Population Pharmacokinetics and Dosing Simulations of Ampicillin and Sulbactam in Hospitalised Adult Patients.

BACKGROUND: The pharmacokinetic variability of ampicillin-sulbactam in adults has not been extensively described, particularly in patients with a reduced renal function (i.e., < 60 mL/min). OBJECTIVE: This study investigated the population pharmacokinetics of ampicillin and sulbactam in patients with a wide range of renal functions and sought to define dosing approaches that have a high likelihood for optimising drug exposure. METHODS: Serial blood samples were collected from 16 adult patients receiving intravenous ampicillin-sulbactam in general wards. Total ampicillin and sulbactam concentrations were measured by chromatographic assay and pharmacokinetic parameters were estimated using Pmetrics®. Monte Carlo simulations were used to evaluate the probability of target attainment (PTA) of free ampicillin and sulbactam concentrations exceeding the minimum inhibitory concentration (MIC) for 60% and 100% of the dosing interval. Fractional target attainment (FTA) was calculated against MIC distributions of common hospital pathogens. A threshold of ≥ 90% and ≥ 95% was used to define both optimal PTA and FTA, respectively. RESULTS: The median (range) age, weight, and serum creatinine of the study population was 68 (40-82) years, 62 (40-82) kg, and 1.4 (0.6-6.4) mg/dL, respectively. The pharmacokinetics of ampicillin and sulbactam were best described by a two-compartment model with serum creatinine most closely associated with clearance for both drugs. The estimated ampicillin and sulbactam clearances were 5.58 L/h and 4.79 L/h, respectively, while the volumes of distribution were 12.6 L and 15.36 L, respectively. Approved dosing regimens of ampicillin-sulbactam were sufficient against MICs ≤ 8 and ≤ 4 mg/L, respectively. A 4-h infusion enabled optimal PTA at higher MICs. For both dosing targets, optimal FTAs were obtained against Streptococcus pneumoniae. CONCLUSION: Optimal FTAs were obtained against the susceptible MIC distributions of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Applying a 4-h infusion will enhance PTA and FTA, particularly at higher MICs.

Indonesian healthcare providers' perceptions and attitude on antimicrobial resistance, prescription and stewardship programs.

Background: A successful antimicrobial stewardship program (ASP) is sustained through improving antimicrobial prescribing by changing prescribing behavior. This requires a better understanding of hospital stakeholders' views regarding antimicrobial resistance (AMR), antimicrobial use and participation in ASP activities. Objectives: Identify perceptions and attitudes among physicians and pharmacists in a public hospital toward AMR, prescription and ASP. Methods: A questionnaire consisting of 45 items was distributed to physicians and pharmacists in a 320-bed public hospital. All responses were formatted into the Likert scale. Results: A total of 78 respondents (73% response rate) completed the questionnaire. The majority of the respondents perceived AMR within hospital as less of a severe problem, and factors outside hospital were considered to be greater contributors to AMR. In addition, interprofessional conflict was identified as a serious concern in relation to implementing ASP. Conclusion: This finding indicates the need to address existing perceptions and attitudes toward ASP activities that may hamper its successful implementation in Indonesia.