Record retrieval
The search strategy identified 3877 articles. Following removal of duplicates, 2776 articles remained. After screening titles and abstracts, 129 articles were included for full-text review (Fig. 1). Nineteen articles met the inclusion criteria and were included in the systematic review [26,42–59].
Characteristics of included studies
Among the 19 articles included, there were eight RCTs [26,42,45–47,51,54,55], eight uncontrolled before-after studies [43,44,48–50,53,57,58], one controlled before-after studies [52], and two interrupted time-series studies [56,59]. One article was an extended study of another [42,46]. Two articles were from the same study but presented different outcomes [54,55]. Fifteen identified studies associated with MRSA [26,42,44–52,54,55,58,59], four with VRE [51,53,56,59], two with C.diff. [56,57], and two with GNB [43,51]. Twelve studies were conducted in the United States [44,49–59], four in Europe [26,42,46,48], two in Asia [45,47], and one in the Middle East [43] (Table 1).
Table 1
Characteristics of included studies
Author (year)
|
Country
|
Study design
|
Control type
|
MDRO type
|
Measured outcomes
|
Staff compliance measured
|
Interventions (duration, months)
|
No. of residents analyzed (baseline)
|
Summary findings
|
Baldwin et al. (2010)[26]
|
Northern Ireland
|
Clustered RCT
|
Concurrent
|
MRSA
|
Colonization
|
Y
|
ED + PI (3, 6, 12)
|
793
|
No effect.
|
Bellini et al. (2015)[42]
|
Switzerland
|
Clustered RCT
|
Concurrent
|
MRSA
|
Colonization;
infections
|
N
|
DC + EC + ED (12)
|
4750
|
No effect.
|
Ben-David et al. (2019)[43]
|
Israel
|
Uncontrolled before-after
|
Historical
|
CRE
|
Acquisition
|
N
|
AE + BP + ED + PI (84)
|
~ 20000
|
Reduction.
|
Bowler et al. (2010)[44]
|
United States
|
Uncontrolled before-after
|
Historical
|
MRSA
|
Colonization
|
N
|
DC + EC + ED (13)
|
687
|
Reduction.
|
Chuang et al. (2015)[45]
|
Hong Kong SAR, China
|
Clustered RCT
|
Concurrent
|
MRSA
|
Colonization
|
Y
|
BP + EC + ED + HH + PI (6, 9, 12, 15)
|
2776
|
No effect.
|
Hequet et al. (2017)[46]
|
Switzerland
|
Clustered RCT
|
Concurrent
|
MRSA
|
Colonization
|
N
|
DC + EC + ED (12, 60)
|
NS
|
No effect.
|
Ho et al. (2012)[47]
|
Hong Kong SAR, China
|
Clustered RCT
|
Concurrent
|
MRSA
|
Infections
|
Y
|
AE + ED + HH + PI (4)
|
2407
|
Reduction.
|
Horner et al. (2012)[48]
|
United Kingdom
|
Uncontrolled before-after
|
Historical
|
MRSA
|
Colonization
|
Y
|
ED + PI (6, 9, 12, 18, 24)
|
2237
|
No effect.
|
Jaqua-Stewart et al. (1999)[49]
|
United States
|
Uncontrolled before-after
|
Historical
|
MRSA
|
Colonization; infections
|
N
|
BP + DC + ED + SC (12, 39)
|
42
|
Reduction.
|
Kauffman et al. (1993)[50]
|
United States
|
Uncontrolled before-after
|
Historical
|
MRSA
|
Colonization
|
N
|
DC (7, 5)
|
321
|
Reduction.
|
Mody et al. (2015)[51]
|
United States
|
Clustered RCT
|
Concurrent
|
MRSA; VRE; GNB
|
Colonization; infections
|
Y
|
BP + ED + HH + PI (24)
|
418
|
Reduction.
|
Morgan et al. (2019)[52]
|
United States
|
Controlled before-after
|
Concurrent
|
MRSA
|
Acquisition; infections
|
N
|
BP (48)
|
75414
|
No effect.
|
Ostrowsky et al. (2001)[53]
|
United States
|
Uncontrolled before-after
|
Historical
|
VRE
|
Colonization
|
Y
|
BP + EC + ED + HH (12, 24)
|
5221
|
Reduction.
|
Peterson et al. (2016)[54]
|
United States
|
Clustered RCT
|
Concurrent
|
MRSA
|
MRSA infections
|
N
|
DC + EC + ED + SC (12, 24)
|
7069
|
Reduction.
|
Schora et al. (2014)[55]
|
United States
|
Clustered RCT
|
Concurrent
|
MRSA
|
Colonization
|
N
|
DC + EC + ED + SC (12, 24)
|
4424
|
Reduction.
|
Schweon et al. (2013)[59]
|
United States
|
Uncontrolled interrupted time series
|
Historical
|
MRSA; VRE; C.diff.
|
Infections
|
Y
|
AE + ED + HH + PI (22)
|
NS
|
No effect.
|
Silverblatt et al. (2000)[56]
|
United States
|
Uncontrolled interrupted time series
|
Historical
|
VRE
|
Colonization
|
N
|
BP + DC + ED + HH (28)
|
NS
|
Absence of outcome.
|
Singh et al. (2018)[57]
|
United States
|
Uncontrolled before-after
|
Historical
|
C.diff
|
C.diff infections
|
N
|
AE + BP + EC + ED + HH (33)
|
~ 9381
|
Reduction.
|
Thomas et al. (1989)[58]
|
United States
|
Uncontrolled before-after
|
Historical
|
MRSA
|
Colonization; MRSA infections
|
N
|
BP + ED (3)
|
164
|
Reduction.
|
Abbreviations: |
AE, administrative engagement; BP, barrier precautions; BSI, bloodstream infection; C.diff., Clostridium difficile; DC, decolonization; ED, education; EC, environmental cleaning; GNB, Gram-negative bacteria; HH, hand hygiene; MRSA, methicillin-resistant Staphylococcus aureus; PI, performance improvement; NS, not specified; SC, source control; UC, usual care; VRE, vancomycin-resistant enterococci |
Effectiveness of IPC interventions on MRSA colonization
Of the 12 studies on MRSA colonization, the directions of intervention effects were divided: half of the studies found insignificant or no effects [26,42,45,46,48,52], while the other half reported significant reductions [44,49–51,55,58]. Seven studies involved at least three intervention components [42,44–46,49,51,55]. The most common interventions were education (83%) [26,42,44–46,48,49,51,55,58], decolonization (50%) [42,44,46,49,50,55], and environmental cleaning (42%) [42,44–46,55] (Fig. 2). The interventions included in each studies are summarized in a table (see Additional file 3). Two studies evaluated the individual effects of barrier precautions and decolonization. One showed that barrier precautions alone did not affect MRSA acquisition controlling for patient demographics, comorbidity, and year of admission (odds ratio, 0.97 [95%CI 0.85–1.12]; p = 0.71) [52], while the other reported decolonizing both the nares and wounds yielded a reduction in mean monthly colonization rate from 22.7–11.5% (p = 0.0001) [50]. Only four studies reported changes in compliance followed by the interventions: three on hand hygiene [26,45,48], and one on barrier precautions [51]. However, the evaluation methods were not standardized (see Additional file 4).
We excluded Hequet et al. (2017) since it is a follow-up study from Bellini et al. (2015) [42,46]. Our meta-analysis of 11 articles showed that IPC interventions were not associated with the reductions in MRSA colonization regardless of the intervention durations (long: pRR 0.81 [95%CI 0.60–1.10]; medium: pRR 0.81 [95%CI 0.25–2.68]; short: pRR 0.95 [95%CI 0.53–1.69]) [26,42,44,45,48–52,55,58]. We present the forest plot for studies evaluating MRSA colonization in an additional figure (see Additional file 5). Nevertheless, IPC interventions including decolonization reported reductions, albeit statistically insignificant, in colonization (range: pRR 0.34 [95%CI 0.22–0.53] to 0.88 [95%CI 0.71–1.10]) while interventions involving barrier precautions (range: pRR 1.00 [95%CI 0.75–1.33] to 1.02 [95%CI 0.74–1.41]) and education (pRR 1.06 [95%CI 0.91–1.23]) had no effects on MRSA colonization (Fig. 3). Our findings did not change when restricted only to studies with concurrent control (long: pRR 0.94 [95%CI 0.83–1.07]; medium: pRR 1.01 [95%CI 0.10-10.21]; short: RR 0.96 [95%CI 0.73–1.26]). The sensitivity analysis demonstrated a significant drop in the I2 with long-term interventions to 1% (p = 0.41); the I2 with medium-term interventions reduced only slightly to 77% (p = 0.04); and, the I2 short-term intervention remained unchanged at 0%. The forest plot for sensitivity analysis is included as an additional figure (see Additional file 6).
Effectiveness of IPC interventions on other outcomes
Three studies employing altogether barrier precautions, hand hygiene and education reported either reduced VRE colonization or free from new acquisition [51,53,56]. Of the two studies reporting reductions, one reported a cluster- and covariate-adjusted hazard ratio (HR) of 0.85 [95%CI 0.45–1.60] (p = 0.61) [51], while another found a relative risk of 0.30 [95%CI 0.20–0.70] (p = 0.001) [53]. Two studies, which included barrier precautions, education, and performance improvement in their IPC programme, found decreases in GNB acquisition. One of them reporting administrative engagement decreased CRE acquisition from 0.5 per 10 000 patient-days at baseline to 0.3 per 10 000 patient-days two years after implementation [43]. The other study, which also included hand hygiene, reported an insignificant cluster- and covariate-adjusted HR of 0.90 [95%CI 0.60–1.33] (p = 0.59) [51]. There were nine studies evaluating the effects of IPC interventions on infections, of which six reported reductions [47,49,51,54,57,58], one had no infection episodes [42], and two found no effects [52,59]. The six studies reporting reductions in infections summarized their results in various metrics with two reporting significant rate ratios ranged from 0.54 [95%CI 0.30–0.97] to 0.61 [95%CI 0.38–0.97] (p = 0.04) [47,51] and four showing relative reductions in infection rates ranging from 25.9–99.7% [49,54,57,58]. The opportunity for meta-analyses in other outcomes was limited due to heterogeneity in study designs and lack of studies.
Effectiveness of IPC interventions on MDRO outcomes involving administrative engagement
All studies actively involving the administrations reported reductions in either colonization or infections [43,47,57,59], although one did not reach 5% significant level [59]. Among the studies that did not result in outcome reductions, both alluded their failures to lack of organizational commitment [26,45].
Study quality
The risk of bias among 19 studies was generally high (Fig. 4a and 4b). Of the eight RCTs [26,42,45–47,51,54,55], all but one were at high risk of bias [47]. The only one with “some concerns” of bias reported significant reductions in MRSA infections requiring hospitalization following the implementation of a multimodal strategy [47]. The main reason for downgrading was that most studies did not appropriately adjust for the imbalance of missing outcome data in the analytical stage. The risk of bias assessment using ROB2 tool is presented in an additional table (see Additional file 7). Similarly, we rated the risk of bias of one non-RCTs as “moderate” [48], while others were as “serious” [43,44,49,50,52,53,56–59]. Unadjusted confounders without randomization was the main cause of degradation. The risk of bias assessment using ROBINS-I is available (see Additional file 8). The controlled before-after study with a moderate-level risk of bias reported a small but insignificant increase in MRSA colonization after the implementation of an IPC programme [48].
Publication bias and small study effects
Funnel plot suggests differences in intervention tendency effects among smaller and larger studies (see Additional file 9). Results from the majority of moderate-sized studies were statistically insignificant but that among studies with small sample size was generally significant. Small-sized studies with low methodological quality produced exaggerated positive intervention effect estimates. Egger’s test also supports the presence of small study effects (intercept=-4.05; p = 0.03).