Matthew Dryden

Infections caused by multidrug-resistant Gram-negative (MDR-GN) bacteria, particularly carbapenem-resistant organisms (CROs), constitute a significant burden in critically ill patients (CIPs). A multidisciplinary, collaborative approach is essential for responsible antibiotic use in CIPs, balancing the necessity for effective treatment with mitigation of antimicrobial resistance (AMR). While the efficacy of existing antibiotics against CROs is increasingly limited due to resistance development and suboptimal pharmacokinetic/pharmacodynamic properties, several barriers impede the widespread adoption of new agents, including selective susceptibility testing, limited availability, high costs, and concerns regarding the fostering of resistance. Antimicrobial stewardship (AMS) strategies aim to optimize antibiotic use; however, there is an ongoing debate between restrictive and enabling approaches for new antibiotics in CIPs with CRO infections. While restrictive strategies focus on limiting antibiotic use to mitigate resistance, they may delay necessary treatment and negatively impact professional culture. Enablement strategies promote informed decision-making and accessibility when needed but require substantial workforce and expertise. In this narrative review and expert opinion, we propose an algorithm supporting a coordinated AMS approach in CIPs, emphasizing the importance of early diagnosis and appropriate therapy. We advocate for an enablement strategy for new antibiotics in CIPs with MDR-GN infections, aiming to reduce mortality and toxicity associated with older agents. This strategy should be integrated into local AMS programmes under the guidance of experienced clinicians.

Objective: Many of the UK overseas territories are small with limited microbiological diagnostic capacity for pathogens and antimicrobial resistance detection. The Covid-19 pandemic highlighted the particular vulnerability of these territories for the emergence of novel infections and antimicrobial resistance. Methods: The UKHSA program with its territory partners implemented rapid automated syndromic molecular diagnostics (RASM), aiming to improve diagnostic capacity. Local laboratory staff were trained in the use of the diagnostics, and guidance was provided to clinicians for requesting tests. Syndromic diagnoses included enteric, respiratory, bloodstream, neurological infection, and antibiotic resistance mechanisms. Data on diagnostic capacity, turnaround times and clinical impact were collected from records before and after implementation of RASM. Results: Turnaround time for results went from an average 14 days to 1 day, and often much shorter. Previously undiagnosed conditions, could now be identified to the microbiological level rapidly in territory, allowing appropriate specific clinical management, infection prevention, improved antimicrobial stewardship and rapid public health response. This technology is simple to operate and maintain with little scope for user error. The speed of microbiological diagnosis for patient management and public health detection and response was greatly enhanced. Conclusion: Rapid microbiological diagnosis on site transformed patient management, the timely investigation and management of outbreaks and clusters, accurate surveillance and antimicrobial stewardship. Targeted RASM is cost effective, reducing the requirement for highly trained scientific staff and expensive logistics around rapid transport to reference laboratories. This innovation improves clinical care and strengthens local preparedness in communicable disease and public health response.

The UK Overseas Territories (UKOTs) are small, often remote territories with historical and territorial links to the UK. They range from densely populated areas (Cayman, Bermuda, Gibraltar) to land with no permanent inhabitants (British Antarctic Territory, South Georgia). However, they are linked by ecosystem instability (the permacrisis) including antimicrobial resistance (AMR), climate change and biodiversity disruption. The Chief Medical Officers of the UKOTs met in June 2024 and were unanimous in their concerns about the threat of global AMR. They have issued this statement on their hopes and expectations for the United Nations’ General Assembly High-Level Meeting, in September 2024. These may be summarized by the hope of achieving united and sustained global political will to reduce the threat of AMR by equitable access to treatments, prevention of AMR by sanitation and accurate diagnostics, and education in health care and the public.

Purpose of review: Global antibiotic resistance is compromising the management of soft tissue infection and Acute Bacterial Skin and Skin Structure Infection (ABSSI). This review describes a novel topical treatment Reactive Oxygen (RO) gel which could compliment and in some situations replace systemic antibiotics. Recent findings: A novel topical treatment RO gel could have an important role in treatment, infection prevention and antimicrobial stewardship. RO is highly antimicrobial against Gram positive and negative bacteria, by slow release of oxygen radicals over a prolonged period of up to 72 h. It prevents and breaks down biofilm and may support healing by cellular signalling. Much clinical investigation remains to be delivered on RO therapy but there seem few disadvantages in its use and early clinical evaluations are extremely promising. Summary: Managing complicated skin and soft tissue infections require more than just antibiotic treatment. Soft tissue infection healing is often compromised by underlying comorbidities and pathology and increasingly the presence of highly antimicrobial-resistant bacteria. This has been highlighted particularly in war and trauma soft tissue infection. The fundamentals of soft tissue infection repair require early surgical drainage and debridement, correction of compromised physiology and treatment of underlying conditions and appropriate antimicrobial treatment. RO therapy could be an important advance.

Viral transmission of SARS-CoV-2, the virus causing COVID-19 is very high within households despite self isolation [1,2].

There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. An observational derivation patient cohort validated by an independent secondary analysis across nine EDs. Logistic and Cox regression, area under the receiver operating characteristic (AUROC) and Kaplan-Meier curves were used to assess performance. Disease progression was identified using a composite endpoint of 28-day mortality, ICU admission and hospitalisation > 10 days. One thousand one hundred seventy-five derivation and 896 validation patients were analysed with respective 28-day mortality rates of 7.1% and 5.0%, and hospitalisation rates of 77.9% and 76.2%. MR-proADM showed greatest accuracy in predicting 28-day mortality and hospitalisation requirement across both cohorts. Patient subgroups with high MR-proADM concentrations (≥ 1.54 nmol/L) and low biomarker (PCT < 0.25 ng/mL, lactate < 2.0 mmol/L or CRP < 67 mg/L) or clinical score (SOFA < 2 points, qSOFA < 2 points, NEWS < 4 points or CRB-65 < 2 points) values were characterised by a significantly longer length of hospitalisation (p < 0.001), rate of ICU admission (p < 0.001), elevated mortality risk (e.g. SOFA, qSOFA and NEWS HR [95%CI], 45.5 [10.0–207.6], 23.4 [11.1–49.3] and 32.6 [9.4–113.6], respectively) and a greater number of disease progression events (p < 0.001), compared to similar subgroups with low MR-proADM concentrations (< 1.54 nmol/L). Increased out-patient treatment across both cohorts could be facilitated using a derivation-derived MR-proADM cut-off of < 0.87 nmol/L (15.0% and 16.6%), with decreased readmission rates and no mortalities. In patients presenting to the ED with a suspected infection, the blood biomarker MR-proADM could most accurately identify the likelihood of further disease progression. Incorporation into an early sepsis management protocol may therefore aid rapid decision-making in order to either initiate, escalate or intensify early treatment strategies, or identify patients suitable for safe out-patient treatment.