Benefits of Adding a Rapid PCR-Based Blood Culture Identification Panel to an Established Antimicrobial Stewardship Program

Abstract

Bloodstream infections (BSI) are an important cause of morbidity and mortality (1). The rise of antimicrobial-resistant organisms in recent years warrants empirical use of broad-spectrum antimicrobials for patients with suspicion of serious infections, including BSI, until organism identification and antimicrobial susceptibility data become available (2). Unfortunately, conventional organism identification and susceptibility reporting require 48 to 72 h to produce final results, leading to a substantial delay in the receipt of appropriate antimicrobial therapy, which has been shown to negatively impact patient outcomes, particularly in the setting of multidrug-resistant organisms (3, 4). That the delay in de-escalation of antimicrobial therapy for infections caused by susceptible organisms can result in longer durations of exposure of these patients to broader-spectrum agents, which may lead to development of resistance, Clostridium difficile infections, microbiome disruption, and increased costs, is equally troubling (5, 6).Several approaches can provide organism identification and detect antimicrobial resistance genes within hours of blood culture positivity, allowing earlier and more effective antimicrobial therapy (7,8). These include fluorescence in situ hybridization, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, and nucleic acid hybridization and amplification assays. Comprehensive, panel-based molecular diagnostic assays that detect all of the major bloodstream pathogens and selected antimicrobial resistance genes are now available for direct testing of positive blood cultures (9, 10, 11). A number of examples in the literature suggest that shortening the time to appropriate therapy due to rapid diagnostic tests may lessen the clinical and economic burden of BSI (12). The greatest impact of rapid diagnostic tests appears to occur when the tests are implemented in combination with antimicrobial stewardship program (ASP) intervention to ensure that the test result is acted on in a timely manner (12). In fact, a recent prospective clinical trial by Banerjee et al. that evaluated a rapid multiplex PCR blood culture identification panel (BCID) found that while BCID reported with templated comments resulted in optimized antibiotic use compared to controls without BCID, the addition of ASP intervention enhanced rates of antimicrobial de-escalation (13).The purpose of the present study was to evaluate the impact of BCID in combination with ASP intervention on antimicrobial use and the clinical and economic outcomes of patients with bloodstream infections compared to conventional organism identification techniques. To account for the incremental contribution of each individual constituent (ASP or BCID) to the study endpoints, three analysis groups were compared: convention organism identification, conventional organism identification with ASP intervention group, and BCID with ASP intervention.

Assessment of Rapid-Blood-Culture-Identification Result Interpretation and Antibiotic Prescribing Practices

“…A study by MacVane and Nolte (12) evaluated the incremental impact of antimicrobial stewardship and BCID by analyzing three groups: conventional organism identification (control group), conventional organism identification with antimicrobial stewardship intervention, and BCID with antimicrobial stewardship intervention. This study showed that antimicrobial stewardship intervention with bloodstream infections improved antibiotic de-escalation but had little impact on the time to effective antimicrobial therapy compared with the control group (12). More striking was the finding that BCID with the antimicrobial stewardship group had a significantly reduced time to effective antibiotic therapy (4.9 h) versus the conventional organism identification/antimicrobial stewardship group (13 h) and the control group (15 h) (12).…”

“…This study showed that antimicrobial stewardship intervention with bloodstream infections improved antibiotic de-escalation but had little impact on the time to effective antimicrobial therapy compared with the control group (12). More striking was the finding that BCID with the antimicrobial stewardship group had a significantly reduced time to effective antibiotic therapy (4.9 h) versus the conventional organism identification/antimicrobial stewardship group (13 h) and the control group (15 h) (12).…”

Effect of Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry (MALDI-TOF MS) Alone versus MALDI-TOF MS Combined with Real-Time Antimicrobial Stewardship Interventions on Time to Optimal Antimicrobial Therapy in Patients with Positive Blood Cultures

“…Despite having the ability to obtain blood culture results up to 1.5 days faster than traditional identification methods, this study shows that without real-time AMS intervention, treatment optimization was significantly delayed. Several studies have established that the use of mRDT in settings with ASPs and microbiology result analysis improves the time to antimicrobial streamlining and various patient outcomes compared to traditional methods of organism identification (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

The Added Cost of Rapid Diagnostic Testing and Active Antimicrobial Stewardship: Is It Worth It?

“…Few studies have measured the financial impact of RDTs with or without antimicrobial stewardship intervention, but of those that have, most have shown a reduction in overall hospital costs (17)(18)(19). The amounts saved have been highly variable, likely due the differing costs of hospitalization at different institutions, the charges included in the analysis, and the bloodstream pathogens included in the study.…”