Summary of the evidence
The purpose of the evidence review was to evaluate the effectiveness of IPC interventions in acute health care facilities to prevent and control CRECRAB-CRPsA-related patient outcomes. Primary outcomes varied as follows:
eleven studies included CRE-related patient outcomes, that is, incidence of CRE infection, CRE bloodstream infection, prevalence of CRE infection and incidence of CRE infection or colonization (
28,
48–
56,
63);
five studies included CRAB-related patient outcomes, that is, incidence of CRAB infection, incidence of CRAB infection or colonization and incidence of CRAB and CRPsA colonization (
50,
57–
59,
62);
Three studies included CRPsA-related patient outcomes, that is, incidence of CRPsA infection and incidence of CRAB and CRPsA colonization (
58,
60,
61).
All included studies were of ITS design from countries in the Americas Region (four of 11 CRE, three of five CRAB and one of three CRPsA studies), Eastern Mediterranean Region (four of 11 CRE, none of three CRAB and three CRPsA studies), European Region (two of 11 CRE, none of five CRAB and one of three CRPsA studies), and the Western Pacific Region (one of 11 CRE, two of five CRAB and one of three CRPsA studies).
CRE: Among the 11 studies evaluating the impact of an IPC intervention on CRE infection or colonization, 10 assessed a multimodal intervention (28, 48–56). Nine of the 10 reported a significant reduction in CRE outcomes after the intervention as demonstrated by a significant reduction in slope (that is, trend; range: −0.01 to −3.55) (28, 50, 51, 53–56) and/or level (that is, immediate change; range: −1.19 to −31.80) (28, 48, 51, 54–56) after the intervention. All included contact precautions as a component of their multimodal strategy. In addition, nine of 10 studies included active patient surveillance (for example, rectal swab collection among at-risk patients on admission and weekly, as well as contact screening, apart from one study that assessed expanded active surveillance as a standalone intervention), monitoring, auditing and feedback (for example, feedback to leadership and health care workers), and patient isolation. Six of 10 included hand hygiene; four of 10 included education and antibiotic stewardship; three of 10 included enhanced environmental cleaning and flagging of positive patients in the electronic medical record; two of 10 included daily chlorhexidine gluconate baths (one study that assessed chlorhexidine gluconate baths as a standalone intervention was excluded); and one of 10 included a rotation of dedicated staffing to the cohort to prevent work overload, environmental surveillance cultures, creation of a multidisciplinary IPC taskforce and intensive care unit (ICU) closure.
Four studies showed a significant reduction both in slope (post-intervention trend: −0.32 to −3.55) and level (immediate change after intervention implementation: −1.19 to −31.80) in the incidence of CRE infection per 10 000 patient-days (28, 54–56). These studies used a multimodal approach of strict contact precautions, enhanced active surveillance (for example, using rectal culture samples from the ICU and step-down unit patients on admission and weekly), contact screening, cohorting for positive cases with dedicated staff and equipment, environmental and staff hand cultures, hand hygiene enforcement, carbapenem prescribing restriction, medical record flagging and an infected patient database to identify readmissions and regular reporting to hospital management and public health authorities.
CRAB: Among the five studies evaluating the impact of an IPC intervention on CRAB infection or colonization, four assessed a multimodal intervention (50, 57–59). Three of the four reported a significant reduction in CRAB outcomes after the intervention as demonstrated by a significant reduction in slope (that is, trend; range: −0.01 to −4.81) (50, 57, 59) and/or post-intervention level (that is, immediate change; −48.86) (50). Among these four studies, all included contact precautions, hand hygiene, education and monitoring, auditing and feedback as components of their multimodal strategy. In addition, three of four included active patient surveillance, patient isolation and enhanced environmental cleaning, two of four included education, and one of four included environmental surveillance cultures, flagging of positive patients in medical records, daily chlorhexidine gluconate baths, antibiotic stewardship and multidisciplinary task force meetings. One study (50) showed both a significant reduction in slope (that is, trend; −4.81) and level (that is, immediate change; −48.86) in the incidence of CRAB infection or colonization per 10 000 patient-days. Enfield et al (50) used a multimodal approach of monitoring, auditing and feedback, pre-emptive isolation for all patients, enhanced staff education on contact precautions, patient and staff cohorting, enhanced antibiotic stewardship, enhanced active surveillance of all patients (wound and respiratory samples) twice weekly and screening of all those in the ICU, chlorhexidine baths, limiting public access to rooms and common areas and environmental cleaning.
CRPsA: Among the three studies evaluating the impact of an IPC intervention on CRPsA infection or colonization, all assessed a multimodal intervention. Two reported a significant reduction in CRPsA outcomes as demonstrated by a significant reduction in slope (that is, trend; −1.36) (61) and/or post-intervention level (that is, immediate change; −0.02) (60). All three studies included active patient surveillance, contact precautions, and monitoring, auditing and feedback as components of their multimodal strategy. In addition, two of three included enhanced environmental cleaning, environmental surveillance cultures and antibiotic stewardship, and one of three included patient isolation, hand hygiene, education, ward closure and removal of automatic urine collection machines.
The GDG considered the overall quality of the evidence as very low to low given the medium to high risk of bias in the study design and implementation and the indirectness of evidence (that is, varying intervention packages, populations and outcomes measured). For some specific outcomes with fewer studies and data points measured, the imprecision of results lowered the quality of evidence.
Additional factors considered when formulating the recommendation
Values and preferences
The GDG recognized that this recommendation may have the following potentially important implications:
Implementing the multimodal strategy might have workload implications for health care workers and other staff and this may affect morale unless managed with consideration and appropriate education (
64).
Patients who are colonized/infected with CRE-CRAB-CRPsA may suffer discrimination in the quality of their health care unless appropriate management structures are put in place. Unless managed with consideration and appropriate education, this may have an emotional impact on the morale of patients colonized/infected with CRE-CRAB-CRPsA. For this reason, health systems should give special consideration to the important management and education aspects related to CRE-CRAB-CRPsA.
It was acknowledged that the literature review did not include studies directly addressing some of these issues. However, based on their extensive clinical experience, the GDG panel members universally supported these considerations regarding patient and staff values.
These aspects are examined in more detail in the next chapters of these guidelines. Despite these issues, the GDG considered the importance of restricting the spread of CRE-CRAB-CRPsA to be of such priority that this recommendation was supported unanimously.
Although no study was found on patient values and preferences with regards to this recommendation, the GDG was confident that patients and the public are strongly supportive of IPC programmes to control CRE-CRAB-CRPsA given the morbidity and mortality risks due to these pathogens. Furthermore, health care providers and policy-makers across all settings are likely to be in support of CRE-CRAB-CRPsA IPC programmes to reduce the harm caused by HAI and AMR due to these pathogens and to achieve safe, quality health service delivery in the context of universal health coverage.
Additionally, principles and lessons from guidance on ethical considerations in public health for other infectious diseases can also be taken into account (42, 65–67). In brief, these guidance documents describe the following key values:
public health necessity (for example, public health powers are exercised under the theory that they are necessary to prevent an avoidable harm);
reasonable and effective means (for example, there must be a reasonable relationship between the public health intervention and achievement of a legitimate public health objective);
proportionality (for example, the human burden imposed should not be disproportionate to the expected benefit);
social justice, distributive justice and equity (for example, the risks, benefits and burdens of public health action are fairly distributed, thus precluding the unjustified targeting of already vulnerable populations);
solidarity and the common good (for example, infectious diseases increase the risks of harm for entire populations; we can all gain from societal cooperation and strong public health facilities to reduce the threat of infection);
effectiveness (for example, public health officials have the duty to avoid doing things that are not working and implement evidence-based measures that are likely to lead to success);
trust, transparency and accountability (for example, public health officials should make decisions that are responsive, evidence-based and disclosed in an open manner);
autonomy (for example, guaranteeing individuals the right to make decisions on their own lives, including health care and treatment options);
participation (for example, public health officials have the responsibility to involve the public and patients);
subsidiarity (for example, decisions should be made as close as possible to the individual and community);
reciprocity (for example, health care workers deserve benefits in exchange for running risks to treat those with infectious diseases, such as actions to minimize these risks by providing a reliable supply of protective equipment).
In relation to the prevention and control of CRE-CRAB-CRPsA, these values can be considered for each of the multimodal strategy components described in the subsequent recommendations. Careful judgement should be used to decide which ones are most relevant according to each specific context and how they can be used to articulate related obligations. Promoting these values requires the active cooperation of multiple individuals and entities who share responsibility for the prevention and control of CRE-CRAB-CRPsA.
Resource implications
The GDG was confident that the recommendation can be accomplished in all countries. However, it did acknowledge that there will be particular resource implications for low- and middle-income countries (LMICs), most notably, limited access to qualified and trained IPC professionals and inadequate microbiology laboratory capacity. At present, a defined career path for IPC does not exist in some countries, thus restricting health care workers’ professional development. Furthermore, human resource capacity is often limited, especially with respect to available doctors and other trained health care professionals. Many countries with experience of implementing IPC programmes, including data from high- and middle-income countries, indicate that it is feasible and effective. However, in settings with limited resources, there is a need for prioritization based on local/regional needs to determine the most important, feasible and effective approaches.
Finally, the GDG agreed that not all countries will have adequate resources and expertise to fully support all aspects of this recommendation when executed to its fullest extent. Although the available evidence is largely limited to high- and middle-resource settings, the panel believes that the resources invested are worth the net gain, irrespective of the context. Thus, the provision of secured budget lines will be important to support the full implementation of the recommendation.
Acceptability
The GDG was confident that key stakeholders are likely to find this recommendation acceptable, while recognizing that it requires widespread and executive support, as well as specific actions for stakeholder engagement. The need for effective advocacy to assist in moving forward the acceptance of the recommendation was noted.