JAC-Antimicrobial Resistance最新文献

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.

Background: An Antimicrobial Prescribing and Stewardship (APS) Competency Framework is an important resource for enhancing the practice of prescribers, in-line with national and global priorities for tackling antimicrobial resistance. Knowledge mobilization of such a framework is essential to maximize its utilization and impact.

Objectives: To utilize a Knowledge to Action (KTA) Framework approach to mobilize knowledge of the national APS Competency Framework, assess current integration and collect feedback from course-leaders of non-medical prescribing (NMP) programs at Higher Education Institutions (HEIs) in the UK.

Methods: UK HEIs accredited to provide NMP training to experienced nurses, pharmacists, and allied health professionals were identified through review of professional regulatory websites. A Microsoft Forms^® survey with consent was developed and piloted; the final link and additional information were emailed to NMP course leads. The results were analysed using Microsoft Excel^® and NVivo15^®.

Results: Of 84 HEIs surveyed, 38 responded (45%). Over half (55%) already integrate the national APS framework in courses, with others signposting to it. Most (63%) found it helpful, though its length and detail posed challenges and some felt it lacked relevance for all students. Participation in the survey increased awareness of the APS framework and other resources for antimicrobial stewardship teaching.

Conclusions: This knowledge mobilization and evaluation demonstrated a high level of utilization of the framework within NMP programmes; feedback from users should be considered in future updates. It highlights the need for ongoing engagement with HEIs to embed AMS principles in all prescriber education to optimize antimicrobial use and reduce resistance.

Background: Correct use of antibiotics ensures necessary treatment for patients while antibiotic resistance is reduced. Respiratory tract infections (RTIs) are common in preschool children. Young children receive a large proportion of the total amount of antibiotics, and also in low-prescribing countries such as Norway.

Objectives: Explore the contacts, rate of antibiotic prescriptions and choice of antibiotics in the treatment of RTIs in preschool children in general practice from 2012 to 2019. Methods Descriptive registry study on complete population data of antibiotic prescriptions administered to Norwegian pre-school children with RTIs, in the period 2012 - 2019, after consultations with a general practitioner.

Results: The total prescription rate was reduced from 28% in 2012 to 19% in 2019. There were small yearly variations in prescription rates. Most antibiotics were prescribed to 1- and 2-year-olds. Upper RTI was the most used diagnosis and accounted for 25% of the total amount of antibiotics prescribed.Total RTI episode rate was 941 episodes/1000 children in 2012, reduced by 17% to 2019 when there were 777 episodes/1000 children. The reduction in antibiotic prescription to children with otitis was associated with a decline in episode rate.More than 81% of prescribed antibiotics were penicillins, only 16% were macrolides and 3% were other antibiotics. The use of phenoxymethylpenicillin increased in the period from 50% in 2012 to 68% in 2019.

Conclusions: There is room for improvement in adherence to guidelines and antibiotic stewardship also in low-prescribing countries. Antibiotic prescribing is closely linked to prescription rates and health-seeking behaviours, offering valuable insights for targeted antibiotic stewardship campaigns.

Globally, there is increasing evidence that incorrect penicillin allergy labels negatively affect patient outcomes, antibiotic prescribing and antimicrobial resistance, leading to growing concern about this patient safety issue and how to resolve it. While many millions of patients worldwide have incorrect penicillin allergy labels, there are too few specialist allergists and a lack of 'point-of-care' tests to address this problem. Numerous research studies now provide evidence of the feasibility and importance of widening access to penicillin allergy assessment. Researchers from two UK-based studies (SPACE and ALABAMA), in collaboration with key stakeholders including patient representatives, gave their views to shape a high-level implementation plan to facilitate widening access to penicillin allergy assessment in the UK. This Viewpoint describes the basis of the implementation plan and summarizes the key actions required for successful delivery. While the plan is intended for the UK, we hope to promote international shared learning and collaboration to address this global problem informed by the UK context.