JAC-Antimicrobial Resistance最新文献

Background: Bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) are still associated with high mortality, and the game-changing drug ceftazidime/avibactam has shown suboptimal pharmacokinetics in some clinical settings. Ceftazidime/avibactam renal dose adjustment has recently been identified as an independent risk factor for mortality.

Objectives: To investigate the effect of ceftazidime/avibactam renal dose adjustment on mortality.

Methods: Patients with KPC-Kp BSI treated with a ceftazidime/avibactam-based regimen were retrospectively collected and analysed. The primary outcome was mortality at 7, 14 and 30 days after the start of definitive ceftazidime/avibactam antibiotic therapy. Renal function was estimated using the CKD-EPI equation.

Results: One hundred and ten patients with KPC-Kp BSI treated with a ceftazidime/avibactam-based regimen were included. Full-dose ceftazidime/avibactam (7.5 g daily) was prescribed to 82 patients (74.5%), while 28 patients (25.5%) received a renal-adjusted dose (17 patients due to chronic renal disease or haemodialysis, 11 patients due to infection-related acute kidney injury), with a median of 1.9 g daily. At multivariable analysis, receiving a reduced dose of ceftazidime/avibactam was independently associated with mortality (HR 4.47, 95% CI 1.09-18.03, P = 0.037), along with intra-abdominal or lower respiratory tract infections as source of BSI (HR 5.42, 95% CI 1.77-16.55, P = 0.003), septic shock (HR 6.99, 95% CI 1.36-35.87, P = 0.020) and SARS-CoV-2 coinfection (HR 10.23, 95% CI 2.69-38.85, P = 0.001).

Conclusions: Dose reduction of ceftazidime/avibactam according to renal function in patients with KPC-Kp BSI seems to be independently associated with higher mortality. This may be possibly due to inadequate exposure provided by the recommended doses for renal impairment.

Background: Antimicrobial stewardship (AMS) programmes seek to reduce the risk of antimicrobial resistance by minimizing inappropriate antimicrobial use. The SARS-CoV-2 coronavirus (COVID-19) pandemic was characterized by initial widespread use of antimicrobials in patients with COVID-19, with potential negative effects on AMS efforts.

Objective: To explore the impact of the pandemic on the AMS workforce in Scottish acute care hospitals.

Method: Individual, semi-structured online interviews were conducted with a purposive sample of clinical staff who had an AMS focused role in Scottish Health Boards. Interviews explored staff experiences of facilitating AMS during the pandemic. Data were analysed using inductive content analysis.

Results: Thirteen staff from seven of 15 Scotland Health Boards participated. The data revealed negative (including staff redeployment and shortages) and positive effects (including improved working relationships and use of technology) on the AMS workforce. Notably, greater appreciation of the work of the AMS team was a positive outcome.

Conclusions: The robust qualitative methods applied in this original study have generated greater understanding of factors that impeded AMS services in Scotland during the pandemic. These findings may resonate internationally. Adaptation to technology and investment in the workforce are recommended to improve the resilience of AMS services in future crises.

Background: Antimicrobial resistance is a global health challenge with profound implications across sectors. Livestock, a significant field at the One Health interface, lacks sufficient information, particularly in low-resource settings such as Malawi.

Objectives: We determined the antimicrobial resistance rates of Escherichia coli isolated from broiler chickens in Malawi and explored the relationship between resistance genes across sectors using genomic analysis.

Methods: In 2023, we isolated 115 E. coli strains from 116 faecal and caecal samples from broiler chickens across Malawi. Antimicrobial susceptibility tests were performed using agar dilution method according to the Clinical Laboratory Standard Institute guidelines. Whole-genome sequencing was performed using Illumina sequencing.

Results: Notably, 50 isolates (44%) were resistant to cefotaxime. We detected ESBL bla _CTX-M genes (bla _CTX-M-55, bla _CTX-M-14, bla _CTX-M-65, bla _CTX-M-27, bla _CTX-M-15, bla _CTX-M-1, and bla _CTX-M-3) in 48 cefotaxime-resistant isolates, which exhibited higher resistance rates to levofloxacin than non-ESBL-encoding isolates (29/48; 60% versus 20/67; 30%). All isolates were susceptible to colistin and carbapenems. High resistance rates were observed for tetracycline and co-trimoxazole commonly used in broiler chickens (90% and 70%, respectively). Sequence type 206 and phylogroup A were predominant (14% and 65%, respectively). In the genetic context of bla _CTX-M genes, whole-genome alignment of the ESBL-producing isolates with reference plasmids from E. coli of various origins indicated significant similarity.

Conclusions: Antimicrobial resistance is highly prevalent among E. coli from broiler chickens in Malawi. Genomic analysis suggests potential transmission pathways for ESBL genes across sectors, necessitating further studies from One Health perspective.

Background: Haemophilus influenzae (Hi) is known as a cause of invasive and non-invasive diseases. Especially ear, nose and throat (ENT) infections are common reasons for antibiotic prescriptions in outpatient settings in Germany. Therefore, antibiotic resistance surveillance is important to provide the basis of recommendations for the empirical usage of antibiotic agents.

Objectives: To provide data on susceptibility rates of oral antibiotics for non-invasive clinical Hi isolates in Germany and to investigate molecular resistance patterns of β-lactams, ciprofloxacin, doxycycline and trimethoprim/sulfamethoxazole.

Methods: Isolates were collected from a sentinel network of diagnostic laboratories in a prospective multicentre prevalence study. Antibiotic susceptibility testing was done with a commercial broth microdilution kit. MICs were interpreted according to EUCAST guidelines. Resistance gene sequencing and WGS were performed to analyze molecular antibiotic resistance patterns and genetic relationships between the isolates.

Results: In total, 215 Hi isolates were collected from 23 laboratories across Germany. The highest resistance rates were found for amoxicillin (n = 30; 14%), cefuroxime (n = 40; 18.6%) and trimethoprim/sulfamethoxazole (co-trimoxazole) (n = 34; 15.8%). Resistance to amoxicillin was mainly due to bla_TEM-1 (n = 29; 96.7%). PBP3 alterations were found in 39 of 40 cefuroxime-resistant isolates (97.5%). Two of the cefuroxime-resistant isolates harboured PBP3 mutation patterns that have not yet been associated with cefuroxime resistance; in one of them, a known lpoA mutation was found. One isolate showed no mutations in PBP3 or lpoA. All co-trimoxazole-resistant isolates (15.8%) showed known mutations in folA and its promoter region. Additionally, point mutations in folP were identified in a subset of these isolates. The most frequent sequence types (STs) were ST57 (n = 10) and ST103 (n = 10). Genetic cluster analysis identified six clusters, but no epidemiological link could be confirmed.

Conclusion: Resistance to oral antibiotics in non-invasive clinical Hi isolates in Germany was generally low. Amoxicillin is estimated to cover 86% of infections involving non-invasive Hi and, therefore, is still effective for the first-line empirical treatment for ENT infections in Germany. Further surveillance of antimicrobial susceptibility in non-invasive Hi isolates is important to ensure the data basis for guidelines of antibiotic usage.

Background: The pressing need for better antimicrobial stewardship (AMS) is invariably reliant on educational interventions in some form.

Objectives: To evaluate the effectiveness of post-qualification educational interventions for AMS behaviour change among health professionals.

Methods: Seven databases were searched for articles published between 2013 and 2024 for post-qualification educational interventions aimed at health professionals to improve AMS. Randomised controlled trials (RCTs) and quasi-experimental designs such as non-randomised trials, controlled and non-controlled before and after studies, and qualitative studies were considered eligible. The quality of studies was assessed using Cochrane Effective Practice and Organization of Care (EPOC) criteria for RCTs and interrupted time series designs, and the Mixed Methods Appraisal Tool (MMAT) for all other studies. Data were extracted, analysed for effectiveness, and synthesised narratively. Registration: PROSPERO international prospective register of systematic reviews (PROSPERO 2023 CRD42023447115).

Results: Forty-six studies were included in the review, with six meeting the EPOC criteria. The remaining forty were assessed using the MMAT. The overall risk of bias for the six studies meeting the EPOC criteria was low, but risk of bias was high for studies assessed using the MMAT. Overall, there was some evidence that formal education alone was effective in this context, but only limited evidence about what type of educational intervention, for which profession, is most effective.

Conclusions: Our review provided an in-depth examination of post-qualification AMS interventions. We found studies were heterogeneous and quality of evidence relatively poor. High quality studies focused on establishing key components of effective educational interventions are required.

Introduction: Antibiotics are frequently prescribed for neonates and children. However, this can be excessive with inappropriate prescribing leading to increased antimicrobial resistance (AMR). Paediatricians are key initiators of antibiotics. Consequently, their awareness, perceptions, readiness and potential barriers towards hospital-based antimicrobial stewardship programmes are of considerable importance, especially in Pakistan with high rates of AMR.

Materials and methods: A web-based cross-sectional survey among paediatricians from June to August 2023 using a validated questionnaire. Paediatricians from all four Provinces and the capital territory of Pakistan were invited from randomly selected public and private sector hospitals.

Results: 383 paediatricians participated (79.8% response rate). Most were male (87.7%), aged 35 years or less (55.4%), working in tertiary care hospitals (68.4%) and undertaking 51-100 child consultations every day (45%). Only 15% reported obtaining training on antibiotic usage, AMR and/or antimicrobial stewardship. Only 7.6% confirmed functional antimicrobial stewardship programmes in their institutions. Most had adequate knowledge of antibiotic use and AMR. However, key issues were not fully understood with only 27.4% believing antibiotics were being overused among children. Paediatricians with less experience, and who undertook fewer consultations per day, had significantly lower knowledge scores. Most participants were prepared to initiate antimicrobial stewardship programmes; however, perceived barriers included a lack of online learning sources, treatment guidelines and support from hospital administration.

Discussion: Paediatricians had appropriate knowledge about antibiotic use and AMR although concerns with antibiotic use. Important barriers to integrating antimicrobial stewardship programmes were identified, which need addressing for these to become routine.

Introduction: We assessed the kinetics of the clearance of integrase strand transfer inhibitors resistance mutations (INSTIs-RMs) and associated factors from people living with HIV (PWH) displaying suppressed viral replication after virological failure (VF) on an INSTI regimen.

Patients and methods: We included PWH with HIV-RNA viral loads ≤20 copies/mL for at least 5 years in whom INSTIs-RM had been identified at least once in a prior RNA resistance genotyping test. HIV DNAs were sequenced by Sanger sequencing (SS) and ultra-deep sequencing (UDS; detection threshold: 5%) every year over the preceding 5 years.

Results: We included 39 PWH in the study. Most (95%) had experienced VF on a raltegravir-containing regimen. The past INSTIs-RMs were not detected in the peripheral blood mononuclear cells of 35 of the 39 (90%) PWH by SS at the end of follow-up. In a longitudinal analysis (2017-21) based on UDS, the previously detected INSTIs-RMs were not detected in 29 of the 35 (83%) PWH. In multivariable analysis, the duration of viral replication and the level of HIV-RNA during prior VF were significantly associated with the persistence of INSTIs-RM, with odds ratios of 1.05 per week of replication (95% CI, 1.00-1.11; P = 0.024) and 8.26 per log₁₀ copies/mL (95% CI, 1.46-46.59; P = 0.017).

Conclusions: We observed a clear trend towards the clearance of archived INSTIs-RM after a long period of virological control leading to changes in the resistance profile in cellular DNA, raising the possibility of studies assessing the recycling of INSTI classes even in the presence of a history of resistance.

Antimicrobial stability is an important consideration for treatment planning and service delivery in outpatient parenteral antimicrobial therapy (OPAT) programmes. Regulation of stability assessment varies by region, and conflicting guidance and standards exist. This leads to disparity of equity in access and limits availability of certain antimicrobials for managing infections in the outpatient setting. This review discusses the degree to which the international regulatory bodies have reached consensus on the regulation of antimicrobial stability testing, specifically for OPAT, and describes the variation in antimicrobial recommendations across regulatory bodies. The three major findings in this review are (i) variation in antimicrobial stability testing guidance, particularly in relation to temperature; (ii) lack of regulatory guidance, specifically in that some regions did not have OPAT guidelines; and (iii) only the UK's NHS has provided non-regulatory OPAT-specific advice on antimicrobial stability testing. In conclusion, harmonization of antimicrobial stability testing to form a global OPAT-specific regulatory framework, particularly considering 'areas of variation' amongst current guidance, is required. We call for the development of a global OPAT antimicrobial stability testing framework with consensus from accepted antimicrobial stability criteria, expert opinion and pharmacopoeial best practice.

Objectives: AmpC β-lactamases are neglected compared with ESBL as a cause of third-generation cephalosporin (3GC) resistance in Enterobacterales in low- and middle-income countries and the burden is unknown. The aim of this study was to investigate the presence of AmpC β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in clinical specimens from three clinical research laboratories in Southeast Asia.

Methods: Stored clinical isolates of E. coli and K. pneumoniae resistant to ceftriaxone or ceftazidime or cefpodoxime and ESBL confirmation test negative were screened using MASTDISCS AmpC, ESBL and Carbapenemase Detection Set-D72C. Short-read WGS was performed to identify ampC genes.

Results: Of 126 isolates collected between 2010 and 2020, 31 (24.6%) and 16 (12.7%) were phenotypically AmpC and inducible AmpC positive by MASTDISCS testing, respectively. All inducible AmpC isolates were ceftriaxone susceptible and 97.7% of AmpC/inducible AmpC isolates tested against cefoxitin were resistant. Through WGS, 17 and eight different STs were detected for the AmpC/inducible AmpC E. coli and K. pneumoniae isolates, respectively. Twelve different β-lactamase resistance genes were detected, with bla _CMY-2 most commonly in AmpC-positive isolates (20/31; 64.5%; 15 chromosomal, five plasmid). All inducible AmpC-positive isolates had the bla _DHA-1 gene (seven chromosomal, nine plasmid).

Conclusions: Though uncommon, AmpC and inducible AmpC β-lactamases in E. coli and K. pneumoniae are an important cause of infection in Southeast Asia. With current testing methods, these infections may be going undetected, resulting in patients receiving suboptimal treatment.