JAC-Antimicrobial Resistance最新文献

Background: Antimicrobial resistance (AMR) is a significant public health challenge. The Antibiotic Guardian (AG) campaign was developed in 2014 by Public Health England (now UK Health Security Agency) to raise increase engagement in personal actions to tackle AMR and promote responsible antibiotic use. The campaign expanded through collaboration with WHO Europe, Africa CDC, South African National Department of Health and the Ministerial Advisory Committee on Antimicrobial Resistance, as well as Belgian Antibiotic Policy Coordination Committee. This study aimed to analyse international AG pledges from 2014 to 2024 with a focus on pledges made on the Africa subpages.

Methods: The AG pledge data was cleaned and sorted to exclude UK pledges. Pledges made on the Africa subpages, including the responses to the knowledge questions, were harmonized. Data sorting, cleaning and preliminary quantitative analysis tasks were performed using Microsoft Excel. Further analysis and visualization were conducted using Datawrapper.

Results: The AG campaign has received 17 053 international pledges from 194 countries across the seven continents. The Africa subpages have cumulatively reached 3997 AGs across 40 African and 21 non-African countries. South Africa, Nigeria, Uganda, Kenya and Ethiopia had the highest pledges from African countries, with most pledges from healthcare professionals. Most AGs heard about the campaign through professional networks and social media. Nearly two-thirds of AGs (61.2%) answered all five knowledge questions correctly.

Conclusion: The AG campaign has evolved into a global effort aimed at addressing AMR through behavioural change. Further promotion and audience-specific strategies are required to reach the most affected subpopulations and ensure pledges translate to reductions in the mis and overuse of antibiotics in Africa.

Background: Blood cultures (BCs) are the gold standard investigation for patients with suspected severe infection and sepsis. Yet, BCs are not consistently obtained prior to antibiotic administration, and sampling practices remain suboptimal. Optimizing BC sampling has important benefits, including reducing inappropriate antibiotic use and improving antimicrobial stewardship. Despite advances in sepsis recognition and management, a significant scope remains to improve BC sampling practices. This scoping review aimed to identify evidence on interventions used to improve BC sampling in higher economically developed countries.

Methods: Database searches of MEDLINE, CINAHL, PubMed and BMJ Open Quality were conducted for studies published between January 2015 and January 2025. Included studies were mapped to the Behaviour Change Wheel (BCW) framework.

Results: Searches identified 3746 records; 23 studies met the inclusion criteria, with two additional studies identified through reference screening. In total, 25 studies were analysed, identifying six intervention types. Common interventions included visual prompts, screening tools, education and training programmes and audit-and-feedback mechanisms. These interventions most frequently mapped to the BCW categories of Environmental Restructuring (32%), Education and Training (28%) and Enablement (25%). Outcome measures varied widely, with no consistent metrics used across studies.

Conclusions: This review identified six intervention types used to improve BC sampling practices, with Environmental Restructuring, Education and Training, and Enablement most commonly employed. Interventions were associated with improvements in timely BC collection and reduced contamination rates. However, heterogeneity in outcome measures and gaps in intervention types highlight the need for standardized metrics and more robust evaluations to optimize BC sampling practices across healthcare settings.

Background: There is a paucity of information on the burden of Klebsiella pneumoniae invasive disease (KPn-ID) in Africa. We conducted a multicentre, observational study on the clinical and microbiological epidemiology of KPn-ID in hospitalized adults in South Africa, focusing on clinical outcomes and KPn susceptibility profiles.

Methods: Surveillance for culture-confirmed KPn from blood and CSF was undertaken from 15 May 2023 to 14 May 2024. Phenotypic antimicrobial susceptibility was analysed, and the presence of carbapenemases was assessed with a lateral flow assay test.

Results: We enrolled 524 of 617 individuals with KPn-ID. The median age was 48 (IQR: 35-61) years, and 84.4% (442/524) were presumed healthcare-associated infections. Comorbidities included HIV (26.9%; 141/524) and diabetes mellitus (16.4%; 86/524). There was a high prevalence of carbapenem resistance (55.0%; 288/524), with the OXA-48 carbapenemase detected in 71.5% (181/253), and OXA-48 and NDM co-detected in 20.9% (53/253) of tested isolates. Colistin resistance was detected in 7.6% (19/251) of tested isolates. The in-hospital case fatality risk (CFR) was 56.5% (296/524). Urethral catheterization [adjusted odds ratio (aOR) 3.30; 95% CI: 1.51-7.23] and an admission quick sepsis-related organ failure assessment score of 1 to 3 (aOR 2.14; 95% CI: 1.25-3.68) were independently associated with in-hospital death. Achieving source control was associated with lower odds of death (aOR 0.18; 95% CI: 0.10-0.30).

Conclusions: We observed a high prevalence of MDR and high CFR in adults with KPn-ID. These data show the urgent need for strategies to mitigate KPn-ID in settings such as ours.

Introduction: Tedizolid, a second-generation oxazolidinone, exhibits potent in vitro activity against Gram-positive bacteria, including Nocardia species, and has a more favourable safety profile than linezolid during prolonged use. However, data on itsCSF penetration and efficacy remain scarce. We describe two cases of Nocardia farcinica brain abscess treated with tedizolid and report measured serum and cerebrospinal fluid (CSF) exposures.

Case reports: Two patients with N. farcinica brain abscesses (MIC for tedizolid 0.75 mg/L) treated with tedizolid as part of combination therapy. Total and unbound concentrations in serum and CSF were quantified using LC-MS/MS, and PK/PD modelling was performed. In case 1, a 60-year-old man with idiopathic CD4 lymphocytopenia initially improved but relapsed while receiving tedizolid 200 mg once daily. The unbound plasma fraction was 15.7%, and CSF exposure remained low, with a predicted fAUC0-24/MIC <3: below the PK/PD threshold used for staphylococcal skin infections. Tedizolid was discontinued, and the patient subsequently died. In case 2, a 72-year-old diabetic patient received 200 mg twice daily. The unbound plasma fraction was higher (30.1%). PK/PD modelling predicted a CSF fAUC0-24/MIC of 7.5, exceeding the proposed efficacy threshold. The patient completed therapy successfully and remained relapse-free after 2 years.

Discussion: These cases highlight moderate CSF penetration of tedizolid and substantial interpatient variability in protein binding. Direct measurement of unbound concentrations was critical for accurate PK/PD assessment. Although higher dosing may improve central nervous system (CNS) exposure and outcomes, tedizolid should not be considered interchangeable with linezolid for CNS nocardiosis. Individualized monitoring of free plasma levels may help optimize dosing strategies.

Objectives: The present study examines methicillin-resistant Staphylococcus aureus isolates lacking mec (MRLM) phenotypic and genotypic traits and clinical features of patients.

Methods: Between October 2021 and February 2023, 13 MRLM isolates were identified among 867 S. aureus clinical isolates and subjected to WGS.

Results: Ten of the 13 MRLMs were resistant to cefoxitin (MICs >4 mg/L), including two that were also resistant to oxacillin. The remaining three isolates were susceptible to both cefoxitin and oxacillin and exhibited typical growth on CHROMagar MRSA. Seven of the 13 isolates harboured the blaZ gene, but the hyperproduction of the β-lactamase encoded by this gene was not predicted. All isolates exhibited low MICs for cefazolin, ceftriaxone, imipenem, and meropenem and demonstrated susceptibility to the fifth-generation cephalosporin ceftobiprole. Ten STs/CCs, encompassing ST5, ST8, ST20, ST25, ST30, ST45 (3 isolates), ST291, ST398 (2 isolates), CC15 and CC22, identified among isolates, were within the range of previously reported MRLM clones. A multitude of previously reported or undocumented mutations/substitutions in PBPs, the pbp4 promoter, GdpP, YjbH and AcrB were identified. Four isolates had truncations or insertions in GdpP. The exploration of clinical features suggests the potential coexistence of MRLM and MSSA populations within each patient in the absence of antimicrobial selective pressure.

Conclusions: The importance of accurate differentiation of MRLMs from MRSAs and MSSAs in routine laboratory testing is underscored by our results, which may allow in-depth investigation of the true epidemiology and clinical implications of MRLMs and the actual efficacy of β-lactams against them.

Background: Antibiotic resistance is a threat to public health driven in part by widespread antibiotic administration. Days of antibiotic spectrum coverage (DASC) is a novel metric to quantify both duration and breadth of antibiotic exposure that has not previously been used as an endpoint in a clinical trial. We calculated DASC using data from the Ceftriaxone to Prevent Pneumonia and Inflammation after Cardiac Arrest (PROTECT) trial to determine the association of ceftriaxone prophylaxis with DASC and with the acquisition of antibiotic resistance genes (ARGs).

Methods: PROTECT randomized out-of-hospital cardiac arrest subjects to ceftriaxone or placebo for 3 days. ARGs were measured from rectal swabs collected at Days 0, 3 and 7 post randomization. DASC was calculated for each subject and compared using a two-sided Mann-Whitney U-test. Correlations between DASC and new ARGs, antibiotic-free days (AFD) and days of therapy (DOT) were tested using Kendall's tau-alpha.

Results: PROTECT enrolled 52 subjects, 26 per treatment group, and treatment groups were similar at baseline. Median DASC scores were lower in the ceftriaxone group (19.5; IQR: 0, 43) compared with placebo (53; IQR: 16, 81). We found no correlation between DASC and new ARGs at either timepoint, or between DASC and AFD. DASC was correlated with DOT.

Conclusions: DASC post intervention was lower in the ceftriaxone group, representing less antibiotic exposure following the intervention. There was no correlation between new ARGs and DASC. Further study is needed to understand the relationship between antibiotic prophylaxis, subsequent antibiotic exposure and resistome changes in the critically ill.

Background and objectives: Antimicrobial resistance (AMR) poses a mounting sustainability challenge to healthcare systems, especially in Southern African settings, where antimicrobial stewardship capacity is limited by resource constraints, with structural challenges exacerbating the problem of resistance. Strengthening education could support the development of AMR-related knowledge, and stewardship skills for health practitioners are key to enhancing antimicrobial use and addressing AMR. This paper investigates how participatory research workshops can support the development of AMR-related health literacy among Zimbabwean health practitioners (doctors, nurses and pharmacists) and how such literacy can promote antimicrobial stewardship.

Methods: Eight interdisciplinary workshops involving 25 health practitioners were conducted at two teaching hospitals in Harare, Zimbabwe. Workshop transcripts were analysed using a combination of a value-creation framework and health literacy. The analysis identified how workshops created immediate, applied and transformative values, supporting stewardship.

Results: The workshops created, based on self-reporting from participants, values enabling practitioners' development of AMR-related health literacy. Functional literacy could strengthen prescribing practices and patient adherence to treatment. Interactive literacy may improve interdisciplinary collaboration. Critical literacy have the potential to support the identification of drivers of AMR in resource-limited contexts in Southern Africa.

Conclusions: Created values and AMR-related health literacy may support antimicrobial stewardship, with workshops providing a context-relevant approach to enhance AMS capacity in Southern African healthcare settings. This educational approach has the potential to contribute to bridging the gap between awareness and stewardship practice. Through integration into professional training, it could support the promotion of sustainable antimicrobial use in Southern African contexts.

Background: Among MDR bacteria, carbapenem-resistant Acinetobacter baumannii (CRAB) is a major concern due to the limited therapeutic options.

Objectives: To identify predictors to aid in the clinical management of critically ill patients.

Methods: We conducted a multicentre prospective study in Italy, enrolling patients with CRAB colonization who were admitted to ICUs between 2020 and 2023. Multivariable logistic regression analysis was performed to identify potential risk factors for CRAB infection. To account for competing risks, we used the cumulative incidence function (CIF) and Fine-Gray regression analysis, providing an accurate assessment of the risk of CRAB infection. Additionally, a logistic regression model was performed to estimate the impact of different types of critically ill patients on the risk of infection.

Results: We included 564 colonized patients, and 381 (67.5%) developed a CRAB infection in the ICU. In the logistic regression model, multisite colonization (OR 2.78; 95% CI: 1.90-4.08; P < 0.001), Charlson comorbidity index (CCI) ≥3 (OR 1.59; 95% CI: 1.00-2.50; P = 0.047), mechanical ventilation (OR 1.48; 95% CI: 1.00-2.18; P = 0.048), male gender (OR 2.06; 95% CI: 1.38-3.10; P < 0.001), and time from ICU admission to colonization ≤12 days (OR 2.00; 95% CI: 1.36-2.94; P < 0.001) were independent predictors of CRAB infection. Findings were confirmed in the Fine-Gray model. In a secondary model, COVID-19 (OR 2.31; 95% CI: 1.30-4.10; P = 0.004) and burn patients (OR 4.84; 95% CI: 1.65-14.17; P = 0.004) were risk factors for CRAB infection.

Conclusions: Early colonization from ICU admission, multisite colonization, CCI, mechanical ventilation and male gender are key risk factors for CRAB infection. These factors support clinicians in the management of critically ill patients with prior CRAB colonization.

Background: Metallo-β-lactamase (MBL)-producing carbapenemase-resistant Enterobacterales infections are associated with significant mortality. Several β-lactam/β-lactamase inhibitor combinations (BL/BLI) with promising activity against MBLs are in the pipeline.

Objective: To investigate the in vitro activity of upcoming BL/BLI agents against Enterobacter hormaechei clinical isolates co-producing NDM and VIM enzymes.

Methods: Eleven E. hormaechei isolates co-harbouring bla _NDM-7 and bla _VIM-1 were identified from 10 patients admitted to a tertiary hospital in Santiago, Chile, between July 2022 and July 2023. Reference broth microdilution (BMD) panels were developed to determine minimum inhibitory concentrations (MICs) to aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol and cefiderocol/xeruborbactam. Cefiderocol population analysis profile-area under the curve (PAP-AUC) was performed in strains exhibiting cefiderocol susceptibility to assess for cefiderocol heteroresistance. Long-read sequencing, using the Oxford Nanopore Technologies platform, was conducted on all isolates to characterize the genomic background of bla _NDM-7 and bla _VIM-1.

Results: Among the 11 E. hormaechei isolates assemblies revealed bla _NDM-7 and bla _VIM-1 were located on separate plasmids. All isolates were susceptible to aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. Cefiderocol susceptibility was variable; the addition of xeruborbactam restored susceptibility.

Conclusions: Our findings indicate that E. hormaechei clinical isolates co-producing NDM and VIM metallo-carbapenemases exhibited susceptibility to all tested novel BL/BLIs, including aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. The combination of cefiderocol and xeruborbactam restored the activity of cefiderocol.