JAC-Antimicrobial Resistance最新文献

Background: Antifungal stewardship (AFS) is the judicious use of today's antifungal agents with the aim of improving patient outcomes and preserving their future effectiveness. Antifungal resistance (AFR) is increasing globally, with more patients at risk of Invasive Fungal Disease (IFD), highlighting the urgent need to standardize AFS practices in the UK. The aim of this position paper is to understand the current AFS landscape in the UK.

Methods: A virtual panel discussion was held from September to October 2023 on an online platform followed by a virtual meeting with nine healthcare professionals from across the UK selected for their expertise on IFD management and AFS. The discussion was structured across four topics: current AFS landscape, key elements of an AFS programme, diagnostics and diagnostic stewardship, and unmet needs in education and training. A thematic analysis was carried out. The results represent the collated and summarized views from these activities.

Results and discussion: Participants reported barriers to implementing AFS and its integration within antimicrobial stewardship (AMS) programmes in the UK. The primary challenge identified was a lack of resources, including funding and staff time. Sub-optimal fungal diagnostics and limited mycology expertise was reported as a barrier to AFS, clinical IFD and AFR surveillance. Approaches to combatting these challenges may include investing in formal mycology networks to serve as centres of clinical expertise and diagnostic hubs.

Conclusion: National standards for AFS services and associated outcome metrics need to be established to set a benchmark for centres to improve AFS.

Background: Antibiotic resistance is an escalating global health issue, with particularly severe implications in low- and middle-income countries (LMICs) such as Nigeria. This study examines antibiotic-resistant bacteria's prevalence and molecular characteristics in daycare centres in Ile-Ife, Nigeria, where high antibiotic use and limited infection control measures present significant challenges.

Methods: Between November 2017 and July 2019, samples were collected from 20 daycare centres, including swabs from fomites and children. Bacterial isolates were identified and assessed for antibiotic susceptibility using standard methods. Molecular techniques, including PCR, were employed to detect resistance genes such as blaSHV, tetA, dfr1 and mecA.

Results: The study found high resistance levels among common pathogens, with S. aureus and other staphylococci showing significant resistance to ampicillin and Augmentin and Gram-negative bacteria exhibiting broad resistance patterns. Resistance genes, including blaSHV and mecA, were identified in multiple isolates, indicating the spread of crucial resistance mechanisms.

Conclusions: The results highlight the critical need for improved surveillance, targeted antimicrobial stewardship and enhanced infection control practices in daycare centres to address the growing threat of antibiotic resistance. This research offers valuable insights into resistance dynamics in paediatric settings and supports the development of strategies to manage the spread of resistant bacteria in LMIC contexts.

Objectives: In the West Bank, antimicrobial resistance (AMR) is increasingly and alarmingly common. Efforts are being made to introduce antimicrobial stewardship programmes (ASPs). This study explores doctors' perceptions of AMR and context-specific barriers and facilitators to ASPs at a critical point in national ASP development.

Methods: Semi-structured interviews were conducted with 22 doctors working in primary healthcare, government and non-governmental hospitals in Nablus in 2019. Two researchers thematically analysed the data.

Results: Participants recognized antibiotic resistance as a major threat to health. Few felt that doctors were well informed about ASPs; many had not heard of them. However, there was willingness to expand and begin new education programmes. Barriers and facilitators to ASPs included: (i) doctors were perceived to 'misuse' antibiotics, lack awareness, favour short-term outcomes, and externalize blame; (ii) patients reportedly treat antibiotics 'like analgesia' with high expectations of doctors; (iii) resource limitations make ASPs and infection control difficult-a lack of drugs, laboratory services, infectious disease specialists, and research to develop local guidelines; and (iv) top-down policy is recommended to restrict access to antibiotics without a prescription, but should be coupled with support, collaboration and community action.

Conclusions: Doctors' appreciation of the severity of the issue, and willingness for the expansion of existing programmes targeted at their own prescribing practices, provides a strong foundation for successful ASPs. A top-down approach to prevent inappropriate antibiotic prescribing is welcomed by participating doctors. If financial and resource limitations could be addressed, a continued multifaceted approach may enable physician, pharmacist and patient behaviours to change.

Background: Escherichia coli, the most common bacterium causing urinary tract infections (UTIs), is increasingly reported as resistant to multiple antibiotics. Swedish surveillance data from hospital and primary health care (PHC) report a 17%-19% prevalence of resistance to ciprofloxacin in E. coli from urine cultures in men over 20 years of age. Surveillance data may include nosocomial infections. However, few studies have described resistance in E. coli in men with community-acquired UTI in PHC. We aimed to describe the microbiological results, including antibiotic resistance in E. coli, in men with lower UTI (LUTI) attending PHC.

Methods: In this retrospective study based on information from electronic medical records, we included patients from 289 PHC centres. For all men aged 18-79 years diagnosed with LUTI in PHC from January 2012 to December 2015, we extracted data on age, UTI diagnosis and results from urine cultures.

Results: A total of 17 987 episodes of lower UTI were identified. E. coli was detected in 62% of positive cultures and 63% of detected E. coli isolates were susceptible to all tested antimicrobials. Resistance in E. coli to the first-choice antibiotics pivmecillinam and nitrofurantoin were 2% and 1%, respectively. Resistance to ciprofloxacin was 9%, and to trimethoprim it was 17%.

Conclusions: Resistance levels for ciprofloxacin in E. coli among men with LUTI in PHC were lower than in surveillance data. The results of this study point to the importance of surveillance of resistance in urine samples from patients with LUTI in PHC in order to choose the right empirical antibiotic treatment.

A shortage of trained personnel poses significant challenges to implementing antimicrobial use (AMU) surveillance systems in low- and middle-income countries (LMICs). Traditional training models, such as workshops, seminars and online courses, often lack the sustained engagement and support necessary for deep learning and skill mastery. This article advocates for mentorship as an effective training method for AMU professionals in LMICs. Drawing on our experiences as mentors and mentees from 1- to 2-year mentorship programmes in Nepal, Pakistan, Papua New Guinea and Timor-Leste between 2019 and 2023, we highlight the challenges and success factors of mentorship. Our insights demonstrate mentorship's value in building expertise and sustaining capacity in AMU surveillance, offering a promising solution to address the personnel shortage in these regions.

Background: Sulbactam is an effective therapy for Acinetobacter baumannii infections. Previous sulbactam pharmacokinetics/pharmacodynamics (PK/PD) analyses established exposure efficacy targets in plasma against A. baumannii pneumonia. Herein, we established sulbactam efficacy targets in epithelial lining fluid (ELF). The PTA following clinical sulbactam regimens was estimated.

Methods: Sulbactam (dosed as ampicillin-sulbactam) bronchopulmonary PK was assessed in the neutropenic murine pneumonia model. The percentage of the dosing interval during which the free drug concentration remained above the MIC (%fT > MIC) required to achieve different efficacy endpoints was estimated in 21 clinical A. baumannii isolates. PTA was assessed using Monte Carlo Simulations and utilizing previously published healthy volunteers sulbactam ELF pharmacokinetics.

Results: Median (IQR) %fT > MIC required to achieve 1-log kill in isolates resistant to both sulbactam and meropenem was 47.51 (39.7-54.2). This target was much higher than isolates with other phenotypes (i.e. sulbactam-susceptible/intermediate and sulbactam-resistant but meropenem susceptible) that required 16.62 (5.3-22.0). The PTA following sulbactam 1 g q6h 0.5h infusion regimen was >90% up to MIC of 2 mg/L while the PTA for MIC 4 mg/L (susceptibility breakpoint) was 81%. Conversely, previous assessment in plasma demonstrated the same regimen exceeded 90% PTA up to MIC of 4 mg/L. Sulbactam 3 g q8h 4h infusion provided PTA >90% for MIC 8 mg/L (sulbactam-intermediate), similar to previous assessment in plasma.

Conclusion: Based on the ELF assessment, the maximum FDA approved dose of sulbactam (1 g q6h 0.5h infusion) provided >90% PTA for isolates with sulbactam MIC only up to 2 mg/L. Nevertheless, sulbactam 3 g q8h for 4 hours of infusion achieved higher PTA and conferred additional benefit against sulbactam-susceptible/intermediate isolates.

Background: The impact of antimicrobial resistance (AMR) on death at the patient level is challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK teaching hospital.

Methods: This retrospective study investigated all deceased patients in 2022. Records of participants were independently reviewed by two investigators for cases of AMR-attributable deaths using a newly proposed patient-level definition.

Results: In total, 758 patients met inclusion criteria. Infection was the underlying cause of death for 11.7% (89/758) and was implicated in the pathway that led to death in 41.1% (357/758) of participants. In total, 4.2% (32/758) of all deaths were AMR-attributable. Median time from index sample collection to death was 4.5 days (IQR 2-10.5 days). The majority of AMR-attributable deaths (56.3%, 18/32) were associated with intrinsic resistance mechanisms, primarily by Enterococcus faecium (20.7%), Enterobacterales carrying repressed chromosomal ampicillinase Cs (AmpCs) (14.7%) and Pseudomonas aeruginosa (11.8%), whereas a minority (43.7%, 14/32) had acquired resistance mechanisms, primarily derepressed chromosomal AmpCs (11.8%) and ESBLs (8.8%). The median time to effective treatment was 32 h 15 min (no difference between subgroups). Only 62.5% (20/32) of AMR-attributable deaths had infection recorded on the death certificate. AMR was not recorded as a cause of death in any of the patients.

Conclusions: Infection and AMR were important causes of death in our cohort, yet they were significantly underreported during death certification. In a low-incidence setting for AMR, pathogen-antimicrobial mismatch due to intrinsic resistance was an equally important contributor to AMR-attributable mortality as acquired resistance mechanisms.

Objective: To explore the role of local public health organisations in antimicrobial stewardship (AMS) and antimicrobial resistance (AMR) surveillance.

Methods: A scoping review was conducted. Peer-reviewed and grey literature from countries within the organisation for economic co-operation and development was searched between 1999 and 2023 using the concepts of local public health, AMR and AMS. Thematic analysis was performed to identify themes.

Results: There were 63 citations illustrating 122 examples of AMS and AMR surveillance activities with local public health involvement. Common AMS activities (n = 105) included healthcare worker education (n = 22), antimicrobial use (AMU) evaluation (n = 21), patient/public education (n = 17), clinical practice guidelines (n = 10), and antibiograms (n = 10). Seventeen citations described local public health activities in AMR surveillance; the majority focussed on communicable diseases (n = 11) and/or AMR organisms (n = 6).

Conclusions: Local public health capabilities should be leveraged to advance high-impact activities to mitigate AMR, particularly in the areas of knowledge translation/mobilisation, optimising surveillance and establishing strategic collaborations.

Policy implications: Future work should focus on better understanding barriers and facilitators, including funding, to local public health participation in these activities.

Background: Antimicrobial misuse and overuse propagate antimicrobial resistance, yet data on factors influencing antibiotic prescription decisions in low-resource settings are limited. We describe factors influencing antimicrobial prescription at a large tertiary care private not-for-profit hospital in Uganda.

Methods: We conducted a descriptive phenomenology qualitative study involving face-to-face in-depth interviews of 12 purposively selected prescribers (four intern doctors, six medical officers and two Internal Medicine physicians) in a private not-for-profit hospital in Kampala, Uganda. Audio recordings and filed notes were transcribed verbatim and analysed manually by content analysis. Emerging themes and sub-themes were recorded and reported.

Results: Three broad themes emerged: experience with antimicrobial use in Uganda, barriers and facilitators to rational antimicrobial prescription and measures to address irrational antimicrobial use. Participants recognized that antibiotics are often used irrationally, prescribed even when there is uncertainty regarding clinical evidence for infection, and influenced by drug promoters, and noted high levels of antibiotic resistance. Patients' symptoms and clinical signs, previous experience using antibiotics, fear of bad outcomes, patient demand and expectations, influence from senior colleagues, the turnaround time of clinical investigations and drug marketers were the barriers and facilitators to antimicrobial prescription. Prescribers also acknowledged the need to update clinical guidelines, set up hospital antibiograms, and provide continuous medical education on rational antimicrobial use.

Conclusions: A complex interplay of intrinsic and extrinsic factors influences antibiotic prescribing decisions in this hospital. Targeted interventions through continuous education and training for prescribers, providing local prescription guidelines and antibiograms and implementing regulations on over-the-counter antibiotic sales are needed to implement robust antimicrobial stewardship programmes to curb antimicrobial resistance successfully.

Background: The ARON study, a randomized controlled trial, assesses a behavioural intervention incorporating clinically guided C-reactive protein (CRP) point-of-care testing and a parental information booklet to reduce inappropriate antibiotic prescriptions for acutely ill children in Belgian primary care.

Objectives: To explore GP and parent views and experiences regarding the ARON trial intervention.

Methods: We conducted a qualitative embedded process evaluation in Belgian general practice. Semi-structured interviews were held with purposively sampled GPs and a convenience sample of mothers of acutely ill children presenting to primary care. Data were analysed using inductive thematic analysis.

Results: Thirty-four interviews were conducted with 17 GPs and 17 parents from the intervention arm, and four themes were identified. The first theme centres on the supportive role of CRP point-of-care testing in reducing diagnostic uncertainty and decreasing inappropriate prescriptions. The second theme explores the use of CRP in managing perceived parental expectations of antibiotics. The third theme discusses the use of intermediate CRP levels (above the trial's 5 mg/L cut-off) as an indicator of serious infection, as opposed to its intended role in the trial as a rule-out factor. The final theme delves into the dual functionality of the booklet, enhancing self-management and offering reassurance through safety-netting advice. A logic model depicts the assumptions and (un)anticipated dynamics underlying the relationships between these themes and their subthemes.

Conclusion: Both GPs and parents consider the intervention to be a helpful complementary tool during consultations for acutely ill children.