BACTEC media has faster time to detection and increased bacterial recovery over the BacT/Alert media in the following categories: overall growth, pathogens, septic events, gram-positive cocci, gram-negative rods, Staphylococcus aureus, and cultures where antimicrobials were dosed up to 48 hours before culture collection.
Two high-performance liquid chromatography methods utilizing a protein precipitation technique were developed to analyze vancomycin in human plasma, mouse serum and bronchoalveolar lavage (BAL) fluid. The mobile phase consisted of ammonium phosphate buffer with acetonitrile. A cross-matrix validation was performed to ensure that the mouse serum was comparable to the original biological matrix of human plasma. Murine BAL samples were run on a saline standard curve. For saline samples, the mobile phase from the human plasma study was used with the addition of 1M sodium hydroxide (0.2%) to avoid interfering peaks. A reversed-phase column was used with an ultraviolet detector set at 240 nm for human plasma and 198 nm for saline to increase peak size. The standard curves were liner over the ranges of 1 to 80 µg/mL for human plasma and 0.1 to 10 µg/mL for saline. These assays are simple, reproducible and accurate. These analytical techniques were successfully applied to analyze vancomycin concentrations in mouse serum and BAL samples.
We have previously demonstrated that a high-dose, prolonged-infusion meropenem regimen (2 g every 8 h [q8h]; 3-hour infusion) can achieve 40% free drug concentration above the MIC against Pseudomonas aeruginosa with MICs of <16 g/ml. The objective of this experiment was to compare the efficacy of this high-dose, prolonged-infusion regimen against carbapenemase-producing Klebsiella pneumoniae isolates with the efficacy against P. aeruginosa isolates having similar meropenem MICs. An in vitro pharmacodynamic model was used to simulate human serum concentrations. Eleven genotypically confirmed K. pneumoniae carbapenemase (KPC)-producing isolates and six clinical P. aeruginosa isolates were tested for 24 h, and time-kill curves were constructed. High-performance liquid chromatography (HPLC) was used to verify meropenem concentrations in each experiment. Meropenem achieved a rapid >3 log CFU reduction against all KPC isolates within 6 h, followed by regrowth in all but two isolates. The targeted %fT>MIC (percent time that free drug concentrations remain above the MIC) exposure was achieved against both of these KPC isolates (100% fT>MIC versus MIC ؍ 2 g/ml, 75% fT>MIC versus MIC ؍ 8 g/ml). Against KPC isolates with MICs of 8 and 16 g/ml that did regrow, actual meropenem exposures were significantly lower than targeted due to rapid in vitro hydrolysis, whereby targeted %fT>MIC was reduced with each subsequent dosing. In contrast, a >3 log CFU reduction was maintained over 24 h for all Pseudomonas isolates with meropenem MICs of 8 and 16 g/ml. Although KPC and P. aeruginosa isolates may share similar meropenem MICs, the differing resistance mechanisms produce discordant responses to a high-dose, prolonged infusion of meropenem. Thus, predicting the efficacy of an antimicrobial regimen based on MIC may not be a valid assumption for KPC-producing organisms.
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