Background
Implementation of the Accelerate Pheno TM Gram-negative platform (RDT) paired with antimicrobial stewardship program (ASP) intervention projects to improve time to institutional-preferred antimicrobial therapy (IPT) for Gram-negative bacilli (GNB) bloodstream infections (BSI). However, few data describe the impact of discrepant RDT results from standard of care (SOC) methods on antimicrobial prescribing.
Methods
A single-center, pre-/post-intervention study of consecutive, non-duplicate blood cultures for adult inpatients with GNB BSI following combined RDT + ASP intervention was performed. The primary outcome was time to IPT. An a priori definition of IPT was utilized to limit bias and allow for an assessment of the impact of discrepant RDT results with the SOC reference standard.
Results
Five hundred fourteen patients (PRE 264; POST 250) were included. Median time to antimicrobial susceptibility testing (AST) results decreased 29.4 hours (p < 0.001) post-intervention, and median time to IPT was reduced by 21.2 hours (p <0.001). Utilization (days of therapy [DOTs]/1000 days present) of broad-spectrum agents decreased (PRE 655.2 vs. POST 585.8; p = 0.043) and narrow-spectrum beta-lactams increased (69.1 vs 141.7; p <0.001). Discrepant results occurred in 69/250 (28%) post-intervention episodes, resulting in incorrect ASP recommendations in 10/69 (14%). No differences in clinical outcomes were observed.
Conclusions
While implementation of a phenotypic RDT + ASP can improve time to IPT, close coordination with Clinical Microbiology and continued ASP follow up are needed to optimize therapy. Although uncommon, the potential for erroneous ASP recommendations to de-escalate to inactive therapy following RDT results warrants further investigation.
Clostridioides difficile infection (CDI) is one of the most common health care-associated infections that can cause significant morbidity and mortality. CDI diagnosis involves laboratory testing in conjunction with clinical assessment. The objective of this study was to assess the performance of various C. difficile tests and to compare clinical characteristics, Xpert C. difficile/Epi (PCR) cycle threshold (CT), and Singulex Clarity C. diff toxins A/B (Clarity) concentrations between groups with discordant test results. Unformed stool specimens from 200 hospitalized adults (100 PCR positive and 100 negative) were tested by cell cytotoxicity neutralization assay (CCNA), C. diff Quik Chek Complete (Quik Chek), Premier Toxins A and B, and Clarity. Clinical data, including CDI severity and CDI risk factors, were compared between discordant test results. Compared to CCNA, PCR had the highest sensitivity at 100% and Quik Chek had the highest specificity at 100%. Among clinical and laboratory data studied, prevalences of leukocytosis, prior antibiotic use, and hospitalizations were consistently higher across all subgroups in comparisons of toxin-positive to toxin-negative patients. Among PCR-positive samples, the median CT was lower in toxin-positive samples than in toxin-negative samples; however, CT ranges overlapped. Among Clarity-positive samples, the quantitative toxin concentration was significantly higher in toxin-positive samples than in toxin-negative samples as determined by CCNA and Quik Chek Toxin A and B. Laboratory tests for CDI vary in sensitivity and specificity. The quantitative toxin concentration may offer value in guiding CDI diagnosis and treatment. The presence of leukocytosis, prior antibiotic use, and previous hospitalizations may assist with CDI diagnosis, while other clinical parameters may not be consistently reliable.
Background
Non-immunoglobulin E (IgE)-mediated hypersensitivity reactions (HSRs) to nafcillin are commonly reported, but scarce data are available to guide appropriate antibiotic change following these reactions. Although cefazolin is an attractive therapeutic alternative in methicillin-susceptible Staphylococcus aureus (MSSA) infections when patients experience an HSR to nafcillin, more data are needed to evaluate the tolerability of cefazolin after switching from nafcillin. The purpose of this study was to describe the tolerability of cefazolin in patients who develop a suspected non-IgE-mediated HSR to nafcillin.
Methods
This was a retrospective, descriptive case series of patients who received nafcillin for an MSSA infection, experienced a suspected non-IgE-mediated HSR, and were switched to cefazolin between October 2015 and November 2019 at a single academic medical center. The primary objective was to identify the percentage of patients who completed cefazolin after experiencing a suspected non-IgE-mediated HSR to nafcillin.
Results
There were 80 patients with 87 prespecified non-IgE-mediated HSRs during the study period. Seventy-one (89%) patients completed cefazolin, with 53 (75%) of these patients completing at least 2 weeks of therapy. One patient was ultimately switched from cefazolin to daptomycin due to concern for treatment failure. Eight patients (10%) did not tolerate cefazolin after switching from nafcillin. Of these, 3 patients experienced an unrelated HSR, whereas 5 patients experienced the same non-IgE-mediated HSR that was attributed to nafcillin and discontinued cefazolin within 7 days. The most common HSR cited was immune-mediated nephritis; however, the majority were clinically presumed but did not meet objective diagnostic criteria.
Conclusions
Treatment with cefazolin after experiencing a suspected non-IgE-mediated HSR to nafcillin appears to be safe, even for patients requiring a prolonged duration of cefazolin.
Definitive therapy with penicillin had similar efficacy compared with alternative β-lactams for the treatment of PSSA bacteremia. However, nafcillin was associated with more ADEs requiring a change in therapy.
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