Implementation of Infectious Diseases Rapid Molecular Diagnostic Tests and Antimicrobial Stewardship Program Involvement in Acute Care Hospitals

Abstract

A survey of acute care hospitals found that rapid molecular diagnostic tests (RMDT) have been widely adopted. Although many hospitals use their antimicrobial stewardship team and/or guidelines to help clinicians interpret results and optimize treatment, opportunities to more fully achieve the potential benefits of RMDT remain.

Rapid molecular diagnostic tests (RMDT) identify the microorganism(s) causing an infection faster than traditional microbiology methods, allowing for earlier optimization of antimicrobial therapy. A meta-analysis of 31 studies found that use of RMDT in bloodstream infections (BSI), compared to conventional microbiologic methods alone, was associated with reduced time to effective therapy, mortality risk, and length of stay.¹ However, the mortality reduction was statistically significant only in the presence of antimicrobial stewardship program (ASP) involvement. The impact of RMDT on outcomes of other types of infection is less clear.^2-4

The extent to which RMDT have been adopted by hospitals and the degree to which ASPs are involved in RMDT interpretation and subsequent interventions are unknown. We conducted a survey to assess prevalence of RMDT use, examine factors associated with RMDT adoption, and describe antimicrobial and diagnostic stewardship efforts related to RMDT .

Methods

The survey was developed based on previous studies of RMDT and optimized via pilot testing by hospital epidemiologists and clinical microbiologists from six hospitals. The final version is available in the Supplemental Material. The survey was emailed to members of the SHEA Research Network (SRN)⁵ and the American Society for Microbiology ClinMicroNet listserv (CMN)⁶ and administered May-July 2019 using Qualtrics software (Qualtrics, Provo, UT). Participation was voluntary and anonymous. Unlike SRN, multiple individuals from a hospital may participate in CMN. We requested that only one member per institution respond to the survey. Because some hospitals participate in SRN and CMN, results from each survey were reported separately. Data were analyzed using Stata/IC 16 (StataCorp, College Station, TX) and Excel 2016 (Microsoft, Redmond, WA). Associations between hospital characteristics and RMDT adoption were assessed using Pearson’s chi-square. The Weill Cornell Medicine Institutional Review Board granted an exemption to this study.

Results

Responses were received from 57 SRN (response rate: 59%) and 90 CMN members (response rate is incalculable because the number of unique institutions participating in CMN is unknown). Table 1 summarizes the characteristics of participating hospitals. The majority were from the US, academic, urban, part of a multi-hospital system, and had an on-site clinical microbiology laboratory.

Table 1.

Characteristics of participating hospitals

	SRN (n=57)	CMN (n=90)
Type of hospital
Academic	41 (72%)	62 (69%)
Non-academic	16 (28%)	28 (31%)
Number of beds
<100	1 (2%)	1 (1%)
101-500	28 (49%)	27 (30%)
501-900	13 (23%)	37 (41%)
>900	15 (26%)	25 (28%)
Region
US	44 (77%)	82 (91%)
West	7 (12%)	6 (7%)
Midwest	12 (21%)	18 (20%)
South	14 (25%)	38 (42%)
Northeast	11 (19%)	20 (22%)
Outside of the US	13 (23%)	8 (9%)
Population
>1 million	35 (61%)	63 (70%)
250,000-1 million	16 (28%)	15 (17%)
<250,000	6 (10%)	12 (13%)
Health system
Part of a multiple health system	37 (65%)	67 (74%)
Independent, single institution	20 (35%)	23 (26%)
Clinical microbiology laboratory
On-site	46 (81%)	76 (84%)
Off-site, centralized health system laboratory	8 (14%)	11 (12%)
Off-site, commercial/reference laboratory	3 (5%)	3 (3%)
The highest training background of the microbiology director
PhD	19 (41%)	47 (62%)
MD/DO with training in pathology	17 (37%)	25 (33%)
MD/DO with training in infectious diseases	10 (22%)	9 (12%)
Master’s Degree or Bachelor’s Degree	4 (9%)	4 (5%)

Abbreviations: CMN, ClinMicroNet of American Society for Microbiology Listserv; SRN, The Society for Healthcare Epidemiology of America Research Network

RMDT for BSI

Fifty (88%) SRN and 73 (81%) CMN hospitals used at least one RMDT for BSI. There were no significant associations between characteristics of participating institutions (e.g., hospital type, number of beds, region) and adoption of RMDT. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and multiplex polymerase chain reaction (PCR) were the most commonly adopted RMDT (Table 2). Factors frequently reported to have been important in the decision to adopt RMDT included: anticipated improvement in antimicrobial use (SRN-82%; CMN-68%), clinical outcomes (SRN-74%; CMN-77%), laboratory efficiency (SRN-52%; CMN-34%), and overall hospital cost savings (SRN-24%; CMN-37%). Twenty-four (48%) SRN and 37 (51%) CMN hospitals had evaluated the impact of RMDT. Reported findings included reduced time to antimicrobial de-escalation (SRN-75%; CMN-92%), reduced length of stay (SRN-25%; CMN-41%), improved laboratory efficiency (SRN-20%; CMN-19%), and overall cost reduction (SRN-13%; CMN-32%). Approximately one-quarter of participants reported a laboratory-based cost increase. Among hospitals that did not use RMDT, the most commonly cited reasons for non-use were cost, lack of evidence of improved outcomes, inadequate insurance reimbursement, and insufficient laboratory space.

Table 2.

Type(s) of rapid molecular diagnostic tests used for diagnosis of bloodstream infections and non-bloodstream infections at participating hospitals^*

	SRN (n = 57)	CMN (n = 90)
Bloodstream infection
MALDI-TOF MS of organisms recovered on solid media after subculture from blood culture broth	32 (56%)	58 (64%)
Multiplex PCR	31 (54%)	54 (60%)
Microarray-based test	19 (33%)	21 (23%)
MALDI-TOF MS directly from positive blood culture broth	19 (33%)	16 (18%)
Rapid FISH/phenotypic-based antimicrobial susceptibility testing	5 (9%)	9 (10%)
Magnetic resonance	2 (4%)	4 (4%)
Peptide nucleic acid-fluorescent in situ hybridization	1 (2%)	10 (11%)
Other	4 (7%)	4 (4%)
None	7 (12%)	16 (18%)
No response	1 (2%)	1 (1%)
Non-bloodstream infection
Clostridioides difficile stool PCR (as either stand-alone test or as part of multi-step testing algorithm)	48 (84%)	77 (86%)
Multiplex PCR – Respiratory pathogen panel	47 (82%)	73 (81%)
Multiplex PCR – Mycobacterium tuberculosis	39 (68%)	56 (62%)
MALDI-TOF MS of organisms recovered on solid media	36 (63%)	77 (86%)
Multiplex PCR - Meningitis/encephalitis panel	35 (61%)	41 (46%)
Multiplex PCR - Gastrointestinal panel	33 (58%)	53 (59%)
Multiplex PCR – Lower respiratory infection panel	12 (21%)	11 (12%)
Other	4 (7%)	13 (14%)
None	1 (2%)	0 (0%)
No response	4 (7%)	7 (8%)

^*The results include either on-site or off-site utilization of these tests.

Abbreviations: CMN, ClinMicroNet of American Society for Microbiology Listserv; MALDI-TOF MS, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; NAAT, nucleic acid amplification test; RMDT, rapid molecular diagnostic tests; SRN, The Society for Healthcare Epidemiology of America Research Network, PCR, polymerase chain reaction

Among hospitals with RMDT for BSI, the laboratory of 40 (80%) SRN and 57 (78%) CMN hospitals directly notified clinical staff of RMDT results. Approximately 50% of those notified the ASP (Supplemental Table 1). Among 47 SRN and 63 CMN hospitals with both RMDT and ASP, 37 (79%) and 52 (83%), respectively, reported that the ASP team routinely reviewed BSI RMDT results. The frequency of review ranged from at least once per week to 24 hours/day, 7 days/week (Supplemental Table 2). Additionally, 27 (54%) SRN and 31 (42%) CMN hospitals provided guidelines for optimization of therapy based upon RMDT results. The location of guidelines varied and included a website, the electronic medical record, and a handbook (Supplemental Table 1).

RMDT for non-BSI

Fifty-two (91%) SRN and 83 (92%) CMN hospitals used one or more RMDT for non-BSI. Clostridioides difficile nucleic acid amplification tests and multiplex PCR for respiratory pathogens were the most commonly adopted tests (Table 2). There were no significant associations between hospital characteristics and adoption of RMDT for non-BSI. Less than half of hospitals had guidelines to assist clinicians in interpreting RMDT results (Supplemental Table 3). Some hospitals restricted clinicians’ ability to order non-BSI RMDT based on factors such as nosocomial versus community-acquired infection, medical condition (e.g., immunocompromised host), recent testing, and requirement for authorization (Supplemental Table 4).

Discussion

RMDT for BSI and non-BSI have been widely adopted by the surveyed hospitals. Consistent with previously published observational studies,¹ many participants reported positive clinical, logistic and financial outcomes in association with implementation of RMDT for BSI. While RMDT may reduce overall healthcare costs, the majority of hospitals without RMDT for BSI reported the cost of new technology as the reason RMDT had not been implemented, perhaps due to budgetary silos which may not account for potential overall cost savings.⁷ Some participants indicated that their hospital had restricted use of RMDT for non-BSI to specific clinical scenarios and/or patient populations in which the result is mostly likely to provide clinical benefit. Such diagnostic stewardship strategies may help to maximize the healthcare value of RMDT.^7-9

Previous studies suggest that RMDT-based ASP interventions can reduce mortality and time to effective therapy and improve antimicrobial use in BSI to a greater extent than use of RMDT alone.¹ We found that in the majority of hospitals with RMDT for BSI the ASP team routinely reviewed RMDT results and that the laboratory directly notified the ASP team of the results in about half of these hospitals. Other reports suggest that guidelines for RMDT interpretation and antimicrobial selection may help hospitals achieve the benefits of RMDT.^7,10 However, clinicians must utilize these guidelines in order for them to impact clinical care.¹⁰ Approximately 50% of participating hospitals reported having guidelines for BSI RMDT and fewer had guidelines for non-BSI RMDT. Although utilization of these guidelines was not assessed, there were differences among hospitals in terms of their availability, with guidelines being located within the laboratory results section of the electronic medical record, the location that provides the easiest access to clinicians within their usual workflow, in <40% of hospitals. Thus, there appeared to be opportunities to improve availability of and access to these clinical decision support tools.

Our study has limitations. The relatively small sample size potentially limits the generalizability of the findings and the ability to detect differences between hospitals that had and had not adopted RMDT. The findings may not be applicable to small, non-academic hospitals in rural settings or outside the US. Participation was voluntary, possibly leading to participation bias. Finally, we cannot be certain that CMN data does not contain multiple responses from individual institutions.

In conclusion, RMDT for BSI and non-BSI have been widely adopted by the participating hospitals and many reported they had observed positive clinical, logistic and financial outcomes associated with implementation of these tests. While the majority of hospitals involved their ASP and/or have developed clinical guidelines to increase the likelihood that RMDT results will lead to timely and appropriate interventions, opportunities to more fully realize the benefits of RMDT remain in many hospitals.