Practical considerations for the Implementation of Syndromic Panels and Diagnostic stewardship in the era of syndromic panel testing
Authors: Subedi S et al
Abstract
Background: The significant advancements in the development of syndromic panel testing for infectious diseases have brought about a paradigm shift in the clinical microbiology laboratory and the practices of Infectious Diseases Physicians. Due to the considerable costs associated with these tests, it is crucial for laboratories and healthcare services to devise implementation strategies and prioritise diagnostic stewardship when incorporating these panels into the laboratory.
Objectives: To describe the implementation considerations and the diagnostic stewardship strategies for integrating syndromic panels in the clinical microbiology laboratory. laboratory.
Sources: Peer reviewed publications were searched through Pubmed and Embase databases. Further citation search was carried out using google scholar.
Content: Evidence from clinical and laboratory studies on syndromic panels of blood stream infection, meningitis and encephalitis, and pneumonia suggest that syndromic panels can improve antimicrobial optimisation and shorten time to targeted therapy, particularly when implemented alongside antimicrobial stewardship interventions. However, there are limited numbers of randomised controlled trials, and many studies are observational, with variable endpoints and limited generalisability. Cost-effectiveness analyses are often model-based and lack real-world validation. Behavioural drivers of inappropriate test use are underexplored, highlighting the need for comprehensive diagnostic stewardship strategies. Effective implementation requires careful panel selection, local validation, and sustained collaboration between clinical microbiology and antimicrobial stewardship teams.
Implications: Incorporation of syndromic panel in clinical microbiology laboratory requires careful consideration of implementation and diagnostic stewardship strategies. Future research should focus on standardising implementation frameworks, generating real-time cost-effectiveness data, and exploring decision-support tools including artificial intelligence to augment antimicrobial stewardship efforts as well as more evidence from low resource settings. Additionally, qualitative research is needed to understand behavioural influences on test utilisation and to develop interventions that promote appropriate use in real-world settings.”
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Guiding Clostridioides difficile Infection Prevention Efforts in a Hospital Setting With AI
Authors: Tang S et al
Abstract
Importance: Increasingly, artificial intelligence (AI) is being used to develop models that can identify patients at high risk for adverse outcomes. However, the clinical impact of these models remains largely unrealized.
Objective: To evaluate the association of an AI-guided infection prevention bundle with Clostridioides difficile infection (CDI) incidence in a hospital setting.
Design, setting, and participants: This prospective, single-center quality improvement study evaluated adult inpatient hospitalizations before (September 1, 2021, to August 31, 2022) and after (January 1, 2023, to December 31, 2023) AI implementation. Data analysis was performed from January to August 2024.
Intervention: A previously validated institution-specific AI model for CDI risk prediction was integrated into clinical workflows at the study site. The model was used to guide infection prevention practices for reducing pathogen exposure through enhanced hand hygiene and reducing host susceptibility through antimicrobial stewardship.
Main outcomes and measures: The primary outcome was CDI incidence rate. Secondary outcomes included antimicrobial use and qualitative assessments of bundle implementation.
Results: Pre-AI and post-AI samples included 39 046 (21 645 [55.4%] female; median [IQR] age, 58 [36-70] years) and 40 515 (22 575 [55.7%] female; median [IQR] age, 58 [37-70] years) hospitalizations, respectively. After adjusting for differences in clinical characteristics, there was no significant reduction in CDI incidence (pre-AI period: 5.76 per 10 000 patient-days vs post-AI period: 5.65 per 10 000 patient-days; absolute difference, -0.11; 95% CI, -1.43 to 1.18; P = .85). Relative reductions greater than 10% in normalized antimicrobial days were seen for piperacillin-tazobactam (-9.64; 95% CI, -12.93 to -6.28; P < .001) and clindamycin (-1.04; 95% CI, -1.60 to -0.47; P = .03), especially for high-risk patients alerted by AI (relative reduction for piperacillin-tazobactam, 16.8%; 95% CI, 8.0%-24.6%). On the basis of qualitative assessments via semistructured interviews and field observations, the study found that health care staff’s experiences with AI-guided workflows varied. In particular, the enhanced hand hygiene protocols were met with poor adherence, whereas pharmacists consistently engaged with the alerts.
Conclusions and relevance: In this quality improvement study, the implementation of an AI-guided infection prevention bundle was not associated with a significant reduction in the already low CDI incidence rate at the study site, but it was associated with reduced CDI-associated antimicrobial use. The results highlight the potential of AI in supporting antimicrobial stewardship. Barriers to implementation, including infrastructure, staff knowledge, and workflow integration, need to be addressed in future applications.
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Antibiotic Resistance: Revisiting Older Antibiotics for Modern Bacterial Challenges.
Authors: Boretti A et al
Abstract
The growing challenge of antibiotic resistance necessitates a strategic re-evaluation of older antibiotics as vital antimicrobial tools. This re-assessment, while facing hurdles, reveals promising possibilities. Understanding bacterial resistance mechanisms is fundamental for effectively utilizing these legacy drugs. Older antibiotics typically have a narrower spectrum than modern ones, emphasizing careful antimicrobial stewardship to prevent overuse and further resistance. Strategies to improve their clinical value include combination therapies with newer antibiotics to overcome resistance and boost efficacy. Furthermore, repurposing and reformulating older antibiotics can enhance their activity against contemporary bacterial strains. Targeted treatment regimens focusing on specific clinical niches or bacterial species where older antibiotics remain effective, are crucial. Streptothricin F exemplifies this renewed potential, particularly against Gram-negative bacteria, a recent research focus. Despite prior concerns about its limited spectrum and resistance potential, recent findings indicate streptothricin F’s re-emerging utility. This antibiotic’s ability to target highly resistant Gram-negative pathogens, such as carbapenem-resistant Enterobacterales, highlights its potential as a valuable therapeutic option. This encouraging discovery underscores the need for further research into streptothricin F’s role in combating drug-resistant Gram-negative pathogens, opening avenues for future investigation.
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Antibiotics are like gold’: a qualitative study of patient perspectives on the use of antibiotics without a prescription.
Authors: Laytner LA et al
Abstract
Background: Using antibiotics without a prescription (non-prescription use) is common in the USA and contributes to antibiotic misuse, potentially harming individuals and threatening public health. At the individual level, safety issues related to non-prescription use include adverse drug reactions and disruption of healthy microbiomes. At the public health level, non-prescription use increases the risk of antimicrobial resistance.
Objectives: This qualitative study explored the reasons and motivations underlying non-prescription use among adult outpatients with varying healthcare coverage and education.
Methods: Purposive sampling was used to recruit participants who endorsed using non-prescription antibiotics in a larger quantitative survey. Participants were patients recruited from six public and two private clinics in Houston and Katy, Texas. All interviews were semistructured and conducted remotely by trained research coordinators in the participant’s preferred language (English or Spanish). Interviews captured elements from two domains of the Kilbourne Theoretical Framework for Advancing Health Disparities Research, including patients’ attitudes and beliefs, resources and various healthcare-system factors that could impact non-prescription use. Thematic analysis revealed the factors and situations that contribute to non-prescription use. Results: Of 86 participants surveyed, 72% were female and 24% had Medicare or private insurance. The thematic analyses on why participants use non-prescription antibiotics are organised into two domains: (1) patient beliefs and experiences and (2) healthcare system barriers. Patient beliefs and experiences revealed four themes: (1) belief that antibiotics relieve many symptoms/illnesses (eg, pain, sore throat, if symptoms/illnesses are persistent, lingering or severe), (2) belief that patients know their own bodies (eg, participants’ perceived self-efficacy in knowing and using medications for their illnesses/symptoms), (3) belief that over-the-counter medicines do not work and (4) belief that antibiotics are like gold (eg, antibiotics are difficult to obtain, valuable and highly effective). Healthcare system barriers revealed two themes: (1) patients encounter obstacles to healthcare (eg, transportation, long wait times, high healthcare costs and lack of reliable telemedicine options) and (2) patients express convenience in using non-prescription antibiotics from multiple sources (eg, leftover prescriptions, social networks or purchased without a prescription).
Conclusions: Barriers to care, the convenience of obtaining non-prescription antibiotics, and patients’ beliefs regarding the powerful value of antibiotics and their agency to direct this aspect of care present challenges that need to be explored to design effective outpatient antibiotic stewardship programmes.
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Performance of Galactomannan, Aspergillus-PCR, and Metagenomic sequencing for the diagnosis of invasive pulmonary aspergillosis in hematological patients
Authors: Chun-Hui Xu
Abstract
Background/purpose(s): Invasive pulmonary aspergillosis (IPA) is a serious fungal infection, and its diagnosis is diverse, especially in patients with hematological disorders. This study aims to determine the optimal diagnostic strategy for IPA in such patients by comparing various microbiological tests.
Methods: A total of 490 blood and 138 bronchoalveolar lavage fluid (BALF) samples collected from 182 IPA and 407 no-IPA patients (based on EORTC/MSGERC criteria) were retrospectively analyzed by metagenomic next-generation sequencing (mNGS), Aspergillus-PCR, and galactomannan (GM) (enzyme immunoassay [EIA] and lateral flow assay [LFA]).
Results: In BALF samples, GM-EIA, GM-LFA, Aspergillus-PCR, and mNGS showed sensitivities of 68.1 %, 53.2 %, 83.0 %, and 59.6 %—all higher than in blood (43.7 %, 34.4 %, 51.7 %, 55.0 %). In blood samples, mNGS had the highest sensitivity (71.9 %) in neutropenic patients, which was further improved when combined with GM-EIA (77.1 %). In non-neutropenic patients, Aspergillus-PCR was the most sensitive assay (47.3 %), with sensitivity improving to 56.4 % when combined with GM-EIA. Blood test sensitivities were lower in patients with prolonged antifungal therapy (≥7 days) vs. <7 days (Aspergillus-PCR: 38.6 % vs. 57.0 %; mNGS: 31.8 % vs. 64.5 %; GM-EIA: 27.3 % vs. 50.5 %; all P < 0.05), with no impact on BALF results.
Conclusion: BALF is critical for accurate IPA diagnosis, particularly in patients with prior antifungal therapy. BALF Aspergillus-PCR offers optimal sensitivity, while blood-based mNGS and PCR are recommended for neutropenic and non-neutropenic patients, respectively. Combining molecular methods with GM testing enhances diagnostic performances. Tailored strategies are essential to improve early detection and clinical outcomes in high-risk hematologic populations.”
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Effects of COVID-19 vaccination and past SARS-CoV-2 infection on subsequent COVID-19 infection in people with HIV
Authors: Xueying Yang
Abstract
Background : This study aims to estimate the time-varying effects of primary and booster COVID-19 vaccination and past SARS-CoV-2 infection on subsequent SARS-CoV-2 infection (including new infection and re-infection) in people with HIV (PWH).
Methods
A population-based cohort was retrieved from the integrated statewide HIV electronic health record (EHR) dataset, COVID-19 vaccination dataset, and COVID-19 diagnoses dataset between March 2, 2020 and April 14, 2022. The pre-specified outcome was any SARS-CoV-2 infection. We used Cox regression to estimate the time-varying effects of primary and booster vaccination and past infection on the risks of subsequent SARS-CoV-2 infection.
Results
A total of 18,509 eligible PWH who had documentation of COVID-19 testing or COVID-19 vaccination records were included for analysis. The effectiveness of primary vaccination against infection, compared with being unvaccinated, was relatively low (26.70 %, 95 % CI: 12.10 %, 38.88 %) at two months, while the effectiveness of a booster dose after two months was high (43.53 %, 95 %CI: 27.54 %, 55.99 %), compared with primary vaccination only (e.g., first two doses of Pfizer or Moderna, or the single dose of Janssen). The effectiveness of past COVID-19 infection during Pre-Delta and Delta dominant periods at one month against reinfection was (67.43 %; 95 %CI: 52.74 %, 77.55 %) and (64.57 %; 95 %CI: 1.39 %, 87.27 %), respectively.
Conclusion
Natural immunity conferred from past COVID-19 infection in PWH against reinfection appeared to be higher than vaccine-induced immunity. Boosters were more effective than the primary series alone in preventing subsequent infection.”
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The synergistic effect of imipenem combined with ceftazidime-avibactam against Klebsiella pneumoniae with alternating resistance to CZA and carbapenem
Authors: Yun-Ying Wang
Abstract
Purposes :The purpose of this study was to explore the mechanisms of resistance of clinically isolated K. pneumoniae, which is alternately resistant to carbapenems and ceftazidime/avibactam (CZA), and therapeutic strategies.
Methods : Whole-genome sequencing was used to determine the resistance mechanisms of K. pneumoniae. In vitro antibiotic induction experiments were used to verify the reversibility of blaKPC mutations in these strains. Checkerboard analysis and growth curve analysis were used to evaluate the efficacy of imipenem (IMP) combined with CZA.
Results: The clinical strains exhibited alternating resistance and susceptibility to IMP and CZA during clinical treatment, namely, resistance-susceptibility-resistance to IMP and susceptibility-resistance-susceptibility to CZA. The resistance mechanism involved blaKPC mutation, which changed from blaKPC2 to blaKPC33 and then back to blaKPC2. In addition, the blaKPC14 in the CZA-resistant K. pneumoniae strain reverted to blaKPC2 after treatment with carbapenem, confirming the reversibility of the blaKPC mutations under the selective pressure of antibiotics. For KPC-producing K. pneumoniae (KPC-Kp) with the above drug-resistant phenotype, the combination of IMP and CZA had synergistic effects, indicating better bactericidal efficacy than IMP, MER, or CZA alone.
Conclusion : This study revealed that CRKP developed CZA resistance due to blaKPC mutation, and carbapenem susceptibility was restored. After retreatment with carbapenem, the strains showed carbapenem resistance, and they regained susceptibility to CZA. For the first time, we showed that the blaKPC mutation was reversible. For such clinical isolates, the combination of IMP and CZA could delay or prevent mutations in blaKPC and have a synergistic effect.”
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Crosstalk between human endogenous retroviruses and exogenous viruses
Authors: Edoardo Pizzioli
Abstract
Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections of human germ-line cells, which are mostly silenced during evolution, but could be de-repressed and play a pathological role. Infection with some exogenous viruses, including herpesviruses, HIV-1 and SARS-CoV-2, was demonstrated to induce the expression of HERV RNAs and proteins.”
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Authors: Guangxu Mao