Cellulitis After Water Exposure – Fishy Microbiology

Skin and soft tissue infections are fairly common infectious presentations almost all physicians have experience with. In general, gram positive organisms tend to predominate in community-acquired cellulitis, usually skin organisms, which manage to get access to the soft tissues through a break in the skin itself. Exposure to water can change the microbiology of skin and soft tissue infections. Indeed, several reviews have highlighted the change in organisms grown from these types of infections (1). These organisms include Chromobacterium violaceum, Edwardsiella tarda, Shewanella spp, and the more commonly known Aeromonas spp and Vibrio spp (2). Let’s go over some of the articles, shall we? 

Water Microbiology:

Just like the lung, skin, and GI tract, the marine environment has its own microbiome. While a PCR from water samples will show several hundreds of organisms, early data suggests that only a handful of bacteria tend to be the most pathogenic. One study evaluated the microbiology from water in the Steinhart Aquarium in San Francisco, California as well as the microbiology from marine animals (3). Vibrio and Aeromon as spp were the most commonly isolated organisms:

Similarly, Japanese seawater and several marine organisms were cultured in another study, with Vibrio and Aeromonas spp also isolated here, along with pseudomonas, micrococcus, and Pasteurella spp isolated (4):

Vibrio, one of the most common organisms, is typically isolated in tropical and subtropical climates and has been found throughout the world, including Denmark, Italy, Japan, Australia, Brazil, and the US (11) 

Vibrio and Aeromonas:

Vibrio and Aeromonas spp tend to make up the majority of cases where water exposure was a thing. The largest retrospective study on SSTI following water exposure came after the 2004 Tsunami that struck Thailand (5). 777 tsunami survivors from 4 hospitals were evaluated, with SSTI being diagnosed in 66.3%. Culture data were obtained in 305 cases, with 72% having polymicrobial infection with gram negatives predominating. Aeromonas spp, E. coli, Klebsiella, and Pseudomonas spp were the most commonly isolated organisms:

Staphylococcus aureus was also isolated, but not at the standard frequency from other SSTI. Similarly, a retrospective review of 11 cases of Aeromonas hydrophila SSTI found that 7 out of 11 cases had preceding water exposure (6). A prospective, multicenter study evaluated 99 patients with Aeromonas infections, with wound infections being the most common manifestation (7). 91% of patients with skin and soft tissue infections had some sort of environmental exposure, and roughly 59% of patients had polymicrobial growth. One of the most curious outbreaks occurred following a charity mud football event in a town southwest of Western Australia (8). 26 cases of SSTI due to A. hydrophila were reported within 24 hours, with all cases being exposed to river water following mud exposure. In a cohort of 219 cases of Aeromonas infection, 19 were isolated from wounds with 13 being injured outdoors (9), while another case study highlights 2 severe cases of Aeromonas (10). One occurred in a patient who had a laceration into his scalp while swimming in a local lake in Lubbock, TX while the other one had been exposed to the Pecos River near Carlsbad, NM after sustaining a blast injury and quenching the fire after jumping into the lake. The latter patient had septic shock with Aeromonas hydrophila bacteremia. 

Similar to Aeromonas, Vibrio spp infection has been reported after contact with contaminated seawater (11). These typically manifest anywhere from 12 hours up to 7 days after exposure, as cellulitis, bullae, or ecchymosis. One of the earlier studies reported 189 wound infections following seawater exposure (12). 50% sustained a wound at the time of exposure, and 69% reported fishing or handling raw seafood 7 days prior to infection. Notably, an increase in the number of Vibrio cases were reported in the months following Hurricane Katrina, of which 18 out of 22 were skin and soft tissue infections (13):

One study (14) reported 1210 cases of non-food related Vibrio infections, with the largest being reported from the Gulf Coast region (57%), followed by the Atlantic region (24%), the Pacific region (16%), and non-coastal regions (3%). Vibrio vulnificus (35%), V. alginolyticus (29%), and V.parahaemolyticus (19%) were the most common species cultured, with the vast majority of samples coming in from wounds (68%). Notably, around 50% of patients who acquired a wound did so at the time of exposure. A retrospective study evaluated a 7-year time period following an initial outbreak of V. vulnificus in Israel (33). 134 cases of V. vulnificus infection were identified, with 81% of patients being injured while purchasing or preparing fish for cooking. Specifically, Tilapia was the source of exposure in 86 out of 104 cases, followed by exposure to the common carp. The severity of disease can be high for both organisms. A retrospective review evaluated 32 patients with necrotizing skin and soft tissue infections (15). 17 had vibrio vulnificus while 15 were infected with Aeromonas spp. The vast majority of patients had some environmental exposure, such as contact with raw seafood, exposure to warm seawater, and falling into a ditch.

The Other Organisms:

While the above two are the most common marine organisms that cause infection, there are other odd bugs to be on the lookout for. One of these is Edwardsiella Tarda. A review of 77 cases noted several risk exposures, including direct exposure to fresh or brackish water, fishing, gardening, or working in a zoo (16). The spectrum of disease is similar to the other 2 organisms. For instance, a retrospective study of 22 patients found 4 of these had SSTI with E. tarda, while 12 had hepatobiliary disease (17). A review of 5 cases of SSTI with E. tarda found 3 of these had been exposed to a marine environment: one fell into brackish water, another one into a canal, and the last one had a puncture wound after stepping on fish-bones (18). One case report of a 57 year old male with liver cirrhosis highlights the aggressive nature of this organism (19). Following a puncture injury to the hand from a catfish fin 2 days prior to presentation, the patient presented with diffuse swelling in the hand, with intraoperative pathology showing necrotic and foul smelling musculature with minimal purulence. The patient had a complicated course, with septic shock, renal failure requiring dialysis, and transhumeral amputation resulting in a favorable outcome. Notably, the catfish that injured the patient had a large mass on its back and died within hours of being placed into a fish tank. 

Infections due to Shewanella spp have also been reported, including abscesses, chronic ulcers, and SSTI complicating burns (21) . One retrospective study (20) noted that both bacteremia and SSTI were the most common types of infection:

44% of cases had preceding exposure to the marine environment. 

The review noted an outbreak of 31 abdominal and biliary tract infections caused by exposure to a shared measuring cup. Ventilator associated pneumonia has also been reported. Polymicrobial growth was also reported, with 53% of cases having more than two organisms growing. Some cases had bacteremia associated with marine flora. Other manifestations include hemorrhagic bullae due to Shewanella algae (22), necrotizing soft tissue infection due to S. halitosis (23) after handling fresh seafood, and cellulitis due to S. putrefaciens (24). 

Another pathogen is streptococcus iniae, an organism that has been observed in freshwater fish and is pathogenic to them as well (25). One case series from the greater Toronto area reported 4 cases, 3 of which were cellulitis (26). All were of Asian descent, however all had exposure to fresh fish. Surveillance identified a total of 11 cases, all having reported injuries while handling whole or partially prepared fresh fish. All were treated with penicillin, ampicillin, or cloxacillin.Finally, Chromobacterium violaceum is another water-borne organism with one review (27) of 131 cases finding SSTI being the second most common manifestation of disease (50%), followed by sepsis (77%). One case reported on a complicated SSTI on a rice paddie farmer, which presented with fatigue along with a pustule on their leg. Subsequent imaging revealed multiple liver abscesses (28). Indeed, disease can be severe as the previously mentioned review notes 66% mortality rate. Erysipelothrix rhusoiopathie, which is typically related to occupational exposure, is another cause of skin and soft tissue infection (34). One older review highlights some interesting things about the organism.  

Antibiotic Therapy:

Several reviews have noted empiric therapy should consist of a third generation cephalosporin + tetracyclines or quinolones (29). Indeed, Aeromonas and Vibrio are resistant to penicillins and first generation cephalosporins, however others have varying susceptibility to these antibiotics (30). Despite this, adding a quinolone or a tetracycline circumvents this issue as basically everything is susceptible to these for the most part. Some data backs up the use of these antibiotics. One early study found that Aeromonas and Vibrio spp tended to be susceptible to third-generation cephalosporins, TMP-SMX, and Imipenem (3):

A late 90s Japanese study found third-generation cephalosporins, bactrim, and quinolones were susceptible to V. vulnificus isolated here (4). For aeromonas, a large prospective study evaluated 99 patients with a variety of infections (7). Piperacillin, third and fourth generation cephalosporins, and ciprofloxacin achieved >90% susceptibility here. 

Time-kill studies suggest the combination of cephalosporins and tetracycline are comparable to quinolones.  In one study of 42 V. vulnificus isolates, growth curves for both minocycline and cefotaxime demonstrated longer inhibitory effect when concentrations higher than MIC was tested, some of which lasted up to 48 hours (31):

When the two antibiotics were tested at nearly 1.5 times above the MIC, there was a reduction of around 3 orders of magnitude in the size of the inoculum that lasted up to 48 hours, suggestive of synergistic activity:

Further kill-time studies found that ciprofloxacin exerted inhibitory effect for the first 24 hours, however bacteria began to grow shortly thereafter (32):

When looking at subinhibitory concentrations of cefotaxime and minocycline, the combined inhibitory effect persisted for over 48 hours. This effect was similar when using levofloxacin at 1.5 times the MIC and ciprofloxacin at 2 times the MIC.

In vivo studies suggest that both moxifloxacin and ceftoaxime-minocycilnie had equivalent survival rates:

In the second part of the experiment, mice treated with a quinolone had a non-statistically different rate of survival when compared to each other:

References:

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