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Guidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities. Geneva: World Health Organization; 2017.

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Guidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities.

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3Evidence-based recommendations on measures for the prevention and control of CRE-CRAB-CRPsA

3.1. Recommendation 1: Implementation of multimodal infection prevention and control strategies

The panel recommends that multimodal IPC strategies should be implemented to prevent and control CRE-CRAB-CRPsA infection or colonization and that these should consist of at least the following:

  • hand hygiene
  • surveillance (particularly for CRE)
  • contact precautions
  • patient isolation (single room isolation or cohorting)
  • environmental cleaning

(Strong recommendation, very low to low quality of evidence)

Rationale for the recommendation

  • Multimodal strategies comprising several elements were used as the intervention in most studies. The recommendation includes those elements included in the reviewed studies that were most strongly supported by evidence and were implemented in an integrated way.
  • Among 11 studies evaluating the impact of an IPC intervention on CRE infection or colonization, 10 assessed a multimodal intervention (28, 4856). Nine of the 10 reported a significant reduction in CRE outcomes post-intervention, thus demonstrating the significant impact of the multimodal intervention (28, 48, 49, 5156).
  • Among five studies evaluating the impact of an IPC intervention on CRAB infection or colonization, four assessed a multimodal intervention (50, 5759). Three of the four reported a significant reduction in CRAB outcomes after the intervention, thus demonstrating the significant impact of the multimodal intervention (50, 57, 59).
  • Among three studies evaluating the impact of an IPC intervention on CRPsA infection or colonization, all assessed a multimodal intervention (58, 60, 61). Two reported a significant reduction in CRPsA outcomes after the intervention, thus demonstrating the significant impact of a multimodal intervention (60, 61).
  • Due to the different methodologies, interventions and outcomes measured, no meta-analysis was performed.
  • The quality of the evidence was low for the most clinically important outcomes (that is, CRE infection, CRAB infection or colonization and CRPsA infection) and very low for all other CRE-CRAB-CRPsA outcomes.
  • Despite the limited available evidence and its very low to low quality, the GDG unanimously recommended that an IPC programme consisting of multimodal strategies to prevent and control the acquisition of and infection with CRE-CRAB-CRPsA should be in place in all acute health care facilities and that the strength of this recommendation should be strong. This decision was based on the:

    large effect of CRE-CRAB-CRPsA infection/colonization reduction reported in 13 of the 17 studies that assessed multimodal interventions for CRE-CRAB-CRPsA;

    panel’s conviction that the existence of such a multimodal IPC programme is necessary to control CRE-CRAB-CRPsA colonization/infection, which is consistent with the reviewed evidence that led to the development and the content of the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) where the use of multimodal strategies is strongly recommended as the most effective approach to successfully implement IPC interventions;

    evidence and international concern about the burden and impact of CRE-CRAB-CRPsA colonization/infection (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2).

Remarks

  • The GDG recognized that most studies were from settings with a high prevalence of CRE-CRAB-CRPsA. Nevertheless, it considered that the IPC principles outlined in this recommendation were equally valid in all prevalence settings.
  • The GDG noted that while the control of large outbreaks was recognized to be very costly, these studies were all conducted in high-to-middle-income countries. Thus, there are concerns regarding the cost implications and the affordability of outbreak control in settings with limited resources.
  • Although the scope of the evidence review and this recommendation address acute care facilities, the GDG considered it equally critical that all types of health care facilities apply similar IPC principles to the control of CRE-CRAB-CRPsA.
  • The GDG recognized that some components of the recommended multimodal intervention could involve potential harms (for example, psychological suffering among isolated patients) or unintended consequences (for example, discrimination of colonized/infected patients) with ethical implications. These were discussed with an ethics review group and considerations resulting from this discussion and mitigation measures were included in the “values and preferences” section, as well as important references in this field.
  • The GDG recognized that implementing this recommendation may be complex in some health systems as it requires a multidisciplinary approach, including executive leadership, stakeholder commitment, coordination and possible modifications to workforce structure and process in some cases. Facility leadership should clearly support the IPC programme aimed at preventing the spread of CRE-CRAB-CRPsA by providing materials and organizational and administrative support through the allocation of a protected and dedicated budget, according to the IPC activity plan. Such an approach was considered to be consistent with Core component 1 in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).
  • The GDG identified that good quality microbiological laboratory support is a very critical factor for an effective IPC programme and implementation of this recommendation.
  • The GDG considered that environmental cleaning was especially important in the area immediately surrounding the patient, that is, the “patient zone” (see Recommendation 6) (61).
  • Education/training and monitoring, auditing and feedback are critical to the success of a multimodal strategy. Emphasis should be placed on these when implementing multimodal interventions and their specific components, particularly in the context of an IPC programme.

    Education/training: Eight of 11 CRE studies mentioned supporting education and training (4855). Among these, seven reported a significant reduction in CRE outcomes (48, 49, 5155). Four of five CRAB studies mentioned education and training (50, 5759), of which three reported a significant reduction in CRAB outcomes (50, 57, 59). All three CRPsA studies mentioned education and training (58, 60, 61), of which two reported a significant reduction in CRPsA outcomes (60, 61).

    Monitoring, auditing and feedback: See Recommendation 8 for more details.

  • Daily patient bathing with chlorhexidine was part of the intervention in a limited number of studies which reported mixed or inconsistent findings (two of 11 CRE; two of five CRAB and none of the three CRPsA studies) (50, 51, 62). However, the GDG considered that it was associated with an insufficient level of evidence to be formally recommended for CRE-CRAB-CRPsA.

Background

Emerging problems with CRE-CRAB-CRPsA infections and colonization are known to increase health care costs, usage of broad spectrum (and sometimes toxic) antimicrobial agents and to be associated with high rates of morbidity and mortality. IPC programmes are known to be effective in controlling many HAI, including those due to CRE-CRAB-CRPsA. However, the details of their effectiveness have sometimes been difficult to define due to differences in health care systems, the nature of various outbreaks and differences related to the background endemicity of CRECRAB-CRPsA. In consideration of these issues, the GDG explored the evidence captured within a systematic review to identify the impact of IPC interventions to reduce infection rates and colonization due to CRE-CRAB-CRPsA.

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, 4856, 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, 5759, 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, 4856). 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, 5356) and/or level (that is, immediate change; range: −1.19 to −31.80) (28, 48, 51, 5456) 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, 5456). 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, 5759). 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, 6567). 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.

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including:

  • Additional well-designed research studies, especially from LMICs, as the available evidence focuses on high-income countries that may be difficult to apply more broadly. In particular, a situation analysis of current CRE-CRAB-CRPsA prevention and control measures in LMICs could provide a baseline for assessing guideline implementation.
  • Impact and ideal composition of multimodal strategies, including minimum standards for IPC training and studies on cost-effectiveness to determine adequate budgeting for CRE-CRAB-CRPsA control activities.
  • Patients’ perceptions, understanding and acceptance of the implementation of these IPC multimodal strategies
  • Impact of an effective IPC programme in support of strategies to improve hygiene and IPC in the community.

3.2. Recommendation 2: Importance of hand hygiene compliance for the control of CRE-CRAB-CRPsA

The panel recommends that hand hygiene best practices according to the WHO guidelines on hand hygiene in health care should be implemented (6).

(Strong recommendation, very low quality of evidence)

Rationale for the recommendation

  • Among CRE studies, six of 11 included hand hygiene (for example, education, auditing of compliance and enforcement) as part of their assessed intervention (4851, 54, 55). Five of the six reported a significant reduction in CRE outcomes after the intervention (48, 49, 51, 54, 55).
  • Among CRAB studies, four of five included hand hygiene as part of their assessed intervention (50, 5759). Three of the four reported a significant reduction in CRAB outcomes after the intervention (50, 57, 59).
  • Among CRPsA studies, one of three included hand hygiene as part of their assessed intervention (58). This study did not report a significant reduction in CRPsA outcomes after the intervention.
  • Despite the limited available evidence and its very low quality, the GDG unanimously recommended to emphasize the importance of appropriate hand hygiene compliance in the control of CRE-CRAB-CRPsA and that the strength of this recommendation should be strong. This decision was based on the:

    panel’s conviction that good hand hygiene compliance is fundamental to all multimodal IPC interventions, which is consistent with the substantial reviewed evidence on the impact of hand hygiene to reduce HAIs and AMR that led to the development and content of the WHO guidelines on hand hygiene in health care (6) and the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13);

    evidence and international concern about the burden and impact of CRE-CRAB-CRPsA colonization/infection (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2).

Remarks

  • The GDG considered that the evidence for the high beneficial impact of good hand hygiene compliance has been reviewed previously in sufficient detail and therefore the WHO recommendations on hand hygiene in health care should be followed (see WHO guidelines on hand hygiene in health care (6)). Effective implementation strategies have been developed, tested and are now used worldwide (68, 69) and practical approaches to implement these strategies at the facility level are described in the WHO guide to implementation and associated toolkit (http://www.who.int/infection-prevention/tools/handhygiene/). The GDG highlighted the importance of using these approaches and resources and adapting them locally.
  • The GDG recognized that hand hygiene compliance and the appropriate use of alcohol-based handrub are very dependent on appropriate product placement and availability as noted in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13). Adequate resources are therefore necessary to ensure these features are met.
  • The GDG emphasized the importance of monitoring hand hygiene practices through the measurement of compliance according to the approach recommended by WHO (7).

Background

Appropriate hand hygiene compliance is considered fundamental to all good IPC programmes and the control of cross-transmission of many pathogens, including CRE-CRAB-CRPsA (see WHO guidelines on hand hygiene in health care (6)). The general evidence to support hand hygiene implementation as part of effective IPC programmes to prevent HAI and AMR has been previously summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) and associated documents (70).

Summary of the evidence

In this section, we examine the evidence that included hand hygiene as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient outcomes. Included studies assessing hand hygiene were of ITS design from countries in the Americas Region (three of 11 CRE, three of five CRAB and one of three CRPsA studies), Eastern Mediterranean Region (one of 11 CRE, none of five CRAB and three CRPsA studies), European Region (one of 11 CRE, none of five CRAB and three CRPsA studies) and the Western Pacific Region (one of 11 CRE, one of five CRAB and none of three CRPsA studies). Hand hygiene was often described as the auditing of hand hygiene practices and supervision and feedback of results, rather than education on hand hygiene alone.

CRE: Six of 11 CRE studies included hand hygiene as part of a multimodal approach (4851, 54, 55). Primary outcomes were the incidence of CRE infection (three of six), CRE bloodstream infection (two of six), the prevalence of CRE infection (one of six) and the incidence of CRE infection or colonization (one of six), including one study with two reported outcomes. Five of the six reported a significant reduction in CRE outcomes post-intervention, including significant slope (that is, trend; range: −0.09 to −3.55) and level estimates (that is, immediate change; range: −1.19 to −31.80) (48, 49, 51, 54, 55).

CRAB: Four of five CRAB studies included hand hygiene as part of a multimodal approach. Primary outcomes were the incidence of CRAB infection (one of four), CRAB infection or colonization (two of four) and CRAB and CRPsA colonization (one study) (50, 5759). Three of the four reported a significant reduction in CRAB outcomes post-intervention, including significant changes in slope estimates (that is, trend; range: −0.01 to −4.81) and one significant change in the level estimate (that is, immediate change; −48.86) (50, 57, 59).

CRPsA: One of three CRPsA studies included hand hygiene as part of a multimodal approach (58). In this study, the primary outcome was the incidence of CRAB and CRPsA colonization. No significant reduction in CRPsA outcomes was reported post-intervention.

The GDG considered the overall quality of the evidence as very low. Hand hygiene was not an intervention component in all studies and it was evaluated only as part of a multimodal strategy and the GRADE assessment was undertaken by pathogen (that is, CRE, CRAB or CRPsA) and outcome (for example, incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection and/or colonization, etc.), rather than according to specific interventions alone.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention as this was not the focus of the literature review. However, this topic has been extensively reviewed previously (see WHO guidelines on hand hygiene in health care (6)). In particular, patients’ points of view regarding the importance of good hand hygiene practices during health care delivery have been explored in many surveys over the past 10 years. Results clearly showed that patients highly value visible compliance with this key preventive measure and consider it as a marker of high quality care (71, 72). In a number of studies, active patient participation in hand hygiene improvement strategies was also included and tested, for example, patients were encouraged to ask health care workers to practice hand hygiene when appropriate (73). Although these experiences have not always led to positive results in terms of improved hand hygiene compliance (74), the GDG was confident that the typical values and preferences of health care providers, policy-makers and patients would favour this intervention. Health care providers, policy-makers and health care workers are likely to place a high value on this recommendation.

Resource implications

The GDG was confident that the resources are worth the expected net benefit from following this recommendation, while recognizing that the procurement of alcohol-based handrub will require a certain level of resources and materials. It was also noted that the implementation of hand hygiene multimodal improvement strategies requires adequate human resources and expertise for local development and adaptation, as well as infrastructures and equipment for execution, although some solutions may likely be low cost.

Feasibility

The GDG was confident that this recommendation can be accomplished in all countries. However, the panel noted that feasibility would hinge on the presence of IPC programmes, IPC expertise and the availability of materials and equipment to assist in appropriate local adaptation.

Acceptability

The GDG was confident that key stakeholders are likely to find this recommendation acceptable.

Research gaps

The GDG discussed the need for further research related to this recommendation, including:

  • the exact relative contribution of good hand hygiene to preventing and controlling CRE-CRAB-CRPsA infection/colonization;
  • effective and feasible measures to monitor hand hygiene compliance among health care workers in limited resource settings.

3.3. Recommendation 3: Surveillance of CRE-CRAB-CRPsA infection and surveillance cultures for asymptomatic CRE colonization

The panel recommends that:

  1. surveillance of CRE-CRAB-CRPsA infection(s) should be performed, and
  2. surveillance cultures for asymptomatic CRE colonization should also be performed, guided by local epidemiology and risk assessment. Populations to be considered for such surveillance include patients with previous CRE colonization, patient contacts of CRE colonized or infected patients and patients with a history of recent hospitalization in endemic CRE settings.

(Strong recommendation, very low quality of evidence)

Rationale for the recommendation

Surveillance for CRE-CRAB-CRPsA infection/s
  • Given the clinical importance of CRE-CRAB-CRPsA infection(s), the GDG considered that regular ongoing active surveillance of infections was required.
Surveillance cultures for asymptomatic CRE colonization
  • Only limited evidence was available for undertaking surveillance cultures for colonization with CRAB and CRPsA. Thus, the GDG decided that this recommendation should focus on CRE surveillance for colonization (see Additional remarks below).
  • The GDG recognized that colonization with CRE usually precedes or is co-existent with CRE infection. Thus, early recognition of CRE colonization helps to identify patients most at-risk of subsequent CRE infection, as well as allowing the earlier introduction of IPC measures (especially those indicated in Recommendation 1) to prevent CRE transmission to other patients and the hospital environment.
  • Among CRE studies, 10 of 11 included active patient surveillance (for example, rectal swab collection among at-risk patients on admission and weekly, contact screening) as part of their assessed intervention (28, 4853, 55, 56, 63). Eight of the 10 reported a significant decrease in CRE outcomes post-intervention (28, 48, 49, 5153, 55, 56).
  • Among CRAB studies, three of five included active patient surveillance as part of their assessed intervention (50, 57, 58). Two of the three reported a significant decrease in CRAB outcomes post-intervention (50, 57).
  • Among three CRPsA studies, all included active patient surveillance as part of their assessed intervention (58, 60, 61). Two studies reported a significant decrease in CRPsA outcomes post-intervention (60, 61).
  • Despite the limited available evidence and its very low to low quality, the GDG unanimously agreed that this recommendation should be strong. This decision was based on the:

    panel’s conviction about the benefit of surveillance as a key core component to prevent and control CRE-CRAB-CRPsA, which is consistent with the reviewed evidence that led to the development and content of the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) where surveillance is already the object of a strong recommendation;

    evidence and international concern about the burden and impact of CRE-CRAB-CRPsA infection and CRE colonization (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2).

Remarks

Surveillance for CRE-CRAB-CRPsA infection/s
  • The GDG unanimously agreed that surveillance of CRE-CRAB-CRPsA infection is essential (that is, clinical monitoring of signs and symptoms of infection and laboratory testing and identification of carbapenem resistance among potential CRE-CRAB-CRPsA isolates from clinical samples).
  • The GDG recognized that laboratory testing and identification of carbapenem resistance among potential CRE-CRAB-CRPsA isolates may not be available or routine in some settings (for example, LMICs). However, given the current situation, the panel unanimously agreed that testing for carbapenem resistance in these pathogens should now be considered as routine in all microbiology laboratories to ensure the accurate and timely recognition of CRE-CRAB-CRPsA.
  • The GDG highlighted that the surveillance of CRE-CRAB-CRPsA infection allows a facility to define the local epidemiology of CRE-CRAB-CRPsA, identify patterns and better allocate resources to areas of need. Reviewing laboratory results over a specified period of time and looking at the demographics, exposures and locations of patients can help a facility to understand where, when and which patients are becoming ill in order to better prevent and control infections.
Surveillance cultures for asymptomatic CRE colonization
  • The GDG recognized that information regarding a patient’s CRE colonization status does not (yet) constitute routine standard of care provided by health systems. However, in an outbreak situation or situations where there is a high risk of CRE acquisition (for example, possible contact with a CRE colonized/infected patient or endemic CRE prevalence), CRE colonization status should be known. The surveillance culture results for the identification of CRE colonization may not have an immediate benefit to the screened patient, but instead they may contribute to the overall IPC response to CRE. It was also noted that information regarding CRE colonization status could potentially have important beneficial effects on the empiric antibiotic treatment plan for screened patients who subsequently develop potential CRE infection.
  • The GDG believes that this recommendation should always apply in an outbreak situation and ideally, also in endemic settings. However, the panel extensively discussed the best approach to surveillance cultures of asymptomatic CRE colonization in a high CRE prevalence (endemic) setting, particularly in low-income settings where resources and facilities are limited and the actual appropriate improvement of IPC infrastructures and best practices may deserve prioritization over surveillance. The panel agreed that there is no one single best approach, but instead the decision should be guided by the local epidemiology, resource availability and the likely clinical impact of a CRE outbreak.
  • The GDG believes that surveillance screening should be based on patient risk assessment (that is, patients who are at a higher risk of CRE acquisition and the potential risk that these patients pose to others in their environment). The following patient risk categories should be considered:

    patients with a previously documented history of CRE colonization or infection;

    epidemiologically-linked contacts of newly-identified patients with CRE colonization or infection (this could include patients in the same room, unit or ward);

    patients with a history of recent hospitalization in regions where the local epidemiology of CRE suggests an increased risk of CRE acquisition (for example, hospitalization in a facility with known or suspected CRE);

    based on the epidemiology of their admission unit, patients who may be at increased risk of CRE acquisition and infection (for example, immunosuppressed patients and those admitted to ICUs, transplantation services or haematology units, etc.).

  • The GDG noted that surveillance cultures of fecal material were the preferred approach for the identification of CRE colonization. Regarding sample collection, culture of feces/rectal swabs or perianal swabs in rare clinical situations (for example, neutropenic patients) were considered the best methods in descending order of accuracy. However, it was recognized that for practical reasons, rectal swabs were often considered to be the most suitable clinical specimen in many health care situations. A minimum of one culture was considered necessary, although additional cultures may increase the detection rate.
  • The GDG noted that surveillance cultures should be performed as soon as possible after hospital admission or risk exposure and that they should be processed and reported promptly to avoid delays in the identification of CRE colonization. The GDG was unable to identify the optimal frequency of testing after admission due to limited and heterogeneous evidence and noted that several studies included a regular screening timetable (for example, weekly or twice-weekly) following the initial on-admission screening.
Additional remarks
  • The GDG recognized that undertaking the recommended surveillance activities could involve potential harms or unintended consequences for the patient (for example, a sense of cultural offensiveness or stigma associated with obtaining a rectal swab or providing a stool (fecal) specimen or discrimination of colonized/infected patients) with ethical implications. These were discussed with an ethics review group and considerations resulting from this discussion and mitigation measures were included in the “values and preferences” section, as well as important references in this field.
  • The GDG noted that several studies had identified the benefits of real-time medical record alerts regarding the CRE colonization/infection status of patients, particularly the improved identification of high-risk patients, and that such alerts helped direct appropriate IPC surveillance and containment efforts.
  • The GDG also considered the evidence available on surveillance cultures for CRAB and CRPsA colonization and concluded that it was not sufficiently relevant to extend the recommendation to these two microorganisms. In particular, it was noted that the value of active surveillance for CRAB and CRPsA colonization, while sometimes beneficial, depends on the clinical setting, epidemiological stage (for example, outbreak) and body sites. It was also recognized that the optimal microbiological methods for CRAB and CRPsA surveillance cultures for colonization require further research.
  • Additionally, the Global Antimicrobial Resistance Surveillance System (GLASS) recommends the inclusion of carbapenem-resistant E coli, K. pneumoniae and Acinetobacter species among national AMR surveillance targets (http://www.who.int/antimicrobial-resistance/en/).

Background

Surveillance of CRE-CRAB-CRPsA infection and surveillance cultures of asymptomatic CRE colonization allow the early introduction of IPC measures to prevent transmission to other patients and the hospital environment. The general evidence to support surveillance as a key element to prevent HAI and the cross-transmission of pathogens has been previously summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Summary of the evidence

In this section, we examine the evidence that included surveillance as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient colonization/infection outcomes.

Included studies assessing active patient surveillance were of ITS design from countries in the Americas Region (five of 11 CRE, two of five CRAB and one of three CRPsA studies), Eastern Mediterranean Region (three of 11 CRE, none of five 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 (none of 11 CRE, one of five CRAB and one of three CRPsA studies). Active patient surveillance for asymptomatic colonization was often described as rectal swab collection among at-risk patients (that is, those housed in the ICU or step-down unit) on admission and weekly or biweekly, as well as contact screening.

CRE: Ten of 11 CRE studies included active patient surveillance as part of their assessed multimodal approach (apart from one study that assessed expanded surveillance as a stand-alone intervention (28, 4853, 55, 56, 63). Primary outcomes were the incidence of CRE infection (seven of 10), CRE bloodstream infection (two of 10), prevalence of CRE infection (one of 10) and incidence of CRE infection/colonization (one of 10), including one study with two reported outcomes. In addition, studies assessed active surveillance of target populations, including high-risk patients, such as those in the ICU (nine of 10), contacts (eight of 10) and those with a history of recent hospitalization (seven of 10). Nine of 10 studies screened patients for CRE colonization on admission and seven of 10 screened patients at least weekly or every other week. Eight of the 10 studies reported a significant reduction in CRE outcomes post-intervention, including a significant change in slope (that is, trend; range: −0.01 to −2.39) and level estimates (that is, immediate change; range: −1.19 to −25.33) (28, 48, 49, 5153, 55, 56).

CRAB: Three of five CRAB studies included active patient surveillance as part of a multimodal approach (50, 57, 58). Primary outcomes were the incidence of CRAB infection or colonization (two of three) and the incidence of CRAB and CRPsA colonization (one of three). Two of the three studies reported a significant reduction in CRAB outcomes post-intervention, including significant changes in slope estimates (that is, trend; range: −0.01 to −4.81) and one significant change in the level estimate (that is, immediate change; −48.86) (50, 57).

CRPsA: All three CRPsA studies included active patient surveillance as part of a multimodal approach (58, 60, 61). The primary outcomes were the incidence of CRPsA infection (two of three) and the incidence of CRAB and CRPsA colonization (one of three) (58, 60, 61). Two studies reported a significant reduction in CRPsA outcomes post-intervention, including one significant change in the slope estimate (that is, trend; −1.36) and one significant change in the level estimate (that is, immediate change; −0.02) (60, 61).

The GDG considered the overall quality of the evidence to be very low. The approach to surveillance often varied between studies. Thus, it was assessed only as part of a multimodal strategy and the GRADE assessment was undertaken for CRE by outcome (for example, incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection/colonization), rather than according to specific interventions alone.

Additional factors considered when formulating the recommendation

Values and preferences

The GDG recognized that there may be concerns about adverse events with obtaining a rectal swab in some clinical scenarios (for example, neutropenic patients, neonates). In such cases, a stool specimen/fecal culture may be obtained or, if not available, a perianal swab.

The GDG also recognized that occasionally there may be other unintended social concerns and consequences in some settings, such as a sense of cultural offensiveness or stigma associated with obtaining a rectal swab or providing a stool specimen/fecal culture and eventually, patient identification as colonized by CRE. In rare situations, this may result in patient refusal to provide the surveillance culture. Appropriate patient communication and efforts to maintain patient dignity and respect should be ensured to mitigate possible misconceptions, including the training of health care workers to increase their awareness of these potential issues.

The panel recognized that the identification of CRE colonization, while potentially beneficial to the patient and the nature of the health care response(s), could also result in inappropriate patient discrimination if the health facility did not have adequate management structures in place to ensure routine clinical care, regardless of colonization status. The panel recognized that this important, potential ethical concern needed to be balanced against the major ethical issues and clinical impact associated with likely widespread CRE transmission if surveillance cultures were not performed. Confidentiality of the data and patient colonization or infectious status should be maintained and shared only through the appropriate channels to minimize potential discrimination.

Although no study was found on patient values and preferences with regards to this intervention (as it was not the focus of the literature review), the panel was confident that overall, the typical values and preferences of patients and health care workers would be supportive of surveillance cultures. The panel also considered that most health care providers and patients in the vast majority of settings are likely to place a higher value on the information regarding colonization with CRE than the above-listed concerns, given the potentially serious health implications of CRE infection.

However, the GDG considered that a patient risk assessment is an important component of a surveillance programme as screening efforts should be focused on “high-risk” patient populations as indicated in the recommendation and in the related remarks, particularly those at risk of CRE acquisition.

Furthermore, the GDG considered that developing a robust communication and information sharing strategy regarding a patient’s CRE colonization status is crucial. This is particularly valid for inter-facility patient transfers as it was noted that many published CRE outbreaks had occurred in facilities where knowledge of an individual patient’s previous surveillance culture results had not been adequately communicated to the receiving health care facility and subsequent CRE transmission had occurred.

Other shared lessons on ethical considerations of surveillance can be found in the WHO discussion paper on addressing ethical issues in pandemic influenza planning (65) as well as in other public health ethics guidance (66, 67).

Resource implications

The GDG recognized that there are financial implications related to surveillance cultures for colonization. However, the GDG considered that these resources are worth the expected net benefit, although this benefit may vary between settings, depending on resources available.

The GDG also recognized that financial and technical support are needed in some settings to strengthen laboratory capacity in order to both undertake appropriate testing for carbapenem resistance and to be able to provide adequate and timely testing of clinical and surveillance culture specimens. In addition, enhanced efforts and training related to the laboratory analysis and interpretation of microbiological results may be required in some settings. Epidemiological and clinical skills are also required to adequately respond to the surveillance culture results. Appropriate treatment should also be available for CRE-CRAB-CRPsA.

Feasibility

The GDG was confident that this recommendation can be accomplished in all countries, but it acknowledged that the above-mentioned resource implications can pose challenges as to its feasibility. The recommendation is likely to require adaptation or tailoring to the cultural setting. Moreover, continuous education to support adequate surveillance may be difficult and challenging in some countries, particularly where there is a low availability or lack of knowledgeable professionals able to teach IPC. In addition, efficient and effective surveillance for both CRE-CRAB-CRPsA infection and CRE colonization requires adequate data collection and an appropriate management infrastructure. For example, the GDG acknowledged that surveillance may be more laborious in systems using paper-based medical records compared to electronic medical records.

Acceptability

The GDG was confident that key stakeholders are likely to find this recommendation acceptable.

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including the following topics.

  • Ideal schedule for CRE surveillance cultures of colonization, as well as for settings where CRE is rare and endemic.
  • Most cost-effective approach to CRE surveillance, in particular for limited resource settings.
  • Optimal cost-effective laboratory methods for CRE surveillance, including isolate characterization (for example, identification of the genotypes).
  • Identification of appropriate methods and definitions to accurately identify clearance of colonization and inform strategies for the discontinuation of active surveillance. This may also have important implications for the morale of CRE-colonized patients as some hope of clearing their CRE colonization may be important to both their future health care and likelihood of future discrimination. Moreover, patients who are no longer carriers, but are nevertheless hospitalized in carrier cohorts due to non-identification of clearance, may be at risk of re-acquisition of CRE.
  • Risk factors for prolonged colonization and acquisition of new CRE strains.
  • Global and national epidemiology of CRE-CRAB-CRPsA infection/s. This is required to assist with an accurate assessment of patients related to their likely risk of colonization with these pathogens, including an understanding of country prevalence data. It was noted that such open disclosure may be associated with some political concerns in some regions. The GDG believed that further reflection and better approaches are required to optimize communication regarding this issue with the aim to achieve transparency, while avoiding alarm.
  • Optimal methods for surveillance for asymptomatic colonization with CRAB and CRPsA. It was noted that the value of screening for CRAB and CRPsA, while sometimes beneficial, depended on the clinical setting, epidemiological stage (for example, sporadic cases versus outbreak, etc.) and the local epidemiology of CRAB and CRPsA.
  • Importantly, the linkage between the availability of surveillance culture results for asymptomatic colonization with CRE-CRAB-CRPsA and the implementation of effective IPC interventions for effective containment.
  • Relevance of approaches to surveillance used for extended-spectrum beta-lactamases (ESBL)-producing Klebsiella spp. for CRE screening.
  • Patient values and preferences concerning the implementation of surveillance cultures for asymptomatic colonization with CRE and communication strategies.

3.4. Recommendation 4: Contact precautions

The panel recommends that contact precautions should be implemented when providing care for patients colonized or infected with CRE-CRAB-CRPsA.

(Strong recommendation, very low to low quality of evidence)

Rationale for the recommendation

  • Among the 11 CRE studies, 10 studies included contact precautions as part of their assessed intervention, while the remaining study included contact precautions as a component of their baseline (pre-intervention) strategy (28, 4856). Nine of the 10 reported a significant reduction in CRE outcomes post-intervention (28, 48, 49, 5156).
  • Among the five CRAB studies, four studies included contact precautions as part of their assessed intervention, while the fifth study included contact precautions in their baseline (pre-intervention) strategy (50, 5759). Three of the four studies reported a significant reduction in CRAB outcomes (50, 57, 59).
  • Among the three CRPsA studies, all included contact precautions as part of their assessed intervention (58, 60, 61). Two reported a significant reduction in CRPsA outcomes post-intervention (60, 61).
  • Despite the limited available evidence and its very low to low quality, the GDG unanimously agreed that the strength of this recommendation should be strong. This decision was based on the:

    inclusion of contact precautions in the IPC guidelines and strongly recommended to be made available, implemented and taught to health care workers at the national and facility levels as part of Core component 2 of effective IPC programmes in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13);

    panel’s concerns regarding the known ready transmissibility of CRE-CRAB-CRPsA by direct or indirect contact with the patient or the patient environment and the proven efficacy and practical applicability of this intervention in reducing transmission of other similar multidrug-resistant pathogens;

    evidence and international concern about the burden and impact of CRE-CRAB-CRPsA colonization/infection (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2).

Remarks

  • In line with other key and internationally recognized guideline documents, the GDG defined “contact precautions” in these guidelines as: (1) ensuring appropriate patient placement; (2) use of personal protective equipment, including gloves and gowns; (3) limiting transport and movement of patients; (4) use of disposable or dedicated patient-care equipment; and (5) prioritizing cleaning and disinfection of patient rooms (see Glossary) (5). The use of patient isolation is addressed in Recommendation 5.
  • The GDG noted that contact precautions should be considered as a standard of care for patients colonized/infected with CRE-CRAB-CRPsA in the vast majority of health systems.
  • It was recognized that health care worker education regarding the principles of IPC and monitoring of contact precautions is crucial.
  • The GDG recognized that in some circumstances, depending on the individual risk assessment of some patients, pre-emptive isolation/cohorting and the use of contact precautions may be necessary until the results of surveillance cultures for CRE-CRAB-CRPsA are available. This was considered to be an important consideration for patients with a history of recent hospitalization in regions where the local epidemiology of CRE suggests an increased risk of CRE acquisition (see Recommendation 3: patient risk categories).
  • Clear communication regarding a patient’s colonization/infection status is important (that is, flagging the medical chart).
  • The GDG recognized that applying contact precautions could involve potential unintended consequences for the patient (for example, patient frustration or discomfort during treatment with contact precautions). These were discussed with an ethics review group and considerations resulting from this discussion and mitigation measures were included in the “values and preferences” section, as well as important references in this field. Furthermore, it was recognized that occupational health issues associated with the use of some personal protective equipment (for example, latex gloves) should also be taken into consideration for health care workers.

Background

Contact precautions are an important fundamental component of the IPC measures necessary to control HAI and other infections. Contact precautions are part of transmission-based precautions and are included in the list of the IPC guidelines strongly recommended to be made available, implemented and taught to health care workers at the national and facility levels as part of Core component 2 of effective IPC programmes (13). These precautions include measures intended to prevent the transmission of infectious agents spread by direct or indirect contact with the patient or the patient environment. These include: (1) ensure appropriate patient placement; (2) use personal protective equipment, including gloves and gowns; (3) limit transport and movement of patients; (4) use disposable or dedicated patient-care equipment; and (5) prioritize cleaning and disinfection of patient rooms (5). The general evidence supporting their implementation is summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Summary of the evidence

In this section, we examine the evidence that included contact precautions as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient outcomes.

Studies assessing contact precautions were of ITS design from countries in the Americas Region (four of 11 CRE, three of five CRAB and two of three CRPsA studies), Eastern Mediterranean Region (three of 11 CRE, none of five CRAB and three CRPsA studies), European Region (two of 11 CRE, none of five CRAB and three CRPsA studies) and the Western Pacific Region (one of 11 CRE, one of five CRAB and one of three CRPsA studies). The intervention related to contact precautions was often not described in detail, but some studies described it as health care workers’ education on contact precautions and the auditing of compliance with contact precautions.

CRE: Ten of the 11 CRE studies included contact precautions as part of a multimodal approach, while the remaining study included contact precautions only in the baseline (pre-intervention) strategy (28, 4856). The primary outcomes were CRE infection (seven of 10), CRE bloodstream infection (two of 10), prevalence of CRE infection (one of 10), and the incidence of CRE infection or colonization (one of 10), including one study with two reported outcomes. Nine of the 10 studies reported a significant reduction in CRE outcomes after the intervention including significant changes in slope estimates (that is, trend; range: −0.01 to −3.55) and level estimates (that is, immediate change; range: −1.19 to −31.80) (28, 48, 49, 5156).

CRAB: Four of the five CRAB studies included contact precautions as part of a multimodal approach, while the fifth study included contact precautions only in their baseline (pre-intervention) strategy (50, 5759). The primary outcomes were the incidence of CRAB infection (one of four), incidence of CRAB infection and colonization (two of four) and the incidence of CRAB and CRPsA colonization (one of four). Three of the four studies reported a significant reduction in CRAB outcomes post-intervention, including significant changes in slope estimates (that is, trend; range: −0.01 to −4.81) and a significant change in the level estimate (that is, immediate change; −48.86) (50, 57, 59).

CRPsA: All three CRPsA studies included contact precautions as part of a multimodal approach (58, 60, 61). The primary outcomes were the incidence of CRPsA infection (two of three) and the incidence of CRAB and CRPsA colonization (one of three). Two reported a significant reduction in CRPsA outcomes after the intervention including one significant change in the slope estimates (that is, trend; −1.36) and one significant change in the level estimate (that is, immediate change; −0.02) (60, 61).

The GDG considered the overall quality of the evidence to be very low to low. The approach to contact precautions often varied between studies. It was assessed only as part of a multimodal strategy and the GRADE assessment was undertaken by pathogen (that is, CRE, CRAB or CRPsA) and outcome (for example, incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection and/or colonization, etc.), rather than according to specific interventions alone.

Additional factors considered when formulating the recommendation

Values and preferences

No study was found on patient values and preferences with regards to this intervention as this was not a component of the literature search strategy. Nevertheless, the GDG recognized that some patients and their relatives may have concerns about the appearance of health care workers using personal protective equipment and may not feel at ease. Appropriate patient education and communication about the importance of contact precautions to avoid the spread of CRE-CRAB-CRPsA to others should be undertaken. Health care workers should be trained to be able to cope with potential misconceptions of contact precautions and to communicate with patients in the best way possible. For health care workers, occupational health issues associated with the use of some protective equipment (for example, latex gloves) should also be taken into consideration. However, the GDG was confident that health care providers, health care workers, policy-makers and patients in all settings are likely to be supportive of the recommendation since the evidence supports the fact that the intervention is linked to improved patient outcomes and protects the health workforce. When feasible, consideration should be given to attribute priority services and priority allocation of dedicated health care personnel and resources to patients who are subject to contact precautions in order to mitigate their frustration, discomfort and potential harm.

Resource implications

The GDG recognized that the application of contact precautions required an increase in resource usage (for example, gowns and gloves), as well as the need for their appropriate disposal and associated costs. The GDG also recognized that the use of contact precautions was often associated with some inconvenience and increase in workload to health care workers managing patients colonized/infected with CRE-CRAB-CRPsA. It was noted that the use of gloves could occasionally be associated with some occupational exposure issues, such as cutaneous reactions. When implementing contact precautions, technical expertise is required for the overall coordination and programme management, which may pose some difficulties in LMICs. Other shared lessons on ethical considerations of personal protective equipment can be found in the WHO discussion paper on addressing ethical issues in pandemic influenza planning (65), as well as in other public health ethics guidance (66, 67).

Despite these concerns, the GDG was confident that the resources required are worth the expected net benefit from following this recommendation.

Feasibility

The GDG was confident that this recommendation can be implemented in all countries, while acknowledging that this may pose some challenges in LMICs.

Acceptability

The GDG was confident that key stakeholders are likely to find this recommendation acceptable, especially since it is consistent with the approved WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including:

  • Resource planning and optimization regarding the use of gowns and gloves (that is, predicting usage patterns to allow an adequate supply of provisions).
  • Efficacy and cost-effectiveness of various types of material used to make gowns. For instance, are disposable gowns superior to non-disposable gowns? Despite the lack of evidence, experts on the GDG agreed that both disposable gowns and non-disposable gowns (with adequate washing) could be used.
  • Identification of when contact precautions should appropriately be ceased among patients colonized/infected with CRE-CRAB-CRPsA.
  • Qualitative research to understand the factors facilitating success for implementation, including the identification of barriers and challenges.
  • Guidance on which patients to prioritize for the implementation of contact precautions in resource-limited settings (for example, those most likely to transmit infection, type of care provided).
  • Patient values and preferences concerning the implementation of contact precautions.

3.5. Recommendation 5: Patient isolation

The panel recommends that patients colonized or infected with CRE-CRAB-CRPsA should be physically separated from non-colonized or non-infected patients using

  1. single room isolation; or
  2. cohorting patients with the same resistant pathogen.

(Strong recommendation, very low to low quality of evidence)

Rationale for the recommendation

  • Among 11 CRE studies, nine included patient isolation as part of their assessed intervention (28, 4855). Eight of the nine reported a significant reduction in CRE outcomes after the intervention (28, 48, 49, 5155).
  • Among the five CRAB studies, three studies included patient isolation as part of their assessed intervention (50, 57, 59). All three studies reported a significant reduction in CRAB outcomes.
  • Among three CRPsA studies, one included patient isolation as part of the assessed intervention and reported a significant reduction in CRPsA outcomes post-intervention (61).
  • Despite the limited available evidence and its very low to low quality, the GDG unanimously agreed that the strength of this recommendation should be strong. This decision was based on the:

    inclusion of patient isolation as an essential element of contact precautions to be used for patients with CRE-CRAB-CRPsA colonization/infection as they represent an increased risk for contact transmission (5, 13);

    panel’s concerns regarding the known ready transmissibility of CRE-CRAB-CRPsA and the proven effectiveness of patient isolation/cohorting in reducing transmission of other similar multidrug-resistant pathogens;

    evidence and international concern regarding the burden and impact of CRE-CRAB-CRPsA colonization/infection (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2).

Remarks

  • It was noted that there is an inconsistency in the use of the terms “isolation” and “cohorting” in some settings. For the purposes of these guidelines, the following standard definitions (5) were used:

    Isolation: patients should be placed in single-patient rooms (preferably with their own toilet facilities) when available. When single-patient rooms are in short supply, patients should be cohorted.

    Cohorting: the practice of grouping together patients who are colonized/infected with the same organism to confine their care to one area and prevent contact with other patients.

  • The purpose of isolation is to separate colonized/infected patients from non-colonized/non-infected patients.
  • The GDG noted that while the strongest evidence for the effectiveness of patient isolation was among patients with CRE colonization/infection, it was the panel’s view that this recommendation was also likely to be effective to prevent cross-transmission among patients colonized/infected with CRAB and/or CRPsA.
  • The GDG noted that patient isolation could be associated with some potential harms and negative unintended consequences (for example, social isolation and psychological consequences, such as depression or anxiety). These were discussed with an ethics review group and considerations resulting from this discussion and mitigation measures were included in the “values and preferences” section, as well as important references in this field. In summary, the GDG believed these could be minimized with appropriate management and that the advantages of patient isolation in terms of preventing cross-transmission of CRE-CRAB-CRPsA outweighed these concerns.
  • The preference is for colonized/infected patients to be managed in single rooms where possible. Cohorting is reserved for situations where there are insufficient single rooms or where cohorting of patients colonized or infected with the same pathogen is a more efficient use of hospital rooms and resources. The GDG believes that patient isolation should always apply in an outbreak situation. Isolation in single rooms may not be possible in endemic situations, particularly in low-income settings where resources and facilities are limited.
  • The GDG noted that there is evidence and clinical experience to support the use of dedicated health care workers to exclusively manage isolated/cohorted patients, although the panel recognized there may be some feasibility issues (see Resource implications and Feasibility).

Background

Patient isolation is an important component of contact precautions and aims to prevent the transmission of infection between patients by physically separating them in single rooms or by cohorting. The general evidence to support patient isolation as an effective IPC intervention to prevent HAI and the cross-transmission of pathogens has been previously summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Summary of the evidence

In this section, we examine the evidence on patient isolation or cohorting as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient outcomes.

Studies assessing patient isolation were of ITS design from countries in the Americas Region (four of 11 CRE, two of five CRAB and one of three CRPsA studies), Eastern Mediterranean Region (two of 11 CRE, none of five CRAB and three CRPsA studies), European Region (two of 11 CRE, none of five CRAB and three CRPsA studies) and the Western Pacific Region (one of 11 CRE, one of five CRAB and none of three CRPsA studies). The intervention of patient isolation was often described as single room isolation when available, otherwise cohorting or geographical separation.

CRE: Nine of the 11 CRE studies included patient isolation as part of a multimodal approach (28, 4855). The primary outcomes were CRE infection (six of nine), CRE bloodstream infection (two of nine), prevalence of CRE infection (one of nine) and the incidence of CRE infection or colonization (one of nine), including one study with two reported outcomes. Eight of the nine studies reported a significant reduction in CRE outcomes after the intervention, including significant changes in slope estimates (that is, trend; range: −0.01 to −3.55) and level estimates (that is, immediate change; range: −1.19 to −31.80) (28, 48, 49, 5155).

CRAB: Three of five CRAB studies included patient isolation as part of a multimodal approach (50, 57, 59). The primary outcomes were the incidence of CRAB infection (one of three) and the incidence of CRAB infection and colonization (two of three). All three studies reported a significant reduction in CRAB outcomes post-intervention, including a significant change in slope estimates (that is, trend; range: −0.01 to −4.81) and a significant change in the level estimate (that is, immediate change; −48.86) (50, 57, 59).

CRPsA: One of three CRPsA studies included patient isolation as part of a multimodal approach (61). The primary outcome was the incidence of CRPsA infection. The study reported a significant reduction in CRPsA outcomes after the intervention including a significant change in the slope estimate (that is, trend; −1.36) (61).

The GDG considered the overall quality of the evidence to be very low to low. The approach to patient isolation often varied between studies. It was assessed only as part of a multimodal strategy and the GRADE assessment was undertaken by pathogen (that is, CRE, CRAB or CRPsA) and outcome (for example, the incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection and/or colonization, etc.), rather than according to specific interventions alone.

Additional factors considered when formulating the recommendation

Values and preferences

The GDG recognized that patient isolation could occasionally be associated with some potentially negative unintended consequences, including a sense of stigma and psychological impact on isolated patients. In addition, some patients may feel some social isolation and have psychological consequences, such as depression or anxiety when managed in a single room (64). Appropriate patient communication and efforts to maintain patient dignity and respect should be emphasized to mitigate potential misconceptions. This may require specific communication training for some health care workers. In cases of prolonged isolation where morale may be affected, patients should be provided with psychological support. Similarly, it was noted that there may be a negative impact on some health care workers who manage such patients in isolation rooms, including a sense of stress and reduced morale. The GDG considered that these issues should be openly recognized and can be adequately addressed if managed appropriately.

It was also recognized that the implementation of this recommendation was likely to have a potential impact on single room availability in hospitals, a need for increased staffing and equipment availability, and an increase in budget allocation for the purchase of disposable protective equipment and the cost of disposal. In some cases, single room and cohort isolation have been shown to be associated with a reduced standard of medical care if not well managed (64). Nevertheless, it was the panel’s view that each of these concerns should be addressed and could be minimized or abolished with an appropriate management structure.

In conclusion, the GDG considered that each of these issues could be minimized with appropriate management and that the advantages of patient isolation in terms of preventing the cross-transmission of CRE-CRAB-CRPsA outweighed these concerns. When feasible, consideration should be given to providing priority services to patients who are subject to isolation or cohorting and priority allocation of dedicated health care personnel and resources in order to mitigate psychological consequences and other potential harm.

Other shared lessons on ethical considerations of patient isolation can be found in the WHO guidance on ethics of tuberculosis prevention, care and control (42) and the WHO discussion paper on addressing ethical issues in pandemic influenza planning (65), as well as in other public health ethics guidance (66, 67). These guidance documents emphasize that the goal (as it relates to patient isolation) should be to protect public health while minimizing human rights violations and ethical concerns. Thus, the “public health necessity” and “distributive justice” (see description of ethical concepts in Recommendation 1) of isolation should be ensured and monitored.

Resource implications

It was recognized that patient isolation may have considerable resource implications, including the need for single rooms. This is particularly relevant in LMICs where single rooms are often scarce. Therefore, the use of patient isolation may impact on the health facility infrastructure. Single room isolation can increase health care worker workload. However, the cohorting of patients colonized/infected with the same pathogen may ease some workload issues in certain circumstances. A reliable implementation of this recommendation is also likely to require adequately trained IPC staff.

The GDG was confident that the resources necessary to separate infected/colonized patients from those who are non-infected/colonized are worth the expected net benefit from following this recommendation.

Feasibility

The GDG was confident that this recommendation can be implemented in most countries, although some support may be required in LMICs. Moreover, the panel acknowledged that the implementation of this recommendation should be undertaken with care and sensitivity to be feasible and to avoid misunderstanding and increased suffering by some patients.

Acceptability

The GDG acknowledged that awareness-raising actions are needed regarding the risks of CRE-CRAB-CRPsA spread and the burden of related patient outcomes to be acceptable to health care facility senior managers who may need to take decisions on increasing the number of single rooms and other resources. Overall, the GDG was confident that key stakeholders are likely to find this recommendation acceptable.

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including:

  • cost-effectiveness and practicality of isolation and cohorting of patients with CRE-CRAB-CRPsA, particularly in LMICs or other settings where there are competing needs;
  • transmission dynamics of CRE-CRAB-CRPsA and the identification of differences between these three groups of pathogens;
  • benefit of dedicated health care worker staff to exclusively manage isolated/cohorted patients;
  • benefit of increased bed spacing on CRE-CRAB-CRPsA acquisition in settings where opportunities for isolation/cohorting are limited;
  • identification of when patient isolation should be appropriately ceased among patients colonized or infected with CRE-CRAB-CRPsA;
  • Patient values and preferences concerning the implementation of patient isolation for CRE-CRAB-CRPsA colonization/infection.

3.6. Recommendation 6: Environmental cleaning

The panel recommends that compliance with environmental cleaning protocols of the immediate surrounding area (that is, the “patient zone”) of patients colonized or infected with CRE-CRAB-CRPsA should be ensured.

(Strong recommendation, very low quality of evidence)

Rationale for the recommendation

  • Among the 11 CRE studies, three included environmental cleaning as part of their assessed intervention (49, 50, 53). Two of the three studies reported a significant reduction in CRE outcomes after the intervention (49, 53).
  • Among the five CRAB studies, three included environmental cleaning as part of their assessed intervention (50, 57, 59). All three reported a significant reduction in CRAB outcomes after the intervention.
  • Among the three CRPsA studies, two included environmental cleaning as part of their assessed intervention (60, 61). Both studies reported a significant reduction in CRPsA outcomes after the intervention.
  • Despite the limited available evidence and its very low quality, the GDG unanimously agreed that the strength of this recommendation should be strong. This decision was based on the:

    known role of environmental contamination in facilitating the transmission of CRE-CRAB-CRPsA and other similar multidrug-resistant pathogens to patients;

    panel’s recognition that environmental cleaning is known to be an effective intervention in reducing the transmission of other multidrug-resistant pathogens that are similar to CRE-CRAB-CRPsA;

    evidence and international concern regarding the burden and impact of CRE-CRAB-CRPsA colonization/infection (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2);

    the fact that a clean and hygienic environment is considered one of the core components of effective IPC programmes according to the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Remarks

  • According to the definition included in the WHO guidelines on hand hygiene in health care (6), the “patient zone” contains the patient and his/her immediate surroundings. Typically, this includes all inanimate surfaces that are touched by or in direct physical contact with the patient, such as the bed rails, bedside table, bed linen, infusion tubing, bedpans, urinals and other medical equipment. It also contains surfaces frequently touched by health care workers during patient care, such as monitors, knobs and buttons and other “high frequency” touch surfaces. Contamination is likely also in toilets and associated items (7).
  • The optimal cleaning agent for environmental cleaning protocols of the immediate surrounding area of patients colonized/infected with CRE-CRAB-CRPsA has not yet been defined. Three CRE-CRAB-CRPsA studies used hypochlorite (generally a concentration of 1000 parts per million [ppm]) as an agent to undertake environmental cleaning (50, 53, 61).
  • The GDG noted that appropriate educational programmes for hospital cleaning staff are crucial to achieve good environmental cleaning.
  • The use of multimodal strategies to implement environmental cleaning was considered essential. This includes institutional policies, structured education, and monitoring compliance with cleaning protocols (75, 76).
  • Assessment of cleaning efficacy by performing environmental screening cultures for CRE-CRAB-CRPsA was noted to be worthwhile in some settings (Recommendation 7).
  • The GDG noted that in some outbreak situations, temporary ward closures were necessary to allow for enhanced cleaning (48, 61).

Background

The general evidence to support environmental cleaning (and maintenance of the built environment) as an effective IPC intervention to prevent HAI and cross-transmission of pathogens has been previously summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Summary of the evidence

In this section, the evidence that included cleaning as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient outcomes was examined.

Studies assessing environmental cleaning were of ITS design from countries in the Americas Region (one of 11 CRE, two of five CRAB and none of three CRPsA studies), Eastern Mediterranean Region (one of 11 CRE, none of five CRAB and three CRPsA studies), European Region (one of 11 CRE, none of five CRAB and one of three CRPsA studies) and the Western Pacific Region (none of 11 CRE, one of five CRAB and one of three CRPsA studies). The intervention of environmental cleaning was often described as “enhanced”, for example, increasing frequency of cleaning, changing the cleaning solution and auditing of practices and feedback.

CRE: Three of the 11 CRE studies included environmental cleaning as part of a multimodal approach (49, 50, 53). The primary outcomes were CRE infection (one of 10), CRE bloodstream infection (one of 10) and the incidence of CRE infection or colonization (one of 10). Two of the three studies reported a significant reduction in CRE outcomes after the intervention including significant change in slope estimates (that is, trend; range: −0.09 to −0.91) (49, 53).

CRAB: Three of the five CRAB studies included environmental cleaning as part of a multimodal approach (50, 57, 59). The primary outcomes were the incidence of CRAB infection (one of three) and the incidence of CRAB infection and colonization (two of three). All three studies reported a significant reduction in CRAB outcomes after the intervention including a significant change in slope estimates (that is, trend; range: −0.01 to −4.81) and a significant change in the level estimate (that is, immediate change; −48.86) (50, 57, 59).

CRPsA: Two of the three CRPsA studies included environmental cleaning as part of a multimodal approach (60, 61). The primary outcomes were the incidence of CRPsA infection. Both reported a significant reduction in CRPsA outcomes after the intervention including a significant change in the slope estimate (that is, trend; −1.36) and a significant change in the level estimate (that is, immediate change; −0.02) (60, 61).

The GDG considered the overall quality of the evidence to be very low. The approach to environmental cleaning often varied between studies. It was assessed only as part of a multimodal strategy and the GRADE assessment was undertaken by pathogen (that is, CRE, CRAB or CRPsA) and outcome (for example, the incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection/colonization, etc.), rather than according to specific interventions alone.

Additional factors considered when formulating the recommendation

Values and preferences

Although there was no study identified on patient values and preferences with regards to this recommendation, the GDG considered that environmental cleaning was likely to have positive implications since most patients and their families prefer hospitals that are demonstrably clean.

Resource implications

The GDG recognized that strengthening environmental cleaning is likely to have resource implications depending on the cleaning product used and in terms of an increased workload for cleaners and potentially enhanced degradation to some vinyl and other surfaces in hospitals.

However, the panel considered that most cleaning products, including hypochlorite, are generally low cost and that salaries for hospital cleaners are also often relatively low. The panel noted that some cleaning agents (for example, hydrogen peroxide), while seemingly effective, can be disruptive to hospital workflow and bed utilisation given the time and equipment required for their use. It was noted that while a number of studies cited the effective use of hypochlorite, it could be associated with occupational health issues unless used according to the correct instructions.

The GDG acknowledged that some LMICs may face basic water, sanitation and hygiene challenges. However, a sufficient and reliable water supply is essential to support basic cleaning. Furthermore, shared hospital items (for example, furniture) should be made of easily cleanable material and should be maintained without any damage that may impede adequate cleaning.

The GDG was confident that this recommendation can be implemented in all countries in the long term, including in limited resource settings, and that the resources required will be worth the net benefit, despite the costs incurred. Implementing a clean and safe environment is a fundamental prerequisite to effective IPC and quality of care. There is a need for institutions to provide the necessary physical and educational resources in order to meet this recommendation.

Feasibility

The GDG believed that this recommendation is feasible in most health care settings, given an appropriate allocation of resources and executive leadership. The panel considered the benefit from this recommendation to be worthwhile in terms of reducing the risk of CRE-CRAB-CRPsA colonization/infection.

Acceptability

The GDG was confident that key stakeholders are likely to find the recommendation acceptable.

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including:

  • optimal cleaning agent and method in terms of efficacy, cost-effectiveness, simplicity of use and availability (particularly in LMICs);
  • the optimal cleaning protocol, particularly in LMICs where clean water may be scarce;
  • standardization of the definition of “enhanced” cleaning (this was described in the evidence in a heterogeneous manner) and its efficacy and effectiveness compared to regular environmental cleaning;
  • CRE-CRAB-CRPsA survival time or persistence in the environment;
  • effectiveness of cleaning protocols for high-risk items, such as bedpans and urinals;
  • optimal educational approach regarding environmental cleaning practices;
  • most accurate monitoring indicators for environmental cleaning.

3.7. Recommendation 7: Surveillance cultures of the environment for CRE-CRAB-CRPsA colonization/contamination

The panel recommends that surveillance cultures of the environment for CRE-CRAB-CRPsA may be considered when epidemiologically indicated.

(Conditional recommendation, very low quality of evidence)

Rationale for the recommendation

  • Among the 11 CRE studies, only one included environmental surveillance cultures as part of their assessed intervention and reported a significant reduction in CRE outcomes post-intervention (55).
  • Among the five CRAB studies, only one included environmental surveillance cultures as part of their assessed intervention and reported a significant reduction in CRAB outcomes after the intervention (59). In addition, one study monitored environmental contamination after cleaning using an adenosine triphosphate (ATP) bioluminescence assay as part of their intervention and found a significant reduction in CRAB outcomes after the intervention (50).
  • Among the three CRPsA studies, two included environmental surveillance cultures as part of their assessed intervention and reported a significant reduction in CRPsA outcomes post-intervention (60, 61).
  • The panel noted that environmental contamination with CRE-CRAB-CRPsA is commonly associated with increased rates of patient colonization and infection with these pathogens, particularly CRAB and CRPsA. All studies used environmental surveillance cultures to monitor the efficacy of hospital cleaning, which was one of the key elements of their multimodal IPC interventions.
  • The evidence was not uniform, of very low quality, and appeared to be strongest for CRAB and CRPsA, rather than CRE. Thus, the GDG considered surveillance cultures of the environment to be a conditional recommendation.

Remarks

  • The panel noted that the correlation of environmental surveillance culture results to the rates of patient colonization/infection with CRE-CRAB-CRPsA should be undertaken with caution and depends on an understanding of the local clinical epidemiological data and resources.
  • Based on expert opinion (and only limited available data), surveillance cultures of the general environment were considered most relevant to CRAB outbreaks. Outbreaks of CRPsA colonization/infection among patients appeared to be more commonly associated with environmental CRPsA contamination involving water and waste-water systems, such as sinks and taps (faucets).
  • Epidemiology, microbiological laboratory capacity and available resources should be evaluated when considering the implementation of this recommendation, hence its “conditional” attribution.

Background

Although environmental contamination with CRE-CRAB-CRPsA is commonly observed when patients are colonized and/or infected with these pathogens, the exact attribution of the environmental contamination to the clinical problem is not always clear, except as a marker of the thoroughness of hospital cleaning. However, environmental surveillance may be a potentially useful measure to assess the level of contamination and the efficacy of cleaning in the surroundings of patients colonized or infected with CRE-CRAB-CRPsA. Considering these issues, the GDG explored the evidence related to the role of environmental surveillance cultures as part of the interventions used to control CRE-CRAB-CRPsA within the systematic review performed as a background to these guidelines.

Summary of the evidence

In this section, the evidence that included environmental surveillance as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient outcomes is examined.

Included studies assessing environmental surveillance were of ITS design from countries in the Americas Region (none of 11 CRE, one of five CRAB and one of three CRPsA studies), Eastern Mediterranean Region (one of 11 CRE, none of CRAB and three CRPsA studies), European Region (none of 11 CRE, none of five CRAB and three CRPsA studies) and the Western Pacific Region (one of 11 CRE, none of five CRAB and one of three CRPsA studies). Environmental surveillance was often described as environmental cultures implemented together with enhanced environmental cleaning.

CRE: One of 11 CRE studies included environmental surveillance as part of a multimodal approach (55). The primary outcome was the incidence of CRE infection. This study reported a significant reduction in CRE infection after the intervention, including a significant change in slope (that is, trend; −0.32) and level estimates (that is, immediate change: −3.93).

CRAB: One of five CRAB studies included environmental surveillance as part of a multimodal approach (59). The primary outcome was the incidence of CRAB infection. The study reported a significant reduction in CRAB infection post-intervention, including a significant change in slope estimate (that is, trend; −0.09). In addition, one study monitored environmental contamination after cleaning using an adenosine triphosphate bioluminescence assay (but not culture) as part of their intervention and also found a significant reduction in CRAB infection and colonization (50).

CRPsA: Two of three CRPsA studies included environmental surveillance as part of a multimodal approach (60, 61). Both primary outcomes were the incidence of CRPsA infection. These studies reported a significant reduction in CRPsA outcomes after the intervention, including one significant change in the slope estimate (that is, trend; −1.36) and in the level estimate (that is, immediate change; −0.02).

The GDG considered the overall quality of the evidence to be very low. The approach to surveillance cultures of the environment often varied between studies. It was assessed only as part of a multimodal strategy as it was not an intervention component in all studies and the GRADE assessment was undertaken by pathogen (that is, CRE-CRAB-CRPsA) and outcome (for example, the incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection and/or colonization, etc.), rather than according to this specific intervention alone. Furthermore, the GDG noted that surveillance cultures of the environment were a component in few studies and the efficacy of the recommendation appeared to vary depending on the responsible pathogen and the epidemiological context. For this reason, the GDG considered this recommendation to be conditional.

Additional factors considered when formulating the recommendation

Values and preferences

The GDG was confident that the typical values and preferences of patients, health care workers, health care providers and policy-makers would favour hospital-based environmental surveillance when linked to environmental cleaning and the timely feedback of results to stakeholders.

Resource implications

The GDG recognized that the collection and microbiological testing of environmental cultures can require a specialized approach and that capacity-building may be required in some health care settings, especially in LMICs. The GDG also recognized that the purpose of environmental cultures was almost universally to inform hospital cleaning initiatives, but capacity-building in cleaning techniques and training may be required to achieve optimal cleaning.

Under certain circumstances, the GDG believed that the additional financial resources required for environmental surveillance cultures are worth the expected net benefit from following this recommendation. However, the GDG recognized that its implementation may be resource-intensive, particularly in LMICs. It was also noted that there will be significant implications regarding available human resources, microbiological/laboratory support, information technology and data management systems for the implementation of this recommendation. Furthermore, laboratory quality standards must be considered as these will affect the outcome of surveillance data and interpretation. Despite these potential resource implications, the GDG regarded the function of environmental surveillance cultures as important under certain conditions.

Feasibility

While feasibility is likely to vary substantially in different settings, the GDG was confident that this recommendation can be accomplished in all countries. However, local human resources (including technical capacities) and laboratory capacity will need to be evaluated and addressed, particularly in LMICs. Additional education will likely be required to help standardize the audit and surveillance process across all countries.

Acceptability

The GDG was confident that key stakeholders are likely to find this conditional recommendation acceptable when applied under the appropriate circumstances. Of note, a priority assessment is required to adequately evaluate environmental surveillance and take decisions.

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including:

  • the most optimal sampling methods to accurately identify environmental contamination with CRE-CRAB-CRPsA and the appropriate laboratory processing of cultures to maximize the identification of these pathogens from such specimens;
  • the most cost-effective approaches to surveillance cultures for CRE-CRAB-CRPsA.

3.8. Recommendation 8: Monitoring, auditing and feeback

The panel recommends monitoring, auditing of the implementation of multimodal strategies and feedback of results to health care workers and decision-makers.

(Strong recommendation, very low to low quality of evidence)

Rationale for the recommendation

  • Among the 11 CRE studies, nine included monitoring, auditing and feedback (for example, feedback of results to leadership and health care workers) as part of their assessed intervention (28, 48, 5056). Eight of the nine reported a significant reduction in CRE outcomes (28, 48, 5156).
  • Among the five CRAB studies, four included monitoring, auditing and feedback as part of their assessed intervention (50, 5759). Three of the four reported a significant reduction in CRAB outcomes (50, 57, 59).
  • Among the three CRPsA studies, all included monitoring, auditing and feedback as part of their assessed intervention (58, 60, 61). Two reported a significant reduction in CRPsA outcomes (60, 61).
  • Despite the limited available evidence and its very low quality, the GDG unanimously agreed that the strength of this recommendation should be strong. This decision was based on the:

    panel’s conviction regarding the benefit of monitoring, auditing and feedback as a key IPC core component to prevent and control CRE-CRAB-CRPsA, which is consistent with the reviewed evidence that led to the development and content of the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13) where these processes are already the object of a strong recommendation;

    evidence and international concern regarding the burden and impact of CRE-CRAB-CRPsA colonization/infection (in particular, see epidemiological data in section 1.1 and specific reasons for developing these recommendations in section 1.2).

Remarks

  • The GDG considered that the monitoring, auditing and feedback of IPC interventions are a fundamental component of any effective intervention and especially important for strategies to control CRE-CRAB-CRPsA.
  • Appropriate training of staff who undertake monitoring of the implementation of multimodal strategies and the feedback of results is crucial.
  • All components of the multimodal strategy intervention should be regularly monitored, including hand hygiene compliance.
  • Monitoring, auditing and feedback of multimodal strategies are a key component of all IPC educational programmes.
  • The GDG agreed that IPC monitoring should encourage improvement and promote learning from experience in a non-punitive institutional culture, thus contributing to better patient care and quality outcomes.

Background

The general evidence to support the monitoring, auditing and feedback of IPC interventions as an effective practical recommendation to prevent HAI and cross-transmission of pathogens has been previously summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Summary of the evidence

In this section, the evidence that included monitoring, auditing and feedback as part of the intervention to prevent and control CRE-CRAB-CRPsA-related patient outcomes is examined.

Studies assessing monitoring, auditing and feedback were of ITS design from countries in the Americas Region (four of 11 CRE, three of five CRAB and two of three CRPsA studies), Eastern Mediterranean Region (two of 11 CRE, none of five CRAB and three CRPsA studies), European Region (two of 11 CRE, none of five CRAB and three CRPsA studies) and the Western Pacific Region (one of 11 CRE, one of five CRAB and one of three CRPsA studies). The intervention of monitoring, auditing and feedback was often described as the monitoring of IPC practices and feedback to both hospital and regional leadership, as well as directly to health care workers.

CRE: Nine of the 11 CRE studies included monitoring, auditing and feedback as part of a multimodal approach (28, 48, 5056). The primary outcomes were CRE infection (six of 10), CRE bloodstream infection (two of 10), prevalence of CRE infection (one of 10) and incidence of CRE infection or colonization (one of 10), including one study with two reported outcomes. Eight of the nine studies reported a significant reduction in CRE outcomes post-intervention, including significant changes in slope (that is, trend; range: −0.01 to −3.55) and level estimates (that is, immediate change; range: −1.19 to −31.8) (28, 48, 5156).

CRAB: Four of the five CRAB studies included monitoring, auditing and feedback as part of a multimodal approach (50, 5759). The primary outcomes were the incidence of CRAB infection (one of four), incidence of CRAB infection and colonization (two of four) and incidence of CRAB and CRPsA colonization (one of four). Three of the four studies reported a significant reduction in CRAB outcomes after the intervention, including a significant change in slope estimates (that is, trend; range: −0.01 to −4.81) and in the level estimate of (that is, immediate change; −48.86) (50, 57, 59).

CRPsA: All three CRPsA studies included monitoring, auditing and feedback as part of a multimodal approach (58, 60, 61). The primary outcomes were the incidence of CRPsA infection (two of three) and the incidence of CRAB and CRPsA colonization (one of three). Two reported a significant reduction in CRPsA outcomes after the intervention including one significant change in the slope estimate (that is, trend; −1.36) and one significant change in the level estimate (that is, immediate change; −0.02) (60, 61).

The GDG considered the overall quality of the evidence to be very low to low. Although monitoring and feedback was a common component of most CRE-CRAB-CRPsA studies, the approach often varied between studies and the GRADE assessment was by outcome (for example, the incidence of infection, incidence of bloodstream infection, prevalence of colonization, incidence of infection and/or colonization, etc.), rather than according to this specific intervention alone.

Additional factors considered when formulating the recommendation

Values and preferences

Although no study was identified on patient or health care worker values and preferences regarding monitoring, auditing and feedback, this was the key focus of the literature review. However, the GDG was confident that both health care workers and patients in all settings would place a high value on this recommendation. The GDG was also of the unanimous view that education and practical training on appropriate approaches for accurate monitoring, auditing and feedback of IPC interventions would be welcomed in all health care settings.

Other shared lessons on ethical considerations of monitoring can be found in the Guidance on ethics of tuberculosis prevention, care and control (42) and the WHO discussion paper on addressing ethical issues in pandemic influenza planning (65). In particular, an effective monitoring system should also consider the extent to which ethical considerations have been incorporated into formal policies.

Resource implications

The GDG was confident that the resources required to undertake effective monitoring, auditing and feedback are worth the expected net benefit and that implementing this recommendation is likely to reduce overall health care costs.

Feasibility

The GDG was confident that this recommendation is feasible in all health care settings.

Acceptability

The GDG was confident that key stakeholders are likely to find this recommendation acceptable as it is consistent with evidence previously summarized in the WHO guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (13).

Research gaps

The GDG discussed the need for further research in several areas related to this recommendation, including:

  • monitoring, auditing and feedback of critical IPC aspects beyond that of hand hygiene (despite its importance), especially related to CRE-CRAB-CRPsA in areas such as environmental cleaning and disinfection and isolation/cohorting initiatives;
  • feedback to patients and caregivers;
  • more innovative, reliable methods of monitoring beyond traditional approaches, for example, electronic monitoring and feedback.
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