Antimicrobial Stewardship Interventions to Optimize Treatment of Infections in Nursing Home Residents: A Systematic Review and Meta-Analysis

Abstract

Effects of antibiotic stewardship program (ASP) interventions to optimize antibiotic use for infections in nursing home (NH) residents remain unclear. The aim of this systematic review and meta-analysis was to assess ASPs in NHs and their effects on antibiotic use, multi-drug-resistant organisms, antibiotic prescribing practices, and resident mortality. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic review and meta-analysis using five databases (1988–2020). Nineteen articles were included, 10 met the criteria for quantitative synthesis. Inappropriate antibiotic use decreased following ASP intervention in eight studies with a pooled decrease of 13.8% (95% confidence interval [CI]: [4.7, 23.0]; Cochran’s Q = 166,837.8, p < .001, I² = 99.9%) across studies. Decrease in inappropriate antibiotic use was highest in studies that examined antibiotic use for urinary tract infection (UTI). Education and antibiotic stewardship algorithms for UTI were the most effective interventions. Evidence surrounding ASPs in NH is weak, with recommendations suited for UTIs.

Keywords

long-term care antimicrobial stewardship program antibiotic use

Background

Infections are a common problem in almost 1.5 million U.S. nursing home (NH) residents (Aliyu et al., 2017). Data from a national dataset of NH assessments estimate that 1.13 to 2.68 million infections exist in NHs, with the most common being urinary tract infections (UTIs), followed by pneumonia, multi-drug-resistant organisms (MDROs), wound infections, and sepsis (Herzig et al., 2017). Up to 79% of NH residents receive antibiotics to treat infection and over 75% are prescribed antibiotics inappropriately (Daneman et al., 2013; van Buul et al., 2012). Inappropriate antibiotic use leads to increased risk of infections such as MDROs, Clostridium difficile, and fungal infections with resistant organisms (Centers for Disease Control and Prevention [CDC], 2019; Montoya et al., 2016).

Employing antibiotic stewardship programs (ASPs) promote appropriate antibiotic use. ASPs can enhance antibiotic prescribing, optimize the treatment of infections, decrease MDRO prevalence, and improve patient outcomes (Baur et al., 2017; Crnich et al., 2015). The importance of ASPs resulted in a call to action by the CDC in 2015, and in 2016, the Centers for Medicare & Medicaid Services (CMS) issued a mandate for NH antibiotic stewardship (CDC, 2015; CMS, 2016). Although CMS standards have improved infection control in NHs, challenges persist (Stone et al., 2020). Infection preventionists (IPs), crucial to ASP implementation are inadequate. CMS guidelines require NHs establish an infection control program that includes at least one trained IP that works at least part-time. Although some NHs employ trained IPs, no specific recommendations for training are provided (CMS, 2016). Furthermore, ASPs remain suboptimal, with 57% of NHs receiving infection control deficiency citation between 2017 and 2019 (Jester et al., 2020).

Despite guidelines for ASPs in NHs, recent studies show that implementation strategies and outcome measures vary ranging from increased adherence to antibiotic treatment guidelines (Feldstein et al., 2018), overall reduction in antimicrobial use (Feldstein et al., 2018; Hui-Chih Wu et al., 2019), to no significant effect on antibiotic use (Raban et al., 2020). Other investigators have identified behavior change techniques that influenced adherence to antibiotic prescribing guidelines (Crayton et al., 2020). To date, there is insufficient evidence regarding which ASP interventions influence antibiotic use, and for which infections they will work best. Our objective was to build on existing reviews of studies of ASPs in NHs by focusing on the differential effects of ASP interventions on antibiotic use, MDROs, antibiotic prescribing practices, and resident mortality.

Research Design and Methods

Data Sources and Search Strategy

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Moher et al., 2009) and registered the protocol in the International Prospective Register of Systematic Reviews (PROSPERO) (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=173455). Four electronic databases were searched: Ovid MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library for original studies published from 1988 to 2020. Search terms included the following index terms, synonyms, and keyword phrases (“nursing home” or “long-term care facility”) AND (“antibiotic/antimicrobial stewardship” or “antibiotic stewardship programs” or “antibiotic use”). Studies were eligible for inclusion if they focused on antimicrobial stewardship intervention(s) in a NH (The full search strategy by database is shown in Supplementary, Appendix B).

Selection Criteria and Study Selection

Studies were included if (a) they present original data; (b) the study designs were randomized controlled trials (RCTs), quasi-experimental studies, or observational studies that evaluated an ASP intervention; (c) they were conducted in NHs or long-term care facilities; and (d) they were published in English language and in peer-reviewed, indexed journals. Excluded were editorials, white papers, review articles, commentaries, and health care settings other than NHs or long-term care facilities. We hand-searched reference lists of included articles to locate additional studies. Titles were screened and abstracts independently assessed and selected by two authors (S.A. and J.I.). Full texts were independently reviewed by two authors based on inclusion criteria. Differences in eligibility were resolved by consensus.

Data Extraction

The following data were extracted by two reviewers (S.A. and S.L.H.): author, year, country, study design, sample and setting, intervention, targeted infection, MDRO rate, antibiotic prescribing practices, antibiotic use, and mortality rate (Supplementary Table 1, Appendix A). Data for the meta-analysis were extracted by two reviewers (S.A. and A.S.). Disagreements were reconciled by consensus.

Quality Appraisal

Studies that met the criteria for review were appraised by two independent reviewers (S.A. and J.L.T.) using the quality assessment tool for quantitative studies developed by the Effective Public Health Practice Project. The eight appraisal components focus on selection bias, study design, confounders, blinding, data collection methods, withdrawals and drop-outs, intervention integrity, and analyses. Component ratings were categorized as strong, moderate, and weak. Next, each study was given a global rating of strong, moderate, or weak. The final score and the level of risk for bias were decided independently by both reviewers. Discrepancies were discussed until resolved (National Collaborating Centre for Methods and Tools, 2004).

Definitions of Variables

Definitions for ASP and inappropriate antibiotic use varied among studies; in some cases, studies lacked clear definition. The authors used criteria specific to each study for determination of antibiotic use. For example, Fleet applied McGeer criteria for infection surveillance and Loeb criteria for antibiotic initiation (Loeb et al., 2001; McGeer et al., 1991), while Furuno employed antibiograms which were created using clinical data and were applicable for empiric prescriptions. We created operational definitions to enable data synthesis across studies: (a) ASP was defined as coordinated interventions developed to improve or measure antibiotic use including appropriate selection, dosing, route, and duration of antimicrobial therapy (CMS, 2016; Jump et al., 2017). (b) Inappropriate antibiotic use was defined as non-compliance with established criteria for antibiotic use in NHs (Loeb et al., 2001; McGeer et al., 1991).

Quantitative Synthesis

Studies that reported sample size and appropriateness of antibiotic prescription as a proportion of the total number of antibiotic prescriptions at time points before and after the ASP were eligible for inclusion in the meta-analysis. For each study, data at both time points were extracted as either the overall percentage of inappropriate antibiotic prescription or the percentage of inappropriate antibiotic prescription for both the intervention and the control groups. Where appropriate prescription was measured as “appropriate,” we subtracted the reported frequency from 100% to obtain an inappropriate antibiotic prescription frequency. We then computed either the group difference in inappropriate antibiotic prescription following the intervention or the absolute difference between the intervention and control groups and its 95% confidence interval (http://sphweb.bumc.bu.edu/otlt/MPHModules/BS/BS704_Confidence_Intervals/BS704_Confidence_Intervals7.html). A pooled effect was estimated for the reduction in inappropriate antibiotic use using a random effects meta-analysis model with results presented as a forest plot. Heterogeneity was assessed using Cochran’s Q test and I² statistics and was considered present if either the Cochran’s Q test p-value was <.05 or I² was >50% (Higgins et al., 2003). To examine heterogeneity, we conducted subgroup analyses (Richardson et al., 2019) by grouping studies by measurement of antibiotic prescription, study design, intervention type, infection type, global study quality, and country where the study was conducted. We also conducted a sensitivity analysis to determine if the removal of one study significantly altered meta-analysis findings (Patsopoulos et al., 2008). To assess the potential for publication bias, we constructed a funnel plot and conducted Rosenthal’s fail-safe N test (Persaud, 1996) and Duval and Tweedie’s trim and fill method (Duval & Tweedie, 2000) to estimate the effect of publication bias. Statistical significance was determined by a p-value <.05. Data were analyzed using Comprehensive Meta-Analysis statistical software (Bio-stat, Inc., Englewood, NJ).

Results

The database searches yielded 2,373 articles. A total of 696 titles and abstracts were screened after removing duplicates. We excluded 661 articles because they were either conducted in facilities such as acute rehabilitation, acute care settings, home care settings, pediatric settings, or were commentaries or editorial letters. Nineteen articles were identified from the study selection process (PRISMA flow diagram, Figure 1).

Figure 1.

PRISMA flow diagram of study selection.

Characteristic of Studies

Supplementary Table 1 (Appendix A) describes the characteristics of the included studies. Study designs included RCT (Naughton et al., 2001), Cluster RCT (Fleet et al., 2014; Loeb et al., 2005; Monette et al., 2007; Pasay et al., 2019; Pettersson et al., 2011), and quasi-experimental (Cooper et al., 2017; Doernberg et al., 2015; Furuno et al., 2014; Gugkaeva & Franson, 2012; Jump et al., 2012; Linnebur et al., 2011; McMaughan et al., 2016; Rahme et al., 2016; Sloane et al., 2020c; Tandan et al., 2019; van Buul et al., 2015; Zabarsky et al., 2008; Zimmerman et al., 2014). Overall, the majority of studies (n = 13) included multiple facilities with sample sizes ranging from 3 to 46 NHs (Doernberg et al., 2015; Fleet et al., 2014; Furuno et al., 2014; Linnebur et al., 2011; Loeb et al., 2005; Monette et al., 2007; Naughton et al., 2001; Pasay et al., 2019; Pettersson et al., 2011; Sloane et al., 2020c; Tandan et al., 2019; van Buul et al., 2015; Zimmerman et al., 2014). Studies conducted within one NH (n = 6) reported either the number of residents (29–547) (Cooper et al., 2017; Gugkaeva & Franson, 2012; McMaughan et al., 2016) or beds (160–520) (Jump et al., 2012; Rahme et al., 2016; Zabarsky et al., 2008). Thirteen studies were conducted in the United States (Cooper et al., 2017; Doernberg et al., 2015; Furuno et al., 2014; Gugkaeva & Franson, 2012; Jump et al., 2012; Linnebur et al., 2011; McMaughan et al., 2016; Naughton et al., 2001; Rahme et al., 2016; Sloane et al., 2020c; Tandan et al., 2019; Zabarsky et al., 2008; Zimmerman et al., 2014); two in Canada (Monette et al., 2007; Pasay et al., 2019); followed by one each in Sweden (Pettersson et al., 2011), the United Kingdom (Fleet et al., 2014), and the Netherlands (van Buul et al., 2015); and one in the United States and Canada combined (Loeb et al., 2005). Five studies did not report data on antibiotic use (Doernberg et al., 2015; Pasay et al., 2019; Sloane et al., 2020c; Tandan et al., 2019; Zimmerman et al., 2014). Four studies reported antibiotic use (Jump et al., 2012; Loeb et al., 2005; Pettersson et al., 2011; Rahme et al., 2016); the remaining 10 studies reported either appropriate or inappropriate antibiotic use.

Quality Appraisal

In total, 10 studies were appraised as having a weak global rating score and high risk of bias (Cooper et al., 2017; Doernberg et al., 2015; Furuno et al., 2014; Gugkaeva & Franson, 2012; Jump et al., 2012; Linnebur et al., 2011; Naughton et al., 2001; Sloane et al., 2020c; van Buul et al., 2015; Zabarsky et al., 2008). Three studies had a moderate global rating score and high risk of bias (McMaughan et al., 2016; Rahme et al., 2016; Tandan et al., 2019), whereas four studies had a moderate global rating score and moderate risk of bias (Fleet et al., 2014; Pasay et al., 2019; Pettersson et al., 2011; Zimmerman et al., 2014). The final two studies had a strong global rating score and moderate risk of bias (Loeb et al., 2005; Monette et al., 2007). Studies were most successful in meeting the criteria for study design and data collection and were least successful in meeting the criteria for statistical adjustment for confounding, blinding to the intervention, and reporting withdrawals and drop-outs. Overall, the risk of bias of the body of studies included in the systematic review was weak to moderate.

Antibiotic Stewardship Interventions Across Studies

The majority of the studies reported multifaceted interventions (Supplementary Table 1, Appendix A). Education strategies including in-service training sessions, meetings, or written supportive materials were used in all but three studies (Gugkaeva & Franson, 2012; Jump et al., 2012; McMaughan et al., 2016), while guidelines for antibiotic stewardship informed interventions for nine studies (Cooper et al., 2017; Furuno et al., 2014; Linnebur et al., 2011; Loeb et al., 2005; Pettersson et al., 2011; Sloane et al., 2020c; Tandan et al., 2019; van Buul et al., 2015; Zabarsky et al., 2008). Four studies distributed pocket cards to prescribers (Loeb et al., 2005; Sloane et al., 2020c; Tandan et al., 2019; Zabarsky et al., 2008); three studies incorporated educational outreach and follow-up visits (Fleet et al., 2014; Jump et al., 2012; Loeb et al., 2005); and two studies participated in recording and reporting strategies (Gugkaeva & Franson, 2012; Sloane et al., 2020c). Four studies used feedback mechanisms to monitor interventions (Doernberg et al., 2015; Pettersson et al., 2011; Zabarsky et al., 2008; Zimmerman et al., 2014). Other included strategies were engaging infectious disease (ID) prescribers or ID pharmacists to develop interventions (Doernberg et al., 2015; Gugkaeva & Franson, 2012; Jump et al., 2012); enabling ID pharmacists-guided training (Linnebur et al., 2011; Pasay et al., 2019); using decision-making aids (McMaughan et al., 2016; Pasay et al., 2019); facilitating technical support (McMaughan et al., 2016); use of a telephone hotline (Rahme et al., 2016); providing continuing education credit (Sloane et al., 2020c); and developing antibiograms to guide antibiotic prescribing (Furuno et al., 2014; Rahme et al., 2016).

Effect of Intervention on MDROs, Antibiotic Prescribing Practices, and Resident Mortality

Six studies examined MDROs: Clostridium difficile, Klebsiella pneumoniae, Proteus spp., Enterobacteriaceae, Escherichia coli, and Methicillin-resistant Staphylococcus aureus before and after the intervention or in the intervention group. One study reported a significant decline in Clostridium difficile (p = .04) (Jump et al., 2012), another study found a reduction in Klebsiella pneumoniae, Proteus spp., and Enterobacteriaceae while Escherichia coli rates remained constant (Tandan et al., 2019). No significant effect was noted on MDRO (Doernberg et al., 2015; Rahme et al., 2016; Sloane et al., 2020c and resistance was high among Escherichia coli isolates (Furuno et al., 2014).

The odds of antibiotics being prescribed inappropriately decreased in four studies (Gugkaeva & Franson, 2012; Linnebur et al., 2011; McMaughan et al., 2016; Monette et al., 2007), whereas three studies reported no significant changes in antibiotic prescribing practices (Fleet et al., 2014; Furuno et al., 2014; van Buul et al., 2015). Although the majority of studies focused on initial implementation of the ASP interventions, three studies examined intervention sustainability. Pasay et al. (2019) performed a 1-year follow-up; however, the authors did not clearly comment on whether the intervention impact persisted. During the 2-year intervention and follow-up period, investigators found that a significant reduction in antibiotic prescribing can be achieved with ASPs. However, it may take years to see a reduction in MDROs (Sloane et al., 2020c). Finally, a significant reduction in inappropriate antibiotic use was maintained for 30 months after beginning the intervention (Zabarsky et al., 2008).

There were no significant differences in resident mortality after the intervention (Linnebur et al., 2011; Loeb et al., 2005; Naughton et al., 2001), whereas mortality rate significantly decreased in one study (95% confidence interval [CI], [−0.5, −0.1]; p = .002) (Pasay et al., 2019).

Meta-Analysis—Effect of Intervention on Antibiotic Use

Ten studies met the criteria for inclusion in the meta-analysis. Of these, five examined inappropriate antibiotic use (Cooper et al., 2017; Gugkaeva & Franson, 2012; McMaughan et al., 2016; Monette et al., 2007; Zabarsky et al., 2008); and six examined absolute differences between the intervention and control groups (Fleet et al., 2014; Linnebur et al., 2011; McMaughan et al., 2016; Monette et al., 2007; Naughton et al., 2001; van Buul et al., 2015). Table 1 provides data regarding inappropriate antibiotic use from each included study. Figure 2 illustrates a forest plot of the pooled decrease in inappropriate antibiotic use and represents data from 1,807 and 1,634 NH residents who were prescribed antibiotics for suspected infection before and after the intervention, respectively.

Table 1.

Inappropriate Antibiotic Use in Nursing Home Residents Before and After the Intervention.

Studies	Inappropriate antibiotic use pre (%)				Inappropriate antibiotic group post (%)			Change in inappropriate antibiotic use
Studies	Intervention group		Control group		Intervention group		Control group	Change in inappropriate antibiotic use
Author (year)	N	%	n	%	n	%	%	% [95% CI]
^a Cooper et al. (2017)	27	77.8	—	—	7	14.3	—	63.5 [33.0, 94.0]
^b Fleet et al. (2014)	135	88.5	117	87.4	—	80.7	94.9	15.3 [15.2, 15.4]
^{a b} Furuno et al. (2014)	96	68.0	—	—	72	55.0	—	13.0 [–2.0, 28.0]
^a Gugkaeva & Franson (2012)	20	40.0	—	—	19	21.0	—	19.0 [–9.0, 47.0]
^b Linnebur et al. (2011)	549	40.0	574	68.0	—	34.0	61.0	–1.0 [–1.1, –0.9]
McMaughan et al. (2016)	118	73.2	118	69.0	—	49.4	71.6	26.2 [25.9, 26.5]
Monette et al. (2007)	274	43.8	157	40.8	—	23.3	35.7	15.4 [15.2, 15.6]
^{a b} Naughton et al. (2001)	226	39.9	—	—	116	32.8	—	7.1 [–4.0, 18.0]
^b van Buul et al. (2015)	328	18.0	379	30.0	—	21.0	23.0	–10.0 [–10.1, –9.9]
^a Zabarsky et al. (2008)	34	67.6	—	—	75	44.0	—	23.6 [4.0, 43.0]

Note. CI = confidence interval.

One group quasi-experimental: pre-post design. ^b Measurement converted from appropriate antibiotic use.

Figure 2.

Forest plot of inappropriate antibiotic use in nursing home residents.

Inappropriate antibiotic use decreased following the intervention in eight of the 10 studies. Among the interventions to reduce inappropriate antibiotic use, education and algorithms promoting antibiotic stewardship for UTIs were most effective. Using a random effects model, the pooled decrease in inappropriate antibiotic use was 13.8% (95% CI: [4.7, 23.0]). Heterogeneity both between (I² = 99.9%) and within (Cochran Q = 166,837.8, p <.001) studies was greater than expected by chance alone. Removing one study from analysis (Zabarsky et al., 2008) did not alter the pooled result (pooled decrease 13.8%, 95% CI = [4.7, 23.0]).

Table 2 presents findings from the subgroup analysis. There were no significant differences in decrease in inappropriate antibiotic use by country in which the study was conducted, measurement of change in antibiotic use, intervention type, or study design. Heterogeneity may be partially explained by infection type and study quality. Decrease in inappropriate antibiotic use was highest in studies that examined change in antibiotic use for UTI (Cooper et al., 2017; McMaughan et al., 2016; Monette et al., 2007; Zabarsky et al., 2008) or were appraised to be of either strong or moderate quality (Fleet et al., 2014; McMaughan et al., 2016; Monette et al., 2007).

Table 2.

Subgroup Analysis of Inappropriate Antibiotic use in Nursing Home Residents.

Variable	Number of studies	Pooled result [95% CI]	p Value
Country where study was conducted
United States	7	19.3 [3.7, 34.9]
Outside United States	3	6.9 [–11.6, 25.4]	.32
Type of infection measured
Urinary tract infection	4	24.4 [15.1, 33.8]
Other infection type	3	–2.7 [–10.5, 5.1]
Not reported	3	15.3 [15.2, 15.4]	<.001
Measurement of change in antibiotic prescription
One group pre- post difference	4	27.0 [8.3, 45.7]
Absolute difference between intervention and control groups	6	8.9 [–1.9, 19.7]	.10
Study design
Randomized controlled trial	3	15.3 [15.2, 15.5]
Quasi-experimental	7	13.4 [3.5, 23.2]	.70
Intervention type
^aEducation	8	16.5 [4.2, 28.8]
^bOther	2	3.9 [–13.0, 20.8]	.24
Study quality
Strong	1	15.4 [15.2, 15.6]
Moderate	2	20.7 [15.2, 15.6]
Weak	7	4.9 [–1.7, 11.5]	.005

Note. CI = confidence interval.

Education = Group discussions, workshops, algorithms, decision-making aids, ^bOther = Pharmacist-led intervention and Resident antimicrobial management plan. p < .05; decrease in inappropriate antibiotic use was highest in those studies that examined change in antibiotic use for urinary tract infection or were deemed to be at lower risk of bias.

Figure 3 illustrates the funnel plot. Asymmetry is noted by three closed circles representing imputed studies. Rosenthal’s fail-safe N test indicates that 5,281 additional studies would need to be added to significantly alter the pooled decrease in inappropriate antibiotic use. However, following adjustment using the trim and fill method (three studies trimmed), the pooled estimate decreased to 7.3%, 95% CI = [−0.9, 15.5].

Figure 3.

Funnel plot representing observed and imputed studies.

Discussion and Implications

In this systematic review and meta-analysis, we assessed the effect of ASP interventions in NHs on antibiotic prescribing patterns, antibiotic use, MDROs, and mortality. Several interventions had clinically significant effects on these outcomes. Antibiotic stewardship interventions that focused on antibiotic use for UTI consistently demonstrated improvements in inappropriate antibiotic use. Through this meta-analysis, we were able to identify additional patterns that may provide some important insights to NHs and researchers.

Although a pooled estimate revealing a 13.8% decrease in inappropriate antibiotic use after implementation of an ASP is encouraging, publication bias was likely present. However, these findings suggest that antimicrobial stewardship interventions in NHs can lead to a modest change in inappropriate antibiotic use and improve adherence to recommended treatment guidelines (High et al., 2009). As explained by our test for heterogeneity, these findings were mostly driven by studies that assessed change in antibiotic use related to UTIs as opposed to studies that assessed pneumonia, respiratory tract infections, soft skin tissue infections, and sepsis of unknown origin. Because 50% of the studies included in our meta-analysis targeted UTIs and 30% of the included studies did not state a targeted infection, it is difficult to ascertain if it were the number of the studies targeting UTIs that drove these differences or the focus on UTIs itself. The literature does describe a series of infections, including UTIs, that have been treated prophylactically as an acceptable practice. Targeted approaches in these cases would seem most efficacious and appropriate to counteract unnecessary antibiotic treatment stemming from outdated accepted practices (Sloane et al., 2020a). Although UTIs are common in NHs, it is important to target other infections, such as skin or soft tissue infections where similar to UTIs, antibiotics are commonly used for prophylactic purposes for recurrent infections (Sloane et al., 2020b). An additional consideration is the assessment of other important infections such as pneumonia, the second most common infection in NHs, where specific guidelines for treatment are unclear (Herzig et al., 2017).

Most interventions that were assessed were categorized as educational; however, the educational approaches varied widely (e.g., surveillance tools, procedures, small group discussions). CDC recognizes that a variety of educational interventions can be used for disseminating antibiotic education information; however, interactive academic detailing (e.g., face-to-face interactive workshops) and the provision of feedback have been found to have the strongest evidence for improving medication prescribing practices (CDC, 2020). As NHs are implementing and modifying their ASPs, it is important that they consider incorporating interventions that have been found to be most efficacious.

In addition to education method, attention to who develops and receives the intervention is important to decrease inappropriate antibiotic prescribing. The CDC states that the most effective ASP educational intervention addresses both nursing staff and prescribers (CDC, 2020). Moreover, the 2016 CMS mandate for ASPs in NHs recognizes the core members of a multidisciplinary ASP to include an IP and a system to monitor antibiotic use. Only nine out of the 19 studies in our review explicitly stated that nurses were included as recipients of the educational intervention while 12 out of the 19 included at least one prescriber. Regarding the intervention development process, three studies included an ID physician and/or an ID pharmacist; however, none included nurses. Incorporating these experts in ASPs could impact antimicrobial use. For example, a recent study found that the presence of ID physicians and ID pharmacists significantly reduced total antimicrobial exposure among hospitalized patients (Livorsi et al., 2020).

Although ID specialists are efficacious in hospitals, however, it should not be assumed that their involvement will be similar in NHs. Unlike hospitals, ID specialists and physicians are usually not on-site in NHs, and pharmacists are only peripherally involved in care. This reality leads to much of the decision making and prescribing taking place via telephone and is based on observations and communication by on-site nursing staff (Crnich et al., 2015). Furthermore, it is challenging to translate hospital findings to NHs for reasons such as limited availability of infection control resources and infection control specialists, lack of ready access to many tests and consultations, and high prevalence of dementia (making it more difficult to obtain medical histories) (Sloane et al., 2020b).

Research and Practice Change Implications

As found in our review, the body of evidence around ASPs is weak. High-quality data on ASPs is needed to guide practice change and program implementation. When conducting studies, investigators should use the CONsolidated standards of reporting trials (CONSORT) and transparent reporting of evaluations with nonrandomized designs (TREND) guidelines to guide and report the design of RCTs and quasi-experimental studies.[AQ6] In addition, now that CMS is requiring that all NHs implement ASPs and the CDC has listed seven core elements essential to an ASP, it is important to assess the efficacy of these changes on antibiotic use (Nicolle, 2014). In a national survey describing the current state of ASPs in NHs, researchers found that antibiotic stewardship implementation had increased after these changes; however, there is still a need to ensure that staff are adequately trained (Stone et al., 2018). Although it is promising that most NHs who participated in the national survey had at least moderately comprehensive ASPs defined as four or five of the seven CDC core elements (Fu et al., 2020), it is possible that respondents were higher performing NHs. Finally, inappropriate antibiotic use has led to fungal infections in NH residents (Montoya et al., 2016). None of the studies assessed fungal infections, suggesting that fungal infections should be included in antibiotic stewardship guidelines to help curb antimicrobial resistance.

Strengths and Limitations

There are several strengths in the design of our study. First, our inclusion criteria that limited our review to quasi-experimental designs and randomized control studies allowed for an analysis of more high-quality studies. Second, we kept our search criteria wide in regard to publication year of the article, which allowed us to capture and compare interventions over time. Third, we included a broad range of ASPs and outcomes, which allowed us to assess the differential effects of ASP interventions on a variety of outcomes.

This systematic review has a number of limitations. Only six out of the 19 studies were RCTs, and approximately half of the studies had methodological weaknesses and high risk of bias. Second, only three of the 19 studies commented on whether the intervention effect lasted after the study period. Future studies should focus on what strategies will lead to sustainable practice change. Finally, because most of the studies pre-date the CMS mandate, there may be a temporal effect on our findings. Nonetheless, we found that ASP interventions result in a small, but statistically significant decrease in inappropriate antibiotic use in NHs.

Conclusion

With a high prevalence of infections and antibiotic use in NHs, ASP interventions are imperative to promote appropriate antibiotic use and reduce the spread of infections and microbial resistance. ASP interventions led to a 13.8% decline in inappropriate antibiotic use suggesting the need for enhanced ASP implementation. Findings of this systematic review and meta-analysis must be interpreted with caution due to methodological weaknesses noted in the included studies. Most did not involve ID experts or nurses when developing interventions, use efficacious educational strategies, or direct the intervention to the appropriate interdisciplinary staff. In the future, NHs should adhere to ASP guidelines to effectively assess their effects on inappropriate antibiotic use.

Supplemental Material

sj-pdf-1-jag-10.1177_07334648211018299 – Supplemental material for Antimicrobial Stewardship Interventions to Optimize Treatment of Infections in Nursing Home Residents: A Systematic Review and Meta-Analysis

Supplemental material, sj-pdf-1-jag-10.1177_07334648211018299 for Antimicrobial Stewardship Interventions to Optimize Treatment of Infections in Nursing Home Residents: A Systematic Review and Meta-Analysis by Sainfer Aliyu, Jasmine L. Travers, S. Layla Heimlich, Joanne Ifill and Arlene Smaldone in Journal of Applied Gerontology

Supplemental Material

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Supplemental material, sj-pdf-2-jag-10.1177_07334648211018299 for Antimicrobial Stewardship Interventions to Optimize Treatment of Infections in Nursing Home Residents: A Systematic Review and Meta-Analysis by Sainfer Aliyu, Jasmine L. Travers, S. Layla Heimlich, Joanne Ifill and Arlene Smaldone in Journal of Applied Gerontology

Supplemental Material

sj-pdf-3-jag-10.1177_07334648211018299 – Supplemental material for Antimicrobial Stewardship Interventions to Optimize Treatment of Infections in Nursing Home Residents: A Systematic Review and Meta-Analysis

Supplemental material, sj-pdf-3-jag-10.1177_07334648211018299 for Antimicrobial Stewardship Interventions to Optimize Treatment of Infections in Nursing Home Residents: A Systematic Review and Meta-Analysis by Sainfer Aliyu, Jasmine L. Travers, S. Layla Heimlich, Joanne Ifill and Arlene Smaldone in Journal of Applied Gerontology

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Sainfer Aliyu

Jasmine L. Travers

Supplemental Material

Supplemental material for this article is available online.

References

Aliyu

Smaldone

Larson

(2017). Prevalence of multidrug-resistant gram-negative bacteria among nursing home residents: A systematic review and meta-analysis. American Journal of Infection Control, 45(5), 512–518. https://doi.org/10.1016/j.ajic.2017.01.022

Baur

Gladstone

B. P.

Burkert

Carrara

Foschi

Döbele

Tacconelli

(2017). Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: A systematic review and meta-analysis. The Lancet Infectious Diseases, 17(9), 990–1001. https://doi.org/10.1016/S1473-3099(17)30325-0

Centers for Disease Control and Prevention. (2015). The core elements of antibiotic stewardship for nursing homes.

Centers for Disease Control and Prevention. (2019). Antibiotic resistant threats in the United States. U.S. Department of Health and Human Services.

Centers for Disease Control and Prevention. (2020). The core elements of antibiotic stewardship for nursing homes. https://www.cdc.gov/longtermcare/prevention/antibiotic-stewardship.html

Centers for Medicare & Medicaid Services. (2016). Reform of requirements for long-term care facilities: Final rule (CMS-3260-P), 2016. https://www.federalregister.gov/documents/2016/10/04/2016-23503/medicare-and-medicaid-programs-reform-of-requirements-forlong-term-care-facilities

Cooper

Faan

Struble

Redman

(2017). A multifaceted, evidence-based program to reduce inappropriate antibiotic treatment of suspected urinary tract infections. Annals of Long-Term Care, 25, 36–43.

Crayton

Richardson

Fuller

Smith

Liu

Forbes

Anderson

Shallcross

Michie

Hayward

Lorencatto

(2020). Interventions to improve appropriate antibiotic prescribing in long-term care facilities: A systematic review. BMC Geriatrics, 20(1), Article 237. https://doi.org/10.1186/s12877-020-01564-1

Crnich

C. J.

Jump

Trautner

Sloane

P. D.

Mody

(2015). Drugs optimizing antibiotic stewardship in nursing homes: A narrative review and recommendations for improvement. Aging, 32, 699–716.

10.

Daneman

Gruneir

Bronskill

S. E.

Newman

Fischer

H. D.

Rochon

P. A.

Anderson

G. M.

Bell

C. M.

(2013). Prolonged antibiotic treatment in long-term care: Role of the prescriber. JAMA Internal Medicine, 173(8), 673–682.

11.

Doernberg

S. B.

Dudas

Trivedi

K. K.

(2015). Implementation of an antibiotic stewardship program targeting residents with urinary tract infections in three community long-term care facilities: A quasi-experimental study using time-series analysis. Antimicrobial Resistance and Infection Control, 4, Article 54. https://doi.org/10.1186/s13756-015-0095-y

12.

Duval

Tweedie

(2000). Trim and fill: A simple funnel-plot–based method of testing and adjusting for publication bias in meta-analysis. Biometrics, 56, 455–463.

13.

Feldstein

Sloane

P. D.

Feltner

(2018). Antibiotic stewardship programs in nursing homes: A systematic review. Journal of the American Medical Directors Association, 19(2), 110–116. https://doi.org/10.1016/j.jamda.2017.06.019

14.

Fleet

Rao

G. G.

Patel

Cookson

Charlett

Bowman

Davey

(2014). Impact of implementation of a novel antimicrobial stewardship tool on antibiotic use in nursing homes: A prospective cluster randomized control pilot study. Journal of Antimicrobial Chemotherapy, 69(8), 2265–2273. https://doi.org/10.1093/jac/dku115

15.

C. J.

Mantell

Stone

P. W.

Agarwal

(2020). Characteristics of nursing homes with comprehensive antibiotic stewardship programs: Results of a national survey. American Journal of Infection Control, 48(1), 13–18. https://doi.org/10.1016/j.ajic.2019.07.015

16.

Furuno

J. P.

Comer

A. C.

Johnson

J. K.

Rosenberg

J. H.

Moore

S. L.

MacKenzie

T. D.

Hall

K. K.

Horshon

J. M.

(2014). Using antibiograms to improve antibiotic prescribing in skilled nursing homes. Infection Control and Hospital Epidemiology, 35(Suppl. 3), S56–61. https://doi.org/10.1086/677818

17.

Gugkaeva

Franson

(2012). Pharmacist-led model of antibiotic stewardship in a long-term care facility. Annals of Long-Term Care: Clinical Care and Aging, 20(10), 22–26.

18.

Herzig

C. T. A.

Dick

A. W.

Sorbero

(2017). Infection trends in US nursing homes, 2006-2013. Journal of the American Medical Directors Association, 18(7), 635.e9–635.e20.

19.

Higgins

J. P.

Thompson

S. G.

Deeks

J. J.

Altman

D. G.

(2003). Measuring inconsistency in meta-analyses. British Medical Journal, 327(7414), 557–560. https://doi.org/10.1136/bmj.327.7414.557

20.

High

K. P.

Bradley

S. F.

Gravenstein

Mehr

D. R.

Quagliarello

V. J.

Richards

Yoshikawa

T. T.

(2009). Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 48(2), 149–171. https://doi.org/10.1086/595683

21.

Hui-Chih Wu

Langford

B. J.

Daneman

Friedrich

J. O.

Garber

(2019). Antimicrobial stewardship programs in long-term care settings: A meta-analysis and systematic review. Journal of the American Geriatrics Society, 67, 392–399.

22.

Jester

D. J.

Peterson

L. J.

Dosa

D. M.

Hyer

(2020). Infection control citations in nursing homes: Compliance and geographic variability. Journal of the American Medical Directors Association, S1525-8610(20), 30974–30979. https://doi.org/10.1016/j.jamda.2020.11.010

23.

Jump

R. L. P.

Gaur

Katz

M. J.

Crnich

C. J.

Dumyati

Ashraf

M. S.

Frentzel

Schweon

S. J.

Sloane

Nace

& Infection Advisory Committee for AMDA—The Society of Post-Acute and Long-Term Care Medicine. (2017). Template for an antibiotic stewardship policy for post-acute and long-term care settings: Infection advisory committee for AMDA—The society of post-acute and long-term care medicine. Journal of the American Medical Directors Association, 18(11), 913–920. https://doi.org/10.1016/j.jamda.2017.07.018

24.

Jump

R. L. P.

Olds

D. M.

Seifi

Kypriotakis

Jury

L. A.

Peron

E. P.

Hirsch

A. A.

Drawz

P. E.

Watts

Bonomo

R. A.

Donskey

C. J.

(2012). Effective antimicrobial stewardship in a long-term care facility through an infectious disease consultation service: Keeping a LID on antibiotic use. Infection Control and Hospital Epidemiology, 33(12), 1185–1192. https://doi.org/10.1086/668429

25.

Linnebur

S. A.

Fish

D. N.

Ruscin

J. M.

Radcliff

T. A.

Oman

K. S.

Fink

Van Dorsten

Liebrecht

Fish

McNulty

Hutt

(2011). Impact of a multidisciplinary intervention on antibiotic use for nursing home-acquired pneumonia. American Journal of Geriatric Pharmacotherapy, 9(6), 442–450e1. https://doi.org/10.1016/j.amjopharm.2011.09.009

26.

Livorsi

D. J.

Nair

Lund

B. C.

Alexander

Beck

B. F.

Goto

Ohl

Vaughan-Sarrazin

M. S.

Goetz

M. B.

Perencevich

E. N.

(2020). Antibiotic stewardship implementation and antibiotic use at hospitals with and without on-site infectious disease specialists. Clinical Infectious Diseases, ciaa388. https://doi.org/10.1093/cid/ciaa388

27.

Loeb

Bentley

D. W.

Bradley

Crossley

Garibaldi

Gantz

McGeer

Muder

R. R.

Mylotte

Nicolle

L. E.

Nurse

Paton

Simor

A. E.

Smith

Strausbaugh

(2001). Development of minimum criteria for the initiation of antibiotics in residents of long-term-care facilities: Results of a consensus conference. Infection Control and Hospital Epidemiology, 22(2), 120–124. https://doi.org/10.1086/501875

28.

Loeb

Brazil

Lohfeld

McGeer

Simor

Stevenson

Zoutman

Smith

Liu

Walter

S. D.

(2005). Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes: Cluster randomised controlled trial. British Medical Journal, 331(7518), Article 669.

29.

McGeer

Campbell

Emori

T. G.

Hierholzer

W. J.

Jackson

M. M.

Nicolle

L. E.

Peppler

Rivera

Schollenberger

D. G.

Simor

A. E.

Smith

P. W.

Wang

E. E.-L.

(1991). Definitions of infection for surveillance in long-term care facilities. American Journal of Infection Control, 19(1), 1–7. https://doi.org/10.1016/0196-6553(91)90154–5

30.

McMaughan

D. K.

Nwaiwu

Zhao

Frentzel

Mehr

Imanpour

Garfinkel

Phillips

C. D.

(2016). Impact of a decision-making aid for suspected urinary tract infections on antibiotic overuse in nursing homes. BMC Geriatrics, 16, Article 81.

31.

Moher

Liberati

Tetzlaff

Altman

D. G.

(2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Annals of Internal Medicine, 151(4), 264–269.

32.

Monette

Miller

M. A.

Monette

Laurier

Boivin

J. F.

Sourial

Le Cruguel

J. P.

Vandal

Cotton-Montpetit

(2007). Effect of an educational intervention on optimizing antibiotic prescribing in long-term care facilities. Journal of the American Geriatrics Society, 55(8), 1231–1235.

33.

Montoya

Cassone

Mody

(2016). Infections in nursing homes: Epidemiology and prevention programs. Clinics in Geriatric Medicine, 32(3), 585–607. https://doi.org/10.1016/j.cger.2016.02.004.

34.

National Collaborating Centre for Methods and Tools. (2004). Qualty assessment tool for quantitative studies. Resource details | National Collaborating Centre for Methods and Tools. https://wwwnccmt.ca/knowledge-repositories/search/14.

35.

Naughton

B. J.

Mylotte

J. M.

Ramadan

Karuza

Priore

R. L.

(2001). Antibiotic use, hospital admissions, and mortality before and after implementing guidelines for nursing home-acquired pneumonia. Journal of the American Geriatrics Society, 49(8), 1020–1024.

36.

Nicolle

L. E.

(2014). Antimicrobial stewardship in long-term care facilities: What is effective? Antimicrobial Resistance and Infection Control, 3(1), 6.

37.

Pasay

D. K.

Guirguis

M. S.

Shkrobot

R. C.

Slobodan

J. P.

Wagg

A. S.

Sadowski

C. A.

Conly

J. M.

Saxinger

L. M.

Bresee

L. C.

(2019). Antimicrobial stewardship in rural nursing homes: Impact of interprofessional education and clinical decision tool implementation on urinary tract infection treatment in a cluster randomized trial. Infection Control and Hospital Epidemiology, 40(4), 432–437. https://doi.org/10.1017/ice.2019.9

38.

Patsopoulos

N. A.

Evangelou

Ioannidis

J. P. A.

(2008). Sensitivity of between-study heterogeneity in meta-analysis: Proposed metrics and empirical evaluation. International Journal of Epidemiology, 37, 1148–1157.

39.

Persaud

(1996). Misleading meta-analysis: “Fail safe N” is a useful mathematical measure of the stability of results. British Medical Journal, 312(7023), Article 125.

40.

Pettersson

Vernby

Mölstad

Lundborg

C. S.

(2011). Can a multifaceted educational intervention targeting both nurses and physicians change the prescribing of antibiotics to nursing home residents? A cluster randomized controlled trial. Journal of Antimicrobial Chemotherapy, 66(11), 2659–2666. https://doi.org/10.1093/jac/dkr312

41.

Raban

M. Z.

Gasparini

Baysari

M. T.

Westbrook

J. I.

(2020). Effectiveness of interventions targeting antibiotic use in long-term aged care facilities: A systematic review and meta-analysis. BMJ Open, 10(1), Article e028494. https://doi.org/10.1136/bmjopen-2018-028494

42.

Rahme

C. L.

Jacoby

H. M.

Avery

(2016). Impact of a hospital’s antibiotic stewardship team on fluoroquinolone use at a long-term care facility. Annals of Long-Term Care: Clinical Care and Aging, 24(6), 13–20.

43.

Richardson

Garner

Donegan

(2019). Interpretation of subgroup analyses in systematic reviews: A tutorial. Clinical Epidemiology and Global Health, 7, 192–198.

44.

Sloane

P. D.

Tandan

Zimmerman

(2020a). Preventive antibiotic use in nursing homes: A not uncommon reason for antibiotic overprescribing. Journal of the American Medical Directors Association, 21, P1181–P1185. https://doi.org/10.1016/j.jamda.2020.07.026

45.

Sloane

P. D.

Zimmerman

Nace

(2020b). Progress and challenges in the management of nursing home infections. Journal of the American Medical Directors Association, 21, 1–14. https://doi.org/10.1016/j.jamda.2019.11.025

46.

Sloane

P. D.

Zimmerman

Ward

Kistler

C. E.

Paone

Weber

D. J.

Wretman

C. J.

Preisser

J. S.

(2020c). A 2-year pragmatic trial of antibiotic stewardship in 27 community nursing homes. Journal of the American Geriatrics Society, 68(1), 46–54. https://doi.org/10.1111/jgs.16059

47.

Stone

Agarwal

Pogorzelska-Maziarz

(2020). Infection preventionist staffing in nursing homes. American Journal of Infection Control, 48(3), 330–332.

48.

Stone

Herzig

C. T. A.

Agarwal

Pogorzelska-Maziarz

Dick

(2018). Nursing home infection control program characteristics, CMS citations, and implementation of antibiotic stewardship policies: A national study. Nursing Home Performance. https://cancerres.unboundmedicine.com/medline/citation/29806527/Nursing_Home_Infection_Control_Program_Characteristics_CMS_Citations_and_Implementation_of_Antibiotic_Stewardship_Policies:_A_National_Study_

49.

Tandan

Sloane

P. D.

Ward

Weber

D. J.

Vellinga

Kistler

C. E.

Zimmerman

(2019). Antimicrobial resistance patterns of urine culture specimens from 27 nursing homes: Impact of a two-year antimicrobial stewardship intervention. Infection Control and Hospital Epidemiology, 40(7), 780–786. https://doi.org/10.1017/ice.2019.108

50.

van Buul

L. W.

van der Steen

J. T.

Achterberg

W. P.

Schellevis

F. G.

Essink

R. T. G. M.

de Greeff

S. C.

Natsch

Sloane

P. D.

Zimmerman

Twisk

J. W. R.

Veenhuizen

R. B.

Hertogh

C. M. P. M

. (2015). Effect of tailored antibiotic stewardship programmes on the appropriateness of antibiotic prescribing in nursing homes. Journal of Antimicrobial Chemotherapy, 70(7), 2153–2162. https://doi.org/10.1093/jac/dkv051

51.

van Buul

L. W.

van der Steen

J. T.

Veenhuizen

R. B.

Achterberg

W. P.

Schellevis

F. G.

Essink

R. T.

van Benthem

B. H.

Natsch

Hertogh

C. M

. (2012). Antibiotic use and resistance in long term care facilities. Journal of the American Medical Directors Association, 13(6), 568.E1–568.E13. https://doi.org/10.1016/j.jamda.2012.04.004

52.

Zabarsky

T. F.

Sethi

A. K.

Donskey

C. J.

(2008). Sustained reduction in inappropriate treatment of asymptomatic bacteriuria in a long-term care facility through an educational intervention. American Journal of Infection Control, 36(7), 476–480. https://doi.org/10.1016/j.ajic.2007.11.007

53.

Zimmerman

Sloane

P. D.

Bertrand

Olsho

L. E.

Beeber

Kistler

Hadden

Edwards

Weber

D. J.

Mitchell

C. M.

(2014). Successfully reducing antibiotic prescribing in nursing homes. Journal of the American Geriatrics Society, 62(5), 907–912. https://doi.org/10.1111/jgs.1278

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