SASPI Ltd.
Systematic review/Scoping review with large effect size
Global landscape of vancomycin-resistant enterococci in hematopoietic stem-cell transplantation patients: a systematic review and meta-analysis
Authors: Seyed Pooria Tadayon Nabavi et al.,
Abstract
Background: One of the main risks of infection after hematopoietic stem cell transplantation (HSCT) is infection by gram-positive bacteria, including vancomycin-resistant enterococci (VRE). Based on the format of a global review and meta-analysis study, this study aims to investigate the incidence of VRE bloodstream infection (BSI) after HSCT in colonized individuals.
Methods: The keywords of the systematic search included vancomycin-resistant enterococci and HSCT. These words were searched in Google Scholar, PubMed/Medline, Scopus, and Web of Science databases from January 1, 2000, to March 1, 2024. Studies that reported the prevalence of vancomycin-resistant enterococci in patients undergoing HSCT were included. The random effects model was used for the meta-analyses. Investigations were conducted according to PRISMA guidelines, and the protocol was registered in PROSPERO: CRD42024543491.
Results: Out of 1100 screened papers, 28 were eligible. The random effects model was established to analyze the incidence of VRE BSI after HSCT. The pooled prevalence of co-infection for Allo-HSCT recipients was 3.023 (95% CI, Z-value = -3.5, p-value < 0.0001), and this value for Auto-HSCT recipients was 11.89 (95% CI, Z-value = -2.923, p-value < 0.001). These results showed that the rate of BSI due to vancomycin-resistant enterococcus in Auto-HSCT recipients is higher than Allo-HSCT.
Conclusions: The prevalence of vancomycin-resistant enterococci in Auto-HSCT recipients is higher than that of Allo-HSCT, possibly due to colonization of the intestines of these people with vancomycin-resistant enterococci before transplantation. VRE Colonization before transplantation increases the likelihood of post-transplant VRE BSI and other bacterial infections, including Gram-negative. The strains should be analyzed by sequencing before and after HSCT for a more detailed investigation..
Systematic review/Scoping review with large effect size
Scrub typhus–leptospirosis co-infection in India: a systematic review and meta-analysis
DOI:- 10.1093/trstmh/trae081
Authors: Siddhant Govekar et al.,
Abstract
Scrub typhus and leptospirosis are re-emerging zoonotic infections with significant morbidity and mortality rates in India. Overlapping aetiological and epidemiological patterns indicate a high possibility of their co-infection in India, which can be a diagnostic challenge due to non-specific clinical features. A systematic search of the PubMed/MEDLINE, Scopus and Embase databases was conducted to identify relevant studies published through 31 August 2023. Studies reporting co-infection of scrub typhus and leptospirosis among the Indian population were included. Data extraction, quality assessment and statistical analysis were performed in accordance with established guidelines. Six studies met the inclusion criteria, comprising a total of 58 co-infection cases. Pooled prevalence of scrub typhus–leptospirosis co-infection among acute undifferentiated febrile illness patients was 3.7% (95% confidence interval [CI] 0.00 to 0.126). Among scrub typhus patients, the prevalence of co-infection with leptospirosis was 13.7% (95% CI 0.027 to 0.304). Significant heterogeneity was observed among the included studies, highlighting the need for cautious interpretation of prevalence estimates. This meta-analysis underscores the clinical importance of scrub typhus–leptospirosis co-infection in India and emphasizes the need for enhanced clinical awareness, improved diagnostic strategies and targeted research efforts to address this emerging infectious disease threat.
Systematic review/Scoping review with large effect size
Dengue Fever in Immunocompromised Patients: A Systematic Review and Meta-Analysis
Authors: Asma Sohail et al.,
Abstract
Objective: Given the complex role of immunity in dengue severity, we aimed to review the clinical course of dengue infection in immunocompromised patients.
Methods: We conducted a systematic review of studies reporting outcomes among immunocompromised patients with laboratory-confirmed dengue infection. Meta-analysis using the Mantel-Haenszel method (fixed effects) was performed for studies with control groups. We registered the study with PROSPERO (No. CRD42021258930).
Results: We included 115 studies. Among these, 30 studies compared immunocompromised (cases) and non-immunocompromised (control) patients, focusing mainly on children (n=22 studies) with malnutrition (n=18). Immunocompromised patients had a higher likelihood of dengue complications (OR 1.87; 95% CI: 1.04 – 3.35]) but a lower likelihood of severe dengue (OR 0.83; 95% CI: 0.69 – 1.00]. No significant difference in mortality was observed. In the 85 studies focused solely on immunocompromised patients, severe dengue and mortality rates were 9% and 4%, respectively, mostly among adult solid organ transplant recipients and those with inflammatory diseases. Immunosuppressive treatment alterations and temporary graft dysfunction were reported.
Conclusions: Immunocompromised patients have an increased risk of dengue-related complications. However, definitive conclusions about the comparative severity of dengue across different immunocompromised patient groups are limited by a lack of robust data, highlighting the need for well-designed future studies.
Highlights:
* Immunocompromised hosts are a growing population at risk of dengue infection
*Immunocompromised hosts have a higher likelihood of dengue-related complications
*Immunocompromised patients do not have a higher likelihood of severe dengue
*Dengue fever has an impact on underlying immunocompromising medical conditions
Multi-centric observational study with large effect
Effectiveness, Safety, and Patterns of Real-World Isavuconazole Use in Europe (2015–2019)
Authors: Dionysios Neofytos et al.,
Abstract
Introduction: Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe.
Methods: A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed.
Results: Data were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2–66.5%) for primary treatment and 73.5% (95% CI, 62.7–81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy.
Conclusions: This study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.
Multi-centric observational study with large effect
Current practice of screening and antimicrobial prophylaxis to prevent Gram-negative bacterial infection in high-risk haematology patients: results from a pan-European survey
Authors: Jannik Stemler et al.,
Abstract
Background: Bacterial infections frequently occur in haematological patients, especially during prolonged neutropenia after intensive chemotherapy, often leading to bloodstream infections and pneumonia.
Objective: Routine antimicrobial prophylaxis (AMP) for high-risk haematology patients is still debated while prevalence of multi-drug resistant (MDR) Gram-negative bacteria (GNB) is rising globally. We aimed to assess the current practice of AMP in this population.
Design: Cross-sectional observational survey study.
Methods: Haematologists and infectious diseases physicians Europewide were invited to an online survey including questions on routine screening for GNB, incidence of MDR-GNB colonization, antimicrobial prophylaxis practices, rates of bloodstream infections (BSI), ICU admission and mortality differentiated by infections due to GNB versus MDR-GNB.
Results: 120 haematology centres from 28 countries participated. Screening for MDR-GNB is performed in 86.7% of centres, mostly via rectal swabs (58.3%). In 39.2% of routine AMP is used, mostly with fluoroquinolones. Estimates of GNB-BSI yielded higher rates in patients not receiving anti-GNB prophylaxis than in those who do for E. coli (10% vs 7%) Klebsiella spp. (10% vs 5%), and Pseudomonas spp. (5% vs 4%). Rates for MDR-GNB infection were estimated lower in centres that administer AMP for MDR E. coli (5% vs 3%) Klebsiella spp. (5% vs 3%), and Pseudomonas spp. (2% vs 1%). In an exploratory analysis, Southern and Eastern European countries expected higher rates of MDR-GNB infections with lower ICU admission and mortality rates which may be subject to estimation bias.
Conclusion: Screening for MDR-GNB is frequently performed. AMP against GNB infections is still often implemented. Estimated BSI rates are rather low, while the rate of MDR-GNB infections rises. Tailored prophylaxis including antimicrobial stewardship becomes more important.
Other specific ASP article suggested by Editorial Board
Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults
DOI:- 10.1093/cid/ciae519
Authors: Anne M Butler et al.,
Abstract
Background: Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults.
Methods: We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18–64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2–90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes.
Results: Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10–0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25–0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09–0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding.
Conclusions: Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.
Other specific ASP article suggested by Editorial Board
Rifaximin prophylaxis causes resistance to the last-resort antibiotic daptomycin
Authors: Adrianna M. Turner et al.,
Abstract
Multidrug-resistant bacterial pathogens like vancomycin-resistant Enterococcus faecium (VREfm) are a critical threat to human health1. Daptomycin is a last-resort antibiotic for VREfm infections with a novel mode of action2, but for which resistance has been widely reported but is unexplained. Here we show that rifaximin, an unrelated antibiotic used prophylactically to prevent hepatic encephalopathy in patients with liver disease3, causes cross-resistance to daptomycin in VREfm. Amino acid changes arising within the bacterial RNA polymerase in response to rifaximin exposure cause upregulation of a previously uncharacterized operon (prdRAB) that leads to cell membrane remodelling and cross-resistance to daptomycin through reduced binding of the antibiotic. VREfm with these mutations are spread globally, making this a major mechanism of resistance. Rifaximin has been considered ‘low risk’ for the development of antibiotic resistance. Our study shows that this assumption is flawed and that widespread rifaximin use, particularly in patients with liver cirrhosis, may be compromising the clinical use of daptomycin, a major last-resort intervention for multidrug-resistant pathogens. These findings demonstrate how unanticipated antibiotic cross-resistance can undermine global strategies designed to preserve the clinical use of critical antibiotics.
Other specific ASP article suggested by Editorial Board
EQUAL ABPA Score 2024: A Tool to Measure Guideline Adherence for Managing Allergic Bronchopulmonary Aspergillosis
DOI:- 10.1111/myc.13810
Authors: Inderpaul Singh Sehgal et al.,
Abstract
Objectives: Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendations.
Methods: We extracted key recommendations from the updated 2024 ISHAM-AWG guidelines, focusing on critical areas: screening and diagnosis of ABPA, managing acute and treatment-dependent ABPA, and monitoring treatment response. Each item was assigned a score ranging from zero to three. We assigned negative scores to interventions not recommended by the guidelines.
Results: We identified 38 items indicative of optimal clinical care for patients with ABPA. The score for screening asthmatics for ABPA was set at three points. For diagnosing ABPA, 16 items were included, with a score ranging from 12 to 16 points, depending on the specific components used (predisposing conditions, serum A. fumigatus-specific IgE and IgG, serum total IgE, blood eosinophil count and chest computed tomography). The management of acute ABPA comprised 11 items, with a maximum score of three points. For treatment-dependent ABPA, there were nine items (scores ranging from −3 to 6). Follow-up care comprised 10 items with a maximum score of 10–13 points, covering imaging, spirometry, testing serum total IgE levels and therapeutic drug monitoring.
Conclusions: The EQUAL ABPA score has been developed as a comprehensive tool to quantify guideline adherence. Future studies will evaluate to which extent guideline adherence is associated with improved clinical outcomes for patients with ABPA.
Other specific ASP article suggested by Editorial Board
A Bundle of the “Top 10” OPAT Publications in 2023
DOI:- 10.1093/ofid/ofae635
Authors: Lindsey M Childs-Kean et al.,
Abstract
Outpatient parenteral antimicrobial therapy (OPAT) has become more common in infectious diseases practice settings. Similarly, OPAT-related publications have also increased. The objective of this article was to summarize clinically important OPAT-related publications from 2023. Eighty-one articles were found on initial search, with 52 meeting inclusion criteria. A survey containing the 19 articles that had at least one citation was sent to an email listserv of multidisciplinary clinicians with OPAT experience. This article summarizes the “top 10” 2023 OPAT articles from the survey results.
Other specific DSP article suggested by Editorial Board, Systematic review/Scoping review with large effect size
Droplet Digital Polymerase Chain Reaction (ddPCR) for Bloodstream Infections: A Meta-Analysis
Authors: Sihan Liu et al.,
Abstract
Summary: The initial metanalysis using a total of 13 studies representing data from 1,477 cases of BSIs and suspected BSI revealed that Droplet Digital Polymerase Chain Reaction (ddPCR) exhibits high sensitivity (pooled sensitivity= 0.74), specificity (pooled specificity= 0.56) with positive likelihood ratio of 1.56 suggesting its potential utility as a tool for the early detection of BSIs and suspected BSIs.
Other specific ISP article suggested by Editorial Board
Developing a European framework for the prevention of communicable diseases: three points for attention
Authors: Daniel H de Vries et al.,
Abstract
The capacity to deliver programmes that prevent and control infectious diseases is a key public health function. The European Centre for Disease Prevention and Control (ECDC) aims to support and strengthen this capacity in European Union/ European Economic Area (EU/EEA) countries as part of its 2021–27 strategy which includes explicit attention to social and behavioural aspects of disease prevention. To achieve its strategic goals, it is important that ECDC improves its knowledge of prevention strategies, actors and activities in EU/EEA countries. In this Perspective, we summarise three challenges to implementing the prevention framework proposed by ECDC: (i) defining, recognising and identifying with ‘prevention’, (ii) integrating new understandings into established ways of thinking, and (iii) the need for more attention to prevention in governance. These challenges are derived from the findings of a project which conducted a preliminary mapping of prevention actors, networks and activities in four EU countries to support the development of a community of practice within the new ECDC prevention framework. This Perspective serves to draw attention to this prevention framework and the three identified challenges for those working on its implementation.
Other specific ISP article suggested by Editorial Board
Subcutaneous tunneling versus conventional insertion of peripherally inserted central catheters in hospitalized patients (TUNNEL-PICC): a multicentre, open-label, randomized, controlled trial
Authors: Eung Tae Kim et al.,
Abstract
Objective: We aimed to evaluate whether subcutaneous tunneling in peripherally inserted central catheters (PICC) placement could reduce the occurrence of central-line associated blood stream infection (CLABSI).
Methods: We conducted an open-label, multicentre, randomized, controlled trial in five tertiary hospitals. Adult hospitalized patients requiring a PICC were randomized in a one-to-one ratio to conventional (cPICC) or tunneled PICC (tPICC) arms using a centralized web-based computer-generated stratified randomization. CLABSI rates between groups were compared in a modified intention-to-treat population. Safety including the incidence of exit-site infection or hemorrhage-associated catheter removal were also compared. This trial was registered with Clinical Research Information Service of Republic of Korea (KCT0005521).
Results: From November 2020 to March 2023, 1,324 participants were enrolled and randomly assigned to tPICC (n=662) and cPICC (n=662). This study was terminated early due to the cohort CLABSI rate being lower than estimated, therefore, the original sample size of 1,694 would render the study underpowered to detect a difference in CLABSI rates. In the tPICC, CLABSI occurred in 13 of 651 participants over 11,071 catheter-days (1.2/1,000 catheter-days), compared with 20 among 650 patients with cPICC over 11,141 catheter-days (1.8/1,000 catheter-days, rate ratio 0.65, 95% CI 0.30–1.38, p=0.30). The incidence of exit-site infection (29 tPICC, 36 cPICC, p=0.5) and hemorrhage-associated catheter removal (11 tPICC, 11 cPICC, p=0.99) was not different between both groups.
Conclusion: Due to insufficient sample size, this study could not demonstrate a statistically significant CLABSI risk reduction in the tPICC group compared to the cPICC group. Both groups had similar rates of exit site infection and bleeding.