A2. PK/PD studies
Oral Abstract Submission
Mohammad H. Al-Shaer, PharmD
Graduate assistant
University of Florida
Gainesville, FL
Disclosure: Nothing to disclose
Kenneth Klinker, PharmD
Associate Professor
University of Florida
Gainesville, FL
Disclosure: Merck & Co., Inc., Kenilworth, NJ: Employee
Charles Peloquin, Pharm.D.
Professor and Director, Infectious Disease Pharmacokinetics Laboratory
University of Florida
Gainesville, FL
Disclosure: Nothing to disclose
Background :
Therapeutic drug monitoring (TDM) is a powerful tool to optimize antibiotic exposure. It seldom has been used for beta-lactams (BLs). We present our BL data in patients admitted to the surgical intensive care unit (SICU).
Methods :
This retrospective study included SICU patients at UF Health (2016 and 2018) who received BL therapy and had TDM. Data collected included demographics, APACHE scores, platelet count, serum creatinine (Scr), infection source, cultures/susceptibilities, BL regimens and plasma concentrations. Clinical cure was defined as resolution of infection-related symptoms at the end of therapy. Microbiologic eradication was defined as eradication of causative organism from the primary source out to 30 days after therapy. Pharmacokinetic and statistical analyses were performed on Phoenix v8.0 and JMP Pro v14.
Results :
127 patients were included. Table 1 shows the baseline characteristics. Median age was 55 years, weight 83 kg. 83 (65%) were male. P. aeruginosa was the most common isolated bacteria (n=38). Lung was the most common source of infection (n=50). Table 2 summarizes the median (IQR) doses, infusion times, calculated free trough concentrations (fCmin) of common BLs, and the reported minimum inhibitory concentrations (MICs). Calculated median time above the MIC (fT>MIC) for 66 (52%) patients was 100%. A total of 99 (79%) patients had clinical cure and 67 (61%) patients had microbiologic eradication. For efficacy, Cmin/MIC ratio predicted the microbiologic eradication in wound infections only (n=15 , OR 1.09 [95% CI 1.01-1.24]). Using stepwise regression, 1-unit increase fT>MIC and APACHE score was associated with 0.84 decrease (p=0.03) and 0.62 increase (p=0.004) in days of therapy, respectively. For safety, Figure 2 shows the increase in Scr vs BL free area under the concentration-time curve from time zero to end of dosing interval (fAUC0-tau). Cefepime fAUC0-tau predicted neurotoxicity (OR per 20 unit increase 1.08 [95% CI: 1.01-1.18]).
Conclusion :
In SICU patients, increase in fT>MIC was associated with shorter treatment duration, and fAUC0-tau increase was associated with increase in Scr and incidence of neurotoxicity. TDM is warranted in this population to optimize therapy.
.png)
.png)
