SURGICAL INFECTIONS Volume 15, Number 5, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/sur.2013.065
Comparison of Skin and Soft Tissue Infections Caused by Vibrio and Aeromonas Species Chien-Ming Chao,1,2 Chih-Cheng Lai,1 Shih-Horng Huang,3 and Sheng-Hsiang Lin 4,5
Abstract
Background: The aim of this study was to compare skin and soft tissue infections (SSTIs) caused by Vibrio and Aeromonas spp. Methods: Patients whose cultures yielded Vibrio or Aeromonas spp. from July 2004 to June 2010 were retrieved from the computerized database of the bacteriology laboratory at a hospital in southern Taiwan. The medical records were reviewed for all patients fulfilling the criteria of monomicrobial Vibrio or Aeromonas spp. SSTIs and the clinical characteristics were analyzed. Results: During the study period, there were 28 patients with Vibrio spp. and 26 patients with Aeromonas spp., respectively. Vibrio vulnificus (n = 25) and A. hydrophila (n = 14) were the most common spp. There were no significant differences in age, gender, underlying diseases between patients with Vibrio and Aeromonas SSTIs. In comparison to Aeromonas SSTIs, more patients with Vibrio SSTIs were complicated with acute respiratory failure (39.3% vs. 3.8%, p = 0.002) and required intensive care unit admission (50.0% vs. 7.7%, p < 0.001). Furthermore, patients with Aeromonas SSTIs had a higher likelihood of discharge alone within 30 days than Vibrio SSTIs (p = 0.049). The difference in in-hospital mortality among the two groups was not statistically significant (p = 0.11). Conclusion: Both Aeromonas and Vibrio spp. cause SSTIs in southern Taiwan and the pathogenicity of Vibrio spp. might be higher than Aeromonas spp.
V
ibrio spp., a genus of gram-negative bacillus, is ubiquitous in marine environments, especially in temperate or subtropical countries, such as Taiwan [1–4]. Acute gastroenteritis is the most common manifestation of Vibrio spp. infection and skin and soft tissue infection (SSTI) is of considerable importance because of the high mortality rate [5–9]. In southern Taiwan, Aeromonas spp. is another common pathogen causing various types of infection, including SSTIs [10–14]. Both Vibrio spp. and Aeromonas spp. can cause SSTIs in human beings by exposure of wounds to aquatic environments. However, the clinical presentations of SSTIs caused by these two pathogens are similar and it is difficult to differentiate one from another bacterium. Better understanding of the epidemiology and the clinical characteristics of SSTIs caused by these two aquatic pathogens is warranted. Our hospital is located in southern Taiwan where both Vibrio and Aeromonas spp. infections are endemic. 1
Department Department 3 Department 4 Department 5 Department 2
of of of of of
Taking advantage of the abundant material for research, we performed this study in southern Taiwan to investigate the clinical manifestations, microbiological characteristics, response to treatment, and outcome of Vibrio and Aeromonas spp. SSTIs in our hospital over a six-year period. Moreover, this study compares the clinical features of patients with SSTIs caused by Vibrio and Aeromonas spp. to find any significant difference between these two clinical conditions. Patients and Methods Hospital setting and patient selection
This study was conducted at the Chi-Mei Medical Center, Liouying branch, a 900-bed hospital in southern Taiwan. Records of patients whose cultures yielded Vibrio or Aeromonas spp. from July 2004 to June 2010 were retrieved from
Intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan. Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan. Surgery, New Taipei City Hospital, New Taipei, Taiwan. Internal Medicine, New Taipei City Hospital, New Taipei, Taiwan. Respiratory Therapy, Fu-Jen Catholic University, New Taipei, Taiwan.
576
VIBRIO AND AEROMONAS SKIN AND SOFT TISSUE INFECTION
the computerized database of the microbiology laboratory. The medical records of all patients were reviewed retrospectively and patients with SSTI caused by Vibrio or Aeromonas spp. were identified. Information regarding patient age, gender, underlying conditions (including history of immunosuppressive agent use, diabetes mellitus, liver cirrhosis, end-stage renal disease and malignant disease), laboratory data, microbiologic reports, antimicrobial susceptibility test results, and patient outcome was collected. During the study period, there were 33 patients and 129 patients with SSTIs caused by Vibrio and Aeromonas spp., respectively. To investigate the real impact of these two pathogens, we excluded five patients and 103 patients with polymicrobial SSTIs including Vibrio and Aeromonas spp. Bacterial isolates and antimicrobial susceptibilities
The methods of identification for Vibrio or Aeromonas isolates were as described in our previous studies [4,10]. Susceptibilities of these isolates were determined using the disk diffusion method as described by the Clinical and Laboratory Standards Institute [15]. Definitions
Skin and soft tissue infection was diagnosed in patients who presented with pain, swelling of the involved site, and patchy, edematous, erythematous or bullous skin lesions. Polymicrobial infections were regarded as those in which other pathogens were isolated from the infection site during the course of Vibrio or Aeromonas spp. infection. Shock was diagnosed in patients with a systolic blood pressure < 90 mm Hg or in patients who required inotropic agents to maintain blood pressure. In-hospital mortality was defined as death from all causes during hospitalization. Statistical analysis
Data were analyzed using SPSS version 11.0 software (IBM Inc., Armonk, NY). Continuous variables were expressed as mean – standard deviation. Comparisons between continuous variables were analyzed using the Wilcoxon rank sum test or the Student independent t test, as appropriate. Comparisons between categorical variables were made using the chisquare or the Fisher exact test. The 30-day probability of live discharge was calculated using Kaplan-Meier analysis and the log-rank test. Statistical significance was set at p < 0.05. Results Clinical characteristics
Among the 28 cases with Vibrio spp. SSTIs, V. vulnificus was the most common pathogens (n = 25), followed by V. parahaemolyticus (n = 2), and V. alginolyticus (n = 1). Among the 26 cases with Aeromonas spp. SSTI, A. hydrophila was the most common pathogen (n = 14), followed by A. veronii biovar sobria (n = 8), and A. veronii biovar veronii (n = 4). Comparison between patients with monomicrobial SSTIs due to Vibrio and Aeromonas spp.
We compared the clinical characteristics of monomicrobial SSTIs due to Vibrio and Aeromonas spp. (Table
577
Table 1. Comparison of Demographics of 26 Patients with Monomicrobial Skin and Soft Tissue Infections (SSTIs) Caused by Aeromonas Spp. and 28 Patients with SSTIs Caused by Vibrio Spp.
Age, years Female Underlying condition Liver cirrhosis Hepatitis B Hepatitis C Diabetes mellitus Active cancer End-stage renal disease Alcoholism Water exposure Location of SSTI Hand Leg
Aeromonas Vibrio spp. spp. n = 26 n = 28 mean – SD mean – SD or n (%) or n (%)
p
63.4 – 13.9 67.5 – 11.7 9 (34.6) 11 (39.3)
0.25 0.94
4 3 4 3 2 2 1 11
(15.4) (11.5) (15.4) (11.5) ( 7.7) ( 7.7) ( 3.8) (42.3)
3 (11.5) 23 (88.5)
6 4 4 8 5 1 0 22
(21.4) (14.3) (14.3) (28.6) (17.9) ( 3.6) ( 0.0) (78.6)
4 (14.3) 24 (85.7)
0.73 > 0.99 > 0.99 0.18 0.42 0.60 0.48 0.014 > 0.99 0.92
SD = standard deviation; SSTI = skin and soft tissue infection
1–3). There were no significant differences in age, gender, or underlying diseases between patients with Vibrio and Aeromonas spp. SSTIs. More patients with Vibrio infections had recalled exposure to aquatic environments than Aeromonas infections. Moreover, patients with Vibrio infections had significantly higher white blood cell (WBC) counts and some aspartate transaminase (AST) concentrations than patients with Aeromonas infections. Higher frequencies of bacteremia and hemorrhagic bullae presented in patients with Vibrio infections than Aeromonas infections. The majority of patients received appropriate initial antibiotic
Table 2. Comparison of Laboratory Results of 26 Patients with Monomicrobial Skin and Soft Tissue Infections (SSTIs) Caused by Aeromonas Spp. and 28 Patients with SSTIs Caused by Vibrio Spp. Aeromonas spp. n = 26 mean – SD
Vibrio spp. n = 28 mean – SD
p
White blood cell 9,175 – 3,315 13,050 – 5,859 0.005 (cells/mcL) Aspartate 39.7 – 15.2 58.8 – 11.3 < 0.001 transaminase (IU/L) Urea nitrogen 24.8 – 15.5 22.3 – 8.3 0.46 (mg/dL) Creatinine (mg/dL) 1.7 – 2.1 1.5 – 0.6 0.63 C-reactive protein 43.6 – 63.1 41.7 – 36.5 0.89 (mg/L) SD = standard deviation
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CHAO ET AL.
Table 3. Comparison of Complication, Treatment, and Outcome of 26 Patients with Monomicrobial Skin and Soft Tissue Infections (SSTIs) Caused by Aeromonas Spp. and 28 Patients with SSTIs Caused by Vibrio Spp.
Bacteremia Shock at initial presentation Hemorrhagic bullae Surgical treatment Repeated debridement Outcome Acute respiratory failure ICU admission In-hospital mortality
Aeromonas spp. n = 26 n (%)
Vibrio spp. n = 28 n (%)
3 (11.5) 5 (19.2)
13 (46.4) 8 (28.6)
0.046 0.63
1 ( 3.8) 18 (69.2) 10 (38.5)
8 (28.6) 24 (85.7) 16 (57.1)
0.025 0.20 0.27
1 ( 3.8)
11 (39.3)
0.002
2 ( 7.7) 0
14 (50.0) 4 (14.3)
< 0.001 0.11
p
ICU = intensive care unit
therapy (third-generation cephalosporins or fluoroquinolones) in both groups (82.1% in Vibrio infections and 76.9% in Aeromonas infections). There was no significant difference in surgical treatment between these two groups. Despite the similar in-hospital mortality rates between these two groups, patients with Vibrio infections were more likely to have acute respiratory failure and require intensive care unit (ICU) admission than patients with Aeromonas infections. Among the 44 hospitalized patients, (26 of Vibrio and 18 of Aeromonas infections), patients with Aeromonas infection had a higher likelihood of discharge alive within 30 days ( p = 0.049) (Figure 1).
Microbiological investigations
The results of in vitro susceptibility testing to antimicrobial agents against Vibrio and Aeromonas isolates are shown in Table 4. There was no significant difference in antimicrobial resistance among Vibrio and Aeromonas isolates. More than 70% of Vibrio or Aeromonas isolates were resistant to ampicillin, ampicillin-sulbactam, and cefazolin. In contrast, more than 90% of isolates were susceptible to ceftriaxone, ceftazidime, cefepime, piperacilintazobactam, ciprofloxacin, and gentamicin. Moreover, all of the isolates were susceptible to imipenem-cilastatin and amikacin. Discussion
This study is the first study to compare the clinical characteristics of patients with SSTIs due to Vibrio and Aeromonas spp. and to have significant findings. Although the clinical presentations of Vibrio and Aeromonas SSTIs were similar, we found several significant differences that may help clinicians distinguish one from another pathogen. First, Vibrio infections were associated with higher WBC count and AST, and more bacteremia and hemorrhagic bullae than Aeromonas infections. Despite no difference in mortality between the groups, complications such as acute respiratory failure and the requirement of ICU admission occurred more frequently in patients with SSTIs caused by Vibrio spp. than Aeromonas spp. Meanwhile, patients with Aeromonas infections had a significantly higher likelihood of discharge alive within one month than the Vibrio infections despite similar medical treatment and surgical management. In summary, Vibrio spp.-related SSTIs seem to be more severe than Aeromonas infections in the similar clinical setting, and increased attention to Vibrio infections is warranted.
FIG. 1. The Kaplan-Meier curves of the 30-day probability of live discharge for patients with skin and soft tissue infections caused by Aeromonas and Vibrio spp. (hazard ratio 1.93, 95% confidence interval 0.93–3.99, p = 0.049, log-rank test).
VIBRIO AND AEROMONAS SKIN AND SOFT TISSUE INFECTION
Table 4. Rates of Vibrio and Aeromonas Isolates Non-Susceptible to 12 Antimicrobial Agents by the Disk Diffusion Method Vibrio isolates n = 28 n (%) Ampicillin Ampicillin-sulbactam Cefazolin Cefuroxime Ceftriaxone Ceftazidime Cefepime Piperacillin-tazobactam Imipenem-cilastatin Ciprofloxacin Gentamicin Amikacin
27 23 20 8 1 1 0 2 0 1 1 0
(96.4) (82.1) (71.4) (28.6) ( 3.6) ( 3.6) ( ( ( (
7.1) 0.0) 3.6) 3.6)
Aeromonas isolates n = 26 n (%) 25 20 22 7 2 2 1 2 0 1 2 0
(96.2) (76.9) (84.6) (26.9) ( 7.7) ( 7.7) ( 3.8) ( 7.7) ( 3.8) ( 7.7)
p > 0.99 0.89 0.33 0.87 0.60 0.60 0.48 > 0.99 > 0.99 > 0.99 0.60 > 0.99
Second, we found about one-fourth of patients with Aeromonas infections and one-half of patients with Vibrio infections had underlying diabetes mellitus or liver cirrhosis. This finding is consistent with previous studies about Aeromonas or Vibrio infections [6–14, 16–19]. In addition, all four fatal cases in this study had liver cirrhosis (n = 3) or diabetes mellitus (n = 2). Both of the above findings suggest that physicians should consider Aeromonas or Vibrio spp. as possible pathogens causing SSTI, especially for patients with diabetes or liver cirrhosis. As noted in previous reports [16–19], these two underlying diseases could not only predispose patients to Aeromonas or Vibrio SSTI, but also could indicate a poorer prognosis in this clinical entity. Third, the antibiotic resistant patterns among Aeromonas and Vibrio spp. were similar in this study. Most of Aeromonas and Vibrio isolates in the present work had in vitro resistance to ampicillin and first-generation cephalosporin. In contrast, third- or fourth-generation cephalosporin and ciprofloxacin showed good in vitro activity against both Aeromonas and Vibrio spp. These findings were consistent with previous studies [12,20] and may suggest that third-generation cephalosporin or a fluoroquinolones should be the drug of choice in this clinical condition. This study has a number of limitations. It is a retrospective study with a small sample size and with all associated limitations. The present work was performed in a hospital in southern Taiwan; therefore, our findings may not be generalized to all other hospitals. However, as our hospital was located in an endemic area for these two pathogens, we had a better opportunity to enroll a greater number of cases as compared to other hospitals. We could not control our analysis for the size of the initial wound, timing of initial surgical debridement, number of surgical debridements per patient, and adequacy of surgical debridement at each operation. Furthermore, not all patients received appropriate initial antibiotic therapy. Despite these limitations, the findings of this study still provide useful information about these soft tissue infections.
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Conclusion
In conclusion, Aeromonas or Vibrio spp. cause SSTIs in southern Taiwan, especially in patients with diabetes mellitus and liver cirrhosis. Although most of the clinical manifestations and microbiologic characteristics are similar for both pathogens, the presentations of Vibrio infections seem to be more toxic than Aeromonas infections. Author Disclosure Statement
The authors report no conflicts of interest. The authors are responsible for the content and writing of the paper. References
1. Lin CJ, Chiu CT, Lin DY, et al. Non-O1 Vibrio cholerae bacteremia in patients with cirrhosis: 5-yr experience from a single medical center. Am J Gastroenterol 1996;91:336– 340. 2. Ko WC, Chuang YC, Huang GC, et al. Infections due to non-O1 Vibrio cholerae in southern Taiwan: Predominance in cirrhotic patients. Clin Infect Dis 1998;27:774–780. 3. Chuang YC, Yuan CY, Liu CY, et al. Vibrio vulnificus infection in Taiwan: report of 28 cases and review of clinical manifestations and treatment. Clin Infect Dis 1992; 15:271–276. 4. Hou CC, Lai CC, Liu WL, et al. Clinical manifestation and prognostic factors of non-cholerae Vibrio infections. Eur J Clin Microbiol Infect Dis 2011;30:819–824. 5. Vollberg CM, Herrera JL. Vibrio vulnificus infection: An important cause of septicemia in patients with cirrhosis. South Med J 1997;90:1040–1042. 6. Chen SC, Chan KS, Chao WN, et al. Clinical outcomes and prognostic factors for patients with Vibrio vulnificus infections requiring intensive care: A 10-yr retrospective study. Crit Care Med 2010;38:1984–1990. 7. Liu JW, Lee IK, Tang HJ, et al. Prognostic factors and antibiotics in Vibrio vulnificus septicemia. Arch Intern Med 2006;166:2117–2123. 8. Tsai YH, Wen-Wei Hsu R, Huang KC, et al. Comparison of necrotizing fasciitis and sepsis caused by Vibrio vulnificus and Staphylococcus aureus. J Bone Joint Surg Am 2011; 93:274–284. 9. Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus: An important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis 2011;15: e157–e166. 10. Chao CM, Lai CC, Tang HJ, et al. Skin and soft-tissue infections caused by Aeromonas species Eur J Clin Microbiol Infect Dis 2013;32:543–547. 11. Chao CM, Gau SJ, Lai CC. Empyema caused by Aeromonas species in Taiwan. Am J Trop Med Hyg 2012; 87:933–935. 12. Chao CM, Lai CC, Tang HJ, et al. Biliary tract infections caused by Aeromonas species Eur J Clin Microbiol Infect Dis 2013;32:245–251. 13. Chao CM, Gau SJ, Lai CC. Aeromonas genitourinary tract infection. J Infect 2012;65:573–575. 14. Lai CC, Ding LW, Hsueh PR. Wound infection and septic shock due to Aeromonas trota in a patient with liver cirrhosis. Clin Infect Dis 2007;44:1523–1524. 15. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Nineteenth informational supplement. Document M100-S19. Wayne, PA: CLSI; 2009.
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16. Kuo Chou TN, Chao WN, Yang C, et al. Predictors of mortality in skin and soft-tissue infections caused by Vibrio vulnificus. World J Surg 2010;34:1669–1675. 17. Tsai YH, Hang TJ, Hsu RW, et al. Necrotizing softtissue infections and primary sepsis caused by Vibrio vulnificus and Vibrio cholerae non-O1. J Trauma 2009; 66:899–905. 18. Tsia YH, Huang KC, Huang TJ, et al. Case reports: Fatal necrotizing fasciitis caused by Aeromonas sobria in two diabetic patients. Clin Orthop Relat Res 2009;467:846– 849. 19. Tsai YH, Hsu RW, Huang TJ, et al. Necrotizing soft-tissue infections and sepsis caused by Vibrio vulnificus compared with those caused by Aeromonas species J Bone Joint Surg Am 2007;89:631–636.
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20. Liu CY, Huang YT, Liao CH, et al. In vitro activities of tigecycline against clinical isolates of Aeromonas, Vibrio, and Salmonella species in Taiwan. Antimicrob Agents Chemother 2008;52:2677–2679.
Address correspondence to: Dr. Sheng-Hsiang Lin Department of Internal Medicine New Taipei City Hospital No. 3, Sec. 1, New Taipei Blvd., San-Chong Dist. New Taipei City 24141 Taiwan E-mail: [email protected]
Comparison of Skin and Soft Tissue Infections Caused by Vibrio and Aeromonas Species Chien-Ming Chao,1,2 Chih-Cheng Lai,1 Shih-Horng Huang,3 and Sheng-Hsiang Lin 4,5
Abstract
Background: The aim of this study was to compare skin and soft tissue infections (SSTIs) caused by Vibrio and Aeromonas spp. Methods: Patients whose cultures yielded Vibrio or Aeromonas spp. from July 2004 to June 2010 were retrieved from the computerized database of the bacteriology laboratory at a hospital in southern Taiwan. The medical records were reviewed for all patients fulfilling the criteria of monomicrobial Vibrio or Aeromonas spp. SSTIs and the clinical characteristics were analyzed. Results: During the study period, there were 28 patients with Vibrio spp. and 26 patients with Aeromonas spp., respectively. Vibrio vulnificus (n = 25) and A. hydrophila (n = 14) were the most common spp. There were no significant differences in age, gender, underlying diseases between patients with Vibrio and Aeromonas SSTIs. In comparison to Aeromonas SSTIs, more patients with Vibrio SSTIs were complicated with acute respiratory failure (39.3% vs. 3.8%, p = 0.002) and required intensive care unit admission (50.0% vs. 7.7%, p < 0.001). Furthermore, patients with Aeromonas SSTIs had a higher likelihood of discharge alone within 30 days than Vibrio SSTIs (p = 0.049). The difference in in-hospital mortality among the two groups was not statistically significant (p = 0.11). Conclusion: Both Aeromonas and Vibrio spp. cause SSTIs in southern Taiwan and the pathogenicity of Vibrio spp. might be higher than Aeromonas spp.
V
ibrio spp., a genus of gram-negative bacillus, is ubiquitous in marine environments, especially in temperate or subtropical countries, such as Taiwan [1–4]. Acute gastroenteritis is the most common manifestation of Vibrio spp. infection and skin and soft tissue infection (SSTI) is of considerable importance because of the high mortality rate [5–9]. In southern Taiwan, Aeromonas spp. is another common pathogen causing various types of infection, including SSTIs [10–14]. Both Vibrio spp. and Aeromonas spp. can cause SSTIs in human beings by exposure of wounds to aquatic environments. However, the clinical presentations of SSTIs caused by these two pathogens are similar and it is difficult to differentiate one from another bacterium. Better understanding of the epidemiology and the clinical characteristics of SSTIs caused by these two aquatic pathogens is warranted. Our hospital is located in southern Taiwan where both Vibrio and Aeromonas spp. infections are endemic. 1
Department Department 3 Department 4 Department 5 Department 2
of of of of of
Taking advantage of the abundant material for research, we performed this study in southern Taiwan to investigate the clinical manifestations, microbiological characteristics, response to treatment, and outcome of Vibrio and Aeromonas spp. SSTIs in our hospital over a six-year period. Moreover, this study compares the clinical features of patients with SSTIs caused by Vibrio and Aeromonas spp. to find any significant difference between these two clinical conditions. Patients and Methods Hospital setting and patient selection
This study was conducted at the Chi-Mei Medical Center, Liouying branch, a 900-bed hospital in southern Taiwan. Records of patients whose cultures yielded Vibrio or Aeromonas spp. from July 2004 to June 2010 were retrieved from
Intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan. Nursing, Min-Hwei College of Health Care Management, Tainan, Taiwan. Surgery, New Taipei City Hospital, New Taipei, Taiwan. Internal Medicine, New Taipei City Hospital, New Taipei, Taiwan. Respiratory Therapy, Fu-Jen Catholic University, New Taipei, Taiwan.
576
VIBRIO AND AEROMONAS SKIN AND SOFT TISSUE INFECTION
the computerized database of the microbiology laboratory. The medical records of all patients were reviewed retrospectively and patients with SSTI caused by Vibrio or Aeromonas spp. were identified. Information regarding patient age, gender, underlying conditions (including history of immunosuppressive agent use, diabetes mellitus, liver cirrhosis, end-stage renal disease and malignant disease), laboratory data, microbiologic reports, antimicrobial susceptibility test results, and patient outcome was collected. During the study period, there were 33 patients and 129 patients with SSTIs caused by Vibrio and Aeromonas spp., respectively. To investigate the real impact of these two pathogens, we excluded five patients and 103 patients with polymicrobial SSTIs including Vibrio and Aeromonas spp. Bacterial isolates and antimicrobial susceptibilities
The methods of identification for Vibrio or Aeromonas isolates were as described in our previous studies [4,10]. Susceptibilities of these isolates were determined using the disk diffusion method as described by the Clinical and Laboratory Standards Institute [15]. Definitions
Skin and soft tissue infection was diagnosed in patients who presented with pain, swelling of the involved site, and patchy, edematous, erythematous or bullous skin lesions. Polymicrobial infections were regarded as those in which other pathogens were isolated from the infection site during the course of Vibrio or Aeromonas spp. infection. Shock was diagnosed in patients with a systolic blood pressure < 90 mm Hg or in patients who required inotropic agents to maintain blood pressure. In-hospital mortality was defined as death from all causes during hospitalization. Statistical analysis
Data were analyzed using SPSS version 11.0 software (IBM Inc., Armonk, NY). Continuous variables were expressed as mean – standard deviation. Comparisons between continuous variables were analyzed using the Wilcoxon rank sum test or the Student independent t test, as appropriate. Comparisons between categorical variables were made using the chisquare or the Fisher exact test. The 30-day probability of live discharge was calculated using Kaplan-Meier analysis and the log-rank test. Statistical significance was set at p < 0.05. Results Clinical characteristics
Among the 28 cases with Vibrio spp. SSTIs, V. vulnificus was the most common pathogens (n = 25), followed by V. parahaemolyticus (n = 2), and V. alginolyticus (n = 1). Among the 26 cases with Aeromonas spp. SSTI, A. hydrophila was the most common pathogen (n = 14), followed by A. veronii biovar sobria (n = 8), and A. veronii biovar veronii (n = 4). Comparison between patients with monomicrobial SSTIs due to Vibrio and Aeromonas spp.
We compared the clinical characteristics of monomicrobial SSTIs due to Vibrio and Aeromonas spp. (Table
577
Table 1. Comparison of Demographics of 26 Patients with Monomicrobial Skin and Soft Tissue Infections (SSTIs) Caused by Aeromonas Spp. and 28 Patients with SSTIs Caused by Vibrio Spp.
Age, years Female Underlying condition Liver cirrhosis Hepatitis B Hepatitis C Diabetes mellitus Active cancer End-stage renal disease Alcoholism Water exposure Location of SSTI Hand Leg
Aeromonas Vibrio spp. spp. n = 26 n = 28 mean – SD mean – SD or n (%) or n (%)
p
63.4 – 13.9 67.5 – 11.7 9 (34.6) 11 (39.3)
0.25 0.94
4 3 4 3 2 2 1 11
(15.4) (11.5) (15.4) (11.5) ( 7.7) ( 7.7) ( 3.8) (42.3)
3 (11.5) 23 (88.5)
6 4 4 8 5 1 0 22
(21.4) (14.3) (14.3) (28.6) (17.9) ( 3.6) ( 0.0) (78.6)
4 (14.3) 24 (85.7)
0.73 > 0.99 > 0.99 0.18 0.42 0.60 0.48 0.014 > 0.99 0.92
SD = standard deviation; SSTI = skin and soft tissue infection
1–3). There were no significant differences in age, gender, or underlying diseases between patients with Vibrio and Aeromonas spp. SSTIs. More patients with Vibrio infections had recalled exposure to aquatic environments than Aeromonas infections. Moreover, patients with Vibrio infections had significantly higher white blood cell (WBC) counts and some aspartate transaminase (AST) concentrations than patients with Aeromonas infections. Higher frequencies of bacteremia and hemorrhagic bullae presented in patients with Vibrio infections than Aeromonas infections. The majority of patients received appropriate initial antibiotic
Table 2. Comparison of Laboratory Results of 26 Patients with Monomicrobial Skin and Soft Tissue Infections (SSTIs) Caused by Aeromonas Spp. and 28 Patients with SSTIs Caused by Vibrio Spp. Aeromonas spp. n = 26 mean – SD
Vibrio spp. n = 28 mean – SD
p
White blood cell 9,175 – 3,315 13,050 – 5,859 0.005 (cells/mcL) Aspartate 39.7 – 15.2 58.8 – 11.3 < 0.001 transaminase (IU/L) Urea nitrogen 24.8 – 15.5 22.3 – 8.3 0.46 (mg/dL) Creatinine (mg/dL) 1.7 – 2.1 1.5 – 0.6 0.63 C-reactive protein 43.6 – 63.1 41.7 – 36.5 0.89 (mg/L) SD = standard deviation
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Table 3. Comparison of Complication, Treatment, and Outcome of 26 Patients with Monomicrobial Skin and Soft Tissue Infections (SSTIs) Caused by Aeromonas Spp. and 28 Patients with SSTIs Caused by Vibrio Spp.
Bacteremia Shock at initial presentation Hemorrhagic bullae Surgical treatment Repeated debridement Outcome Acute respiratory failure ICU admission In-hospital mortality
Aeromonas spp. n = 26 n (%)
Vibrio spp. n = 28 n (%)
3 (11.5) 5 (19.2)
13 (46.4) 8 (28.6)
0.046 0.63
1 ( 3.8) 18 (69.2) 10 (38.5)
8 (28.6) 24 (85.7) 16 (57.1)
0.025 0.20 0.27
1 ( 3.8)
11 (39.3)
0.002
2 ( 7.7) 0
14 (50.0) 4 (14.3)
< 0.001 0.11
p
ICU = intensive care unit
therapy (third-generation cephalosporins or fluoroquinolones) in both groups (82.1% in Vibrio infections and 76.9% in Aeromonas infections). There was no significant difference in surgical treatment between these two groups. Despite the similar in-hospital mortality rates between these two groups, patients with Vibrio infections were more likely to have acute respiratory failure and require intensive care unit (ICU) admission than patients with Aeromonas infections. Among the 44 hospitalized patients, (26 of Vibrio and 18 of Aeromonas infections), patients with Aeromonas infection had a higher likelihood of discharge alive within 30 days ( p = 0.049) (Figure 1).
Microbiological investigations
The results of in vitro susceptibility testing to antimicrobial agents against Vibrio and Aeromonas isolates are shown in Table 4. There was no significant difference in antimicrobial resistance among Vibrio and Aeromonas isolates. More than 70% of Vibrio or Aeromonas isolates were resistant to ampicillin, ampicillin-sulbactam, and cefazolin. In contrast, more than 90% of isolates were susceptible to ceftriaxone, ceftazidime, cefepime, piperacilintazobactam, ciprofloxacin, and gentamicin. Moreover, all of the isolates were susceptible to imipenem-cilastatin and amikacin. Discussion
This study is the first study to compare the clinical characteristics of patients with SSTIs due to Vibrio and Aeromonas spp. and to have significant findings. Although the clinical presentations of Vibrio and Aeromonas SSTIs were similar, we found several significant differences that may help clinicians distinguish one from another pathogen. First, Vibrio infections were associated with higher WBC count and AST, and more bacteremia and hemorrhagic bullae than Aeromonas infections. Despite no difference in mortality between the groups, complications such as acute respiratory failure and the requirement of ICU admission occurred more frequently in patients with SSTIs caused by Vibrio spp. than Aeromonas spp. Meanwhile, patients with Aeromonas infections had a significantly higher likelihood of discharge alive within one month than the Vibrio infections despite similar medical treatment and surgical management. In summary, Vibrio spp.-related SSTIs seem to be more severe than Aeromonas infections in the similar clinical setting, and increased attention to Vibrio infections is warranted.
FIG. 1. The Kaplan-Meier curves of the 30-day probability of live discharge for patients with skin and soft tissue infections caused by Aeromonas and Vibrio spp. (hazard ratio 1.93, 95% confidence interval 0.93–3.99, p = 0.049, log-rank test).
VIBRIO AND AEROMONAS SKIN AND SOFT TISSUE INFECTION
Table 4. Rates of Vibrio and Aeromonas Isolates Non-Susceptible to 12 Antimicrobial Agents by the Disk Diffusion Method Vibrio isolates n = 28 n (%) Ampicillin Ampicillin-sulbactam Cefazolin Cefuroxime Ceftriaxone Ceftazidime Cefepime Piperacillin-tazobactam Imipenem-cilastatin Ciprofloxacin Gentamicin Amikacin
27 23 20 8 1 1 0 2 0 1 1 0
(96.4) (82.1) (71.4) (28.6) ( 3.6) ( 3.6) ( ( ( (
7.1) 0.0) 3.6) 3.6)
Aeromonas isolates n = 26 n (%) 25 20 22 7 2 2 1 2 0 1 2 0
(96.2) (76.9) (84.6) (26.9) ( 7.7) ( 7.7) ( 3.8) ( 7.7) ( 3.8) ( 7.7)
p > 0.99 0.89 0.33 0.87 0.60 0.60 0.48 > 0.99 > 0.99 > 0.99 0.60 > 0.99
Second, we found about one-fourth of patients with Aeromonas infections and one-half of patients with Vibrio infections had underlying diabetes mellitus or liver cirrhosis. This finding is consistent with previous studies about Aeromonas or Vibrio infections [6–14, 16–19]. In addition, all four fatal cases in this study had liver cirrhosis (n = 3) or diabetes mellitus (n = 2). Both of the above findings suggest that physicians should consider Aeromonas or Vibrio spp. as possible pathogens causing SSTI, especially for patients with diabetes or liver cirrhosis. As noted in previous reports [16–19], these two underlying diseases could not only predispose patients to Aeromonas or Vibrio SSTI, but also could indicate a poorer prognosis in this clinical entity. Third, the antibiotic resistant patterns among Aeromonas and Vibrio spp. were similar in this study. Most of Aeromonas and Vibrio isolates in the present work had in vitro resistance to ampicillin and first-generation cephalosporin. In contrast, third- or fourth-generation cephalosporin and ciprofloxacin showed good in vitro activity against both Aeromonas and Vibrio spp. These findings were consistent with previous studies [12,20] and may suggest that third-generation cephalosporin or a fluoroquinolones should be the drug of choice in this clinical condition. This study has a number of limitations. It is a retrospective study with a small sample size and with all associated limitations. The present work was performed in a hospital in southern Taiwan; therefore, our findings may not be generalized to all other hospitals. However, as our hospital was located in an endemic area for these two pathogens, we had a better opportunity to enroll a greater number of cases as compared to other hospitals. We could not control our analysis for the size of the initial wound, timing of initial surgical debridement, number of surgical debridements per patient, and adequacy of surgical debridement at each operation. Furthermore, not all patients received appropriate initial antibiotic therapy. Despite these limitations, the findings of this study still provide useful information about these soft tissue infections.
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Conclusion
In conclusion, Aeromonas or Vibrio spp. cause SSTIs in southern Taiwan, especially in patients with diabetes mellitus and liver cirrhosis. Although most of the clinical manifestations and microbiologic characteristics are similar for both pathogens, the presentations of Vibrio infections seem to be more toxic than Aeromonas infections. Author Disclosure Statement
The authors report no conflicts of interest. The authors are responsible for the content and writing of the paper. References
1. Lin CJ, Chiu CT, Lin DY, et al. Non-O1 Vibrio cholerae bacteremia in patients with cirrhosis: 5-yr experience from a single medical center. Am J Gastroenterol 1996;91:336– 340. 2. Ko WC, Chuang YC, Huang GC, et al. Infections due to non-O1 Vibrio cholerae in southern Taiwan: Predominance in cirrhotic patients. Clin Infect Dis 1998;27:774–780. 3. Chuang YC, Yuan CY, Liu CY, et al. Vibrio vulnificus infection in Taiwan: report of 28 cases and review of clinical manifestations and treatment. Clin Infect Dis 1992; 15:271–276. 4. Hou CC, Lai CC, Liu WL, et al. Clinical manifestation and prognostic factors of non-cholerae Vibrio infections. Eur J Clin Microbiol Infect Dis 2011;30:819–824. 5. Vollberg CM, Herrera JL. Vibrio vulnificus infection: An important cause of septicemia in patients with cirrhosis. South Med J 1997;90:1040–1042. 6. Chen SC, Chan KS, Chao WN, et al. Clinical outcomes and prognostic factors for patients with Vibrio vulnificus infections requiring intensive care: A 10-yr retrospective study. Crit Care Med 2010;38:1984–1990. 7. Liu JW, Lee IK, Tang HJ, et al. Prognostic factors and antibiotics in Vibrio vulnificus septicemia. Arch Intern Med 2006;166:2117–2123. 8. Tsai YH, Wen-Wei Hsu R, Huang KC, et al. Comparison of necrotizing fasciitis and sepsis caused by Vibrio vulnificus and Staphylococcus aureus. J Bone Joint Surg Am 2011; 93:274–284. 9. Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus: An important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis 2011;15: e157–e166. 10. Chao CM, Lai CC, Tang HJ, et al. Skin and soft-tissue infections caused by Aeromonas species Eur J Clin Microbiol Infect Dis 2013;32:543–547. 11. Chao CM, Gau SJ, Lai CC. Empyema caused by Aeromonas species in Taiwan. Am J Trop Med Hyg 2012; 87:933–935. 12. Chao CM, Lai CC, Tang HJ, et al. Biliary tract infections caused by Aeromonas species Eur J Clin Microbiol Infect Dis 2013;32:245–251. 13. Chao CM, Gau SJ, Lai CC. Aeromonas genitourinary tract infection. J Infect 2012;65:573–575. 14. Lai CC, Ding LW, Hsueh PR. Wound infection and septic shock due to Aeromonas trota in a patient with liver cirrhosis. Clin Infect Dis 2007;44:1523–1524. 15. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Nineteenth informational supplement. Document M100-S19. Wayne, PA: CLSI; 2009.
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16. Kuo Chou TN, Chao WN, Yang C, et al. Predictors of mortality in skin and soft-tissue infections caused by Vibrio vulnificus. World J Surg 2010;34:1669–1675. 17. Tsai YH, Hang TJ, Hsu RW, et al. Necrotizing softtissue infections and primary sepsis caused by Vibrio vulnificus and Vibrio cholerae non-O1. J Trauma 2009; 66:899–905. 18. Tsia YH, Huang KC, Huang TJ, et al. Case reports: Fatal necrotizing fasciitis caused by Aeromonas sobria in two diabetic patients. Clin Orthop Relat Res 2009;467:846– 849. 19. Tsai YH, Hsu RW, Huang TJ, et al. Necrotizing soft-tissue infections and sepsis caused by Vibrio vulnificus compared with those caused by Aeromonas species J Bone Joint Surg Am 2007;89:631–636.
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20. Liu CY, Huang YT, Liao CH, et al. In vitro activities of tigecycline against clinical isolates of Aeromonas, Vibrio, and Salmonella species in Taiwan. Antimicrob Agents Chemother 2008;52:2677–2679.
Address correspondence to: Dr. Sheng-Hsiang Lin Department of Internal Medicine New Taipei City Hospital No. 3, Sec. 1, New Taipei Blvd., San-Chong Dist. New Taipei City 24141 Taiwan E-mail: [email protected]
