Introduction
Health care-associated infections (HAI) are one of the most common adverse events in care delivery and both the endemic burden and the occurrence of epidemics of HAI are a major public health problem. HAI have a significant impact on morbidity, mortality and quality of life and present an economic burden at the societal level. However, a large proportion of these infections is preventable by effective infection prevention and control (IPC) measures (8–10).
Carbapenem-resistant gram-negative bacteria, namely, carbapenem-resistant Enterobacteriaceae (CRE) (for example, Klebsiella pneumoniae, Escherichia coli), Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPsA), are a matter of national and international concern as they are an emerging cause of HAI that pose a significant threat to public health (1). These bacteria are difficult to treat due to high levels of antimicrobial resistance (AMR) and are associated with high mortality. Importantly, they have the potential for widespread transmission of resistance via mobile genetic elements (11).
Rationale for the development of CRE-CRAB-CRPsA guidelines
Since the publication of an expert consensus document on the core components for infection prevention and control by the World Health Organization (WHO) in 2009 (12), threats posed by epidemics, pandemics and AMR have become increasingly evident as ongoing universal challenges and they are now recognized as top priorities for action on the global health agenda. Effective IPC is the cornerstone of such action to control AMR and the spread of multidrug-resistant pathogens, such as CRE-CRAB-CRPsA. This is emphasized by the International Health Regulations (IHR), which identify effective IPC as a key strategy for dealing with public health threats of international concern. More recently, the United Nations Sustainable Development Goals (SDGs) highlighted the importance of IPC as a contributor to safe, effective high-quality health service delivery, particularly those related to water, sanitation and hygiene (WASH) and quality and universal health coverage. In 2016, WHO released the updated Guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13). These new guidelines form a key part of WHO strategies to prevent current and future threats, strengthen health service resilience and help combat AMR. During the guideline development process and the many detailed discussions by the Guideline Development Group (GDG) members, it became clear that the specific threat posed by infections due to CRE-CRAB-CRPsA required specific attention, including having clear, practical IPC guidelines on how best to manage this rapidly emerging problem. CRE-CRAB-CRPsA infections are particularly notable because they are associated with high morbidity and mortality, as well as the potential to cause outbreaks and contribute to the spread of resistance. Furthermore, it was recognized that colonization with CRE-CRAB-CRPsA precedes or is co-existent with CRE-CRAB-CRPsA infection almost universally. Thus, early recognition of CRE-CRAB-CRPsA colonization is likely to help identify patients most at risk of subsequent CRE-CRAB-CRPsA infection. This will also allow the earlier introduction of IPC measures in health care settings to prevent pathogen transmission to other patients and the hospital environment. For this reason, it was agreed that a key priority should be the development of WHO IPC guidelines specifically targeting the prevention and control of colonization and infection with CRE-CRAB-CRPsA in health care settings.
Objectives
The objectives of the guidelines are to provide:
evidence-based recommendations on the early recognition and specific required IPC practices and procedures to effectively prevent the occurrence and control the spread of CRE-CRAB-CRPsA colonization and/or infection in acute health care facilities;
an evidence-based framework to help inform the development and/or strengthening of national and facility IPC policies and programmes to control the transmission of CRE-CRAB-CRPsA in a variety of health care settings.
The recommendations included in these guidelines build upon the overarching IPC standards set by the WHO publication Guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) and, in this context, they are meant to align with fundamental IPC principles and to strengthen their uptake.
Target audience
The CRE-CRAB-CRPsA guidelines are intended to support IPC improvement at the health care facility and national level, both in the public services and private sector. At the facility level, the main target audience is local IPC teams and/or professionals in charge of planning, developing and implementing local IPC programmes. This includes senior managers (for example, chief executive officers) and, ultimately, all health care workers providing patient care. At the national level, this document provides guidance primarily to policy-makers responsible for the establishment and monitoring of national IPC programmes and the delivery of AMR national action plans within ministries of health.
The guidelines are also relevant for national and facility safety and quality leads and managers, regulatory bodies and allied organizations, including academia, national IPC professional bodies, non-governmental organizations involved in IPC activity and civil society groups.
The guidelines focus primarily on acute health care facilities. However, the core principles and practices of IPC to be applied as a control measure against the emergence and spread of CRE-CRAB-CRPsA are common to any facility where health care is delivered. Therefore, these guidelines should also be implemented with some adaptations by primary and long-term care facilities (LTCFs) as they develop and review their IPC programmes.
Although legal, policy and regulatory contexts may vary, these guidelines are relevant to both high- and low-resource settings.
Methods
The guidelines were developed following the methods outlined in the 2014 WHO handbook for guideline development (14). The development process included six main stages: (1) identification of the PICO (Population/Participants, Intervention, Comparator, Outcome/s) question (an approach commonly used to formulate research questions); (2) performing a systematic review for the retrieval of the evidence; (3) developing an inventory of national and regional IPC action plans and strategic documents; (4) assessment and synthesis of the evidence; (5) formulation of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach; and (6) writing of the guidelines and planning for the dissemination and implementation strategies.
The development of the guidelines involved the formation of four main groups to guide the process: the WHO Guideline Steering Group, the GDG, the Systematic Reviews Expert Group and the External Peer Review Group. The WHO Steering Group identified the primary critical outcomes and topics, formulated the research questions and identified the systematic review teams, the guideline methodologist and members of the GDG. The GDG included international experts in IPC and infectious diseases, public health, researchers and patient representatives, as well as country delegates and stakeholders from the six WHO regions.
The systematic review assessed the following research question: What is an effective approach to preventing and controlling the acquisition of and infection with CR and/or CRAB and/or CRPsA among inpatients in health care facilities? Studies with no time limit applied and conference abstracts from the last five years (2012–2016) were included. Search terms included three concepts: (1) carbapenemase/carbapenem resistance; (2) core IPC measures; and (3) CRE and/or CRAB and/or CRPsA (that is, CRE-CRAB-CRPsA) colonization and/or infection rates.
The CRE-CRAB-CRPsA literature review used the risk of bias criteria developed for the Cochrane Effective Practice and Organization of Care (EPOC) reviews. Based on the systematic reviews, the GDG formulated recommendations using the GRADE approach. Finally, the GDG identified research gaps and implications for research. Additionally, a review of the guidelines was conducted by the WHO Public Health Ethics Consultation Group and feedback was incorporated accordingly.
Recommendations
The 2016 WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) provided an initial foundation for the development of the recommendations for the prevention and control of CRE-CRAB-CRPsA. The GDG evaluated the relevance of the core components, together with the evidence emerging from the new systematic review specifically on CRE-CRAB-CRPsA. It identified eight key recommendations that apply to the facility level and which can be used to improve the development of national policy on the prevention and control of CRE-CRAB-CRPsA transmission and infection across health sectors.
The eight recommendations are summarized in , including the strength of each recommendation and the quality of the supporting evidence. Of note, the numbered list of IPC recommendations included in the guidelines is not intended to be a ranking order of the importance of each recommendation. As countries and facilities implement the recommendations (or undertake actions to review and strengthen their existing IPC programmes), they may decide to prioritize specific components depending on the context, previous achievements and identified gaps, with the long-term aim to build a comprehensive approach as detailed across all eight recommendations.
Summary of recommendations for the prevention and control of CRE, CRAB and CRPsA.
Guideline implementation
The successful implementation of these guidelines is dependent on a robust implementation strategy and a defined and appropriate process of adaptation and integration into relevant regional, national and facility-level policies and strategies. These CRE-CRAB-CRPsA guidelines should be integrated with the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) and the national action plans for AMR. Such IPC implementation is crucial for the achievement of strategic objective 3 of the AMR Global Action Plan adopted by all Member States at the World Health Assembly in 2015. Support by national decision-makers, key stakeholders, partner agencies and organizations is also critical to enable effective implementation and to address research gaps (as outlined in the guidelines), particularly in limited resource settings.
