Evaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill Curves.

The effects of combining fosfomycin with various antimicrobial agents were evaluated in vitro by broth microdilution checkerboard and time-kill kinetic studies. Checkerboard analyses were used to evaluate the following 30 Gram-negative isolates: 5 Pseudomonas aeruginosa, 5 Acinetobacter baumannii-Acinetobacter calcoaceticus species complex, and 20 Enterobacteriaceae isolates. No isolate exhibited antagonism when fosfomycin was tested in combination, and synergy was observed in more than 25% of the drug combinations tested. The most frequent instances of synergy occurred when testing fosfomycin with ß-lactams. Two isolates of Pseudomonas aeruginosa, 2 of Klebsiella pneumoniae, and 1 of the A. baumannii-A. calcoaceticus species complex that exhibited synergy when fosfomycin was tested in combination were subjected to time-kill kinetic analyses for confirmation. Time-kill assays confirmed synergistic activity. These data indicated that combination therapy with fosfomycin may be beneficial.

Activity of fosfomycin when tested against US contemporary bacterial isolates.

Fosfomycin and comparators were susceptibility tested against over 2200 contemporary clinical isolates from US medical centers. Fosfomycin was active against Enterobacterales (MIC50/90, 4/16 µg/mL), including multidrug-resistant isolates. Potent activity was exhibited against gram-positive organisms, including Staphylococcus aureus (MIC50/90, 4/8 µg/mL). Fosfomycin may provide a promising alternative option for treatment of infections where resistant bacteria may occur.

Correction to: PK-PD Compass: bringing infectious diseases pharmacometrics to the patient's bedside.

The original version of this article contained incorrect Supplementary Files. The correct Supplementary Files are published with this erratum.

PK-PD Compass: bringing infectious diseases pharmacometrics to the patient's bedside.

Antimicrobial stewardship programs face many challenges, one of which is a lack of guidance regarding antimicrobial dose, interval, and duration. There is no tool that considers patient demographic, pathogen susceptibility, and pharmacokinetic-pharmacodynamic (PK-PD) targets for efficacy in order to evaluate appropriate antimicrobial dosing regimens. The PK-PD Compass, an educational mobile application, was developed to address this unmet need. The application consists of a Monte Carlo simulation algorithm which integrates pharmacokinetic (PK) and PK-PD data, patient-specific characteristics, and pathogen susceptibility data. Through the integration of these data, the application allows practitioners to assess the percent probability of PK-PD target attainment for 35 intravenous antimicrobial agents across 29 infection categories. Population PK models for each drug were identified, evaluated, and refined as needed. Susceptibility breakpoints were based upon FDA and CLSI criteria. By incorporating these data into one interface, clinicians can select the infection, pathogen, and antimicrobial agents of interest and obtain the percent probability of PK-PD target attainment for each regimen based upon patient-specific characteristics. The antimicrobial dosing regimens provided include those recommended by standard guidelines and reference texts. However, unlike these references, potential choices are prioritized based on percent probabilities of PK-PD target attainment. Such data will educate clinicians on selecting optimized antibiotic regimens through the lens of PK-PD.

Real-time interpretation of novel events across childhood.

Despite extensive evidence that adults and children rapidly integrate world knowledge to generate expectancies for upcoming language, little work has explored how this knowledge is initially acquired and used. We explore this question in 3- to 10-year-old children and adults by measuring the degree to which sentences depicting recently learned connections between agents, actions and objects lead to anticipatory eye-movements to the objects. Combinatory information in sentences about agent and action elicited anticipatory eye-movements to the Target object in adults and older children. Our findings suggest that adults and school-aged children can quickly activate information about recently exposed novel event relationships in real-time language processing. However, there were important developmental differences in the use of this knowledge. Adults and school-aged children used the sentential agent and action to predict the sentence final theme, while preschool children's fixations reflected a simple association to the currently spoken item. We consider several reasons for this developmental difference and possible extensions of this paradigm.