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INTRODUCTION — Soft tissue infections can occur after both freshwater and saltwater exposure, particularly if there is associated trauma. Trauma can be caused by living creatures or by inanimate objects found in the aquatic environment. In addition, some aquatic creatures can transmit soft tissue infections outside the water environment. This can occur, for example, with the use of leeches for medicinal purposes to relieve venous congestion at surgical sites as Aeromonas spp, a normal inhabitant of the foregut of leeches, may contaminate the wound and cause a secondary wound infection .
Although the array of microorganisms that can produce soft tissue infections following water exposure is extremely large, this discussion will focus on five bacteria that most commonly produce soft tissue infections in association with exposure to water or water-related animals. These include Aeromonas species, Edwardsiella tarda, Erysipelothrix rhusiopathiae, Vibrio vulnificus, and Mycobacterium marinum. The acronym AEEVM will be used here when referring to these organisms.
The epidemiology, clinical manifestations, diagnosis, and empiric treatment of AEEVM infections and specific treatment of Edwardsiella spp and M. marinum infections will be reviewed here. Treatment of Aeromonas spp, Erysipelothrix spp, and V. vulnificus infections is presented separately. (See "Aeromonas infections" and "Vibrio vulnificus infections" and "Erysipelothrix infection".)
EPIDEMIOLOGY — Local trauma or injury, which can be either minor or major, coupled with water exposure is a common theme that predisposes to many of the AEEVM-related infections.
Trauma — Trauma leading to infection with AEEVM includes puncture wounds due to fishhooks and fish spines and lacerations due to boat motor propeller blades and a variety of other inanimate objects present in areas of wading and swimming. In addition to trauma by accidental puncture, bites from fish, alligators, crocodiles, sharks, and turtles can transmit AEEVM infections [2-4].
A case series demonstrates the importance of trauma as a predisposing condition for extraintestinal infections caused by AEEVM . Twenty-three (82 percent) of 28 patients seen over a four-year period had preceding acute injuries. Twelve (52 percent) were injured while in a lake or river and subsequently developed musculoskeletal and soft tissue infections due to Aeromonas species.
Water exposure — A variety of types of water exposure can result in infection due to AEEVM. This includes fresh water, salt water, brackish water, water in swimming pools, and aquariums. In a series of 63 cases of M. marinum infection from France, 84 percent were linked to fish tank exposure . Infections due to V. vulnificus are more often limited to salt or brackish water exposure.
The first published outbreak of Aeromonas wound infection was reported in 2004 . The outbreak occurred among participants in mud football in Western Australia with an attack rate estimated to be over 40 percent. It was theorized that the players had skin abrasions and cuts that predisposed to secondary infection due to Aeromonas hydrophila. The organism was recovered from a water sample taken from a river that was used to irrigate the field before play.
E. tarda is an uncommon human pathogen primarily associated with gastrointestinal disease. However, wound infections, including myonecrosis, have occurred when wounds are exposed to a marine environment [8-10].
Gender predominance — Gender predilection is an intriguing feature of both extraintestinal Aeromonas and Vibrio spp infections. A Mayo Clinic series found that 90 percent of cases were in males, a finding that has been noted by others . There is no explanation for the male predominance among patients with Aeromonas infections. Increased exposure of males to outdoor activities does not explain this association .
Gender predominance is also seen with Vibrio spp infections, approximately 75 percent of which occur in males [12,13]. Studies in mice have shown that high serum iron is associated with increased mortality in animals infected with V. vulnificus ; it is therefore possible that lower iron stores in females may make them less likely to develop infection due to this organism.
Underlying diseases — Patients with underlying hepatic disease or cancer have an increased risk of infection caused by AEEVM and may present with life-threatening infections [15-17]. These patients are at particularly high risk of infection due to Aeromonas spp, V. vulnificus, and E. tarda. Disseminated disease from a primary soft tissue focus of infection is common in these immunocompromised patients.
CLINICAL MANIFESTATIONS — AEEVM can produce a variety of skin and soft tissue infections including cellulitis, abscess formation, wound infection, ecthyma gangrenosum, and necrotizing soft tissue processes (eg, fasciitis and myositis) . It is difficult to determine the etiology of an infection based upon clinical features alone, since other organisms, such as beta-hemolytic streptococci and Staphylococcus aureus, can cause similar manifestations.
The clinical presentation and severity of illness can be extremely variable (table 1). This is related, in part, to underlying immunologic or hepatic disorders seen in some patients who are at increased risk of AEEVM infections. (See 'Underlying diseases' above.)
Rapidly progressive soft tissue infection with fever and, in high-risk patients, sepsis may occur with Aeromonas spp and V. vulnificus infection. Consideration should be given to V. vulnificus as an etiologic agent in a patient with an aggressive soft tissue infection with bulla formation (eg, bullous cellulitis) and soft tissue necrosis (picture 1). (See "Vibrio vulnificus infections".)
In contrast, soft tissue infections due to M. marinum and E. rhusiopathiae are generally indolent and are not associated with systemic toxicity.
M. marinum lesions usually appear as papules on an extremity, especially on the elbows, knees, and dorsum of feet and hands, progressing subsequently to shallow ulceration and scar formation. Most lesions are solitary, although occasional "ascending" lesions develop with "sporotrichoid spread" (ie, resembling sporotrichosis), which is also called nodular lymphangitis (picture 2). Clinical involvement of regional nodes is uncommon. (See "Clinical features and diagnosis of sporotrichosis", section on 'Lymphocutaneous sporotrichosis' and "Lymphangitis", section on 'Nodular lymphangitis'.)
In a case series of 31 patients with M. marinum cutaneous disease, the upper extremity was affected in 27 patients (90 percent), and lymphatic or local spread was seen during the initial examination or during observation in 25 patients (81 percent) .
E. rhusiopathiae most commonly causes a localized cutaneous eruption, erysipeloid, on the fingers or hands of fishermen or seafood packers who suffer minor trauma while handling contaminated shrimp, crab, or fish [19,20]. (See "Erysipelothrix infection".)
E. tarda soft tissue infections are unusual and have been associated with a spectrum of manifestations from a simple cellulitis similar to cellulitis due to S. aureus and beta-hemolytic streptococci to fulminant wound infection complicated by bacteremia in patients with underlying liver disease .
DIAGNOSIS — Diagnostic tests to identify the causative agent should always be performed. Gram stain (and acid-fast staining when indicated) and culture should be performed on specimens taken from soft tissue drainage or biopsies. The culture should be incubated at two temperatures: 35ºC and 28 to 32ºC, since M. marinum is restricted to growth at the lower temperatures, especially on primary isolation. Other diagnostic tools, including histopathology, immunohistochemistry (IC), and polymerase chain reaction (PCR) from full-thickness skin biopsy, may be useful to help secure a diagnosis of M. marinum soft tissue infection, although IC and PCR may not be readily available in most clinical laboratories .
Blood cultures should be obtained when systemic toxicity is present or in patients with underlying hepatic disease or cancer.
It is essential to obtain a thorough exposure history from patients who present with soft tissue infections, since microbiologic data may not be available. Questions must be directed at occupational and home exposures and hobbies of the patient. It is important to note even minor or seemingly trivial trauma in the history, which could account for the initiation of infection. Recent travel history must be obtained, since a saltwater-related pathogen may not be considered if the patient lives in a noncoastal community.
Differential diagnosis — Skin and soft tissue findings following water exposure can be due to noninfectious causes in addition to AEEVM infection. Injuries sustained in a freshwater or marine environment may result from bites or venomous stings of aquatic organisms as well as from accidental trauma. As an example, catfish farming has become popular in the Midwest and Southeast regions of the United States, and catfish spine envenomation is a common noninfectious complication that can mimic certain aspects of waterborne infections. Severe pain promptly following the injury is typical, and the skin and soft tissue develops local swelling and erythema . Soft tissue necrosis at the envenomation site can occur as can secondary infection with progression of local findings. (See "Marine envenomations from corals, sea urchins, fish, or stingrays".)
TREATMENT — Management of soft tissue infections following water exposure includes:
●Assessment to determine whether treatment requires hospitalization
●Empiric antibiotic administration
●Assessment of tetanus vaccination status (since tetanus has been reported in this setting )
●Surgical consultation for potential debridement in patients with necrotizing infections
A thorough history will dictate whether empiric therapy to include coverage for AEEVM is indicated. Even with a history of trauma associated with water exposure, we recommend empiric coverage for beta-hemolytic streptococci and S. aureus. The latter two types of bacteria account for the large majority of community-acquired soft tissue infections and can colonize normal skin and produce infections at injury sites. We also administer broad-spectrum coverage to cover multiple organisms, since polymicrobial infection is typical of water-related infections. In the Mayo Clinic series, for example, 65 percent of cultures had more than one pathogen isolated . Polymicrobial infection is not surprising since local trauma precedes infection in many cases and the injury occurs in the outdoor environment.
When to hospitalize — The need to hospitalize patients for treatment of AEEVM infections should be individualized. There are no established guidelines to assist in this decision. Nevertheless, one should more strongly consider hospitalization in patients with underlying hepatic disease, cancer, or immunocompromise. Because of their underlying disease, these patients do not always manifest signs of systemic toxicity related to infection, and they are more likely to develop complications such as sepsis, bacteremia, or death.
Patients with systemic symptoms (eg, fever, chills, rigors) and leukocytosis are another group that should be considered for hospitalization and treatment. This is particularly applicable to older adult and diabetic patients. If ambulatory management is initially selected, then outpatient reevaluation should be performed at 24 to 48 hours. The ambulatory patient should have family members or friends who will be available to monitor the patient and to secure travel to a medical facility if clinical deterioration occurs and for follow-up appointments.
Empiric antibiotic treatment — No randomized controlled studies have evaluated empiric antibiotic regimens for treatment of soft tissue infections following water exposure. Treatment regimens are based on the most likely organisms to cause infection in this setting, in vitro susceptibility studies, and treatment case series with some organisms. We recommend the following antibiotics for initial empiric therapy whether treatment is ambulatory (oral) or inpatient (parenteral):
●Either a first-generation cephalosporin (cephalexin 500 mg orally four times daily or cefazolin 1 g intravenously [IV] every eight hours) OR clindamycin (300 mg orally four times daily or 600 mg IV every eight hours in those patients with immediate hypersensitivity reactions to penicillin) PLUS
●Levofloxacin (750 mg once daily) PLUS either of the following if the epidemiologic risk is present:
•Doxycycline (100 mg twice daily) for coverage of Vibrio species if seawater exposure
Empiric antibiotic coverage should not include coverage for M. marinum infection in most cases, since the presentation is subacute and without associated systemic toxicity. Instead, a specimen (eg, lesion aspirate, biopsy) should be obtained and the microbiology laboratory notified that M. marinum is suspected so that appropriate culture conditions will be included. If acid-fast staining is positive or if the exposure history and physical examination findings suggest M. marinum infection (eg, laceration from an aquarium), then we suggest that specific treatment for M. marinum infection should be initiated.
Directed antibiotic therapy — We recommend initial broad-spectrum empiric therapy be subsequently "tailored" to a more narrow spectrum coverage when specific pathogens are identified in clinical specimens by the microbiology laboratory based upon the isolates susceptibility results.
Aeromonas — Directed antibiotic coverage for Aeromonas spp infection is based on the results of susceptibility testing of the specific isolate. Specific treatment regimens are presented separately. (See "Aeromonas infections".)
Edwardsiella tarda — Antibiotic therapy for E. tarda infection should be based upon in vitro susceptibility testing. Most isolates are susceptible to:
Erysipelothrix rhusiopathiae — Although erysipeloid skin lesions may resolve spontaneously within three weeks, we recommend antibiotic therapy as it shortens the clinical illness and prevents relapse. Treatment of Erysipelothrix is presented separately. (See "Erysipelothrix infection".)
Vibrio vulnificus — Patients with a presumptive diagnosis of V. vulnificus septicemia from a serious wound infection should be started immediately on antibiotic therapy and aggressively managed in an intensive care unit. Specific antibiotic treatment is discussed separately. (See "Vibrio vulnificus infections".)
Mycobacterium marinum — In contrast with treatment for M. tuberculosis, the most appropriate therapeutic regimen for M. marinum has not been defined in clinical trials but is based on in vitro susceptibility testing, clinical experience, and case reports.
A number of different treatment modalities have been used for cutaneous disease caused by M. marinum [24,25]. These include simple observation for minor lesions, surgical excision, the use of antituberculous agents, and the use of single-antibiotic agents [26,27]. By standard susceptibility testing, M. marinum isolates are usually susceptible to rifampin and ethambutol, intermediately susceptible to streptomycin, and resistant to isoniazid and pyrazinamide. Isolates are also susceptible to clarithromycin, sulfonamides, or trimethoprim-sulfamethoxazole and susceptible or intermediately susceptible to doxycycline and minocycline.
A reasonable approach to the management of M. marinum consists of treatment with two active agents for one to two months after resolution of symptoms (total duration is typically three to four months) . Therapy could include clarithromycin (500 mg orally twice daily) together with either ethambutol (15 mg/kg orally once daily) OR rifampin (600 mg orally once daily). For minimal disease, some favor single-drug therapy with one of the following regimens:
●Clarithromycin (500 mg orally twice daily)
In the French series of 63 patients cited above, all patients were treated with antibiotics for a median of 14 weeks (range 1 to 25 months) . Fifty-five of the 63 patients (87 percent) were cured; treatment failure was associated with involvement of deeper structures and not with the antibiotic regimen chosen. Sixty-three percent of patients received a combination regimen, the most common of which was clarithromycin plus rifampin; minocycline or doxycycline were the most frequent drugs employed as monotherapy usually administered for infection confined to the skin and soft tissues.
The rate of clinical response is quite variable, and a minimum of four to six weeks of therapy should be given before considering that the patient may not be responding. Surgical debridement may also be important, especially for disease involving the closed spaces of the hand or disease that responds poorly to drug therapy [25,32]. If a lesion is excised surgically, many clinicians provide antibiotic coverage during the perioperative period. It is not clear if longer durations of antibiotic treatment after surgery offer any additional advantage.
Duration of treatment — There are no clinical trials that have evaluated length of treatment for soft tissue infections due to AEEVM organisms. Except for M. marinum infections, we suggest a duration of antimicrobial therapy for most AEEVM soft tissue infections of 10 to 14 days. Occasional patients will continue to have local signs of infection at the end of two weeks of treatment. We suggest continued oral antibiotic therapy in these patients until resolution of all erythema has occurred. In patients with necrotizing soft tissue infections, treatment duration should be individualized and a longer course of parenteral treatment may be necessary.
For treatment of M. marinum, we recommend continuing treatment for one to two months after resolution of symptoms (total duration is typically three to four months) [28,33].
There are no strict guidelines to indicate when to switch therapy from parenteral to oral agents. We generally switch to oral therapy after the patient is afebrile and the skin findings have begun to resolve; this usually takes three to five days.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Skin and soft tissue infections".)
SUMMARY AND RECOMMENDATIONS
●Soft tissue infections can occur after both freshwater and saltwater exposure, particularly if there is associated trauma. The most common bacteria to produce soft tissue infections in association with exposure to water or water-related animals include AEEVM organisms: Aeromonas species, Edwardsiella tarda, Erysipelothrix rhusiopathiae, Vibrio vulnificus, and Mycobacterium marinum. (See 'Introduction' above.)
●Patients with underlying hepatic disease or cancer have an increased risk of infection caused by AEEVM and may present with life-threatening infections. (See 'Underlying diseases' above.)
●AEEVM can produce a variety of skin and soft tissue infections including cellulitis, abscess formation, wound infection, ecthyma gangrenosum, and necrotizing soft tissue processes (eg, fasciitis and myositis). Rapidly progressive soft tissue infection with fever and, in high-risk patients, sepsis may occur with Aeromonas spp and V. vulnificus infection. In contrast, soft tissue infections due to M. marinum and E. rhusiopathiae are generally indolent and are not associated with systemic toxicity. (See 'Clinical manifestations' above.)
●Diagnostic tests including Gram stain (and acid-fast staining when indicated) and culture should be performed on specimens taken from soft tissue drainage or biopsies. (See 'Diagnosis' above.)
●Besides AEEVM infection, skin and soft tissue findings following water exposure can be due to noninfectious causes, including injuries resulting from bites or venomous stings of aquatic organisms. (See 'Differential diagnosis' above.)
●Management of soft tissue infections following water exposure includes (see 'Treatment' above):
•Assessment to determine whether treatment requires hospitalization
•Empiric antibiotic administration
•Assessment of tetanus vaccination status
•Surgical consultation for potential debridement in patients with necrotizing infections
●We recommend empiric antibiotic coverage for patients who develop a soft tissue infection following water exposure (see 'Water exposure' above) to include coverage for both S. aureus and beta-hemolytic streptococci and the AEEVM organisms, except for M. marinum (Grade 1B). Appropriate antibiotics for initial empiric therapy include (see 'Empiric antibiotic treatment' above):
•Either a first-generation cephalosporin (cephalexin 500 mg orally four times daily or cefazolin 1 g intravenously [IV] every eight hours) OR clindamycin (300 mg orally four times daily or 600 mg IV every eight hours in those patients with immediate hypersensitivity reactions to penicillin) PLUS
•Levofloxacin (750 mg once daily) PLUS either of the following if the epidemiologic risk is present:
•Doxycycline (100 mg twice daily) for coverage of Vibrio species if seawater exposure
●Initial broad-spectrum empiric therapy should be changed to a more narrow spectrum coverage when specific pathogens are identified in clinical specimens by the microbiology laboratory based upon the isolates susceptibility results. (See 'Directed antibiotic therapy' above.)
●In most cases, a duration of antimicrobial therapy for AEEVM soft tissue infections is 10 to 14 days. (See 'Duration of treatment' above.)
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