Necrotizing Fasciitis due to Streptococcus constellatus in a Patient with Uncontrolled Diabetes and Bilateral Diabetic Foot Ulceration

NSTI is a rare but potentially fatal limb- and life-threatening emergency.^1,2 NSTI is classified into 3 types. Type 1 is a polymicrobial infection from gram-positive cocci, gram-negative rods, and anaerobes, such as Clostridium or Bacteroides spp. Type 2 is a monomicrobial infection associated with group A β-hemolytic streptococci. Type 3 is linked to gram-negative marine organisms. Type 1 NSTI is the most common type to occur in patients with diabetes.^1,3 While the quantity of reports is small, NSTI and bacteremia from members of the Streptococcus milleri have been reported.^4-7 The bacteria in this group—Streptococcus anginosus, Streptococcus constellatus, and Streptococcus intermedius—are normal flora of the oropharyngeal, gastrointestinal, and genitourinary tracts. While these bacteria have a proclivity for abscess formation, associated bacteremia and sepsis are rare and are more likely to occur in patients with diabetes or underlying malignancies.^4-10 However, the reported incidence of bacteremia and sepsis is rising.^1,11 Prompt surgical debridement of infected wounds and antibiotic therapy are the mainstays of treatment.^1,4,5,7,9,10 This case report presents the clinical course of a patient with poorly controlled diabetes who was found to have necrotizing fasciitis and bacteremia secondary to S constellatus.

A 69-year-old female with history of seizure disorder, poorly controlled diabetes, hypertension, dyslipidemia, and migraine headaches presented to the emergency room with altered mental status secondary to sepsis from severe diabetic foot ulcer on the left foot. Abnormal vital signs on presentation included tachycardia and tachypnea. The patient received a fluid bolus and broad-spectrum antibiotics immediately upon arrival. Podiatry was consulted for evaluation of the lower extremities. The patient reported noticing an open wound on the bottom of her left foot 2 weeks prior, with worsening redness and swelling extending up the leg over the past week. The patient did not recall any trauma but admitted to lack of protective sensation in her lower extremities. Despite this, she acknowledged feeling disproportionate pain in her left foot during ambulation. The patient also reported having an asymptomatic wound to the right hallux.

Focused examination of the lower extremities revealed a necrotic lesion at the left plantar fifth metatarsal head (Figure 1A). Induration was present at the lesion and its surrounding area. Localized dusky discoloration of the skin, as well as edema and erythema extending to the level of the mid-calf, were noted. Left lateral foot pain worsened on palpation, and the presence of malodor was noted. These focused physical examination findings were consistent with a deep space abscess. Concomitantly, the right foot had a full-thickness ulceration at the distal hallux that probed to bone and had purulent drainage.

Radiographs of the left foot revealed cortical irregularity at the fifth metatarsophalangeal joint with associated soft tissue emphysema (Figure 1B). Radiographs of the right foot revealed cortical erosion at the tuft of the distal phalanx of the right hallux. MRI of the left foot showed soft tissue emphysema adjacent to the fifth metatarsal bone, tracking proximally towards the hindfoot. Laboratory findings used to calculate the LRINEC score included 4 points for a C-reactive protein level of 31 mg/dL, 2 points for serum sodium of 130 mmol/L, 1 point for blood glucose level of 565 mg/dL, 1 point for hemoglobin of 13.5 g/dL, and 1 point for total leucocyte count of 19,200/µL. The points combined for a total of 9, wherein a LRINEC score of 6 or higher confers an increasing risk for necrotizing fasciitis. Other notable laboratory results were hemoglobin A_1c of 14.4% and an erythrocyte sedimentation rate of 65 mm/hr. Both blood cultures grew S constellatus.

Once hemodynamically stable, the patient was taken to the operating room. The entire left forefoot was noted to be necrotic with extensive phlegmon, malodor, and purulence concentrated at the fifth metatarsal extending to the proximal one-third of the bone. Overall, the severity of the intraoperative findings necessitated an open transmetatarsal amputation for source control. A bone biopsy of the fifth metatarsal proximal shaft was sent for culture and histological exam. The patient also underwent partial amputation of the right hallux. A bone biopsy of the proximal margin was sent for culture and histological exam. Resorbable calcium sulfate beads (OsteoSet; Stryker, Kalamazoo, MI) mixed with 1 g vancomycin powder were applied to both surgical sites. Vancomycin was selected due to the concern for the potential presence of methicillin-resistant Staphylococcus aureus based on the Gram stain result from the blood culture; speciation and sensitivities were pending. Resorbable beads were selected for use due to the reduced risk of inflammatory reaction and to allow for sustained release of antimicrobial therapy over time.² Deep wound cultures for both feet grew S constellatus. The bone biopsy from the left fifth metatarsal proximal shaft was also positive for S constellatus. Results of biopsy culture from the proximal margin of the right hallux proximal phalanx were negative.

Given that blood cultures, deep wound cultures on both feet, and bone biopsy from the left foot were all positive for S constellatus, the Infectious Disease department recommended initiation of a 6-week course of intravenous ceftriaxone, 2 g daily. The patient was taken back to the operating room 2 days after the initial procedure for repeat surgical debridement, removal and replacement of antibiotic-impregnated beads, and further resection of the fifth metatarsal as proximal margin (Figure 2). The surgical site was again packed open with antibiotic beads. With continued positive response of the patient on parental antibiotic
therapy and following serial wide debridement, delayed primary closure of surgical site was possible at 5 days after the initial surgery (Figure 3 and 4). The surgical sites on both feet healed without complication (Figure 5).

Presented here is a case of NSTI caused by S constellatus, a member of the S milleri group, considered as group F Streptococci. These resident florae of the oropharyngeal, gastrointestinal, and genitourinary tracts are small, gram-positive, catalase-negative, nonmotile, microaerophilic, facultative anaerobes that can be α-, β-, or non-hemolytic.^4-11S constellatus was first identified from a dental abscess causing oral infection, which was consistent with the propensity for these bacteria to cause abscess formation and subsequent infection.^9,10 The species is typically associated with superficial and polymicrobial infection.^4,8 While bacteremia and hematogenous spread is rare, there have been reports of septic emboli, septic thrombophlebitis, and hematogenous spread to the brain, liver, spleen, subdural space, bone, and heart.^4,5,9

Associated underlying comorbidities and patients of older age have been reported to have a greater potential for hematogenous spread due to the reduced ability of the host to stave off infection.^4,8,12 Several studies looking at infection caused by the S milleri group have found around half of the cases occur in patients with 1 or more comorbidities, the most common being diabetes.^8-10 One study found that 34% of all skin and soft tissue infections occurred in patients with diabetes.⁹ Malignancy, both solid organ and hematogenous, was the second most common.^8,10 Skin and soft tissue infection accounted for 68% to
72% of cases in 2 studies.^8,9

Symbiosis with anaerobic bacteria is also theorized to propagate hematogenous spread due to further inhibition of host immune response.^4,13 One case report of fatal Fournier’s gangrene with Clostridium ramosum found associated sepsis and blood cultures positive for S constellatus.¹³ The authors postulated that the anaerobic clostridial infection near the gastrointestinal and genitourinary tract in an immunocompromised patient led to the ability of S constellatus to become pathogenic and enter the bloodstream.

Case reports specific to NSTI caused by S constellatus originating from a diabetic foot ulceration are rare. Only 2 similar cases could be found in the literature.^14,15 One case involved a 66-year-old man with poorly controlled type 2 diabetes and NSTI caused by group B and group F Streptococcus originating from a wound on the right hallux.¹⁴ A limb- and life-sparing transmetatarsal amputation, in conjunction with antibiotic therapy, resulted in a positive outcome for this patient. The second case involved a 48-year-old man with a diabetic foot ulceration to the plantar right first metatarsal head that was also treated successfully with transmetatarsal amputation following serial debridement, antibiotic therapy, and adjunctive hyperbaric oxygen therapy.¹⁵ Both cases referenced share similarities with the patient in this case report. All patients had a diabetic foot ulceration complicated by NSTI due to S constellatus, which was the source of bacteremia and sepsis, and all underwent transmetatarsal amputation with successful resolution.

Presentation of NSTI—disproportionate pain, systemic inflammation, rapid local necrosis with blistering, and worsening sepsis—and treatment of local or widespread S constellatus infection remains the same for all cases of NSTI.⁷ Early diagnosis and wide, aggressive surgical debridement in conjunction with antibiotic therapy are critical.^4,5,7,9 This is particularly important in elderly and immunocompromised patients and those with bacteremia. Mortality rates reported with localized infection range from 2% to 5% and increase to 10% in those with widespread disease.^8-10 Fortunately, bacteria in the S milleri group are often sensitive to penicillin, ampicillin, ceftriaxone, vancomycin, and cefuroxime.^4-6,11,12 Variable susceptibility to tetracycline, clindamycin, and erythromycin has been reported.⁴ Prompt diagnosis of NSTI, aggressive surgical debridement, and appropriate antibiotic therapy can result in successful limb and life salvage for these patients.

The primary limitation of this study is that it is a case report that lacks long-term follow-up. The rarity of this condition makes it difficult to garner more than a single case report in a short period of time. This case study does, however, support other case reports presenting similar findings and the necessity for rapid and aggressive intervention.^4-7,11-15 Long-term follow-up was also difficult in those cases. Reasons for this are speculative but may be due to other reasons reported for loss to follow-up, including older age and the presence of comorbidities.¹⁶

Presented here is a rare case of NSTI and bacteremia secondary to S constellatus. Treatment for this limb- and life-threatening condition using the following algorithm—immediate source control with wide and aggressive surgical debridement, initial empiric broad-spectrum antibiotic therapy followed by tailored antibiotics based on deep operative cultures, and staged closure—resulted in resolution.