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There’s Something Toxic in the Water

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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

Risk Factor Frequency
Alcoholic cirrhosis

Liver disease – cirrhosis and chronic hepatitis

Alcohol abuse, but no known liver disease

Hereditary hemochromatosis

Diabetes, renal failure, rheumatoid arthritis, lymphoma

31-43%

24-31%

12-27%

12%

7-8%

 

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:

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ABOUT THE AUTHORS

Brit Long, MD is an EM Attending Physician at San Antonio Uniformed Services Health Education Consortium.

Alex Koyfman, MD is a Clinical Assistant Professor of Emergency Medicine at UT Southwestern Medical Center and an Attending Physician at Parkland Memorial Hospital. He is also Editor-in-Chief for emDocs.

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