Prophylactic Antibiotics Reduce Pancreatic Necrosis in Acute Necrotizing Pancreatitis: A Meta-Analysis of Randomized Trials

Yao, Lanlin; Huang, Xiaofeng; Li, Yuqin; Shi, Ruihua; Zhang, Guoxin

doi:10.1159/000318780

Cited by 42 publications

(29 citation statements)

References 67 publications

(55 reference statements)

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“…Overall, 6 of the 18 studies concluded that prophylactic antibiotics significantly reduced total mortality, which includes 17 RCTs, 18,[20][21][22][23][24] while 4 studies concluded that prophylactic antibiotics significantly reduced the incidence of pancreatic necrosis. 18,20,25,26 The two most recent studies included, 20,21 supported the use of antibiotics. Ukai et al 20 included six RCTs in which antibiotics (within 72 hours) were administered early in patients with acute necrotising pancreatitis, with the exclusion of studies with delayed or indeterminate timing of antibiotic administration.…”

Section: Mortality In Pancreatitis: Are Antibiotics Protective?mentioning

confidence: 99%

“…As mentioned above, 6 of the 18 studies included in the current review were associated with reduced mortality when prophylactic antibiotics were used and the remaining 12 meta-analyses did not recommend the use of prophylactic antibiotic as there was no significant reduction in mortality with them. [25][26][27][30][31][32][33][34][35][36][37][38] These meta-analyses used a combined total of 14 RCTs with total study population varied from 329 to 841 patients.…”

Section: Mortality In Pancreatitis: Are Antibiotics Protective?mentioning

confidence: 99%

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Prophylactic antibiotics in acute pancreatitis: endless debate

Mourad

Evans

Kalidindi

et al. 2017

annals

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INTRODUCTION The development of pancreatic infection is associated with the development of a deteriorating disease with subsequent high morbidity and mortality. There is agreement that in mild pancreatitis there is no need to use antibiotics; in severe pancreatitis it would appear to be a logical choice to use antibiotics to prevent secondary pancreatic infection and decrease associated mortality. MATERIALS AND METHODS A non-systematic review of current evidence, meta-analyses and randomized controlled trials was conducted to assess the role of prophylactic antibiotics in acute pancreatitis and whether it might improve morbidity and mortality in pancreatitis. RESULTS Mixed evidence was found to support and refute the role of prophylactic antibiotics in acute pancreatitis. Most studies have failed to demonstrate much benefit from its routine use. Data from our unit suggested little benefit of their routine use, and showed that the mortality of those treated with antibiotics was significantly higher compared with those not treated with antibiotics (9% vs 0%, respectively, P = 0.043). In addition, the antibiotic group had significantly higher morbidity (36% vs 5%, respectively, P = 0.002). CONCLUSIONS Antibiotics should be used in patients who develop sepsis, infected necrosis-related systemic inflammatory response syndrome, multiple organ dysfunction syndrome or pancreatic and extra-pancreatic infection. Despite the many other factors that should be considered, prompt antibiotic therapy is recommended once inflammatory markers are raised, to prevent secondary pancreatic infection. Unfortunately, there remain many unanswered questions regarding the indications for antibiotic administration and the patients who benefit from antibiotic treatment in acute pancreatitis.

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Section: Mortality In Pancreatitis: Are Antibiotics Protective?mentioning

confidence: 99%

Section: Mortality In Pancreatitis: Are Antibiotics Protective?mentioning

confidence: 99%

Prophylactic antibiotics in acute pancreatitis: endless debate

Mourad

Evans

Kalidindi

et al. 2017

annals

View full text Add to dashboard Cite

show abstract

“…This is still a much debated issue, given the fact that a great number of papers, with remarkable heterogeneities in experimental designs and clinical groups addressing this question have been published so far. More notably, a group of recently published meta-analyses have failed to show a convincing role for prophylactic antibiotics in these patients, and since then, most groups have moved towards abolishing this practice [18,19,20,21]. Alternatively, the use of non-absorbable antibiotics via the oral route (selective digestive decontamination) as a strategy to reduce the rates of pancreatic necrosis has been recently proposed with some promising results [22,23].…”

Section: Antibiotic Therapy In Sapmentioning

confidence: 99%

Necrotizing Pancreatitis: Update and When to Operate

Refinetti¹,

Martinez²

2012

CMD

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About 20% of the cases of acute pancreatitis present in a severe form, known as necrotizing pancreatitis. Although this entity was first described centuries ago, many questions about it remain open and as a consequence, many studies are currently published addressing this subject nowadays. We performed a throughout research in the literature, with special attention to the articles published in the last five years and indexed to the PubMed. The following headings were used: Pancreatitis, Surgical procedures, Necrosis. The initial research rendered about 1800 articles, and the ones published in the last five years were evaluated. Some older, but remarkable articles were also included given their importance to this matter. As we further describe, treatment of acute pancreatitis involves a great number of questions, among which the most important are the ones related to the terminology of pancreatic collections, prognostic markers, use of antibiotics, type of diet employed and the approach to infected necrosis. Many radical changes could be seen over the last years on all these topics and a constant updating must be necessarily done by the ones involved in the treatment of this disease.

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“…Although polymicrobial infections caused by anaerobes and aerobes, including Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, and Bacteroides fragilis are frequent in patients with SAP (2, 4, 13, 19), antibiotic prophylaxis is not recommended; however, in case of infectious complications, treatment with, e.g., a fluoroquinolone or a carbapenem is indicated (1,4,12,16,21,23,25).…”

mentioning

confidence: 99%

“…There is a 40 to 60% risk of pancreatic infections in patients with necrotizing pancreatitis, so antibacterial treatment is justified. Actually, carbapenems or ciprofloxacin are recommended (1,5,12,21,25). However, in contrast to ciprofloxacin, moxifloxacin is active against anaerobes; furthermore, its pharmacokinetic profile is more favorable than that of ciprofloxacin, as the concentrations of moxifloxacin in pancreatic tissue exceed the corresponding serum concentrations 3-fold (22), compared to a 1:1 ratio for ciprofloxacin (6,15).…”

mentioning

confidence: 99%

Activity of Moxifloxacin, Imipenem, and Ertapenem against Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, and Bacteroides fragilis in Monocultures and Mixed Cultures in an In Vitro Pharmacokinetic/Pharmacodynamic Model Simulating Concentrations in the Human Pancreas

Schubert

Dalhoff

2012

Antimicrob Agents Chemother

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The activities of moxifloxacin, imipenem, and ertapenem against pathogens causing severe necrotizing pancreatitis were studied in an in vitro pharmacokinetics/pharmacodynamics (PK/PD) model. Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, and Bacteroides fragilis were exposed in monocultures and mixed cultures to concentrations of the three agents comparable to those in the human pancreas. Moxifloxacin was more active than the two carbapenems in monocultures and mixed cultures, reducing the numbers of CFU more drastically and more rapidly. Infectious complications are the major determinant of morbidity and mortality in patients with severe acute pancreatitis (SAP), in particular in patients with necrotizing pancreatitis. Although polymicrobial infections caused by anaerobes and aerobes, including Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, and Bacteroides fragilis are frequent in patients with SAP (2, 4, 13, 19), antibiotic prophylaxis is not recommended; however, in case of infectious complications, treatment with, e.g., a fluoroquinolone or a carbapenem is indicated (1,4,12,16,21,23,25).Thus, we assessed the pharmacokinetics/pharmacodynamics (PK/PD) of moxifloxacin, imipenem, and ertapenem against SAP pathogens by simulating the regimens that either are recommended for treatment of SAP (carbapenems) or are commercially available (moxifloxacin).(Part of the data in this publication were presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, MA, September 2010, and at the 21st conference of the European Society of Clinical Microbiology and Infectious Diseases, Milan, Italy, May 2011.) Drug concentrations were deduced by log-linear regression from published data following infusions of 400 mg moxifloxacin (22) and 1,000 mg each of imipenem (3, 18) and ertapenem (24). The following maximal total drug concentrations (C max ), time to C max (T max ), and elimination half-life (t 1/2 ) in human pancreatic tissue were deduced from these published data: for moxifloxacin, C max ϭ 4.6 mg/liter, T max ϭ 5 h, and t 1/2 ϭ 8; for imipenem, C max ϭ 16 mg/liter, T max ϭ 0.25 h, and t 1/2 ϭ 1.3 h; for ertapenem, C max ϭ 1.3 mg/liter, T max ϭ 0.5 h, and t 1/2 ϭ 4 h. For calculation of free drug concentrations, the following was considered. First, binding of antibiotics to serum proteins was assessed (moxifloxacin, 40% [20]; imipenem, 20% [11]; ertapenem, 95% [17]). Second, all agents bind predominantly to albumin. Third, albumin concentrations in serum amount to 4.5%, compared to 1.3% in pancreatic juice (7,8). This difference in albumin content was considered for the calculation of free drug concentrations in serum and pancreatic tissue, respectively.E. coli ATCC 11775, E. cloacae ATCC 13047, E. faecalis ATCC 19433, and B. fragilis ATCC 25285 served as indicator strains. The Enterobacteriaceae were cultivated aerobically in cation-adjusted Mueller-Hinton broth, and B. fragilis in monoculture as well as B. fragilis and E. coli in mixed culture were grown anae...

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Prophylactic Antibiotics Reduce Pancreatic Necrosis in Acute Necrotizing Pancreatitis: A Meta-Analysis of Randomized Trials

Cited by 42 publications

References 67 publications

Prophylactic antibiotics in acute pancreatitis: endless debate

Prophylactic antibiotics in acute pancreatitis: endless debate

Necrotizing Pancreatitis: Update and When to Operate

Activity of Moxifloxacin, Imipenem, and Ertapenem against Escherichia coli, Enterobacter cloacae, Enterococcus faecalis, and Bacteroides fragilis in Monocultures and Mixed Cultures in an In Vitro Pharmacokinetic/Pharmacodynamic Model Simulating Concentrations in the Human Pancreas

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