Chromobacterium violaceum Periareolar Infection, First Non-Lethal Case in Colombia: Case Report and Literature Review

Chromobacterium violaceum is a facultative anaerobic, Gram-negative rod found in different ecosystems, especially tropical and subtropical areas. Human infections are rare, and just a few cases have been reported in literature. In this paper, we present the first non-lethal infection due to Chromobacterium violaceum, in an adult male with polycystic kidney disease in Colombia. Periareolar soft tissue infection was documented with isolation of Chromobacterium violaceum. Clinical manifestations, treatment, and outcome are shown.


Introduction
Chromobacterium violaceum is a facultative anaerobic, Gram-negative rod of the Neisseriaceae family that is considered an opportunistic pathogen. It is mainly found in water and soil; transmission is by contact with organic material and (to a lesser extent) by contaminated water ingestion [1,2]. Mortality rates range between 65 and 80% [2]. Until 2021, 200 cases had been reported worldwide, with two in Colombia-one of them in a child [3] and the latter in an adult [4], both with fatal outcomes. In this paper, we present the first non-fatal soft tissue infection due to Chromobacterium violaceum in an adult with polycystic kidney disease in Colombia, with a favorable outcome.

Case Report
A 47-year-old man (an employee of the hotel sector from Bogotá) with a past medical history of polycystic kidney disease presented to the emergency room with complaints of one week of erythema and purulent drainage of the anterior chest wall associated with a fever of up to 38.5 • C. He received cephalexin during a three-day course without any improvement.
Upon physical examination, he was in no acute distress, and his skin exam was remarkable for an erythematous left periareolar nodule with swelling, warm, and purulent discharge (Figure 1), along with signs of systemic inflammatory response without clinical findings of sepsis organic dysfunction ( Table 1). The patient started on therapy with intravenous clindamycin. However, he deteriorated due to the worsening of chronic kidney disease with the further requirement of renal replacement therapy.  The patient was taken to surgery, where a 15-cm abscess with skin necrosis over the area of renitence was found. The cytochemical results of the abscess showed abundant leukocytes and the isolation of Chromobacterium violaceum ( Figure 2). Antibiograms were not made, and blood cultures were negative. The patient continued intravenous clindamycin with no improvement at the third day of admission, so doxycycline was started at a 100 mg BID dosage with partial response. At day five of admission, he was taken to another surgical procedure, and negative pressure therapy was placed over his wound. This therapy allows one to draw fluid from an infected site using a vacuum system, which is  The patient was taken to surgery, where a 15-cm abscess with skin necrosis over the area of renitence was found. The cytochemical results of the abscess showed abundant leukocytes and the isolation of Chromobacterium violaceum ( Figure 2). Antibiograms were not made, and blood cultures were negative. The patient continued intravenous clindamycin with no improvement at the third day of admission, so doxycycline was started at a 100 mg BID dosage with partial response. At day five of admission, he was taken to another surgical procedure, and negative pressure therapy was placed over his wound. This therapy allows one to draw fluid from an infected site using a vacuum system, which is especially useful for deep, complicated, and nonhealing wounds. The antibiotic was again changed to tigecycline at a 50 mg BID dosage for ten days. especially useful for deep, complicated, and nonhealing wounds. The antibiotic was again changed to tigecycline at a 50 mg BID dosage for ten days. After five days of tigecycline, he underwent surgery again, negative pressure therapy was withdrawn, and the wound was covered with a fasciocutaneous flap. He was discharged after completing 10 days of antibiotic treatment, with no signs of systemic inflammatory response and with adequate closure of the skin wound ( Figure 3).

Discussion
Chromobacterium violaceum is a facultative anaerobic, carbohydrate fermenter, catalase-positive, and Gram-negative bacillus. It grows on blood, chocolate, and MacConkey agar within 18-24 h and can produce pigmented colonies due to the production of violacein, a metabolite with apoptotic activity on some cells [5]. Nonetheless, it can also grow as unpigmented colonies. After five days of tigecycline, he underwent surgery again, negative pressure therapy was withdrawn, and the wound was covered with a fasciocutaneous flap. He was discharged after completing 10 days of antibiotic treatment, with no signs of systemic inflammatory response and with adequate closure of the skin wound ( Figure 3).
Infect. Dis. Rep. 2021, 13, FOR PEER REVIEW 3 especially useful for deep, complicated, and nonhealing wounds. The antibiotic was again changed to tigecycline at a 50 mg BID dosage for ten days. After five days of tigecycline, he underwent surgery again, negative pressure therapy was withdrawn, and the wound was covered with a fasciocutaneous flap. He was discharged after completing 10 days of antibiotic treatment, with no signs of systemic inflammatory response and with adequate closure of the skin wound ( Figure 3).

Discussion
Chromobacterium violaceum is a facultative anaerobic, carbohydrate fermenter, catalase-positive, and Gram-negative bacillus. It grows on blood, chocolate, and MacConkey agar within 18-24 h and can produce pigmented colonies due to the production of violacein, a metabolite with apoptotic activity on some cells [5]. Nonetheless, it can also grow as unpigmented colonies.

Discussion
Chromobacterium violaceum is a facultative anaerobic, carbohydrate fermenter, catalasepositive, and Gram-negative bacillus. It grows on blood, chocolate, and MacConkey agar within 18-24 h and can produce pigmented colonies due to the production of violacein, a metabolite with apoptotic activity on some cells [5]. Nonetheless, it can also grow as unpigmented colonies.
This microorganism adheres through the CopE membrane protein, which induces rearrangement in the actin cytoskeleton, thus leading to damage in epithelial cells. Furthermore, metalloproteinase (MMP-2) with elastase activity facilitates the production of abscesses, and two type III secretion systems, which are involved in the signal transduction cascade that favor cytotoxicity by allowing for pore formation in host cell membranes, have been described [5].
Skin and soft tissue infections due to this Gram-negative bacteria mainly occur in patients with risk factors-either environment-related, such as exposure to organic or contaminated surfaces (especially if there is a loss of continuity of the skin) or host-related, such as chronic immunosuppression conditions like diabetes mellitus, chronic granulomatous disease (CGD), and glucose-6-phosphate dehydrogenase (G6PD) deficiency [6].
There are two ways to explain the susceptibility to Chromobacterium violaceum infections in patients with these last two conditions: The first is related to the dysfunction of the phagocytic cell to eliminate the bacteria, since the production of peroxide is altered due to the deficiency of NADPH and NADPH oxidase. The hydrogen peroxide necessary for phagocytic activity comes from two routes: first after the action of lysosomal enzymes and acid hydrolases, and second through the action of the enzyme NADPH oxidase. Catalasepositive microorganisms such as Chromobacterium violaceum disable the production of lysosomal hydrogen peroxide, leaving only the NADPH route in charge of its production for phagocytic action. Thus, in conditions like CGD and G6PD deficiency where NADPH production is compromised, there is a major susceptibility to infections due to these microorganisms [7]. The second mechanism refers to the inadequate formation of the inflammasome; it has been reported that NADPH pathway is directly involved with the regulation of the latter, so any alteration in the NADPH production (as in CGD and G6PDH) would directly affect the destruction of inflammasome-dependent microorganisms, such as Burkholderia cepacia and Chromobacterium violaceum [8][9][10].
The association of Chromobacterium violaceum infection with CGD has been previously described, mainly in children since the hereditary nature of the disease and almost none in adults with skin and soft tissue infections [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Nonetheless, this association does not seem to be directly related to an increase in mortality [28]. Fewer cases of infections in patients with G6PDH deficiency have been reported, perhaps because of the rarity of the disease, so it is not possible to set a mortality trend in this condition [29,30]. In our patient, the only triggering factor corresponded to an insect bite, which had been previously reported in two cases [12,22].
To date, 27 cases of skin and soft tissue infection by Chromobacterium violaceum have been reported in adults (Table 2), mainly described in males of ages between 20 and 50 years old, with an average of 46 years. Most of them have presented with an acute onset of symptoms, frequently requiring hospitalization in the first week [16,19,20,22,25,27]: 44% of infections have presented with bacteremia and 51% have led to sepsis, with mortality as high as 22%. Bacterial growth in culture has ranged from 15 to 72 h, except for a single reported case of 10 days. In most cases, the definitive treatment was found to be a betalactam and fluoroquinolone combination, consistent with most reported susceptibility profiles where resistance to penicillins, aminopenicillins, and cephalosporins, as well as sensitivity to carbapenems and fluoroquinolones, is frequent ( Table 2).
The patient in this case presented a severe clinical course, with organ dysfunction and with requirement of multiple surgical procedures to control the infectious source. The patient had an inappropriate response to initial antimicrobial therapy, which is consistent with previous reported cases where broad spectrum antibiotic combinations were required for control of the infection. However, in comparison with the two other reported cases in Colombia, both of them with fatal outcomes, he did not present bacteremia during his clinical course. In fact, bacteremia and sepsis were present in all of the reviewed cases of skin and soft tissue infections with fatal outcomes, suggesting that the dissemination of the infection into the bloodstream is a strong predictor of adverse outcomes and mortality.      In Colombia, this is the first case of non-lethal infection by Chromobacterium violaceum, and it was the first one of skin and soft tissue infection (Table 3). In Latin America, it corresponds to the first case of non-lethal skin and soft tissue infection [18]

Conclusions
Chromobacterium violaceum has been reported since 1927 as the cause of severe infections, with a trend towards immunocompromised populations and patients of reproductive age with skin trauma. Thus far, the inflammasome and NADPH pathway dysfunction are the most studied predisposing factors for infection, while the presence of bacteremia is a strong predictor of adverse outcomes and mortality. The mechanisms of antibiotic resistance are not yet clear, but carbapenems and fluoroquinolones are the most widely used antibiotics in hospitalized patients.
Many factors contributed to clinical cure in the presented case, including an adequate control of infectious source and tissue debridement, the absence of bloodstream infection, and a strong antibiotic therapy. More studies are required to understand the dynamics of this microorganism and its clinical implications. Informed Consent Statement: Written informed consent was obtained from the patient to publish this paper.