Scenario:
A patient presents to the medicine floor with acute necrotizing pancreatitis (ANP). As acute pancreatitis is associated with high morbidity and mortality with most deaths occurring in patients with acute necrotizing pancreatitis, the team discusses whether or not the patient would benefit from prophylactic use of antibiotics to minimize morbidity and mortality.
Search Question: Clearly state the question (including outcomes or criteria to be tracked)
Is antibiotic prophylaxis beneficial in reducing morbidity and mortality in patients with acute necrotizing pancreatitis?
Identify the PICO Elements:
P = patients with acute necrotizing pancreatitis
I = antibiotic prophylaxis
C = no prophylaxis
O = reduced morbidity and mortality
PICO search terms:
| P | I | C | O |
| Patients with acute necrotizing pancreatitis | Antibiotic prophylaxis | No antibiotic use | Reduced morbidity and mortality |
| Acute necrotizing pancreatitis | Administration of prophylactic antibiotics | Lack of antibiotic prophylaxis | Sepsis and mortality reduction |
| Pancreatic necrosis | Prophylactic parenteral antibiotics | No prophylaxis | Decreased mortality |
Search tools and strategy used:
Databases used: Science Direct, PubMed, Google Scholar
Terms used: antibiotic prophylaxis for acute necrotizing pancreatitis, antibiotic use for patients with acute necrotizing pancreatitis, acute necrotizing pancreatitis and prophylaxis
Articles returned:
– Science Direct: +last 10 years
o antibiotic prophylaxis for acute necrotizing pancreatitis – 1,459 results
o antibiotic use for patients with acute necrotizing pancreatitis – 3,916 results
o acute necrotizing pancreatitis and prophylaxis – 1,790 results
– PubMed: +last 15 tears
o antibiotic prophylaxis for acute necrotizing pancreatitis – 420 results
o antibiotic use for patients with acute necrotizing pancreatitis – 1,103 results
o acute necrotizing pancreatitis and prophylaxis – 1,538 results
– Google Scholar: +last 15 years
o antibiotic prophylaxis for acute necrotizing pancreatitis – 11,300 results
o antibiotic use for patients with acute necrotizing pancreatitis – 21,100 results
o acute necrotizing pancreatitis and prophylaxis – 26,300 results
How I narrowed down my chosen articles:
I narrowed my choices to a few selected articles based on the type of study done, namely meta-analysis, systematic review and randomized controlled trials to ensure a high level of evidence. I chose articles that directly answered my PICO question and compared the use of antibiotic prophylaxis with no prophylaxis OR administration of antibiotics as a treatment as opposed to a prophylactic measure. I chose articles which measured certain outcomes including infected pancreatic necrosis (IPN), non-pancreatic infections (NPN), mortality, sepsis and surgical intervention.
Chosen articles:
| Article 1:Prophylactic Antibiotic Administration Reduces Sepsis and Mortality in Acute Necrotizing Pancreatitis: A Meta-AnalysisSharma, Virender Kumar; Howden, Colin W.* |
| Link: https://journals.lww.com/pancreasjournal/Fulltext/2001/01000/Prophylactic_Antibiotic_Administration_Reduces.5.aspx |
| Abstract:Severe acute pancreatitis is frequently complicated by local and systemic infections resulting in substantial morbidity, mortality, and health care costs. Antibiotic prophylaxis may prevent some infections. We searched for randomized, controlled trials comparing antibiotic prophylaxis with no prophylaxis in patients with acute necrotizing pancreatitis (ANP). Only trials that used antibiotics that reach minimum inhibitory concentration (MIC) in necrotic pancreatic tissue were included. We calculated relative risk reduction (RRR), absolute risk reduction (ARR), and number needed to treat (NNT) for individual trials and pooled data. Antibiotic prophylaxis significantly reduced sepsis by 21.1% (NNT = 5) and mortality by 12.3% (NNT = 8) compared with no prophylaxis. There was also a nonsignificant trend toward a decrease in local pancreatic infections (ARR = 12%; NNT = 8). Antibiotic prophylaxis decreases sepsis and mortality in patients with ANP. All patients with ANP should be given prophylaxis with an antibiotic with proven efficacy in necrotic pancreatic tissue. |
| Type of study:Meta-analysis of randomized controlled trials |
| Main Points:- MEDLINE database search of randomized controlled trials comparing the use of antibiotic prophylaxis with no prophylaxis in patients with ANP- Relative risk reduction, absolute risk reduction and number needed to treat were calculated- Breslow-Day test for homogeneity done to ensure appropriate pooling- Overall rates of pancreatic infection, sepsis and mortality were calculated- 6 randomized controlled trials were identified overall but only 3 included as these focused on patients with acute necrotizing pancreatitis- 2 included patients with severe ANP without pancreatic necrosis on CT and one compared prophylaxis with 2 different antibiotics- 84 patients received antibiotic prophylaxis, 76 control patients did not. Both groups received standard care for pancreatitis – supportive treatment- 1 trial found significant reduction in sepsis in the antibiotic prophylaxis group and 1 trial found significant reduction in mortality in the prophylaxis group- Results – revealed significant improvement in sepsis and mortality in patients with ANP receiving antibiotic prophylaxis with a trend toward reduction in pancreatic infection- Limitations – combining results of different trials, minor variation in inclusion criteria, different antibiotics used for prophylaxis and different protocols used to diagnose pancreatic infection |
| Why I chose it:I chose this article because it’s a meta-analysis of randomized controlled trials directly answering my PICO question. It analyzed articles comparing the use of antibiotic prophylaxis to no prophylaxis in patients with acute necrotizing pancreatitis. This article clearly listed its limitations at the end of the conclusion which gives it credibility. |
| Article 2:Early prophylactic antibiotics administration for acute necrotizing pancreatitis: a meta-analysis of randomized controlled trialsTomohiko Ukai · Satoru Shikata · Machiko Inoue · Yoshinori Noguchi · Hisato Igarashi · Shuji Isaji · Toshihiko Mayumi · Masahiro Yoshida · Yousuke C. Takemura |
| Link:https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/pdfdirect/10.1002/jhbp.221 |
| Abstract:Background The effectiveness of prophylactic antibiotics use for acute necrotizing pancreatitis has been explored and a number of systematic reviews have been published with conflicting results. The timing of antibiotics administration can be fundamental to their effectiveness, but thus far no re- views have focused on the timing of administration. Methods A systematic review of randomized controlled tri- als (RCTs) of prophylactic antibiotics for acute necrotizing pancreatitis was conducted using MEDLINE (PubMed), CINAHL and Japana Centra Revuo Medicina. Trials in which antibiotics were administered within 72 h after onset of symp- toms or 48 h after admission were included. Our primary out- comes were the mortality rate and the incidence of infected pancreatic necrosis, and secondary outcomes were the inci- dence of non-pancreatic infection and the incidence of surgi- cal intervention.Results The search revealed six RCTs with a total of 397 pa- tients. The mortality rates were significantly different for those taking antibiotics (7.4%), and controls (14.4%) (odds ra- tio [OR], 0.48; 95% confidence interval [CI], 0.25–0.94). Also, early prophylactic antibiotics use was associated with reduced incidence of infected pancreatic necrosis (antibiotics 16.3%, controls 25.1%; OR, 0.55; 95% CI, 0.33–0.92). Conclusion Early use of prophylactic antibiotics for acute necrotizing pancreatitis is associated with reduced mortality and lower incidence of infected pancreatic necrosis. |
| Type of study:Systematic review and meta-analysis of randomized controlled trials |
| Main points:- MEDLINE (PubMed), CINAHL and JAPANA Centra Revuo Medicina used to conduct systematic review of prophylactic antibiotic use for acute necrotizing pancreatitis- Primary outcomes – mortality rate and incidence of infected pancreatic necrosis- Secondary outcomes – incidence of non-pancreatic infection and incidence of surgical intervention- 6 randomized controlled trials identified, total of 397 patients- Antibiotic prophylaxis was also found to be associated with a reduction in incidence of infected pancreatic necrosis- Infected pancreatic necrosis – 564 patients in 9 trials comparing prophylactic antibiotics with no prophylaxis on IPN. Prophylaxis treatment found to have significant effects on reduction of IPN- Mortality – antibiotics were not associated with a significant reduction in mortality- Nonpancreatic infection – 8 studies reported in patients with NPN, antibiotic prophylaxis was not found to be significant in reducing NPN |
| Why I chose this article:I chose this article because it is a systematic review/meta-analysis of RCTs which is a high level of evidence. It directly answered my PICO question with focused primary and secondary outcomes measured. |
| Article 3:Meta-analysis of prophylactic parenteral antibiotic use in acute necrotizing pancreatitis Žilvinas Dambrauskas1, 2, Antanas Gulbinas1, 2, Juozas Pundzius1, Giedrius Barauskas1 |
| Link:https://pubmed.ncbi.nlm.nih.gov/17485956/ |
| Abstract:Background: Acute pancreatitis is a potentially serious condition. It carries an overall mortality rate of 10-15%. Infectious complications account for approximately 80% of deaths from acute pancreatitis, and the question arises whether or not prophylactic antibiotics are useful in the prevention of these complications. Therefore, we performed an evidence-based analysis to assess the effect of available prophylactic antimicrobial treatment on the development of infected necrosis and sepsis, need for surgery, and mortality.Methods: A comprehensive PubMed search was performed evaluating the value of prophylactic administration of parenteral antibiotics in patients with acute necrotizing pancreatitis. Only articles published in English language between January 1990 and May 2006 were included. The search strategy initially generated 692 articles related to antibiotics in the treatment of acute pancreatitis. This number was reduced to 97 publications related to clinical trials on the same topic. Finally, 10 randomized clinical trials concerning prophylactic parenteral antibiotics in patients with acute necrotizing pancreatitis were identified. We have performed a meta-analysis using the random-effects model to assess the impact of prophylactic antibiotics on development of infected pancreatic necrosis and sepsis, need for surgery, and overall mortality.Results: Patients with necrotizing acute pancreatitis should receive effective antibiotic prophylaxis (i.e., carbapenems intravenously) to decrease the risk of infected necrosis and sepsis and need of surgery.Conclusions: While providing new insights into key aspects of antibiotic prophylaxis, this evidence-based analysis highlights the need for further clinical trials regarding the indications for antibiotic prophylaxis. |
| Type of study:Meta-analysis |
| Main points:- PubMed search performed evaluating parenteral administration of antibiotics in patients with acute necrotizing pancreatitis- 692 articles identified, 10 randomized clinical trials included in the study.- Random-effects model used to assess the effect of prophylactic antibiotics on potential development of infected pancreatic necrosis and sepsis, need for surgery and mortality.- Only series with CT-proven pancreatic necrosis were included in the meta-analysis- Overall, 1,279 patients included in the meta-analysis. 641 received prophylactic antibiotics and 638 were the control group.- Primary outcomes – infected necrosis, mortality- Secondary outcomes – need for surgery, incidence of sepsis- Infected necrosis – 324 patients experienced infected necrosis, 113 in prophylactic group and 211 in control group. Antibiotic prophylaxis was associated with reduction in risk of occurrence of infected necrosis- Mortality – 209 patients died, 88 in prophylactic group and 121 in control group. Antibiotic prophylaxis was associated with significant reduction in mortality rate.- Need for surgery – 167 patients had surgery, 59 in prophylactic group and 108 in control group. Tx with antibiotics was associated with reduced need to go to surgery- Sepsis – 307 patients were septic, 90 in prophylactic group and 217 in the control group. Antibiotics were associated with reduced incidence of sepsis.- Antibiotic prophylaxis was found to be superior compared to no prophylaxis or antibiotic treatment but not done prophylactically.- Patients should receive antibiotics prophylactically, namely carbapenems. |
| Why I chose this article:This article is a meta-analysis and directly answers my PICO question. Its primary and secondary outcomes measured what I was looking to measure. This article broke down the numbers of patients in each group and each primary/secondary outcome very clearly, listing the number of patients in the prophylactic and control group and their outcomes. 1,279 patients were including in this meta-analysis which is a nice sample size and gives credibility to its results. I also like that this article compared antibiotic prophylaxis to antibiotic treatment, both have use of antibiotics but one is prophylactic and one is not. |
| Article 4:Prophylactic antibiotics reduce pancreatic necrosis in acute necrotizing pancreatitis: a meta-analysis of randomized trialsLinhua Yao, Xiayue Huang, Yuqin Li, Ruihua Shi, Guoxin Zhang |
| Link:https://www.karger.com/Article/Pdf/318780 |
| Abstract:Background and Aim: The use of prophylactic antibiotics to prevent infection and reduce mortality in patients with acute necrotizing pancreatitis (ANP) remains controversial. The aim of this study is to perform a systematic review of the data from randomized controlled trials to compare prophy- lactic antibiotic treatment of patients with ANP versus pla- cebo. Methods: A computerized literature search was con- ducted using Medline, PubMed, EMBase and Cochrane Cen- tral Register of Controlled Trials (CENTRAL) for relevant articles published in English from January 1990 to March 2010. MeSH terms and keywords used to identify articles in- cluded ‘antibiotic’, ‘pancreatitis’, and ‘randomized’. Outcome measures were infected pancreatic necrosis (IPN), mortality, nonpancreatic infection (NPN) and need for surgical inter- vention. Results: Nine trials involving 564 patients were in- cluded. Analysis suggested that IPN was significantly re- duced by treatment with antibiotics (RR 0.73, 95% CI 0.54– 0.98, p = 0.04). Mortality (p = 0.1), NPN (p = 0.07), and need for surgical intervention (p = 0.17) were not significantly re- duced by antibiotic treatment. Subsequent subgroup analysis confirmed that antibiotics were statistically superior to controls in reducing of infected necrosis (p = 0.003) and also mortality (p = 0.02) in single-blinded randomized controlled trials. Conclusion: Prophylactic antibiotic treatment reduced occurrence of IPN, but did not affect mortality, NPN, or surgi- cal intervention in patients with ANP. |
| Type of study:Meta-analysis of randomized trials |
| Main points:- Computerized literature search conducted using Medline, PubMed, EMBase and Cochrane Central Register of Controlled Trials- 9 trials identified including 564 patients- Trials from single-blinded, double-blinded, single-center and multi-center studies were included. Different antibiotics were used and tested- Fixed-effects and random-effects were used to pool data according to heterogeneity- Infected pancreatic necrosis – results showed that antibiotic prophylaxis was found to significantly reduce rate of infected pancreatic necrosis (IPN) and results with different antibiotic agents didn’t differ- Mortality – antibiotics weren’t found to significantly reduce mortality, only when using cephalosporins was mortality somewhat effected- Nonpancreatic infection – antibiotics weren’t found to significant reduce nonpancreatic infection- Surgical interventions – antibiotics weren’t found to reduce the need for surgical intervention |
| Why I chose this article:This article is a meta-analysis of randomized trials which is a high level of evidence. It directly answered my PICO question and measured primary and secondary outcomes. 9 trials were included in this study which is more than many other meta-analyses I saw, lending to its credibility. |
| Article 5:Prophylactic Antibiotic Treatment in Patients with Predicted Severe Acute Pancreatitis: a placebo-controlled, double-blind trial Rainer Isenmann, Michael Runzi, Martina Kron, Haral Goebell, Hans G. Berger |
| Link:https://www.gastrojournal.org/article/S0016-5085(03)02150-4/fulltext |
| Abstract: |
| Type of study:Double-blind, randomized, multicenter trial |
| Main points:- Double-blind, randomized, multicenter trial with a sample size of 200 patients.- 114 patients with acute pancreatitis + either C-reactive protein over 150 mg/L and/or necrosis on CT with contrast- Patients received either IV ciprofloxacin (2 x 400 mg/day) + metronidazole (2 x 500 mg/day) or a placebo.- If a patient’s condition worsened for example infectious complicates, multiple organ failure sepsis or systemic inflammatory response syndrome (SIRS) then the prophylactic/placebo regimen was stopped and open antibiotics were started.- 58 patients received the antibiotic combination and 56 patients received the placebo.- Results – 28% of patients in the antibiotic prophylaxis group required open antibiotic treatment compared with 46% of patients in the placebo group.- 12% of patients in the antibiotic group developed infected pancreatic necrosis compared with 9% of patents in the placebo group.- Mortality was 5% in the antibiotic group and 7% in the placebo group.- Prophylactic antibiotics were found to lower the risk of progression to infectious complications, MODS and SIRS and minimize mortality. |
| Why I chose this article:I chose this article because it is a double-blind, randomized multicenter trial yielding evidence of high credibility. It directly answered my PICO question by comparing the effect of antibiotic prophylaxis vs placebo in patients with severe acute necrotizing pancreatitis. |
| Article 6:Effect of Antibiotic Prophylaxis on Acute Necrotizing Pancreatitis: Results of a randomized controlled trialJohn Slavin1, Paula Ghaneh1, Robert Sutton1, Mark Hartley1, Peter Rowlands2, Conall Garvey2, Mark Hughes2 and John Neoptolemos1 |
| Link:https://onlinelibrary-wiley-com.york.ezproxy.cuny.edu/doi/full/10.1111/j.1440-1746.2008.05758.x |
| Abstract:Background and Aims: This study addresses whether antibiotic prophylaxis is beneficial for acute necrotizing pancreatitis.Methods: This randomized, controlled trial enrolled 276 patients with severe acute pancreatitis. There were 56 patients with 30% or more necrosis proved by contrast-enhanced computerized tomography who were eligible for randomization: 29 in the study group and 27 in the control group, who received i.v. imipenem–cilastatin (3 × 500 mg/day) within 72 h of the onset of symptoms for 7–14 days, and no antibiotic prophylaxis, respectively. The primary end-point was the incidence of infectious complication. The secondary end-points were mortality, the incidence of necrosectomy for infected necrosis, the incidence of organ complication and hospital courses.Results: Characteristics of baseline data were similar in the two groups. No significant differences were found in the incidence of infected pancreatic necrosis (37% vs 27.6%), mortality (10.3% vs 14.8%) and the incidence of operative necrosectomy (29.6% vs 34.6%) between the study group and the control group (P > 0.05). The incidence of extrapancreatic infections, organ complications and hospital courses between the groups were also not significantly different. However, a significantly increased incidence of fungal infection was observed in the study group versus the control group (36.1% vs 14.2%, P < 0.05).Conclusion: There was no benefit in the outcomes when antibiotic prophylaxis was routinely used in patients with acute necrotizing pancreatitis. |
| Type of study:Randomized controlled trial |
| Main points:- Randomized controlled trial with a sample size of 276 patients with severe acute pancreatitis.- 56 patients had 30% or more pancreatic necrosis shown through CT with contrast. 29 were placed in the study group and 27 in the control group.- The study group received IV imipenem-cilastatin (3 x 500 mg/day) within 3 days of onset of symptoms. Duration of treatment lasted 7-14 days.- The control group received no antibiotic prophylaxis.- Primary outcome was the incidence of infectious complications. Secondary outcomes included mortality, incidence of necrosectomy secondary to pancreatic necrosis, organ complication and hospital courses.- Results – no significant differences were found between the two groups regarding incidence of infected pancreatic necrosis, mortality and incidence of operative necrosectomy.- There was no statistically significant difference found between the two groups, when antibiotic prophylaxis was used in patients with acute necrotizing pancreatitis and when it was not. |
| Why I chose this article:I chose this article because it is a randomized controlled trial and it directly answers my PICO question. It is also the first article I came across which did not find any real benefit to using antibiotic prophylaxis in patients with acute necrotizing pancreatitis. |
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample/Setting(# of subjects/ studies, cohort definition etc. ) | Outcome(s) studied | Key Findings | Limitations and Biases |
| Sharma, Virender Kumar; Howden, Colin W.* 2001 | Meta-analysis of randomized controlled trials | MEDLINE database search of randomized controlled trials. 6 randomized controlled trials identified, 3 included. 84 patients in study group, 76 in the control group. | Compared the use of antibiotic prophylaxis with no prophylaxis in management of acute necrotizing pancreatitis. | Results revealed significant improvement in sepsis and mortality in patients with acute necrotizing pancreatitis receiving antibiotic prophylaxis with a trend toward reduction in pancreatic infection. | Combined results of different trials, minor variation in inclusion criteria, different antibiotics used for prophylaxis and different protocols used to diagnose pancreatic infection. |
| Tomohiko Ukai · Satoru Shikata · Machiko Inoue · Yoshinori Noguchi · Hisato Igarashi · Shuji Isaji · Toshihiko Mayumi · Masahiro Yoshida · Yousuke C. Takemura 2015 | Systematic review and meta-analysis of randomized controlled trials | MEDLINE (PubMed), CINAHL and JAPANA Centra Revuo Medicina used to conduct systematic review. 6 randomized controlled trials identified, total of 397 patients. Another outcome studied with 9 trials and 564 patients. | Effect of prophylactic antibiotic use on mortality rate, incidence of infected pancreatic necrosis, incidence of non-pancreatic infection and incidence of surgical intervention. | Antibiotic prophylaxis was found to be associated with a reduction in incidence of infected pancreatic necrosis. Less benefit regarding mortality and non-pancreatic infections. | Each trial included was aimed at antibiotic use vs non-use and did not have a primary interest in timing of antibiotics administration. Definition of time which regimen was started differed among the trials included in the study. |
| Žilvinas Dambrauskas1, 2, Antanas Gulbinas1, 2, Juozas Pundzius1, Giedrius Barauskas1 2007 | Meta-analysis | PubMed search performed. 692 articles identified, 10 randomized clinical trials included in this study. 1,279 patients included in the meta-analysis – 641 received prophylactic antibiotics and 638 were in the control group. | Evaluated parenteral administration of prophylactic antibiotics in patients with acute necrotizing pancreatitis. | Antibiotic prophylaxis was found to be superior compared to no prophylaxis or antibiotic treatment not done prophylactically regarding outcomes of infected necrosis, mortality, need for surgery and incidence of sepsis. | Number of patients in the sample size is relatively small and the power to evaluate differences in the clinical outcomes wasn’t calculated. |
| Linhua Yao, Xiayue Huang, Yuqin Li, Ruihua Shi, Guoxin Zhang 2010 | Meta-analysis of randomized trials | Computerized literature search conducted using Medline, PubMed, EmBase and Cochrane Central Register of Controlled Trials. 9 trials identified including 564 patients. | Studied if prophylactic antibiotics reduced pancreatic necrosis in acute necrotizing pancreatitis. | Antibiotic prophylaxis was found to significantly reduce the rate of infected pancreatic necrosis (IPN) and results with different antibiotic agents didn’t differ. Less to no benefit found regarding mortality, nonpancreatic infection and surgical intervention. | Search was limited to human studies, no other limitations or biases stated. |
| Rainer Isenmann, Michael Runzi, Martina Kron, Haral Goebell, Hans G. Berger 2003 | Double-blind randomized multicenter trial |
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