Lower Extremity Salmonella Abscess with Vascular Thrombosis and Wall Destruction

Abstract

Abstract

Background:

We present a case of lower extremity non-typhoidal Salmonella abscess, arterial thrombosis, and arterial wall destruction that occurred in the setting of malnutrition, poorly controlled diabetes mellitus, and subsequent immunoincompetence.

Conclusion:

Issues in pathogen identification, necrotizing infection management, and pathogen virulence factors related to pathogen persistence and neutrophil trafficking are reviewed.

The overall incidence of reported infection because of non-typhoidal Salmonella (NTS) has increased over the past 15 y in Western countries, causing an estimated 1.2 million infections and 450 deaths annually [1]. Non-typhoidal Salmonella can cause not only self-limited acute gastrointestinal infections, but also bacteremia with or without extra-intestinal focal infections, most commonly in the immunocompromised host. Salmonella enterica serotype Enteritidis is one of the most common serotypes of NTS and is responsible for an increasing number of human illnesses in the United States. Many NTS infections usually arise via a foodborne route commonly resulting in a self-limiting gastroenteritis, but approximately 3%–10% of cases become invasive, resulting in serious infection and potentially fatal septic shock [2]. We present an unusual case of invasive salmonellosis with lower extremity arterial thrombosis, perforation, and abscess, with an unexpected route of infection.

Clinical History

A 60-year-old male presented to the emergency department with increasing right medial thigh pain and swelling of four weeks duration as well as a six-month history of a 50- to 60-pound unintentional weight loss with a normal oral intake. He reported no injury, insect bites, or injections of the right thigh. Past history was remarkable for hypertension, hypercholesterolemia, and uncontrolled type 2 diabetes mellitus with poor medication compliance; a review of systems was otherwise unremarkable. A drug screen noted cocaine positivity consistent with prior admissions for intravenous drug use (IVDU).

Physical Examination and Diagnosis

On admission, he was afebrile, tachypneic, and tachycardic but otherwise hemodynamically appropriate. Examination revealed a tender, non-pulsatile mass in his right medial thigh without overlying skin abnormality. Laboratory investigation disclosed leukocytosis (11,000 with a left shift), hyperglycemia (244 mg/dL), and a hemoglobin A_1C of 10.9%; other laboratory values were appropriate. Computed tomography (CT) scan with intravenous contrast of the right lower extremity demonstrated a complex, multi-loculated abscess deep to the rectus femoris and sartorius muscles, encasing a thrombosed, calcified superficial femoral artery (SFA) with air within the vessel and distal reconstitution above the knee (Fig. 1).

FIG. 1.

Axial computed tomography (CT) scan with intravenous contrast of the right lower extremity demonstrating a typical abscess with gas as well as a thrombosed superficial femoral artery with a pocket of gas within the lumen.

Intervention

Empiric antimicrobial coverage with vancomycin and piperacillin-tazobactam given prior recent hospitalization and diabetes mellitus preceded operation for source control. With initial incision, subcutaneous emphysema was found that was absent from the CT scan four hours prior. The abscess cavity was filled with thick purulence encasing a thrombosed SFA with multiple holes throughout the vessel wall (Fig. 2). These perforations likely allowed abscess cavity gas to enter the lumen of the vessel. Given distal SFA reconstitution and the absence of limb ischemia on examination, bypass was not undertaken. The SFA was dissected to healthy-appearing tissue outside of the abscess cavity and each end was suture ligated; no arteriovenous fistula was noted (Fig. 3).

FIG. 2.

Intra-operative image of welling purulence upon abscess cavity entry.

FIG. 3.

Intra-operative image of proximal and distal superficial femoral artery dissection and control prior to suture ligation.

The incision was packed open for planned re-operation. A total of three re-operations were undertaken for debridement of tissue that appeared healthy during the prior exploration consistent with a necrotizing soft tissue infection. Final coverage was undertaken with a vastus medialis muscle flap to cover the arterial stumps and fill the abscess cavity. The fascia was repaired over a closed suction drain with the skin and subcutaneous tissue packed open.

Follow-Up and Outcomes

Cultures from both the incision and blood grew pan-sensitive Salmonella enteritidis and antibiotics were tapered to intravenous ceftriaxone 2 g/d for six weeks. Given historic features suggesting immune incompetence, human immunodeficiency virus (HIV) and hepatitis C assays were obtained, which were negative. Six-week follow-up revealed a well-healed incision and no evidence of limb ischemia or pseudoaneurysm formation.

Discussion

Salmonella are flagellated gram-negative faculatively anaeobic bacilli from the family Enterobacteriaceae. Non-typhoidal Salmonella are widely disseminated in nature and transmission to human beings is usually through a contaminated food source. Salmonella serovar Enteritidis is a type of NTS with a broad host range and has become one of the most common serotypes causing salmonellosis [3]. Disease severity depends on the interface between bacterial virulence factors and host immune competence. In the otherwise healthy, immune competent host, extra-intestinal non-typhoidal Salmonella (EI NTS) infections are relatively rare. Accordingly, infection risk is increased with immune incompetence whether innate or acquired diabetes mellitus, malignant disease, HIV infection, and therapeutic immunosuppression [4].

Soft tissue infections are an uncommon salmonellosis manifestation. A retrospective study found that 39.5% of 129 patients with NTS had extra-intestinal focal infection, but only 0.8% had a soft tissue infection [4]. To our knowledge, the case presented here is unique as there are no other published reports of NTS infections presenting as a combined arteritis, arterial thrombosis, necrotizing soft tissue infection, and bacteremia.

The pathogenic capacity of different NTS serovars is dependent upon the virulence potential of the bacteria and the susceptibility of the host. Salmonella enterica harbor a diverse assortment of virulence genes required for adhesion, invasion, intra-cellular survival, and replication [5]. Cytokine production in Salmonella pathology takes place by activation of complex and interconnected signaling pathways, changing the expression of certain genes, allowing S. enteritidis to escape the host immune system and colonize systemic sites [6]. Additionally, Salmonella interfere with intra-cellular trafficking of lysosomes and endosomes, enhancing their virulence and persistence once engulfed [7]. In fact, Salmonella have been reported to evade d-amino oxidase in neutrophils by expressing an importer specific for d-alanine that provides an alternate substrate for the oxidase [8]. Additionally, Salmonella with Salmonella pathogenicity island-1 (SP-1) utilize a zinc exporter (ZntA) to cripple toll-like receptor (TLR) signaling driven zinc accumulation and zinc-dependent intra-macrophage destruction [9]. Moreover, it has been described in a murine model that gut microbiota absence augments mesenteric lymph node pathogen colonization by Salmonella, and that colonization leads to increases in interleukin-12 driven interferon-gamma production [10].

These latter observations in particular suggest that the organism responsible for this patient's infection were not derived from skin, but from his gut microbiome and were carried to that site by chemoattraction of neutrophils already laden with Salmonella, perhaps from mesenteric lymph nodes. Most commonly, the pathogenesis of arterial infections caused by Salmonella is most often the result of bacterial invasion of a pre-existing arterial lesion during a period of bacteremia, seeding a diseased arterial wall most commonly at the site of artherosclerotic plaque. We propose that although this particular patient had pre-existing plaque, his primary infection was that of an extra-arterial hematoma via primary immune effector cell Salmonella carriage. The infected hematoma likely drove the local inflammatory response leading to arterial thrombosis. Both abscess and arteritis are powerful triggers for neutrophil trafficking leading to high local concentrations of elastase and matrix metallo-proteinases that augmented local damage and the subsequent destruction of the superficial femoral artery (SFA) vessel wall. It is unlikely that all the vessel perforations were caused by punctures from IVDU because they were all larger than 5 mm and many were in areas devoid of plaque. It is likely, however, that the initial puncture—most likely from IVDU—created the hematoma that became infected subsequently.

The successful management of EI NTS that presents as a soft tissue infection includes prompt surgical drainage and debridement of infected tissue as well as use of bactericidal antibiotics coupled with scheduled repeat evaluation of tissue health and viability. Given the panoply of virulence factors and the difficulty in eradicating this pathogen from arterial walls, current recommendations include high-dose bactericidal therapy for at least six weeks. More prolonged therapy appears reasonable if inflammatory biomarkers such as C-reactive protein, and white blood cell count and differential fail to normalize. At present, there is no effective method of monitoring Salmonella presence in an arterial wall other than tissue biopsy. Perhaps as our ability to detect and correctly categorize DNAemia progresses, therapeutic decision-making may rely on precision-driven thresholds.

Conclusion

Presented here is a unique case of EI NTS infection that originated as a soft tissue infection of an extremity in a vulnerable host with presumed weight-loss–driven microbiota coupled with diabetes mellitus and weight-loss–promoted immune incompetence. Empiric therapy including resuscitation and empiric antimicrobial management coupled with excisional debridement as for any other soft tissue infection is essential in restoring homeostasis and identifying the causative pathogen(s). Advances in pathogen detection for early identification and tailoring of therapy duration await ongoing progress in molecular diagnostics such as the detection of blood-borne bacterial DNA. Seemingly unlikely infections may be more readily understood in light of virulence factors as well as alterations in host defense including increasingly prominently, the microbiome.