Pharmacovigilance Data as a Trigger to Identify Antimicrobial Resistance and Inappropriate Use of Antibiotics: A Study Using Reports from The Netherlands Pharmacovigilance Centre.

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and pharmacovigilance has the potential to strengthen current antimicrobial stewardship strategies. This study aimed to characterize AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre; (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs); (3) Results: Between 1998 and January 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n = 89; 35%), colistin (n = 30; 11.9%), cipro-floxacin (n = 16; 6.3%), doxycycline (n = 14; 5.5%), and aztreonam (n = 12; 4.8%). The PTs used included off label use (n = 91; 36.1%), drug ineffective (n = 71; 28.2%), product use in unapproved indication (n = 28; 11.1%), pathogen resistance (n = 14; 5.6%), and drug resistance (n = 13; 5.2%). 54% of the reports were on Watch antibiotics and 19% were involved in the Reserve group. In the Watch group, "off label use" and "product use in unapproved indication" were the most frequent PTs and the majority of reports on Reserve antibiotics were coded as "Off label". A sharp increase in the number of reports was observed in the three consecutive years with 21 in 2013, 54 in 2014, and 83 in 2015; (4) Conclusions: In addition to existing AMR monitoring strategies, pharmacovigilance databases can serve as a source of data on suspected resistance and inappropriate use. Future research should explore how these AMR-relevant MedDRA Terms are used in resource-limited settings with less capacity to generate laboratory-confirmed resistance data.

Strengthening capacity for clinical research in sub-Saharan Africa: partnerships and networks.

Global research collaboration, through partnerships and networks, is an effective way to deliver highly impactful and sustainable research that is collectively owned and promoted for the global good. Many models exist for effective North-South collaborations that are built on trust and balanced benefits. The European & Developing Countries Clinical Trials Partnership (EDCTP) model emphasises capacity development in clinical trials and product-focused implementation research. To ensure effectiveness and sustainability, capacity development requires a long-term perspective, an integrated system-wide approach, and local ownership and leadership from countries experiencing high disease burdens. Guided by these principles, the EDCTP2 programme, established in 2014, has developed and strengthened human capital and institutional capacities in 39 countries in sub-Saharan Africa to undertake high-quality clinical research guided by good clinical and regulatory practices. Projects in these countries have involved 238 African and 163 European institutions. To date, EDCTP has supported 171 Fellows and 232 postgraduate trainees. EDCTP-short-term training activities have equipped 9628 researchers and medical personnel. The EDCTP capacity-building described here includes its Regional Networks of Excellence and its Consortia for public health emergencies which provide the foundation for sustained efforts against emerging and re-emerging global health threats.

Pharmacovigilance network as an additional tool for the surveillance of antimicrobial resistance.

BACKGROUND: The WHO Programme for International Drug Monitoring (PIDM) is a large Pharmacovigilance network of countries sharing Adverse Drug Reaction (ADR) reports. Pharmacovigilance Experts have suggested that antimicrobial resistance (AMR) is an overlooked adverse event. We undertook this study to investigate the potential role of Pharmacovigilance databases in the surveillance of AMR. METHODS: Using the AWaRe (Access, Watch and Reserve) list and the WHO Priority Pathogens List, we established a list of antimicrobials and carried out a VigiBase search via VigiAccess, looking for ADR reports with Preferred Terms (PTs) that contained AMR-relevant information. Identified Terms were matched with codes from the Medical Dictionary for Regulatory Activities (MedDRA Version 21.1). RESULTS: Records on 86 drugs were retrieved with a total of 1 170 751 ADR reports submitted between 1968 and 2018. Seventeen PTs suggesting suspected resistance, ineffectiveness, inappropriate use, or medication error were used to code 15 250 reports. The most frequently used PTs were "Drug Ineffective" (45.6%), "Off label use" (9.5%) and "Pathogen Resistance" (8.9%). A group of six agents (Amoxicillin, Cefalotin, Ciprofloxacin, Clarithromycin, Levofloxacin and Daptomycin) accounted for 38% (n = 5806) of all 15 250 AMR-relevant ADR reports. The PTs most frequently used in 5806 reports were grouped in 4 categories: drug ineffectiveness (62.5%), resistance (19.2%), off-label use (12.1%) and prescription errors (6.2%). CONCLUSION: Our findings suggest that Pharmacovigilance databases could serve as a tool in tracking antimicrobial use and resistance especially in settings where laboratory capacity is still in its development stages. National Pharmacovigilance centers could play a proactive role in stimulating the reporting of AMR-relevant ADRs which can serve as a basis for resistance suspicion alerts. Further studies focusing on the narrative and other clinical pharmacology details in ADR reports are required.

Antimicrobial stewardship: can we add pharmacovigilance networks to the toolbox?

BACKGROUND: Antimicrobial resistance (AMR) is no longer an expected upcoming threat; it has become a real public health concern, challenging all existing control tools, requiring multidisciplinary innovative solutions. Antimicrobial stewardship (AMS) programs require a set of tools and skills which can be put to service by health systems. However, there is an immense capacity gap between health systems in developed countries compared to developing ones. Systems in developed countries can rely on well-established laboratory services that can carry out microbial cultures and drug susceptibility tests. For many low- and middle-income countries (LMICs) with limited laboratory resources, it will take time and long-term investments to have systems that can timely and reliably perform laboratory-based AMR monitoring. In the meantime, we must explore the possibility of using other indirect measures that can provide estimates of the growing burden of AMR in settings with weak laboratory capacity. OBJECTIVES: In this point of view, we describe the potential contribution of the global pharmacovigilance (PV) networkers in the process of mapping and estimating the AMR burden in settings with less laboratory coverage and capacity, within the framework of AMS. CONCLUSION: The heavy toll caused by AMR will not be brought down by a singular interventional approach, it will require a multidisciplinary and multifaceted set of strategies. Closing the laboratory capacity gap will require tremendous long-term investments, but the AMR data scarcity is a question that cannot wait any longer. The global pharmacovigilance network is a robust scientific community with experience in tracking suspected adverse events caused by new and old medicinal products. As AMR becomes a global health issue, AMS programs need all available tools to address resistance data scarcity and inform appropriate of antimicrobials. The solid global pharmacovigilance infrastructure could play an important role in countries with limited laboratory coverage and capacity.