The clinical value of mNGS of bronchoalveolar lavage fluid versus traditional microbiological tests for pathogen identification and prognosis of severe pneumonia (NT-BALF):study protocol for a prospective multi-center randomized clinical trial.

BACKGROUND: Early, rapid, and accurate pathogen diagnosis can help clinicians select targeted treatment options, thus improving prognosis and reducing mortality rates of severe pneumonia. Metagenomic next-generation sequencing (mNGS) has a higher sensitivity and broader pathogen spectrum than traditional microbiological tests. However, the effects of mNGS-based antimicrobial treatment procedures on clinical outcomes and cost-effectiveness in patients with severe pneumonia have not been evaluated. METHODS: This is a regional, multi-center, open, prospective, randomized controlled trial to evaluate that whether the combination of mNGS and traditional testing methods could decrease 28-day call-cause mortality with moderate cost-effectiveness. A total of 192 patients with severe pneumonia will be recruited from four large tertiary hospitals in China. Bronchoalveolar lavage fluid will be obtained in all patients and randomly assigned to the study group (mNGS combined with traditional microbiological tests) or the control group (traditional microbiological tests only) in a 1:1 ratio. Individualized antimicrobial treatment and strategy will be selected according to the analysis results. The primary outcome is 28-day all-cause mortality. The secondary outcomes are ICU and hospital length of stay (LOS), ventilator-free days and ICU-free days, consistency between mNGS and traditional microbiological tests, detective rate of mNGS and traditional microbiological tests, turn-out time, time from group allocation to start of treatment, duration of vasopressor support, types and duration of anti-infective regimens, source of drug-resistant bacteria or fungi, and ICU cost. DISCUSSION: The clinical benefits of mNGS are potentially significant, but its limitations should also be considered. TRIAL REGISTRATION: ChineseClinicalTrialRegistry.org, ChiCTR2300076853. Registered on 22 October 2023.

Value-based comparison of ambulatory children with respiratory diseases in an emergency department and a walk-in clinic: a retrospective cohort study in Québec, Canada.

OBJECTIVE: To compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases. DESIGN: A retrospective cohort study. SETTING: This study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays. PARTICIPANTS: Inclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients. RESULTS: We included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)). CONCLUSIONS: The incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.

Antibiotic Prescribing Patterns for Urinary Tract Infections and Pneumonia by Prescriber Type and Specialty in Nursing Home Care, 2016-2018.

OBJECTIVE: To identify whether differences in antibiotic prescribing practices by prescriber type and specialization in nursing home (NH) care exist for urinary tract infection (UTI) and pneumonia. DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: This national study included antibiotic dispensings to traditional Medicare beneficiaries aged ≥65 years with UTI or pneumonia infections residing long-term (≥100 days) in US NHs between 2016 and 2018. METHODS: Minimum Data Set assessment data were linked to Medicare data [Part D prescription drug, inpatient hospital (MedPAR), prescriber characteristics, and enrollment]. We compared antibiotic prescribing patterns by prescriber type [physician vs advanced practice practitioner (AP)] and NH specialization (≥90% vs <90% of all associated medication dispensings to NH residents). Antibiotic dispensing measures included the total number of dispensings and duration of therapy (median number of days supplied) by antibiotic class. RESULTS: There were 264,735 antibiotic dispensings prescribed by 32,437 prescribers for 140,360 residents in 14,035 NHs. NH specialists were less likely to prescribe fluoroquinolones for UTI (22.9% NH specialist physician, 23.9% non-NH specialist physician, 21.3% NH specialist AP, 24.2% non-NH specialist AP), but more likely to prescribe fluoroquinolones for pneumonia (38.9%, 37.8%, 38.8%, 37.3%, respectively). Over time, NH specialists reduced fluoroquinolone prescribing for pneumonia to a greater extent than non-NH specialists. The duration of therapy was similar across prescriber groups for UTI, but longer among non-NH specialist APs for several antibiotic classes for pneumonia, including tetracyclines, glycopeptides and lipoglycopeptides, and metronidazole. CONCLUSIONS AND IMPLICATIONS: There were differences in antibiotic prescribing patterns by prescriber type and specialization in NH care between 2016 and 2018. Understanding how antibiotic prescribing differs based on prescriber characteristics is essential to inform antibiotic stewardship efforts. Tailoring antibiotic stewardship efforts to prescribers by NH specialization is rational given differences in antibiotic prescribing patterns based on NH specialization.

Population pharmacokinetics and dose optimization of levofloxacin in elderly patients with pneumonia.

AIMS: Levofloxacin is a quinolone antibiotic with a broad antibacterial spectrum. It is frequently used in elderly patients with pneumonia. The pharmacokinetic profile of elderly patients changes with age, but data on the pharmacokinetics of levofloxacin in these patients are limited. The aim of this study was to establish a population pharmacokinetic model of levofloxacin in elderly patients with pneumonia and to optimize individualized dosing regimens based on this newly developed model. METHODS: This is a prospective, open-label pharmacokinetic study in elderly patients with pneumonia. Blood samples were collected using an opportunistic approach. The plasma concentrations of levofloxacin were determined by high-performance liquid chromatography. A population pharmacokinetic model was established using nonlinear mixed-effect model software. Monte Carlo simulations were used for dose simulation and dose optimization. RESULTS: Data from 51 elderly patients with pneumonia were used for the population pharmacokinetic analysis. A one-compartment model with first-order elimination was most suitable for describing the data, and the estimated glomerular filtration rate was the only covariate that had a significant impact on the model. The final model estimated that the mean clearance of levofloxacin in elderly patients with pneumonia was 5.26 L/h. Monte Carlo simulation results showed that the optimal dosing regimen for levofloxacin was 750 mg once a day in elderly patients with pneumonia, with a minimum inhibitory concentration of 2 mg/L. CONCLUSIONS: The population pharmacokinetic model of levofloxacin in elderly patients with pneumonia was established, and the dose optimization of levofloxacin was completed through Monte Carlo simulation.

Antibiotic prescription for outpatients with influenza and subsequent hospitalisation: A cohort study using insurance data.

Background: Whether prophylactic administration of antibiotics to patients with influenza reduces the hospitalisation risk is unknown. We aimed to examine the association between antibiotic prescription in outpatients with influenza infection and subsequent hospitalisation. Methods: We conducted a cohort study using health insurance records of Japanese clinic and hospital visits between 2012 and 2016. Participants were outpatients (age, 0-74 years) with confirmed influenza infection who were prescribed anti-influenza medicine. The primary outcomes were the hospitalisation risk from all causes and pneumonia and the duration of hospitalisation due to pneumonia. Results: We analysed 903,104 outpatient records with 2469 hospitalisations. The risk of hospitalisation was greater in outpatients prescribed anti-influenza medicine plus antibiotics (0.31% for all causes and 0.18% for pneumonia) than in those prescribed anti-influenza medicine only (0.27% and 0.17%, respectively). However, the risk of hospitalisation was significantly lower in patients prescribed peramivir and antibiotics than in those prescribed peramivir only. Patients who received add-on antibiotics had a significantly longer hospital stay (4.12 days) than those who received anti-influenza medicine only (3.77 days). In all age groups, the hospitalisation risk from pneumonia tended to be greater in those who received antibiotics than in those prescribed anti-influenza medicine only. However, among older patients (65-74 years), those provided add-on antibiotics had an average 5.24-day shorter hospitalisation due to pneumonia than those provided anti-influenza medicine only (not significant). Conclusions: In outpatient cases of influenza, patients who are prescribed antibiotics added to antiviral medicines have a higher risk of hospitalisation and longer duration of hospitalisation due to pneumonia.

Population pharmacokinetics and model-based dosing optimization of teicoplanin in elderly critically ill patients with pneumonia.

PURPOSE: To evaluate the population pharmacokinetics and pharmacodynamics of teicoplanin in elderly critically ill patients with pneumonia for optimal dosages. METHODS: Fifteen critically ill patients (9 men) ≥ 60 years received teicoplanin 6 mg/kg for three doses followed by standard maintenance doses (6 mg/kg q24h) with renal dosing adjustment. Serial plasma samples from all patients were analyzed simultaneously by population pharmacokinetic modeling using NONMEM. Probability of target attainment (PTA) was calculated through Monte Carlo simulations for various dosing regimens to achieve adequate systemic exposures. RESULTS: The median (interquartile range, IQR) age, body mass index, and creatinine clearance (CrCl) was 75 (64-78) years, 22.5 (20.8-25.4) kg/m2, and 64 (47-106) mL/min, respectively. The median (IQR) peak and trough concentration was 46.5 (42.7-51.0) and 8.7 (7.2-9.5) mg/L. The population pharmacokinetic model showed slower clearance (CL) and larger peripheral volume of distribution (V2) in patients with reduced CrCl: CL (L/h) = 0.629 × (CrCl/64)0.656, V2 (L) = 55.7 × (CrCl/64)-0.665. Model-based simulations showed PTAs ≥85% only for higher-dose regimens (12 mg/kg) up to an MIC of 0.5 mg/L. CONCLUSIONS: Standard teicoplanin dosages for pneumonia may provide inadequate systemic exposures in elderly critically ill patients. High-dose regimens should be considered as empiric therapy or for less susceptible pathogens.

Healthcare Resource Utilization, Cost and Clinical Outcomes in Patients Diagnosed with COPD Initiating Tiotropium Bromide/Olodaterol versus Fluticasone Furoate/Umeclidinium/Vilanterol Based on Exacerbation History.

Background: ATS and GOLD guidelines recommend treating low-exacerbation risk COPD patients with dual (LAMA/LABA) agents and reserving triple therapy (TT; LAMA/LABA and inhaled corticosteroids [ICS]) for severe cases with higher-exacerbation risk. However, TT often is prescribed across the COPD spectrum. This study compared COPD exacerbations, pneumonia diagnosis, healthcare resource utilization, and costs for patients initiating tiotropium bromide/olodaterol (TIO/OLO) and a TT, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), stratified by exacerbation history. Methods: COPD patients who initiated TIO/OLO or FF/UMEC/VI between 06/01/2015-11/30/2019 (index date=first pharmacy fill-date with ≥30 consecutive treatment days) were identified from the Optum Research Database. Patients were ≥40 years old and continuously enrolled for 12 months during the baseline period and ≥30 days during follow-up. Patients were stratified into GOLD A/B (0-1 baseline non-hospitalized exacerbation), No exacerbation (subset of GOLD A/B), and GOLD C/D (≥2 non-hospitalized and/or ≥1 hospitalized baseline exacerbation). Baseline characteristics were balanced with propensity score matching (1:1). Adjusted risks of exacerbation, pneumonia diagnosis, and COPD and/or pneumonia-related utilization and costs were evaluated. Results: Adjusted exacerbation risk was similar in GOLD A/B and No exacerbation subgroups, and lower in GOLD C/D for FF/UMEC/VI versus TIO/OLO initiators (hazard ratio: 0.87; 95% CI: 0.78, 0.98, p=0.020). Adjusted pneumonia risk was similar between cohorts across the GOLD subgroups. Adjusted COPD and/or pneumonia-related population annualized pharmacy costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators across subgroups, p<0.001. Adjusted COPD and/or pneumonia-related population annualized total healthcare costs were significantly higher for FF/UMEC/VI versus TIO/OLO initiators in the GOLD A/B and No exacerbation, subgroups, p<0.001 (cost ratio [95% CI]: 1.25 [1.13, 1.38] and 1.21 [1.09, 1.36], respectively), but similar in the GOLD C/D subgroup. Conclusion: These real-world results support ATS and GOLD recommendations for treating low-exacerbation risk COPD patients with dual bronchodilators and TT for more severe, higher-exacerbation risk COPD patients.

Derivation and validation of a risk assessment model for drug-resistant pathogens in hospitalized patients with community-acquired pneumonia.

OBJECTIVE: To derive and validate a model for risk of resistance to first-line community-acquired pneumonia (CAP) therapy. DESIGN: We developed a logistic regression prediction model from a large multihospital discharge database and validated it versus the Drug Resistance in Pneumonia (DRIP) score in a holdout sample and another hospital system outside that database. Resistance to first-line CAP therapy (quinolone or third generation cephalosporin plus macrolide) was based on blood or respiratory cultures. SETTING: This study was conducted using data from 177 Premier Healthcare database hospitals and 11 Cleveland Clinic hospitals. PARTICIPANTS: Adults hospitalized for CAP. EXPOSURE: Risk factors for resistant infection. RESULTS: Among 138,762 eligible patients in the Premier database, 12,181 (8.8%) had positive cultures and 5,200 (3.8%) had organisms resistant to CAP therapy. Infection with a resistant organism in the previous year was the strongest predictor of resistance; markers of acute illness (eg, receipt of mechanical ventilation or vasopressors) and chronic illness (eg, pressure ulcer, paralysis) were also associated with resistant infections. Our model outperformed the DRIP score with a C-statistic of 0.71 versus 0.63 for the DRIP score (P < .001) in the Premier holdout sample, and 0.65 versus 0.58 (P < .001) in Cleveland Clinic hospitals. Clinicians at Premier facilities used broad-spectrum antibiotics for 20%-30% of patients. In discriminating between patients with and without resistant infections, physician judgment slightly outperformed the DRIP instrument but not our model. CONCLUSIONS: Our model predicting infection with a resistant pathogen outperformed both the DRIP score and physician practice in an external validation set. Its integration into practice could reduce unnecessary use of broad-spectrum antibiotics.

National emergency department trends for endogenous endophthalmitis: an increasing public health challenge.

BACKGROUND/OBJECTIVE: To characterize incidence rates and identify risk factors for admission and mortality in patients with endogenous endophthalmitis (EE) in the United States (US). SUBJECTS/METHODS: Patients with EE were identified using the Nationwide Emergency Department (NEDS) Database from 2006 to 2017 in this cross-sectional study. Subjects were required to have diagnoses of both endophthalmitis and septicaemia using contemporary International Classification of Diseases diagnosis codes. Incidence rates, mortality rates and demographics were evaluated. Risk factors for admission and mortality were identified using weighted logistic regression analysis. RESULTS: A total of 6400 patients with EE were identified. Incidence increased from 0.10 (95% confidence interval [CI]: 0.07-0.12) per 100,000 in the US population in 2006 to 0.25 (95% CI: 0.21-0.30) in 2017 (p < 0.05). Most were female (55.4%), insured with Medicare (53.5%), were in the first income quartile earnings (29.3%) [bottom 25% income bracket], lived in the South (40.5%), and presented to metropolitan teaching hospitals (66.6%). Mortality increased from 8.6% (95% CI: 3.8-18.3%) in 2006 to 13.8% (95% CI: 9.7-19.2%) in 2017 (p = 0.94). Factors predicting admission included older age (odds ratio [OR] 32.59; [95% CI 2.95-359.78]) and intravenous drug use (OR 14.90 [95% CI: 1.67-133.16]). Factors associated with increased mortality included: human immunodeficiency virus infection/immune deficiencies (OR 2.58 [95% CI: 1.26-5.28]), heart failure (OR 2.12 [95% CI: 1.47-3.05]), and hepatic infections/cirrhosis (OR 1.89 [95% CI: 1.28-2.79]). Pneumonia and renal/urinary tract infections (UTI) were associated with both increased hospital admission [(pneumonia OR 9.64 (95% CI: 1.25-74.35, p = 0.030), renal/UTI OR 4.09 (95% CI: 1.77-9.48)] and mortality [(pneumonia OR 1.64 (95% CI: 1.17-2.29, p = 0.030), renal/UTI OR 1.87 (95% CI: 1.18-2.97)]. Patients with diabetes mellitus (DM) had decreased odds ratio for mortality (OR 0.49 [95% CI: 0.33-0.73]). CONCLUSION: EE has increased in incidence throughout US. The two systemic factors that conferred both an increase in mortality and admission were pneumonia, and renal/UTI. Additional exploration of the potential protective association of DM with decreased mortality in this context is needed.

Pharmacokinetic/pharmacodynamic analysis of high-dose tigecycline, by Monte Carlo simulation, in plasma and sputum of patients with hospital-acquired pneumonia.

WHAT IS KNOWN AND OBJECTIVE: To Investigate the pharmacokinetic/pharmacodynamic (PK/PD) parameters of high-dose tigecycline in plasma and sputum of patients with hospital-acquired pneumonia (HAP), and provide a therapeutic regimen of multidrug-resistant bacteria (MDRB) infections. METHODS: Blood/sputum samples were collected at intervals after tigecycline had reached a steady-state. Tigecycline concentrations in specimens were determined by high-performance liquid chromatography (HLPC), PK parameters were evaluated by WinNonlin software using a non-compartment model. The probability of target attainments (PTAs) at different minimal inhibitory concentrations (MICs) were calculated for achieving the PK/PD index with Crystal Ball software by 10,000-patient Monte Carlo Simulation. RESULTS: In plasma, the maximum concentration (Cmax ) and area under the concentration-time curve from 0 to 12 h (AUC0-12h ) were 2.21 ± 0.17 mg/L and 15.29 ± 1.13 h mg/L, respectively. In sputum, they were 2.48 ± 0.21 mg/L and 19.46 ± 1.82 h mg/L, respectively. The mean lung penetration rate was 127.27%. At the MIC ≤4 mg/L, the PTAs in plasma and sputum were 100.00%. When the MIC increased to 8 mg/L, the PTAs in plasma and sputum mostly were < 90.00% according to two criteria. WHAT IS NEW AND CONCLUSION: In this study, we explored PK/PD of high-dose tigecycline in plasma and sputum. From a PK/PD perspective, high-dose tigecycline had greater therapeutic outcomes in HAP treatment caused by MDRB. Antimicrobial-drug concentrations should be determined to optimize their clinical use.

[Analysis of outcome indicators in clinical trials on Chinese medicine as adjuvant therapy for severe pneumonia].

This study analyzed the outcome indicators in randomized controlled trial(RCT) on Chinese medicine as adjuvant therapy for severe pneumonia in the past years, laying a foundation for the design of clinical trials on and construction of core outcome set(COS) for severe pneumonia. To be specific, related RCT was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov(from January 1,2011 to April 9,2022). Then data in the trials were extracted, and the quality of included RCT was assessed according to Cochrane handbook, followed by descriptive analysis of the use of outcome indicators. A total of 11 833 articles were screened out, and finally 34 RCTs were included(2 were protocols). The included trials involved 109 outcome indicators with emergence frequency of 320, which were mainly classified into 9 categories: physicochemical indicators(54, frequency 167), time to achieve the efficacy(15, frequency 38), clinical effective rate(10, frequency 36), quality of life(11, frequency 35), symptoms and signs(7, frequency 18), traditional Chinese medicine(TCM) syndrome(4, frequency 13), safety(3, frequency 8), economic evaluation(1, frequency 1), other indicators(4, frequency 4). The indicators with high frequency followed the order: total effective rate, arterial oxygen partial pressure, C-reactive protein, white blood cell count, arterial blood carbon dioxide partial pressure. A total of 5 articles(14.71%) reported the main outcome indicators and 11 articles(32.35%) adopted the efficacy on TCM syndromes as the outcome indicator. There are many problems in the selection of outcome indicators in RCT on the treatment of severe pneumonia with Chinese medicine, mainly manifested as the disregard of clinical endpoint indicators, the inappropriate selection of surrogate indicators, and the non-standard evaluation criteria for the efficacy on TCM syndrome. It is suggested that the evaluation system for the efficacy of Chinese medicine on severe pneumonia should be established in accordance with the method for international COS to improve the quality of clinical trials.

Population pharmacokinetic/pharmacodynamic study suggests continuous infusion of ceftaroline daily dose in ventilated critical care patients with early-onset pneumonia and augmented renal clearance.

OBJECTIVES: Ceftaroline could be suitable to treat early-onset ventilator-associated pneumonia (VAP) because of its antibacterial spectrum. However, augmented renal clearance (ARC) is frequent in ICU patients and may affect ceftaroline pharmacokinetics and efficacy. The objective of the study was to explore the impact of ARC on ceftaroline pharmacokinetics and evaluate whether the currently recommended dosing regimen (600 mg every 12 h) is appropriate to treat VAP in ICU patients. METHODS: A population pharmacokinetic model was developed using pharmacokinetic data from 18 patients with measured creatinine clearance (CLCR) ranging between 83 and 309 mL/min. Monte Carlo simulations were conducted to determine the PTA and the cumulative fraction of response (CFR) against Streptococcus pneumoniae and MRSA for five dosing regimens. Study registered at ClinicalTrials.gov (NCT03025841). RESULTS: Ceftaroline clearance increased non-linearly with CLCR, with lower concentrations and lower probability of reaching pharmacokinetic/pharmacodynamic targets when CLCR increases. For the currently recommended dosing regimen, the probability of having unbound ceftaroline concentrations above the MIC over the entire dose range is greater than 90% for MICs below 0.125 mg/L. Considering the distribution of MICs, this regimen would not be effective against MRSA infections (CFR between 21% and 67% depending on CLCR), but would be effective against S. pneumoniae infections (CFR >86%). CONCLUSIONS: The recommended dosing regimen of ceftaroline seems sufficient for covering S. pneumoniae in ICU patients with ARC, but not for MRSA. Among the dosing regimens tested it appears that a constant infusion (50 mg/h) after a loading dose of 600 mg could be more appropriate for MRSA infections.

Effects of utilization management on health outcomes: evidence from urinary tract infections and community-acquired pneumonia.

BACKGROUND: Utilization management policies are pervasive in the Medicare Part D program. We assess the effect of utilization management restrictions in the Medicare Part D program on the quality of care in two clinical areas - community-acquired pneumonia (CAP) and urinary tract infections (UTI). METHODS: In this study, we identified new cases of CAP and UTI from Medicare claims data from 2010 to 2016. We assessed the relationship between exposure to utilization management for antibiotic medications suitable for treating these conditions and adverse health outcomes, based on the Agency for Healthcare Research and Quality prevention quality indicators. RESULTS: We identified 147,526 cases of CAP and 632,407 UTI cases in our data. In these samples, the adverse event rate varied from 3.6 to 5.7%. The probability of an adverse event increased by 0.75 (p = 0.061) percentage points for each ten percentage point increase in exposure to quantity limits (one form of utilization management) among people with CAP. There was no relationship between utilization management and adverse events in the UTI cohort. CONCLUSIONS: In some circumstances, exposure to utilization management policies-particularly quantity limits-may adversely affect health.

Value of syndromic panels in the management of severe community-acquired pneumonia.

Community-acquired pneumonia requiring hospital admission is a prevalent and potentially serious infection, especially in high-risk patients (e.g., those requiring ICU admission or immunocompromised). International guidelines recommend early aetiological diagnosis to improve prognosis and reduce mortality. Syndromic panels that detect causative pathogens by molecular methods are here to stay. They are highly sensitive and specific for detecting the targets included in the test. A growing number of studies measuring their clinical impact have observed increased treatment appropriateness and decreased turnaround time to aetiological diagnosis, need for admission, length of hospital stay, days of isolation, adverse effects of medication and hospital costs. Its use is recommended a) per a pre-established protocol on making the diagnosis and managing the patient, b) together with an antimicrobial stewardship programme involving both the Microbiology Service and the clinicians responsible for the patient, and c) the final evaluation of the whole process. However, we recall that microbiological diagnosis with traditional methods remains mandatory due to the possibility that the aetiological agent is not included among the molecular targets and to determine the antimicrobial susceptibility of the pathogens detected.

Cost impact analysis of novel host-response diagnostic for patients with community-acquired pneumonia in the emergency department.

BACKGROUND: There is significant over-prescription of antibiotics for suspected community-acquired pneumonia (CAP) patients as bacterial and viral pathogens are difficult to differentiate. To address this issue, a host response diagnostic called MeMed BV (MMBV) was developed that accurately differentiates bacterial from viral infection at the point of need by integrating measurements of multiple biomarkers. A literature-based cost-impact model was developed that compared the cost impact and clinical benefits between using the standard of care diagnostics combined with MMBV relative to standard of care diagnostics alone. METHODS: The patient population was stratified according to the pneumonia severity index, and cost savings were considered from payer and provider perspectives. Four scenarios were considered. The main analysis considers the cost impact of differences in antibiotic stewardship and resulting adverse events. The first, second, and third scenarios combine the impacts on antibiotic stewardship with changes in hospital admission probability, length of hospital stay and diagnosis related group (DRG) reallocation, and hospital admission probability, length of stay, and DRG reallocation in combination, respectively. RESULTS: The main analysis results show overall per-patient savings of $37 for payers and $223 for providers. Scenarios 1, 2, and 3 produced savings of $137, $189, and $293 for payers, and $339, $713, and $809 for providers, respectively. LIMITATIONS: Models are simulations of real-world clinical processes, and are not sensitive to variations in clinical practice driven by differences in physician practice styles, differences in facility-level practice patterns, and patient comorbidities expected to exacerbate the clinical impact of CAP. Hospital models are limited to costs and do not consider differences in revenue associated with each approach. CONCLUSIONS: Introducing MMBV to the current SOC diagnostic process is likely to be cost-saving to both hospitals and payers when considering impacts on antibiotic distribution, hospital admission rate, hospital LOS, and DRG reallocation.

Modelled Target Attainment after Temocillin Treatment in Severe Pneumonia: Systemic and Epithelial Lining Fluid Pharmacokinetics of Continuous versus Intermittent Infusions.

The objective of this article is to describe the population pharmacokinetics (PK) of temocillin administered via continuous infusion (CI) versus intermittent infusion (II) in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Thirty-two mechanically ventilated patients who were treated for pneumonia with 6 g of temocillin daily for in vitro sensitive pathogens were assigned to either the II (2 g every 8 h over 0.5 h) or the CI (6 g over 24 h after a loading dose of 2 g) group. A population pharmacokinetic model was developed using unbound plasma, and total ELF concentrations of temocillin and related Monte Carlo simulations were performed to assess PTAs. The area under the concentration-time curve from 0 to 24 h (AUC0-24) ELF/plasma penetration ratio was 0.73, at steady state, for both modes of infusion and whatever the level of creatinine clearance. Monte Carlo simulations showed that for the minimal pharmacodynamic (PD) targets of 50% T > 1× MIC (II group) and 100% T > 1× MIC (CI group), PK/PD breakpoints were 4 mg/L in plasma and 2 mg/L in ELF and 4 mg/L in plasma and ELF, respectively. The breakpoint was 8 mg/L in ELF for both modes of infusion in patients with creatinine clearance (CLCR) < 60 mL/min/1.73 m2. While CI provides better PKPD indexes, the latter remain below available recommendations for systemic infections, except in the case of moderate renal impairment, thereby warranting future clinical studies in order to determine the efficacy of temocillin in severe pneumonia.

The current definition, epidemiology, animal models and a novel therapeutic strategy for aspiration pneumonia.

In the 21st century, aspiration pneumonia (ASP) is very common in older patients, and has a high mortality rate. ASP is diagnosed following confirmation of inflammatory findings in the lungs and overt aspiration or the existence of dysphagia. It is dominant in hospitalized community-acquired pneumonia (CAP), nursing and healthcare-associated pneumonia (NHCAP), and hospital-acquired pneumonia (HAP). The incidence of ASP is increasing every year. The human and experimental animal data revealed that micro-aspiration due to dysphagia during the night is the central mechanism of ASP. Therefore, the precise assessment of swallowing function is the key to diagnose ASP. From a therapeutic point of view, an appropriate administration of antibiotics, as well as a comprehensive approach for dysphagia plays a pivotal role in the prognosis and recovery from ASP. The non-pharmacologic approach, including swallowing rehabilitation and oral care, and a pharmacologic approach including ACE inhibitors and bronchodilators, are essential modalities for treatment and prevention of ASP. The clinical data of NHCAP provides us with a promising treatment strategy for ASP.

A Statewide Collaborative Quality Initiative to Improve Antibiotic Duration and Outcomes in Patients Hospitalized With Uncomplicated Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is a common cause for hospitalization and antibiotic overuse. We aimed to improve antibiotic duration for CAP across 41 hospitals participating in the Michigan Hospital Medicine Safety Consortium (HMS). METHODS: This prospective collaborative quality initiative included patients hospitalized with uncomplicated CAP who qualified for a 5-day antibiotic duration. Between 23 February 2017 and 5 February 2020, HMS targeted appropriate 5-day antibiotic treatment through benchmarking, sharing best practices, and pay-for-performance incentives. Changes in outcomes, including appropriate receipt of 5 ± 1-day antibiotic treatment and 30-day postdischarge composite adverse events (ie, deaths, readmissions, urgent visits, and antibiotic-associated adverse events), were assessed over time (per 3-month quarter), using logistic regression and controlling for hospital clustering. RESULTS: A total of 41 hospitals and 6553 patients were included. The percentage of patients treated with an appropriate 5 ±â€…1-day duration increased from 22.1% (predicted probability, 20.9% [95% confidence interval: 17.2%-25.0%]) to 45.9% (predicted probability, 43.9% [36.8%-51.2%]; adjusted odds ratio [aOR] per quarter, 1.10 [1.07-1.14]). Thirty-day composite adverse events occurred in 18.5% of patients (1166 of 6319) and decreased over time (aOR per quarter, 0.98 [95% confidence interval: .96-.99]) owing to a decrease in antibiotic-associated adverse events (aOR per quarter, 0.91 [.87-.95]). CONCLUSIONS: Across diverse hospitals, HMS participation was associated with more appropriate use of short-course therapy and fewer adverse events in hospitalized patients with uncomplicated CAP. Establishment of national or regional collaborative quality initiatives with data collection and benchmarking, sharing of best practices, and pay-for-performance incentives may improve antibiotic use and outcomes for patients hospitalized with uncomplicated CAP.

Immune checkpoint inhibitor-related adverse events in lung cancer: Real-world incidence and management practices of 1905 patients in China.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune-related adverse events (irAEs) remain poorly understood, especially in a real-world setting. METHODS: A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD-L1) monotherapy, anticytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy. RESULTS: In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28-87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3-5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0-1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD-L1 expression (≥1%) and who received first-line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p < 0.001). CONCLUSIONS: The incidence rate of irAEs was 26.9% in a real-world setting. IrAEs might be related to a better DCR, but clinicians should be more aware of irAE recognition and management in clinical practice.