JAC-Antimicrobial Resistance最新文献

Introduction: This study aims to assess the impact of proactive Infectious Disease Specialist (IDS) interventions, in addition to standard antimicrobial stewardship (AMS) practices, triggered by real-time microbiological alerts, on improving the appropriateness and timeliness of antimicrobial prescriptions in hospitalized patients with bloodstream infections (BSIs).

Methods: We conducted a prospective, single-center, pre-post interventional study at the University Hospital of Modena, Italy. Adult inpatients with monomicrobial BSIs between June 2022 and March 2023 were included. During the intervention phase (November 2022-March 2023), real-time microbiological alerts were automatically delivered to IDS consultants, who proactively reviewed therapy. Primary outcomes included the time to effective therapy (TTE) and the time to appropriate therapy (TTA). Secondary outcomes encompassed the duration of antimicrobial therapy, 14 and 30-day mortality from BSI, and hospital length of stay.

Results: A total of 446 BSI episodes were analyzed (211 pre-intervention, 235 post-intervention). Post-intervention, the rate of appropriate therapy significantly increased (97.4% versus 76.2%, P < 0.001), and TTE was significantly shorter (0.63 versus 0.87 days, P = 0.022). No statistically significant reduction in TTA was observed (1.97 versus 2.37 days, P = 0.081). Early IDS intervention (<48 h) was associated with the shortest TTE and TTA. No significant differences were observed in mortality or hospital stay. Kaplan-Meier analysis showed a higher probability of receiving effective and appropriate therapy earlier in the post-intervention phase (log-rank test P = 0.014; 0.072, respectively). Subgroup analysis showed TTE improvements across MDR pathogens.

Conclusions: A proactive intervention of IDS, based on automatic microbiological alert, in addition to routine AMS activities, is significantly associated with improved prescription appropriateness, reducing TTE.

Background: Dentists are responsible for 10% of all antibiotic prescriptions. It is estimated that, in certain situations, up to 80% of antibiotic prescriptions in dentistry may be inappropriate. The aim of this study was to explore Spanish dentists' attitudes, perceptions, and contextual factors influencing antibiotic use and misuse in clinical practice.

Methods: From July to December 2022, we conducted focus groups with 31 dentists from Spain Data were analysed using thematic analysis with a pragmatic orientation to address the research objectives. Inclusion criteria required participants to be dentistry graduates or oral medicine specialists (stomatologists) and actively working as dentists. The sample was selected through key informants and the snowball method. We ensured methodological quality by adhering to the COREQ checklist.

Results: We formed seven synchronous online focus groups with 31 participants. Dentists acknowledged the problem of antibiotic resistance, identifying fear, working conditions and burnout and patient trust as factors contributing to inappropriate prescribing. Despite this awareness, dentists did not see themselves as key agents of change in combating antibiotic resistance. However, they expressed interest in further education on the topic.

Conclusions: These findings underscore the need for educational interventions that highlight dentists' role in antimicrobial stewardship. By situating these interventions within the One Health framework, dentists can be empowered to translate their leadership in oral health into active participation in the prudent use of antibiotics. Strengthening this role has practical implications for multidisciplinary strategies to combat antimicrobial resistance.

Background: Vancomycin-resistant Enterococcus faecium (VREfm) bloodstream infections (BSIs) pose significant management challenges with uncertainties relating to the optimal daptomycin dose for treatment.

Methods: A retrospective cohort study of adult patients receiving ≥3 days of definitive treatment for a first episode VREfm BSI between 2015 and 2022 was undertaken. Daptomycin doses were classified as low (≤7.9 mg/kg), medium (8.0 to 9.9 mg/kg) or high (≥10 mg/kg). We aimed to assess the association between daptomycin dose and in-hospital 30-day all-cause mortality in addition to other clinical outcomes (hospital length of stay, transfer to the ICU within 48 hours and microbiological failure). In addition, we undertook a comparative analysis of mortality and other outcomes in vanB VREfm BSIs receiving definitive daptomycin and teicoplanin treatment.

Results: A total of 191 patients received definitive daptomycin (n = 111) or teicoplanin (n = 80) therapy and were included in two separate analyses. Of the 111 daptomycin patients, most received high-dose daptomycin (59.5%), with 29.7% and 10.8% receiving medium and low doses, respectively. All-cause 30-day in-hospital mortality was 17.1% and there was no association between daptomycin dose groups and in-hospital 30-day mortality (log rank P = 0.369). Microbiological failure was associated with dose (P = 0.036): 33.3% in the low dose group, 12.1% for medium and 19.7% for high. No mortality difference was observed between vanB VREfm BSIs treated with daptomycin or teicoplanin [adjusted cause-specific hazard ratio 0.67 (95% CI: 0.28-1.59)].

Conclusions: In this contemporary study of predominantly high daptomycin doses, there was no association between daptomycin dose and 30-day in-hospital mortality but we did observe an association with microbiological failure.

Background and objectives: Antibiotic guidelines are a component of antimicrobial stewardship for optimizing antibiotic use. To evaluate the compliance with the national guidelines and the WHO AWaRe Antibiotic Book for the empirical treatment for community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in critical care units (CCUs) in Vietnam.

Methods: In this 7-day observational study, 51 participating CCUs consecutively enrolled patients aged ≥18 years from March to July 2019. We assessed the compliance for empirical antibiotic prescription using the national guidelines and the WHO AWaRe Antibiotic Book.

Results: We included 500 patients with CAP and 249 patients with AECOPD. The rates of overall compliance with the national guidelines and the WHO AWaRe Antibiotic Book were 54.4% (272/500) and 43.2% (216/500) for CAP; and 48.2% (120/249) and 7.2% (18/249) for AECOPD, respectively. The overall case fatality at 7 days was 4.0% (20/500) in patients with CAP, and 2.0% (5/249) in patients with AECOPD with no significant difference between those receiving compliant and non-compliant regimens by either guideline. The average cost of empirical antibiotic regimens for CAP was lowest at US$3.10 ($3.02-$3.17) per Defined Daily Dose (DDD) for the full compliant regimens versus US$15.26 ($12.72-$17.81) per DDD for the non-compliant regimen according to the WHO AWaRe Antibiotic Book.

Conclusions: Our study indicates that the compliance with the antibiotic guidance was suboptimal in CCUs in Vietnam. Compliance with guidelines for empirical antibiotic therapy could be associated with lower costs.

Background and objectives: Penicillin allergy (penA) records prevent first-line penicillin antibiotic use, but more than 90% are incorrect after formal testing and can be removed ('de-labelled'). We developed an implementation intervention package that supports a multi-professional non-allergy workforce to deliver penicillin allergy de-labelling (PADL) in a UK hospital. To explore the experiences of doctors, nurses, pharmacists and medicines optimization pharmacy technicians (MOPTs) of the implementation intervention package.

Methods: Process evaluation utilizing semi-structured interviews with doctors, nurses, pharmacists and MOPTs with a target sample size of 20. Inductive reflexive thematic analysis was used to analyse the data.

Results: Fifteen interviews were conducted between 7 November 2024 and 25 March 2025 with six doctors, five pharmacists and four MOPTs. PADL aligned well with the medicine's reconciliation process, the process of accurately listing a person's current medicines, which meant it better aligned with pharmacists' and MOPTs' roles than doctors' roles. Healthcare worker (HCW) confidence to deliver PADL remained low among some doctors and pharmacists, but all reported that with time and support PADL would embed. Competing priorities in an inadequately resourced healthcare setting made PADL challenging. Professional bodies formally defining PADL as a core role for their HCWs would increase engagement with PADL. The PADL champion role was identified as key to the implementation of PADL.

Conclusions: Competing priorities were limiting PADL engagement and as such PADL needs to be a core part of a HCW's role for it to be prioritized. The champion is required to support PADL as a shared responsibility and needs to be available until the process is embedded into ways of working.

Objectives: WGS has become a key tool for diagnosing Mycobacterium tuberculosis infections, but discrepancies between genotypic and phenotypic drug susceptibility testing can hinder effective treatment and surveillance. This study investigated the impact of resistant subpopulations and compensatory mutations in WGS-based rifampicin resistance prediction.

Methods: Based on a dataset of 35 538 clinical M. tuberculosis samples, the sensitivity and specificity of resistance classification were evaluated with and without considering subpopulations and compensatory mutations.

Results: By lowering the fraction of reads required to identify a resistance-associated variant in a sample from 0.90 to 0.05, the sensitivity increased significantly from 94.3% to 96.4% without a significant impact on specificity. Allowing compensatory mutations to predict resistance further lowered the false negative rate. Finally, we found that samples with resistant subpopulations were less likely to be compensated than homogeneous resistant samples. Further analysis of these samples revealed distinct clusters with differing amounts of within-sample diversity, pointing towards different mechanisms of resistance acquisition, such as within-host evolution and secondary infections.

Conclusions: Our results indicate that a substantial fraction of false negative calls in WGS-based rifampicin resistance prediction can be explained by masked resistant subpopulations. The genetic diversity within the heterogeneous samples is consistent with at least 28% of the rifampicin resistance arising from secondary infections.

Background and objectives: Paediatric respiratory tract infections can be a common reason for antibiotic prescribing in primary healthcare. Despite stewardship efforts, prescribing patterns often diverge from evidence-based guidelines. There are limited explorations of how parental beliefs and behaviours shape clinical decision-making. This qualitative study explored parental perspectives on antibiotic treatment-seeking behaviour in Ireland.

Methods: We carried out semi-structured interviews with 20 parents who had children under 8 years old in Ireland. The interviews were guided by the COM-B (Capability, Opportunity, Motivation - Behaviour) model. The interview data was analysed inductively, using reflexive thematic analysis. Following this, relevant themes and subthemes were mapped to the domains of the COM-B.

Results: The study identified three key themes: (i) experiencing perceived knowledge gaps in antimicrobial resistance (AMR) and antibiotic use captured how participants described negotiating AMR as a personal health risk while also experiencing AMR as a distant policy; (ii) navigating professional gatekeepers described the role of consulting with the general practitioner (GP), the out-of-hours doctor paradox, trusting the pharmacist and seeing receptionists as hidden gatekeepers who all shaped access to care; and (iii) deciding when to act reflected how people sought pragmatic reassurance and managed illness escalation anxiety in making decisions about seeking treatment.

Conclusions: The study underscores the need for socio-culturally tailored antimicrobial resistance messaging and interventions that address both parental concerns and systemic barriers. By centring parental voices, this research highlights opportunities to strengthen antimicrobial stewardship through improved communication, recognition and expanded roles for the primary healthcare team.

Objectives: In this multicentre, prospective study, we aimed to describe the use of isavuconazole in critically ill adult patients in ICU, in terms of patient characteristics, infection characteristics and outcomes.

Methods: Prospective, observational study of ICU patients treated with isavuconazole from January 2023 to 30 April 2025 in 17 centres (ISA-SITA study within the MULTI-SITA project).

Results: A total of 177 ICU patients treated with isavuconazole were included in the study. Most patients showed at least one European Organisation for Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC) or FUNgal Diseases in adult patients in Intensive Care Unit (FUNDICU) host factor (141/177, 79.7%). Overall, 82/177 patients (46.3%) had either proven or probable invasive mould disease (6 and 76, respectively, mostly invasive pulmonary aspergillosis). In patients with proven or probable disease, 30-day mortality was 44.0%, and 90-day mortality was 62.2%. In multivariable analyses, SOFA score (HR 1.14 per one point increase, 95% CI 1.03-1.26, P = 0.010) and concomitant bacterial pneumonia (HR 2.32, 95% CI 1.17-4.59, P = 0.016) were associated with 30-day mortality, whereas prior hospitalization (HR 2.26, 95% CI 1.19-4.27, P = 0.013) and SOFA score (HR 1.17 per one point increase, 95% CI 1.07-1.28, P < 0.001) were associated with 90-day mortality.

Conclusions: Diverse patterns of isavuconazole use were observed in a large cohort of critically ill adult patients, and the drug was well tolerated. Mortality was lower than many previous estimates in critically ill patients and could serve as a basis for future standardized comparisons.

Background: The hospital environment is a proven hotspot for antimicrobial-resistant bacteria, which may be released through hospital wastewater into the environment and municipal wastewater. The aim of this study was to monitor the occurrence of and perform molecular characterization of MDR ESBL Enterobacterales isolated from Parirenyatwa Hospital wastewater, Harare, Zimbabwe.

Methods: This was a cross-sectional study. Enterobacterales from sixty-four 500 mL samples of hospital wastewater from three drainage sites of Parirenyatwa Hospital were isolated. A modified double disc synergy test was used to confirm ESBL Enterobacterales before genotyping with multiplex PCR.

Results: The majority of isolates came from the main hospital drainage site. All the isolated Enterobacterales showed MDR. Of the 33 Enterobacterales isolated from hospital wastewater, 8 (24%) were ESBL-producing: 5/8 (63%) Escherichia coli, 2/8 (25%) Klebsiella pneumoniae, and 1/8 (12%) Citrobacter freundii. The multiple antibiotic resistance index (MARI) obtained from the ESBL-producing Enterobacterales isolates ranged from 0.5 to 0.75. Seven (87.5%) isolates harboured the bla _CTX-M gene and five (62.5%) isolates had the bla _TEM gene, with four (50%) isolates containing both genes. Three isolates contained the bla _CTX-M gene only and one contained only bla _TEM. The bla _SHV gene was not detected.

Conclusions: MDR ESBL-producing Enterobacterales were identified from Parirenyatwa Hospital wastewater. The MARI greater than 0.2 indicated that these isolates were from a high-risk source of contamination.

[This corrects the article DOI: 10.1093/jacamr/dlaf103.].