==== Front BMC Gastroenterol BMC Gastroenterol BMC Gastroenterology 1471-230X BioMed Central London 1563 10.1186/s12876-020-01563-x Research Article Compositional and drug-resistance profiling of pathogens in patients with severe acute pancreatitis: a retrospective study Fan Ning 1 Hu Yong 2 Shen Hong 3 Liu Shengjie 4 Zhao Guang 5 Sun Lanju 5 Li Chunyan 6 Zhao Xin 7 Li Yanning 1 Wang Jianhua 1 http://orcid.org/0000-0002-1071-3333Cui Yunfeng nkyycyf@163.com 58 1 grid.410648.f0000 0001 1816 6218Department of Surgery, Beichen Chinese Medicine Hospital, Tianjin University of Traditional Chinese Medicine, Tianjin, China 2 grid.413247.7Zhongnan Hospital of Wuhan University, No. 167, Donghu Road, Wuchang District, Wuhan, 430000 China 3 Department of Surgery, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, China 4 grid.410648.f0000 0001 1816 6218Tianjin University of Traditional Chinese Medicine, Tianjin, China 5 grid.265021.20000 0000 9792 1228Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, Tianjin, China 6 Department of Gastroenterology, Affiliated Hospital of Panzhihua University, Nanchong, China 7 grid.414008.90000 0004 1799 4638Department of Breast Surgery,Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China 8 grid.265021.20000 0000 9792 1228Department of Surgery, Tianjin Nankai Hospital, Nankai Clinical School of Medicine, Tianjin Medical University, 122 Sanwei Road Nankai District, Tianjin, China 1 12 2020 1 12 2020 2020 20 40517 7 2020 26 11 2020 © The Author(s) 2020Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background Infection is one of the important causes of death in patients with severe acute pancreatitis (SAP), but the bacterial spectrum and antibiotic resistance are constantly changing. Making good use of antibiotics and controlling multi-drug-resistant (MDR) bacterial infections are of vital importance in improving the cure rate of SAP. We conducted a retrospective study in the hope of providing references for antibiotic selection and control of drug-resistant bacteria. Methods Retrospective analysis was performed on the data of patients hospitalized in our hospital due to acute pancreatitis (AP) in the past 5 years. General data were classified and statistically analyzed. Subsequently, the bacterial spectrum characteristics and the data related to drug-resistant bacterial infection of 569 AP patients were analyzed. Finally, unconditional logistic regression analysis was conducted to analyze the risk factors of MDR infection. Results A total of 398 patients were enrolled in this study and the hospitalization data and associated results were analyzed. A total of 461 strains of pathogenic bacteria were detected, including 223 (48.4%) gram-negative bacterial strains, 190 (41.2%) gram-positive bacterial strains and 48 (10.4%) fungal strains. The detection rates of resistance in gram-negative and gram-positive bacterial strains were 48.0% (107/223) and 25.3% (48/190), respectively. There were significant differences between the MDR group and the non-MDR group for the factors of precautionary antibiotic use, kinds of antibiotics used, receipt of carbapenem, tracheal intubation, hemofiltration and number of hospitalization days in the intensive care unit. Unconditional logistic regression revealed 2 risk factors for MDR bacterial infection. Conclusions Our results illustrate that gram-negative bacteria were the most common pathogens in SAP infection, and the proportion of gram-positive bacteria increased notably. The rate of antibiotic resistance was higher than previously reported. Unconditional logistic regression analysis showed that using more types of antibiotics and the number of hospitalization days in the ICU were the risk factors associated with MDR bacterial infection. Keywords Severe acute pancreatitisMulti-drug resistant bacteriaBacteria spectrumAntibiotic resistanceRisk factorsissue-copyright-statement© The Author(s) 2020 ==== Body Introduction Acute pancreatitis (AP) is an inflammatory injury with pancreatic edema, hemorrhage and necrosis caused by the self-digestion of pancreatic tissue. Clinical features include acute upper abdominal pain and the elevation of amylase or lipase. AP is classified as mild acute pancreatitis (MAP), moderate to severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). SAP is a critical condition with poor prognosis in the clinic. The mortality rate may be up to 30% [1] due to local and systemic complications, including systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS) or multiple organ dysfunction syndrome (MODS) in the early stage [2−4]. Subsequently, infectious pancreatic necrosis (IPN) will appear in approximately 40 to 70% of patients in the second stage [5, 6], and the mortality rate can be as high as 32 to 50% [7–8] Currently, the treatment of IPN has evolved from open surgery to comprehensive treatment based on minimally invasive techniques, such as endoscopic treatments, percutaneous drainage and minimally invasive necrotic tissue removal [9−11]. Antibiotics are used for almost the entire treatment process [12]. This is because pancreatic and peripancreatic infectious necrosis is mainly caused by intestinal bacterial translocation [13, 14]. However, existing control methods cannot effectively prevent this process, a series of complex infections, such as MDR bacterial infections and fungal infections, often occur in the course of disease development. As such, it is necessary to actively seek prevention and treatment strategies; early use of antibacterial drugs to prevent pancreatic infection is a common method. Because some antibacterial drugs cannot effectively act on the pancreas in the case of systemic drug delivery, there is no effective antibacterial drug that can penetrate necrotic tissue without a blood supply, which increases the difficulty of antibiotic treatment [15]. However, imipenem, clindamycin, piperacillin, fluoroquinolone and metronidazole have sufficient tissue penetration and bactericidal properties for infectious pancreatic necrosis and have certain advantages in preventing and treating IPN [16]. There is still controversy about the prophylactic use of antibiotics to prevent infection [17, 18]. How to identify pancreatic infections early, how to choose antibacterial drugs and how to time treatments are still major problems to be solved in the clinic. The main purpose of this study includes two aspects. First, analyzing the characteristics of the bacterial spectrum and the changes in antibiotic resistance in AP patients is helpful to guide the preventive and empirical use of antibiotics. Second, the analysis of the risk factors for MDR bacterial infections can help doctors avoid particular treatments when controlling infections and delay or reduce MDR bacterial infections as much as possible. Methods General information The data of MAP, MSAP and SAP patients hospitalized in our hospital were collected respectively, according to their diagnoses at the time of discharge. The time range of MAP and MSAP groups was from January 1, 2019 to December 31, 2019. The SAP group collected data over the past five years from January 1, 2015 to December 31, 2019. The patients in SAP group were divided into MDR group and Non-MDR group according to whether they had MDR infection. All patients must meet inclusion and exclusion criteria. Inclusion and exclusion criteria The inclusion criteria were as follows: (1) the patients met the AP diagnostic criteria proposed by the Atlanta consensus meeting [19], and (2) the results of the bacterial culture confirmed the pathogen diagnosis for infection. The exclusion criteria were as follows: (1) patients experiencing pregnancy-associated pancreatitis (2) the presence of a malignant tumor, (3) long-term use of immunosuppressive agents or patients with immune deficiency diseases, and (4) patients with incomplete hospitalization data. Data collection instructions Bacterial culture data and drug sensitivity test data were collected, including abdominal drainage fluid, sputum, blood, bile, deep venous catheter, and urine. The pathogens from the same patient and specimens were not counted repeatedly. The date collection time points were as follows: at admission, 2 weeks after admission, 1 month after admission, and when the patient's clinical condition showed a major turning point. These changes include: (1) the body temperature was above 38 °C or below 36 °C; (2) the patient experienced tachycardia, persistent hypotension (systolic blood pressure below 90 mmHg) or shortness of breath; (3) the patient experienced chills; (4) white blood cell counts increased or were extremely low (white blood cell count (WBC): 18,000 cells /mm3 or WBC < 4000 cell/mm3); (5) platelet counts were < 150,000 cell/mm3, (6) the patient experienced an unexplained elevated CRP in the immunosuppressed state; (7) creatinine levels were > 2.0 mg/dL; or (8) other suspected conditions worsened [20−22]. Risk factors were selected according to the factors that may cause MDR infection as reported in previous literature and clinically invasive procedures [23−26]. Definitions MDR bacteria were defined by the following criteria [27]: (1) third-generation cephalosporin-resistant, (2) β-lactam-resistant Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumonia, and Serratia marcescens), (3) MDR gram-negative rods defined as other gram-negative rods not susceptible to at least one agent in three or more antimicrobial categories (e.g., Acinetobacter baumannii, and Pseudomonas aeruginosa), (4) methicillin-resistant Staphylococcus aureus (MRSA), (5) methicillin-resistant, coagulase-negative staphylococci (MRCNS), and (6) vancomycin-resistant Enterococcus species (VRE). Strain treatment The specimens were cultured using a French BioMerieux BacT/ALERT 3D automatic blood training instrument and a CO2 incubator. A VITEK 2 compact automatic microbiological analyzer was used to identify the positive specimens for drug susceptibility tests. The susceptibility test was based on a breakpoint set by the American Association of Clinical Laboratory Standards (CLSI) in 2015 to determine drug resistance [28]. The quality control strains included Escherichia coli ATCC25922, Enterobacter cloacae ATCC700323, Staphylococcus aureus ATCC29213 and Streptococcus pneumoniae ATCC49619. Statistical analysis WHONET V.5.6 for Windows (WHO Collaborating Center, Boston) was used to collect the data and analyze the pathogens for drug resistance. SPSS V.22.0 for Windows (SPSS Inc., Chicago, IL) was used for statistical analysis, and enumeration data were checked by the chi-square test according to whether the measurement data were normally distributed. A t-test or rank sum test was performed. Fisher's exact test was used for the dichotomous contingency table, according to variable types. A univariate analysis was included in the unconditional logistic regression analysis model to calculate odds ratios (ORs) along with 95% confidence intervals (CIs) to assess the strength of any association, and a 2-sided P < 0.05 was considered statistically significant. Results Clinical data comparison A total of 569 AP patients were retrieved, 127 were excluded owing to the lack of bacterial culture, and 398 were eligible according to the exclusion criteria. There were 198 patients in MAP group, 29 in MSAP group and 171 in SAP group. A detailed study flow-diagram is shown in Fig. 1. Statistical analysis showed that the total hospitalization days was significantly different among the MAP group, MSAP group and SAP group (P = 0.000). The death rate of the SAP group was significantly higher than that of the MAP group and MSAP group (P = 0.000). This is consistent with the severity of the disease (Table 1).Table 1 Clinical data from the MAP, MSAP and SAP group Items MAP MSAP SAP Eligible number 198 29 171  Male 111 18 97  Femal 87 11 74 Age 54.5 ± 16.7 53.8 ± 15.4 52.4 ± 16.3 Etiology  Chololithiasis 129 15 83  Hyperlipidaemia 44 8 36 Alcohol 15 6 28 Others 10 0 24 Total hospitalization days 8.0 ± 3.6 24.0 ± 14.4 54 ± 43.6 Death rate in hospital 0 0 22 Of the 171 patients with SAP, 97 were male and 74 were female, with an average age of 52.4 ± 16.3 years old. The patients were divided into an MDR group (81 cases, 47.4%) and a non-MDR group (90 cases, 52.6%) according to whether MDR bacterial infection was present. There were no significant differences in sex, age, cause of disease, severity of SAP, number of fungal infections and total hospitalization days between the two groups (Table 2).Table 2 Clinical data from the MDR group and non-MDR group Characteristic MDR (n = 81) non-MDR (n = 90) P-value Gender  Male 44 (54.3%) 53 (58.9%) 0.547  Female 37 (45.7%) 37 (41.1%) Age 52.4 ± 16.9 52.3 ± 15.7 0.972 Cause  Biliary 38 (46.9%) 45 (50.0%) 0.678  Hyperlipidemia 19 (23.5%) 17 (18.9%) 0.464  Alcohol 13 (16.1%) 15 (16.7%) 0.913  Othersa 11 (13.6%) 13 (14.4%) 0.683 BISAP score 3.0 ± 1.0 2.6 ± 1.1 0.206 CTSI score 6.6 ± 1.4 6 ± 1.5 0.104 APACHE II score 15.6 ± 8.6 14.1 ± 6.5 0.204 MODS 45 (55.6%) 38 (42.2%) 0.082 SIRSb 81 (100.0%) 90 (100.0%) – Fungal infection 28 (34.6%) 21(23.3%) 0.105 Total hospitalization days 45.3 36.1 0.062 Death rate in hospital 15 (18.5%) 7 (7.8%) 0.036 aSAP with unknown etiology bAll patients had SIRS complications, and we were unable to perform independent statistical analyses Distribution of pathogens A total of 654 strains of pathogenic bacteria were detected, including 348 strains of gram-negative bacteria, 259 strains of gram-positive bacteria and 48 strains of fungi (Fig. 1). In the SAP group, 461 pathogenic strains were detected, among which 223 strains were gram-negative and 190 strains were gram-positive. Escherichia coli was the dominant bacterium in gram-negative bacteria, while enterococcus faecium was the dominant bacteria group in gram-positive bacteria. All the fungi were detected in the SAP group . The source and strain quantities of pathogens are shown in Fig. 2.Fig. 1 Flow diagram of the patients with AP in the study Main bacterial composition and MDR distribution in SAP group A total of 223 strains of gram-negative bacteria were detected in the SAP group, including 99 strains of MDR and 8 strains of extensively drug-resistant bacteria (XDR) Pseudomonas aeruginosa. For gram-positive bacteria, the detection rate of MDR bacteria was 25.3% (48/190). There were 48 strains of fungus and no resistant strains (Figs. 3, 4).Fig. 2 Strains composition diagram Fig. 3 Distribution of pathogen strains in the SAP group Antibiotic resistance analysis in SAP group Gram-negative The detection rates of extended-spectrum beta-lactamases (ESBL) in Escherichia coli and Klebsiella pneumoniae were 82.7% (43/52) and 65% (26/40), respectively. Escherichia coli and Klebsiella pneumoniae were sensitive to carbapenems, but the resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannii to carbapenems were all over 50%. The main bacterial strains were sensitive to piperacillin/tazobactam, except for Acinetobacter baumannii. The main gram-negative bacteria were sensitive to cefoperazone/sulbactam. A strain of tigecycline-resistant Klebsiella pneumoniae was detected (Fig. 5).Fig. 4 Main bacterial composition and MDR distribution in SAP group Gram-positive The detection rate of MRSA was 10.5% (20/190) and that of MRCNS was 2.1% (4/190). Among the enterococci, the resistance rates of Enterococcus faecium to benzyl penicillin and ampicillin were 85.2% and 83.3%, respectively, while the resistance rates of Enterococcus faecalis were both 42.3%. The resistance rates of Enterococcus faecium and Enterococcus faecalis to high concentration gentamicin combined with ampicillin were 64.8% and 57.7%, respectively. There were no strains resistant to vancomycin, temozolomide or linezolid (Fig. 6).Fig. 5 The main gram-negative bacteria resistance rate Fig. 6 Main gram-positive bacteria resistance rate Comparison of MDR infection factors A total of 12 risk factors for MDR bacterial infection in the MDR and non-MDR groups were compared and included the following: precautionary antibiotic use, kinds of antibiotics used, use of carbapenem antibiotics, use of aminoglycoside antibiotics, average number of days of antibiotic use, endoscopic operation, intraperitoneal catheterization, venipuncture, preservation of the catheter, tracheal intubation, hemofiltration and number of hospitalization days in the ICU. Univariate analysis revealed 6 statistically significant infection factors, namely, precautionary antibiotic use (P = 0.030), kinds of antibiotic used (P = 0.005), use of carbapenem antibiotics (P = 0.009), tracheal intubation (P = 0.029), hemofiltration (P = 0.047) and number of hospitalization days in the ICU (P = 0.018) (Table 3).Table 3 comparison of infection factors between the MDR group and non-MDR group Infection factors MDR (n = 81) non-MDR (n = 90) P-value Precautionary antibiotics 44 (54.3%) 34 (37.8%) 0.030 Kinds of antibiotics 3 2 0.005 Carbapenems 58 (71.6%) 47 (52.2%) 0.009 Aminoglycosides 8 (9.9%) 7 (7.8%) 0.628 Antibiotic daysa 34.1 27.0 – Endoscopic operationb 10 (12.3%) 10 (11.1%) 0.802 Intraperitoneal catheterizationc§ 81 (100.0%) 90 (100.0%) – Venipunctured 81(100.0%) 90 (100.0%) – Catheter preservationd 81 (100.0%) 90 (100.0%) – Tracheal intubation 26 (32.1%) 16 (17.8%) 0.029 Hemofiltration 9 (11.1%) 3 (3.3%) 0.047 Hospitalization days in the ICU 13 4 0.018 aBecause of the social and human factors, the credibility of the data was low, so it was excluded. bIncluding ERCP, ENBD, endoscopic ultrasonography-guided puncture drainage, etc. cIntraperitoneal catheterization included intraoperative abdominal catheterization and B ultrasound/CT guided abdominal puncture drainage dAll patients were included and were unable to perform independent statistical analyses Risk factors MDR bacterial infection was the dependent variable, and the independent variables were precautionary antibiotic use, kinds of antibiotics used, receipt of carbapenem, receipt of aminoglycosides, endoscopic operation, tracheal intubation, hemofiltration and number of hospitalization days in the ICU. The independent variables were assigned from X1 to X8. Classification covariates were set to dummy variables, and 2 dummy variables were generated by X2 (X2(1) represented 3 < n < 7, X2(2) represented n ≥ 7). X2(1) was a high-risk factor for MDR bacterial infection (OR 3.319; 95% CI 1.486–7.414; P = 0.003), and X8 was a moderate risk factor for MDR bacterial infection (OR 1.048; 95% CI 1.002–1.095; P = 0.039) (Table 4).Table 4 Unconditioned logistic regression analysis of risk factors for MDR infection Risk factors B S.E Wald df P-value OR 95% CI X2 9.464 2 0.009 X2(1) 1.200 0.410 8.557 1 0.003 3.319 1.486–7.414 X2(2) − 0.586 0.990 0.350 1 0.554 0.557 0.080–3.874 X8 0.047 0.023 4.251 1 0.039 1.048 1.002–1.095 B, partial regression coefficient; S.E, standard error; OR, odds ratio; CI, confidence Interval. X2, kinds of antibiotics; X2(1) represented 3 < n < 7, X2(2) represented n ≥ 7; X8, hospitalization days in ICU Discussion Our study found that there was no significant difference in the severity of SAP between the MDR and non-MDR groups. The mortality rate in the MDR group was significantly higher than that in the non-MDR group, which indicated that MDR bacterial infection was an important cause of death in SAP patients. This is because as the disease progresses, compensatory anti-inflammatory response syndrome (CARS) and SIRS compound one other and gradually worsen, resulting in mixed antagonistic response syndrome (MARS) [29]. The advantage of a proinflammatory response over an anti-inflammatory response is gradually reversed, and the patient sustains low levels of inflammation with severe immunosuppression development eventually [30]. SAP changes from an early aseptic chemical inflammation to a secondary multisite MDR bacterial infection; uncontrolled pancreatic and severe systemic infections cause sepsis, infectious bleeding, digestive tract spasms and other complications leading to death [31]. However, such findings must be interpreted cautiously because they are probably correlated with the fact that the peak of death occurred in the first and second stage, which was more frequent among patients who were more severely ill, while the MDR bacterial infection occurred later. The total hospitalization days did not differ significantly between the two groups, which was related to the abandonment of treatment in some patients. Precautionary antibiotic use, kinds of antibiotics used, receipt of carbapenem, tracheal intubation, hemofiltration and number of hospitalization days in the intensive care unit were significantly higher in the MDR group. This indicates that the above interventions were important causes of MDR bacterial infections. Endoscopic surgery was a safe treatment measure for patients [32]. Unconditional logistic regression showed that ICU hospitalization was a risk factor for MDR bacterial infection [33]. When 4 to 6 different kinds of antibiotics used in patients, the risk of MDR bacterial infection was approximately 3 times that of patients given 1 to 3 antibiotics; therefore, we can draw the conclusion that using a variety of antibiotics increases the risk of MDR bacterial infection [34]. SAP infection was caused by pathogens that passed through the blood and bile duct systems or retrograded through the duodenum and ascended into the main pancreatic duct. At the same time, intestinal pathogens crossed the intestinal barrier and then translocated into the lymphatic system and the parenteral system to cause infection [35]. Although gram-negative bacteria were still dominant, the proportion of gram-positive bacteria increased notably compared with 27.9% and 23.9% reported by Ma [4] and Su [36]. One of the reasons is that drainage or postoperative infections occur after the appearance of pancreatic or anastomotic fistula, leading to the emergence of multiple infection foci. However, the reason for the increase in the number of enterococci in SAP patients remains unclear and may be related to the prophylactic use of antibiotics [37]. Fernanda S. Soares [38] et al. found that prophylactic use of meropenem in SAP-affected mice induced Enterococcus colonization of the small intestine and gradually became predominant in the gut, which led to an increase in the number of gram-positive bacteria. A multihospital prospective clinical study showed that the intestinal population of Enterococcus was higher and more positively correlated with the serum levels of IL-6 in SAP patients than in MAP patients, suggesting that the increase in enterococci contributes to the severity of this disease [39]. The resistance rates of Escherichia coli and Klebsiella pneumoniae to quinolones were higher than those of nonfermentative bacteria, but the resistance rates to aminoglycosides were the opposite. Resistance to third generation cephalosporins by Enterobacteriaceae, which represents the major mechanism of antimicrobial resistance among Escherichia coli isolates [40]. Of the nonfermentative bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii gradually exhibited resistance to carbapenems through an active efflux system and decreased permeability of the outer membrane [41, 42]. The drug resistance rates were higher than those of Escherichia coli and Klebsiella pneumoniae; therefore, it was necessary to combine treatment with β-lactamase inhibitors in the clinic [43]. The resistance rates of Escherichia coli and Klebsiella pneumoniae to cephalosporins were high, while the rates of Acinetobacter baumannii to ceftazidime and cefepime were higher than those of Pseudomonas aeruginosa. The rates of the main gram-negative bacteria to aztreonam were also higher, but Klebsiella pneumoniae and Acinetobacter baumannii were more sensitive to the compound sulfamethoxazole. The detection rate of resistant Enterococcus faecium was higher than that of Enterococcus faecalis, and the resistance rates of these two bacteria to penicillin were quite different; additionally, the resistance rates to high concentration gentamicin were all over 50%, which was consistent with previous reports [44]. Therefore, the antibacterial effect was poorer for those pathogens when using aminoglycoside-penicillin or benzyl-penicillin for synergistic effects and screening should be performed for clinical use. The detection rate of resistance in Staphylococcus epidermidis was higher than that in Staphylococcus aureus; however, the resistance rates of Staphylococcus aureus to quinolones and gentamicin were higher than those of Staphylococcus epidermidis. This is due to the formation of staphylococcus biofilms as an immune evasion and drug resistance mechanism [45]. Staphylococcus epidermidis was more sensitive to tetracycline, which was similar to the resistance of Staphylococcus aureus to compound sulfamethoxazole. The prophylactic use of antibiotics for the prevention of secondary pancreatic infection remains controversial [1, 46], and the relevant guidelines are not recommended for patients with SAP and aseptic necrosis [47]. Although prophylactic use of carbapenem antibiotics may lead to bacterial translocation, according to the characteristics of the spectrum, drug sensitivity and antibiotic characteristics, the most appropriate method of empirical antibiotic treatment is meropenem. A short-term, full dose regimen of broad-spectrum antibacterials, especially carbapenems, in the early stage of SAP can eliminate sensitive pathogens quickly, reduce the dual-infection, and reduce the production of drug-resistant strains caused by bacterial flora disturbance. Subsequent use of antimicrobial agents should be based on the results of drug susceptibility testing of pathogens to ensure an effective antibacterial effect, shorten the course of treatment, reduce the production of drug-resistant strains and reduce the probability of fungal infection [48]. In our study, 53% of patients with MDR bacterial infection had received prophylactic antibiotic treatment, and 38% of patients had not received preventive antibiotic treatment. There was no statistical difference between the use of prophylactic antibiotics and MDR bacterial infection. Our study reports for the first time that more kinds of antibiotics and ICU hospitalization are associated with the development of MDR bacterial infections. This can help clinicians make a better choice to treat AP patients. However, our research also has some limitations. First, this is a single-center retrospective study with a small sample size and further research with larger sample sizes is needed. Moreover, there may be some deviation in the type and quantity of pathogenic bacteria because of the complexity of clinical treatment. Finally, our study cannot completely rule out the key factors for MDR bacterial infections. Conclusions The bacterial spectrum and drug resistance characteristics of SAP patients provide a certain reference for the empirical use of antibiotics and the regulation of intestinal microecological treatments. Our study found that gram-negative bacteria were the most common pathogens in SAP infection, and the proportion of gram-positive bacteria increased notably. Besides, more kinds of antibiotics and ICU hospitalization are risk factors for MDR bacterial infections. Abbreviations SAPSevere acute pancreatitis IPNInfectious pancreatic necrosis MDRMulti-drug resistant SIRSSystemic inflammatory response syndrome ARDSAcute respiratory distress syndrome MODSMultiple organ dysfunction syndrome MRSAMethicillin-resistant Staphylococcus aureus VREVancomycin-resistant Enterococcus species MRCNSMethicillin-resistant coagulasenegative staphylococci ORsOdds ratios CIsConfidence intervals ICUIntensive care units XDRExtensively drug resistant ESBLExtended Spectrum Beta-Lactamases CARSCompensatory anti-inflammatory response syndrome MARSMixed antagonistic response syndrome Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Ning Fan, Yong Hu and Hong Shen contributed equally to this work Acknowledgements We thank the Association of Pancreatic Disease Specialized Committee of Tianjin Integrated Chinese and Western Medicine for their collaboration and assistance during the study. We thank all surgical colleagues from the Department of Surgery in Tianjin Nankai Hospital who have collaborated in this study. Authors’ contributions YFC and YH conceived and designed the study. NF, YH, GZ, SL and LS performed the experiments. CL, XZ, YL and JW wrote the paper. YH and HS reviewed and edited. All authors read and approved the final manusript. Funding This study was funded by key project of Science and Technology of Tianjin Municipal Committee for health and family planning and Foundation of Tianjin Clinical Medical Research Center of Acute Abdomen with integrated Chinese and Western medicine. Availability of data and materials The datasets analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate This is a retrospective study and has been reviewed by the Medical Ethics Committee of Tianjin NanKai Hospital (NKYY_YX_IRB_2018_002_01). As the study was retrospective, no informed consent was required. All patients are anonymous and their information is not public. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. ==== Refs References 1. Mourad MM Evans R Kalidindi V Navaratnam R Dvorkin L Bramhall SR Prophylactic antibiotics in acute pancreatitis: endless debate Ann R Coll Surg Engl 2017 99 107 112 10.1308/rcsann.2016.0355 27917667 2. van Dijk SM Hallensleben NDL van Santvoort HC Fockens P van Goor H Bruno MJ Acute pancreatitis: recent advances through randomised trials Gut 2017 66 2024 2032 10.1136/gutjnl-2016-313595 28838972 3. Wolbrink DRJ Kolwijck E Ten Oever J Horvath KD Bouwense SAW Schouten JA Management of infected pancreatic necrosis in the intensive care unit: a narrative review Clin Microbiol Inf 2020 26 18 25 10.1016/j.cmi.2019.06.017 4. Ma HX He L Cai SW Xin XL Shi HD Zhou L Analysis of the spectrum and resistance of pathogen causing sepsis in patients with severe acute pancreatitis Zhonghua wai ke za zhi [Chinese journal of surgery] 2017 55 378 383 5. Mallédant Y Malbrain ML Reuter DA What's new in the management of severe acute pancreatitis? Intensive Care Med 2015 41 1957 1960 10.1007/s00134-015-3903-1 26077091 6. Tugal D Lynch M Hujer AM Rudin S Perez F Bonomo RA Multi-drug-resistant Klebsiella pneumoniae pancreatitis: a new challenge in a serious surgical infection Surg Inf 2015 16 188 193 10.1089/sur.2012.175 7. Petrov MS Shanbhag S Chakraborty M Phillips AR Windsor JA Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis Gastroenterology 2010 139 813 820 10.1053/j.gastro.2010.06.010 20540942 8. van Santvoort HC Bakker OJ Bollen TL Besselink MG Ahmed Ali U Schrijver AM A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome Gastroenterology 2011 141 1254 1263 10.1053/j.gastro.2011.06.073 21741922 9. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013;13:e1–15. 10. Hu Y Jiang X Li C Cui Y Outcomes from different minimally invasive approaches for infected necrotizing pancreatitis Medicine 2019 98 e16111 10.1097/MD.0000000000016111 31192974 11. Hu Y Li C Zhao X Cui Y An endoscopic or minimally invasive surgical approach for infected necrotizing pancreatitis: a systematic review and meta-analysis Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva 2019 111 471 480 31021167 12. Mowbray NG Ben-Ismaeil B Hammoda M Shingler G Al-Sarireh B The microbiology of infected pancreatic necrosis Hepatob Pancr Dis Int 2018 17 456 460 10.1016/j.hbpd.2018.08.007 13. Baron EJ Miller JM Weinstein MP Richter SS Gilligan PH Thomson RB Jr A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)(a) Clin Inf Dis 2013 57 e22 e121 10.1093/cid/cit278 14. Jiang X Shi JY Wang XY Hu Y Cui YF The impacts of infectious complications on outcomes in acute pancreatitis: a retrospective study Military Med Res 2020 7 38 10.1186/s40779-020-00265-5 15. Manes G Rabitti PG Menchise A Riccio E Balzano A Uomo G Prophylaxis with meropenem of septic complications in acute pancreatitis: a randomized, controlled trial versus imipenem Pancreas 2003 27 e79 83 10.1097/00006676-200311000-00018 14576501 16. Trudel JL Wittnich C Brown RA Antibiotics bioavailability in acute experimental pancreatitis J Am Coll Surg 1994 178 475 479 8167885 17. Tian H Chen L Wu X Li F Ma Y Cai Y Infectious complications in severe acute pancreatitis: pathogens, drug resistance, and status of nosocomial infection in a university-affiliated teaching hospital Dig Dis Sci 2020 65 2079 2088 10.1007/s10620-019-05924-9 31691173 18. Baron TH DiMaio CJ Wang AY Morgan KA American gastroenterological association clinical practice update: management of pancreatic necrosis Gastroenterology 2020 158 67–75 e1 19. Banks PA Bollen TL Dervenis C Gooszen HG Johnson CD Sarr MG Classification of acute pancreatitis–2012: revision of the Atlanta classification and definitions by international consensus Gut 2013 62 102 111 10.1136/gutjnl-2012-302779 23100216 20. Shapiro NI Wolfe RE Wright SB Moore R Bates DW Who needs a blood culture? A prospectively derived and validated prediction rule J Emerg Med 2008 35 255 264 10.1016/j.jemermed.2008.04.001 18486413 21. Canzoneri CN Akhavan BJ Tosur Z Andrade PEA Aisenberg GM Follow-up blood cultures in gram-negative bacteremia: Are they needed? Clin Inf Dis 2017 65 1776 1779 10.1093/cid/cix648 22. Coburn B Morris AM Tomlinson G Detsky AS Does this adult patient with suspected bacteremia require blood cultures? JAMA 2012 308 502 511 10.1001/jama.2012.8262 22851117 23. Vazirani J Wurity S Ali MH Multidrug-resistant pseudomonas aeruginosa keratitis: risk factors, clinical characteristics, and outcomes Ophthalmology 2015 122 2110 2114 10.1016/j.ophtha.2015.06.007 26189185 24. Venier AG Leroyer C Slekovec C Talon D Bertrand X Parer S Risk factors for Pseudomonas aeruginosa acquisition in intensive care units: a prospective multicentre study J Hosp Inf 2014 88 103 108 10.1016/j.jhin.2014.06.018 25. Werge M Novovic S Roug S Knudsen JD Feldager E Gluud LL Evaluation of local instillation of antibiotics in infected walled-off pancreatic necrosis Pancreatology 2018 18 642 646 10.1016/j.pan.2018.06.005 29958817 26. Sonmezer MC Ertem G Erdinc FS Kaya Kilic E Tulek N Evaluation of Risk Factors for Antibiotic Resistance in Patients with Nosocomial Infections Caused by Pseudomonas aeruginosa 2016 2016 1321487 27. Lee HS, Lee SK, Park DH, Lee SS, Seo DW, Kim MH, et al. Emergence of multidrug resistant infection in patients with severe acute pancreatitis. Pancreatology [et al] 2014;14:450–453. 28. Bobenchik AM Deak E Hindler JA Charlton CL Humphries RM Performance of Vitek 2 for antimicrobial susceptibility testing of Enterobacteriaceae with Vitek 2 (2009 FDA) and 2014 CLSI breakpoints J Clin Microbiol 2015 53 816 823 10.1128/JCM.02697-14 25540403 29. Iskander KN Osuchowski MF Stearns-Kurosawa DJ Kurosawa S Stepien D Valentine C Sepsis: multiple abnormalities, heterogeneous responses, and evolving understanding Physiol Rev 2013 93 1247 1288 10.1152/physrev.00037.2012 23899564 30. Novotny AR Reim D Assfalg V Altmayr F Friess HM Emmanuel K Mixed antagonist response and sepsis severity-dependent dysbalance of pro- and anti-inflammatory responses at the onset of postoperative sepsis Immunobiology 2012 217 616 621 10.1016/j.imbio.2011.10.019 22204813 31. Yong FJ Mao XY Deng LH Zhang MM Xia Q Continuous regional arterial infusion for the treatment of severe acute pancreatitis: a meta-analysis Hepatob Pancr Dis Int 2015 14 10 17 10.1016/S1499-3872(14)60290-3 32. da Costa DW Boerma D van Santvoort HC Horvath KD Werner J Carter CR Staged multidisciplinary step-up management for necrotizing pancreatitis Br J Surg 2014 101 e65 79 10.1002/bjs.9346 24272964 33. Peng Y Bi J Shi J Li Y Ye X Chen X Multidrug-resistant Pseudomonas aeruginosa infections pose growing threat to health care-associated infection control in the hospitals of Southern China: a case-control surveillance study Am J Infect Control 2014 42 1308 1311 10.1016/j.ajic.2014.08.006 25444305 34. Huang X Li G Yi L Li M [The epidemiology of multidrug-resistant bacteria colonization and analysis of its risk factors in intensive care unit] Wang J Zhonghua wei zhong bing ji jiu yi xue 2015 27 667 671 26255016 35. Fishman JE Levy G Alli V Zheng X Mole DJ Deitch EA The intestinal mucus layer is a critical component of the gut barrier that is damaged during acute pancreatitis Shock (Augusta, Ga) 2014 42 264 270 10.1097/SHK.0000000000000209 36. Su MS Lin MH Zhao QH Liu ZW He L Jia N Clinical study of distribution and drug resistance of pathogens in patients with severe acute pancreatitis Chin Med J 2012 125 1772 1776 22800898 37. Howard TJ Temple MB Prophylactic antibiotics alter the bacteriology of infected necrosis in severe acute pancreatitis J Am Coll Surg 2002 195 759 767 10.1016/S1072-7515(02)01494-1 12495307 38. Soares FS Amaral FC Silva NLC Valente MR Santos LKR Yamashiro LH Antibiotic-induced pathobiont dissemination accelerates mortality in severe experimental pancreatitis Front Immunol 2017 8 1890 10.3389/fimmu.2017.01890 29375557 39. Tan C Ling Z Huang Y Cao Y Liu Q Cai T Dysbiosis of intestinal microbiota associated with inflammation involved in the progression of acute pancreatitis Pancreas 2015 44 868 875 10.1097/MPA.0000000000000355 25931253 40. Trecarichi EM Giuliano G Cattaneo C Ballanti S Criscuolo M Candoni A Bloodstream infections caused by Escherichia coli in onco-haematological patients: Risk factors and mortality in an Italian prospective survey 2019 14 e0224465 41. Lai CC Chen CC Lu YC Chuang YC Tang HJ In vitro activity of cefoperazone and cefoperazone-sulbactam against carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa Inf Drug Resist 2019 12 25 29 10.2147/IDR.S181201 42. Potron A Poirel L Nordmann P Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii : mechanisms and epidemiology Int J Antimicrob Agents 2015 45 568 585 10.1016/j.ijantimicag.2015.03.001 25857949 43. Ambrose PG Lomovskaya O Griffith DC Dudley MN VanScoy B β-Lactamase inhibitors: what you really need to know Curr Opin Pharmacol 2017 36 86 93 10.1016/j.coph.2017.09.001 29096172 44. Wang JT Chang SC Wang HY Chen PC Shiau YR Lauderdale TL High rates of multidrug resistance in Enterococcus faecalis and E. faecium isolated from inpatients and outpatients in Taiwan Diagn Microbiol Inf Dis 2013 75 406 411 10.1016/j.diagmicrobio.2013.01.004 45. Otto M Staphylococcus epidermidis pathogenesis Methods Mol Biol (Clifton, NJ) 2014 1106 17 31 10.1007/978-1-62703-736-5_2 46. Ukai T Shikata S Inoue M Noguchi Y Igarashi H Isaji S Early prophylactic antibiotics administration for acute necrotizing pancreatitis: a meta-analysis of randomized controlled trials J Hepato-Biliary Pancr Sci 2015 22 316 321 10.1002/jhbp.221 47. Tenner S Baillie J DeWitt J Vege SS American College of Gastroenterology guideline: management of acute pancreatitis Am J Gastroenterol 2013 108 1400–15 16 23287939 48. Schwender BJ Gordon SR Gardner TB Risk factors for the development of intra-abdominal fungal infections in acute pancreatitis Pancreas 2015 44 805 807 10.1097/MPA.0000000000000334 25872170