Download Infection control and prevention measures to reduce the spread of

J Antimicrob Chemother 2014; 69: 1185 – 1192
doi:10.1093/jac/dkt525 Advance Access publication 23 January 2014
Infection control and prevention measures to reduce the spread
of vancomycin-resistant enterococci in hospitalized patients:
a systematic review and meta-analysis
Giulia De Angelis1, Maria Adriana Cataldo2, Chiara De Waure3, Silvia Venturiello1, Giuseppe La Torre4, Roberto Cauda1,
Yehuda Carmeli5 and Evelina Tacconelli1,6*
1
Division of Infectious Diseases, Catholic University, Rome, Italy; 22nd Infectious Diseases Division, National Institute for Infectious
Diseases, Rome, Italy; 3Institute of Hygiene, Catholic University, Rome, Italy; 4Clinical Medicine and Public Health Unit, Sapienza University
of Rome, Rome, Italy; 5Division of Epidemiology, Tel Aviv University, Tel Aviv, Israel; 6Division of Infectious Diseases, Medizinische Klinik,
Universitätsklinikum Tübingen, Tübingen, Germany
*Corresponding author. Innere Medizin I, Raum 925, Ebene 3 Gebäude Nord, Universitätsklinikum Tübingen, Otfried-Müller-Straße 12, D-72076 Tübingen,
Germany. Tel: +49-(0)7071-29-85020; Fax: +49-(0)7071-29-25074; E-mail: [email protected]
Received 1 September 2013; returned 5 October 2013; revised 6 December 2013; accepted 11 December 2013
Objectives: Vancomycin-resistant enterococci (VRE) represent a major problem in healthcare settings worldwide.
It is still unclear which is the most effective infection control and prevention (ICP) measure to reduce the spread of
hospital-acquired VRE.
Methods: Cochrane databases, MEDLINE, EMBASE and CINAHL were searched until June 2012 to find studies
comparing wards/hospitals where ICP measures to prevent VRE transmission were investigated. In the absence
of heterogeneity, a fixed-effects model was used to estimate the pooled risk ratio (RR). Study quality was
assessed according to Cochrane Effective Practice and Organisation of Care (EPOC) criteria.
Results: The search strategy retrieved 549 studies and 9 studies (1 randomized clinical trial, 3 controlled clinical
trials and 5 interrupted time series) with 30 949 participants were included. The overall study quality was low.
Implementation of hand hygiene was associated with a 47% decrease in the VRE acquisition rate (pooled RR
0.53, 95% CI 0.39 – 0.73, I 2 26%) while contact precautions did not significantly reduce the VRE acquisition
rate (pooled RR 1.08, 95% CI 0.63 –1.83, I 2 0%). Due to the low number of studies, meta-analysis was not applied
for surveillance screening, environmental cleaning and antibiotic formulary interventions. No studies were available on the effectiveness of isolation and cohorting of patients and staff.
Conclusions: Available evidence on the ICP measures to reduce VRE spread in adult hospitalized patients is poor.
This systematic review suggests a significant role for the implementation of hand hygiene. Further studies with
appropriate study design are urgently needed to define ICP measures able to reduce the acquisition of VRE
among hospitalized patients.
Keywords: hand hygiene, contact precaution, screening
Introduction
Vancomycin-resistant enterococci (VRE) were first identified as
hospital-associated pathogens in Europe during the mid-1980s and
have rapidly disseminated worldwide.1 In the USA, Enterococcus
spp. and the vancomycin-resistant phenotype were responsible for
13% and 3%, respectively, of all healthcare-associated infections
reported to the National Healthcare Safety Network during 2009–
10.2 In Europe, from 2007 to 2011, most countries have reported
an increasing trend of vancomycin resistance among Enterococcus
faecium responsible for severe infections, with Greece and Ireland
reaching proportions .25%.3
The first guidelines for the control of VRE infections in hospitals
were published in 1994 by the Hospital Infection Control Practices
Advisory Committee (HICPAC).4 The HICPAC suggested the following measures to reduce cross-transmission among hospitalized
patients: restriction of vancomycin use; education of hospital
staff and the promotion of handwashing with antiseptic soap or
a waterless antiseptic agent; routine screening for vancomycin
resistance among isolates from clinical samples; contact isolation
# The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
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Systematic review
for patients with VRE colonization or infection; and rectal surveillance cultures. Guidelines from the Society for Healthcare
Epidemiology of America emphasized all the previous interventions including routine use of active surveillance cultures.5
However, VRE is still endemic in many countries. Controversies
remain about the most efficacious infection control and prevention (ICP) measures to reduce the rate of hospital spread. In addition, a few studies have evaluated the cost-effectiveness of these
ICP measures. For example, Montecalvo et al.6 estimated that the
net saving due to enhanced infection control strategies to reduce
the transmission of VRE in an endemic hospital for 1 year was
$190000. As it is unclear which is the most effective ICP measure to reduce the transmission of VRE among hospitalized
patients, a systematic review of the literature and meta-analyses
were performed.
Methods
Types of studies and participants
Studies comparing the impact of different intervention policies to prevent
VRE transmission were planned to be included. The following interventions
were investigated: hand hygiene measures; contact precautions; screening cultures to identify those individuals colonized or infected with VRE;
isolation unit or ward; room isolation; cohorting patients, defined as physical segregation of a group of VRE-positive patients from patients not
known to be VRE positive; cohorting patients and staff, defined as above
plus nursing by designated staff; environmental cleaning interventions;
antibiotic formulary interventions; and ward closure. Contact precautions
were defined as standard precautions (i.e. hand hygiene, personal protective equipment guided by risk assessment and the extent of contact anticipated with blood and body fluids, or pathogens) plus gown and gloves
upon room entry of a patient/resident colonized or infected with VRE
and using disposable single-use or patient/resident-dedicated non-critical
care equipment. Randomized clinical trials (RCTs), controlled clinical trials
(CCTs), interrupted time series (ITSs) and controlled before-and-after studies were considered eligible for inclusion only. Data limited to adult
patients (≥18 years old) were retrieved. No restriction of language was
applied.
Objectives and outcome measures
The primary objective was determining the effects of different ICP measures on the incidence of VRE colonization/infection in adult hospitalized
patients. Therefore, the primary outcome was the calculation of the risk
of VRE colonization and/or infection defined as the number of patients
with newly acquired VRE colonization or infection (i.e. not present at
study inclusion).
The secondary objectives were to determine the effects of different ICP
measures aimed at minimizing the spread of VRE on the risk of death at
30 days follow-up, prolonged hospitalization, adverse effects and hospital
costs. Studies reporting a different primary outcome were excluded.
Search methods for identification of studies
We searched the following electronic databases for relevant studies:
Cochrane Wounds Group Specialised Register (searched 15 June 2012);
the Cochrane Central Register of Controlled Trials (CENTRAL) (the
Cochrane Library 2012, issue 6); Ovid MEDLINE (1950 to May Week 5
2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations; 13 June
2012); Ovid EMBASE (1980 to 2012 Week 23); and EBSCO CINAHL (1982
to 14 June 2012). The search strategy is available as Supplementary data
at JAC Online. The references of retrieved articles were checked for additional
relevant articles not identified by the search strategy. The study authors
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were contacted in case of missing data. The studies were excluded if authors
provided no reply or insufficient data to reliably confirm inclusion.
Selection of studies, data extraction and management
The abstracts of all papers identified by the search were appraised for eligibility independently by two members of the review team. Full copies of
articles were obtained for all papers meeting (or appearing to meet) the
inclusion criteria. Members of the review team were not permitted to
appraise or review any paper on which they had been an author at any
stage of the appraisal process. Data were independently extracted by
two review authors. The data extraction was discussed in case of disagreement and the justification for excluding studies from the analysis was
documented.
Assessment of risk of bias in included studies
We assessed the risk of bias of included studies according to the detailed
criteria developed by the Cochrane Effective Practice and Organisation
of Care (EPOC) group.7 The risk of bias was assessed independently
by two reviewers without blinding to the journal or study authorship.
Discrepancies were resolved by discussion or involvement of a third review
author if required.
Assessment of heterogeneity
We assessed both clinical and statistical heterogeneity. In the absence of
clinical and statistical heterogeneity, we applied a fixed-effects model to
pool data. If evidence of significant ‘extra’ variability was identified
between a sufficient number of studies to inform the distribution of effects
(at least four), a DerSimonian and Laird random-effects model was
applied. The overall consistency between trials was measured by the I 2
statistic.8 Substantial heterogeneity was considered for I 2 values .50%.
Publication bias was measured by the Begg funnel plot.9
Data synthesis
We compared the results for intervention and control groups and analysed
the data using ReviewManager 5. We presented the results with 95% CIs
and reported estimates for dichotomous outcomes as risk ratio (RR) and
for continuous outcomes as difference in means. Data from studies with
different design were not combined.10 We calculated cluster-adjusted
effect sizes using the inverse variance method.11 None of the included
studies provided an estimate of the intracluster correlation coefficient
(ICC) that was therefore derived from the available literature.12,13 In the
absence of specific data for the outcome of interest (VRE acquisition),
since the range of ICCs of studies in primary care is estimated to be between
0.01 and 0.1, a value of 0.05 was considered the most appropriate.
Results
Results of the search
The search strategy retrieved 549 records. After deduplication and
examination of the titles and abstracts, all but 134 studies were
eliminated and excluded from further review (Figure 1). Full-text
copies of the remaining studies were obtained and subjected to
further evaluation. One hundred and twenty-five of these studies
were excluded and the reasons for their exclusion were noted.
Finally, nine publications met the eligibility criteria and were
selected for review.14 – 22
Characteristics of the included studies
The main characteristics of the studies included are shown in
Table 1. Seven studies were carried out in the USA,14,15,17 – 21 one
JAC
Systematic review
Potentially relevant abstracts identified and screened for retrieval (n = 549)
Studies not concerning the impact of infection control interventions on
VRE infection or colonization (n = 415)
125 studies excluded because:
– study design (n = 44)
– no intervention policies applied to reduce VRE acquisition (n = 27)
– evaluation of a different primary outcome (n = 36)
– authors contacted and studies excluded for no response or insufficient
data (n = 13)
– type of intervention other than the ones included in the protocol (n = 5)
Studies included in the meta-analyses (n = 9)
Figure 1. Study selection for the meta-analyses.
in the UK16 and one in Canada.22 All studies were performed in
university hospitals. Baseline VRE prevalence was defined as
the proportion of positive patients at the perirectal area on
admission and/or periodically during the hospitalization in
the majority of the studies.14 – 20 VRE colonization at hospital
admission ranged from 0.5% to 58%. One study was a cluster
RCT,18 three were CCTs15,20,22 and five were ITSs.14,16,17,19,21 The
oldest studies were published in 199620 and 1999,16,21 following
in 2006,17,19 2007,15 2009,22 201014 and 2011.18 The main intervention was different among studies and was always included
in a multifaceted approach, which represents a more complex
strategy including two or more single interventions. The following
ICP measures were evaluated: environmental cleaning;17,22
handwashing measures;16,19 contact precautions;14,15,20 and
antibiotic formulary intervention.16,21 One study evaluated the
efficacy of screening cultures in association with contact precautions.18 No studies evaluated the efficacy of unit/ward closure
and cohorting patients or staff. Studies describing the
age16,18,20,21 and gender18,20 of the study population did not
show any significant difference between intervention and
control groups. In the cluster RCT,18 eligible intensive care units
(ICUs) were randomly assigned to the intervention or to existing
practice. In the three CCTs, the unit of randomization was represented by beds,20 by the whole medical ICU15 or by rooms previously occupied by VRE-positive patients.22 The overall quality of
the studies was poor (see Figure 2).
Effects of interventions
Primary outcome: VRE acquisition rate
Eight studies investigated the impact of the intervention on the
VRE acquisition rate.14 – 20,22 The study by Weiss et al. 21 was limited to the evaluation of the impact of the intervention on the
VRE surgical site infection (SSI) rate and therefore was not
included in the analysis of primary outcome.
Efficacy of contact precautions in preventing VRE acquisition.
Four studies14,15,18,20 evaluated the effect of contact precautions
in preventing VRE acquisition. One study14 was not included in the
meta-analysis because of a different study design (ITS). Contact
precautions did not significantly reduce the VRE acquisition rate
(pooled RR 1.08, 95% CI 0.63 – 1.83; fixed-effects model)
(Figure 3). No statistical heterogeneity was detected among
studies.
Efficacy of hand hygiene measures in preventing
VRE acquisition. Two studies16,19 were included in the analysis.
The implementation of hand hygiene measures was associated
with a significant decrease in the VRE acquisition rate (pooled
RR 0.53, 95% CI 0.39 –0.73; fixed-effects model). Low heterogeneity was detected between studies (I 2 ¼ 26%) (Figure 4).
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Systematic review
Table 1. Main characteristics of studies included in the systematic review
Study
design
Reference
Country
Setting
Bearman 201014
USA
ITS
surgical ICU
Bearman 200715
USA
CCT
medical ICU
Bradley 199916
UK
ITS
haematology unit
Hayden 200617
USA
ITS
medical ICU
Huskins 201118
USA
Lai 200619
USA
cluster
RCT
ITS
medical-surgical
ICU
medical ICU
Slaughter 199620
USA
CCT
medical ICU
Weiss 199921
Williams 200922
USA
Canada
ITS
CCT
surgical unit
all hospital
except ICU
Description of the intervention
contact precautions versus universal gloving with
emollient-impregnated gloves without contact
precautions
contact precautions versus universal gloving
without contact precautions
piperacillin/tazobactam replaced ceftazidime as
first-line treatment of febrile neutropenia plus
enhanced infection control measures
educational intervention to improve environmental
cleaning
active surveillance; pre-emptive universal gloves;
universal gloves and gown for VRE-positive patients
use of alcohol-based, waterless hand antiseptic in
place of plain and antimicrobial soap
universal use of gloves and gowns versus universal
gloving alone
antibiotic restriction policies
terminal cleaning and visual inspection versus terminal
cleaning, environmental culture and closing of the
room pending negative results
Efficacy of environmental cleaning in preventing
VRE acquisition. Two studies17,22 were included in the analysis.
The implementation of environmental cleaning did not significantly
reduce the VRE acquisition rate in both studies. The results were not
combined in a meta-analysis because of different study designs
(CCT and ITS).
Efficacy of antibiotic formulary interventions in preventing VRE
acquisition. Two studies evaluated the effect of antibiotic formulary interventions in preventing VRE acquisition.16,21 Since the two
studies evaluated different VRE outcomes (VRE acquisition rate
and VRE SSIs), they were not combined in a meta-analysis. In
one study,16 during the intervention period, the VRE acquisition
rate progressively decreased. However, a return to ceftazidime in
a post-intervention period, despite maintaining hand hygiene
teaching and surveillance, was associated with a new increase in
the VRE acquisition rate. In the second study,21 during the 3 year
intervention period, no SSIs due to VRE were observed, while
2.4% of SSIs were caused by VRE in the post-intervention period.
Efficacy of screening cultures in preventing VRE acquisition. Only
one study18 evaluated the effect of screening cultures to detect
unknown colonized patients (at hospital admission, weekly and
at discharge) in association with expanded use of contact precautions as compared with standard of care on the incidence of VRE
colonization and infection in adult ICUs. In control ICUs, screening
cultures were performed but the ICU staff was not informed about
the results. The intervention was not effective in reducing the incidence of VRE colonization and infection.
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Compliance with the
intervention
67% (contact precautions)
versus 78% (universal
gloving)
75.7% (contact precautions)
versus 87% (gloves)
not reported
87% (intervention period)
versus 48%
(pre-intervention period)
not reported
not reported
79% (gloves and gowns)
versus 62% (gloves)
not reported
not reported
Secondary outcomes: length of hospitalization, mortality,
costs and adverse effects
The duration of hospitalization was evaluated in five studies.14,15,17,18,20 The implementation of contact precautions15,20
was not associated with a decreased length of stay (Figure 5). In
one study,17 the implementation of environmental cleaning did
not have a significant impact in decreasing the duration of hospitalization. One study20 evaluated 30 day all-cause mortality, which
showed no difference in ICU and in-hospital mortality between
intervention and control groups. Possible adverse effects of interventions and costs were not evaluated by any of the included studies.
Publication bias
Publication bias was assessed using a funnel plot of all studies,
which showed a slight asymmetry around the pooled point estimate, although the limited number of studies does not allow
the exclusion of publication bias.
Discussion
A number of strategies have been studied for the prevention of
VRE spread among adult hospitalized patients. Our meta-analysis,
including nine studies (one cluster RCT, three CCTs and five ITSs)
for a total of 30 949 patients, showed that the implementation
of hand hygiene measures was associated with a 47% decrease
in the VRE acquisition rate. In contrast, we could not demonstrate
that the implementation of contact precautions, isolation unit or
ward, single-room isolation, cohorting patients and/or staff and
ward closure significantly reduce the VRE acquisition rate in hospitalized patients.
JAC
Systematic review
Blinded assessment of primary outcomes
Selective outcome reporting
Random sequence generation (selection bias)
Baseline characteristics
Completeness of outcome data
?
Protection against detection bias
–
Shape of the intervention effect was specified
Protection against contamination
?
Protection against secular trends
Baseline measurement
Bearman 2007
Allocation concealment (selection bias)
Handwashing has been proven to be an important component
of interventions for the control of hospital-acquired pathogens,
including methicillin-resistant Staphylococcus aureus (MRSA).23 – 29
Two studies were included in this meta-analysis. In the first
one,19 the introduction of alcohol-based waterless antiseptic
alone was effective in reducing the transmission rate of VRE in a
medical ICU. However, the study was observational and hand
hygiene compliance was not monitored before and after the intervention. In the second study,16 the authors performed an intensive education programme to improve hand hygiene compliance
with alcoholic chlorhexidine hand rub or gel and observed a
decrease in the VRE incidence. The intervention also included a
?
+
–
–
?
Bearman 2010
+
–
+
–
+
?
Bradley 1999
+
––
+
–
+
?
Hayden 2006
+
––
+
–
+
?
?
+
–
+
?
+
–
+
?
+
Huskins 2011
?
+
+
+
Lai 2006
Slaughter 1996
–
–
+
?
+
+
?
Weiss 1999
Williams 2009
––
––
–
+
?
+
?
?
–
+
?
?
–
–
+
Figure 2. Risk of bias summary figure (+, low risk of bias; ?, unclear risk of
bias; 2, high risk of bias).
Study or subgroup
Bearman 2007
Huskins 2011
Slaughter 1996
log(RR)
SE
change in antibiotic policy for febrile neutropenia, so the effect of
hand hygiene promotion as a single measure cannot be demonstrated. In addition, no measure of hand hygiene compliance and
no clear hand hygiene promotion after the intervention period were
performed.
The implementation of contact precautions on the incidence of
multidrug-resistant microorganisms in hospitalized patients have
been assessed in many studies with heterogeneous
results.14,15,17,19,20,30,31 One of the major limitations of these
studies is that the self-reported rate of compliance with contact
precautions usually exceeded that observed by the study personnel monitoring compliance. In the RCT by Huskins et al.,18 the
authors observed that the use of barrier precautions by healthcare
workers (HCWs) was less than that required. Slaughter et al. 20
were not able to show a positive effect of universal gowning
added to universal gloving in endemic situations. The lack of a
no gloves – no gowns control group limited the conclusion concerning the importance of the use of gloves as a contact barrier.
VRE are known to contaminate and survive in the hospital
environment,32 to be extremely resistant in the environment
and routine cleaning with bleach-based products was often not
associated with effective cleaning.33 The risk of transmission of
VRE from contaminated environments to patients depends on
several factors, such as the density of VRE in stools, cleaning practices, patient comorbidities and the intensity of medical care.
Huang et al. 34 showed, in a retrospective cohort study, that the
risk of acquiring MRSA and VRE is higher in patients admitted in
rooms where an MRSA- or VRE-positive patient has been admitted
before. One study included in our review22 observed that obtaining environmental samples before room entry of a new patient did
not significantly decrease the risk of VRE transmission when compared with visual inspection. As a limitation, adherence to terminal cleaning procedures was not measured. The second
retrieved study17 found that enforcing cleaning measures was
associated with a decrease in environmental contamination but
not VRE acquisition among inpatients. It is possible that the
short periods of observation (58 days each) limited the possibility
to observe any effect of the intervention.
Antibiotic use has been identified as one of the most important
risk factors for VRE acquisition. In case –control studies, colonization and infection with VRE have been associated with exposure to
vancomycin, third-generation cephalosporins, antibiotics active
against anaerobes, ciprofloxacin and aminoglycosides.35,36 In a
prospective cohort study including 864 patients starting antibiotics, the incidence of colonization by antibiotic-resistant bacteria,
including VRE, for 1000 days of therapy was 14 for carbapenems,
9 for glycopeptides and 6 for third-generation cephalosporins and
Physical barriers Control
RR
total total Weight IV, fixed, 95% CIt
–0.2916 0.76
0.208 0.47
0.0783 0.37
Total (95% CI)
Heterogeneity: c2 = 0.31 , df = 2 (P = 0.86); I2 = 0%
Test for overall effect: Z = 0.27 (P = 0.78)
257
5434
93
192 12.8%
3705 33.4%
88 53.9%
5784
3985 100.0% 1.08 (0.63, 1.83)
RR
IV, fixed, 95% CI
0.75 (0.17, 3.31)
1.23 (0.49, 3.09)
1.08 (0.52, 2.23)
0.01
0.1
1
Favours physical barriers
10
100
Favours control
Figure 3. Efficacy of contact precaution in preventing VRE colonization/infections. IV, inverse variance.
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Systematic review
Study or subgroup
Bradley 1999
Lai 2006
Hand hygiene
events
total
25
19
Control group
events total
131
19
Weight
RR
M-H, fixed, 95% CI
43
29
102
80
62.7%
37.3%
0.45 (0.30, 0.69)
0.66 (0.41, 1.08)
Total (95% CI)
210
44
72
Total events
Heterogeneity: c2 = 1.36, df = 1 (P = 0.24); I2 = 26%
Test for overall effect: Z = 3.91 (P < 0.0001)
182
100.0%
0.53 (0.39, 0.73)
RR
M-H, fixed, 95% CI
0.01
0.1
1
10
100
Favours hand hygiene Favours control
Figure 4. Efficacy of hand hygiene measures in preventing VRE colonization/infections. M –H, Mantel– Haenszel.
Study or subgroup
Bearman 2007
Slaughter 1996
SE
Weight
Mean difference
IV, fixed, 95% CI
0.8 2.0464
0.7 4.4131
82.3%
17.7%
0.80 (–3.21, 4.81)
0.70 (–7.95, 9.35)
100.0%
0.78 (–2.86, 4.42)
Mean difference
Total (95% CI)
Heterogeneity: c2 = 0.00, df = 1 (P = 0.98); I2 = 0%
Test for overall effect: Z = 0.42 (P = 0.67)
Mean difference
IV, fixed, 95% CI
–100
–50
Favours experimental
0
50
100
Favours control
Figure 5. Impact of contact precautions on reducing duration of hospitalization. IV, inverse variance.
quinolones.37 A systematic review of 13 quasi-experimental studies on the efficacy of vancomycin restriction on VRE acquisition
rate showed results ranging from a reduction of 82.5% to an
increase of 475%.38 In our review, a meta-analysis was precluded
by the heterogeneity of the two included studies. In one study, the
authors changed antibiotic policy by replacing ceftazidime with
piperacillin/tazobactam16 and, in the other, the authors restricted
the use of vancomycin, ceftazidime, imipenem, aztreonam and
ciprofloxacin.21 A significant reduction of the VRE acquisition
rate was documented by Bradley et al.,16 while Weiss et al.21 did
not observe any change in VRE SSIs. In the study by Bradley
et al.,16 the intervention was combined with hand hygiene promotion. The study by Weiss et al.21 was not designed to test the intervention specifically on VRE acquisition and no data on antibiotic
usage were reported.
The main limitation of this review was the impossibility to
evaluate studies reporting on a single intervention. However, the
meta-analysis showed a clear impact of hand hygiene in reducing
the incidence of VRE colonization and infection and should be
taken into consideration when designing bundles for infection
control and prevention of VRE in the hospital setting. Due to the
heterogeneity of interventions, it was impossible to clearly define
the impact of other single interventions on VRE acquisition. The
overall quality of the papers was low. The control group was usually not clearly defined, nor were the applied ‘standard precautions’. All but three studies16,21,22 were performed in ICUs,
limiting the generalizability of the results. In addition, as we did
not search for unpublished data or the grey literature, we recognize the possibility of missing information regarding outcomes
and other variables that could be considered key to the interpretation of the results.
The research agenda needs to move to multicentre studies
applying well-defined multifaceted interventions, including hand
1190
hygiene implementation, using a randomized study design with
randomized allocation to interventions. This would provide better
evidence as well as the power to measure cost-effectiveness and
exclude important bias. If observational designs are preferred,
study protocols should be clearly designed to guarantee the
quality of data analysis and reporting. Sample size calculation
should clearly state the hypothesis according to different levels
of endemicity to avoid inconclusive results. The main outcome
should be clearly described and calculated. The efficacy of interventions and their sustainability remain poorly defined because of
the heterogeneity in study design and insufficient study quality to
enable adequate causal inference. Notably, evidence is needed to
show that interventions do not have possible adverse effects.
Antimicrobial stewardship studies should consider multiple outcomes including both Gram-positive (VRE and MRSA) and
Gram-negative bacteria (extended-spectrum b-lactamase or carbapenemase producers) and Clostridium difficile. In particular, we
believe that there is an urgent need for studies on ICP measures
including both Gram-positive and Gram-negative bacteria. More
attention should be paid to the efficacy of prevention of VRE transmission in non-ICU wards. Trials assessing the hospital costs of
such measures are also needed.
Funding
This study was carried out as part of our routine work.
Transparency declarations
None to declare.
Systematic review
Supplementary data
The search strategy is available as Supplementary data at JAC Online
(http://jac.oxfordjournals.org/).
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