The comparative efficacy of ceftazidime-avibactam and meropenem-vaborbactam for treatment of carbapenem-resistant Enterobacteriaceae (CRE) infections remains unknown. This was a multicenter, retrospective cohort study of adults with CRE infections who received ceftazidime-avibactam or meropenem-vaborbactam for ≥72 hours from February 2015 to October 2018. Patients with a localized urinary tract infection and repeat study drug exposures after the first episode were excluded. The primary endpoint was clinical success compared between treatment groups. Secondary endpoints included 30- and 90-day mortality, adverse events (AE), 90-day CRE infection recurrence, and development of resistance in patients with recurrent infection. A post hoc subgroup analysis was completed comparing patients who received ceftazidime-avibactam monotherapy, ceftazidime-avibactam combination therapy, and meropenem-vaborbactam monotherapy. A total of 131 patients were included (ceftazidime-avibactam, n = 105; meropenem-vaborbactam, n = 26), 40% of whom had bacteremia. No significant difference in clinical success was observed between groups (62% versus 69%; P = 0.49). Patients in the ceftazidime-avibactam arm received combination therapy more often than patients in the meropenem-vaborbactam arm (61% versus 15%; P < 0.01). No difference in 30- and 90-day mortality resulted, and rates of AE were similar between groups. In patients with recurrent infection, development of resistance occurred in three patients that received ceftazidime-avibactam monotherapy and in no patients in the meropenem-vaborbactam arm. Clinical success was similar between patients receiving ceftazidime-avibactam and meropenem-vaborbactam for treatment of CRE infections, despite ceftazidime-avibactam being used more often as a combination therapy. Development of resistance was more common with ceftazidime-avibactam monotherapy.
Implementation of the Verigene Gram-positive blood culture test led to reductions in time to acceptable antibiotic overall (1.9 versus 13.2 h, respectively; P ؍ 0.04) and time to appropriate antibiotic for patients with vancomycin-resistant Enterococcus (4.2 versus 43.7 h; P ؍ 0.006) and viridans group Streptococcus (0.2 versus 7.1 h; P ؍ 0.02). Enterococci and streptococci are frequent causes of bloodstream infections (BSIs), which are associated with high mortality when inappropriately treated (1). Timely initiation of appropriate antibiotics is vital, as this permits effective targeting of causative pathogens, decreased antimicrobial exposure, and possible cost savings. Therefore, rapid molecular tests are being used with increasing frequency to facilitate antimicrobial stewardship efforts. The FDA-cleared Verigene Gram-positive blood culture test (BC-GP) (Nanosphere, Inc., Northbrook, IL) detects bacterial DNA from blood cultures positive for Staphylococcus, Streptococcus, Enterococcus, and Listeria spp. It also identifies mecA, which confers methicillin resistance in staphylococci, and vanA and vanB genes, which confer vancomycin resistance in enterococci.We previously published a targeted treatment algorithm based on BC-GP results (2). In this study, we evaluated clinical outcomes associated with implementation of the BC-GP technology and targeted treatment algorithm in patients with streptococcal and enterococcal bacteremia in comparison with traditional microbiological methods. The primary outcome was time to appropriate antibiotic. Secondary outcomes included time to acceptable antibiotic, time to culture clearance, length of stay (LOS), and mortality.This study, approved by the University of North Carolina Institutional Review Board, used a quasiexperimental design comparing pre-and postintervention groups over 17 months. Patients with blood cultures positive for Gram-positive cocci (GPC) in pairs and/or chains were included. Subjects were excluded if they had polymicrobial blood cultures, had positive cultures for Streptococcus or Enterococcus spp. in both the case and control periods, or were still hospitalized or if the positive blood culture was classified as a contaminant (i.e., one bottle positive for viridans group streptococci [VGS]). Additionally, if a subject had a second blood culture that was positive for the same organism within 14 days of the first culture, the second culture was excluded.In the preintervention period, Gram stain results were documented in the electronic medical record (EMR) system and phoned to the patient's primary team. After BC-GP implementation, Gram stain results were still phoned to the primary team; however, if the stain was positive for GPC in pairs and/or chains, the BC-GP test was performed. The result was communicated by microbiology laboratory staff to the pharmacist on call, who referred to a treatment algorithm based on local susceptibility patterns and clinical guidelines to recommend targeted therapy (2). BC-GP results were confirmed by conventional...
Background: Data on the effectiveness of definitive oral (PO) antibiotics for BSIs in preparation for discharge from hospital are lacking, particularly for Gram-positive bacterial BSIs (GP-BSI). The objective of this study was to determine rates of treatment failure based on bioavailability of PO antimicrobial agents used for GP-BSI. Methods: This was a single-center, retrospective cohort study of adult inpatients admitted to an academic medical center over a three-year period. Patients with a non-staphylococcal GP-BSI who received intravenous antibiotics and were then switched to PO antibiotics for at least a third of their treatment course were included. The cohort was stratified into high (⩾90%) and low (<90%) bioavailability groups. The primary endpoint was the proportion of patients experiencing clinical failure in each group. Secondary endpoints included clinical failure stratified by antibiotic group, bactericidal versus bacteriostatic PO agents, and organism. Results: A total of 103 patients met criteria for inclusion, which failed to reach the a priori power calculation. Of the patients included, 26 received high bioavailability agents and 77 received low bioavailability agents. Infections originated largely from a pulmonary source (30%) and were caused primarily by streptococcal species (75%). Treatment failure rates were 19.2% in the high bioavailability group and 23.4% in the low bioavailability group ( p = 0.66). Clinical failure stratified by subgroups also did not yield statistically significant differences. Conclusions: Clinical failure rates were similar among patients definitively treated with high or low bioavailability agents for GP-BSI, though the study was underpowered to detect such a difference.
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