Antimicrobial therapy for infected necrotizing pancreatitis: microbiology, antimicrobial resistance and pharmacokinetics

Abstract

Acute pancreatitis is among the most common gastrointestinal disorders requiring hospitalization and can be complicated by serious infections. Approximately 20% of patients progress to necrotizing pancreatitis, of whom ∼30% develop infected pancreatic necrosis, a complication associated with mortality rates of 15%-35% that often necessitates invasive interventions and intensive care treatment. Serious extra-pancreatic infections are also commonly reported in acute pancreatitis patients. This review summarizes current perspectives on antimicrobial therapy for infected pancreatic necrosis, with an emphasis on microbiology and pharmacokinetics. The microbiological spectrum found in infected pancreatic necrosis is predominantly enteric, reflecting translocation of gut flora into necrotic tissue, with Gram-negative bacteria such as Escherichia coli and Klebsiella spp. being most frequently isolated. Enterococci and Candida species are also commonly identified and have been associated with adverse outcome7444444s, while anaerobes are probably underreported due to inherent culture limitations and antibiotic use. Notably, prolonged hospitalization and cumulative antibiotic exposure select for antimicrobial-resistant and difficult-to-treat pathogens. On the basis of robust evidence, prophylactic antibiotics are not clinically effective in preventing infectious complications. Although carbapenems have traditionally been favoured for treatment of infected pancreatic necrosis on the basis of presumed superior tissue penetration, pharmacokinetic studies suggest that non-carbapenem beta-lactams such as piperacillin-tazobactam and cefepime may achieve adequate tissue penetration as well, particularly when administered as extended infusions. Comparative efficacy studies of antibiotic treatment strategies with clinical endpoints are needed.