The Effect of Clinical Concentrations of Meropenem (MEM), Ceftolozane/tazobactam (C/T), and Ceftazidime/avaibactam (CZA) on Time to Detection (TTD) and Growth of Pseudomonas aeruginosa (PSA) in bioMerieux BacT/ALERT(®)FA Plus Blood Culture (BC) Bottles

BACKGROUND: Antimicrobial binding agents (ABA) are added to BC bottle media to reduce TTD and prevent false negatives that may result when BCs are obtained in patients receiving antibiotics. Sparse data are available on the effectiveness of ABA containing BacT/ALERT(®)FA Plus BC bottles against MEM, C/T and CZA, which are often administered as high dose and/or prolonged infusion regimens for suspected PSA infections. METHODS: BC bottles were inoculated with 10ml of fresh whole blood collected from healthy volunteers. The blood was spiked to achieve mean peak, midpoint, and trough concentrations of MEM (40, 20 and 5 µg/mL), C/T (150, 50, and 8 µg/mL), and CZA (90, 25, and 10 µg/mL), respectively. A control bottle containing no antibiotic was included. BC bottles were then inoculated with 7–30 colony forming units (CFU)/bottle of either a MEM susceptible (MEM-S) (MIC = 0.5 µg/mL, C/T = 0.5 µg/mL, CZA = 2 µg/mL) or MEM resistant (MEM-R) PSA (MIC = 8 µg/mL, C/T = 4 µg/mL, CZA = 8 µg/mL) isolate. Matching bottles were entered into a BacT/ALERT(®)-3D detection instrument and a standard incubator at 37° C for up to 72h. Each series was conducted in duplicate. TTD was measured in the detection instrument, and CFUs were counted at 0, 4, 12, 24, 36, 48, 60, and 72h in incubated bottles. RESULTS: Control PSA grew to 7.4 × 10(8)/mL with a TTD of 15.5–19.5 hours. Both PSA grew in the presence of MEM trough concentrations with TTD of 21.3 ± 3.3 hours. However, midpoint and peak concentrations inhibited growth of the MEM-S PSA. The MEM-R PSA grew in the presence of all MEM concentrations, with a TTD of 18.6 ± 0.5 hours. Both PSA grew in the presence of C/T trough concentrations with TTD of 23.0 ± 2.6 hours, but were inhibited by midpoint and peak C/T concentrations. For CZA, both PSA grew in the presence of trough concentrations with TTD of 20.1 ± 1.9 hours. Peak CZA concentrations inhibited growth of both PSA, while midpoint concentrations inhibited growth of the MEM-S isolate. CONCLUSION: These are the first data to show that BacT/ALERT BC bottles containing ABA may not sufficiently inactivate achievable concentrations of MEM, C/T or CZA, which could result in false negatives. In patients already receiving one of these antibiotics, BCs should be collected just prior to the next dose to increase the probability of PSA detection. DISCLOSURES: All authors: No reported disclosures.