SASPI Ltd.
RCTs having large positive / negative effect,
Other specific ASP article suggested by Editorial Board
Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections
Authors: The BALANCE Trial Investigators
Abstract
Background: Bloodstream infections are associated with substantial morbidity and mortality. Early, appropriate antibiotic therapy is important, but the duration of treatment is uncertain.
Methods: In a multicenter, noninferiority trial, we randomly assigned hospitalized patients (including patients in the intensive care unit [ICU]) who had bloodstream infection to receive antibiotic treatment for 7 days or 14 days. Antibiotic selection, dosing, and route were at the discretion of the treating team. We excluded patients with severe immunosuppression, foci requiring prolonged treatment, single cultures with possible contaminants, or cultures yielding Staphylococcus aureus. The primary outcome was death from any cause by 90 days after diagnosis of the bloodstream infection, with a noninferiority margin of 4 percentage points.
Results: Across 74 hospitals in seven countries, 3608 patients underwent randomization and were included in the intention-to-treat analysis; 1814 patients were assigned to 7 days of antibiotic treatment, and 1794 to 14 days. At enrollment, 55.0% of patients were in the ICU and 45.0% were on hospital wards. Infections were acquired in the community (75.4%), hospital wards (13.4%) and ICUs (11.2%). Bacteremia most commonly originated from the urinary tract (42.2%), abdomen (18.8%), lung (13.0%), vascular catheters (6.3%), and skin or soft tissue (5.2%). By 90 days, 261 patients (14.5%) receiving antibiotics for 7 days had died and 286 patients (16.1%) receiving antibiotics for 14 days had died (difference, −1.6 percentage points [95.7% confidence interval {CI}, −4.0 to 0.8]), which showed the noninferiority of the shorter treatment duration. Patients were treated for longer than the assigned duration in 23.1% of the patients in the 7-day group and in 10.7% of the patients in the 14-day group. A per-protocol analysis also showed noninferiority (difference, −2.0 percentage points [95% CI, −4.5 to 0.6]). These findings were generally consistent across secondary clinical outcomes and across prespecified subgroups defined according to patient, pathogen, and syndrome characteristics.
Conclusions: Among hospitalized patients with bloodstream infection, antibiotic treatment for 7 days was noninferior to treatment for 14 days. (Funded by the Canadian Institutes of Health Research and others; BALANCE ClinicalTrials.gov number, NCT03005145.)
Systematic review/Scoping review with large effect size,
Other specific ISP article suggested by Editorial Board
The effect of pre-COVID and post-COVID vaccination on long COVID: a systematic review and meta-analysis
Authors: King Ngai Chow et al.,
Abstract
Highlights
* We reviewed 25 studies on the relationship between vaccination and long COVID
* We performed meta-analysis with the Der Simonian and Laird random effects model
* 2-dose pre-COVID vaccination was associated with 24% reduced odds of long COVID
* 1-dose post-COVID vaccination was associated with 15% reduced odds of long COVID
* Vaccination could partially protect against long COVID and maintain quality of life
Background: Long COVID affects millions of people and results in a substantial decrease in quality of life. Previous primary studies and reviews attempted to study the effect of vaccination against long COVID, but these studies varied in the cut-off time of long COVID. We adhered to the WHO’s definition of long COVID and conducted a systematic review and meta-analysis on the effect of pre-COVID and post-COVID vaccination on long COVID.
Methods: We obtained data from 13 databases up to 18 February 2024, including peer reviewed and preprint studies. Our inclusion criteria were: (1) long COVID definition as 3 months or beyond, (2) comparing long COVID symptoms between vaccinated and unvaccinated groups, (3) subjects received vaccinations either before or after infected with COVID, (4) the number of doses received by participants was specified. We extracted study characteristics and data and computed the summary odds ratio (OR) with the DerSimonian and Laird random effects model. We then performed subgroup analyses based on the main vaccine brand and long COVID assessment method. ROBINS-I framework was used for assessment of risk of bias and the GRADE approach was used for evaluating the certainty of evidence.
Findings: We included data from 25 observational studies (n=14,128,260) with no randomised controlled trials. One-dose pre-COVID vaccination did not have an effect on long COVID (number of studies = 10, summary OR = 1.01, 95% CI = 0.88-1.15, p-value = 0.896). Two-dose pre-COVID vaccination was associated with a 24% reduced odds of long COVID (number of studies = 15, summary OR = 0.76, 95% CI = 0.65-0.89, p-value = 0.001) and 4 symptoms (fatigue, headache, loss of smell, muscle pain) out of 10 symptoms analysed. The OR of three-dose pre-COVID vaccination against overall long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.31, 95% CI = 0.05-1.84, p-value = 0.198). One-dose post-COVID vaccination was associated with a 15% reduced odds of long COVID (number of studies = 5, summary OR = 0.85, 95% CI = 0.73-0.98, p-value = 0.024). The OR of two-dose post-COVID vaccination against long COVID was statistically insignificant but was far away from 1 (number of studies = 3, summary OR = 0.63, 95% CI = 0.38-1.03, p-value = 0.066).
Interpretation: Our study suggests that 2-dose pre-COVID vaccination and 1-dose post-COVID vaccination are associated with a lower risk of long COVID. Since long COVID reduces quality of life substantially, vaccination could be a possible measure to maintain quality of life by partially protecting against long COVID.
Systematic review/Scoping review with large effect size
State-of-the-Art Review: Ocular Infections
DOI: 10.1093/cid/ciae434
Authors: Miriam B Barshak et al.,
Abstract
Eye infections are common and often generate visits to emergency departments, primary care settings, and ophthalmology or other eye care clinicians. Most episodes are managed without infectious disease (ID) specialty input. Infectious disease specialists are often consulted regarding severe or immediately sight-threatening infection, diagnostic uncertainty, antimicrobial resistance, intolerance or failure of standard treatment, or concern for associated extraocular infection or comorbidities. Diagnosing and managing ocular infections can be inherently challenging. For ID specialists, there may be additional challenges in performing the exam and in understanding the anatomy, the ophthalmologist’s note, the natural course of these infections, and the medical and interventional treatment options. Here we highlight some common and uncommon ocular infections with a goal of addressing these challenges.
Systematic review/Scoping review with large effect size
Ocular Infections in International Travelers
Authors: Francesca F. Norman et al.,
Abstract
Introduction: Ophthalmological conditions in international travelers may be associated with low mortality but high morbidity. Eye involvement in travelers is less frequently reported than febrile, gastrointestinal and respiratory infections, but data probably represent a degree of under-notification.
Methods: An extensive narrative review of the main viral, bacterial, fungal and parasitic infections affecting the eye in travelers was performed.
Main findings: Common respiratory tract viral infections may cause ocular complications in travelers, human influenza viruses have been associated with conjunctivitis and emerging avian influenza subtypes may also affect the eye. Vector-borne viral infections may affect travelers, usually with systemic symptoms, but eye disease may be the first presenting feature. A spectrum of manifestations have been described with dengue, chikungunya and Zika infections, including conjunctivitis, anterior uveitis, posterior uveitis with chorioretinitis and macular involvement. Staphylococcus spp, Streptococcus spp, and Pseudomonas spp (especially associated with use of contact lenses) are common causes of keratitis, however, resistance patterns to antimicrobials might vary depending on area of travel. Less frequent infections, such as Burkholderia pseudomallei, associated with environmental exposure, and Bartonella spp. may rarely present with ophthalmological involvement in travelers. Fungal ocular infections, especially after ocular trauma caused by plants and contact lens use, should be considered in patients with stromal keratitis not improving with antibiotic eye drops. Parasitic eye infections tend to occur in tropical areas, but some, such as acanthamoebic keratitis or Toxoplasma spp retinitis, are found worldwide. Increasing exposure to animals, undercooked food consumption or poor hygiene during international travels might be leading to the emergence of certain parasitic eye diseases.
Conclusions: Clinical features, with identification of risk factors and geographical region of exposure, can assist in the definitive diagnosis of imported ophthalmological infections. Management of imported eye infections requires a multi-disciplinary approach involving ophthalmologists, travel medicine/infectious diseases physicians and other specialists.
Systematic review/Scoping review with large effect size
Infectious uveitis: a comprehensive systematic review of emerging trends and molecular pathogenesis using network analysis
Authors: Muhammad Arif Asghar et al.,
Abstract
Background: Infectious uveitis is a significant cause of visual impairment worldwide, caused by diverse pathogens such as viruses, bacteria, fungi, and parasites. Understanding its prevalence, etiology, pathogenesis, molecular mechanism, and clinical manifestations is essential for effective diagnosis and management.
Methods: A systematic literature search was conducted using PubMed, Google Scholar, Web of Science, Scopus, and Embase, focusing on studies published in the last fifteen years from 2009 to 2023. Keywords included “uveitis,” “infectious uveitis,” “viral uveitis,” and others. Rigorous inclusion and exclusion criteria were applied, and data were synthesized thematically. Gene symbols related to infectious uveitis were analyzed using protein-protein interaction (PPI) networks and pathway analyses to uncover molecular mechanisms associated with infectious uveitis.
Results: The search from different databases yielded 97 eligible studies. The review identified a significant rise in publications on infectious uveitis, particularly viral uveitis, over the past fifteen years. Infectious uveitis prevalence varies geographically, with high rates in developing regions due to systemic infections and limited diagnostic resources. Etiologies include viruses (39%), bacteria (17%), and other pathogens, substantially impacting adults aged 20–50 years. Pathogenesis involves complex interactions between infectious agents and the ocular immune response, with key roles for cytokines and chemokines. The PPI network highlighted IFNG, IL6, TNF, and CD4 as central nodes. Enriched pathways included cytokine-cytokine receptor interaction and JAK-STAT signaling. Clinical manifestations range from anterior to posterior uveitis, with systemic symptoms often accompanying ocular signs. Diagnostic strategies encompass clinical evaluation, laboratory tests, and imaging, while management involves targeted antimicrobial therapy and anti-inflammatory agents.
Conclusion: This review underscores the complexity of infectious uveitis, driven by diverse pathogens and influenced by various geographical and systemic factors. Molecular insights from PPI networks and pathway analyses provide a deeper understanding of its pathogenesis. Effective management requires comprehensive diagnostic approaches and targeted therapeutic strategies.
Systematic review/Scoping review with large effect size
Nontuberculous Mycobacterial Infective Endocarditis: A Systematic Review of Clinical Characteristics and Outcomes
DOI: 10.1093/ofid/ofae688
Authors: Durga Shankar Meena et al.,
Abstract
Background: Nontuberculous Mycobacterial Infective Endocarditis (NTM IE) is a rare infection, and several outbreaks have been reported in the last two decades. However, the clinical spectrum is still poorly understood. This systematic review aimed to evaluate the clinical characteristics and outcomes in NTM IE.
Methods: We searched the major electronic databases (PubMed, Scopus, and Google Scholar) with appropriate keywords till December 2023. We include studies based on predefined diagnostic criteria, and relevant data on clinical presentation and treatment outcomes was collected. The study was registered with PROSPERO with registration number: CRD42023492577.
Results: A total of 97 studies, encompassing 167 patients with NTM IE, were reviewed. The earliest cases were reported in 1975, involving M. chelonae and M. fortuitum. Mycobacterium chimaera was the most prevalent species (38.9%), though rapidly growing NTMs (RGM) were more common overall (59.3% vs. 40.7%) compared to slow-growing NTMs (SGM). Disseminated NTM infection occurred in 84% of cases, with bone marrow infiltration and osteomyelitis as frequent manifestations. Prosthetic valves were the main risk factor, present in 63.5% of cases. In native valve IE, nearly all cases (n=27, 96%) were attributed to RGM. The overall mortality rate was 44.9%, with conservative management without surgery associated with poorer outcomes (66.7% vs. 30.6%). Mortality was comparable between SGM and RGM IE, although relapses were more common in SGM IE (17.6% vs. 1.9%).
Conclusions: This review highlights the changing epidemiology of NTM IE with the emergence of RGM IE. Disseminated infections in the setting of prosthetic valves warrant NTM evaluation. The high mortality rate necessitates the role of early surgery.
Systematic review/Scoping review with large effect size
Congenital Syphilis—Comprehensive Narrative Review of Alternative Antibiotic Treatment for Use in Neonates
Authors: Villarreal, Diana D et al.,
Abstract
Congenital syphilis rates increased 10-fold from 2012 to 2022 in the United States. Currently, the therapeutic standard of care is 10 days of intravenous aqueous crystalline penicillin G, with very limited evidence for alternatives. A long course of intravenous antibiotic requires hospitalization that is both costly and burdensome for the child and the family. Fortunately, Treponema pallidum retains susceptibility to other antibiotics based on minimum inhibitory concentrations. Based on the evidence of safety and efficacy of different antibiotics for use in neonates, ceftriaxone emerges as a potential parenteral candidate, and amoxicillin emerges as a potential oral candidate for the treatment of congenital syphilis. Other therapeutic alternatives include cefotaxime (where available), ampicillin, doxycycline, cefixime, and linezolid.
Other specific DSP article suggested by Editorial Board
Diagnosing infectious encephalitis: a Narrative review
Authors: Sabine E. Olie et al.,
Abstract
Background: Diagnosing infectious encephalitis can be challenging as it can be caused by a wide range of pathogens, with viruses being the most common cause. In a substantial number of patients, no pathogen is identified despite a clinical diagnosis of infectious encephalitis. Recent advancements in diagnostic testing have introduced new methods to address this diagnostic challenge and improve pathogen detection.
Objectives: To provide a comprehensive clinical approach for diagnosing infectious encephalitis and explore novel diagnostic methods.
Sources: We searched PubMed to identify relevant literature on diagnosing encephalitis in English up to the September 1st 2024as well as included articles known by the authors.
Content: Clinical characteristics may suggest a specific cause of infectious encephalitis, but are insufficient to guide treatment decisions. Therefore, cerebrospinal fluid (CSF) examination remains the cornerstone of the diagnostic process, with CSF leukocyte count being the most reliable predictor for central nervous system (CNS) infections. CSF features can be normal, however, in a proportion of patients presenting with infectious encephalitis. A definite diagnosis of infectious encephalitis is established by microbiological or histopathological tests in approximately 50% of patients. Additional investigations, including neuroimaging or EEG, can provide evidence for encephalitis or help to identify alternate conditions, although their role is primarily supportive. Emerging diagnostic techniques, including next generation sequencing metagenomics and unbiased serology (PhipSeq), have the potential to increase the proportion of patients with a confirmed diagnosis. However, these techniques are not yet practical due to their complex analysis, long turnaround times and high costs.
Implications: Microbiological confirmation is paramount in the diagnosis of infectious encephalitis, but it is currently established in about half of cases. While novel techniques show promise to increase the proportion of cause specific diagnoses, they are not yet suitable for routine use. This highlights the ongoing need for advancements in diagnostic methods.
Other specific DSP article suggested by Editorial Board
Global Trends in the Application of Droplet Digital PCR Technology in the Field of Infectious Disease Pathogen Diagnosis: A Bibliometric Analysis from 2012 to 2023
Authors: Xiaojie Yang et al.,
Abstract
Background: This study discusses the development trends and current applications of digital droplet PCR technology in pathogen diagnostics.
Methods: A bibliometric analysis was conducted by retrieving droplet digital pcr related articles published between January 1,2012 to December31, 2023, from the Web of Science Core Collection.
Results: A total of 3,513 authors from 66 countries published 508 research papers across 203 academic institutions. The keyword clustering network shows that the main advantages of ddPCR are absolute quantification, high sensitivity, and high tolerance to PCR inhibitors. The keyword timeline shows that current research hotspots include continuous pathogen nucleic acid monitoring, trace sample detection, and resistance mutation identification.
Conclusion: The application of ddPCR in pathogen diagnosis is expanding, offering key advantages in absolute quantification, high sensitivity, and inhibitor tolerance, meeting emerging needs in nucleic acid monitoring and resistance detection.
Other specific ASP article suggested by Editorial Board
Not Just an Oxymoron: The Utilitarian’s Guide to Antimicrobial Stewardship in Transplant Infectious Diseases
DOI: 10.1111/tid.14399
Authors: Chelsea A. Gorsline et al.,
Abstract
Solid organ transplant and hematopoietic cell transplant patients face an increased risk of infectious diseases, greater exposure to antibiotics, and heightened risk of multidrug-resistant organisms (MDROs) due to their immunosuppressed state. Antimicrobial stewardship programs (ASP) are essential in reducing the incidence of MDRO by conserving antimicrobial use, minimizing treatment durations, and improving the appropriate use of diagnostic testing. However, the role of ASP in transplant infectious diseases (TID) is still evolving, necessitating greater collaboration between ASP and transplant programs. This collaboration will mitigate infection risks, reduce infection-associated costs, and improve outcomes. This article reviews the key components for implementing ASP in TID, especially for those that are establishing or growing their ASP to include TID, including specific goals, structure and funding, ASP initiatives (including antibiotic allergy delabeling, diagnostic stewardship, and antiviral/antifungal stewardship), metrics, and educational opportunities.