2025/01/12 by Hjalmar van Santvoort, Rogier P. Voermans, Nicholas J. Zyromski +1 · 1 voice
Medicine · #Appendicitis Diagnosis and Management #Pancreatic and Hepatic Oncology Research #Pancreatitis Pathology and Treatment
paper · pdf · doi:10.1093/bjs/znaf007
openalex publication_date 2025/01/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
Acute pancreatitis is a relatively common cause of urgent hospital admission1. Although most patients with acute pancreatitis manifest a relatively mild and self-limiting disease course (albeit characterized clinically by a variable episode of severe abdominal pain and vomiting), up to a third will have severe disease1. To date, there is no specific medication to treat acute pancreatitis, and the mainstays of management are correct establishment of diagnosis, analgesia, nutritional and organ support together with surveillance for complications2. The pathobiology of the early stages of acute pancreatitis is characterized by an intense systemic inflammatory response involving a complex interplay between pro- and anti-inflammatory cytokines, a range of cellular mediators of inflammation and a variable ‘host’ response to injury, particularly in the pulmonary and renal vascular endothelial beds2,3. Gut dysfunction related to splanchnic hypoperfusion, change in microbiome and host intestinal inflammatory response is a constituent component of this early response4. Bacterial infection is not thought to play a major part in the early stages of acute pancreatitis4. As a result, antibiotics are not effective. This is reflected in the recommendations of a range of national and international guidelines with those produced by the International Association of Pancreatology and the American Pancreatic Association and also those of the American College of Gastroenterology making the statement that antibiotics should not be used routinely as prophylaxis in the early stages of acute pancreatitis or in the later stages in those patients with sterile necrosis5,6. Antibiotics do, however, have a role in the treatment of culture-positive infections, as prophylaxis for intervention, and together with procedures such as drainage/debridement they form a component of the treatment of infected necrosis7. Despite these clear, consistent recommendations, antibiotics are continually overused both in the early and later stages of the disease in patients with mild, moderately severe and severe acute pancreatitis8. Antibiotic overuse in acute pancreatitis is a global phenomenon, occurring in all healthcare systems and across academic and community medical centres9. Inappropriate antibiotic usage in acute pancreatitis is not associated with patient benefit, may lead to harm, and increases the risks of emergence of resistant flora. The reasons underlying antibiotic overuse or misuse in acute pancreatitis are diverse and include both clinical and healthcare organizational factors. Clinically, the picture of the intense systemic inflammatory response of early acute pancreatitis, characterized by fever, hypotension and raised inflammatory markers (SIRS) can be indistinguishable from infection. Inflammatory markers, including leukocyte count and C-reactive protein levels, can also be elevated. The decision to use antibiotics should not simply be attributed to careless or ignorant prescribing. In the context of an acutely ill patient, in a condition with currently no specific ‘anti-pancreatitis’ treatment, the drive to treat is clear. If clinicians cannot be certain that infection is absent, anxiety over potential undertreatment of a patient with apparent sepsis will also drive empiric antibiotic prescribing. In terms of healthcare organization, patients with acute pancreatitis typically present to emergency rooms and the initial management for the majority is undertaken in community or rural medical centres. In these settings, in the likely absence of clinicians with expertise in pancreatology, it is easy to see how antibiotics can be prescribed. Even in larger tertiary or academic medical centres the decisions to initiate antibiotic therapy are often taken by junior non-attending (non-consultant) staff. In both the setting of the rural or community hospital and the junior non-attending prescriber, these individuals are less likely to be familiar with guideline advice in relation to the use of antibiotics in acute pancreatitis. Antibiotic stewardship and the embedding of this practice in the practical management of acute pancreatitis is one potential solution to this problem. A component of a selective and more nuanced policy to antibiotic use is the use of a procalcitonin-measurement based algorithm10. Procalcitonin is regarded as a hormokine, sharing characteristics of both hormones and cytokines and having roles in maintaining vascular endothelial tone in response to bacterial infection10. Procalcitonin concentrations increase rapidly in response to a pro-inflammatory stimulus of bacterial origin and decrease after successful treatment. Algorithms based on measurement of procalcitonin have been developed as a means of differentiating bacterial sepsis from a systemic inflammatory response in a range of settings—in community practice, emergency room medicine, and in critical care11. Procalcitonin is more sensitive than clinical assessment and routine laboratory markers of sepsis (such as leukocyte count and C-reactive protein) in detecting infection in patients with pancreatitis12. The PROCAP study was a randomized trial of the use of a procalcitonin-measurement algorithm to guide antibiotic use in patients with acute pancreatitis. Participants were randomly assigned (1 : 1) to procalcitonin-guided care or usual care13. Guidance was to stop or not start antibiotics following a test value of less than 1.0 ng/ml and to start or continue antibiotics following a test value of 1.0 ng/ml or more. Two hundred and sixty patients were enrolled and randomly assigned to a treatment group (132 to procalcitonin-guided care and 128 to usual care). Fifty-nine patients (45%) in the procalcitonin-guided care group were prescribed antibiotics compared with 79 (63%) in the usual care group (adjusted risk difference −15.6% (95% c.i. −27.0 to −4.2); P = 0.0071). The odds ratio for the treatment effect was 0.49 (95% c.i. 0.29 to 0.83; P = 0.0077). There was no difference in adverse events between the groups. The study concluded that procalcitonin-guided care can reduce antibiotic use without increasing infection or harm in patients with acute pancreatitis13. More can be done to guide antibiotic use than simply measurement of procalcitonin. In the social media age, it is feasible to use cell phone applications to guide antibiotic decision making. In hospitals that use an electronic patient record, these algorithms can be incorporated into all antibiotic prescribing. Further, antibiotic stewardship is part of good medical practice for patients with suspected infectious disease. Antimicrobial stewardship strategies focus on improving the quality of antimicrobial use and include obtaining cultures, commencing antibiotics only in case of a proven or high suspicion of infection, adjusting antibiotics accordingly and stopping antibiotics based on clear criteria. Multiple studies concerning various infectious diseases have shown that antimicrobial stewardship programmes improve clinical outcomes, reduce adverse events, length of hospitalization, financial healthcare burden, and the development of individual and societal antimicrobial resistance14,15. The Dutch Pancreatitis Study group is currently conducting an RCT to evaluate the benefit of antimicrobial stewardship principles in patients with necrotizing pancreatitis. While awaiting the results of this trial, it is advised that antibiotic prescribing is reviewed daily during the in-patient course with joint input from pharmacists and microbiologists being key to holistic management. In this way, incorrect prescribing of antibiotics can be reduced, correct antibiotic use, ideally driven by appropriate sensitivities can be undertaken and the risks of emergence of multiresistant flora as a result of indiscriminate use of antibiotics mitigated. It is important to establish a correct diagnosis. Acute abdominal pain, elevated pancreatic enzymes, and abnormal enzymatic liver function tests can be seen in patients presenting with acute cholangitis. This is an example of a setting where early antibiotic therapy is useful and thus establishing a diagnosis of acute pancreatitis is critical and CT scan is appropriate where there is diagnostic uncertainty. Role of prophylactic antibiotics (see Table 1). Antibiotics are appropriate if a patient has a concomitant infection, but this is used as treatment rather than prophylaxis. Role of procalcitonin measurement. This should be considered when an empirical decision to treat with antibiotics is being considered. Antibiotic misuse in patients with acute pancreatitis is widespread and constitutes an important iatrogenic harm. Recognizing the importance of antibiotics and at the same time minimizing the individual and population risks from emergence of resistant flora from indiscriminate overuse is a key responsibility for all those who care for patients with acute pancreatitis. Practical guide for antimicrobial therapy decision making in acute pancreatitis Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. percutaneous catheter drainage endoscopic necrosectomy laparoscopic cholecystectomy Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. percutaneous catheter drainage endoscopic necrosectomy laparoscopic cholecystectomy Practical guide for antimicrobial therapy decision making in acute pancreatitis Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. percutaneous catheter drainage endoscopic necrosectomy laparoscopic cholecystectomy Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. Do not start antibiotics if <1 ng/ml Stop empiric antibiotics if <1 ng/ml Consider starting antibiotics if >1 ng/ml Continue antibiotics if >1 ng/ml and already on antibiotics. percutaneous catheter drainage endoscopic necrosectomy laparoscopic cholecystectomy The authors have no funding to declare. The authors have no conflicts of interest to declare. Hjalmar van Santvoort (Methodology, Visualization, Writing—original draft, Writing—review & editing), Rogier Voermans (Visualization, Writing—original draft, Writing—review & editing), Nicholas Zyromski (Writing—original draft, Writing—review & editing), and Ajith Siriwardena (Conceptualization, Project administration, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing)