SASPI Ltd.
Multi-centric observational study with large effect
Epidemiology of human metapneumovirus among children with severe or very severe pneumonia in high pneumonia burden settings: the PERCH study experience
Authors: Ryo Miyakawa et al.,
Abstract
Objectives: After respiratory syncytial virus (RSV), human metapneumovirus (hMPV) was the second-ranked pathogen attributed to severe pneumonia in the PERCH study. We sought to characterize hMPV-positive cases in high burden settings, which have limited data, by comparing to RSV-positive and other cases.
Methods: Children aged 1-59 months hospitalized with suspected severe pneumonia and age/season-matched community controls in seven African and Asian countries had nasopharyngeal/oropharyngeal swabs tested by multiplex PCR for 32 respiratory pathogens, among other clinical and lab assessments at admission. Odds ratios adjusted for age and site (aOR) were calculated using logistic regression. Etiologic probability was estimated using Bayesian nested partial latent class analysis. Latent class analysis identified syndromic constellations of clinical characteristics.
Results: HMPV was detected more frequently among cases (267/3887, 6.9%) than controls (115/4976, 2.3%), among cases with pneumonia chest X-ray findings (8.5%) than without (5.5%), and among controls with respiratory tract illness (3.8%) than without (1.8%; all p≤0.001). HMPV-positive cases were negatively associated with the detection of other viruses (aOR=0.18), especially RSV (aOR=0.11; all p<0.0001), and positively associated with the detection of bacteria (aORs 1.77, p=0.03). No single clinical syndrome distinguished hMPV-positive from other cases. Among hMPV-positive cases, 65.2% were aged <1 year and 27.5% had pneumonia danger signs; positive predictive value was 74.5%; mortality was 3.9%, similar to RSV-positive (2.4%) and lower than other cases (9.6%).
Conclusions: HMPV-associated severe pediatric pneumonia in high burden settings was predominantly in young infants and clinically indistinguishable from RSV. HMPV-positives had low case fatality, similar to that in RSV-positives.
Multi-centric observational study with large effect
Total burden of hepatitis B and C attributed to injecting drug use in 204 countries and territories from 1990 to 2021: Analyses based on the Global Burden of Disease Study 2021
Authors: Liang Huang et al.,
Abstract
Highlights:
– Significant rise in HBV and stable HCV burdens from IDU observed from 1990 to 2021.
– Regional disparities are notable, with India showing the highest national deaths.
– Central Asia and Eastern Europe display steep increases in HBV and HCV trends.
– Findings underscore the need for targeted interventions for IDU-related HBV and HCV control.
Objectives: This study assesses the global, regional, and national burden of hepatitis B (HBV) and hepatitis C (HCV) related to injecting drug use (IDU) from 1990 to 2021.
Methods: Data from the global burden of disease study 2021 were analyzed to quantify deaths, age-standardized mortality rates (ASMR), disability-adjusted life years (DALYs), and age-standardized DALYs rates (ASDR) due to HBV and HCV from IDU across 204 countries. Trends was evaluated using estimated annual percentage change. Analyzing the association between ASDR and SDI using a loess regression model.
Results: From 1990 to 2021, the global burden of deaths and DALYs due to HBV and HCV attributed to IDU showed an increasing trend, especially among males, whose mortality rates were significantly higher than females. In 2021, global deaths due to HBV from IDU were 13,050.8, with an ASMR of 0.15 per 100,000 and an ASDR of 5.3, both showing an increasing trend with estimated annual percentage changes (EAPCs) of 1.09 and 0.96, respectively. HCV deaths reached 231,764.4, with an ASMR of 2.68 (EAPC: 0.38) and a relatively stable ASDR trend (EAPC: 0.01). Although raw death rates for HCV have increased, the ASMR and ASDR have remained stable or slightly declined, highlighting different trends across sexes and regions. India had the highest national deaths, while the highest ASDRs were in the Republic of Moldova (HBV) and Mongolia (HCV). South Asia recorded the highest regional deaths for both HBV and HCV. Positive correlations between ASDRs for HBV and HCV with SDI were observed.
Conclusion: The burden of HBV and HCV due to IDU has increased from 1990 to 2021, especially among males, with significant regional and national disparities. Targeted drug prohibition interventions and policies are needed.
Multi-centric observational study with large effect, Other specific DSP article suggested by Editorial Board, Other specific ASP article suggested by Editorial Board
Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows
Authors: Rebecca E Colman
Abstract
Background: Drug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis.
Methods: We conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing.
Findings: Between April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed.
Interpretation: This multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis.
Position Statement based on review/RCTs
Preventing central line-associated bloodstream infections: A position paper of the International Society for Infectious Diseases, 2024 update
Authors: Victor Daniel Rosenthal et al.,
Abstract
Highlights:
– The CLABSI rates continue to be very high, especially in resource-limited regions.
– CLABSIs are associated with extra hospital stays, costs, and mortality.
– This document presents the main risk factors for CLABSI.
– We updated the recommendations for CLABSI prevention, including those for LMICs.
A panel of experts convened by the International Society for Infectious Diseases (ISID) has reviewed and consolidated current recommendations for preventing vascular catheter infections, particularly central line-associated bloodstream infections (CLABSIs). This review provides healthcare professionals with insights into key issues such as the rates of CLABSI in high-income countries and low- and middle-income countries, the attributable extra length of stay, cost and mortality, and risk factors. This position paper highlights evidence-based strategies for preventing infections, applicable to both high-income and low- and middle-income countries.
RCTs having large positive / negative effect
A phase 3 randomized trial of sulopenem vs. ertapenem in patients with complicated intraabdominal infections
Authors: Michael W. Dunne et al.,
Abstract
Objective: To demonstrate the noninferiority of intravenous (IV) sulopenem to IV ertapenem, each followed by an oral regimen, in adults with complicated intraabdominal infections (cIAI).
Methods: Hospitalized adults with cIAI were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid twice daily or 5 days of IV ertapenem followed by oral ciprofloxacin/metronidazole or amoxicillin-clavulanate depending on baseline pathogen susceptibility. The target treatment duration was 7-10 days. The primary (FDA-specified) endpoint was clinical response at Day 28 [Test-of-Cure (TOC)] in the micro-Modified Intent to Treat (micro-MITT) population.
Results: 674 patients were randomized. The two treatment arms were well-balanced. E. coli (395 patients) and B. fragilis (111 patients) were the most frequently isolated pathogens. Clinical success rates in the micro-MITT population were 81.9% (204/249) for sulopenem-treated patients and 87.9% (233/265) for ertapenem-treated patients. The lower bound of the confidence interval (CI) for the treatment difference of the primary endpoint was below the prespecified non-inferiority margin of -10.0 [treatment difference -6.0%, 95% CI [-12.2, 0.2]. In all other analysis populations, the lower limit of the 95% CI was above -10.0. Treatment emergent adverse events (all, 26.0% [87/335] vs 23.4% [78/333]; related, 6.0% [20/335] vs 5.1% [17/333]) were similar for sulopenem and ertapenem, respectively. Most events were mild to moderate in severity. There were more serious adverse events in the sulopenem arm (7.5% [25/335] vs 3.6% [12/333]), only two of which were considered possibly drug-related.
Conclusions: Sulopenem IV followed by oral sulopenem etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down in treating cIAI in the micro-MITT population. This finding should be interpreted in the context of country regulations, as endpoint timing, primary analysis population and noninferiority margin may vary regionally. Both IV and oral sulopenem were well-tolerated; the oral formulation allowed patients with resistant pathogens to step down from IV therapy.
Clinical Trial Registration: NCT03358576.
Systematic review/Scoping review with large effect size
How well do different COVID-19 vaccines protect against different viral variants? A systematic review and meta-analysis
Authors: Thi Ngoc Anh Hoang et al.,
Abstract
While the efficacy of coronavirus disease 2019 (COVID-19) vaccines has been evaluated in numerous trials, comprehensive evidence on how protection by different vaccines has varied over time remains limited. We aimed to compare protective effects of different vaccines against different viral variants. To achieve this, we searched Medline, Cochrane Library and Embase for randomized controlled trials assessing the efficacy of COVID-19 vaccines. Forest plots using Mantel–Haenszel and random-effects models were generated showing risk ratios (RRs) and 95% CIs by vaccines and variants. We included 36 studies with 90 variant-specific primary outcomes. We found a RR of 0.26 (95% CI 0.21 to 0.31) against all variants overall, with the highest protective effects against the wild-type (RR 0.13; 95% CI 0.10 to 0.18), followed by Alpha (RR 0.26; 95% CI 0.18 to 0.36), Gamma (RR 0.34; 95% CI 0.21 to 0.55), Delta (RR 0.39; 95% CI 0.28 to 0.56) and Beta (RR 0.49; 95% CI 0.40 to 0.62) variants. Nucleic acid vaccines showed the highest protection levels against all variants (RR 0.11; 95% CI 0.08 to 0.15), followed by protein subunit, inactivated virus and viral vector. In conclusion, we found high but heterogenous levels of protection for most COVID-19 vaccines, with decreasing protective effects for vaccines based on traditional technologies as SARS-CoV-2 variants emerged over time. Novel nucleic acid-based vaccines offered substantially higher and more consistent protection.
Other specific ASP article suggested by Editorial Board
Global Meningococcal Initiative: Insights on antibiotic resistance, control strategies and advocacy efforts in Western Europe
Authors: Ray Borrow et al.,
Abstract
In Western Europe, many countries have robust and well-established surveillance systems and case reporting mechanisms. IMD incidence across Western Europe is low with a predominance of meningococcal serogroup B (MenB). Case confirmation and antimicrobial susceptibility testing is often standardised in this region, with many countries also having robust vaccination programmes in place. Both MenB and MenACWY vaccines form part of National Immunisation Programmes (NIPs) in most European countries, with Sweden only offering vaccination in special circumstances. Despite these established programmes, there remains a critical need for advocacy efforts in affecting change in diagnosis, testing, and treatment. Recent campaigns, such as the World Meningitis Day digital toolkit, have helped raise awareness and draw attention to meningococcal disease. Awareness around antibiotic resistance has also led to the identification of antibiotic-resistant meningococcal strains, with an increase, albeit small, in these strains noted across the region. Countries such as Spain, Portugal, Germany, Switzerland, and France have either reported strains resistant to penicillin, ciprofloxacin and/or isolates with a reduced susceptibility to third-generation cephalosporins.
Other specific ASP article suggested by Editorial Board
Relationship between clarithromycin MICs and treatment responses in Mycobacterium avium complex pulmonary disease Get access Arrow
DOI: 10.1093/cid/ciae546
Authors: Joong-Yub Kim et al.,
Abstract
Background: Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic lung condition with rapidly increasing prevalence worldwide. Macrolides like azithromycin and clarithromycin are the backbone of long-term antibiotic therapy for progressive MAC-PD. The impact of minimum inhibitory concentrations (MICs), especially within the susceptible range, for macrolides on treatment responses remains unclear.
Methods: We analyzed adult patients who started treatment for MAC-PD between 1 March 2009 and 1 March 2022 at Seoul National University Hospital. Patients were categorized into four groups according to the clarithromycin MICs of their causative strains at treatment initiation. Logistic regression was employed to evaluate the impact of clarithromycin MICs on the microbiological cure rate. Companion drugs and their MICs, alongside clinical characteristics like age, sex, body mass index, cavity presence, acid-fast bacilli smear positivity, causative species, and erythrocyte sedimentation rate were adjusted in multivariable analysis.
Results: Four-hundred thirty-six patients (median age, 65 years; 34% men) were included. Microbiological cure rates were 51.8%, 51.9%, 50.0%, and 18.2% for patients with clarithromycin MICs ≤0.5, 1–2, 4–8, and ≥32 µg/mL, respectively (P=0.181). No significant differences in microbiological cure rates were observed across varying levels of clarithromycin MICs within the susceptible range (≤8 µg/mL). Relative to patients with clarithromycin-susceptible strains, patients with MICs ≥32 µg/mL had an odds ratio of 0.25 for achieving microbiological cure (95% confidence interval, 0.06–1.07; P=0.06).
Conclusions: Treatment responses were comparable among patients with strains having clarithromycin MICs within the susceptible range, but were likely to be worse for patients with strains having MICs ≥32 µg/mL.
Other specific ASP article suggested by Editorial Board
Evidence-Informed Provision of Doxycycline Post-Exposure Prophylaxis for Prevention of Bacterial Sexually Transmitted Infections Get access Arrow
DOI: 10.1093/cid/ciae527
Authors: Julia C Dombrowski et al.,
Abstract
Doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. In the United States, doxy-PEP is in an early stage of integration into clinical practice, and national guidelines for its use were recently released. The goal of this manuscript is to provide practical guidance for clinicians who are considering or currently prescribing doxy-PEP. We address five clinical questions using post hoc analyses of data from the DoxyPEP randomized controlled trial and discuss the potential implications and limitations of each question with the goal of informing clinical practice and implementation of doxy-PEP programs. The questions address patient eligibility criteria for doxy-PEP, the expected benefit and associated doxy-PEP doses for the average patient, the initial number of doses prescribed, and laboratory monitoring of persons taking doxy-PEP.
Other specific ASP article suggested by Editorial Board
Heartfelt Impact: A Descriptive Analysis of Ceftaroline-Containing Regimens in Endocarditis due to Methicillin-Resistant Staphylococcus aureus
Authors: Kaylee E. Caniff et al.,
Abstract
Introduction: Infective endocarditis (IE) due to methicillin-resistant Staphylococcus aureus (MRSA) is characterized by frequent treatment failure to first-line agents and high mortality, necessitating use of alternative management strategies. Ceftaroline fosamil (CPT) is a cephalosporin antibiotic with activity against MRSA but without regulatory approval for the indication of IE. This study describes clinical experience with CPT-based regimens utilized in MRSA-IE.
Methods: This is a retrospective, observational, descriptive analysis of patients from two major urban medical centers in Detroit, Michigan from 2011 to 2023. Included adult patients (≥ 18 years) had ≥ 1 positive blood culture for MRSA, met definitive clinical criteria for IE, and received CPT for ≥ 72 h. The primary outcome was treatment failure, defined as a composite of 30-day all-cause mortality from index culture or failure to improve or resolve infectious signs/symptoms after CPT initiation.
Results: Seventy patients were included. The median (interquartile range [IQR]) age was 51 (34–63) years and 45.7% were male. Persons with injection drug use (PWID) made up 55.7% of the cohort and right-sided IE was the most prevalent subtype (50.0%). CPT was frequently employed second-line or later, often in combination with vancomycin (10.0%) or daptomycin (72.9%). Overall, 31.4% experienced treatment failure and 30-day all-cause mortality occurred in 15.7%.
Conclusions: These findings illustrate the challenges posed by MRSA-IE, including frequent treatment failures, and highlight the utilization of CPT as salvage therapy. Comparative studies are needed to more clearly define its role in MRSA-IE.
Other specific ASP article suggested by Editorial Board
Proper duration of antibiotics after video-assisted thoracoscopic surgery for the treatment of thoracic empyema
Authors: Ahlam Ashkar et al.,
Abstract
Background: When chest tube drainage does not adequately resolve thoracic empyema, video assisted thoracoscopic surgery (VATS) is often needed. However, the proper duration of antibiotics after VATS is poorly defined. Consequently, the objective of this study was to evaluate if short antibiotic durations post-VATS was equally effective compared to longer durations.
Methods: Patients with thoracic empyema treated with VATS were identified retrospectively by a query of the hospital billing database. The bacterial causes of the empyema were divided into 8 different categories while the antibiotic duration after VATS was divided into two groups which included antibiotics ˂ 14 days and antibiotics >14 days. The primary outcome measured was rates of empyema recurrence. Statistical comparisons were conducted between the antibiotic duration groups overall and when stratified based on the different bacterial causes.
Results: 137 patients were included in this study with the main cause of empyema being culture negative empyema (37.2%) while alpha haemolytic Streptococcus spp. was the most cultured bacteria (26.3%). There was no statistical difference (p = 0.5168), in the rates of empyema recurrence, when short antibiotic durations (median 11.6 days)were compared to longer antibiotic durations (median 29.1 days)post-VATS. Nor was there a statistical difference in recurrence rates when stratifying based on bacterial cause.
Conclusion: This study reinforces that antibiotic durations less than 14 days post-VATS are equally effective as prolonged antibiotic durations. However, to determine the proper duration of antibiotic therapy post-VATS, a prospective clinical trial is needed to reduce complications of prolonged antibiotic therapies for these patients.
Other specific ASP article suggested by Editorial Board
CAF to the rescue! Potential and challenges of combination antifungal therapy for reducing morbidity and mortality in hospitalized patients with serious fungal infections
DOI: 10.1093/ofid/ofae646
Authors: Samantha E Jacobs et al.,
Abstract
The global burden of invasive fungal disease (IFD) is substantial and escalating. Combination antifungal therapy (CAF) may improve patient outcomes by reducing development of resistance, improving drug penetration and rate of fungal clearance, and allowing for lower, less toxic antifungal drug doses; yet, increased cost, antagonism, drug-drug interactions, and toxicity are concerns. Clinical practice guidelines recommend antifungal monotherapy, rather than CAF, for most IFDs due to a lack of comparative randomized clinical trials. An examination of the existing body of CAF research should frame new hypotheses and determine priorities for future CAF clinical trials. We performed a systematic review of CAF clinical studies for invasive candidiasis, cryptococcosis, invasive aspergillosis, and mucormycosis. Additionally, we summarize findings from animal models of CAF and assess laboratory methods available to evaluate CAF efficacy. Future CAF trials should be prioritized according to animal models showing improved survival and observational clinical data supporting efficacy and safety.
Other specific ASP article suggested by Editorial Board
A Comparison of Different Strategies for Optimizing the Selection of Empiric Antibiotic Therapy for Pneumonia Caused by Gram-Negative Bacteria in Intensive Care Units (ICUs): Unit-Specific Combination Antibiograms Versus Patient-Specific Risk Factors
DOI: 10.1093/ofid/ofae643
Authors: Walaiporn Wangchinda et al.,
Abstract
Background: Guidelines suggest dual anti-pseudomonal therapy for empiric treatment of pneumonia caused by Gram-negative bacteria in ICU patients. Additionally, consideration of local susceptibility data and patient-specific risk factors for resistance is recommended for selecting optimal empiric regimens. However, data assessing how to best do this are lacking, and it is unclear whether a local susceptibility data-based or a patient specific risk factor-based approach will better drive appropriate empiric treatment. This study aims to compare these two strategies.
Methods: This retrospective study was divided into two periods. In period I, Gram-negative respiratory cultures from ICU patients were used to develop unit-specific combination antibiograms, and individual patient charts were reviewed to assess the impact of risk factors on antimicrobial susceptibility to develop a risk-factor based treatment algorithm. Optimal empiric regimens based on these two strategies were then defined. In period II, these regimens were hypothetically applied to patients to compare rates of appropriate empiric therapy and overuse by the two methods.
Results: Risk factor-based regimens had a higher appropriateness rate compared to regimens derived from antibiograms (89.9% vs 83.7%). Additionally, applying antibiogram based regimens resulted in a higher prevalence of antibiotic overuse than a patient-specific risk factor based approach (69.8% vs. 40.3%), with excess overuse driven by a higher frequency of unnecessary use of combination therapy.
Conclusion: Both strategies provided high rates of appropriateness in empiric antibiotic selection. However, the patient-specific risk factor-based approach demonstrated a higher rate of appropriate therapy and offered advantages in reducing rates of unnecessary combination therapy.
Other specific ASP article suggested by Editorial Board
Evaluation of Crushed Posaconazole Delayed Release Tablets in Lung Transplant Recipients
DOI: 10.1111/tid.14402
Authors: Rachael Gordon et al.,
Abstract
Background: Invasive fungal infections can cause serious complications after lung transplant; therefore, prophylaxis with posaconazole is common. The posaconazole delayed-release (DR) tablet is preferred. Although the package insert states DR tablets cannot be crushed, recent data suggest it is reasonable. We hypothesized that crushed posaconazole DR tablets could reach therapeutic levels in lung transplant recipients.
Methods: A retrospective study of lung transplant recipients between January 2018 and July 2023, who received crushed posaconazole DR for at least 5 days was completed. Posaconazole troughs were evaluated, and differences were compared between subjects who were therapeutic to those who were subtherapeutic. A cost analysis was also performed.
Results: Thirty subjects received crushed posaconazole DR and 50% were therapeutic. The median trough was 1 mg/L for those who were therapeutic and 0.4 mg/L for those who were not (p < 0.001). The median cumulative dose was 2000 mg, and there were no significant differences in the incidence of diarrhea or tube feeds. More subjects in the therapeutic group were loaded (33% vs. 13%), although this was not statistically significant (p = 0.39). No subjects had breakthrough aspergillus one month after starting crushed therapy.
Conclusion: Crushed posaconazole DR tablets are a viable and cost savings option, but loading doses and higher maintenance doses may be required to reach therapeutic levels. Those who received loading doses (intravenously or crushed) followed by a daily crushed dose of 400 mg were more likely to be therapeutic. Limitations of our study include that it is single-center, small in sample size, and retrospective.
Other specific DSP article suggested by Editorial Board
High mortality rates among individuals misdiagnosed with tuberculosis: a matched retrospective cohort study of individuals diagnosed with tuberculosis in Brazil
Authors: Ryan R Thompson et al.,
Abstract
We conducted a matched retrospective cohort study comparing mortality among individuals receiving a false-positive tuberculosis diagnosis (n=3701) to individuals correctly diagnosed with TB (n=8595) in Brazil from 2007-2016. Over an average 5.4-year follow-up period, we estimated a mortality rate ratio of 1.95 (95% confidence interval: 1.80, 2.11) for individuals incorrectly diagnosed with TB compared to controls. The leading causes of death among the misdiagnosed were malignant neoplasms (40.9%) and respiratory system disorders (15.9%), conditions with symptoms similar to tuberculosis. Our findings highlight the need for improved follow-up care after identification of false-positive cases to increase survival for this high-risk population.
Other specific DSP article suggested by Editorial Board
High utility of bronchoalveolar lavage fluid metagenomic next-generation sequencing approach for etiological diagnosis of pneumonia
Authors: Lingyu Jiang et al.,
Abstract
Background: For patients with pneumonia, the rapid detection of pathogens is still a major global problem in clinical practice because traditional diagnostic techniques for infection are time-consuming and insensitive. Metagenomic next-generation sequencing (mNGS) is a novel technique that has the potential to improve pathogen diagnosis. This study aimed to investigate the microbiological diagnostic ability of mNGS compared with conventional culture and to determine the optimal time to test patients for pneumonia.
Methods: A prospective study using data from June 2020 to June 2021 was performed at a tertiary teaching hospital in China. We included 56 patients from all adult patients with a clinical diagnosis of pneumonia. Blood and bronchoalveolar lavage fluid (BALF) samples were taken for simultaneous mNGS and conventional culture testing.
Results: All 56 patients underwent both conventional culture and mNGS. Of these patients, 37 were diagnosed with severe pneumonia and 17 were diagnosed with non-severe pneumonia. The top three pathogenic bacteria detected by mNGS were Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Enterococcus faecium was detected more frequently in the non-severe pneumonia group (4 vs. 0, p < 0.05). The findings revealed that the detection rate of mNGS (84%) was superior to that of conventional culture methods (48%). Notably, the percentage of mNGS-positive BALF samples (46/56, 82.14%) was significantly greater than that of blood samples (27/56, 48.21%). The etiological comparison demonstrated that mNGS-positive samples, which received clinical approval, tended to be associated with a more normalized temperature, lower PCO2 levels, and a higher SOFA score than mNGS-negative samples (p = 0.022, p = 0.0.028, and p = 0.038, respectively).
Conclusions: In this study, we discovered that the etiology of lung infections frequently involves multiple pathogens. The use of mNGS in BALF is instrumental for detecting nonviral pathogens associated with lung infections. Although the rate of positive blood NGS results is significantly influenced by various clinical factors, for patients suspected of having viral, Legionella, or tsutsugamushi infections, plasma mNGS could serve as a complementary diagnostic tool.
Other specific ISP article suggested by Editorial Board
Genomic analysis confirmed the importation of first mPox Clade Ib case in Kerala, India from Dubai, UAE
Authors: Anita M. Shete et al.,
Abstract
Highlights
– Importation of first mPox Clade Ib case in India.
– Deletion in C3L gene in clade 1b might lead to false negative mpox clades
– Integrating genomic & epidemiological data to understand Clade-specific mutations
Other specific ISP article suggested by Editorial Board
Non-pharmaceutical interventions to reduce influenza transmission in households: a systematic review and meta-analysis
Authors: Jessica Y. Wong et al.,
Abstract
Highlights
-Non-pharmaceutical interventions (NPI) play an important role in influenza control.
-Most countries recommended face masks and hand hygiene as NPIs in households.
-We identified nine randomized controlled trials for face masks and hand hygiene.
-Hand hygiene and face masks did not affect household transmission.
-Within-household NPIs would be effective when implemented soon after symptom onset.
Background: Influenza pandemic plans often recommend non-pharmaceutical interventions (NPIs) in household settings, including hand hygiene and face masks. We reviewed the evidence supporting the recommendations of these measures to prevent the spread of influenza in households.
Methods: We performed systematic reviews between 26 May and 30 August 2022 in Medline, PubMed, EMBASE, and CENTRAL to identify evidence for the effectiveness of selected measures recommended by representative national influenza pandemic plans. We prioritized evidence from randomized controlled trials conducted during influenza pandemics and seasonal influenza epidemics. Fixed-effects models were used to estimate the overall effects. Systematic reviews were registered in the OSF registry (https://osf.io/8kyth).
Results: We selected 9 NPIs for evidence review. We identified 9 randomized-controlled trials related to hand hygiene and face masks in household settings. 2 studies reported that measures could delay the introduction of influenza virus infections into households. However, we did not identify evidence from randomized controlled trials that indicated a substantial effect of hand hygiene and face masks in preventing the spread of influenza within households.
Conclusion: Limited evidence indicated that within-household measures may likely be effective only when implemented before or as soon as possible after symptom onset in an infected case. Improving the evidence base for NPIs in households and elsewhere is a continuing priority.
Funding: World Health Organization and the Strategic Topic Grants Scheme
Other specific ISP article suggested by Editorial Board
Performance of a large language model for identifying central line-associated bloodstream infections (CLABSI) using real clinical notes
DOI: 10.1017/ice.2024.141
Authors: Hawra J. Al Lawati et al.,
Abstract
A surveillance system for measuring patient-level antimicrobial adverse drug events (ADE) may support stewardship activities, however, design and implementation questions remain. In this national survey, stewardship experts favored simple, laboratory-based ADE definitions although there were tensions between feasibility, ability to identify attribution without chart review, and importance of specific ADE.