An Unusual Presentation of Salmonella: Cellulitis, Gastroenteritis, and Bacteremia

Introduction

The genus Salmonella comprises gram-negative, motile, facultative intracellular microorganisms, which are recognized as one of the most common causes of gastroenteritis and enterocolitis [1]. Extraintestinal manifestations, however, are less frequent and typically occur in predisposed hosts [2,3].

Cellulitis caused by Salmonella is relatively uncommon compared with infections caused by common bacteria such as Staphylococcus aureus or Streptococcus pyogenes. A large surveillance study identified 38 237 non-typhoidal Salmonella isolates, of which only 3.7% were from extraintestinal sources; among these, abscess or pus accounted for a very small proportion (0.1% of total isolates), highlighting the rarity of soft-tissue involvement [3].

Although soft-tissue involvement is recognized as a rare complication, the concurrent occurrence of bacteremia, cellulitis without abscess formation, and gastroenteritis has seldom been reported. To the best of our knowledge, only 1 comparable case describing this triad has been reported in the literature [4]. Notably, cellulitis without abscess formation, as seen in our patient, appears to be exceptionally rare. This case report seeks to inform clinicians regarding this uncommon triad and to underscore the importance of Salmonella as an occasional etiological agent of invasive disease beyond the gastrointestinal tract.

Case Report

A 75-year-old man with a history of peripheral arterial disease with stenosis of the distal right superficial femoral artery and occlusion of the right anterior tibial artery, a cerebrovascular accident, coronary artery disease, hypertension, hyperlipidemia, type 2 diabetes, and compensated cirrhosis of the liver presented with 4 days of non-bloody watery diarrhea occurring 3 to 4 times daily, followed by progressive right lower-extremity pain, erythema, warmth, and edema. He denied fever, chills, nausea, vomiting, unusual food exposures, or sick contacts and reported eating eggs daily that were purchased from the same supermarket. Notably, he had been hospitalized in the prior month for bilateral lower-extremity bullae, with a residual right calf ulcer present at admission.

On arrival, he was afebrile and hemodynamically stable. Physical examination revealed right lower-extremity edema extending from the foot to the mid-shin with overlying erythema, warmth, and no purulent drainage, as well as an ulcer measuring approximately 1×1 cm on the posterolateral aspect of the right calf with partial-thickness involvement and no necrosis or drainage, and without focal bone tenderness (Figure 1A, 1B). Laboratory testing showed a WBC count of 4.3×109/L, procalcitonin of 1.73 ng/mL, and lactic acid of 1.25 mmol/L. One set of blood cultures was obtained prior to initiation of empiric antibiotics. Stool testing using the BioFire FilmArray gastrointestinal polymerase chain reaction (PCR) panel and wound culture of the ulcer were obtained after antibiotic initiation. Lower-extremity ultrasound revealed no deep vein thrombosis, and computed tomography (CT) of the lower extremity showed diffuse subcutaneous edema without fluid collection.

Given the diagnosis of non-purulent cellulitis based on clinical findings in the setting of a chronic ulcer and multiple comorbidities, the initial differential diagnosis included streptococcal cellulitis as well as gram-negative or polymicrobial infection. Empiric intravenous vancomycin and piperacillin–tazobactam were initiated. A wound care consultation was obtained. Local wound management consisted of leaving the ulcer open to air without debridement or topical antimicrobial therapy, as there was no evidence of necrotic tissue, purulence, or devitalized tissue requiring intervention.

Unexpectedly, a stool PCR was positive for Salmonella species and cultures obtained from blood and wound grew Salmonella enterica, which was pan-sensitive to all tested antibiotics (Table 1). Serotyping of the isolate was not performed. The initial blood culture became positive after approximately 12 h of incubation. The concordance of stool PCR and positive blood and wound cultures supports a true infection. These findings established the diagnosis of concurrent bacteremia, cellulitis, and gastroenteritis. The Infectious Disease service was consulted for assistance with management. A 2D transthoracic echocardiogram showed no evidence of endocarditis.

The patient was transitioned to a 7-day course of intravenous ceftriaxone. Two sets of repeat blood cultures obtained on hospital day 2 were negative. Resolution of erythema and edema was noted by hospital day 3. Glycemic control remained stable during hospitalization. Contact precautions were implemented for infection control. Vascular surgery consultation was not pursued, as there was no clinical evidence of acute limb ischemia or an indication for surgical intervention. The patient was discharged in stable condition. At 3-week follow-up with the Infectious Diseases service, there was sustained resolution of lower-extremity erythema and edema. At 3-month telephone follow-up, he reported no recurrence of symptoms.

Discussion

Salmonella enterica is a facultative intracellular gram-negative bacillus capable of causing a wide clinical spectrum of disease, from self-limited gastroenteritis to invasive infection including bacteremia and focal soft-tissue involvement or osteomyelitis. Extraintestinal manifestations are uncommon, occurring in approximately 4% to 8% of infections [2,3,5]. They are more frequently seen in infants, older adults, and patients with comorbidities including immunocompromising conditions, chronic liver disease, and diabetes [3,6–8]. Among patients with Salmonella bacteremia, prior studies have shown that diabetes mellitus, hypertension, and chronic lung disease are significantly associated with the development of extraintestinal focal infections, whereas malignancy and immunosuppressive therapy are less frequently associated [9]. In our patient, long-standing diabetes, peripheral arterial disease, hypertension, and cirrhosis likely contributed to local tissue vulnerability and bacterial seeding, resulting in cellulitis in the setting of bacteremia and gastroenteritis.

Soft-tissue involvement is an even rarer form of extraintestinal disease, occurring in only 2.9% of invasive Salmonella infections in prior studies [10]. Several case reports have described isolated cutaneous or soft-tissue infections without clear evidence of concurrent gastrointestinal illness [8,11,12]. The precise mechanism of infection in these cases remains uncertain. In the present case, 2 hypotheses may be considered. Hematogenous seeding of compromised tissue is a recognized pathway in invasive Salmonella infections. Alternatively, direct inoculation of Salmonella into a disrupted skin barrier may have occurred. In this patient, chronic peripheral arterial disease and a chronic ulcer on the affected limb may have created a portal of entry. Peripheral arterial disease and associated skin ulceration are well-recognized risk factors for soft-tissue infection due to impaired tissue perfusion, delayed wound healing, and reduced local immune defense [13–16]. At the same time, concurrent diarrhea could have facilitated local contamination and secondary infection. The temporal association between diarrheal illness and cellulitis raises the possibility of this mechanism.

Cutaneous Salmonella infections are uncommon and frequently mimic more typical bacterial cellulitis caused by streptococci or staphylococci, making culture confirmation essential [4]. In the published literature, cutaneous Salmonella infections described as soft-tissue involvement or “cellulitis” have most often been abscesses or purulent collections [4,8,11,17–20]. Presentations without abscess formation, as in our patient, appear to be exceptionally rare. This may reflect early hematogenous seeding or superficial tissue involvement without progression to localized suppuration, with host factors such as underlying vascular disease and impaired tissue perfusion potentially limiting abscess formation. In this case, CT imaging was performed to evaluate for abscess and demonstrated no drainable fluid collection. Further imaging, such as magnetic resonance imaging or bone scintigraphy, was not pursued due to low clinical suspicion for osteomyelitis, given the superficial ulcer, absence of focal bone tenderness, and rapid clinical response. Stool PCR testing detects bacterial DNA and does not differentiate viable organisms from residual nucleic acid; however, the concurrent isolation of Salmonella enterica from blood and wound cultures supports true infection in this case.

In addition to focal soft-tissue infection, Salmonella bacteremia can lead to invasive complications, including endocarditis, particularly in patients with underlying cardiovascular disease. In this patient, transthoracic echocardiography showed no evidence of endocarditis. Salmonella bacteremia has also been associated with other endovascular infections, including involvement of atherosclerotic plaques, vascular grafts, and mycotic aneurysm formation [21–23]. Vascular grafts, advanced age (>60 years), male sex, atherosclerosis, pre-existing aortic aneurysm, and sustained or relapsing bacteremia are recognized risk factors for Salmonella endovascular infection [21,23,24]. Patients with these risk factors who present with fever, abdominal, back, or chest pain should be considered for further evaluation of possible endovascular infection [22,24]. In this case, although the patient had certain risk factors, there were no known vascular grafts or aortic aneurysm and he did not exhibit clinical features suggestive of vascular infection during hospitalization or follow-up; therefore, additional vascular imaging was not pursued.

There are no established treatment guidelines for Salmonella cellulitis. According to the Johns Hopkins Antibiotic Guide, treatment duration for Salmonella bacteremia with soft-tissue involvement is guided by host factors and the presence of deep-seated infection, with 7 to 14 days recommended for immunocompetent patients [25]. Given that the patient was immunocompetent, demonstrated rapid clinical improvement with clearance of bacteremia, and had no evidence of deep-seated infection (eg, endocarditis or osteomyelitis), a 7-day course of antibiotics was selected.

This case illustrates the importance of considering Salmonella infection in patients presenting with cellulitis in the context of recent diarrheal illness, particularly when vascular disease or skin disruption is present. Awareness of this potential dual mechanism – hematogenous seeding and direct inoculation – can aid in timely diagnosis and appropriate management to prevent complications.

Conclusions

To the best of our knowledge, very few cases have been reported of Salmonella enterica infection presenting with bacteremia, cellulitis, and gastroenteritis in the same patient. This case highlights the need to consider Salmonella species in atypical soft-tissue infections, particularly when cellulitis occurs in the context of concurrent diarrhea or skin disruption such as a chronic ulcer, especially among individuals with diabetes, peripheral arterial disease, or other chronic comorbidities. Early culture confirmation and pathogen-directed therapy are key to achieving favorable outcomes. From a public health perspective, heightened clinical awareness and surveillance for invasive Salmonella infection in high-risk populations may facilitate earlier diagnosis and targeted management.