges due to high mortality, morbidity, and healthcare costs. Implementing accurate and timely diagnostic strategies is pivotal for guiding optimized antimicrobial therapy and addressing the growing threat of antimicrobial resistance. Areas Covered: This review examines emerging microbiological diagnostic methods for nLRTIs. Although widely utilized, traditional culture-based techniques are hindered by prolonged processing times, limiting their clinical utility in timely decision-making. Advanced molecular tools, such as real-time PCR and multiplex PCR, allow rapid pathogen identification but are constrained by predefined panels. Metagenomic next-generation sequencing (mNGS) provides comprehensive pathogen detection and resistance profiling yet faces cost, complexity, and interpretation challenges. Non-invasive methods, including exhaled breath analysis using electronic nose (e-nose) technology, gene expression profiling, and biomarker detection, hold promise for rapid and bedside diagnostics but require further validation to establish clinical applicability. Expert Opinion: Integrating molecular, metagenomic, biomarker-associated, and traditional diagnostics is essential for overcoming limitations. Continued technological refinements and cost reductions will enable broader clinical implementation. These innovations promise to enhance diagnostic accuracy, facilitate targeted therapy, and improve patient outcomes while contributing to global efforts to mitigate antimicrobial resistance.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high morbidity and mortality rates. Guidelines that consider local epidemiologic data are fundamental for identifying optimal treatment strategies. However, Korea has no HAP/VAP guidelines. This study was conducted by a committee of nine experts from the Korean Academy of Tuberculosis and Respiratory Diseases Respiratory Infection Study Group using the results of Korean HAP/VAP epidemiologic studies. Eleven key questions for HAP/VAP diagnosis and treatment were addressed. The Convergence of Opinion on Suggestions and Evidence (CORE) process was used to derive suggestions, and evidence levels and recommendation grades were in accordance with the Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. Suggestions were made for the 11 key questions pertinent to diagnosis, biomarkers, antibiotics, and treatment strategies for adult patients with HAP/VAP. Using the CORE process and GRADE methodology, the committee generated a series of recommendations for HAP/VAP diagnosis and treatment in the Korean context.

Intensive care unit (ICU) clinicians stop antibiotics more often, with a negative infection: point-of-care test (PCR-POCT). Simulated cases of diagnostic uncertainty regarding infection resolution led clinicians to choose options such as procalcitonin (PCT) and/or PCR-POCTs +/- de-escalation to aid stop decisions. We hypothesised that a direct infection indicator, PCR-POCT, would influence stop judgements more than indirect PCT. Accordingly, we tested antibiotic-stop decisions when presented with a negative PCR-POCT despite borderline-positive PCT.

Observational prospective study.

ICU.

66 ICU clinicians from University hospitals.

Clinicians saw four scenarios of different clinico-biological trajectories: (1) clear improvement, (2) clear worsening, (3) discordant-clinically better/biologically worse and (4) discordant-clinically worse/biologically better. Participants gave an initial decision (stop/continue/continue-escalate/continue-de-escalate). Then PCR-POCT and/or PCT was offered (accept/decline). After a negative PCR-POCT and borderline-positive PCT result, a final antibiotic decision was taken.

Proportion of stop decisions before versus after test results per scenario. The association of the final decision with the clinician's change in confidence, willingness to request the biomarker(s) and the case trajectory was determined.

Fewer clinicians than expected stopped antibiotics versus baseline (36%, 94/264 vs 42%, 110/264, p=0.045). This was so in three of four scenarios, significantly less in the improvement (p<0.001) and the discordant clinically better scenario (p=0.024). PCT was requested more frequently than PCR-POCT (61% vs 53%, p<0.001). PCT requesters (vs declining) were significantly less inclined to stop antibiotics (p<0.001), while PCR-POCT requesting led to more stopping (p<0.001), before knowing the test results.

A negative PCR-POCT result did not increase clinicians' inclination to stop antibiotics when alongside a borderline-positive PCT. This reflects clinicians' natural risk aversion. PCT was more popular than PCR-POCT, but PCR-POCT was more likely to aid stop decisions.Their comparison, role, utility and selective deployment for influencing antibiotic-stop decisions more effectively require a large randomised controlled trial.