Theoretical approach to local infusion of antibiotics for infected pancreatic necrosis.
OBJECTIVE
Infected pancreatic necrosis is a major complications of acute pancreatitis. If drainage is required, local administration of antibiotics through transmural nasocystic or percutaneous catheter may allow increasing local antibiotic concentrations. Drug diffusion becomes the main factor influencing local drug tissue penetration. The present study aims at providing the rationale for the design of new research protocols evaluating the efficacy of local antibiotics for infected pancreatic necrosis.


METHODS
A review of microbiological data was performed for the most common organisms causing the infection, antibiotics spectrum and minimum inhibitory concentrations (MIC). A search of the physico-chemical properties of antibiotics was performed to calculate the diffusion coefficients. An estimation of the antibiotic concentrations in pancreatic tissue was obtained using a mathematical model. Efficacy factors (EF) were calculated and the stability of the antibiotic solutions were evaluated to optimize the dosing regimen.


RESULTS
Piperacillin, vancomycin and metronidazole achieve high concentrations in the surrounding tissue very fast. Imipenem, ceftriaxone, ciprofloxacin, gentamicin, linezolid and cloxacillin achieve intermediate concentration values. Tigecycline, showed the lowest concentration values (<2 mg/L). Calculated EF is highest for piperacillin and imipenem short after administration and near to surface diffusion area (0.5 cm), but EF of imipenem is higher at deeper areas and longer time after administration.


CONCLUSIONS
Considering obtained results, some solutions are proposed using saline as diluent and 25 °C of temperature during administration. Imipenem has the best theoretical results in empiric local treatment. Linezolid and tigecycline solutions are not recommended.
Department of Pharmacy, University Hospital of Santiago de Compostela, Spain. Electronic address: jaime.gonzalez.lopez@sergas.es.
Jaime
J
González-López
Department of Gastroenterology, University Hospital of Santiago de Compostela, Spain.
Fernando
F
Macías-García
Department of Gastroenterology, University Hospital of Santiago de Compostela, Spain.
José
J
Lariño-Noia
Department of Gastroenterology, University Hospital of Santiago de Compostela, Spain.
Juan Enrique
JE
Domínguez-Muñoz
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004058:Diffusion; D004355:Drug Stability; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D007267:Injections; D059413:Intraabdominal Infections / Q000188:drug therapy* / Q000209:etiology* / Q000382:microbiology; D010179:Pancreas / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications*; D019999:Pharmaceutical Solutions; D007507:Therapeutic Irrigation
D000900:Anti-Bacterial Agents; D019999:Pharmaceutical Solutions; D015378:Imipenem
Acute necrotizing pancreatitis; Antimicrobials diffusion; Local antibiotic; Pancreatic drainage; Wall-off necrosis