Peritonitis Caused by Aeromonas Species at a Hospital in Southern Taiwan

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1 ORIGINAL ARTICLE Peritonitis Caused by Aeromonas Species at a Hospital in Southern Taiwan Wei-Ting Lin 1,2, Shih-Yang Su 3, Chih-Cheng Lai 4, Tsung Chih Tsai 5, Shiow-Jen Gau 6 and Chien-Ming Chao 4,7 Abstract Objective This study was conducted to investigate the clinical characteristics of patients with Aeromonas peritonitis, particularly secondary peritonitis. Methods Patients with Aeromonas peritonitis treated between July 2004 and December 2011 were identified from the computerized database of a regional hospital in southern Taiwan. The medical records of these patients were retrospectively reviewed. Results A total of 50 patients with Aeromonas peritonitis were identified. Nine cases were classified as spontaneous bacterial peritonitis, and 41 cases were classified as secondary peritonitis. The most common etiology of secondary peritonitis was acute appendicitis (n=26), followed by small bowel perforation (n=7) and colon perforation (n=6). The patients with spontaneous bacterial peritonitis were more likely to be immunocompromised (p=0.0013) and more frequently had an initial presentation of shock (p=0.0129), an abnormal liver function (p<0.05) and concomitant bacteremia (p=0.0024) than the patients with secondary peritonitis. Although the patients with secondary peritonitis had higher levels of inflammatory parameters, including leukocytes and C-reactive protein, and more frequent polymicrobial infections, their survival outcome rates, such as in-hospital mortality, were significantly lower (p=0.0007). The overall in-hospital mortality rate was 20%, and initial shock was the only independent prognostic factor for mortality (p=0.012). Conclusion The clinical characteristics, including outcomes, of patients with spontaneous and secondary Aeromonas peritonitis differ. In-hospital mortality is significantly associated with the initial presentation of shock. Key words: Aeromonas, peritonitis, mortality (Intern Med 52: , 2013) () Introduction Aeromonas species, Gram-negative rods, are ubiquitous in aquatic environments (1-3). In temperate and subtropical countries, such as Taiwan (4-6), human infections caused by these pathogens are not uncommon. The portal of entry of Aeromonas species usually involves the ingestion of food contaminated with aeromonads or wound exposure to environmental sources (1-3). The gastrointestinal tract is the most common site of Aeromonas spp. infection (1-3); however, extraintestinal types of Aeromonas infection, including bacteremia, pneumonia, empyema, necrotizing fasciitis, arthritis, endocarditis, meningitis, urinary tract infections, biliary tract infections and skin and soft tissue infections, have also been reported (1-3, 7-15). Peritonitis caused by Aeromonas spp. is rare, with most reports focusing on spontaneous bacterial peritonitis (16-18) or peritoneal dialysis peritonitis (19-21). In contrast, knowledge regarding secondary peritonitis caused by Aeromonas is limited (22). Im- Department of Orthopaedics, Chi Mei Medical Center, Taiwan, Department of Physical Therapy, Shu Zen College of Medicine and Management, Taiwan, Department of Emergency Medicine, Tainan Municipal Hospital, Taiwan, Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Taiwan, Department of Surgery, Chi Mei Medical Center, Liouying, Taiwan, Department of Laboratory Medicine, Chi Mei Medical Center, Liouying, Taiwan and Department of Nursing, Min-Hwei College of Health Care Management, Taiwan Received for publication January 19, 2013; Accepted for publication June 30, 2013 Correspondence to Dr. Chien-Ming Chao, ccm870958@yahoo.com.tw 2517

2 proving the understanding of the clinical characteristics of Aeromonas peritonitis, including secondary peritonitis, is warranted. Therefore, the aim of our study was to investigate the clinical characteristics of Aeromonas peritonitis, including secondary and spontaneous peritonitis. Furthermore, this study attempted to identify the differences between patients with spontaneous and secondary peritonitis caused by Aeromonas spp. Materials and Methods Hospital setting and patient selection We conducted this study at a 900-bed hospital located in southern Taiwan. Patients with clinical isolates of ascites yielding Aeromonas species treated between July 2004 and December 2011 were identified based on the computerized database of laboratory medicine. We retrospectively reviewed the medical records and collected the demographic data of the identified patients. Moreover, the laboratory results, microbiological reports and patient outcome data were collected. Bacterial isolates and antimicrobial susceptibility All clinical isolates were identified using conventional biochemical methods and further confirmed using the API- 20E System (biomérieux Vitek Inc., Hazelwood, MO, USA), ID 32 GN System (biomérieux Vitek Inc.) or Vitek 2 ID-GNB identification card (biomérieux Inc., Durham, NC, USA), as described in previous studies (23, 24). Antimicrobial susceptibility tests of the clinical isolates were performed using the disk diffusion method, as previously described (25). Definitions Peritonitis was diagnosed in patients with clinical peritoneal inflammation in addition to positive cultures of ascites. Spontaneous bacterial peritonitis was defined as peritonitis without any apparent intra-abdominal surgically indicated conditions. In contrast, secondary peritonitis was defined as peritonitis with a surgically treatable source. Patients with a systolic blood pressure of <90 mmhg or who required inotropic agents to maintain blood pressure were defined as having a shock status. A polymicrobial infection was diagnosed if other non-aeromonas pathogens grew from the ascites. Inappropriate use of antibiotics was defined as the use of antimicrobial agents in vitro against non-susceptible clinical isolates. In-hospital mortality was classified as mortality due to any etiology during the course of hospitalization. Patients with any one of the following conditions, including liver cirrhosis, diabetes mellitus, end-stage renal disease, immunosuppressant use and malignancy, were classified as having an immunocompromised condition. Statistical analysis Table 1. Clinical Characteristics of the 50 Patients with Peritonitis Caused by Aeromonas Species No (%) of patients with spontaneous bacterial peritonitis (n = 9) No (%) of patients with secondary bacterial peritonitis (n = 41) p value Age, years 68.4 ± ± Female, n (%) 4 (44.4) 12 (29.3) Underlying condition Liver cirrhosis 9 (100.0) 4 (9.8) < Active cancer 5 (55.6) 8 (19.5) Diabetes mellitus 2 (22.2) 4 (9.8) Hepatitis C 5 (55.6) 2 (4.9) Hepatitis B 2 (22.2) 1 (2.4) Alcoholism 2 (22.2) 0 (0.0) End-stage renal disease 4 (44.4) 3 (7.3) Receiving immunosuppressants 2 (22.2) 2 (4.9) Immunocompromised status 9 (100.0) 14 (34.1) Initial presentations Abdominal pain 6 (66.7) 39 (95.1) Fever 4 (44.4) 16 (39.0) Shock 5 (55.6) 5 (12.2) Diarrhea 1 (11.1) 4 (9.8) Laboratory findings White blood cell (cell/ul) ± ± Neutrophil count (cell/ul) ± ± Lymphocyte count (cell/ul) ± ± Hemoglobin (g/dl) 10.8 ± ± 1.5 < Platelet count (cell/ul) ± ± Aspartate transaminase (IU/L) 98.6 ± ± 15.1 < Total bilirubin (mg/dl) 5.0 ± ± 1.3 < Albumin (g/dl) 2.5 ± ± Urea nitrogen (mg/dl) 20.5 ± ± Creatinine (mg/dl) 1.8 ± ± C-reactive protein (mg/l) 49.4 ± ± Polymicrobial infection 0 (0.0) 39 (95.1) < Concomitant bacteremia 3 (33.3) 0 (0.0) Initial appropriate antibiotic 0 (0.0 9 (22.0) Surgical intervention 0 (0.0) 37 (90.2) < Intensive care unit admission 6 (66.7) 14 (34.1) Use of mechanical ventilation 6 (66.7) 13 (31.7) In-hospital mortality 6 (66.7) 4 (9.8) Continuous variables are presented as the mean ± standard deviation. Continuous variables were compared using the Wilcoxon rank sum test or Student s independent t-test. Categorical variables were compared using the Chi-square test or Fisher s exact test. The Chi-square test was used to analyze the outcomes, and a multivariate logistic regression analysis was applied for independent risk factors for mortality. Statistical significance was defined as p<0.05. Clinical characteristics Results The clinical characteristics of the 50 patients with peritonitis caused by Aeromonas species are summarized in Table 1. The patients ranged in age from 16 to 76 years (mean, 59.2 years). Most patients were men (n=34, 68%), and more than half of the patients were older than 65 years 2518

3 Table 2. Rates of Aeromonas Species that were Not Susceptible to 12 Antimicrobial Agents according to the Disk Diffusion Method No of isolates (%) (n = 50) Ampicillin 48 (96) Ampicillin-sulbactam 31 (62) Cefazolin 37 (74) Cefuroxime 10 (20) Ceftriaxone 2 (4) Ceftazidime 2 (4) Cefepime 1 (2) Piperacillin-tazobactam 3 (6) Imipenem 1 (2) Ciprofloxacin 3 (6) Gentamicin 3 (6) Amikacin 0 (0) Table 3. Risk Factors for Mortality from Peritonitis Caused by Aeromonas Species Characteristics Survivor Mortality Univariate Multivariate (n = 40) (n = 10) analysis analysis p value p value Elderly (age> 65 years) 18 (45.0) 9 (90.0) Female 9 (22.5) 7 (70.0) Immunocompromised 13 (32.5) 100 (100.0) conditions Initial shock 3 (7.5) 7 (70.0) Spontaneous peritonitis 3 (7.5) 6 (60.0) Polymicrobial infection 36 (90.0) 3 (30.0) Bacteremia 1 (2.5) 2 (20.0) Inappropriate antibiotic treatment 9 (22.5) 0 (0.0) Microbiological investigations of age (n=27, 54%). Malignancy and liver cirrhosis were the most common underlying diseases, and hepatobiliary cancer represented the most common type of cancer. Nearly half of the patients were immunocompromised (n=23, 46%). The most common clinical manifestation of Aeromonas infection was abdominal pain (n=45, 90%), followed by fever (n=20, 40%). Initial shock was noted in 10 patients (20%). Leukocytosis was noted in 32 (64%) patients. The majority (78%) of patients had polymicrobial peritonitis. The most common non-aeromonas pathogen obtained from the patients with polymicrobial infections was Escherichia coli (n=32), followed by P. aeruginosa (n=9) and Klebsiella species (n=7). Only three (6%) patients had concurrent Aeromonas bacteremia. Twenty patients (40%) were admitted to the intensive care unit, and 19 patients had acute respiratory failure. The overall in-hospital mortality rate was 20%. Comparison between patients with spontaneous versus secondary peritonitis Nine cases were classified as spontaneous bacterial peritonitis and 41 cases were classified as secondary peritonitis. The most common etiology of secondary peritonitis was acute appendicitis (n=26), followed by small bowel perforation (n=7), colon perforation (n=6), traumatic jejunum perforation and adhesion ileus. We further compared the clinical characteristics of the patients with spontaneous bacterial peritonitis and those with secondary peritonitis (Table 1). Liver cirrhosis, hepatitis C, alcoholism, end-stage renal disease, an immunocompromised status, initial shock and concomitant bacteremia were more frequently noted in the patients with spontaneous bacterial peritonitis. In contrast, polymicrobial infections and surgical intervention were more frequently noted in the patients with secondary peritonitis. Regarding the laboratory findings, the patients with secondary peritonitis had higher levels of white blood cells, neutrophils, lymphocytes, hemoglobin, platelets and C-reactive protein. In contrast, the patients with spontaneous bacterial peritonitis had higher levels of aspartate transaminase and total bilirubin. Overall, the in-hospital mortality rate was significantly lower in the patients with secondary peritonitis. The in vitro non-susceptible rates of Aeromonas species to various antimicrobial agents are shown in Table 2. Overall, all of the clinical isolates were susceptible to amikacin, while imipenem was active against most (98%) of the isolates. A total of 96% of the isolates were not susceptible to ampicillin, and more than 70% of the isolates were not susceptible to cefazolin. Third- and fourth-generation cephalosporins and ciprofloxacin showed good in vitro activity against more than 90% of the clinical isolates. Outcome analysis According to a univariate analysis, significant risk factors for in-hospital mortality included an age >65 years, female gender, immunocompromised status, initial shock, spontaneous bacterial peritonitis and monomicrobial infection (Table 3). However, only initial shock was significantly associated with in-hospital fatality according to a multivariate analysis (p=0.012). Discussion This study was conducted to investigate the clinical characteristics of patients with Aeromonas peritonitis, particularly secondary Aeromonas peritonitis. Moreover, we compared the clinical differences between patients with spontaneous versus secondary peritonitis and showed that there are significant differences between these two groups. In this study, we found that patients with spontaneous bacterial peritonitis are more likely to be immunocompromised and more frequently have initial shock, an abnormal liver function and concomitant bacteremia than patients with secondary peritonitis. Although the patients with secondary peritonitis had higher levels of inflammatory parameters, including leukocytes and C-reactive protein, and more frequent polymicrobial infections, their outcomes, including inhospital mortality, were significantly worse than those of the patients with spontaneous bacterial peritonitis. Hung et al. (22) performed a similar comparison between 22 patients with spontaneous Aeromonas peritonitis and 27 patients with secondary peritonitis. A higher prevalence of underlying 2519

4 liver cirrhosis (96 vs. 7%, p<0.001) was noted in the spontaneous peritonitis group, while spontaneous peritonitis was more likely to be monomicrobial (100% vs. 15%, p<0.001) and complicated by bacteremia (50% vs. 7%, p=0.011). These findings suggest that these two clinical entities, spontaneous and secondary Aeromonas peritonitis, are significantly different. In this study, the primary cause of disease in the 41 patients with secondary peritonitis included acute appendicitis, perforation of the small bowel or colon and ileus, and most of these patients were complicated with polymicrobial infections. Based on these findings, surgeons should send peritoneal fluid for culture if turbid ascites is found during surgery, and Aeromonas species are one of the causative pathogens of peritonitis, with the exception of E. coli and enterococci, which are common etiologies of intra-abdominal infections. In this study, only nine patients had spontaneous Aeromonas peritonitis. Consistent with the findings of a previous study by Wu et al. (17) conducted in Taiwan, most of the patients had clinical manifestations of abdominal pain, fever and hypotension, and the mortality rate was high. Therefore, Aeromonas should be considered to be a possible pathogen of spontaneous bacterial peritonitis in endemic areas, such as Taiwan, and can cause fatal disease. In the present work, the in-hospital mortality rate was only 20%. This is relatively lower than that observed in a previous study conducted in Spain (16) that showed the overall case-fatality rate to be 57% among a total of 34 cases of Aeromonas peritonitis. This difference may be due to the higher prevalence of chronic hepatic disease (73%) and bacteremia (74%) in that study (16). According to a multivariate analysis in a logistic regression model, initial shock was found to be an independent predictor for inhospital mortality in this study of patients with spontaneous and secondary peritonitis. This finding is consistent with the results of a study of spontaneous Aeromonas bacterial peritonitis (18) by Choi et al. conducted in Korea that reported that septic shock is the only independent prognostic factor of in-hospital mortality (p=0.02). In the present study, almost all of the isolates (96%) were not susceptible to ampicillin, a finding that is a typical characteristic of Aeromonas species. In contrast, third- and fourth-generation cephalosporins, aminoglycoside, fluoroquinolones and imipenem demonstrated good in vitro activity against these isolates. The antibiotic susceptibility patterns of the clinical isolates were similar to those reported in previous studies (2, 3, 18). In summary, fluoroquinolones and at least third-generation cephalosporin as well as aminoglycosides should be considered the antibiotic treatments of choice for patients with Aeromonas peritonitis (3, 18). This study had one major limitation regarding the identification of Aeromonas species. Previous reports (26, 27) have shown that it may be unreliable to accurately identify Aeromonas to the species level without the use of comprehensive biochemical methods. For example, two reports demonstrated that A. hydrophila, which was initially identified using conventional biochemical tests, should be classified as A. aquariorum (26, 27), which is further reclassified as Aeromonas dhakensissp. nov. comb nov. (28) based on advanced molecular methods. Therefore, genotypic analyses are one of the best methods for accurately Aeromonas species. However, we did not maintain the clinical isolates obtained for molecular methods for use in identification in this retrospective study. Therefore, information regarding the role of each Aeromonas species in the current issue is scarce. In conclusion, the clinical features of patients with spontaneous versus secondary peritonitis caused by Aeromonas species differ. 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