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

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. 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. 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.</p

Identification of activated B cells and antibody secreting cells in peripheral blood following Ty21a vaccination.

<p>PBMCs were collected from vaccinated or control (Ctrl) subjects at the indicated time points and analysis of different B cell populations was performed by flow cytometry. (A) Gating strategy for FACS analysis of activated B cells (ABC, blue) or antibody secreting cells (ASC, red). (B) Representative dot plots showing the proportions of ABC (CD20^hi CD71⁺) and ASC (CD20^- CD71⁺) in vaccinated and Ctrl individuals at the indicated time points. (C and D). Proportions of ABC and ASC in vaccinated and Ctrl individuals at the indicated time points. Dots represent individual values; bars indicate mean ± SEM. Statistical analysis was performed using one way ANOVA with Dunnett’s multiple comparison test for comparisons between individuals of the same group at different time points (pre- versus post-vaccination) (*, P< 0.05; **, P< 0.01).</p

Induction of anti-OmpC/F-specific porin antibodies in serum and stool after Ty21a vaccination.

<p>(A) IgM and (B) IgG, OmpC/F-specific antibody titers in serum samples from vaccinated subjects were analyzed by ELISA at the indicated time points after vaccination; participant numbers assigned according to increasing IgG reactivity. (C and D) Kinetics of anti-OmpC/F IgM (C) and IgG (D) antibody titers in vaccinated or control (Ctrl) individuals. Dots represent individual values; bars indicate mean ± SEM. (E) <i>S</i>. Typhi OmpC/F-specific IgA was determined from stool samples from vaccinated or Ctrl subjects by ELISA. Dots represent individual values; bars represent mean ± SEM. Statistical analysis was performed using one way ANOVA with Dunnett’s multiple comparison test for comparisons between individuals of the same group at different time points (pre- versus post-vaccination) (*, P< 0.05; **, P< 0.01 ***, P<0.001).</p

Activation profile of OmpC/F-specific CD4⁺ T cells after Ty21a vaccination.

<p>PBMCs were collected from vaccinated or control (Ctrl) subjects at the indicated time points. Activation of CD4⁺ T cells was assessed by flow cytometry after 24 h incubation with the indicated antigen. (A) Gating strategy for FACS analysis. (B) Representative dot plots showing the proportions of CD4⁺ CD40L⁺ T cells of Ctrl (upper panels) or vaccinated (lower panels) subjects after stimulation with <i>S</i>. Typhi OmpC/F porins or tetanus toxoid (TT). (C and D) Proportions of CD4⁺ CD40L⁺ T cells stimulated with TT (C) or OmpC/F (D) at the indicated time points. Dots represent individual values; bars represent mean ± SEM. (E) Representative dot plot showing IFN- γ and TNF-α production out of CD4⁺ CD40L⁺ cells after stimulation using medium or OmpC/F porins. (F) Proportions of OmpC/F-specific polyfunctional cells (IFN- γ ⁺ and/or TNF- α⁺) out of CD4⁺ CD40L⁺ T cells at indicated time points after vaccination in responder individuals. Statistical analysis in panels C and D was performed using one way ANOVA with Dunnett’s multiple comparison test for comparisons between individuals of the same group at different time points (pre- versus post-vaccination) or unpaired Student’s <i>t</i> test with Welch’s correction for comparison between Ctrl and vaccinated groups. Statistical analysis in panel F was performed using paired Student’s <i>t</i> test for comparison between individuals of the same group (Day 11 versus Day 60) (*, P< 0.05; **, P< 0.01).</p

Study design.

<p>CONSORT flow diagram indicating the number of participants that have been included and have completed the study.</p

Study demographic details.

<p>Study demographic details.</p

Data_Sheet_1_Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults—A randomized blinded controlled trial.docx

BackgroundEchinacea purpurea has clinical antiviral activity against respiratory viruses and modulates immune functions. In this study, we compared higher doses of new Echinacea formulations with conventional formulations at lower, preventive doses for therapy of respiratory tract infections (RTIs).MethodsIn this randomized, blinded, controlled trial, healthy adults (n = 409) were randomized between November 2018 and January 2019 to one of four Echinacea formulations, which were taken in case of an RTI for up to 10 days. New formulations A (lozenges) and B (spray) delivered an increased dose of 16,800 mg/d Echinacea extract during days 1–3 and 2,240–3,360 mg/d afterward; as controls, conventional formulations C (tablets) and D (drops) delivered a lower daily dose of 2,400 mg, usually taken for prevention. The primary endpoint was time to clinical remission of first RTI episodes based on the Kaplan–Meier analysis of patient-reported, investigator-confirmed, respiratory symptoms assessed for up to 10 days. In a sensitivity analysis, the mean time to remission beyond day 10 was calculated by extrapolating the treatment effects observed on days 7 to 10.ResultsA total of 246 participants (median age 32 years, 78% female participants) were treated for at least one RTI. Recovery by day 10 (complete absence of symptoms) was achieved in 56 and 44% of patients with the new and conventional formulations, respectively, showing a median time to recovery of 10 and 11 days, respectively (p = 0.10 in intention-to-treat analysis, p = 0.07 in per-protocol analysis). In the extrapolated sensitivity analysis, new formulations resulted in a significantly shorter mean time to remission (9.6 vs. 11.0 days, p ConclusionIn adults with acute RTI, new Echinacea formulations with higher doses resulted in faster viral clearance than conventional formulations in prophylactic dosages. The trend for faster clinical recovery was not significant by day 10 but became so upon extrapolation. A dose increase during acute respiratory symptoms might improve the clinical benefits of orally administered Echinacea formulations.Trial registrationThe study was registered in the Swiss National Clinical Trials Portal (SNCTP000003069) and on ClinicalTrials.gov (NTC03812900; URL https://clinicaltrials.gov/ct2/show/NCT03812900?cond=echinacea&draw=3&rank=14).</p

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Data spreadshee

Pneumococcal load distribution in NP samples from the South African cohort.

<p>Comparison between invasive (present in both NP and WB samples of the same patient; n = 36) and non-invasive serotypes (present in NP samples only; n = 145). Each plot represents a sample. The bold bars indicate the mean bacterial concentration for each group (Student's <i>t</i>-test, <i>P</i><0.001).</p

<i>S</i>. <i>pneumoniae</i> serotypes distribution determined by the 40 <i>S</i>. <i>pneumoniae</i> serotype real-time PCR typing assay (40-PCR).

<p>(A) in NP samples (n = 562) of patients from Cambodia (n = 149), France (n = 45), South Africa (n = 227), Mali (n = 86) and Brazil (n = 55), (B) in WB samples (n = 102) of patients from France (n = 5), Mali (n = 16) and South Africa (n = 81). Each column represents the cumulative number of patients for a given serotype.</p