Prognostic value of pretreatment procalcitonin and neutrophil-lymphocyte ratio in extensive-stage small-cell lung cancer.

BACKGROUND: To investigate the influence of pretreatment neutrophil-to-lymphocyte ratio (NLR) and procalcitonin (PCT) on progression-free survival (PFS) in extensive-stage small-cell lung cancer (SCLC) patients. METHOD: A total of 100 extensive-stage SCLC patients were enrolled in our study. Patients were stratified according to the median values of pretreatment NLR and PCT levels: low NLR group (NLR ≤3.17), high NLR group (NLR＞3.17), low PCT group (PCT ≤0.06; ng/ml), high PCT group (PCT＞0.06; ng/ml). The Kaplan-Meier method and multivariable Cox regression model were used to reveal the prognostic effects of pretreatment NLR and PCT on PFS. RESULTS: The median PFS of the total extensive-stage SCLC patients was 6.0 months. The median PFS of low pretreatment NLR group (NLR ≤3.17) was not significantly different from that of high pretreatment NLR group (6.2 months vs 5.8 months; p = .675). Patients with low pretreatment PCT (PCT ≤0.06; ng/ml) had significantly better PFS than patients with high pretreatment PCT (PCT＞0.06; ng/ml) (6.9 months vs 5.7 months; p = .043). With the multivariable Cox regression analysis, the response to first-line chemotherapy (p ≤ .001) and pretreatment PCT (HR = 0.516; 95%CI 0.326-0.817; p = .005) were identified as independent factors associated with PFS. CONCLUSION: Pretreatment PCT is an independent factor associated with PFS in extensive-stage SCLC patients treated with first-line chemotherapy, but pretreatment NLR reflects no significant prognostic value in our study.

Precisión diagnóstica de la procalcitonina para la bacteriemia en el servicio de urgencias: una revisión sistemática / Diagnostic accuracy of procalcitonin for bacteremia in the emergency department: a systematic review

Introducción. La obtención de hemocultivos (HC) se realiza en el 15% de los pacientes atendidos con sospecha de infección en los Servicios de Urgencias Hospitalarios (SUH) con unarentabilidad diagnóstica variable (2-20%). La mortalidad a 30 días de los pacientes con bacteriemia es dos o tres veces mayor que el resto con el mismo proceso. La procalcitonina (PCT) es un biomarcador que se ha utilizado como herramienta de ayuda en la predicción de bacteriemia en los SUH. El objetivo principal de esta revisión sistemática es investigar la precisión diagnóstica de la PCT para predecir bacteriemia verdadera en los pacientes adultos atendidos con sospecha clínica de infección enel SUH, así como identificar un valor específico de PCT como el más relevante desde el punto de vista diagnóstico de decisión clínica que pueda recomendarse para la toma de decisiones. Método. Se realiza una revisión sistemática siguiendo la normativa PRISMA en las bases de datos de PubMed, Web of Sciencie, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase y ClinicalTrials.gov desde enero de 2010 hasta 31 mayo 2023 sin restricción de idiomas y utilizando una combinación de términos MESH: “Bacteremia/Bacteraemia/Blood Stream Infection”, “Procalcitonin”, “Emergencies/Emergency/ Emergency Department” y “Adults”. Se incluyeron estudios de cohortes observacionales y parcialmente una revisión sistemática. No se realizaron técnicas de metaanálisis, pero los resultados se compararon narrativamente. Resultados. Se identificaron un total de 1.372 artículos de los cuales se analizaron finalmente 20 que cumplían los criterios de inclusión. Los estudios incluidos representan un total de 18.120 HC procesados con 2.877 bacteriemias (15,88%). Diez estudios fueron calificados de calidad alta, 9 moderada y 1 baja. El ABC-COR de todos los estudios se sitúa desde 0,68 (IC 95%: 0,59-0,77) hasta 0,98 (IC 95%: 0,97-0,99). . ...Conclusiones. ... . (AU)

Introduction. Obtaining blood cultures (HC) is performed in 15% of the patients treated with suspicion of infection in the Hospital Emergency Services (ED) with a variable diagnostic yield (2-20%). The 30-day mortality of patients with bacteremia is two or three times higher than the rest with the same process. Procalcitonin (PCT) is a biomarker that has been used as a tool to help predict bacteremia in HEDs. The main objective of this systematic review is to investigate the diagnostic accuracy of PCT in predicting true bacteraemia in adult patients treated with clinical suspicion of infection in the ED, as well as to identify a specific PCT value as the most relevant from the clinical decision diagnostic point of view that can be recommended for decision making. Method. A systematic review was performed following the PRISMA guidelines in the PubMed, Web of Science, EMBASE, Lilacs, Cochrane, Epistemonikos, Tripdatabase and ClinicalTrials. gov databases from January 2010 to May 31, 2023 without language restrictions and using a combination of MESH terms: “Bacteremia/ Bacteraemia/ Blood Stream Infection”, “Procalcitonin”, “Emergencies/ Emergency/ Emergency Department” and “Adults”. Observational cohort studies and partially an systematic review were included. No meta-analysis techniques were performed, but the results were compared narratively. Results. A total of 1,372 articles were identified, of which 20 that met the inclusion criteria were finally analyzed. The included studies represent a total of 18,120 processed HC with 2,877 bacteraemias (15.88%). Ten studies were rated as high, 9 moderate and 1 low quality. The AUC-COR of all the studies ranges from 0.68 (95% CI: 0.59-0.77) to 0.98 (95% CI: 0.97- 0.99). The PCT value >0.5 ng/ml is the most widely used and proposed in up to ten of the works included in this systematic review, whose estimated mean yield is an AUC-COR of 0.833. ...Conclusions. ... (AU)

Management of Ventilator-Associated Pneumonia: Guidelines.

Two recent major guidelines on diagnosis and treatment of ventilator-associated pneumonia (VAP) recommend consideration of local antibiotic resistance patterns and individual patient risks for resistant pathogens when formulating an initial empiric antibiotic regimen. One recommends against invasive diagnostic techniques with quantitative cultures to determine the cause of VAP; the other recommends either invasive or noninvasive techniques. Both guidelines recommend short-course therapy be used for most patients with VAP. Although neither guideline recommends use of procalcitonin as an adjunct to clinical judgment when diagnosing VAP, they differ with respect to use of serial procalcitonin to shorten the length of antibiotic treatment.

Safety of Procalcitonin Guided Early Discontinuation of Antibiotic Therapy among Children Receiving Cancer Chemotherapy and Having Low-Risk Febrile Neutropenia: A Randomized Feasibility Trial (ProFenC Study).

In low-risk febrile neutropenia (LR-FN), the safety of early discontinuation of empiric antibiotics without marrow recovery is not well established. This study aimed to evaluate the safety of procalcitonin (PCT) guided early discontinuation of antibiotics in LR-FN. In this trial, children with LR-FN with an afebrile period of at least 24 h, sterile blood culture, and negative/normalized PCT were randomized at 72 h of starting antibiotics into two groups: intervention arm and standard arm. The antibiotics were stopped in the intervention arm regardless of absolute neutrophil count (ANC), while in the standard arm, antibiotics were continued for at least 7 days or until recovery of ANC (>500/mm3). The primary objective was to determine the treatment failure rates, and the secondary objective was to compare the duration of antibiotics and all-cause mortality between the two arms. A total of 46 children with LR-FN were randomized to either the intervention arm (n = 23) or the standard arm (n = 23). Treatment failure was observed in 2/23 (8.7%) of patients in the intervention arm compared to 1/23 (4.3%) in the standard arm [RR: 2 (95% CI: 0.19-20.6); p = 0.55]. The median duration of antibiotics in the intervention arm and standard arm were 3 days vs 7 days (P= <0.001). There was no mortality in this study. PCT-guided early discontinuation of empirical antibiotics in LR-FN is feasible. There was no significant difference observed in treatment failure between the early discontinuation of antibiotics vs standard therapy. The total duration of antibiotic exposure was significantly lesser in the discontinuation arm. Further, larger multicenter studies are needed to confirm the finding of this study.

Efficacy of curcumin gel as an adjunct to scaling and root planing on salivary procalcitonin level in the treatment of patients with chronic periodontitis: a randomized controlled clinical trial.

THE AIM OF THE STUDY: To evaluate the effect of curcumin gel combined with scaling and root planing (SRP) on salivary procalcitonin in periodontitis treatment. MATERIALS AND METHODS: seventy patients were selected from the Department of Oral Medicine and Periodontology, Faculty of Dentistry, Mansoura University, and sixteen patients were excluded. Patients in groups II and III included stage II grade A periodontitis. The participants were classified into three groups: group I as a negative control group (individuals with healthy gingiva), group II (SRP) were treated with SRP, and group III (curcumin gel) which was applied weekly for four weeks after SRP. Clinical indices (plaque index (PI), gingival index (GI), clinical attachment level (CAL), and probing depth (PD)) and saliva samples for procalcitonin (PCT) assessment using an enzyme-linked immunosorbent assay (ELISA) test were collected and measured at both baselines and after six weeks. RESULTS: This randomized controlled clinical trial registered on ClinicalTrials.gov (NCT05667376) and first posted at 28/12/2022 included Fifty-four patients (20 male; 34 female). Regarding the age and sex distribution, there was no statistically significant difference between the three studied groups (p > 0.05). There was no significant statistical difference regarding PI, GI, PPD, and CAL between group II and group III at baseline p (> 0.05). However, there was a significant statistical difference regarding the clinical parameters at baseline of both group II and group III as compared to group I (p ≤ 0.05). At six weeks after treatment, group III showed greater improvement in the PI, PD, and CAL as opposed to group II (p ≤ 0.05). Regarding PCT values, at baseline, there wasn't a statistically significant difference between group II and group III (p > 0.05). However, there was a significant statistical difference between group II, group III, and group I (p ≤ 0.05). At six weeks after treatment, there was a statistically significant decrease in PCT levels of both group II and III (p ≤ 0.05). CONCLUSION: The application of curcumin gel was found to have a significant effect on all clinical indices as opposed to SRP.

The budget impact of procalcitonin-guided antibiotic stewardship compared to standard of care for patients with suspected sepsis admitted to the intensive care unit in Belgium.

In Belgium, antibiotic resistance leads to approximately 530 deaths with a €24 million financial burden annually. This study estimated the impact of procalcitonin-guided antibiotic stewardship programs to reduce antibiotic consumption versus standard of care in patients with suspected sepsis. A decision analytic tree modelled health and budget outcomes of procalcitonin-guided antibiotic stewardship programs for patients admitted to the intensive care unit (ICU). A literature search, a survey with local clinical experts, and national database searches were conducted to obtain model input parameters. The main outcomes were total budget impact per patient, reduction in number of antibiotic resistance cases, and cost per antibiotic day avoided. To evaluate the impact of parameter uncertainty on the source data, a deterministic sensitivity analysis was performed. A scenario analysis was conducted to investigate budget impact when including parameters for reduction in length of ICU stay and mechanical ventilation duration, in addition to base-case parameters. Based on model predictions, procalcitonin-guided antibiotic stewardship programs could reduce the number of antibiotic days by 66,868, resulting in €1.98 million savings towards antibiotic treatment in current clinical practice. Antibiotic resistance cases could decrease by 7.7% (6.1% vs 9.2%) in the procalcitonin-guided setting compared with standard of care. The base-case budget impact suggests an investment of €1.90 per patient. The sensitivity analysis showed uncertainty, as the main drivers can alter potential cost savings. The scenario analysis indicated a saving of €1,405 per patient, with a reduction of 1.5 days in the ICU (14.8 days vs 12.8 days), and a reduction of 22.7% (18.1-27.2%) in mechanical ventilation duration. The associated sensitivity analysis was shown to be robust in all parameters. Procalcitonin-guided antibiotic stewardship programs are associated with clinical benefits that positively influence antimicrobial resistance in Belgium. A small investment per patient to implement procalcitonin testing may lead to considerable cost savings.

Immunoaffinity LC-MS/MS Quantification of the Sepsis Biomarker Procalcitonin Using Magnetic- and Polystyrene-Bead Immobilized Polyclonal Antibodies.

Procalcitonin (PCT) is a biomarker for bacterial sepsis, and accurate quantification of PCT is critical for sepsis diagnosis and treatment. Immunological PCT quantification methods are routinely used in clinical laboratories, yet there is a need for harmonization of PCT quantification protocols. An orthogonal method to clinical immunological assays, such as LC-MS/MS, is required. In this study, a highly sensitive and robust immunoaffinity LC-MRM quantitative method for detecting procalcitonin in human serum has been developed. An initial comparison of immunocapture of PCT with a polyclonal anti-PCT antibody immobilized on polystyrene nanoparticles (Latex) and magnetic beads demonstrated superior performance with magnetic beads. Three tryptic PCT peptides from the N- and C-terminal regions of PCT were selected for LC-MS/MS quantification. For PCT quantification, an LLOQ of 0.25 ng/mL of PCT in human serum was achieved using a sample volume of 1 mL. The method's trueness and precision consistently lie within the 15% margin. The parallel measurement of three PCT peptides may allow future differentiation of intact PCT vs other PCT forms originating from potential degradation, processing, or polymorphisms. An established and validated LC-MRM-based quantification of PCT will be relevant as an orthogonal method for harmonization and standardization of clinical assays for PCT.

The potential clinical value of pairing procalcitonin and lung ultrasonography to guide antibiotic therapy in patients with community-acquired pneumonia: a narrative review.

INTRODUCTION: Lower respiratory tract infections (LRTIs) are among the most frequent infections and are prone to inappropriate antibiotic treatments. This results from a limited accuracy of diagnostic tools in identifying bacterial pneumonia. Lung ultrasound (LUS) has excellent sensitivity and specificity in diagnosing pneumonia. Additionally, elevated procalcitonin (PCT) levels correlate with an increased likelihood of bacterial infection. LUS and PCT appear to be complementary in identifying patients with bacterial pneumonia who are likely to benefit from antibiotics. AREAS COVERED: This narrative review aims to summarize the current evidence for LUS to diagnose pneumonia, for PCT to guide antibiotic therapy and the clinical value of pairing both tools. EXPERT OPINION: LUS has excellent diagnostic accuracy for pneumonia in different settings, regardless of the examiner's experience. PCT guidance safely reduces antibiotic prescription in LRTIs. The combination of both tools has demonstrated an enhanced accuracy in the diagnosis of pneumonia, including CAP in the ED and VAP in the ICU, but randomized controlled studies need to validate the clinical impact of a combined approach.

Respiratory multiplex PCR and procalcitonin to reduce antibiotic exposure in severe SARS-CoV-2 pneumonia: a multicentre randomized controlled trial.

OBJECTIVES: We aimed at assessing the efficacy and safety on antibiotic exposure of a strategy combining a respiratory multiplex PCR (mPCR) with enlarged panel and daily procalcitonin (PCT) measurements, as compared with a conventional strategy, in adult patients who were critically ill with laboratory-confirmed SARS-CoV-2 pneumonia. METHODS: This multicentre, parallel-group, open-label, randomized controlled trial enrolled patients admitted to 13 intensive care units (ICUs) in France. Patients were assigned (1:1) to the control strategy, in which antibiotic streamlining remained at the discretion of the physicians, or interventional strategy, consisting of using mPCR and daily PCT measurements within the first 7 days of randomization to streamline initial antibiotic therapy, with antibiotic continuation encouraged when PCT was >1 ng/mL and discouraged if < 1 ng/mL or decreased by 80% from baseline. All patients underwent conventional microbiological tests and cultures. The primary end point was antibiotic-free days at day 28. RESULTS: Between April 20th and November 23rd 2020, 194 patients were randomized, of whom 191 were retained in the intention-to-treat analysis. Respiratory bacterial co-infection was detected in 48.4% (45/93) and 21.4% (21/98) in the interventional and control group, respectively. The number of antibiotic-free days was 12.0 (0.0; 25.0) and 14.0 (0.0; 24.0) days, respectively (difference, -2.0, (95% CI, -10.6 to 6.6), p=0.89). Superinfection rates were high (51.6% and 48.5%, respectively). Mortality rates and ICU lengths of stay did not differ between groups. DISCUSSION: In severe SARS-CoV-2 pneumonia, the mPCR/PCT algorithm strategy did not affect 28-day antibiotics exposure nor the major clinical outcomes, as compared with routine practice.

How to best use procalcitonin to diagnose infections and manage antibiotic treatment.

OBJECTIVES: Procalcitonin (PCT) is a host-response biomarker that has shown clinical value for assessing the likelihood of bacterial infections and guiding antibiotic treatment. Identifying situations where PCT can improve clinical care is therefore highly important. METHODS: The aim of this narrative review is to discuss strategies for the usage and integration of PCT into clinical routine, based on the most recent clinical evidence. RESULTS: Although PCT should not be viewed as a traditional diagnostic marker, it can help differentiate bacterial from non-bacterial infections and inflammation states - particularly in respiratory illness. Several trials have found that PCT-guided antibiotic stewardship reduces antibiotic exposure and associated side-effects among patients with respiratory infection and sepsis. Studies have demonstrated that patient-specific decisions regarding antibiotic usage is highly complex. Factors to consider include: the clinical situation (with a focus on the pretest probability for bacterial infection), the acuity and severity of presentation, as well as PCT test results. Low PCT levels help rule out bacterial infection in patients with both low pretest probability for bacterial infection and low-risk general condition. In high-risk individuals and/or high pretest probability for infection, empiric antibiotic treatment is mandatory. Subsequent monitoring of PCT helps track the resolution of infection and guide decisions regarding early termination of antibiotic treatment. CONCLUSIONS: PCT possesses high potential to improve decision-making regarding antibiotic treatment - when combined with careful patient assessment, evidence-based clinical algorithms, and continuous notification and regular feedback from all antibiotic stewardship stakeholders. Medical Journals such as Clinical Chemistry and Laboratory Medicine (CCLM) have played a critical role in reviewing and dissemination the high-quality evidence about assays for PCT measurement, observational research regarding association with outcomes among different populations, and interventional research proofing its effectiveness for patient care.

Use of biomarkers to individualize antimicrobial therapy duration: a narrative review.

BACKGROUND: Reducing the overuse of antimicrobials is imperative for the sake of minimizing antimicrobial-associated adverse effects, optimizing resource utilization, and curtailing the rise in multidrug-resistant organisms. Biomarkers reflect the host responses to infection and may assist with minimizing unnecessary antimicrobial usage. OBJECTIVES: To review the literature pertaining to the performance of biomarkers specifically used to guide the duration of antimicrobial therapy (AMT). SOURCES: Randomized controlled trials, observational studies, and meta-analyses assessing biomarker-guided approaches to AMT decision-making and their impact on the duration of therapy were reviewed. CONTENT: Several randomized controlled trials and real-world observational studies have shown that a procalcitonin (PCT)-guided strategy can help clinicians individualize the duration of AMT, particularly among non-critically ill patients hospitalized with suspected respiratory tract infections when using a PCT cut-off value of <0.25 µg/L and critically ill patients with respiratory tract infections or undifferentiated sepsis when using a PCT cut-off value of <0.5 µg/L or ≥80% decline in the peak level. C-reactive protein is a non-specific marker of inflammation that may also assist with an early discontinuation of AMT; however, data are limited. Haematological biomarkers are prone to variance between individuals and are often influenced by medications and non-infectious conditions, making them less reliable for the purposes of AMT decision-making. Novel biomarkers such as multi-protein signatures and host gene expression tests have shown promise as tools to better differentiate between bacterial and non-bacterial infections; clinical studies are needed to determine whether they can be used to help optimize the duration of AMT. IMPLICATIONS: Studies have demonstrated that a PCT-guided strategy, when utilized appropriately, can help guide clinicians to individualize and often reduce the duration of AMT, especially in patients hospitalized with respiratory tract infections and those admitted to the intensive care unit with suspected respiratory tract infections or sepsis. The impact of utilizing other biomarkers is less clear and requires further study.

PROCALCITONIN GUIDED ANTIBIOTIC STEWARDSHIP: A BALKAN EXPERT CONSENSUS STATEMENT.

Sepsis as a consequence of infection is a frequent cause of death among critically ill patients. The most common sites of infection are lover respiratory tract, abdominal, urinary tract and catheter-associated blood stream infections. Early empiric, broad-spectrum therapy in those with severe sepsis and/or shock with the aim of reducing mortality may lead to antibiotic overuse, resistance and increased costs. Among numerous serum biomarkers, procalcitonin (PCT) has proved to be one of the most reliable ones in the diagnosis of sepsis. An important means of limiting antibiotic resistance is the antibiotic stewardship program, especially in intensive care units with critically ill patients and prevalence of multiple drug-resistant pathogens. The PCT-guided antibiotic stewardship was first started in Western Europe and Asia-Pacific countries, as well as in the United States. Considering that this method has proven to be effective in reducing antibiotic consumption while improving clinical outcome, a group of experts from the Balkan region decided to make their own recommendations and PCT protocol. When creating this protocol for initiation and duration of antibiotic treatment, they especially reviewed the literature for lower respiratory tract infection and sepsis. In the protocol, they have included the severity of illness, clinical assessment, and PCT levels. Developing a consensus on the clinical algorithm by eminent experts/specialists in various fields of medicine should enable clinicians to use PCT for initiation of antibiotic therapy and monitoring PCT to stop antibiotics earlier. It is crucial that the PCT-guided algorithm becomes an integral part of institutional stewardship program.

Procalcitonin for antimicrobial stewardship among cancer patients admitted with COVID-19.

Background: Procalcitonin (PCT) has been used to guide antibiotic therapy in bacterial infections. We aimed to determine the role of PCT in decreasing the duration of empiric antibiotic therapy among cancer patients admitted with COVID-19. Methods: This retrospective study included cancer patients admitted to our institution for COVID-19 between March 1, 2020, and June 28, 2021, with a PCT test done within 72 hr after admission. Patients were divided into two groups: PCT <0.25 ng/ml and PCT ≥0.25 ng/ml. We assessed pertinent cultures, antibacterial use, and duration of empiric antibacterial therapy. Results: The study included 530 patients (median age, 62 years [range, 13-91]). All the patients had ≥1 culture test within 7 days following admission. Patients with PCT <0.25 ng/ml were less likely to have a positive culture than were those with PCT ≥0.25 ng/ml (6% [20/358] vs. 17% [30/172]; p<0.0001). PCT <0.25 ng/ml had a high negative predictive value for bacteremia and 30 day mortality. Patients with PCT <0.25 ng/ml were less likely to receive intravenous (IV) antibiotics for >72 hr than were patients with PCT ≥0.25 ng/ml (45% [162/358] vs. 69% [119/172]; p<0.0001). Among patients with PCT <0.25 ng/ml and negative cultures, 30 day mortality was similar between those who received IV antibiotics for ≥72 hr and those who received IV antibiotics for shorter durations (2% [2/111] vs. 3% [5/176], p=0.71). Conclusions: Among cancer patients with COVID-19, PCT level <0.25 ng/ml is associated with lower likelihood of bacterial co-infection and greater likelihood of a shorter antibiotic course. In patients with PCT level <0.25 ng/ml and negative cultures, an antibiotic course of >72 hr may not be necessary. PCT could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19. Funding: This research was supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports MD Anderson Cancer Center's Clinical Trials Office.

Biomarkers as point-of-care tests to guide prescription of antibiotics in people with acute respiratory infections in primary care.

BACKGROUND: Acute respiratory infections (ARIs) are by far the most common reason for prescribing an antibiotic in primary care, even though the majority of ARIs are of viral or non-severe bacterial aetiology. It follows that in many cases antibiotic use will not be beneficial to a patient's recovery but may expose them to potential side effects. Furthermore, limiting unnecessary antibiotic use is a key factor in controlling antibiotic resistance. One strategy to reduce antibiotic use in primary care is point-of-care biomarkers. A point-of-care biomarker (test) of inflammation identifies part of the acute phase response to tissue injury regardless of the aetiology (infection, trauma, or inflammation) and may be used as a surrogate marker of infection, potentially assisting the physician in the clinical decision whether to use an antibiotic to treat ARIs. Biomarkers may guide antibiotic prescription by ruling out a serious bacterial infection and help identify patients in whom no benefit from antibiotic treatment can be anticipated. This is an update of a Cochrane Review first published in 2014. OBJECTIVES: To assess the benefits and harms of point-of-care biomarker tests of inflammation to guide antibiotic treatment in people presenting with symptoms of acute respiratory infections in primary care settings regardless of patient age. SEARCH METHODS: We searched CENTRAL (2022, Issue 6), MEDLINE (1946 to 14 June 2022), Embase (1974 to 14 June 2022), CINAHL (1981 to 14 June 2022), Web of Science (1955 to 14 June 2022), and LILACS (1982 to 14 June 2022). We also searched three trial registries (10 December 2021) for completed and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in primary care patients with ARIs that compared the use of point-of-care biomarkers with standard care. We included trials that randomised individual participants, as well as trials that randomised clusters of patients (cluster-RCTs). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on the following primary outcomes: number of participants given an antibiotic prescription at index consultation and within 28 days follow-up; participant recovery within seven days follow-up; and total mortality within 28 days follow-up. We assessed risk of bias using the Cochrane risk of bias tool and the certainty of the evidence using GRADE. We used random-effects meta-analyses when feasible. We further analysed results with considerable heterogeneity in prespecified subgroups of individual and cluster-RCTs. MAIN RESULTS: We included seven new trials in this update, for a total of 13 included trials. Twelve trials (10,218 participants in total, 2335 of which were children) evaluated a C-reactive protein point-of-care test, and one trial (317 adult participants) evaluated a procalcitonin point-of-care test. The studies were conducted in Europe, Russia, and Asia. Overall, the included trials had a low or unclear risk of bias. However all studies were open-labelled, thereby introducing high risk of bias due to lack of blinding. The use of C-reactive protein point-of-care tests to guide antibiotic prescription likely reduces the number of participants given an antibiotic prescription, from 516 prescriptions of antibiotics per 1000 participants in the control group to 397 prescriptions of antibiotics per 1000 participants in the intervention group (risk ratio (RR) 0.77, 95% confidence interval (CI) 0.69 to 0.86; 12 trials, 10,218 participants; I² = 79%; moderate-certainty evidence).  Overall, use of C-reactive protein tests also reduce the number of participants given an antibiotic prescription within 28 days follow-up (664 prescriptions of antibiotics per 1000 participants in the control group versus 538 prescriptions of antibiotics per 1000 participants in the intervention group) (RR 0.81, 95% CI 0.76 to 0.86; 7 trials, 5091 participants; I² = 29; high-certainty evidence). The prescription of antibiotics as guided by C-reactive protein tests likely does not reduce the number of participants recovered, within seven or 28 days follow-up (567 participants recovered within seven days follow-up per 1000 participants in the control group versus 584 participants recovered within seven days follow-up per 1000 participants in the intervention group) (recovery within seven days follow-up: RR 1.03, 95% CI 0.96 to 1.12; I² = 0%; moderate-certainty evidence) (recovery within 28 days follow-up: RR 1.02, 95% CI 0.79 to 1.32; I² = 0%; moderate-certainty evidence). The use of C-reactive protein tests may not increase total mortality within 28 days follow-up, from 1 death per 1000 participants in the control group to 0 deaths per 1000 participants in the intervention group (RR 0.53, 95% CI 0.10 to 2.92; I² = 0%; low-certainty evidence). We are uncertain as to whether procalcitonin affects any of the primary or secondary outcomes because there were few participants, thereby limiting the certainty of evidence. We assessed the certainty of the evidence as moderate to high according to GRADE for the primary outcomes for C-reactive protein test, except for mortality, as there were very few deaths, thereby limiting the certainty of the evidence. AUTHORS' CONCLUSIONS: The use of C-reactive protein point-of-care tests as an adjunct to standard care likely reduces the number of participants given an antibiotic prescription in primary care patients who present with symptoms of acute respiratory infection. The use of C-reactive protein point-of-care tests likely does not affect recovery rates. It is unlikely that further research will substantially change our conclusion regarding the reduction in number of participants given an antibiotic prescription, although the size of the estimated effect may change.  The use of C-reactive protein point-of-care tests may not increase mortality within 28 days follow-up, but there were very few events. Studies that recorded deaths and hospital admissions were performed in children from low- and middle-income countries and older adults with comorbidities.  Future studies should focus on children, immunocompromised individuals, and people aged 80 years and above with comorbidities. More studies evaluating procalcitonin and potential new biomarkers as point-of-care tests used in primary care to guide antibiotic prescription are needed.  Furthermore, studies are needed to validate C-reactive protein decision algorithms, with a specific focus on potential age group differences.

[Effect of Tetrastigma hemsleyanum on sepsis and mechanism based on network pharmacology and experimental verification].

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1ß, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1ß, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lß, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.

PAnTher Cub: procalcitonin-guided antibiotic therapy for febrile neutropenia in children and young people with cancer - a single-arm pilot study.

BACKGROUND: Febrile neutropenia (FN) is a common complication of cancer treatment in children and young people, and many episodes are over-treated. Procalcitonin, may be an appropriate tool to guide the stopping of antibiotics in those at low risk of serious bacterial infection. Supportive care trials in this population have proven to be difficult to undertake. This single-arm pilot study aimed to evaluate whether a study using a procalcitonin-guided stopping-rule for antibiotics in paediatric FN is possible. METHODS: Daily procalcitonin levels were performed during episodes of FN and clear guidance given for antibiotic discontinuation. Episode data and quantitative feasibility data were collected alongside interviews with professionals and ethnographic observations. Analysis was descriptive. RESULTS: Of 32 patients and families approached, 28 patients consented, and 13 had febrile neutropenia. In total, 16 episodes were included in the study. All relevant FN episodes had data captured, with adequate data collection. There were no significant safety events. In 4/8 (50%) of episodes without clear microbiologically documented or clinical infection, antibiotics were reduced in duration or in spectrum. Interviews with professionals revealed the importance of the research, the value of key individuals in the study team, particular challenges of this protocol and suggestions for study improvements. CONCLUSIONS: Studies to evaluate procalcitonin-guided approaches to stopping antibiotics in paediatric FN are possible.

The Role of Procalcitonin in Predicting Necessity of Antivenom Administration and Clinical Severity in Snake Bites.

One of the most important steps for preventing deaths due to snake bites is to administer snake antivenom to the eligible patients in a swift manner. In our study, we aimed to investigate whether procalcitonin is useful for predicting the clinical severity and the necessity of antivenom therapy at the early stages in patients presenting with snake bite. A total of 78 patients over the age of 18 who applied to the emergency department within the first 24 hours were included in this retrospective cross-sectional study. Age and sex of patients, severity of snake bites, total antivenom vials administered, observation periods and outcomes were recorded. Patients were graded according to their clinical severity after the snake bite. Procalcitonin, complete blood count and biochemical parameters of the patients were recorded. According to their clinical severity, the patients' grades were as follows: 21 (26.9%) patients were grade 0; 21 patients (26.9%) were grade 1; 16 patients (20.5%) were grade 2; and 20 patients (25.6%) were grade 3. Snake antivenom was administered to 57 (73.1%) patients. There was a statistically significant difference between procalcitonin levels of patients in respect to their grade (P < 0.001). Sensitivity and specificity of procalcitonin levels of 13.45 and above were 100% and 100% respectively, both for the need of antivenom administration and for the blister formation in the patients. According to our study, we believe that elevated procalcitonin levels should alert the clinicians for possible blister formation, higher clinical severity, and increased requirement for antivenom administration.

Antibiotic practice patterns with procalcitonin levels in patients with acute lower respiratory tract infection.

OBJECTIVES: Procalcitonin (PCT) testing is FDA approved to guide antibiotic therapy in patients with lower respiratory tract infection (LRTI). However, its utilization and impact on real-world antibiotic prescribing behavior are unknown. We investigated the rate of PCT testing to evaluate an association between initial PCT level and antibiotic prescription patterns for patients with suspected LRTI within a large integrated health system. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study (January 1, 2016, through December 31, 2017) was performed in patients 18 years and older who were hospitalized with LRTI and had a PCT measurement. Antibiotic changes were noted before and 36 hours after initial PCT results. Antibiotic concordance was determined using a PCT cutoff value of 0.25 mcg/L. Concordance was defined as (1) patients received antibiotics after a PCT of at least 0.25 mcg/L resulted or (2) antibiotics were withheld after a PCT less than 0.25 mcg/L resulted. RESULTS: PCT testing occurred in 18% of hospitalized patients with LRTI. Among 1606 patients, antibiotic concordance with PCT results was 55%. Among the discordant population, 77% of patients received antibiotics in the setting of a low PCT level compared with 23% who did not receive antibiotics at a high PCT level. There were no statistical differences between LRTI types between patients with PCT-discordant and PCT-concordant care. CONCLUSIONS: Within a real-world environment of patients hospitalized with LRTI, PCT testing was low and the PCT levels did not appear to influence antibiotic prescribing behavior. Our findings suggest that clinicians continue to prioritize clinical judgment over initial PCT levels when prescribing antibiotics for suspected LRTIs.

Antibiotics duration guided by biomarkers in hospitalized adult patients; a systematic review and meta-analysis.

BACKGROUND: The impact of using biomarkers to determine the duration of antibiotics therapy has been studied. However, the question remains in clinical practice whether these biomarkers are reliable to determine antibiotics duration. AIM: This study is aimed to see if employing c-reactive protein (CRP) and Procalcitonin (PCT) to determine the duration of antibiotic use in hospitalized adult patients is both effective and safe. METHODS: Search databases that were used are Pubmed, Cochrane library, and Embase. Only randomized controlled trials conducted in adult (≥18 years) hospitalized patients were included. The primary outcome assessed is the duration of antibiotics used. Secondary outcomes assessed are the length of hospitalization, recurrence of infection/rehospitalization, in-hospital mortality, and 28-day mortality. RESULTS: For the primary outcome, which is the duration of antibiotics use, PCT guided therapy significantly decreased the duration of antibiotics used in both sepsis and respiratory tract infections. For the secondary outcomes, there was no statistically significant difference in the outcomes of length of hospitalization, recurrence of infection/rehospitalization, and 28-day mortality. However, in-hospital mortality was significantly reduced (p = .02). CRP guided reduced antibiotic use duration, but there was no statistically significant difference in other outcomes including length of hospital stay, 28-day mortality, and infection recurrence. CONCLUSION: Procalcitonin-guided antibiotics therapy was shown to be effective and safe in the reduction of antibiotics duration in both sepsis and respiratory tract infections. More research is needed to prove that CRP-guided therapy is safe and effective to determine the antibiotic duration in adult hospitalized patients. REVIEW REGISTRATION NUMBER: PROSPERO (CRD42021264167).

Biomarkers in Chronic Obstructive Pulmonary Disease: Emerging Roles of Eosinophils and Procalcitonin.

Antibiotics can improve the prognosis in patients with exacerbation of chronic obstructive pulmonary disease. However, the overuse of antibiotics can carry serious adverse effects for patients (gastrointestinal infections) and for society (bacterial resistance). Likewise, systemic corticosteroids may also help these patients, but also carries severe adverse effects like osteoporosis, muscle loss, and diabetes, in many patients. Whenever safe methods exist to reduce these two treatment modalities, they should be implemented. The blood biomarkers procalcitonin and the fraction of leukocytes known as eosinophil granulocytes have been proven in randomized controlled trials (RCTs), to effectively, significantly, and substantially assist in reducing the use of these two potent, yet toxic medication types. In this review, the background and main clinical results are discussed, explaining the rationale for biomarker-guided clinical decisions. Also, the main expected effects, their sizes, and importantly the limitations to such a strategy are described. Clinical evidence is prioritized with main weight on RCTs and meta-analyses of these and regarding outcomes, and focus is set on the safety of such a biomarker-guided strategy, as well as the effects on medicine reduction. In an epoch of increasing demands to physicians from patients and politicians to cure and reduce symptoms, the Hippocratic phrase of "primum non nocere" or "first, do no harm" seems more than ever of contemporary importance.