There’s Something Toxic in the Water

When exposure can be dangerous: Vibrio and Aeromonas infections.

Necrotizing soft tissue infections (NSTI) can include cellulitis, fasciitis and myositis. These severe infections are associated with significant tissue destruction, toxicity, morbidity and mortality. Necrotizing fasciitis is often divided into several categories, dependent on the number and types of microbes.

Type I is polymicrobial, while type II is typically monomicrobial, most commonly group A streptococcal species. Other dangerous microbes associated with NSTI include Vibrio vulnificus and Aeromonas hydrophila. Rather than focus on NSTI, this article will cover infections associated with Vibrio and Aeromonas.

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Case 1:

A 63-year-old male presents with a right lower leg infection. He is from out of town and is visiting family. He’s been enjoying the open ocean with jet skiing. He cut himself on the right leg the other day, but continued to have fun in the water. The next morning he developed severe redness with pain over the wound. He has a history of diabetes. On exam, he is febrile, hypotensive and tachycardic, with erythema involving the entire right lower leg. He has significant pain to palpation. His WBC is elevated but sodium is low, and after morphine 4 mg IV, his pain is unchanged. You suspect NSTI, but what could be the underlying microbe? Does this affect your management?

Vibrio vulnificus

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This species is an aerobic gram-negative bacterium that is typically found in marine environments with saltwater, especially the East and West coasts of the U.S. and the Gulf of Mexico.(^1-3) Numbers reach their peak typically in the summer with increasing water temperatures. Oysters and other shellfish often contain elevated numbers of the bacteria when compared to surrounding water.(^1-3)

Infections most commonly include the gastrointestinal (GI) tract with raw seafood ingestion, septicemia and wound infections. However, infections are rare, with rates approximating 0.5 cases per 100,000 persons per year.(^4-6) The majority of cases with septicemia due to Vibrio are associated with the GI form, and over 95% of seafood-related deaths are due to Vibrio infection.^2,7 GI and skin infections can result in systemic toxicity.(^7-9) We are going to focus on wound infections resulting in severe illness.

Vibrio possesses several attributes that impact its ability to cause infection in the human body. The bacteria contain a capsular polysaccharide that protects against the immune system and can undergo variation.(¹⁰⁾ Vibrio also produces several toxins that increase its virulence.(^7,11) Interestingly, microbial growth depends on iron; with higher transferrin saturation levels with iron, bacteria grow at faster rates.(^12-14)

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Infections are usually the result of exposure to saltwater containing the organism, commonly with recreational water activities.(^8,9) In those with significant risk factors, minor skin wounds may cause severe infections and even NSTI.(^2,8) These risk factors are shown in Table 1.(^2,8,16)  Men are at greater risk of infection when compared to women (85% are male), as are older patients.(¹⁵⁾

Table 1. Risk Factors for Vibrio Infection.^2,8,16

Most skin infections are mild with localized cellulitis. However, severe infection may develop in several hours in those with risk factors.(^2,17) NSTI associated with Vibrio progresses faster than that due to MRSA.(¹⁸⁾ Septicemia is usually associated with ingestion of infected, undercooked shellfish. Up to one-third of the patients with septicemia will become hypotensive within 12 hours of admission, with 75% of patients having bullous skin lesions.(^2,3) Patients may demonstrate thrombocytopenia and disseminated intravascular coagulation. Unfortunately, mortality in the septicemia form is high, up to 40%.(^2,8,16,19) This may reach 90% in those with hypotension.(¹⁹⁾

Definitive diagnosis of infection due to this microbe requires culture, though PCR can be used as well.²⁰ However, results will not be available in the ED, and physicians should consider Vibrio in those with risk factors, bullous skin lesions, hypotension and fever.(^21,22) You know how to treat sepsis: resuscitation with intravenous (IV) fluids and antibiotics is imperative. Mortality increases with greater delays between symptom onset and antibiotic therapy.(^4,8)

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What antibiotics target this organism? In those with severe toxicity, doxycycline 100 mg and either cefotaxime or ceftriaxone are recommended.(^2,7,8,19) A fluoroquinolone like ciprofloxacin can be used in place of doxycycline.(²³⁾ This combination improves survival when compared to a regimen including a first/second-generation cephalosporin and an aminoglycoside.(¹⁹⁾ You will want to add an agent that covers methicillin-resistant Staphylococcus aureus (MRSA) and reduces toxin production associated with necrotizing fasciitis such as clindamycin or linezolid. Source control is vital, especially in those with severe skin infection and NSTI. Surgical consultation for debridement is recommended. In fact, up to 10% of patients will require amputation.(^8,24)

Prognosis remains poor in those with NSTI and sepsis, with 37% dying within several days despite debridement/amputation and antibiotics.(²⁵⁾ Mortality is also higher in those with hypotension, thrombocytopenia, leukopenia, hypoalbuminemia and those with hepatic disease and diabetes.(^2,8,19,21)

Case #1 Conclusion:

The patient is in septic shock, and you are concerned for NSTI due to Vibrio. You order 30cc/kg of IV lactated ringers, doxycycline, ceftriaxone and clindamycin. You also call your surgeon and discuss the case. She agrees the patient likely has NSTI and will begin readying her team for surgery. The intensivist agrees with your plan as well.

Case #2:

A 70-year-old male with history of hepatitis C and cirrhosis presents with severe left thigh pain. He has been fishing on a freshwater lake, but two days ago cut himself with a knife on the left thigh. He didn’t think anything of the wound, washed it with some water from the lake, and kept fishing. He has now noticed severe pain and redness.

Aeromonas

Aeromonas species are gram-negative, facultative anaerobic rods typically found in freshwater, though they can be present in saltwater and sewage.(^26-29) While they grow in a variety of climates, they are found in greater numbers in warmer months, similar to Vibrio.(^26,27) Other factors increasing microbial numbers include nutrient rich water and microbes grow in chlorinated water as well.(^28,29) Aeromonas can infect fish, reptiles, amphibians and mammals; however, only motile species cause disease in humans.(^30,31)

Aeromonas is classically known for causing GI illness; however, the species’ ability to cause symptoms varies, with microbes isolated from asymptomatic patients.(^32-35) As of yet, it has been  difficult predicting what strains will cause disease. Several strains release toxins that can increase microbial virulence.(^36,37)

Freshwater or brackish water exposure is the most common cause of infection in humans. Diarrhea may be bloody or non-bloody and acute or chronic. Wound infections can range from mild to severe and usually involve the extremities. Similar to Vibrio, Aeromonas infections affect men three times more frequently than women. More severe illness can occur in those with malignancies, hepatobiliary disease, immunocompromise and trauma.

Skin infections include cellulitis most commonly, but infection can be associated with myonecrosis and rhabdomyolysis.(^38-42) Most otherwise healthy patients have mild infections, but those with immunocompromise and other risk factors can have rapidly progressive infection with bullae and sepsis within hours. Case reports are present linking Aeromonas to NSTI.(⁴³⁾ Three species of Aeromonas are most commonly associated with skin infections: A. hydrophila, A. veronii, and A. schubertii.(^30,31,44)

For patients with skin infection, risk factors for Aeromonas and cellulitis, begin resuscitation and provide antibiotics. Be sure to discuss your suspicion of Aeromonas infection with the lab for any cultures sent. Choosing the right antibiotic can be tricky, as Aeromonas is typically resistant to penicillin.

However, trimethoprim-sulfamethoxazole, fluoroquinolones, tetracyclines and second/third generation cephalosporins are efficacious.(^44-51)  These species can also produce an inducible beta-lactamase.(⁵¹⁾ If the patient is toxic and Aeromonas infection is suspected, start with doxycycline, ceftriaxone or ciprofloxacin, and an anti-MRSA agent. Seems similar to Vibrio, right? While NSTI is rare, in those with risk factors for severe disease and evidence of NSTI on history and exam, discuss with surgery for debridement.

Case #2 Conclusion:

The patient appears sick with cellulitis. With his freshwater exposure, you provide IV doxycycline, ceftriaxone  and clindamycin with IV fluids. You admit him to the hospital for further management.

Key Points:

• While NSTI is most commonly polymicrobial or the result of Staphylococcus or Streptococcus infection, other microbes include Vibrio and Aeromonas.
• Vibrio and Aeromonas can result in GI illness, septicemia and/or skin infection.
• Vibrio is associated with saltwater exposure, while Aeromonas is more commonly associated with freshwater.
• Risk factors for severe infection and NSTI include male gender, diabetes, immunocompromise and older age.
• Antibiotics that cover Vibrio and Aeromonas include tetracyclines, ceftriaxone and fluoroquinolones.

References:

1. Morris JG Jr, Black RE. Cholera and other vibrioses in the United States. N Engl J Med 1985;312:343.
2. Blake PA, Merson MH, Weaver RE, et al. Disease caused by a marine Vibrio. Clinical characteristics and epidemiology. N Engl J Med 1979; 300:1.
3. Daniels NA. Vibrio vulnificus oysters: pearls and perils. Clin Infect Dis 2011; 52:788.
4. Klontz KC, Lieb S, Schreiber M, et al. Syndromes of Vibrio vulnificus infections. Clinical and epidemiologic features in Florida cases, 1981-1987. Ann Intern Med 1988; 109:318.
5. Johnston JM, Becker SF, McFarland LM. Vibrio vulnificus. Man and the sea. JAMA 1985;253:2850.
6. Hoge CW, Watsky D, Peeler RN, et al. Epidemiology and spectrum of Vibrio infections in a Chesapeake Bay community. J Infect Dis 1989; 160:985.
7. Baker-Austin C, Oliver JD. Vibrio vulnificus: new insights into a deadly opportunistic pathogen. Environ Microbiol. 2018 Feb. 20 (2):423-430.
8. Dechet AM, Yu PA, Koram N, Painter J. Nonfoodborne Vibrio infections: an important cause of morbidity and mortality in the United States, 1997-2006. Clin Infect Dis 2008; 46:970.
9. Yoder JS, Hlavsa MC, Craun GF, et al. Surveillance for waterborne disease and outbreaks associated with recreational water use and other aquatic facility-associated health events–United States, 2005-2006. MMWR Surveill Summ 2008; 57:1.
10. Wright AC, Simpson LM, Oliver JD, Morris JG Jr. Phenotypic evaluation of acapsular transposon mutants of Vibrio vulnificus. Infect Immun 1990; 58:1769.
11. Gavin HE, Satchell KJF. RRSP and RID Effector Domains Dominate the Virulence Impact of Vibrio vulnificus MARTX Toxin. J Infect Dis 2019; 219:889.
12. Brennt CE, Wright AC, Dutta SK, Morris JG Jr. Growth of Vibrio vulnificus in serum from alcoholics: association with high transferrin iron saturation. J Infect Dis 1991; 164:1030.
13. Kim CM, Park RY, Choi MH, et al. Ferrophilic characteristics of Vibrio vulnificus and potential usefulness of iron chelation therapy. J Infect Dis 2007; 195:90.
14. Kim CM, Park YJ, Shin SH. A widespread deferoxamine-mediated iron-uptake system in Vibrio vulnificus. J Infect Dis 2007; 196:1537.
15. Lee SH, Chung BH, Lee WC. Retrospective analysis of epidemiological aspects of Vibrio vulnificus infections in Korea in 2001-2010. Jpn J Infect Dis 2013; 66:331.
16. Tacket CO, Brenner F, Blake PA. Clinical features and an epidemiological study of Vibrio vulnificus infections. J Infect Dis 1984; 149:558.
17. Park SD, Shon HS, Joh NJ. Vibrio vulnificus septicemia in Korea: clinical and epidemiologic findings in seventy patients. J Am Acad Dermatol 1991; 24:397.
18. Tsai YH, Wen-Wei Hsu R, Huang KC, Huang TJ. Comparison of necrotizing fasciitis and sepsis caused by Vibrio vulnificus and Staphylococcus aureus. J Bone Joint Surg Am. 2011 Feb. 93(3):274-84.
19. Liu JW, Lee IK, Tang HJ, et al. Prognostic factors and antibiotics in Vibrio vulnificus septicemia. Arch Intern Med 2006; 166:2117.
20. Tsai YH, Chen PH, Yu PA, Chen CL, Kuo LT, Huang KC. A multiplex PCR assay for detection of Vibrio vulnificus, Aeromonas hydrophila, methicillin-resistant Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus agalactiae from the isolates of patients with necrotizing fasciitis. Int J Infect Dis. 2019 Apr. 81:73-80.
21. Lee YC, Hor LI, Chiu HY, Lee JW, Shieh SJ. Prognostic factor of mortality and its clinical implications in patients with necrotizing fasciitis caused by Vibrio vulnificus.Eur J Clin Microbiol Infect Dis. 2014 Jun. 33(6):1011-8.
22. Hong G, Wu B, Lu C, Li M, Zhao G, Lu Z.Emergency treatment of 16 patients with necrotizing fasciitis caused by Vibrio vulnificus infection complicated with septic shock. Chin Med J (Engl). 2014 May. 127(10):1984-6.
23. Jang HC, Choi SM, Kim HK, et al. In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis. PLoS One 2014; 9:e101118.
24. Chao WN, Tsai CF, Chang HR, et al. Impact of timing of surgery on outcome of Vibrio vulnificus-related necrotizing fasciitis. Am J Surg 2013; 206:32.
25. Tsai YH, Huang TJ, Hsu RW, et al. Necrotizing soft-tissue infections and primary sepsis caused by Vibrio vulnificus and Vibrio cholerae non-O1. J Trauma. 2009 Mar. 66(3):899-905.
26. Holmes P, Niccolls LM, Sartory DP. The ecology of mesophilic Aeromonas in the aquatic environment. In: The Genus: Aeromonas, First Edition, Austin B, Altwegg M, Gosling PJ, Joseph SW (Eds), John Wiley & Sons, Ltd, Chicester 1996. p.127.
27. Martin-Carnahan A, Joseph SW. Aeromonas. In: Bergey’s Manual of Systematic Bacteriology, Second Edition, Brenner, Krieg, Staley, Garrity (Eds), Williams and Wilkins, New York 2005. Vol 2.
28. Burke V, Robinson J, Gracey M, et al. Isolation of Aeromonas spp. from an unchlorinated domestic water supply. Appl Environ Microbiol 1984; 48:367.
29. Burke V, Robinson J, Gracey M, et al. Isolation of Aeromonas hydrophila from a metropolitan water supply: seasonal correlation with clinical isolates. Appl Environ Microbiol 1984; 48:361.
30. Gosling PJ. Aeromonas species in diseases of animals. In: The Genus: Aeromonas, First Edition, Austin B, Altwegg M, Gosling PJ, Joseph SW (Eds), John Wiley & Sons, Ltd, Chicester 1996. p.175.
31. Janda JM, Abbott SL. Human pathogens. In: The Genus: Aeromonas, First Edition, Austin B, Altwegg M, Gosling PJ, Joseph SW (Eds), John Wiley & Sons, Ltd, Chicester 1996. p.175.
32. Joseph SW. Aeromonas gastrointestinal disease: A case study in causation? In: The Genus: Aeromonas, First Edition, Austin B, Altwegg M, Gosling PJ, Joseph SW (Eds), John Wiley & Sons, Ltd, Chichester 1996. p.311.
33. Figueras MJ, Aldea MJ, Fernández N, et al. Aeromonas hemolytic uremic syndrome. A case and a review of the literature. Diagn Microbiol Infect Dis 2007; 58:231.
34. Janda JM, Abbott SL. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev 2010; 23:35.
35. Hofer E, Reis CM, Theophilo GN, et al. [Aeromonas associated with an acute diarrhea outbreak in São Bento do Una, Pernambuco]. Rev Soc Bras Med Trop 2006; 39:217.
36. Galindo CL, Sha J, Fadl LL, et al. Host immune responses to aeromonas virulence factors. Curr Immunol Rev 2006; 2:13.
37. Grim CJ, Kozlova EV, Sha J, et al. Characterization of Aeromonas hydrophila wound pathotypes by comparative genomic and functional analyses of virulence genes. MBio 2013; 4:e00064.
38. Hanson PG, Standridge J, Jarrett F, Maki DG. Freshwater wound infection due to Aeromonas hydrophila. JAMA 1977; 238:1053.
39. Tena D, González-Praetorius A, Pérez-Pomata MT, Bisquert J. [Rapidly progressive myonecrosis by Aeromonas veronii biotype sobria]. An Med Interna 2006; 23:540.
40. Adamski J, Koivuranta M, Leppänen E. Fatal case of myonecrosis and septicaemia caused by Aeromonas hydrophila in Finland. Scand J Infect Dis 2006; 38:1117.
41. Easow JM, Tuladhar R. Aeromonas hydrophila wound infection following a tiger bite in Nepal. Southeast Asian J Trop Med Public Health 2007; 38:867.
42. Tena D, Aspiroz C, Figueras MJ, et al. Surgical site infection due to Aeromonas species: report of nine cases and literature review. Scand J Infect Dis 2009; 41:164.
43. Grim CJ, Kozlova EV, Ponnusamy D, et al. Functional genomic characterization of virulence factors from necrotizing fasciitis-causing strains of Aeromonas hydrophila. Appl Environ Microbiol 2014; 80:4162.
44. Janda JM, Abbott SL. Evolving concepts regarding the genus Aeromonas: an expanding Panorama of species, disease presentations, and unanswered questions. Clin Infect Dis 1998; 27:332.
45. Motyl MR, McKinley G, Janda JM. In vitro susceptibilities of Aeromonas hydrophila, Aeromonas sobria, and Aeromonas caviae to 22 antimicrobial agents. Antimicrob Agents Chemother 1985; 28:151.
46. Overman TL, Janda JM. Antimicrobial susceptibility patterns of Aeromonas jandaei, A. schubertii, A. trota, and A. veronii biotype veronii. J Clin Microbiol 1999; 37:706.
47. Vila J, Marco F, Soler L, et al. In vitro antimicrobial susceptibility of clinical isolates of Aeromonas caviae, Aeromonas hydrophila and Aeromonas veronii biotype sobria. J Antimicrob Chemother 2002; 49:701.
48. Cattoir V, Poirel L, Aubert C, et al. Unexpected occurrence of plasmid-mediated quinolone resistance determinants in environmental Aeromonas spp. Emerg Infect Dis 2008; 14:231.
49. Sánchez-Céspedes J, Figueras MJ, Aspiroz C, et al. Development of imipenem resistance in an Aeromonas veronii biovar sobria clinical isolate recovered from a patient with cholangitis. J Med Microbiol 2009; 58:451.
50. Aravena-Román M, Inglis TJ, Henderson B, et al. Antimicrobial susceptibilities of Aeromonas strains isolated from clinical and environmental sources to 26 antimicrobial agents. Antimicrob Agents Chemother 2012; 56:1110.
51. Schadow KH, Giger DK, Sanders CC. Failure of the Vitek AutoMicrobic system to detect beta-lactam resistance in Aeromonas species. Am J Clin Pathol 1993; 100:308.