Towards comprehensive clinical trials for new tuberculosis drug regimens: policy recommendations from a stakeholder analysis.

BACKGROUND: Research and development (R&D) of new drugs and regimens against tuberculosis (TB) is evolving to meet new challenges and face limited investments in the sector. To effectively improve and fill existing gaps, researchers and trialists should engage a broad spectrum of stakeholders. With this study, we aim to map the interests in TB R&D raised by the main stakeholders in the TB field. METHODS: We conducted semistructured, short interviews to gather insight and viewpoints on innovation on TB drugs and regimens R&D of policy-makers, national TB programme officers, donors, funders, non-governmental organisations and research institutions.A composite measure of the relevance of topics that emerged was computed by implementing different models considering the importance for researchers and the urgency to implement those changes during the trial, the number of citations each topic received, and the maximum value of the influence of stakeholders who had raised the topic. RESULTS: 50 stakeholders, out of 56 identified, were interviewed and almost half were policy-makers and governmental institutions. Several stakeholders highlighted the importance of disseminating information about clinical trials' methodology and emerging preliminary results, followed by the need to pursue early discussion around access and pricing of safe and effective TB innovations, although different categories of stakeholders prioritised different topics. Using different methods for ranking topics, the results remained almost unchanged. Notably, post-trial operational research ranked higher in models with higher weight for the parameter considering the number of citations. CONCLUSION: Researchers and research consortia embarking on phase 2 and 3 clinical trials should consider a broad set of elements when planning and designing trials' protocols, all aiming at lowering the price and improving access to emerging TB innovations, besides meeting regulatory criteria. This can only be achieved by consulting and engaging relevant stakeholders in the discussion.

Burden of Antimicrobial Resistance Among Women with Post-Partum Infections in Low-Middle Income Countries: A Systematic Review.

BACKGROUND: Due to the rising incidence of multidrug-resistant (MDR) pathogens, especially in Low-Middle-Income Countries (LMIC), post-partum infections represent a significant treatment challenge. METHODS: We performed a systematic review of the literature from January 2005 to February 2023 to quantify the frequency of maternal post-partum infections due to MDR pathogens in LMICs, focusing on methicillin-resistant Staphylococcus aureus (MRSA) and/or extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales. SECONDARY OBJECTIVES: description of antimicrobials' prescriptions. FINDINGS: We included 22 studies with 14,804 total bacterial isolates from 12 countries, mostly from WHO African-Region. Twelve papers described wound- and 10 puerperal-infections. Seven were high-quality articles. Seventeen studies reported data on MRSA, and 18 on ESBL-producing Enterobacterales. Among high-quality studies, MRSA ranged from 9.8% in Ghana to 91.2% in Uganda; ESBL-producing Enterobacterales ranged from 22.8% in Ukraine to 95.2% in Uganda. Nine articles, mostly on C-sections, described different protocols for antibiotic prophylaxis and/or post-partum treatment. INTERPRETATION: We described a high burden of post-partum infections caused by MRSA and/or ESBL-producing Enterobacterales in LMICs, but only a few studies met quality standards. There is an urgent need for high-quality studies to better describe the real burden of antimicrobial resistance in low-resource settings and inform policies to contain the spread of multidrug-resistant organisms.