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Genomic surveillance of multidrug-resistant Enterobacterales in a long-term care facility in Northern Italy based on a point prevalence screening.
Authors: Bianconi I et al
Abstract
Long-term care facilities (LTCFs) are increasingly recognised as settings where multidrug-resistant organisms (MDROs) persist and circulate. A point prevalence screening study conducted in 2022 in an LTCF in the Autonomous Province of Bolzano/Bozen, Northern Italy, provided a collection of MDR Enterobacterales isolates from residents and staff. This study aimed to characterise the clonal structure, transmission dynamics, and resistance mechanisms of these isolates through high-resolution genomic analysis. Whole-genome sequencing was performed on third-generation cephalosporin- and/or carbapenem-resistant isolates of Klebsiella pneumoniae, Escherichia coli, Morganella morganii, and Proteus mirabilis. Isolates underwent core genome multilocus sequence typing, phylogenetic reconstruction, and resistance gene profiling using Kleborate and ResFinder. K. pneumoniae isolates formed five major clusters, with ST39 confined to a single section, suggesting intra-section transmission. ST405 and ST307, both high-risk clones, were also detected, with ST307 harbouring the carbapenemase gene blaKPC-3. CTX-M-15 was present in 90% of K. pneumoniae isolates. E. coli isolates showed high genomic diversity with limited evidence of clonal transmission. M. morganii and P. mirabilis displayed mixed patterns, with sporadic introductions and one clonal cluster for P. mirabilis. Genomic surveillance revealed complex transmission networks within this LTCF, involving both clonal expansion and heterogeneous strain circulation. Organisational factors such as patient transfers, shared staff, and communal living likely contributed to MDROs dissemination. The predominance of CTX-M-15 and detection of carbapenemase-producing K. pneumoniae underscore the need for targeted infection control strategies. Integration of genomic data with contextual factors supports continuous genomic monitoring, antimicrobial stewardship, and environmental decontamination in LTCFs.
Other specific DSP article suggested by Editorial Board
The antimicrobial treatment guidelines quality and reporting assessment: A systematic review.
Authors: Homs-Estévez A, et al
Abstract
Background and objective: Inappropriate use of antimicrobial agents accelerates the emergence and spread of resistance. Antimicrobial treatment guidelines (ATG) stand between evidence and clinical practice as they are designed to guide policy decision framework for all stakeholders promoting the prudent use of antimicrobials in bedside care. The trustworthiness of these decision-making instruments relies on their methodological quality and reporting. The aim of this systematic review is to critically appraise the methodological quality and reporting of antimicrobial treatment guidelines using the AGREE II, AGREE-REX tools and the RIGHT checklist respectively.
Materials and methods: A systematic review was conducted. ATGs from public institutions and hospitals with over 500 beds were identified through a systematic search using the Google search engine and by consulting members of the AFinf workgroup (https://gruposdetrabajo.sefh.es/afinf/en/). Screening and data extraction were performed in duplicate. Quality and reporting were assessed using the validated checklists AGREE II, AGREE REX and RIGHT. Central tendency, dispersion, and correlations were calculated and compared using Student’s t-test. Results are de-identified.
Prospective protocol: https://osf.io/cey2v RESULTS: N=22. The mean scores for AGREE II, AGREE-REX, and RIGHT were generally low: 31.0% (95% CI: 23.7%-38.3%), 20.4% (95% CI: 15.6%-25.1%), and 28.7% (95% CI: 23.4%-34.0%) respectively. Low rates were observed for development rigour (10.2%); reference existing reviews (4.6%); quality assurance (4.6%); conflict of interests disclosure (4.6%); values and preferences (1.9%) while clarity (94.8%) and implementability (37.7%) rated the highest. Strong correlations among AGREE II and AGREE-REX (corr=0.9092) and RIGHT (corr=0.9203).
Conclusion: There is room for improvement in the quality and reporting of current ATGs in Spain, especially at hospital level, where they have greater potential to optimize antibiotic prescribing practices.
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Severe community-acquired pneumonia: a paradigm shift toward precision diagnostics, microbiology, and targeted management.
Authors: Martin-Loeches I, et al
Abstract
Purpose of review: Severe community-acquired pneumonia (sCAP) remains one of the most lethal infectious syndromes in critical care, with mortality remaining persistently high despite decades of antimicrobial and supportive care advances. This review appraises recent developments in diagnostics, microbiology, and host-response biology, and advocates for a fundamental shift toward precision-driven management.
Recent findings: High-resolution molecular diagnostics have exposed the true complexity of sCAP, revealing a substantial viral burden and a polymicrobial ecosystem that challenges traditional pathogen-centric models. Yet, this diagnostic revolution has failed to translate into meaningful antimicrobial stewardship, reflecting a persistent disconnect between detection and decision-making. At the same time, multiomic and transcriptomic studies have redefined sCAP as a biologically heterogeneous syndrome, characterized by divergent host-response states ranging from hyperinflammation to immune dysfunction. These insights are beginning to reshape therapy, supporting phenotype-directed immunomodulation, including selective corticosteroid use and biomarker-guided interventions such as interleukin-1 blockade. In parallel, artificial intelligence and radiomics are emerging as powerful tools capable of integrating complex, multidimensional data, although their clinical utility remains largely unrealized. Summary: sCAP should no longer be approached as a uniform infectious disease but as a spectrum of biologically distinct endotypes. The future lies in integrating pathogen detection with real-time host profiling and advanced analytics to enable truly personalized care. Without this paradigm shift, further gains in outcomes are unlikely.
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High dose, subcutaneous injections of benzathine penicillin G (SCIP) to prevent rheumatic fever: a single arm, phase IIa trial of safety and pharmacokinetics
Authors: Julie Bennett
Abstract
Objectives: This Phase-IIa trial evaluates the safety and pharmacokinetics of high-dose, 10 weekly subcutaneous injections of penicillin (SCIP) in young people with a history of acute rheumatic fever (ARF).
Methods: Participants received 7.2-10.8 MU (13.8-20.7mL) of Bicillin-LA® via subcutaneous injection in Wellington, New Zealand. A subset underwent intensive safety monitoring and serial dried blood spot collection for penicillin assay. Penicillin concentrations informed a population pharmacokinetic model based on 169 data points from 31 participants. The proportion of time penicillin concentrations remained above a range of plausible pharmacological correlates of protection was estimated for SCIP and compared with estimates for intramuscular benzathine penicillin G (BPG).
Results: Fifty-five participants received SCIP at least once, totalling 182 doses. No recurrent ARF or breakthrough streptococcal throat infections were reported. Model-based simulations indicated that SCIP outperformed intramuscular BPG in maintaining protective concentrations across nearly all plausible pharmacological target correlates of protection (10-20ng/mL). SCIP performed even more favourably when considering modified weight-based dosing or missed BPG injections.
Conclusions: SCIP is safe and well tolerated, demonstrating favourable penicillin exposure for most individuals. Future research should explore the effectiveness of SCIP over longer periods and in diverse populations and settings.
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A Novel Machine Learning Approach for Predicting Prognosis of SFTS Patients in the Early Stages of Disease
Authors: Li, Siqi
Abstract
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease characterized by high morbidity and mortality rates. Timely detection and prognosis prediction are critical for implementing effective clinical interventions. This study aimed to develop a binary classification machine learning model utilizing early clinical and laboratory indicators to predict the prognosis of SFTS patients, facilitating early clinical decision-making.
Methods: We conducted a retrospective study including 233 SFTS patients diagnosed from October 2021 to May 2024. Clinical and laboratory data at initial diagnosis were collected and subjected to baseline analysis and correlation analysis to identify significant indicators. Using the area under the receiver operating characteristic curve as an indicator of model performance, select the analytical model among machine learning (LR) models, XGBOOST, LightGBM, and random forest. A binary classification machine learning model for predicting survival outcomes was constructed using a logistic regression algorithm in conjunction with identified metrics. The model’s performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV). The model was externally validated using a separate cohort of 73 patients.
Result: A total of 233 patients were included in this study, among whom 146 (62.7%) survived and 87 (37.3%) died, with 208 assigned to the internal cohort (177 to the training set and 31 to the test set) and the external validation cohort consisted of 73 patients, including 52 survivors (71.2%) and 21 mortality cases (28.8%). Based on the AUC, the LR model (0.750) is selected, where the values of XGBOOST, LightGBM, and random forest are 0.649, 0.661, and 0.716, respectively. The logistic regression model, incorporating age, lactate dehydrogenase (LDH), albumin, activated partial thromboplastin time (APTT), and platelet count, demonstrated robust predictive accuracy with an AUC of 0.913 (95% CI: 0.821–1.000) for the test set and 0.923 (95% CI: 0.842–1.000) for the external validation set. The model exhibited an accuracy of 0.863, with a sensitivity of 0.952 and an NPV of 0.977. The specificity and PPV were 0.827 and 0.690, respectively. These results indicate that the model maintains robust discriminative performance in an independent cohort, suggesting its potential utility as a screening tool with high sensitivity and favorable NPV.
Conclusion: The model constructed using the first diagnostic indicators described above can accurately determine the patient’s prognosis, which can help the clinician intervene earlier as well as take the necessary life-saving measures, and has the potential to improve the survival rate of SFTS patients.”
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Synergistic Effects of Amikacin With Imipenem and Ciprofloxacin Against Multidrug-Resistance Uropathogenic Escherichia coli
DOI: 10.1155/cjid/3283079
Authors: Moharerpour
Abstract
Introduction: There are limited therapeutic options available for treating aminoglycoside- and carbapenem-resistant Gram-negative bacteria. Therefore, there is an urgent need for novel effective antimicrobial agents. Numerous studies have reported the enhanced efficacy of antibiotic combinations against multidrug-resistant (MDR) strains compared to monotherapy. This study aimed to investigate the potential synergistic effects of amikacin in combination with imipenem and ciprofloxacin against clinical isolates of MDR Escherichia coli to identify the most promising antibiotic combinations for treating infections caused by these isolates.
Methods: In this experimental study, 20 MDR E. coli isolates were examined. The minimum inhibitory concentration (MIC) and checkerboard method were determined for amikacin, imipenem, and ciprofloxacin.
Results: MIC determination revealed ciprofloxacin MICs of 4–512 μg/mL, imipenem 0.125–32 μg/mL, and amikacin 1–128 μg/mL. Resistance rates were 55% (11/20) for amikacin, 100% (20/20) for ciprofloxacin, and 55% (11/20) for imipenem. Synergistic effects were observed between amikacin and imipenem in 50% of isolates (10/20) and between amikacin and ciprofloxacin in 40% (8/20), with no antagonistic interactions detected.
Conclusions: The combination of amikacin with imipenem or ciprofloxacin resulted in synergistic and additive effects in some cases. These findings suggest that antibiotic combination therapy could serve as an effective strategy in managing infections caused by antibiotic-resistant isolates.”
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Evaluation of an oral bedaquiline regimen for treating multidrug-resistant TB in China: a randomized trial
Authors: Gao, J.
Abstract
Introduction: Bedaquiline (BDQ) is recommended in China as component of oral short-course regimens (SCR) for MDR-TB patients. However, the efficacy and safety of BDQ containing oral SCRs remain insufficiently validated in large-scale, well-designed clinical trials involving the Chinese population.
Methods: A randomized, non-inferiority, open-label trial was conducted at 17 hospital clinics in China, enrolling adult patients with MDR-TB. Participants were assigned in a 1:1 ratio to receive either a 40-week oral BDQ-containing SCR or a 40-week oral non BDQ-containing SCR. The primary endpoint was the proportion of participants achieving favorable outcome at the end of treatment. The non-inferiority margin of the difference in proportion between the BDQ and control groups in the modified intent-to-treat (mITT) population was set at -15%.
Results: A total of 217 participants were randomized. Among 182 patients in the mITT population, the BDQ-containing SCR group achieved an 80.0% favorable outcome compared to 59.8% in the non-BDQ group, with an adjusted difference of 22.27% (95% CI 9.41–35.13%). BDQ-containing SCR was also associated with higher proportions of modified favorable outcomes and cure rates. Additionally, BDQ-containing SCR resulted in a higher culture conversion rate at the end of treatment and a shorter time to culture conversion. Serious adverse events occurred in 16 of 110 participants (14.5%) in the BDQ-containing SCR group and 25 of 107 participants (23.4%) in the non-BDQ-containing SCR group.
Conclusion: 40-week BDQ-SCR proved non-inferior and superior, safe, and well tolerated in Chinese patients with MDR-TB. Further investigation into the long-term safety and efficacy of the BDQ-containing regimen is still needed in China. ClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022.
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Clinical epidemiology, genospecies distribution, and in vitro susceptibility to novel agents among Burkholderia cepacia complex bloodstream infections in Taiwan
Authors: Huang, ST
Abstract
Purpose: Burkholderia cepacia complex (BCC) showed increased resistance to recommended therapeutic agents, including levofloxacin, ceftazidime, meropenem and trimethoprim/sulfamethoxazole (TMP/SMX). BCC genospecies have different antibiogram patterns, so genospecies dynamics may affect overall susceptibility rates. This study analyzed the clinical epidemiology of BCC bloodstream infections (BSIs), assessed in vitro susceptibility of novel antibiotics, and explored prognostic factors for outcomes of BCC BSIs
Methods: We performed molecular identification to species level and antimicrobial susceptibility test to 12 antibiotics by the CLSI broth microdilution method. The 14-day mortality was used to evaluate the outcomes of BCC BSIs. Multivariate logistic regression was used for outcome analysis
Results: From January 2021 to December 2023, the study included 122 BCC isolates and 100 adult patients with evaluable clinical outcome. Among 122 isolates, we identified 97 isolates of B. cenocepacia, 14 of B. contaminans and 11 of non-cenocepacia and non-contaminans Burkholderia by recA or hisA analysis. Cefiderocol and ceftazidime/avibactam both showed potent activity across different genospecies. Aztreonam/avibactam and ceftolozane/tazobactam showed similar and even lower activity compared to ceftazidime and meropenem. Source control was associated with better survival (adjust odds ratio, 0.02; 95% CI 0.003-0.12). Neither regimens of antibiotic therapy nor genospecies was associated with 14-day survival
Conclusions: The study highlighted the survival benefit of source control, instead of therapeutic regimens. Further, in vitro potency of cefiderocol and ceftazidime/avibactam may have a potential role to improve outcomes among patients with BCC BSIs”