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Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization (PAHO/WHO), Washington, DC
Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization (PAHO/WHO), Washington, DC
Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization (PAHO/WHO), Washington, DC
Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization (PAHO/WHO), Washington, DC
Address correspondence to Pilar Ramón-Pardo, MD, PhD, Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization (PAHO/WHO)., 525 23 Rd Street NW, Washington, DC 20037.
Antimicrobial Resistance Special Program, Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization (PAHO/WHO), Washington, DC
This systematic review (SR) aims to summarize the evidence about screening strategies to detect carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) to prevent healthcare-associated infections (HAIs).
•
No randomized trials were identified. Sixteen studies met our inclusion criteria and were included in the review.
•
Studies showed a decline of CRE, CRAB, CRPA infection and colonization rates after the implementation of screening strategies.
•
The certainty of the evidence was assessed as low for all outcomes, mainly due to the serious risk of bias and co-interventions.
•
Most studies included active surveillance cultures as part of a bundle intervention which precludes determining the independent effect of screening strategies.
Objective
This systematic review aims to summarize the evidence on the effects of screening strategies to detect carbapenem-resistant gram-negative bacteria (Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa).
Methods
Eligible studies were randomized trials, non-randomized controlled trials, controlled before-after studies, and interrupted time series. We conducted searches in CENTRAL, PUBMED, Embase, Epistemonikos, and in multiple databases available in the Virtual Health Library (LILACS, Scielo, WHO IBECS, and PAHO IBECS). All the searches covered the period until 4 June 2021. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned standardized form. When possible, we intended to conduct meta-analyses using a random-effect model. We assessed the certainty of the evidence (CoE) and summarized the results using the GRADE approach.
Results
Our search strategy yielded 57,451 references. No randomized trials were identified. Sixteen studies (one controlled before-after study and 15 interrupted time series) met our inclusion criteria and were included in the review. Most studies were conducted in tertiary care general hospitals from the United States, Europe, and Asia. Eleven studies included adult patients hospitalized in general wards and intensive care units, one was carried out in a neonatal intensive care unit, two in hematology or oncology units, and one in a solid organ transplantation department. Eleven studies were conducted in the setting of an outbreak. Regarding the detection strategy used, all studies included screening strategies for high-risk patients at the moment of admission and 7 studies reported a contact surveillance strategy. Most studies were conducted in settings where infection prevention and control measures were concomitantly installed or reinforced. Data were not suitable for meta-analysis, so the results were presented as a narrative synthesis. Most studies showed a decline in the prevalence of both infection and colonization rates after the implementation of a policy of active surveillance, but the CoE is low. Screening strategies may result in little to no difference in the risk of all-cause mortality and the length of hospital stay.
Conclusions
Existing evidence may favor the use of surveillance culture to carbapenem-resistant gram-negative bacteria, but its quality is poor, so solid conclusions cannot be drawn. Well-conducted randomized trials or high-quality quasi-experimental studies are needed to improve the certainty of the existing evidence. These studies should assess the effect of the addition of screening strategies as a single intervention and measure clinically important outcomes such as infection, length of hospital stay, and mortality.
The Centers for Disease Control and Prevention of the United States define carbapenem-resistant gram-negative bacteria as enterobacteria non-susceptible to any carbapenem antibiotics (MIC ≥4 mg/L for doripenem, meropenem or imipenem or ≥2 mg/L for ertapenem) or documented to produce a carbapenemase.
Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa are some examples. For decades, the prevalence of resistance to carbapenem antibiotics has been increasing due to the proliferation of different resistance mechanisms, resulting in a serious public health problem worldwide due to the current absence of effective therapeutic alternatives, which translates into a mortality rate between 34% to 70%.
Prevalence and 30-day all-cause mortality of carbapenem-and colistin-resistant bacteraemia caused by Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae: Description of a decade-long trend.
European Centre for Disease Prevention and Control Systematic Review of the Effectiveness of Infection Control Measures to Prevent the Transmission of Carbapenemase-Producing Enterobacteriaceae Through Cross-Border Transfer of Patients.
Tomczyk, S., Zanichelli, V., Grayson, ML, et al. (2019). Control de enterobacterias resistentes a carbapenémicos, Acinetobacter baumannii y Pseudomonas aeruginosa en establecimientos de salud: una revisión sistemática y un nuevo análisis de estudios cuasiexperimentales. Enfermedades infecciosas clínicas: una publicación oficial de la Sociedad de Enfermedades Infecciosas de América. 2019;68: 873–884.
The World Health Organization's guideline for the prevention and control of gram-negative bacteria resistant to carbapenems recommends a set of measures to prevent and control infections caused by carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). These measures include surveillance cultures and some behavioral interventions such as hand hygiene, contact precautions, patient isolation (single room isolation or cohorting), and environmental cleaning.
Guidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae Acinetobacter Baumannii and Pseudomonas Aeruginosa in Health Care Facilities.
Surveillance interventions to detect CRE, CRAB, and CRPA infections encompass different alternatives such as clinical monitoring of signs and symptoms of infection, active surveillance cultures, and laboratory tests to identify resistance to carbapenems.
Guidelines for the Prevention and Control of Carbapenem-Resistant Enterobacteriaceae Acinetobacter Baumannii and Pseudomonas Aeruginosa in Health Care Facilities.
Despite efforts to control carbapenem-resistant infections, there is no conclusive evidence about which is the best surveillance method and which patients to evaluate, and when.
There are no updated systematic reviews assessing prevention and control strategies interventions with a focus on surveillance and detection strategies. This review aims to provide a rigorous summary of the evidence about the effect of screening strategies to detect carbapenem-resistant gram-negative bacteria, including CRE, CRAB, and CRPA, in the prevention of healthcare-associated infections.
European Centre for Disease Prevention and Control Systematic Review of the Effectiveness of Infection Control Measures to Prevent the Transmission of Carbapenemase-Producing Enterobacteriaceae Through Cross-Border Transfer of Patients.
Tomczyk, S., Zanichelli, V., Grayson, ML, et al. (2019). Control de enterobacterias resistentes a carbapenémicos, Acinetobacter baumannii y Pseudomonas aeruginosa en establecimientos de salud: una revisión sistemática y un nuevo análisis de estudios cuasiexperimentales. Enfermedades infecciosas clínicas: una publicación oficial de la Sociedad de Enfermedades Infecciosas de América. 2019;68: 873–884.
These ‘Preferred Reporting Items for Systematic reviews and Meta-Analyses’ (PRISMA) guidelines for reporting systematic reviews and meta-analyses were followed
Cochrane Effective Practice and Organisation of Care (EPOC). EPOC Resources for review authors, 2017. Accessed March 29, 2022. epoc.cochrane.org/epoc-resources-review-authors.
to include other study designs. We included randomized trials, non‐randomized controlled trials, interrupted time series (ITS) with at least three-time points before and after the start of the intervention, and controlled before‐and‐after (CBA) studies with at least two sites in each comparison group. We excluded other study designs and studies evaluating the effects on animal models or in vitro conditions.
Types of participants, interventions, and outcomes
We considered patients of any age admitted or transferred to a healthcare facility. No exclusion criteria regarding race, ethnicity, gender, or comorbidities were applied. The review considered studies assessing the impact of any strategy of surveillance for CRE, CRAB, and CRPA, applied individually or as part of a multimodal strategy to control healthcare-associated infections. We considered strategies aimed at screening hospitalized patients, close contacts of a case, patients with risk factors, or all patients during endemic periods. The comparison of interest was no surveillance strategy or standard of care.
We considered the following outcomes as relevant: (1) Documented infection by CRE, CRAB, or CRPA, (2) Colonization by CRE, CRAB, or CRPA, (3) All-cause mortality (4) Length of hospital stay.
Electronic searches
We conducted a comprehensive search in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, Embase, and databases available in the Virtual Health Library (LILACS, Scielo, WHO IBECS, and PAHO IBECS). The searches covered from the date of inception to June 4, 2021. No study design, publication status, or language restriction was applied (see Appendix B - Search strategies). To identify articles that could have been missed in the electronic searches, we scanned the reference lists of all included studies and relevant systematic reviews.
Selection of studies
The results of the literature search were incorporated into Epistemonikos's L•OVE platform. There, they were de-duplicated by an algorithm that compares unique identifiers (database ID, DOI, trial registry ID), and citation details (ie author names, journal, year of publication, volume, number, pages, article title, and article abstract). All the articles that entered the L•OVE platform were classified by a multiclass deep neural network classifier into 4 different categories: primary study, systematic review, broad synthesis, and ‘other articles’. The detailed development and validation process of this algorithm has been described elsewhere.
Two researchers used the inclusion criteria to independently screen the titles and abstracts of the articles classified as primary studies by the boolean search described above. We obtained the full reports for all titles that appeared to meet the inclusion criteria or required further analysis and then decided about their inclusion.
We recorded the reasons for excluding trials at any stage and outlined the study selection process in a PRISMA flow diagram, which we adapted for this project.
Extraction and management of data
Using standardized forms, 2 reviewers independently extracted data from each included study. We collected the following information: study design, setting, participant characteristics, and study eligibility criteria; details about the intervention and comparison; the outcomes assessed and the time they were measured; economic analysis; and the risk of bias assessment. We resolved disagreements by discussion and one arbiter adjudicated unresolved disagreements.
Risk of bias assessment
The risk of bias for each randomized trial was assessed by using the 'Risk of bias' tool (RoB 2.0: a revised tool to assess the risk of bias in randomized trials).
We considered the effect of assignment on the intervention for this review. Two reviewers independently assessed 5 domains of bias for each outcome result of all reported outcomes and time points. These five domains of bias are (1) the randomization process, (2) deviations from intended interventions (effects of assignment to interventions at baseline), (3) missing outcome data, (4) measurement of the outcome, and (5) selection of reported results. Answers to signaling questions and collectively supporting information led to a domain‐level judgment in the form of 'Low risk of bias', 'Some concerns', or 'High risk of bias'. These domain‐level judgments informed an overall 'risk of bias' judgment for each result.
The risk of bias for each study was assessed by using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS‐I),
GRADE Guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence.
a tool for assessing the risk of bias in non‐randomized studies of interventions which considers the following bias domains: (1) confounding, (2) selection of participants into the study, (3) classification of interventions, (4) deviations from intended interventions (effect of assignment to intervention), (5) missing data, (6) measurement of outcomes, and (7) selection of the reported results. We judged each domain as low risk, moderate risk, serious risk, critical risk, or no information, and evaluated individual bias items as described in the ROBINS-I guidance.
Discrepancies between review authors were resolved by discussion. If necessary, a third review author was consulted to reach a decision.
Measures of intervention effect and data synthesis
The data was not suitable for meta-analysis. If we had been able to pool the results of the different trials, we would have expressed the estimate of the treatment effect of an intervention as risk ratios (RR) or odds ratios (OR) along with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes, we would have used the mean difference and standard deviation (SD) to summarize the data using a 95% CI.
The results of the search and the selection of the studies were presented in flow charts and tables that follow the recommendations of the PRISMA statement.
For any outcomes where it was not possible to calculate an effect estimate, a narrative synthesis was presented, describing the studies in terms of the direction and the size of effects, and any available measure of precision.
For the main comparisons and outcomes, we prepared GRADE Summary of Findings (SoF) tables.
For the outcomes where data were available from more than one study, we intended to conduct a formal quantitative synthesis (meta-analysis) for studies clinically homogeneous using RevMan 5
or other software, using the inverse variance method with the random-effects model and to assess inconsistency by visual inspection of the forest plots and using the I² index.
The certainty of the evidence (CoE) for all outcomes was judged using the Grading of Recommendations Assessment, Development, and Evaluation working group methodology (GRADE Working Group).
The domains considered were: risk of bias, consistency, directness, precision, and reporting bias. Certainty was adjudicated as high, moderate, low, or very low. For the main populations, comparisons, and outcomes, we prepared Summary of Findings (SoF) tables.
The search retrieved 57,451 records. We considered 189 references as potentially eligible and retrieved and evaluated their full texts. No randomized trials were identified. Sixteen studies were finally included.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
Most studies were conducted in tertiary care general hospitals from the United States, Europe, and Asia, and included adult patients hospitalized on general wards and intensive care units. One study was carried out in a neonatal intensive care unit (NICU),
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
including contact precautions, monitoring, audit, and feedback of preventive measures, patient isolation, or cohorts, hand hygiene, environmental sanitation, and cleaning.
The strategy and definitions employed to select which patients to consider for surveillance cultures varied among studies: all studies included surveillance cultures to high-risk patients
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
None of the studies included a point prevalence survey strategy.
High-risk patients were defined as: (1) Patients admitted at high risk-units (ICU, step-down units, long‐term acute care hospital, hemato-oncology unit, NICU),
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
Appendix D. provides the complete description of the characteristics of the included studies.
Risk of bias in the included studies
All included studies had serious issues with bias due to confounding, deviation from intended intervention, and bias in the selection of the reported results. Overall, 7 studies had a serious risk of bias and 9 studies had a critical risk of bias Table 1. summarizes the risk of bias assessment of each domain.
Table 1Risk of bias in the included studies assessed by ROBINS-I tool
Study
Bias due to confounding
Bias in selection of participants into the study
Bias in classification of interventions
Bias due to deviations from intended interventions
Bias due to missing data
Bias in measurement of outcomes
Bias in selection of the reported result
Overall risk of bias
Baek et al 2020
C
M
C
S
NI
M
S
C
Ben-David et al 2010
M
L
M
S
L
L
M
S
Borer et al 2011
S
S
M
NI
L
L
M
S
Ciobotaro et al 2011
C
M
S
M
NI
M
S
C
Gagliotti et al 2014
C
M
S
M
NI
M
S
C
Hayden et a 2015
S
M
M
M
NI
M
M
S
Li S et al 2019
S
M
M
S
S
M
L
S
Otter et al 2019
C
M
M
NI
NI
M
M
C
Viale et al 2011
C
M
S
M
S
M
S
C
Nagao et al 2011
M
M
M
S
NI
M
S
S
Geladari A et al 2017
C
M
M
M
M
M
C
C
Li M et al 2019
M
M
M
C
NI
M
C
C
Spyridopoulou K 2020
C
M
M
M
NI
M
C
C
Kousouli E 2017
C
S
M
C
NI
S
S
C
Goto et al 2016
S
M
M
S
NI
M
S
S
Valencia-Martín R et al 2019
S
NI
M
M
NI
M
S
S
C, Critical; L, Low; M, Moderate; NI, No information S, Serious.
The included studies correspond to interrupted time series and controlled before-after studies. It was not possible to pool results in a meta-analysis since there was substantial variability in the study setting, patient characteristics, interventions, and ways of reporting the outcome data. Therefore the results are presented as a narrative synthesis.
The main results are presented in the Summary of Findings table. Effect of screening strategies to detect carbapenem-resistant gram-negative bacteria Table 2.
Table 2Summary of findings table
screening strategies to prevent health care-associated infections
Patients
Hospitalized patients
Intervention
Screening strategies to detect carbapenem-resistant gram-negative bacteria (CRE, CRAB, CRPA)
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
One study assessing surveillance alone reported that no differences were observed on mortality rate in the ICU (pre-intervention period: 8.8%; post-intervention period: 9.0%).
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
The certainty of the evidence was downgraded in one level for risk of bias since the studies showed bias regarding confounding factors, deviation from intended intervention and bias in selection of the reported result.
In several studies, active surveillance was implemented as part of a multimodal of interventions. We did not downgrade the certainty of the evidence for indirectness because their results were similar to those where active surveillance was implemented alone.
LOW
Screening strategy may result in little to no difference in the risk of all-cause mortality.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
One study assessing surveillance alone reported that no differences were observed in the length of ICU hospital stay (pre-intervention period: median 1 day (IQR= 1-6); post-intervention period: median 1 day (IQR=1-6))
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
The certainty of the evidence was downgraded in one level for risk of bias since the studies showed bias regarding confounding factors, deviation from intended intervention and bias in selection of the reported result.
In several studies, active surveillance was implemented as part of a multimodal of interventions. We did not downgrade the certainty of the evidence for indirectness because their results were similar to those where active surveillance was implemented alone.
LOW
Screening strategies may result in little to no difference in the length of hospital stay.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
One study assessing surveillance alone reported an increase in infection by 13.04% every month (95% CI: 5.2- 21.5) during the pre-intervention period and a decrease in the infection rate during the intervention period (monthly percent change, −3.57%; 95% CI −6.9 to −0.1).
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
On the other hand, from 7 studies assessing surveillance as part of a multimodal intervention, 6 reported a significant reduction in the infection rate after the implementation of surveillance cultures.
The certainty of the evidence was downgraded in one level for risk of bias since the studies showed bias regarding confounding factors, deviation from intended intervention and bias in selection of the reported result.
In several studies, active surveillance was implemented as part of a multimodal of interventions. We did not downgrade the certainty of the evidence for indirectness because their results were similar to those where active surveillance was implemented alone.
LOW
Screening strategies may reduce the risk of carbapenem-resistant gram-negative bacteria infection.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Two studies assessed surveillance alone. One study reported a decrease in the colonization rate during the intervention period (monthly percent change −3.02% (95% CI: −4.7 to −1.3).
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Another study reported an increase in the CRE colonization rate from 1.0 per 1,000 admissions when the intervention was implemented to 2.7, but the proportion of positive screens remained at approximately 0.4% (range 0.2%-0.6%) throughout the study period.
All the 7 studies assessing surveillance as part of a multimodal intervention reported a significant reduction in colonization rate after the implementation of surveillance cultures.
The certainty of the evidence was downgraded in one level for risk of bias since the studies showed bias regarding confounding factors, deviation from intended intervention and bias in selection of the reported result.
In several studies, active surveillance was implemented as part of a multimodal of interventions. We did not downgrade the certainty of the evidence for indirectness because their results were similar to those where active surveillance was implemented alone.
LOW
Screening strategies may reduce the risk of carbapenem-resistant gram-negative bacteria colonization
GRADE, Grading of Recommendations Assessment, Development and Evaluation.
Interrupted time series (ITS) studies provide moderate quality evidence.
GRADE Guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence.
† The certainty of the evidence was downgraded in one level for risk of bias since the studies showed bias regarding confounding factors, deviation from intended intervention and bias in selection of the reported result.
‡ In several studies, active surveillance was implemented as part of a multimodal of interventions. We did not downgrade the certainty of the evidence for indirectness because their results were similar to those where active surveillance was implemented alone.
We identified two interrupted time series assessing the effect of screening strategies to detect carbapenem-resistant gram-negative bacteria. In both studies, the strategy was oriented to the detection of CRE.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
compared the CRE infection rate between the pre-intervention period (where a multimodal intervention was implemented) and the intervention period (where active surveillance was implemented in addition to previous strategies) in high-risk adult patients. During the pre-intervention period, the monthly percent change of CRE infection rate was 13.04% (95% CI: 5.2-21.5) and the infection rate peaked at 4.32% (7/162). During the intervention period, a total of 2,162 high-risk patients were admitted to the ICU. Most of these patients (1,916/2,063; 92.9%) qualified for CRE active screening (according to the following criteria: age >65 years; hospital stay >7 days; carbapenems, third- or fourth-generation cephalosporin or fluoroquinolone treatment for >3 days during 2 weeks before admission to the ICU; hematological malignancies; and immunosuppressive agent treatment for >1 week during 1 month before admission to the ICU). The incidence of CRE colonization significantly decreased, with a monthly percent change of −3.02% (95% CI: −4.7 to −1.3). Meanwhile, the incidence of CRE infection significantly decreased, with a monthly percent change of −3.57% (95% CI: −6.9 to −0.1).
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
This study also reported that no differences were observed on length of ICU stay (pre-intervention period: median 1 day (IQR= 1-6); post-intervention period: median 1 day (IQR=1-6)) and mortality in ICU (pre-intervention period: 232/2637, (8.8%); intervention period: 247/2735 (9.0%)).
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
) compared a limited screening program (pre-intervention period) to an enhanced screening program (intervention period). The number of positive cultures for CRE per month decreased from a peak of 10 in the pre-intervention period to a mean of 3 (range 1-5) per month over the last quarter of the study (intervention period). During the intervention period, the number of new cases of colonization or infection detected per month increased (from 18 to 50) in proportion to the number of surveillance cultures obtained (from 2,621, when the enhanced screening approach was started to 10,589).
The monthly rate of CRE detection per 1,000 admissions increased from 1.0/1,000 admissions when the intervention was implemented to 2.7/1,000 admissions, but the proportion of positive screens remained at approximately 0.4% (854/220,814 screens, range 0.2%-0.6%) throughout the study period.
Effect of screening strategies to detect carbapenem-resistant gram-negative bacteria as part of a multimodal intervention
We identified 14 studies that included screening strategies in addition to other measures to control CRE, CRAB, or CRPA infection or colonization. Thirteen corresponded to interrupted time series
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Baek et al reported that after implementing the reinforced program (without active surveillance) the incidence of bacteremia caused by CRE in healthcare-associated infections was 6.0/1,000 patients-days on neonatal intensive care units. After implementing the enhanced program (with active surveillance cultures, in addition to other measures), the incidence decreased to 0.0/1,000 patient-days. The incidence of CRE infections decreased gradually from 45.0 to 18.5/1,000 patient-days during the intervention period.
which included adult patients hospitalized in ICU and step-down units, the number of infections with CRE (specifically Klebsiella pneumoniae) increased gradually from 3 to 5 cases each month (ie 1.08 cases/10,000 patient-days) to 22-24 cases each month (ie 6.93 cases/10,000 patient-days) during the pre-intervention period (detection of CRE was based on culture of clinical samples only). During the intervention period, active surveillance cultures were implemented in addition to other infection control measures. The incidence of infection with CRE decreased from 6.93 cases/10,000 patient-days during the last quarter of the pre-intervention period to 1.8 cases/10,000 patient-days during the intervention period.
Borer et al reported that CRE infection was identified in 370 patients (49.5% during the pre-intervention and 51.5% during the post-intervention period), including adult patients hospitalized in high-risk wards. Two hundred and five (55%) infections were hospital-acquired. During the pre-intervention period, where no detection strategy was implemented, CRE infection incidence per 10,000 patient-days was 5.26. After the implementation of a package of interventions, the incidence decreased to 2.91, followed by 1.91, 1.28, and 0.18. Positive colonization prevalence was 10.4, 6.09, 3.65, and 2.31 positive rectal cultures per 100 patients admitted by year for May-December 2007, 2008, 2009, and January-May 2010, respectively (intervention period).
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
In another study that included patients admitted to the intensive care unit, Ciobotaro et al compared a limited surveillance strategy that was performed during the pre-intervention period (months 1-13). Between months 5 and 12, an average of 5 new patients per month were diagnosed with CRE (colonized), for an incidence of 3.4/10,000 patient-days. During the 13-14 months, the incidence peaked at 8.2/10,000 patient-days. During the intervention period, active surveillance culture was implemented as part of a multimodal intervention (14-56 months). The average incidence of CRE cases declined from 6.6/10,000 patient-days to 2.5/ 10,000 patient-days. From months 25 to 56, the average incidence of CRE infection was 0.5/10,000 patient-days, which was 16-fold lower than the peak incidence. The rate of cross-infection decreased significantly from 6% at the beginning of the intervention period to 2.7% at the end of the study.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
Gagliotti et al reported a linear increase of incident cultures positive for CRE over time in the pre-intervention period, while the number of cases remained stable after the launch of the infection control measures (including active surveillance culture). Considering the patients hospitalized in 5 Health Trusts that provided detailed data on incident cases, a downward trend was observed in incidence during the intervention period (from 32 to 15 cases per 100,000 hospital patient-days), where active surveillance of CRE was implemented in addition to other measures.
Hayden et al reported that the prevalence of CRE (specifically Klebsiella pneumoniae) rectal colonization was stable during the pre-intervention period (average, 45.8%; 95% CI 42.1%‐49.5%), declined early in the intervention period, and then reached a plateau (34.3%; 95% CI 32.4%‐36.2%) in adults hospitalized in all general medical wards and high‐risk units. Average rates of CRE in any clinical culture decreased from 3.7 events/1,000 patient-days in the pre-intervention period (95% CI: 3.4-4.09) to 2.5 events/1,000 patient-days (95% CI 2.2 to -2.8) in the intervention period. CRE bacteremia decreased from 0.9 events/1,000 patient-days (95% CI 0.8-1.1) in the pre-intervention period to 0.4 events/10,00 patient-days in the intervention period (95% CI 0.3-0.5). The multimodal intervention resulted in a 32% reduction in the rate of isolation of CRE from any clinical culture and a 56% reduction in CRE bacteremia.
This study also reported that no difference was observed on the length of hospital stay (pre-intervention period: median 28 days (IQR: 16‐43); post-intervention period: median 26 days, [IQR 17‐39]) and in‐hospital mortality (pre-intervention period: 21.5%; post-intervention period: 17.6%).
In another study, Li et al reported that the monthly incidence of CRE colonization/infection in hospitalized adults was 10.08 (95% CI 4.43-17.46) cases per 1,000 ICU patient-days at the baseline (no intervention was performed and only regular culture surveys were conducted). Infection-prevention and control (IPC) interventions were associated with a clear significant decrease to 3.18 (95% CI 2.98-6.18) but was followed by several increases in the incidence. The prevalence rates stabilized and decreased during the implementation of the modified IPC intervention (5.76, 95% CI 2.77-6.34) and follow-up periods (5.78; 95% CI 3.52-8.47) as compared to the baseline period. The monthly incidence of ICU-acquired CRE was 10.08 (95% CI 4.43-16.43) cases per 1,000 ICU patient-days at baseline, and IPC interventions were associated with a decrease to 3.12 (95% CI 2.98-5.40) but was followed by several increases in the incidence. The prevalence rates stabilized and decreased during the implementation of the modified IPC interventions (5.62; 95% CI 0.69-6.34) and follow-up periods (2.84, 95% CI 2.80-2.89) as compared to the baseline period.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Spyridopoulou K et al reported that the admission prevalence of CRE (Klebsiella pneumonia) colonisation (p < 0.001 for linear trend) and the incidence rate of CRE colonization (P = .072 for linear trend) were declining during the intervention period when a multimodal intervention (including active surveillance cultures) was implemented in a hematology unit of a tertiary-care hospital. The monthly prevalence of CRE colonization among hospitalized patients progressively decreased from 15.9% to 0% and the colonization incidence during hospitalization decreased from 10.6/1,000 patient-days to 0/1,000 patient-days during the intervention period.
More importantly, this study reported that the intervention measures halted the increasing incidence of CRE blood-stream infections observed in the pre-intervention period and eventually resulted in a decline from 1.58/1,000 patient-days in the beginning of the first intervention period to 0/1,000 patient-days in the third intervention period.
Viale et al assessed the implementation of a multimodal intervention including active surveillance of high-risk adult patients and contacts. The study reported that the monthly incidence of CRE bloodstream infections increased at a rate of 0.05 cases/10,000 patient days per month (incidence rate ratio: 1.05, 95% CI 0.99-1.11) during the pre-intervention period (where no detection strategies were mentioned). During the intervention period 1,571 CRE-positive cultures were detected, with Klebsiella being the CRE most frequently isolated (1,501/1,571, 95%). Following the intervention, the incidence rate of CRE bloodstream infections (risk reduction 0.96, 95% CI 0.92-0.99) and CRE colonization (risk reduction 0.96, 95% CI 0.95-0.97) significantly decreased over 30 months.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
Valencia-Martín et al explored the use of enhanced infection control measures including active surveillance culture in the setting of CRAB infection in adult patients admitted to ICU and wards. The incidence density of CRAB (infected or colonized) was 10.9 cases/1,000 patients-days at the beginning of the infection control program implementation. The incidence density of CRAB bacteremia at the beginning of the program was 0.026 cases/1,000 patients-days. Three trimesters later, no new cases of CRAB bacteremia were observed.
Nagao et al included surveillance cultures in addition to other measures to help control CRPA infection or colonization in a hemato-oncology unit. Seventeen patients infected with CRPA were identified (11 had active CRPA infection) during the pre-intervention study period, where a multimodal intervention was performed. During the intervention period, active surveillance, restriction of carbapenem use and other measures to ensure strict adherence to the infection control measures were implemented and the rate of CRPA infection was reduced to zero.
Goto et al assessed infection control measures on veterans who were admitted to acute care wards and intensive care units (active surveillance program in addition to other interventions) to prevent hospital-onset gram-negative bacteremia, including a subgroup analysis from those multidrug-resistant gram-negative. Hospital-onset multidrug resistant bacteremia had a significant decline in intercept (-19.8; 95% CI -27.6-11.0) and downward change of slopes from +1.0% per month (95% CI 0.6-1.5) to -0.4% per month (95% CI -0.6% to -0.3%) before and after implementation. Hospital-onset gram-negative bacteremia incidence rates showed a significant change of slope by the end of the initiative, from +0.3%/mo) to –0.4%/mo. However, specific CRE (Klebsiella pneumonia) and CRPA rates data was not available. The study also showed no differences between both periods on length of hospital stay (pre-intervention= range 5.4-6.0; intervention period: range 4.8-5.4).
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Geladari et al compared the implementation of a multimodal intervention (including active surveillance cultures) with a pre-intervention period without infection control measures. The monthly incidence of CRE, CRAB and CRPA infections increased from 1.9 cases/1,000 patient-days to 3.9 cases/1,000 patient-days during the pre-intervention period. During the intervention period, 74/250 patients colonized by CRE (Klebsiella pneumonia), CRPA or CRAB were found. Over this period, there was a significant decline in the incidence of colonization (from 19% to 9%). At the same time, the prevalence of colonization increased from 36% in the first week to 50% in the 69th week (intervention period). During the intervention period, monthly incidence of infection caused by carbapenem-resistant bacteria increased from 2.8 to 6.9/1,000 bed-days.
compared limited surveillance cultures with active surveillance cultures in addition to infection control measures to all adult ICU patients. During the study period, 351 patients with bloodstream infections caused by CRE, CRAB, and CRPA were identified and the yearly incidence rate of bloodstream infections for all hospital patients changed from 0.91/1.04 per 1,000 patient-days during pre-intervention period to 0.87/0.78/1.05/1.26 per 1,000 patient-days during the intervention period. For ICU patients, the incidence rate was 21.03/19.63 and 17.32/14.45/22.85/25.02 per 1,000 patient-days, respectively. No significant trend was found for the pre-intervention period, as well as no significant trend change within the intervention period. The study also showed no differences between both periods on length of hospital stay (total hospital: pre-intervention, range 3.92-4.10; intervention period, range 3.89-4.19. ICU: pre-intervention, range 16.37-24.06; intervention period, range 16.20-20.61).
We conducted a comprehensive systematic review and identified 16 studies that reported data on the impact of detection strategies for control of CRE, CRAB and CRPA as part of the healthcare-associated infections control process. No randomized controlled trials were identified.
Most of the studies (n=13) included adult patients hospitalized on general wards, intensive care units or other high-risk units. Only one study was carried out in the neonatal intensive care unit
The characteristics of the detection strategies varied across studies but all were focused on high-risk patients and/or contacts, on admission or weekly. On the other hand, the definition of main outcomes (infection or colonization) was not reported in two studies,
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
Most studies showed a decline in infection or colonization rates after the implementation of active surveillance cultures. Also, studies reported that active surveillance cultures may result in no difference in the length of hospital stay or the risk of all-cause mortality. However, the certainty of the evidence was assessed as low for all outcomes, mainly due to serious risk of bias of the included studies and the presence of co-interventions since active surveillance cultures were implemented as part of a bundle intervention which precludes determining the independent effect of active surveillance in these studies. Due to the poor quality in data reporting of most studies, it was not possible to assess whether there are differences between the different agents.
None of the studies conducted an economic impact analysis. Considering the expensive cost of these screening strategies and null results regarding length of hospital stay and mortality, cost-effective analysis is needed.
We performed a thorough search to identify other relevant systematic reviews. One systematic review assessed the efficacy of several infection prevention and control interventions on CRE, CRAB, or CRPA in inpatient healthcare facilities. The review included 17 low quality EPOC studies and in accordance with our results, most of the studies reported a significant post-intervention reduction in all outcomes.
Tomczyk, S., Zanichelli, V., Grayson, ML, et al. (2019). Control de enterobacterias resistentes a carbapenémicos, Acinetobacter baumannii y Pseudomonas aeruginosa en establecimientos de salud: una revisión sistemática y un nuevo análisis de estudios cuasiexperimentales. Enfermedades infecciosas clínicas: una publicación oficial de la Sociedad de Enfermedades Infecciosas de América. 2019;68: 873–884.
However, most of the studies included multimodal interventions, including contact precautions, active surveillance cultures, patient isolation or cohort among others. The review also reported that active surveillance cultures were not performed on 3 studies, and they report a significant reduction on infection/colonization outcomes.
Tomczyk, S., Zanichelli, V., Grayson, ML, et al. (2019). Control de enterobacterias resistentes a carbapenémicos, Acinetobacter baumannii y Pseudomonas aeruginosa en establecimientos de salud: una revisión sistemática y un nuevo análisis de estudios cuasiexperimentales. Enfermedades infecciosas clínicas: una publicación oficial de la Sociedad de Enfermedades Infecciosas de América. 2019;68: 873–884.
European Centre for Disease Prevention and Control Systematic Review of the Effectiveness of Infection Control Measures to Prevent the Transmission of Carbapenemase-Producing Enterobacteriaceae Through Cross-Border Transfer of Patients.
Infection prevention and control measures and tools for the prevention of entry of carbapenem-resistant Enterobacteriaceae into healthcare settings: guidance from the European Centre for Disease Prevention and Control.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
and concluded that evidence is limited by the lack of data from controlled studies reporting single infection control measures but bundle of interventions.
European Centre for Disease Prevention and Control Systematic Review of the Effectiveness of Infection Control Measures to Prevent the Transmission of Carbapenemase-Producing Enterobacteriaceae Through Cross-Border Transfer of Patients.
The ECDC guidance recommended active screening for all patients who are “at-risk” for carriage of CRE, defined as individuals with the following profile: (1) a history of an overnight stay in a healthcare setting in the last 12 months, (2) dialysis-dependent or cancer chemotherapy in the last 12 months, (3) known previous carriage of CRE in the last 12 months and (4) epidemiological linkage to a known carrier of a CRE.
Infection prevention and control measures and tools for the prevention of entry of carbapenem-resistant Enterobacteriaceae into healthcare settings: guidance from the European Centre for Disease Prevention and Control.
This review has several limitations. The main limitation comes from the low quality of the available evidence identified. There were no randomized trials and most studies had substantial limitations, poor quality of the data and report of the results. On the other hand, most studies evaluated surveillance cultures as part of a set of measures for infection-prevention and control. The type of patients, the measures that were already implemented in the hospitals where the intervention was carried out and the accompanying measures of the multimodal interventions varied widely across the different studies. This makes it difficult to infer what was the specific contribution of surveillance cultures and to establish the differential efficacy in different populations or settings.
We did not identify studies in which the detection strategy included a point prevalence survey strategy. Non comparative studies addressing this approach might not have been identified by our search strategy. Finally, publication bias is of particular concern in this review because of the large number of studies with no full-text available (only published as an abstract).
Ideally, randomized controlled trials should be conducted to increase the certainty of the evidence. However, conducting a trial on this intervention may be difficult for practical reasons but also because the measure has become standard practice in many centers. High quality non-randomized studies that include a detailed report of the intervention (for example, following the TIDieR checklist
), provide a clear definition of the main outcomes and conduct a rigorous analysis of the results would be valuable to shed light on this important topic.
Prevalence and 30-day all-cause mortality of carbapenem-and colistin-resistant bacteraemia caused by Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae: Description of a decade-long trend.
European Centre for Disease Prevention and Control
Systematic Review of the Effectiveness of Infection Control Measures to Prevent the Transmission of Carbapenemase-Producing Enterobacteriaceae Through Cross-Border Transfer of Patients.
Tomczyk, S., Zanichelli, V., Grayson, ML, et al. (2019). Control de enterobacterias resistentes a carbapenémicos, Acinetobacter baumannii y Pseudomonas aeruginosa en establecimientos de salud: una revisión sistemática y un nuevo análisis de estudios cuasiexperimentales. Enfermedades infecciosas clínicas: una publicación oficial de la Sociedad de Enfermedades Infecciosas de América. 2019;68: 873–884.
Cochrane Effective Practice and Organisation of Care (EPOC). EPOC Resources for review authors, 2017. Accessed March 29, 2022. epoc.cochrane.org/epoc-resources-review-authors.
GRADE Guidelines: 18. How ROBINS-I and other tools to assess risk of bias in nonrandomized studies should be used to rate the certainty of a body of evidence.
A multifaceted intervention strategy for eradication of a hospital-wide outbreak caused by carbapenem-resistant Klebsiella pneumoniae in Southern Israel.
An effective intervention to limit the spread of an epidemic carbapenem-resistant Klebsiella pneumoniae strain in an acute care setting: from theory to practice.
The effect of a nationwide infection control program expansion on hospital-onset gram-negative rod bacteremia in 130 veterans health administration medical centers: an interrupted time-series analysis.
Infection-prevention and control interventions to reduce colonisation and infection of intensive care unit-acquired carbapenem-resistant Klebsiella pneumoniae: a 4-year quasi-experimental before-and-after study.
Impact of individualised active surveillance of carbapenem-resistant enterobacteriaceae on the infection rate in intensive care units: a 3-year retrospective study in a teaching hospital of People's Republic of China.
Impact of a hospital-wide multifaceted programme for reducing carbapenem-resistant Enterobacteriaceae infections in a large teaching hospital in northern Italy.
Infection prevention and control measures and tools for the prevention of entry of carbapenem-resistant Enterobacteriaceae into healthcare settings: guidance from the European Centre for Disease Prevention and Control.
Funding: This review was commissioned by PAHO through a public tender.
Conflict of interest: All authors declare no financial relationships with any organization that might have a real or perceived interest in this work. There are no other relationships or activities that might have influenced the submitted work.
Interrupted time series (ITS) studies provide moderate quality evidence.
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