ABSTRACT
Objective: To describe the use of next-generation sequencing (NGS) and to determine whether NGS leads to changes in antimicrobial management. Design and setting: This retrospective cohort study included patients aged ≥18 years admitted to a single tertiary-care center in Houston, Texas, with an NGS test performed between January 1, 2017, and December 31, 2018. Patients: In total, 167 NGS tests were performed. Most patients were of non-Hispanic ethnicity (n = 129), white (n = 106), and male (n = 116), with a mean age of 52 years (SD, 16). Moreover, 61 patients were immunocompromised: solid-organ transplant (n = 30), patients with human immunodeficiency virus (n = 14), and rheumatology patients on immunosuppressive therapy (n = 12). Results: Of the 167 NGS tests performed, 118 (71%) were positive. Test results associated with a change in antimicrobial management were found in 120 (72%) of 167 cases, with an average of 0.32 (SD, 1.57) fewer antimicrobials after the test. The largest change in antimicrobial management was in glycopeptide use (36 discontinuations) followed by antimycobacterial drug use (27 additions among 8 patients). Also, 49 patients had negative NGS results, but only 36 patients had their antibiotics discontinued. Conclusions: Plasma NGS testing is associated with a change in antimicrobial management in most cases. We observed a decrease in glycopeptide use after NGS results, which highlights physicians' comfort in withdrawing methicillin-resistant Staphylococcus aureus (MRSA) coverage. In addition, antimycobacterial coverage increased, corresponding with early mycobacterial detection by NGS. Further studies are needed to determine effective ways to use NGS testing as an antimicrobial stewardship tool.
ABSTRACT
INTRODUCTION: Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. METHODS: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16 s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. RESULTS: On univariate analysis, factors associated with severe CDI included the presence of toxin A/B in stools (odds ratio [OR] 2.14 [1.05-4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09-6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxin A/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. CONCLUSION: Use of metronidazole for non-CDI indications within 90 days prior to diagnosis and presence of toxin A/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.
