Dionysios Ntais

Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are associated with substantial morbidity, mortality and therapeutic uncertainty, particularly in critically ill and immunocompromised patients. Imipenem/cilastatin/relebactam (IMI/REL) combines the established carbapenem imipenem with cilastatin, a dehydropeptidase-I inhibitor, and relebactam, a diazabicyclooctane beta-lactamase inhibitor that restores imipenem activity against selected class A and class C beta-lactamase-mediated resistance mechanisms. Methods: A targeted narrative review was undertaken to identify and provide an overview of published observational studies and conference abstracts reporting clinical outcomes with IMI/REL in patients with confirmed or suspected MDR P. aeruginosa infection. Evidence was summarized descriptively, because the available studies were heterogeneous in design, infection site, patient severity, pathogen mix, susceptibility testing and outcome definitions. Results: Real-world IMI/REL data remain limited but are increasingly informative. IMI/REL was commonly used in high-risk patients, including those with pneumonia, bacteremia, intensive care admission, prior antimicrobial exposure, polymicrobial infection or limited alternative treatment options. Reported clinical success or clinical cure was observed in approximately 56–70.2% of patients, although interpretation is limited by non-comparative designs, small patient populations and mixed-pathogen populations. Thirty-day all-cause mortality varied widely, broadly reflecting baseline severity, infection site and salvage-therapy use. Emergence of IMI/REL non-susceptibility was variably reported, but some recent studies report high rates of treatment-emergent resistance; this requires caution and remains an important area for surveillance. Conclusions: IMI/REL appears to be a clinically useful option for susceptible MDR P. aeruginosa infections, particularly in patients with limited alternatives. Available real-world evidence should be interpreted cautiously, because most data derive from retrospective uncontrolled cohorts.

Background: Coronavirus disease 2019 (COVID-19) is an acute respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severe disease may require hospitalisation and respiratory support, which can cause longer-term morbidity. Patient utility data are limited, especially for severe disease where data collection can be challenging or unethical. A vignette study was designed to estimate utility values for COVID-19 disease states. Methods: A sample of United Kingdom (UK)-based adults ( N = 500) completed the EQ-5D-5 L questionnaire for eight vignettes as patient proxies in September 2021. Vignettes qualitatively described hospitalisation and disease severity permutations, informed by a large UK-based COVID-19 infection survey. Recruitment was stratified to reflect UK demographics. EQ-5D utilities were derived using the appropriate UK value set. Results: Recovery without long-term sequelae had the highest utility (mean [standard deviation]: 0.87 [0.14]), followed by pre-infection (0.73 [0.22]). The intensive care unit state had the lowest utility (–0.38 [0.14]). Mild and moderate outpatient states reported similar utility (0.29 [0.26] vs. 0.31 [0.27]). The severe general hospital ward state had lower utility than the high dependency unit state (–0.18 [0.24] vs. − 0.11 [0.25]). Recovery with long-term sequelae had low utility (0.21 [0.29]). Conclusions: Mean utility values declined as COVID-19 disease state severity increased, suggesting that COVID-19 is likely to impact patient quality of life, in line with published literature. However, the evolving nature of COVID-19 may limit the generalisability of findings to the current disease landscape. Nevertheless, generation of utility values using a vignette-based approach represents a reasonable alternative where collection patient health-related quality of life data is infeasible, albeit with some limitations. Trial registration: Not applicable.

Background/Objectives: Pneumococcal conjugate vaccines (PCVs) were first introduced in the pediatric UK National Immunization Programme (NIP) in 2006 and subsequently led to a significant decline in invasive pneumococcal disease (IPD). In 2020, the UK NIP reduced the pediatric PCV dosing schedule from two infant doses and one toddler dose (2 + 1) to one infant dose and one toddler dose (1 + 1). This analysis evaluated the public health impact of pediatric vaccination with PCV15 versus PCV13 under a 1 + 1 schedule. Methods: A population-level compartmental model was previously adapted to the UK setting. The impact on the IPD incidence of vaccination with PCV15 versus PCV13 under a 1 + 1 schedule was evaluated over a 20-year time horizon. The uncertainty regarding the vaccine efficacy (VE) of PCV13 and PCV15 under a 1 + 1 schedule was investigated through a probabilistic sensitivity analysis, i.e., the PCV VE under a 1 + 1 schedule was assumed to be 0–24% lower than the PCV VE under a 2 + 1 schedule. Results: Relative to the initial IPD incidence, vaccination with PCV13 and PCV15 under a 1 + 1 schedule resulted in the IPD incidence in children <2 years old increasing by 11.1% (95% region: 8.4–14.5%) and 3.5% (0.2–7.7%), respectively, over the time horizon. At the end of the time horizon, in the overall population, PCV15 would lead to a 6.0% lower IPD incidence than PCV13 (10.70 IPD cases per 100,000 versus 11.38 per 100,000, respectively). Conclusions: Switching from PCV13 to PCV15 for routine pediatric vaccinations under the 1 + 1 dosing schedule in the UK led to a lower IPD incidence in both the pediatric and overall populations.