REVIEW ARTICLE
Skin, Soft Tissue and Systemic Bacterial Infections Following Aquatic Injuries and Exposures James H. Diaz, MD, DrPH and Fred A. Lopez, MD
Abstract: Bacterial infections following aquatic injuries occur commonly in fishermen and vacationers after freshwater and saltwater exposures. Internet search engines were queried with the key words to describe the epidemiology, clinical manifestations, diagnostic and treatment strategies and outcomes of both the superficial and the deeper invasive infections caused by more common, newly emerging and unusual aquatic bacterial pathogens. Main findings included the following: (1) aquatic injuries often result in gram-negative polymicrobial infections with marine bacteria; (2) most marine bacteria are resistant to 1st- and 2nd-generation penicillins and cephalosporins; (3) nontuberculous, mycobacterial infections should be considered in lateonset, culture-negative and antibiotic-resistant marine infections; (4) superficial marine infections and pre-existing wounds exposed to seawater may result in deeply invasive infections and sepsis in immunocompromised patients. With the exception of minor marine wounds demonstrating localized cellulitis, most other marine infections and all gram-negative and mycobacterial marine infections will require therapy with antibiotic combinations. Key Indexing Terms: Aquatic infections; Marine infections; Aquatic bacteria; Marine bacteria; Marine mycobacteria; Fish pathogens; Aquaculture-related fish infections. [Am J Med Sci 2015;349 (3):269–275.]
B
acterial infections following aquatic injuries occur commonly and usually on the extremities in fishermen and vacationers worldwide after freshwater and saltwater exposures. Although many species of bacteria have been isolated from marine wounds, superficial soft tissue and invasive systemic infections following aquatic injuries and exposures may be caused by a small number of bacterial species, including Aeromonas hydrophila, Edwardsiella tarda, Erysipelothrix rhusiopathiae, Mycobacterium marinum and Vibrio vulnificus. In addition to these species, several other aquatic bacteria and mycobacteria have recently been identified as emerging or unusual causes of superficial and invasive infections following marine injuries and exposures, including Chromobacterium violaceum, Shewanella species, Streptococcus iniae and Mycobacterium fortuitum. The objectives of this review were to describe the epidemiology, presenting clinical manifestations, diagnostic and treatment strategies and outcomes of both the superficial and the deeper invasive infections caused by more common, newly emerging and unusual aquatic bacterial pathogens. From the Program in Environmental and Occupational Health Sciences (JHD), School of Public Health, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, Louisiana; and Department of Medicine (FAL), Section of Infectious Diseases, School of Medicine, New Orleans, Louisiana. Submitted March 19, 2014; accepted in revised form August 29, 2014. The authors have no conflicts of interest to disclose. Correspondence: James H. Diaz, MD, Program in Environmental and Occupational Health Sciences, School of Public Health, Louisiana State University Health Sciences Center (LSUHSC), 2020 Gravier Street, Third Floor, New Orleans, LA 70112 (E-mail: [email protected]).
The American Journal of the Medical Sciences
METHODS Internet search engines, including PubMed, Medline, Ovid, Google and Google Scholar, were queried with the key words to meet the objectives of this review article. Because this article reviewed existing scientific publications and did not involve human or animal subjects, institutional review board approval was not required.
RESULTS Epidemiology and Microbiology Descriptive Epidemiology of Aquatic Infections Following the Thai Tsunami The greatest worldwide experiences in managing acute and chronic skin and soft tissue infections (SSTIs) following aquatic injuries and exposures occurred during the ensuing years after a massive tsunami struck southern Thailand on December 26, 2004. Shortly after the disaster, Hiransuthikul et al1 reported acute SSTIs in 515 of 777 (66.3%) patients transferred to 4 referral hospitals in Bangkok with SSTIs following crush injuries to the legs. Wound and/or purulent drainage cultures were obtained in 396 (76.9%) of these patients.1 Most infections were polymicrobial in etiology (71.8%), and the most common organisms isolated were gram-negative bacteria, including Aeromonas species (22.6%), Escherichia coli (18.1%), Klebsiella pneumoniae (14.5%), Pseudomonas aeruginosa (12.0%) and Proteus species (7.3%).1 Only 4.5% of the isolates were gram-positive bacteria, most commonly Staphylococcal species.1 Later, hundreds of vacationing Swedish tsunami survivors were transferred to hospitals in Sweden for further in-patient care.2 Appelgren et al2 reported 15 cases of lateonset, chronic posttraumatic SSTIs caused by rapidly growing marine mycobacteria in Swedish tsunami survivors. These mycobacterial infections occurred 20 to 105 days (median 5 60 days) after the initial trauma in undamaged skin near sutured traumatic wounds or skin grafts.2 All these cases required specific therapy with antimycobacterial medications.2 The course of infection was protracted in all cases with healing by 12 months in most cases.2 The most important lessons learned from the acute and chronic management of SSTIs in these tsunami survivors with contaminated aquatic injuries included the early predominance of gram-negative causative organisms, especially aquatic Aeromonas species, in polymicrobial infections and the possibility of late-onset rapidly growing mycobacterial infections when conventional bacterial cultures remained inconclusive. Microbiology of Skin, Soft Tissue and Systemic Infections Following Aquatic Injuries and Exposures Although Staphylococcus aureus, Streptococcus species, P aeruginosa and several other bacterial species have been recovered from infected minor wounds after marine exposures, some of the more uniquely marine bacterial pathogens recovered following more severe injuries in aquatic environments
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have included Aeromonas species, C violaceum, E tarda, marine Mycobacterium species, Shewanella species and V vulnificus (Table 1). Nevertheless, empiric treatment of SSTIs that develop shortly after marine water exposure should still include coverage of S pyogenes and S aureus in addition to marine water–associated organisms. Such a regimen could include a 1st-generation cephalosporin or clindamycin plus a fluoroquinolone like levofloxacin or ciprofloxacin plus doxycycline (if at increased risk for V vulnificus infection). Pathogen-Specific Clinical Manifestations Aeromonas Species Aeromonas species are gram-negative rods found in warm soil and fresh and brackish waters worldwide as aquatic animal commensals and pathogens.3 Most are capable of producing enterotoxins and hemolysins and causing acute hemorrhagic diarrhea and invasive SSTIs in both immunocompetent and immunocompromised patients following aquatic injuries and exposures, including near-drowning.3 Aeromonas wound infections may occur following freshwater traumatic injuries, such as alligator, fish, snake and leech bites.3 Aeromonasinfected lesions usually occur on extremities or other body regions with open wounds that were immersed in contaminated freshwater during warmer months.3,4 Within 24 hours, infected wounds exhibit erythema, edema and purulent discharge indistinguishable from streptococcal cellulitis.3 Fever and chills will ensue in untreated or improperly treated cases and can progress to invasive infections, especially in the immunocompromised patients, with necrotizing fasciitis, necrotizing myositis and osteomyelitis.3,4 Although most Aeromonas SSTIs occur following aquatic immersions, Vally et al4 were the 1st to report Aeromonas infections following mud exposures in an outbreak of A hydrophila wound infections in 26 mud football players in 2002. None of the players reported any immunocompromising illnesses, and all recovered uneventfully with antibiotic therapy.4 In general, Aeromonas isolates encountered in human infections are susceptible to fluoroquinolones, tetracyclines, aminoglycosides, carbapenems, monobactams and 3rd- and 4th-generation cephalosporins; variable levels of susceptibility have been reported for trimethoprim-sulfamethoxazole.5 In addition to wound drainage and debridement, Aeromonas wound infections should be treated initially with either a fluoroquinolone or a 3rd-generation cephalosporin with the possible addition of an aminoglycoside until culture and antibiotic sensitivity results are reported and rule out Pseudomonas coinfections.5,6 Chromobacterium violaceum Chromobacterium violaceum, an aerobic, gram-negative bacillus, is an ubiquitous saprophyte found in soil and water in tropical and subtropical regions worldwide, including the southeastern United States.7,8 Although widely distributed geographically, C violaceum is a low-grade pathogen that causes few infections in immunocompetent persons and is often dismissed as a bacterial contaminant in positive cultures.7 The organism grows rapidly on ordinary culture media and is typically identified visually by the violet color of its colonies.7,8 Nonpigmented strains of C violaceum are less commonly found than pigmented strains but do co-exist with pigmented strains and can cause mixed SSTIs.8,9 Most cases are reported from temperate and tropical regions with high case fatality rates (CFRs) in the immunocompromised patients.10 In 1982, Macher et al10 reported 12 cases of C violaceum infections in the United States
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in patients with chronic granulomatous disease, 7 of whom died of invasive septicemia 7 days to 15 months after initial infections. The possibility of neutrophil dysfunction should be considered when evaluating patients who present with fulminant infections secondary to this organism. The portal of entry for C violaceum is usually a skin injury from a laceration or fish bite followed by exposure to brackish or stagnant water. An ulcerated skin lesion with a bluish purulent discharge develops at the initial injury site with regional swelling usually on an extremity. Within days, hematogenous dissemination may occur, more commonly in the immunocompromised patients, with high fevers and disseminated macular skin lesions that progress to abscesses. Abscesses may also occur in bone, liver, lung and spleen. Because of the rarity of this infection, treatment recommendations are limited. The organism is generally susceptible to aminoglycosides, fluoroquinolones, tetracyclines, carbapenems, chloramphenicol and trimethoprim-sulfamethoxazole but resistant to most penicillins and cephalosporins.8,9 Because of high CFRs, treatment of suspected C violaceum infections should begin immediately with drainage of all purulent abscess collections and empiric administration of combination intravenous antibiotic therapy, which can be narrowed once susceptibilities become available.9 Treatment length is typically prolonged when abscesses are present. Edwardsiella tarda Edwardsiella tarda, a gram-negative rod of the family Enterobacteriaceae, is a notorious aquaculture pathogen and causative agent of emphysematous putrefactive disease of catfish.11 In 2001, Slaven et al12 described a series of 11 cases in Louisiana with culture-confirmed extraintestinal E tarda infections during the period, 1993 to 1999, with 5 wound infections (3 with marine exposures), 5 abscesses requiring surgical drainage and 1 case of bacteremia. The investigators concluded that extraintestinal E tarda infections were uncommon compared with intestinal infections, frequently presented with wound abscesses requiring surgical incision and drainage in patients with marine injuries or exposures and could cause extensive myonecrosis and fatal septic shock in the immunocompromised patients, especially in patients with chronic liver disease.12 The authors recommended therapy with antibiotics that are effective against gram-negative bacteria (ie, ampicillin, cepahalosporins such as cefazolin and ceftazidime, aminoglycosides, fluoroquinolones) in all cases of extraintestinal E tarda infections.12 Shewanella Species Shewanella species are saprophytic gram-negative bacteria that are distributed in warm and temperate regions worldwide and are part of the normal microflora of the marine environment. There are more than 50 species of Shewanella, all of which produce yellowish brown mucoid colonies that emit hydrogen sulfide in culture. Several Shewanella species have been recently recognized as emerging causes of soft tissue and invasive infections after seawater exposures, including Shewanella algae (most common), Shewanella haliotis, Shewanella putrefaciens and Shewanella xiamenensis.13,14 The most commonly reported clinical manifestations of Shewanella infections are deep ulcers associated with hemorrhagic bullae usually on the lower extremities, otitis externa, otitis media, biliary tract infection and bacteremia.13–15 Non-healing ulcers have resulted in necrotizing fasciitis, compartment syndromes requiring decompressive fasciotomies and osteomyelitis.15 Shewanella sepsis has been associated with endocarditis and meningitis.13 Volume 349, Number 3, March 2015
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TABLE 1. Bacterial causes of skin, soft tissue and systemic infections following aquatic injuries and exposures Bacteriology and Organism epidemiology Clinical manifestations Diagnosis Treatment Aeromonas hydrophila
Gram-negative rod in fresh and brackish water; incidence increases in warm months; may follow alligator, fish, leech and snake bites; associated with near-drowning; incubation: 24–48 hr Chromobacterium Gram-negative rod in wet violaceum tropical soils and brackish to stagnant water; follows minor injuries and fish bites; associated with immunosuppression, especially chronic granulomatous disease; incubation: 24–48 hr Edwardsiella tarda Gram-negative rod in fresh and brackish water; causes disease in catfish; follows catfish spine punctures; associated with immunosuppression, especially hepatic disease; incubation: 24–48 hr Erysipelothrix Nonsporulating gram-positive rhusiopathiae rod and environmentally stable commensal living in exterior slime of fish; often follows minor wounds sustained when filleting fish; incubation: 24–48 hr Mycobacterium fortuitum
Mycobacterium marinum
Cellulitis, pyodermasfuruncles, necrotizing infections
Microbiologic culture
Cellulitis, pustules, ulcers with Microbiologic black necrotic bases and culture bluish purulent discharges
Pyodermas, necrotizing infections—myonecrosis
Microbiologic culture
Erysipelas
Microbiologic culture
Resistant to penicillins and 1st-generation cephalosporins; most sensitive to aminoglycosides, 3rd- and 4th-generation cephalosporins, fluoroquinolones Resistant to ampicillin and most cephalosporins; generally susceptible to aminoglycosides, fluoroquinolones, tetracyclines, carbapenems, trimethoprimsulfamethoxazole Sensitive to most broadspectrum antibiotics with gram-negative coverage, including ampicillin, cephalosporins, such as cefazolin and cefatzidime, aminoglycosides and fluoroquinolones Typically resistant to sulfonamides, aminoglycosides and vancomycin; sensitive to penicillins, carbapenems, cephalosporins, fluoroquinolones, daptomycin and clindamycin Antimicrobial therapy should be guided by susceptibility testing of early isolates in most cases; usually susceptible to ciprofloxacin, clarithromycin, doxycycline or minocycline, sulfonamides and amikacin
Acid-fast, fresh and saltwater, After weeks to months, lower Microbiologic culture, HPLC; rapidly growing extremity erythematous papules progress to molecular PCRmycobacterium; infections fluctuant violaceous based testing; associated with footbath + furuncles (boils) that either antibiotic pedicures and with ulcerate or resolve with susceptibilities ichthyotherapy administered scarring by mycobacteria-colonized doctor fish; incubation: 3– 12 wk Acid-fast saltwater Localized red-violet verrucous Microbiologic acid- Susceptible to clarithromycin, mycobacterium; infections raised patches with fast stains on ethambutol, rifampin and associated with minor lymphadenitis, drainage, trimethoprimlacerations sustained lymphadenopathy and aspirates and sulfamethoxazole (usually 2 cleaning saltwater possibly sporotrichoid biopsies; acid-fact agents in combination) aquariums (fish tank nodular ulcerations along bacterial culture granulomas) or may follow lymphatic drainage routes; crab bites and spine deep infections may occur punctures by sea urchins in untreated cases and in and crustaceans sustained immunocompromised during handling and patients preparation of fresh seafood; incubation: 1 wk to months, mean 21 d (Continued)
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TABLE 1.
(Continued )
Organism
Bacteriology and epidemiology
Clinical manifestations
Diagnosis
Treatment
Shewanella putrefaciens
Gram-negative rod in Cellulitis, pyodermas, deep Microbiologic Resistant to penicillins and saltwater; contaminates ulcers, necrotizing fasciitis culture, PCR 1st- and 2nd- generation shellfish, especially clams; and compartment cephalosporins; sensitive to associated with nearsyndromes aminoglycosides, 3rd- and drowning, ingestion of raw 4th- generation shellfish, exposures of precephalosporins, existing wounds or carbapenems and dermatoses to saltwater, fluoroquinolones especially in the immunocompromised patients; incubation: 4–24 wk Streptococcus iniae Gram-positive beta-hemolytic Impetigo and cellulitis Microbiologic Susceptible to many streptococcus in fresh and culture antibiotics with gram brackish water; commensal positive coverage, including colonization of fish penicillin, cephalosporins, surfaces; associated macrolides and with minor wounds trimethoprimsustained during preparation sulfamethoxazole of fresh fish, especially farm-raised tilapia Vibrio vulnificus Curved gram-negative bacilli Cellulitis, hemorrhagic bullae, Microbiologic Sensitive to 3rd-generation that thrive in warm ulcers, necrotizing culture of wound cephalosporins, such as saltwater, especially in the infections with fasciitis and drainage, ceftazidime, ceftriaxone or Gulf of Mexico; associated compartment syndromes; aspirates, cefotaxime, doxycycline with puncture wounds ecthyma gangrenosum and biopsies; blood and fluoroquinolones sustained in saltwater and septicemia with high case cultures ingestion of raw/ fatality undercooked oysters, especially by males with chronic liver diseases (alcoholic cirrhosis); incubation: 3–7 d PCR, polymerase chain reaction; HPLC, high-pressure liquid chromatography.
Shewanella pneumonia, cholecystitis and peritonitis have been reported following aspiration or ingestion of seawater in near-drowning.13,14 Besides seawater exposure and ingestion of raw seafood, other common risk factors for Shewanella infections have included minor trauma or lacerations in marine environments, pre-existing lower extremity ulcers and immunocompromise.15 The diagnosis of Shewanella infections can be established by positive blood or lesion aspirate cultures, but the speciation of Shewanella causative strains requires molecular characterization by polymerase chain reaction (PCR).13–15 Most species are sensitive to a broad range of antibiotics, including aminoglycosides, 3rd- and 4th-generation cephalosporins, carbapenems and fluoroquinolones. Shewanella algae is resistant to penicillins and 1st- and 2nd-generation cephalosporins.13 For invasive infections, especially in immunosuppressed patients, most authorities recommend initial intravenous antibiotic therapy with a beta-lactam, such as a 3rd- or 4th-generation cephalosporin (such as cefotaxime, ceftazidime or cefepime if the isolate is susceptible) combined with either an aminoglycoside or a fluoroquinolone (such as ciprofloxacin or levofloxacin) followed by susceptibility directed oral antibiotic therapy.13–15 Early surgical consultation is also recommended for drainage of bullous lesions, debridement of ulcers and monitoring for potential extremity compartment syndromes requiring decompressive fasciotomies.
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Vibrio vulnificus Vibrio vulnificus has emerged as a highly virulent bacterial pathogen that can cause 3 types of infections: (1) acute gastroenteritis from eating raw or undercooked shellfish; (2) invasive sepsis following ingestion of raw or undercooked shellfish, especially oysters and (3) necrotizing wound infections following marine injuries and exposures.16,17 Vibrio vulnificus is a halophilic, gram-negative, curved rod-shaped bacterium that prefers temperatures above 18°C and is freeliving in marine environments with low to moderate salinities.16,17 Increasing seasonal temperatures and decreasing coastal salinity levels seem to have favored a greater concentration of Vibrio bacilli by the filter-feeding shellfish of the U.S. Atlantic seaboard and the Gulf of Mexico, especially by oysters (Crassostrea virginica).18–20 Men are uniquely predisposed to V vulnificus infections for several reasons, including occupational and recreational exposures to fish and shellfish, higher serum iron levels, increased rates of alcoholism and chronic liver disease and lower levels of protective estrogens.19,21 Other predisposing, non–genderrelated host risk factors for V vulnificus infections include all hematological conditions that increase serum iron levels (hemochromatosis, thalassemia major); chronic liver disease (cirrhosis, hepatitis, hepatoma) or liver transplant; diabetes mellitus; end-stage renal disease and immune suppression by steroid therapy, cancer chemotherapy, splenectomy or AIDS.19,21 Volume 349, Number 3, March 2015
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Necrotizing skin infections or sepsis following marine injuries, or ingestion of, or exposure to raw seafood or seawater, especially during the warmer spring and summer months, should prompt suspicion of V vulnificus infections.20,22 Gram stains on aspirates from bullous lesions or discharges from necrotic ulcers may demonstrate the characteristic gram-negative curved bacilli.19,22 Blood cultures will also be positive for V vulnificus in 30% of wound infections with secondary sepsis and in 70% to 100% of cases of primary invasive sepsis.19,22 Antibiotic therapy should be instituted immediately because delays in the initiation of antibiotic therapy for 24 hours have been associated with a 33% CFR and delays greater than 72 hours with a 100% CFR.19,22,23 The U.S. Centers for Disease Control and Prevention has recommended a 3rd-generation cephalosporin, specifically ceftazidime, plus doxycycline, as initial empiric antibiotic combinations for suspected V vulnificus infections.24 Other 3rdgeneration cephalosporins that can be used with a tetracyclinelike agent include ceftriaxone or cefotaxime; fluoroquinolones like ciprofloxacin have also proven to be effective.25,26 Early surgical consultation for wound debridement and monitoring for compartment syndromes are also indicated as early surgical management of V vulnificus wounds and has also been demonstrated to decrease high mortality rates.23–25 Skin and Soft Tissue Infections Following Seafood Handling, Preparation and Ichthyotherapy Some SSTIs may follow the unprotected handling and filleting of certain infected fish species, including fish farm– raised species, such as catfish and tilapia. Erysipelothrix rhusiopathiae. Erysipelothrix rhusiopathiae is a gram-positive, nonsporulating rod frequently misidentified microscopically as other nonsporulating rods, such as Lactobacillus species and Listeria monocytogenes.27 Erysipelothrix rhusiopathiae is alpha-hemolytic on blood agar and can be misidentified in culture as S viridians.27 Microbiological differentiation of E rhusiopathiae from other gram-positive bacilli usually requires a positive test for hydrogen sulfide on triple sugar iron agar or DNA detection by PCR.27 In fish, the organism can persist for long periods in the exterior slime without causing cutaneous infections.27 Erysipelothrix rhusiopathiae infections typically manifest 1 to 2 days after skin injuries incurred while handling or preparing colonized fish.27 Most human infections are of 2 cutaneous forms, localized cutaneous (erysipeloid) and generalized cutaneous; both are characterized by painful, throbbing erythematous and intensely pruritic lesions.27 Unlike cutaneous infections, invasive systemic E rhusiopathiae infections are unusual and characterized by bacteremia and possible associated infective endocarditis (IE).28 Erysipelothrix rhusiopathiae IE more commonly involves the aortic valve and has higher CFRs (40%) than other types of IE.28 The organism is sensitive to penicillins, carbapenems, cephalosporins, fluoroquinolones, daptomycin and clindamycin but is typically resistant to vancomycin, sulfonamides and aminoglycosides.29 Because vancomycin is often administered empirically for the treatment of presumed IE, the rapid microbiological differentiation of E rhusiopathiae from other gram-positive organisms is critical.28 Mycobacterium Species. The aquatic, atypical mycobacteria are the acid-fast pathogenic agents of piscine mycobacteriosis and can cause external and solid organ granulomas in more than 150 fish species.30 Aquatic mycobacteria thrive at temperatures of 30 to 33°C in both fresh and saltwater environments and are chlorine and iodine resistant.30 Mycobacterium marinum is the most common cause of external granulomas in fish handlers and Copyright © 2014 by the Southern Society for Clinical Investigation.
aquarium workers.30,31 Mycobacterium marinum infections typically begin as localized areas of red-violet verrucous or crusted plaques at inoculation sites 7 or more days (mean 5 21 days) after puncture wounds or minor lacerations in marine environments on the cooler, distal regions of the extremities.31,32 Solitary or multiple granulomatous nodules will develop later in the inoculation site and may ulcerate with a yellowish purulent discharge.31,32 In some cases, metastatic nodular lesions can develop in a linear or sporotrichoid manner along the proximally draining lymphatic routes, ulcerate and become secondarily infected.32 Deeper, invasive infections, including septic arthritis, bursitis, tenosynovitis and osteoarthritis, may occur in indolent or untreated cases and, less often, in the immunocompromised patients.32 Diagnostic techniques include acid-fast stains and culture of nodule discharges, aspirates or biopsies and PCR identification of mycobacterial nucleic acids in confusing cases.33 Unlike indolent fish tank granulomas caused by M marinum, other more rapidly growing marine mycobacteria, such as Mycobacterium abscessus and M fortuitum, have caused persistent furunculosis following contaminated marine injuries in tsunami survivors.2 Late-onset posttraumatic SSTIs caused by rapidly growing marine mycobacteria were reported in 15 survivors of the tsunami in Thailand in 2004.2 Among these cases, M abscessus was isolated in 7 cases and M fortuitum in 6 cases.2 Mycobacterium perigrinum and Mycobacterium mageritense were each isolated in single cases.2 Most patients were treated with antimycobacterial drugs and other antimicrobials as indicated for early- and late-onset co-infections with Burkholderia pseudomallei and Cladophilophora bantiana.2 Some of the more unusual outbreaks of mycobacterial furunculosis have been caused by rapidly growing M fortuitum isolates following freshwater footbaths and pedicures at U.S. nail salons.34 Winthrop et al34 investigated an outbreak of 110 cases of conventional culture-negative furunculosis among customers of the same northern California nail salon. Cultures from 34 cases were positive for rapidly growing mycobacteria, 32 for M fortuitum.34 Most patients had multiple boils; all patients had undergone footbaths at the salon, and razor-shaving of the lower legs was identified as a highly significant risk factor for mycobacterial infection compared with control patrons who had pedicures without shaving (odds ratio 5 4.8, confidence interval 5 2.1–11.1).34 Cultures from all footbaths at the nail salon yielded M fortuitum, and the acid-fast bacilli isolates from 3 footbaths and 14 patients were identical by pulse-field gel electrophoresis.34 Other unusual outbreaks of mycobacterial furunculosis have been caused by rapidly growing M fortuitum isolates following ichthyotherapy using freshwater doctor fish in the United Kingdom.35 Doctor fish (Garra rufa) are freshwater cyprinoid fish and natural inhabitants of the river basins of central Eurasia that are imported in large numbers to nail and foot spas worldwide for the removal of dead or hyperkeratotic skin on the feet during ichthyotherapy.35 Mycobacterium marinum is typically susceptible to macrolides like clarithromycin, sulfonamides/trimethoprimsulfamethoxazole, ethambutol and rifampin/rifabutin. A typical treatment consists of 2 of these agents in combination (ie, clarithromycin plus ethambutol or clarithromycin plus rifampin) for approximately 3 to 4 months (finishing 4–8 weeks after symptom resolution).33,36 Mycobacterium fortuitum isolates are typically susceptible to quinolones like ciprofloxacin or levofloxacin, newer macrolides like azithromycin/ clarithromycin, sulfonamides, minocycline/doxycycline and
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amikacin.33 Combination therapy for at least 4 months with at least 2 agents to which the organism is susceptible is recommended.33 Similar combination therapy with oral agents can be used to treat nonserious SSTI caused by M abscessus. Serious skin infections caused by M abscessus are typically initially treated with combination of intravenous agent(s) such as amikacin plus cefoxitin with the possible addition of imipenem. Susceptibility testing and consultation with an infectious disease specialist are helpful in managing these patients, particularly with the recognition of acquired fluoroquinolone and macrolide resistance in rapidly growing mycobacteria.33 Streptococcus iniae. Streptococcus iniae, a gram-positive, b-hemolytic streptococcus unassigned to a Lancefield group, was 1st identified in 1976 as the cause of subcutaneous abscesses in Amazon freshwater dolphins in U.S. aquariums and is now recognized as a major fish pathogen capable of causing epizootic outbreaks of invasive streptococcal disease in farm-raised fish.37–39 Streptococcus iniae initially colonizes the surface of the fish causing cellulitis, which can be complicated by invasive meningoencephalitis, with 30% to 50% mortality in affected aquaculture ponds.38 The 1st human cases of S iniae invasive infections were reported from Toronto in 1996 in patients who had recently prepared fresh, whole farm-raised fish.40 Weinstein et al40 identified 11 patients with invasive S iniae infections, with cellulitis of the hands in 8 cases, endocarditis in 1 case and either arthritis or cellulitis in the remaining cases. All the patients had recently handled live or freshly killed fish, and 8 patients suffered percutaneous injuries while preparing the fish and developed cellulitis within 24 hours of their injuries.40 Four patients had chronic underlying diseases, including diabetes, chronic renal failure and rheumatic heart disease.40 In all 11 cases, invasive S iniae infection was culture-confirmed and was matched by pulse-field gel electrophoresis to S iniae isolates obtained from the surfaces of infected tilapia from local aquaculture farms.40 In all cases, the S iniae isolates were sensitive to a broad range of antibiotics, including penicillins, aminoglycosides, cephalosporins, macrolides and trimethoprim-sulfamethoxazole.40
DISCUSSION
demonstrating localized cellulitis or spreading erysipeloid-type reactions, most other marine infections and all gram-negative and mycobacterial marine infections will require therapy with antibiotic combinations. REFERENCES 1. Hiransuthikul N, Tantisiriwat W, Lertutsahakul K, et al. Skin and soft-tissue infections among tsunami survivors in southern Thailand. Clin Infect Dis 2005;41:93–6. 2. Appelgren P, Farnebo F, Dotevall L, et al. Late-onset porttraumatic skin and soft-tissue infections caused by rapid-growing mycobacteria in tsunami survivors. Clin Infect Dis 2008;47:11–6. 3. Lamy B, Kodjo A, Laurent F, et al. Prospective nationwide study of Aeromonas infections in France. J Clin Microbiol 2009;47:1234–7. 4. Vally H, Whittle A, Cameron S, et al. Outbreak of Aeromonas hydrophila wound infections associated with mud football. Clin Infect Dis 2004;38:1084–9. 5. Janda JM, Abbott SL. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev 2010;23:35–73. 6. Chen PL, Ko WC, Wu CJ. Complexity of B-lactamases among clinical Aeromonas isolates and its clinical implications. J Microbiol Immunol Infect 2012;45:398–403. 7. Midani S, Rathore M. Chromobacterium violaceum infection. South Med J 1998;91:464–6. 8. Brown KL, Stein A, Morrell DS. Ecthyma gangrenosum and septic shock syndrome secondary to Chromobacterium violaceum. J Am Acad Dermatol 2006;54:S224–8. 9. Lee J, Kim JS, Nahm CH, et al. Two cases of Chromobacterium violaceum infection after injury in a subtropical region. J Clin Microbiol 1999;37:2068–70. 10. Macher AM, Casale BT, Fauci AS. Chronic granulomatous disease of childhood and Chromobacterium violaceum infections in the South Eastern United States. Ann Intern Med 1982;97:51–2. 11. Meyer FP, Bullock GL. Edwardsiella tarda, a new pathogen of channel catfish (Ictalurus punctatus). Appl Microbiol 1973;25:155–6. 12. Slaven EM, Lopez FA, Hart SM, et al. Myonecrosis caused by Edwardsiella tarda: a case report and case series of extraintestinal E. tarda infections. Clin Infect Dis 2001;32:1430–3.
Control and Prevention of Aquatic Infections All persons with well-established risk factors for increasing severity of marine infections, including those with open wounds, suppressed immune systems, liver disease, hemochromatosis, alcoholism, diabetes mellitus, hematological disease, chronic renal disease, AIDS and cancer, should be cautioned about the risks of marine infections through exposures to marine animals, seawater, the preparation of live or freshly killed seafood and the ingestion of seawater or consumption of raw or undercooked seafood, especially oysters.
16. Oliver JD. Wound infections caused by Vibrio vulnificus and other marine bacteria. Epidemiol Infect 2005;133:383–91.
CONCLUSIONS AND RECOMMENDATIONS
17. Lillis RA, Dugan V, Mills T, et al. A fish hook and liver disease: revisiting an old enemy. J La State Med Soc 2002;154:20–5.
Clinicians should always maintain a high index of suspicion regarding potentially catastrophic bacterial infections following marine injuries and exposures, especially V vulnificus in the Gulf of Mexico, C violaceum in the Western Pacific and Shewanella infections in the Mediterranean and Western Pacific. Initial antibiotic therapy in cases of unknown bacterial etiologies should be based on the initial clinical manifestations of impetigo, erysipelas, cellulitis, pyodermas or necrotizing soft tissue infections. With the exception of minor marine wounds
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13. Vignier N, Barreau M, Olive C, et al. Human infection with Shewanella putrefaciens and S. algae: report of 16 cases in Martinique and review of the literature. Am J Trop Med Hyg 2013;89:151–6. 14. Poovorawan K, Chatsuwan T, Lakananurak N, et al. Shewanella haliotis associated with severe soft tissue infection, Thailand, 2012. Emerg Infect Dis 2013;19:1019–21. 15. Chen YS, Liu YC, Yen MY, et al. Skin and soft-tissue manifestations of Shewanella putrefaciens infection. Clin Infect Dis 1997;25:225–9.
18. Froelich B, Oliver JD. The interactions of Vibrio vulnificus and the oyster Crassotrea virginica. Microb Ecol 2013;65:807–16. 19. 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;15:157–66. 20. Shapiro RL, Altekruse S, Hutwagner L, et al. The role of Gulf Coast oysters harvested in the winter months in Vibrio vulnificus infections in the United States, 1988–1996. J Infect Dis 1998;178:752–9.
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21. Menon MP, Yu PA, Iwamato M, et al. Pre-existing medical conditions associated with Vibrio vulnificus septicaemia. Epidemiol Infect 2013;10:1–4.
31. Piersimoni C, Scarparo C. Extrapulmonary infections associated with nontuberculous mycobacteria in immunocompetent persons. Emerg Infect Dis 2009;15:1351–8.
22. Slaven EM, Lopez FA. Vibrio vulnificus. Infect Dis Clin Pract 2000; 24:77–80.
32. Lahey T. Invasive Mycobacterium marinum infections. Emerg Infect Dis 2003;9:1496–8.
23. Chen SC, Lee YT, Tsai SJ, et al. Antibiotic therapy for necrotizing fasciitis caused by Vibrio vulnificus: retrospective analysis of an 8 year period. J Antimicrob Chemother 2012;67:488–93.
33. Griffith DE, Aksamit T, Brown-Elliott BA, et al; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med 2007;175:367–416.
24. United States Centers for Disease Control and Prevention (CDC). Vibrio vulnificus. 2013. Available at: http://www.cdc.gov/vibrio/vibriov. html. Accessed October 29, 2014. 25. Hsueh P-R, Lin C-Y, Tang H-J, et al. Vibrio vulnificus in Taiwan. Emerg Infect Dis 2004;10:1363–8. 26. Piper KE, Steckelberg JM, Patel R. In vitro activity of daptomycin against clinical isolates of gram-positive bacteria. J Infect Chemother 2005;11:207–9. 27. Romney M, Cheung S, Montessori V. Erysipelothrix rhusiopathiae endocarditis and presumed osteomyelitis. Can J Infect Dis 2001;12: 254–6. 28. Hill DC, Ghassemian JN. Erysipelothrix rhusiopathiae endocarditis: clinical features of an occupational disease. South Med J 1997;90: 1147–8. 29. Venditti M, Gelfusa V, Tarasi A, et al. Antimicrobial susceptibilities of E. rhusiopathiae. Antimicrob Agents Chemother 1990;34:2038–40. 30. Decostere A, Hermans K, Haesebrouck F. Piscine mycobacteriosis: a literature review covering the agent and the disease it causes in fish and humans. Vet Microbiol 2004;99:159–66.
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34. Winthrop KL, Abrams M, Yakrus M, et al. An outbreak of mycobacterial furunculosis associated with a footbath at a nail salon. N Engl J Med 2002;346:1366–71. 35. Verner-Jeffreys DW, Baker-Austin C, Pond MJ, et al. Zoonotic disease pathogens in fish used for pedicure. Emerg Infect Dis 2012; 18:1006–8. 36. Safdar N, Abad CL, Kaul DR, et al. Clinical problem solving. Skin deep. N Engl J Med 2012;366:1336–40. 37. Pier GB, Madin SH. Streptococcus iniae sp. Nov., a beta-hemolytic streptococcus isolated from an Amazon freshwater dolphin, Inia geoffrensis. Int J Syst Bacteriol 1976;26:545–53. 38. Kitao T, Aoki T, Sakoh R. Epizootic caused by b-hemolytic Streptococcus species in cultured freshwater fish. Fish Pathol 1981;15:301–7. 39. Baiano JCF, Barnes AC. Towards control of Streptococcus iniae. Emerg Infect Dis 2009;15:1891–6. 40. Weinstein MR, Litt M, Kertesz DA, et al. Invasive infections due to a fish pathogen, Streptococcus iniae. N Engl J Med 1997;337:589–94.
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Skin, Soft Tissue and Systemic Bacterial Infections Following Aquatic Injuries and Exposures James H. Diaz, MD, DrPH and Fred A. Lopez, MD
Abstract: Bacterial infections following aquatic injuries occur commonly in fishermen and vacationers after freshwater and saltwater exposures. Internet search engines were queried with the key words to describe the epidemiology, clinical manifestations, diagnostic and treatment strategies and outcomes of both the superficial and the deeper invasive infections caused by more common, newly emerging and unusual aquatic bacterial pathogens. Main findings included the following: (1) aquatic injuries often result in gram-negative polymicrobial infections with marine bacteria; (2) most marine bacteria are resistant to 1st- and 2nd-generation penicillins and cephalosporins; (3) nontuberculous, mycobacterial infections should be considered in lateonset, culture-negative and antibiotic-resistant marine infections; (4) superficial marine infections and pre-existing wounds exposed to seawater may result in deeply invasive infections and sepsis in immunocompromised patients. With the exception of minor marine wounds demonstrating localized cellulitis, most other marine infections and all gram-negative and mycobacterial marine infections will require therapy with antibiotic combinations. Key Indexing Terms: Aquatic infections; Marine infections; Aquatic bacteria; Marine bacteria; Marine mycobacteria; Fish pathogens; Aquaculture-related fish infections. [Am J Med Sci 2015;349 (3):269–275.]
B
acterial infections following aquatic injuries occur commonly and usually on the extremities in fishermen and vacationers worldwide after freshwater and saltwater exposures. Although many species of bacteria have been isolated from marine wounds, superficial soft tissue and invasive systemic infections following aquatic injuries and exposures may be caused by a small number of bacterial species, including Aeromonas hydrophila, Edwardsiella tarda, Erysipelothrix rhusiopathiae, Mycobacterium marinum and Vibrio vulnificus. In addition to these species, several other aquatic bacteria and mycobacteria have recently been identified as emerging or unusual causes of superficial and invasive infections following marine injuries and exposures, including Chromobacterium violaceum, Shewanella species, Streptococcus iniae and Mycobacterium fortuitum. The objectives of this review were to describe the epidemiology, presenting clinical manifestations, diagnostic and treatment strategies and outcomes of both the superficial and the deeper invasive infections caused by more common, newly emerging and unusual aquatic bacterial pathogens. From the Program in Environmental and Occupational Health Sciences (JHD), School of Public Health, Louisiana State University Health Sciences Center (LSUHSC), New Orleans, Louisiana; and Department of Medicine (FAL), Section of Infectious Diseases, School of Medicine, New Orleans, Louisiana. Submitted March 19, 2014; accepted in revised form August 29, 2014. The authors have no conflicts of interest to disclose. Correspondence: James H. Diaz, MD, Program in Environmental and Occupational Health Sciences, School of Public Health, Louisiana State University Health Sciences Center (LSUHSC), 2020 Gravier Street, Third Floor, New Orleans, LA 70112 (E-mail: [email protected]).
The American Journal of the Medical Sciences
METHODS Internet search engines, including PubMed, Medline, Ovid, Google and Google Scholar, were queried with the key words to meet the objectives of this review article. Because this article reviewed existing scientific publications and did not involve human or animal subjects, institutional review board approval was not required.
RESULTS Epidemiology and Microbiology Descriptive Epidemiology of Aquatic Infections Following the Thai Tsunami The greatest worldwide experiences in managing acute and chronic skin and soft tissue infections (SSTIs) following aquatic injuries and exposures occurred during the ensuing years after a massive tsunami struck southern Thailand on December 26, 2004. Shortly after the disaster, Hiransuthikul et al1 reported acute SSTIs in 515 of 777 (66.3%) patients transferred to 4 referral hospitals in Bangkok with SSTIs following crush injuries to the legs. Wound and/or purulent drainage cultures were obtained in 396 (76.9%) of these patients.1 Most infections were polymicrobial in etiology (71.8%), and the most common organisms isolated were gram-negative bacteria, including Aeromonas species (22.6%), Escherichia coli (18.1%), Klebsiella pneumoniae (14.5%), Pseudomonas aeruginosa (12.0%) and Proteus species (7.3%).1 Only 4.5% of the isolates were gram-positive bacteria, most commonly Staphylococcal species.1 Later, hundreds of vacationing Swedish tsunami survivors were transferred to hospitals in Sweden for further in-patient care.2 Appelgren et al2 reported 15 cases of lateonset, chronic posttraumatic SSTIs caused by rapidly growing marine mycobacteria in Swedish tsunami survivors. These mycobacterial infections occurred 20 to 105 days (median 5 60 days) after the initial trauma in undamaged skin near sutured traumatic wounds or skin grafts.2 All these cases required specific therapy with antimycobacterial medications.2 The course of infection was protracted in all cases with healing by 12 months in most cases.2 The most important lessons learned from the acute and chronic management of SSTIs in these tsunami survivors with contaminated aquatic injuries included the early predominance of gram-negative causative organisms, especially aquatic Aeromonas species, in polymicrobial infections and the possibility of late-onset rapidly growing mycobacterial infections when conventional bacterial cultures remained inconclusive. Microbiology of Skin, Soft Tissue and Systemic Infections Following Aquatic Injuries and Exposures Although Staphylococcus aureus, Streptococcus species, P aeruginosa and several other bacterial species have been recovered from infected minor wounds after marine exposures, some of the more uniquely marine bacterial pathogens recovered following more severe injuries in aquatic environments
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have included Aeromonas species, C violaceum, E tarda, marine Mycobacterium species, Shewanella species and V vulnificus (Table 1). Nevertheless, empiric treatment of SSTIs that develop shortly after marine water exposure should still include coverage of S pyogenes and S aureus in addition to marine water–associated organisms. Such a regimen could include a 1st-generation cephalosporin or clindamycin plus a fluoroquinolone like levofloxacin or ciprofloxacin plus doxycycline (if at increased risk for V vulnificus infection). Pathogen-Specific Clinical Manifestations Aeromonas Species Aeromonas species are gram-negative rods found in warm soil and fresh and brackish waters worldwide as aquatic animal commensals and pathogens.3 Most are capable of producing enterotoxins and hemolysins and causing acute hemorrhagic diarrhea and invasive SSTIs in both immunocompetent and immunocompromised patients following aquatic injuries and exposures, including near-drowning.3 Aeromonas wound infections may occur following freshwater traumatic injuries, such as alligator, fish, snake and leech bites.3 Aeromonasinfected lesions usually occur on extremities or other body regions with open wounds that were immersed in contaminated freshwater during warmer months.3,4 Within 24 hours, infected wounds exhibit erythema, edema and purulent discharge indistinguishable from streptococcal cellulitis.3 Fever and chills will ensue in untreated or improperly treated cases and can progress to invasive infections, especially in the immunocompromised patients, with necrotizing fasciitis, necrotizing myositis and osteomyelitis.3,4 Although most Aeromonas SSTIs occur following aquatic immersions, Vally et al4 were the 1st to report Aeromonas infections following mud exposures in an outbreak of A hydrophila wound infections in 26 mud football players in 2002. None of the players reported any immunocompromising illnesses, and all recovered uneventfully with antibiotic therapy.4 In general, Aeromonas isolates encountered in human infections are susceptible to fluoroquinolones, tetracyclines, aminoglycosides, carbapenems, monobactams and 3rd- and 4th-generation cephalosporins; variable levels of susceptibility have been reported for trimethoprim-sulfamethoxazole.5 In addition to wound drainage and debridement, Aeromonas wound infections should be treated initially with either a fluoroquinolone or a 3rd-generation cephalosporin with the possible addition of an aminoglycoside until culture and antibiotic sensitivity results are reported and rule out Pseudomonas coinfections.5,6 Chromobacterium violaceum Chromobacterium violaceum, an aerobic, gram-negative bacillus, is an ubiquitous saprophyte found in soil and water in tropical and subtropical regions worldwide, including the southeastern United States.7,8 Although widely distributed geographically, C violaceum is a low-grade pathogen that causes few infections in immunocompetent persons and is often dismissed as a bacterial contaminant in positive cultures.7 The organism grows rapidly on ordinary culture media and is typically identified visually by the violet color of its colonies.7,8 Nonpigmented strains of C violaceum are less commonly found than pigmented strains but do co-exist with pigmented strains and can cause mixed SSTIs.8,9 Most cases are reported from temperate and tropical regions with high case fatality rates (CFRs) in the immunocompromised patients.10 In 1982, Macher et al10 reported 12 cases of C violaceum infections in the United States
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in patients with chronic granulomatous disease, 7 of whom died of invasive septicemia 7 days to 15 months after initial infections. The possibility of neutrophil dysfunction should be considered when evaluating patients who present with fulminant infections secondary to this organism. The portal of entry for C violaceum is usually a skin injury from a laceration or fish bite followed by exposure to brackish or stagnant water. An ulcerated skin lesion with a bluish purulent discharge develops at the initial injury site with regional swelling usually on an extremity. Within days, hematogenous dissemination may occur, more commonly in the immunocompromised patients, with high fevers and disseminated macular skin lesions that progress to abscesses. Abscesses may also occur in bone, liver, lung and spleen. Because of the rarity of this infection, treatment recommendations are limited. The organism is generally susceptible to aminoglycosides, fluoroquinolones, tetracyclines, carbapenems, chloramphenicol and trimethoprim-sulfamethoxazole but resistant to most penicillins and cephalosporins.8,9 Because of high CFRs, treatment of suspected C violaceum infections should begin immediately with drainage of all purulent abscess collections and empiric administration of combination intravenous antibiotic therapy, which can be narrowed once susceptibilities become available.9 Treatment length is typically prolonged when abscesses are present. Edwardsiella tarda Edwardsiella tarda, a gram-negative rod of the family Enterobacteriaceae, is a notorious aquaculture pathogen and causative agent of emphysematous putrefactive disease of catfish.11 In 2001, Slaven et al12 described a series of 11 cases in Louisiana with culture-confirmed extraintestinal E tarda infections during the period, 1993 to 1999, with 5 wound infections (3 with marine exposures), 5 abscesses requiring surgical drainage and 1 case of bacteremia. The investigators concluded that extraintestinal E tarda infections were uncommon compared with intestinal infections, frequently presented with wound abscesses requiring surgical incision and drainage in patients with marine injuries or exposures and could cause extensive myonecrosis and fatal septic shock in the immunocompromised patients, especially in patients with chronic liver disease.12 The authors recommended therapy with antibiotics that are effective against gram-negative bacteria (ie, ampicillin, cepahalosporins such as cefazolin and ceftazidime, aminoglycosides, fluoroquinolones) in all cases of extraintestinal E tarda infections.12 Shewanella Species Shewanella species are saprophytic gram-negative bacteria that are distributed in warm and temperate regions worldwide and are part of the normal microflora of the marine environment. There are more than 50 species of Shewanella, all of which produce yellowish brown mucoid colonies that emit hydrogen sulfide in culture. Several Shewanella species have been recently recognized as emerging causes of soft tissue and invasive infections after seawater exposures, including Shewanella algae (most common), Shewanella haliotis, Shewanella putrefaciens and Shewanella xiamenensis.13,14 The most commonly reported clinical manifestations of Shewanella infections are deep ulcers associated with hemorrhagic bullae usually on the lower extremities, otitis externa, otitis media, biliary tract infection and bacteremia.13–15 Non-healing ulcers have resulted in necrotizing fasciitis, compartment syndromes requiring decompressive fasciotomies and osteomyelitis.15 Shewanella sepsis has been associated with endocarditis and meningitis.13 Volume 349, Number 3, March 2015
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TABLE 1. Bacterial causes of skin, soft tissue and systemic infections following aquatic injuries and exposures Bacteriology and Organism epidemiology Clinical manifestations Diagnosis Treatment Aeromonas hydrophila
Gram-negative rod in fresh and brackish water; incidence increases in warm months; may follow alligator, fish, leech and snake bites; associated with near-drowning; incubation: 24–48 hr Chromobacterium Gram-negative rod in wet violaceum tropical soils and brackish to stagnant water; follows minor injuries and fish bites; associated with immunosuppression, especially chronic granulomatous disease; incubation: 24–48 hr Edwardsiella tarda Gram-negative rod in fresh and brackish water; causes disease in catfish; follows catfish spine punctures; associated with immunosuppression, especially hepatic disease; incubation: 24–48 hr Erysipelothrix Nonsporulating gram-positive rhusiopathiae rod and environmentally stable commensal living in exterior slime of fish; often follows minor wounds sustained when filleting fish; incubation: 24–48 hr Mycobacterium fortuitum
Mycobacterium marinum
Cellulitis, pyodermasfuruncles, necrotizing infections
Microbiologic culture
Cellulitis, pustules, ulcers with Microbiologic black necrotic bases and culture bluish purulent discharges
Pyodermas, necrotizing infections—myonecrosis
Microbiologic culture
Erysipelas
Microbiologic culture
Resistant to penicillins and 1st-generation cephalosporins; most sensitive to aminoglycosides, 3rd- and 4th-generation cephalosporins, fluoroquinolones Resistant to ampicillin and most cephalosporins; generally susceptible to aminoglycosides, fluoroquinolones, tetracyclines, carbapenems, trimethoprimsulfamethoxazole Sensitive to most broadspectrum antibiotics with gram-negative coverage, including ampicillin, cephalosporins, such as cefazolin and cefatzidime, aminoglycosides and fluoroquinolones Typically resistant to sulfonamides, aminoglycosides and vancomycin; sensitive to penicillins, carbapenems, cephalosporins, fluoroquinolones, daptomycin and clindamycin Antimicrobial therapy should be guided by susceptibility testing of early isolates in most cases; usually susceptible to ciprofloxacin, clarithromycin, doxycycline or minocycline, sulfonamides and amikacin
Acid-fast, fresh and saltwater, After weeks to months, lower Microbiologic culture, HPLC; rapidly growing extremity erythematous papules progress to molecular PCRmycobacterium; infections fluctuant violaceous based testing; associated with footbath + furuncles (boils) that either antibiotic pedicures and with ulcerate or resolve with susceptibilities ichthyotherapy administered scarring by mycobacteria-colonized doctor fish; incubation: 3– 12 wk Acid-fast saltwater Localized red-violet verrucous Microbiologic acid- Susceptible to clarithromycin, mycobacterium; infections raised patches with fast stains on ethambutol, rifampin and associated with minor lymphadenitis, drainage, trimethoprimlacerations sustained lymphadenopathy and aspirates and sulfamethoxazole (usually 2 cleaning saltwater possibly sporotrichoid biopsies; acid-fact agents in combination) aquariums (fish tank nodular ulcerations along bacterial culture granulomas) or may follow lymphatic drainage routes; crab bites and spine deep infections may occur punctures by sea urchins in untreated cases and in and crustaceans sustained immunocompromised during handling and patients preparation of fresh seafood; incubation: 1 wk to months, mean 21 d (Continued)
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TABLE 1.
(Continued )
Organism
Bacteriology and epidemiology
Clinical manifestations
Diagnosis
Treatment
Shewanella putrefaciens
Gram-negative rod in Cellulitis, pyodermas, deep Microbiologic Resistant to penicillins and saltwater; contaminates ulcers, necrotizing fasciitis culture, PCR 1st- and 2nd- generation shellfish, especially clams; and compartment cephalosporins; sensitive to associated with nearsyndromes aminoglycosides, 3rd- and drowning, ingestion of raw 4th- generation shellfish, exposures of precephalosporins, existing wounds or carbapenems and dermatoses to saltwater, fluoroquinolones especially in the immunocompromised patients; incubation: 4–24 wk Streptococcus iniae Gram-positive beta-hemolytic Impetigo and cellulitis Microbiologic Susceptible to many streptococcus in fresh and culture antibiotics with gram brackish water; commensal positive coverage, including colonization of fish penicillin, cephalosporins, surfaces; associated macrolides and with minor wounds trimethoprimsustained during preparation sulfamethoxazole of fresh fish, especially farm-raised tilapia Vibrio vulnificus Curved gram-negative bacilli Cellulitis, hemorrhagic bullae, Microbiologic Sensitive to 3rd-generation that thrive in warm ulcers, necrotizing culture of wound cephalosporins, such as saltwater, especially in the infections with fasciitis and drainage, ceftazidime, ceftriaxone or Gulf of Mexico; associated compartment syndromes; aspirates, cefotaxime, doxycycline with puncture wounds ecthyma gangrenosum and biopsies; blood and fluoroquinolones sustained in saltwater and septicemia with high case cultures ingestion of raw/ fatality undercooked oysters, especially by males with chronic liver diseases (alcoholic cirrhosis); incubation: 3–7 d PCR, polymerase chain reaction; HPLC, high-pressure liquid chromatography.
Shewanella pneumonia, cholecystitis and peritonitis have been reported following aspiration or ingestion of seawater in near-drowning.13,14 Besides seawater exposure and ingestion of raw seafood, other common risk factors for Shewanella infections have included minor trauma or lacerations in marine environments, pre-existing lower extremity ulcers and immunocompromise.15 The diagnosis of Shewanella infections can be established by positive blood or lesion aspirate cultures, but the speciation of Shewanella causative strains requires molecular characterization by polymerase chain reaction (PCR).13–15 Most species are sensitive to a broad range of antibiotics, including aminoglycosides, 3rd- and 4th-generation cephalosporins, carbapenems and fluoroquinolones. Shewanella algae is resistant to penicillins and 1st- and 2nd-generation cephalosporins.13 For invasive infections, especially in immunosuppressed patients, most authorities recommend initial intravenous antibiotic therapy with a beta-lactam, such as a 3rd- or 4th-generation cephalosporin (such as cefotaxime, ceftazidime or cefepime if the isolate is susceptible) combined with either an aminoglycoside or a fluoroquinolone (such as ciprofloxacin or levofloxacin) followed by susceptibility directed oral antibiotic therapy.13–15 Early surgical consultation is also recommended for drainage of bullous lesions, debridement of ulcers and monitoring for potential extremity compartment syndromes requiring decompressive fasciotomies.
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Vibrio vulnificus Vibrio vulnificus has emerged as a highly virulent bacterial pathogen that can cause 3 types of infections: (1) acute gastroenteritis from eating raw or undercooked shellfish; (2) invasive sepsis following ingestion of raw or undercooked shellfish, especially oysters and (3) necrotizing wound infections following marine injuries and exposures.16,17 Vibrio vulnificus is a halophilic, gram-negative, curved rod-shaped bacterium that prefers temperatures above 18°C and is freeliving in marine environments with low to moderate salinities.16,17 Increasing seasonal temperatures and decreasing coastal salinity levels seem to have favored a greater concentration of Vibrio bacilli by the filter-feeding shellfish of the U.S. Atlantic seaboard and the Gulf of Mexico, especially by oysters (Crassostrea virginica).18–20 Men are uniquely predisposed to V vulnificus infections for several reasons, including occupational and recreational exposures to fish and shellfish, higher serum iron levels, increased rates of alcoholism and chronic liver disease and lower levels of protective estrogens.19,21 Other predisposing, non–genderrelated host risk factors for V vulnificus infections include all hematological conditions that increase serum iron levels (hemochromatosis, thalassemia major); chronic liver disease (cirrhosis, hepatitis, hepatoma) or liver transplant; diabetes mellitus; end-stage renal disease and immune suppression by steroid therapy, cancer chemotherapy, splenectomy or AIDS.19,21 Volume 349, Number 3, March 2015
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Necrotizing skin infections or sepsis following marine injuries, or ingestion of, or exposure to raw seafood or seawater, especially during the warmer spring and summer months, should prompt suspicion of V vulnificus infections.20,22 Gram stains on aspirates from bullous lesions or discharges from necrotic ulcers may demonstrate the characteristic gram-negative curved bacilli.19,22 Blood cultures will also be positive for V vulnificus in 30% of wound infections with secondary sepsis and in 70% to 100% of cases of primary invasive sepsis.19,22 Antibiotic therapy should be instituted immediately because delays in the initiation of antibiotic therapy for 24 hours have been associated with a 33% CFR and delays greater than 72 hours with a 100% CFR.19,22,23 The U.S. Centers for Disease Control and Prevention has recommended a 3rd-generation cephalosporin, specifically ceftazidime, plus doxycycline, as initial empiric antibiotic combinations for suspected V vulnificus infections.24 Other 3rdgeneration cephalosporins that can be used with a tetracyclinelike agent include ceftriaxone or cefotaxime; fluoroquinolones like ciprofloxacin have also proven to be effective.25,26 Early surgical consultation for wound debridement and monitoring for compartment syndromes are also indicated as early surgical management of V vulnificus wounds and has also been demonstrated to decrease high mortality rates.23–25 Skin and Soft Tissue Infections Following Seafood Handling, Preparation and Ichthyotherapy Some SSTIs may follow the unprotected handling and filleting of certain infected fish species, including fish farm– raised species, such as catfish and tilapia. Erysipelothrix rhusiopathiae. Erysipelothrix rhusiopathiae is a gram-positive, nonsporulating rod frequently misidentified microscopically as other nonsporulating rods, such as Lactobacillus species and Listeria monocytogenes.27 Erysipelothrix rhusiopathiae is alpha-hemolytic on blood agar and can be misidentified in culture as S viridians.27 Microbiological differentiation of E rhusiopathiae from other gram-positive bacilli usually requires a positive test for hydrogen sulfide on triple sugar iron agar or DNA detection by PCR.27 In fish, the organism can persist for long periods in the exterior slime without causing cutaneous infections.27 Erysipelothrix rhusiopathiae infections typically manifest 1 to 2 days after skin injuries incurred while handling or preparing colonized fish.27 Most human infections are of 2 cutaneous forms, localized cutaneous (erysipeloid) and generalized cutaneous; both are characterized by painful, throbbing erythematous and intensely pruritic lesions.27 Unlike cutaneous infections, invasive systemic E rhusiopathiae infections are unusual and characterized by bacteremia and possible associated infective endocarditis (IE).28 Erysipelothrix rhusiopathiae IE more commonly involves the aortic valve and has higher CFRs (40%) than other types of IE.28 The organism is sensitive to penicillins, carbapenems, cephalosporins, fluoroquinolones, daptomycin and clindamycin but is typically resistant to vancomycin, sulfonamides and aminoglycosides.29 Because vancomycin is often administered empirically for the treatment of presumed IE, the rapid microbiological differentiation of E rhusiopathiae from other gram-positive organisms is critical.28 Mycobacterium Species. The aquatic, atypical mycobacteria are the acid-fast pathogenic agents of piscine mycobacteriosis and can cause external and solid organ granulomas in more than 150 fish species.30 Aquatic mycobacteria thrive at temperatures of 30 to 33°C in both fresh and saltwater environments and are chlorine and iodine resistant.30 Mycobacterium marinum is the most common cause of external granulomas in fish handlers and Copyright © 2014 by the Southern Society for Clinical Investigation.
aquarium workers.30,31 Mycobacterium marinum infections typically begin as localized areas of red-violet verrucous or crusted plaques at inoculation sites 7 or more days (mean 5 21 days) after puncture wounds or minor lacerations in marine environments on the cooler, distal regions of the extremities.31,32 Solitary or multiple granulomatous nodules will develop later in the inoculation site and may ulcerate with a yellowish purulent discharge.31,32 In some cases, metastatic nodular lesions can develop in a linear or sporotrichoid manner along the proximally draining lymphatic routes, ulcerate and become secondarily infected.32 Deeper, invasive infections, including septic arthritis, bursitis, tenosynovitis and osteoarthritis, may occur in indolent or untreated cases and, less often, in the immunocompromised patients.32 Diagnostic techniques include acid-fast stains and culture of nodule discharges, aspirates or biopsies and PCR identification of mycobacterial nucleic acids in confusing cases.33 Unlike indolent fish tank granulomas caused by M marinum, other more rapidly growing marine mycobacteria, such as Mycobacterium abscessus and M fortuitum, have caused persistent furunculosis following contaminated marine injuries in tsunami survivors.2 Late-onset posttraumatic SSTIs caused by rapidly growing marine mycobacteria were reported in 15 survivors of the tsunami in Thailand in 2004.2 Among these cases, M abscessus was isolated in 7 cases and M fortuitum in 6 cases.2 Mycobacterium perigrinum and Mycobacterium mageritense were each isolated in single cases.2 Most patients were treated with antimycobacterial drugs and other antimicrobials as indicated for early- and late-onset co-infections with Burkholderia pseudomallei and Cladophilophora bantiana.2 Some of the more unusual outbreaks of mycobacterial furunculosis have been caused by rapidly growing M fortuitum isolates following freshwater footbaths and pedicures at U.S. nail salons.34 Winthrop et al34 investigated an outbreak of 110 cases of conventional culture-negative furunculosis among customers of the same northern California nail salon. Cultures from 34 cases were positive for rapidly growing mycobacteria, 32 for M fortuitum.34 Most patients had multiple boils; all patients had undergone footbaths at the salon, and razor-shaving of the lower legs was identified as a highly significant risk factor for mycobacterial infection compared with control patrons who had pedicures without shaving (odds ratio 5 4.8, confidence interval 5 2.1–11.1).34 Cultures from all footbaths at the nail salon yielded M fortuitum, and the acid-fast bacilli isolates from 3 footbaths and 14 patients were identical by pulse-field gel electrophoresis.34 Other unusual outbreaks of mycobacterial furunculosis have been caused by rapidly growing M fortuitum isolates following ichthyotherapy using freshwater doctor fish in the United Kingdom.35 Doctor fish (Garra rufa) are freshwater cyprinoid fish and natural inhabitants of the river basins of central Eurasia that are imported in large numbers to nail and foot spas worldwide for the removal of dead or hyperkeratotic skin on the feet during ichthyotherapy.35 Mycobacterium marinum is typically susceptible to macrolides like clarithromycin, sulfonamides/trimethoprimsulfamethoxazole, ethambutol and rifampin/rifabutin. A typical treatment consists of 2 of these agents in combination (ie, clarithromycin plus ethambutol or clarithromycin plus rifampin) for approximately 3 to 4 months (finishing 4–8 weeks after symptom resolution).33,36 Mycobacterium fortuitum isolates are typically susceptible to quinolones like ciprofloxacin or levofloxacin, newer macrolides like azithromycin/ clarithromycin, sulfonamides, minocycline/doxycycline and
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amikacin.33 Combination therapy for at least 4 months with at least 2 agents to which the organism is susceptible is recommended.33 Similar combination therapy with oral agents can be used to treat nonserious SSTI caused by M abscessus. Serious skin infections caused by M abscessus are typically initially treated with combination of intravenous agent(s) such as amikacin plus cefoxitin with the possible addition of imipenem. Susceptibility testing and consultation with an infectious disease specialist are helpful in managing these patients, particularly with the recognition of acquired fluoroquinolone and macrolide resistance in rapidly growing mycobacteria.33 Streptococcus iniae. Streptococcus iniae, a gram-positive, b-hemolytic streptococcus unassigned to a Lancefield group, was 1st identified in 1976 as the cause of subcutaneous abscesses in Amazon freshwater dolphins in U.S. aquariums and is now recognized as a major fish pathogen capable of causing epizootic outbreaks of invasive streptococcal disease in farm-raised fish.37–39 Streptococcus iniae initially colonizes the surface of the fish causing cellulitis, which can be complicated by invasive meningoencephalitis, with 30% to 50% mortality in affected aquaculture ponds.38 The 1st human cases of S iniae invasive infections were reported from Toronto in 1996 in patients who had recently prepared fresh, whole farm-raised fish.40 Weinstein et al40 identified 11 patients with invasive S iniae infections, with cellulitis of the hands in 8 cases, endocarditis in 1 case and either arthritis or cellulitis in the remaining cases. All the patients had recently handled live or freshly killed fish, and 8 patients suffered percutaneous injuries while preparing the fish and developed cellulitis within 24 hours of their injuries.40 Four patients had chronic underlying diseases, including diabetes, chronic renal failure and rheumatic heart disease.40 In all 11 cases, invasive S iniae infection was culture-confirmed and was matched by pulse-field gel electrophoresis to S iniae isolates obtained from the surfaces of infected tilapia from local aquaculture farms.40 In all cases, the S iniae isolates were sensitive to a broad range of antibiotics, including penicillins, aminoglycosides, cephalosporins, macrolides and trimethoprim-sulfamethoxazole.40
DISCUSSION
demonstrating localized cellulitis or spreading erysipeloid-type reactions, most other marine infections and all gram-negative and mycobacterial marine infections will require therapy with antibiotic combinations. REFERENCES 1. Hiransuthikul N, Tantisiriwat W, Lertutsahakul K, et al. Skin and soft-tissue infections among tsunami survivors in southern Thailand. Clin Infect Dis 2005;41:93–6. 2. Appelgren P, Farnebo F, Dotevall L, et al. Late-onset porttraumatic skin and soft-tissue infections caused by rapid-growing mycobacteria in tsunami survivors. Clin Infect Dis 2008;47:11–6. 3. Lamy B, Kodjo A, Laurent F, et al. Prospective nationwide study of Aeromonas infections in France. J Clin Microbiol 2009;47:1234–7. 4. Vally H, Whittle A, Cameron S, et al. Outbreak of Aeromonas hydrophila wound infections associated with mud football. Clin Infect Dis 2004;38:1084–9. 5. Janda JM, Abbott SL. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev 2010;23:35–73. 6. Chen PL, Ko WC, Wu CJ. Complexity of B-lactamases among clinical Aeromonas isolates and its clinical implications. J Microbiol Immunol Infect 2012;45:398–403. 7. Midani S, Rathore M. Chromobacterium violaceum infection. South Med J 1998;91:464–6. 8. Brown KL, Stein A, Morrell DS. Ecthyma gangrenosum and septic shock syndrome secondary to Chromobacterium violaceum. J Am Acad Dermatol 2006;54:S224–8. 9. Lee J, Kim JS, Nahm CH, et al. Two cases of Chromobacterium violaceum infection after injury in a subtropical region. J Clin Microbiol 1999;37:2068–70. 10. Macher AM, Casale BT, Fauci AS. Chronic granulomatous disease of childhood and Chromobacterium violaceum infections in the South Eastern United States. Ann Intern Med 1982;97:51–2. 11. Meyer FP, Bullock GL. Edwardsiella tarda, a new pathogen of channel catfish (Ictalurus punctatus). Appl Microbiol 1973;25:155–6. 12. Slaven EM, Lopez FA, Hart SM, et al. Myonecrosis caused by Edwardsiella tarda: a case report and case series of extraintestinal E. tarda infections. Clin Infect Dis 2001;32:1430–3.
Control and Prevention of Aquatic Infections All persons with well-established risk factors for increasing severity of marine infections, including those with open wounds, suppressed immune systems, liver disease, hemochromatosis, alcoholism, diabetes mellitus, hematological disease, chronic renal disease, AIDS and cancer, should be cautioned about the risks of marine infections through exposures to marine animals, seawater, the preparation of live or freshly killed seafood and the ingestion of seawater or consumption of raw or undercooked seafood, especially oysters.
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CONCLUSIONS AND RECOMMENDATIONS
17. Lillis RA, Dugan V, Mills T, et al. A fish hook and liver disease: revisiting an old enemy. J La State Med Soc 2002;154:20–5.
Clinicians should always maintain a high index of suspicion regarding potentially catastrophic bacterial infections following marine injuries and exposures, especially V vulnificus in the Gulf of Mexico, C violaceum in the Western Pacific and Shewanella infections in the Mediterranean and Western Pacific. Initial antibiotic therapy in cases of unknown bacterial etiologies should be based on the initial clinical manifestations of impetigo, erysipelas, cellulitis, pyodermas or necrotizing soft tissue infections. With the exception of minor marine wounds
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21. Menon MP, Yu PA, Iwamato M, et al. Pre-existing medical conditions associated with Vibrio vulnificus septicaemia. Epidemiol Infect 2013;10:1–4.
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32. Lahey T. Invasive Mycobacterium marinum infections. Emerg Infect Dis 2003;9:1496–8.
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24. United States Centers for Disease Control and Prevention (CDC). Vibrio vulnificus. 2013. Available at: http://www.cdc.gov/vibrio/vibriov. html. Accessed October 29, 2014. 25. Hsueh P-R, Lin C-Y, Tang H-J, et al. Vibrio vulnificus in Taiwan. Emerg Infect Dis 2004;10:1363–8. 26. Piper KE, Steckelberg JM, Patel R. In vitro activity of daptomycin against clinical isolates of gram-positive bacteria. J Infect Chemother 2005;11:207–9. 27. Romney M, Cheung S, Montessori V. Erysipelothrix rhusiopathiae endocarditis and presumed osteomyelitis. Can J Infect Dis 2001;12: 254–6. 28. Hill DC, Ghassemian JN. Erysipelothrix rhusiopathiae endocarditis: clinical features of an occupational disease. South Med J 1997;90: 1147–8. 29. Venditti M, Gelfusa V, Tarasi A, et al. Antimicrobial susceptibilities of E. rhusiopathiae. Antimicrob Agents Chemother 1990;34:2038–40. 30. Decostere A, Hermans K, Haesebrouck F. Piscine mycobacteriosis: a literature review covering the agent and the disease it causes in fish and humans. Vet Microbiol 2004;99:159–66.
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