Is Moxifloxacin a Treatment Option for Pancreatic Infections? A Pharmacometric Analysis of Serum and Pancreatic Juice

Postoperative local infection is a major complication after pancreatic surgery. The aim of this prospective clinical trial was to assess the potential of moxifloxacin (MXF) to treat pancreatic infections from a pharmacokinetic (PK)/pharmacodynamic (PD) perspective. The PK of MXF in serum and pancreatic juice, via an inserted tube in the pancreatic duct, was determined in 19 patients up to day 7 after pancreatoduodenectomy. PK data in both specimens was analyzed with NONMEM 7.3. Intraoperative swipes were performed for microbiological examination. PK/PD target attainment was assessed in both matrices using unbound area under the plasma concentration-time curve/minimum inhibitory concentration (MIC) targets of >= 30 and >= 100, for gram-positive and gram-negative pathogens, respectively. A 2-compartment population PK model in which the measurements in pancreatic juice were assigned to a scaled peripheral compartment best described the PK in both specimens simultaneously. Median (10th-90th percentile) area under the plasma concentration-time curve values after the third dose were 28.9 mg center dot h/L (18.6-42.0) in serum and 55.8 mg center dot h/L (23.7-81.4) in pancreatic juice. Target attainment rate for the intraoperatively isolated bacterial strains was >= 0.88 after the third MXF dose. For gram-negatives, high probability of target attainment >= 0.84 was observed in serum for MIC <= 0.125 mg/L and in pancreatic juice for MIC <= 0.25 mg/L. For gram-positives, the probability of target attainment was 0.84-1 in serum for MIC <= 0.5 mg/L and in pancreatic juice for MIC <= 1 mg/L. In conclusion, penetration of MXF into pancreatic juice was substantial. The PK/PD analysis indicated that treatment of pancreatic infections by isolates with MIC <= 0.25 mg/L (gram-negative) and <= 1 mg/L (gram-positive) should be evaluated in further studies.