New genomic surveillance studies reveal circulation of multidrug-resistant Enterobacterales in Europe.
ECDC, 25 Nov 2024

Two studies published in Eurosurveillance marking European Antibiotic Awareness Day and World AMR Awareness Week raise the alarm about the spread of bacteria resistant to carbapenems in both healthcare and community settings across Europe. E. coli lineage with emerging resistance pattern spreads in the community. A data analysis from 17 Eur. Union and European Economic Area (EU/EEA) countries shows an increasing spread of the carbapenem-resistant bacteria E. coli sequence type (ST)131. Worldwide, E. coli is the pathogen associated with the most deaths attributable to antimicrobial resistance, and the specific type of E. coli ST 131 is frequently associated with multi-drug resistance. The study analysed epidemiological data of almost 600 E. coli ST131 isolates, provided by national reference laboratories from different EU countries. One group of isolates stood out for potential association with urinary tract infections in the community due to the relatively low median age of patients (57 years), a high proportion of female patients and the frequent detection of isolates from urine samples. These data suggest there is a much wider spread of carbapenem-resistant Enterobacterales infections in the community in the EU/EEA.

UN calls for action, accountability on antimicrobial resistance
UN 26 September 2024

The UN General Assembly convened a High-Level Meeting on antimicrobial resistance (AMR) for the second time during its 79th session (UNGA 79) in New York in September 2024. Drug-resistant infections know no borders, meaning no single country can respond to AMR alone. This meeting is an important opportunity for world leaders to collectively address the looming threat AMR poses to global health, food security, and achieving the 2030 Sustainable Development Goals. Organized by the President of the General Assembly, a multi-stakeholder hearing on AMR took place on 15 May 2024, as part of the preparatory process for the High-level Meeting. The hearing was a key moment for stakeholders from across different sectors to contribute, ahead of intergovernmental negotiations on the political declaration. The hearing was supported by WHO, the Food and Agriculture Organization of the United Nations, the United Nations Environment Programme, the World Organisation for Animal Health (also known collectively as the Quadripartite organizations) and other relevant partners.

A Landscaping Assessment and Call-to-Action to Improve: Access to Novel Reserve Antibiotics in 14 Low- and Middle-Income Countries.
Motta F, et al. Pub Health Challenges. 2024. 3(4), e70005.

Antimicrobial resistance (AMR) presents a significant global mortality burden which particularly affects the low- and middle-income countries (LMICs). This article characterizes the AMR landscape across 14 LMICs and describes an introductory pathway for novel Reserve antibiotics. This mixed-method study was completed in 14 LMICs in Africa, the Americas, Asia and Europe through a combination of qualitative interviews with physicians and public health experts (PHEs), and a quantitative survey of physicians, supported by an assessment of secondary materials relating to antibiotic introduction and AMR burden. A total of 54 physicians and 17 PHEs were interviewed, and 209 physicians participated in the survey. Top unmet needs across public and private settings were the access to new antibiotics to better manage drug-resistant infections, the affordability and adequate safety profile for prescribed antibiotics. Enhancing diagnostics to identify drug-resistant infections and improving appropriate access to novel Reserve antibiotics in LMICs can address AMR-related morbidity, mortality and healthcare costs. This study has helped to identify common barriers and pathways to Reserve antibiotic access, irrespective of the level of preparedness of countries.

Antibiotic resistance incidence or proportions: where does the greatest burden lie?
Walker MK, Kadri SS. Lancet Infect Dis. 2024 Dec;24(12):1291-1293.

Author’s ability to accurately assess changes in the overall burden of resistant pathogens, the effects of these changes on key clinical outcomes, and the effects of control interventions on antibiotic resistance, is crucial in preventing antibiotic resistance. Output from antibiotic resistance surveillance is routinely presented as resistance proportions (i.e., percentage isolates resistant) or as incidence (i.e., resistant infection episodes per population per unit time). Proportion-based surveillance data help guide clinicians on empirical antibiotic selection for individual patients and incidence provides an epidemiological picture of the population-based burden. For example, although a change in carbapenem resistance from 2% to 3% represents a 50% relative increase, it only represents a small absolute increase in a population in which carbapenem-resistant infections are very rare. So, an increase in the incidence of carbapenem-resistant Enterobacterales from two per 100 000 people per year to three per 100 000 people per year does not suggest whether it is due to more Enterobacterales infections, increased carbapenem resistance within Enterobacterales, or both.

Duration of antibiotic therapy for multidrug resistant Pseudomonas aeruginosa pneumonia: is shorter truly better?
Truong CN, et al. BMC Infect Dis. 2024 Sep 3;24(1):911

The limited literature has demonstrated higher rates of recurrence for non-glucose fermenting gram-negative bacilli with short course therapy, raising the concern of optimal treatment duration for these pathogens. Therefore, authors aimed to compare the outcomes for patients receiving shorter therapy treatment (≤ 8 days) versus longer regimen (> 8 days) for the treatment of multidrug resistant (MDR) Pseudomonas pneumonia. A single-centre, retrospective cohort study was conducted to evaluate adult patients receiving an antimicrobial regimen with activity against MDR P. aeruginosa in respiratory culture between 2017 and 2020 for a minimum of 6 consecutive days. Of 427 patients with MDR P. aeruginosa respiratory isolates, 85 patients were included. Baseline characteristics were similar among groups with a median age of 65.5 years and median APACHE 2 score of 20. Roughly 75% had ventilator-associated pneumonia. Compared to those who received ≤ 8 days of therapy, no difference was seen for clinical success in patients treated for more than 8 days (80% vs. 65.5%, p = 0.16). The number of 30-day and 90-day in-hospital mortality, 30-days relapse, and other secondary outcomes did not significantly differ among the treatment groups.

Patient and public understanding of antimicrobial resistance: a systematic review and meta-ethnography
Wojcik G, et al. JAC Antimicrob Resist. 2024 Aug 7;6(4):dlae11

In this study systematic search of 12 electronic databases, including CINAHL, MEDLINE, PsycINFO, PubMed and Web of Science to identify qualitative primary studies exploring patient and public understanding of AMR published between 2012 and 2022. Thirteen papers reporting 12 qualitative studies were synthesized, that reported data from 466 participants aged 18–90 years. Five themes were identified from these original studies, which supported the development of a conceptual model that illustrates the tension between two different assumptions, that is, how can antibiotics be used for the collective good whilst balancing the immediate needs of individual patients. The meta-ethnography-generated conceptual model illustrates many factors affecting the public’s perception of AMR, including laypeople’s own knowledge, beliefs and attitudes around antibiotic use, the relationship with the healthcare provider and the wider context, including the overwhelming influence of the media and public health campaigns.

Drivers of virulence and antimicrobial resistance in Gram-negative bacteria in different settings: A genomic perspective.
Singh A, et al. Infect Genet Evol. 2024 Oct;124:105666.

Recent genomics-driven research has provided insights into the transmission and evolutionary dynamics of major enteric pathogens such as E.coli, K. pneumoniae, Vibrio cholerae, H. pylori and Salmonella spp. Studies entailing the identification of various dominant lineages of some of these organisms based on artificial intelligence and machine learning point to the possibility of a system for prediction of antimicrobial resistance (AMR) as some lineages have a higher propensity to acquire virulence and fitness advantages. The aim of this review is to discuss virulence and AMR in Gram-negative pathogens, the spillover of AMR and methodological advancements aimed at addressing it through a unified One Health framework applicable to the farms, the environment, different clinical settings and the human gut. The next major challenge for public health epidemiologists is understanding the interactions and functioning of these pathogens at the community level, both in the gut and outside.

Pseudomonas aeruginosa Biofilm Formation: Antibiofilm Strategies and Conventional Methods of Evaluation
Ma'aitah S, et al.  Jour of Basic and Applied Research in Biomedicine,10(1): 11-28, Published: Oct 12, 2024.

This review provides a detailed examination of biofilm development stages attachment, maturation, and dissemination and highlights the role of specific genes in each stage, with a focus on quorum sensing as a key regulatory mechanism governing bacterial communication within biofilms. It also evaluates conventional methods for analysing P. aeruginosa biofilm phenotypes, discussing their purposes, advantages, and limitations. Accordingly, future research should focus on standardizing protocols, advancing imaging technologies, and targeting biofilm-specific mechanisms. Collaborative efforts across disciplines and translational research will be essential for developing effective therapies. This review aims to deepen understanding of P. aeruginosa biofilm dynamics and highlight the implications for developing effective therapies against biofilm-associated infections.

AVR/I/SSAPDB: A Comprehensive & Specialised Knowledgebase of Antimicrobial Peptides to Combat VRSA, VISA, and VSSA
Kumar Mondal R, et al. Research Square 04 September 2024

The rise of multi-drug resistant (MDR) bacteria, possessing a severe threat to global health, underscores the urgent need for novel antimicrobial agents to combat these resistant strains effectively. Authors are introducing the Anti-Vancomycin-Resistant/Intermediate/Susceptible S. aureus. Peptide Database (AVR/I/SSAPDB), a manually curated comprehensive and specialized knowledgebase dedicated to antimicrobial peptides (AMPs) that target VRSA, VISA, and VSSA with clinical and non-clinical significance. Authors database sources data from PubMed, cataloguing 491 experimentally validated AMPs with detailed annotations on peptides, activity, and cross-references to external databases like PubMed, UniProt, PDB, and Drug Bank. Authors are hoping that this resource will be helpful to the scientific community in developing targeted peptide-based therapeutics, providing a crucial tool for combating VRSA, VISA, and VSSA, and addressing a major public health concern.

Transmission Dynamics and Novel Treatments of High Risk Carbapenem-Resistant Klebsiella pneumoniae: The Lens of One Health.
Zhu J, et al. Pharmaceuticals (Basel). 2024 Sep 12;17(9):1206.

The carbapenem-resistant K. pneumoniae (CRKP) has experienced various changes and discoveries in recent years regarding its frequency, transmission traits, and mechanisms of resistance. In this comprehensive review, authors present an in-depth analysis of the global epidemiology of K. pneumoniae, they elucidate resistance mechanisms underlying its spread and explore evolutionary dynamics concerning carbapenem-resistant hypervirulent strains as well as KL64 strains of K. pneumoniae and then discuss recent therapeutic advancements and effective control strategies while providing insights into future directions. By going through up-to-date reports, authors found that the ST11 KL64 CRKP subclone with high risk demonstrated significant potential for expansion and survival benefits, likely due to genetic influences. In addition, it should be noted that phage and nanoparticle treatments still pose significant risks for resistance development.