Cost-Effectiveness Analysis of Multiplex PCR with Magnetic Resonance Detection versus Empiric or Blood Culture-Directed Therapy for Management of Suspected Candidemia

Abstract

c Candida bloodstream infections (BSI) are associated with significant morbidity, mortality, and increased health care costs. Early treatment is essential, because delayed therapy detrimentally impacts clinical outcomes. The FDA recently approved the first culture-independent direct molecular detection method for Candida BSIs (T2Candida). The speed and sensitivity of this assay give it the potential to improve patient care, but the reagents and instrumentation are expensive. We used an analytic decision tree model to compare the cost-effectiveness of T2Candida-directed antifungal therapy (T2DT) to that of either empirical therapy (ET) or blood culture-directed therapy (BCDT). The costs included those of T2Candida testing, antifungal treatment, and hospital length of stay. The effectiveness measure was survival status at hospital discharge. T2DT was less costly and more effective than BCDT but was less costly and less effective than ET with an echinocandin (incremental cost-effectiveness ratio, $111,084 per additional survivor). One-way sensitivity analyses demonstrated that the cost-effectiveness of T2DT was highly dependent on Candida BSI prevalence and the cost of antifungal therapy and T2Candida test reagents. The use of T2DT reduced the number of unnecessarily treated patients by 98% relative to that with ET. Reduced drug exposure might lessen the possibility of drug-related adverse events and may also prevent the development of antifungal resistance or emergence of drug-resistant Candida species. The greatest benefit of T2Candida appears to be the ability to confidently withhold or stop empirical antifungal therapy in low-to-moderate-risk patients who are unlikely to benefit from treatment. C andida spp. are the fourth leading cause of bloodstream infections (BSI) in hospitalized patients and the third most common cause of BSI in the intensive care unit (ICU) (1). These infections are not only prevalent but are also associated with significant morbidity, mortality, and increased heath care costs. Attributable mortality rates range from 5 to 71%, depending on the patient population (2). Early treatment of infected patients is critical, because delays in effective therapy significantly impact outcomes (3-5), but difficulties in making a microbiological diagnosis often contribute to delayed treatment.Blood culture is the current gold standard for diagnosing Candida BSI; however, culture is relatively insensitive and requires several days to complete. As a result of the limitations of culture, patients with risk factors for invasive candidiasis (IC) are often given immediate empirical antifungal therapy (6). Although empirical therapy reduces delays, it also subjects some patients to unnecessary treatment, which in turn increases expenses, may cause adverse side effects, and potentially contributes to the emergence of antifungal resistance (7-10). More rapid and sensitive diagnostic methods are needed for the early and accurate diagnosis of Candida BSI.The U.S. Food and Drug Administration (FDA) recently approv...

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

“…Instead, upregulation of the azole efflux pumps encoded by genes of the ATP binding cassette (ABC) or the major facilitator superfamilies (MFS) is the more important mechanism of resistance through changes in the regulation of their expression by mutations in the transcription factors, e.g., TAC1 and MRR1 (C. albicans) and CgPDR1 (C. glabrata) (Vermitsky et al, 2006;Morschhäuser et al, 2007). Candida species also have plasticity in their genomes with movement within chromosomes, which can alter both efflux pump and ERG11 expression (Perlin and Wiederhold, 2017).…”

“…T2Candida was significantly more likely to be positive than cBCs (45 versus 24%, P < 0.0001) (Clancy et al, 2018). Another study found T2Candida was clinically more effective than blood culture for the management of suspected candidemia, but slightly less effective than empiric therapy (Walker et al, 2016). Prospective randomized controlled trials are required to fully evaluate the impact of the T2Candida on patient outcomes and hospital-associated costs.…”

Syndromic Panel-Based Testing in Clinical Microbiology

“…WBC counts are typically elevated, with a prevalence of neutrophils, in cases of bacterial meningitis (Table 5). In cases of fungal, viral, and tuberculous meningitis, WBC counts may also be elevated but generally to a lesser degree than with bacterial meningitis and often in the context of lymphocytosis (70)(71)(72)(73). A detailed patient evaluation, including vaccination history, and consideration of seasonality, geography, and local epidemiology may aid in narrowing the differential diagnoses; however, microbiologic testing of CSF is generally required to establish a definitive diagnosis.…”

“…Traditionally, the laboratory diagnosis of bacterial meningitis has been made by using Gram staining and culture of CSF, with molecular testing for herpes simplex virus 1 (HSV-1), HSV-2, and enterovirus, in particular, playing an important role in the diagnosis of viral CNS infections (73,74). For some causes of CNS infections, such as arboviruses, serology is considered the diagnostic method of choice.…”

Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit

“…Some of these strategies include the use of PCR to detect the most common fluconazole-resistant species (i.e., C. krusei and C. glabrata) or to detect all Candida strains, regardless of species. Although another study has focused on the economics of Candida infections within the bloodstream [30], our analysis has focused on non-neutropenic patients with severe peritonitis, for the following reasons: Candida peritonitis is a major cause of invasive candidiasis in patients in ICUs [31], the use of echinocandin for this indication is off-label, and there is particular benefit for clinicians to rationalize echinocandin prescriptions in this context.…”