Abstract
Abstract
Background:
Complicated intra-abdominal infections are serious conditions that require urgent source control and antibiotic treatment. The purpose of this study was to evaluate the epidemiology and bacterial causation of such infections using blood and peritoneal cultures of Korean patients with peritonitis originating from viscus perforation.
Methods:
The medical records of 419 consecutive patients who underwent emergency surgery because of bowel perforation from January 2007 to December 2011 were analyzed. Clinical characteristics, peri-operative conditions, perforation sites, and mortality data were obtained. Bacterial distributions and antibiotic resistance were evaluated using blood and peritoneal culture reports.
Results:
The most common perforation site was the colon (165; 39.4%), and the overall mortality rate was 11.2%. Blood cultures were performed in 182 patients, and 20 patients (11.0%) had a positive culture. Blood culture positivity was significantly higher for colon perforations (17.7%) than perforations elsewhere (p=0.039). A peritoneal culture was performed for each of 210 patients (50.1%), and 145 of those patients (69.0%) had a positive culture. Enterococcus faecium (35.2%) was the most common gram-positive bacterium, and Escherichia coli was the most common gram-negative organism. There were 276 community-acquired infections (CAI) (65.9%) and 143 hospital-acquired infections (HAI) (34.1%). Escherichia coli producing extended-spectrum β-lactamases were more common in the HAI than in the CAI group (p=0.016).
Conclusions:
The compositions and antibiotic resistances of micro-organisms found in this study are similar to those reported previously. A multicenter prospective study is needed of this disease state in South Korea.
I
Although some guidelines on empiric antibiotics for IAIs have been published, most studies on causative bacteria were performed before the 2000s [1–3,5]. Furthermore, few studies have been published on peritonitis in Korean populations. The purpose of this study was to evaluate the epidemiology and bacterial distribution, as identified from blood and peritoneal cultures, of secondary peritonitis caused by hollow viscus perforation in Korean patients who had undergone an emergency operation.
Patients and Methods
This study was approved by the Severance Hospital Institutional Review Board (approval no. 4-2013-0802).
Patients
The medical records of 419 consecutive patients with hollow viscus perforation who underwent emergency surgery from January 2007 to December 2011 were reviewed retrospectively. Patients with perforated appendicitis or cholecystitis were excluded because peritoneal cultures were not obtained routinely during laparoscopic surgery. The following data were extracted: Underlying disease, presence of peri-operative hypotension (systolic blood pressure <90 mm Hg), systemic inflammatory response status (including sepsis, severe sepsis, and septic shock as defined in the American College of Chest Physicians/Society of Critical Care Medicine guidelines [9]), pre-operative antibiotics, post-operative laboratory tests, re-operation, length of stay (LOS) in an intensive care unit (ICU), LOS in a hospital, days on mechanical ventilation, and date of death if relevant.
Pathology and culture data
Information about perforation sites was obtained from the operative notes or pathology reports, and the sites were classified as follows: Stomach or duodenum, small bowel, or colon (including rectum). Results of peritoneal and blood cultures were collected by reviewing microbial culture studies. Infections were classified as community-acquired (CAI) or hospital-acquired (HAI) based on the timing of the diagnosis of the IAI using a 48-h post-hospitalization cut-off to distinguish between the two [10,11]. Infections diagnosed after 48 h of hospitalization, such as with perforation during chemotherapy or other therapeutic intervention besides intraperitoneal infections, were classified as HAI.
A peritoneal culture was defined as a test performed on aspirated or swabbed intraperitoneal fluid during surgery or on drainage fluid after the immediate post-operative period. When patients had suspected sepsis (temperature >38.3°C or shock), a blood culture was performed from more than two sites pre-operatively. When three bottles of blood samples were obtained, the occurrence of an organism in two was interpreted as a positive finding, and when two bottles of blood were drawn, the occurrence of an organism in one was considered a positive finding.
Microbiological tests
Antibiotic-resistant organisms were defined as follows: Vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus spp. (MRS), Escherichia coli producing an extended-spectrum beta-lactamase (ESBL), Klebsiella pneumoniae with ESBL, carbapenem-resistant Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Acinetobacter baumannii (CRAB).
The isolates were identified using conventional biochemical methods (VITEK systems; bioMerieux, Hazelwood, MO). Antimicrobial susceptibilities were measured using disk-diffusion methods or the VITEK-2 N131 card (bioMerieux). Results were interpreted using the guidelines issued by the Clinical and Laboratory Standards Institute (CLSI) in 2009 [12].
Statistical analysis
Continuous variables are expressed as means±standard deviations or medians (ranges). The χ2 or Fisher exact test, as appropriate, was used to compare categorical variables. Statistical analysis was performed using SPSS version 20.0 (IBM, Inc., Armonk, NY), and two-sided p values <0.05 were considered significant.
Results
Demographics and clinical characteristics
Of the 419 study subjects, 270 (64.4%) were male, and the mean age was 59.3±15.9 y. One hundred fourteen patients (27.2%) had received a corticosteroid or chemotherapy within one year of the operation. Fifty-nine (14.1%) had endocrine disease. In the emergency room, 40 (14.8%) had hypotension, 127 (30.3%) sepsis, 34 (8.1%) severe sepsis, and 20 (4.8%) septic shock.
Monotherapy was given to 166 patients (39.6%) and combination therapy to 253 patients (60.4%). Piperacillin-tazobactam (116; 69.9%) was the single agent most frequently used, followed by a carbapenem (18; 10.8%) and a second- (16; 9.6%) or third-generation (8; 4.8%) cephalosporin. For combination therapy, a triple regimen (second-or third-generation cephalosporin+aminoglycoside+metronidazole) (90; 35.6%) was most common. Regimens such as a third-generation cephalosporin plus metronidazole (30; 11.9%), piperacillin-tazobactam plus metronidazole (30), and a third-generation cephalosporin in combination with aminoglycoside (23; 9.1%) also were prescribed. When the appropriateness of antibiotic use was analyzed, an inappropriate antibiotic was found to have been used in 36 patients (8.6%). Post-operative hypotension developed in 96 patients (22.9%). The mean LOS in the hospital was 17 d (range 1–201 d), and 46 patients (11%) underwent re-operation. Two hundred seventy-six patients (65.9%) had a CAI and 143 (34.1%) an HAI. Forty-seven patients (11.2%) died in the hospital (Table 1).
Cardiologic disease: hypertensive disease, ischemic disease, heart failure, cardiac dysrhythmias, valvular disease. Pulmonary disease: chronic obstructive disease, pulmonary tuberculosis, pneumothorax, interstitial lung disease. Endocrine disease: diabetes mellitus, hyperthyroidism, hypothyroidism, adrenal disease. Nephrologic disease: chronic renal dysfunction, end-stage renal disease, nephrotic syndrome, nephritic syndrome. Immunosuppression: taking immunosuppressant or corticosteroid or receiving chemotherapy within one year from the operation.
ED=emergency department; ICU=intensive care unit; MV=mechanical ventilation; SIRS=systemic inflammatory response syndrome.
The most common site of perforation was the colon or rectum (n=165), followed by the stomach or duodenum (n=136) and the small bowel (n=105). Thirteen patients had one or more perforations in multiple sites. In the CAI group, perforation of the stomach or duodenum (74.3%) was more common than perforation of the small bowel (62.9%), large bowel (61.8%), or multiple sites (53.8%) (p=0.081).
A peritoneal culture was performed in 210 patients (50.1%), and microorganisms were identified in 145 (69%). Blood cultures were performed in 182 patients (43.4%), and microorganisms were found in 20 (11.0%). Blood culture positivity was significantly more common in cases of colon perforation (17.7%) than in the others (p=0.039). Enterococcus spp. and E. coli were identified more often in patients with perforation of the lower gastrointestinal tract (p=0.002 and 0.030, respectively). Klebsiella spp. also were found more frequently in patients with small bowel perforation (p=0.009). However, there was no influence of perforation site on mortality rate, peritoneal culture positivity, or antibiotic resistance rate (p=0.911, 0.331, and 0.151, respectively) (Table 2).
Linear by linear association.
Microbiology of blood cultures
A blood culture was positive in 20 patients. The gram-positive bacteria identified were Streptococcus spp. (5; 25%), Staphylococcus epidermidis (4; 20%), E. faecium (3; 15%), and E. avium (1; 5%). The gram-negative bacteria were E. coli (7; 35%), P. aeruginosa (2; 10%), and Bacillus spp. and Micrococcus spp. (1 each; 5%). The anaerobes were Bacteroides spp. (4; 20%), with one being B. fragilis. Candida albicans was identified in one patient (Table 3).
Microbiology of peritoneal cultures
A peritoneal culture was positive in 145 patients (69.0%). The most common organism was E. faecium (51; 35.2%), followed by E. coli (29; 20%), Candida albicans (25; 17.2%), and P. aeruginosa (17; 11.7%). The gram-positive bacteria identified were E. faecium (51; 35.2%), E. faecalis (12; 8.3%), and other enterococci (14; 9.7%). The staphylococcal species identified were S. aureus (10; 6.9%) and coagulase-negative staphylococci (13; 9.0%). Streptococcus spp. were identified in 11 patients (7.6%). The gram-negative bacteria were E. coli (29; 20%), P. aeruginosa (17; 11.7%), K. pneumoniae (16; 11%), Enterobacter aerogenes (7; 4.8%), and A. baumannii (12; 8.3%). For anaerobic organisms, Bacteroides spp. were isolated from eight patients (5.5%), and two patients (1.4%) had B. fragilis. Twenty-five patients (17.2%) had C. albicans, which was the most frequent yeast, and non-albicans Candida was identified in 11 patients (7.6%) (Tables 4 and 5).
Antibiotic resistance is described as vancomycin-resistant Enterococcus, methicillin-resistant Staphylococcus spp., Escherichia coli with extended-spectrum β-lactamase (ESBL), Klebsiella pneumoniae with ESBL, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii.
Fisher exact test.
CAI=community-acquired infection; CRAB=carbapenem-resistant Acinetobacter baumannii; CRPA=carbapenem-resistant Pseudomonas aeruginosa; ESBL=extended-spectrum β-lactamase; HAI=hospital-acquired infection; MRS=methicillin-resistant Staphylococcus spp.; VRE=vancomycin-resistant Enterococcus.
Difference between community-acquired and hospital-acquired infections
A blood culture was performed for 152 of the 276 patients in the CAI group and in 30 of the 143 patients in the HAI group. There was no statistically significant difference in the culture execution rate between the groups (11.8% vs. 6.7%; p=0.536).
The peritoneal culture positivity rates were 65.0% and 74.7% in the CAI and HAI groups, respectively, which was not a significant difference (p=0.173). Antibiotic-resistant organisms were more common in the HAI group (15.4% vs. 27.6%; p=0.032), and the mortality rate was higher in this group (16.1% vs. 8.7%; p=0.023) (see Table 4). Enterococcus faecium was the gram-positive bacterium detected most commonly in both groups (31.3% and 40%). The second most common organisms were other enterococci and Streptococcus spp. (9; 11.3%) in the CAI group and E. faecalis (7; 10.8%) in the HAI group.
Regarding gram-negative bacteria, in the CAI group, E. coli (20; 25%) was the most common pathogen, followed by K. pneumoniae (8; 10%) and P. aeruginosa (6; 7.5%). In the HAI group, P. aeruginosa (11; 16.9%) and E. coli (9; 13.8%) were the most common pathogens, and ESBL-producing E. coli was significantly more common in this group than in the CAI group (p=0.016). The positivities for VRE, MRS, ESBL Klebsiella pneumoniae, CRPA, and CRAB in the two groups were not significantly different (Table 5).
Clinical outcomes according to antibiotic resistance
Among 210 patients who underwent a peritoneal culture, 43 patients with resistant organisms had longer durations of hospitalization, ICU stay, and mechanical ventilation than the others (p <0.001, <0.001, and 0.021, respectively), but there was no significant difference in the mortality rate. Patients with CRAB had more post-operative shock and a higher mortality rate than patients without (Table 6).
Mann-Whitney U test.
Fisher exact test.
CRAB=carbapenem-resistant Acinetobacter baumannii.
Discussion
Intra-abdominal infections are classified as complicated or uncomplicated and are defined as infections that extend beyond the originating viscus perforation and lead to more diffuse peritonitis or abscess formation [13]. In this study, appendicitis and biliary tract disease cIAIs were excluded. In patients with a cIAI, E. coli was the most common gram-negative pathogen, followed by K. pneumoniae, Enterobacter spp., and P. aeruginosa, whereas Streptococcus spp., Enterococcus spp., and Staphylococcus were the major gram-positive pathogens [13]. Among anaerobe or yeast isolates, Bacteroides and Candida spp. are most frequent [4,14–19]. In the present study, Enterococcus spp. and E. coli were the most common pathogens isolated from peritoneal cultures, which is consistent with the results of previous studies.
Blood culture positivity was higher after colon than other perforations, which probably is related to the normal gastrointestinal flora of the colon [20]. The number of anaerobes increases rapidly beginning in the distal ileum, which increases the likelihood of bacterial translocation and bacteremia [1,20,21]. Accordingly, the early use of proper antibiotics is more important in patients with secondary peritonitis caused by colon perforation.
Several etiologic studies on cIAIs reported that the most common infecting organism was E. coli (18%–71%), and that the prevalence of K. pneumoniae, Streptococcus spp., and B. fragilis was 7%–11%, 14%–38%, and 6%–35%, respectively. In addition, patients with an HAI had similar isolation rates for E. coli (19%–42%) and K. pneumoniae (7%–10%), but a higher prevalence of Enterococcus spp. (21%–35%) and yeast (13%–33%). Furthermore, some studies found that Enterococcus and yeast were related to a higher mortality rate in patients with secondary peritonitis [3,22–24]. In the present study, the prevalence of these organisms was higher in the HAI than in the CAI group, and patients with an HAI had a high prevalence of P. aeruginosa (16.9%) [13].
Somewhat surprisingly, the isolation rate of Enterococcus was greater in the present study than in other studies (51.7% vs. 5.5%–21.5%) [24–26]. Ruiter et al. reported that the more severe secondary peritonitis is, the longer the ICU stay and the greater the risk of Enterococcus spp. colonization; consequentially, the presence of Enterococcus implies tertiary peritonitis [23,27]. Although our patients had cIAIs, complicated appendicitis or complicated cholecystitis cases were excluded. In fact, only cases of peritonitis secondary to hollow viscus perforation were included. Thus, Enterococcus infections were identified more frequently because the proportion of pre-operative peritonitis was higher than in previous reports, which was about 56% post-operatively compared with 100% in the present study [25].
Regarding the rate of resistance to antibiotics, VRE accounted for 20.8% of all Enterococcus, MRS for 40.9% of all Staphylococcus, ESBL-producing E. coli 24.1% of all E. coli, and ESBL-producing K. pneumoniae 37.5% of all of this genus, whereas CRPA and CRAB accounted for 35.3% and 50% among P. aeruginosa and A. baumannii, respectively. Furthermore, the prevalence of ESBL-producing E. coli was significantly higher in the HAI group, but the prevalence of other antibiotic-resistant organisms was non-significantly different in the two groups. In the Study for Monitoring Antimicrobial Resistance Trends (SMART), the in vitro activities of several antimicrobial agents on gram-negative bacilli have been examined since 2002 [28]. According to the report issued by the Asia-Pacific SMART Group, the rates of ESBL-producing E. coli and K. pneumoniae were 34.0% and 22.3% of all these organisms, respectively. More specifically, resistance rates in one university hospital in South Korea were 30.4% and 25.0%, respectively. Isolation rates of ESBL-producing E. coli and K. pneumoniae also were higher in the HAI group than in the CAI group [29]. Our results showed similar peritoneal microbiology and antibiotic resistance patterns in patients with cIAIs.
Several previous studies published in South Korea attest that the five most prevalent organisms in general patients are E. coli (19.3%–21.1%), S. aureus (16.6%–17.8%), coagulase-negative staphylococci (13.1%–13.8%), P. aeruginosa (9.7%–11.7%), and K. pneumoniae (9.4%–10.0%). The proportions of VRE, MRSA, ESBL-producing E. coli, ESBL-producing K. pneumoniae, CRPA, and CRAB were 21%–29%, 64%–69%, 12%–20%, 29%–33%, 23%–29%, and 22%–56%, respectively [6,7]. The resistance rates and the proportions of peritoneal organisms found in the present study concur with those in previous reports, with the exception of enterococci, which were the most common bacterium in the present study.
The mortality rates of cIAIs depend on the source of infection. Several studies of secondary peritonitis in the 1980s and 1990s reported a mortality rate of 3%–28% in cases of stomach or duodenal perforation, 20%–38% for small bowel perforation, and 20%–45% for colon perforation [16]. In the Complicated Intra-abdominal Infection Observational Worldwide (CIAOW) study [19], a mortality rate of 10.1% was reported, which is similar to the 10.3%–15.3% observed in the present study.
Conclusion
Although this study is limited by its single location and retrospective design, it provides meaningful information because of the relatively large number of patients enrolled and the lack of a previous report on the epidemiology or bacteriology of secondary peritonitis in South Korea. Further prospective multicenter studies on this topic are needed.
Author Disclosure Statement and Contributions
The authors have no competing interest to declare.
JGL designed the study. SHL and HS collected and analyzed the data. JYJ analyzed the results and wrote the manuscript. JYC and DY took part in critical revision of the manuscript. All authors read and approved the final manuscript.
