Actinomyces turicensis Necrotizing Soft-Tissue Infection of the Thigh in a Diabetic Male

Case Report

A 45-year-old obese Hispanic male with no significant medical history presented to the emergency department with nausea, vomiting, and subjective fever. Bedside glucometry revealed a blood glucose concentration of 518 mg/dL with subsequent urinalysis demonstrating 2⁺ ketones, supporting a diagnosis of diabetic ketoacidosis. At the time of admission, the patient had a fever of 101.6^○F, tachycardia, and tachypnea. Initial laboratory data showed a white blood cell (WBC) count of 20,380 cells/mcL (81.6% neutrophils), an anion gap of 18, and a beta-hydroxybutyrate concentration of >46 mg/dL. After 14 hours of insulin and fluid resuscitation, the anion gap was closed, and the patient was no longer in diabetic ketoacidosis; however, he remained febrile with a high WBC count (17,690 cells/mcL). In addition, the patient had an elevated procalcitonin concentration (2.45 ng/mL). Twenty-four hours after admission, the patient complained of significant pain in his right medial thigh. On physical examination, there was a clear 15 × 19 cm region of erythema, induration, and significant tenderness to palpation. A CT scan demonstrated stranding and reticulation of the soft tissue. Numerous foci of air were present, compatible with a gas-producing infection or necrotizing fasciitis. The patient received vigorous fluid resuscitation and intravenous antimicrobial drugs (vancomycin and piperacillin/tazobactam). He was soon taken to the operating room for excision and debridement of the infected area.

The initial excisional debridement and irrigation of the site demonstrated brown and nonviable fascia overlying the adductor longus with sparing of the muscle beneath. The incision produced dishwater-colored fluid that was sent for culture and sensitivity testing. From inserting a hand into the incision, it became evident that the infection had spread along the fascial plane, as minimal pressure separated the fascial layers. The subcutaneous tissue was noted to be infected; therefore, the incision was carried proximally until healthy tissue was reached. A large skin flap, roughly 10 × 5 cm, was harvested because of the frank necrosis of the tissue beneath. The great saphenous vein was directly involved and so was excised. On the subsequent day, the site was re-examined and irrigated. In addition, vacuum therapy was placed over the site with subsequent treatment with vacuum changes. Forty-eight hours post-operatively, the patient was afebrile, with stable vital signs and a normal WBC count. Intra-operative fluid cultures grew 3⁺ Actinomyces turicensis and 2⁺ unidentified anaerobic gram-negative bacilli.

Discussion

We describe a case of a rare microbial cause of NSTI. The patient presented with an illness characterized by rapid clinical progression requiring aggressive medical and surgical intervention. The onset of illness was characterized by localized pain out of proportion to the appearance of the site, with erythema and induration. Interestingly, the infection presented in a patient with newly diagnosed diabetes mellitus in the setting of ketoacidosis. The following discussion will involve (1) a review of prior Actinomyces spp. infections, (2) microbiological identification, and (3) management of NSTIs.

From a review of the literature, it is apparent that NSTIs resulting from Actinomyces spp. are infrequently reported. The most common sites of these infections are cervicofacial (50%), abdominal (20%), and thoracic (15%) [5]. We identified only 31 cases of primary NSTIs of the abdominal wall caused by Actinomyces spp., and only one of these implicated Actinomyces turicensis. Most of these reports originated from Asia, and the infections were managed primarily by surgery [6]. A seven-year review of infections caused by Actinomyces spp. demonstrated 116 clinical presentations by Actinomyces turicensis of which 38 were skin related; none of these infections was necrotizing [7]. The most significant presentation of Actinomyces appears to be abscess formation. These skin abscesses have been noted particularly in breast tissue, although deep organ-space abscesses (hepatic, pulmonary, and pelvic) also have been described. [8]. Our research found no reports of Actinomyces turicensis causing NSTIs of the medial thigh. Most notably, the infection occurred in the absence of antecedent trauma, offering no clear mechanism of inoculation. In cases without a defined portal of entry, the proposed mechanism of infection stems from transient bacteremia secondary to immunocompromised status secondary to diabetic ketoacidosis. Historically, these cases usually are caused by group A streptococci arising from asymptomatic pharyngeal carriage [2]. Actinomyces can be normal oral flora in patients with poor dentition or prior oral trauma/surgery. The current presentation of an Actinomyces NSTI is novel, as the aforementioned portals of entry were not identified in this patient.

Confirmation of Actinomyces requires collection from a sterile, preferably surgical, site. Successful isolation and identification of these bacteria occur in only a small fraction of cases; a high failure rate of culturing exists because of prior empiric antibiotic coverage, inhibition of Actinomyces growth secondary to polymicrobial infection, inadequate culture conditions, or insufficient short-term incubation [9]. In this case, we utilized matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify Actinomyces in the operative fluid culture. This modality provides a more rapid identification than is possible with traditional automated identification platforms. A more thorough discussion of the microbiological diagnosis can be found in reference 10. The MALDI-TOF technique is a promising method of identification, with success occurring 92%–97% of the time [11,12]. Other presentations where Actinomyces spp. represent a more common underlying pathogen, for example, mandibular osteomyelitis, have utilized MALDI-TOF for identification of the organism [13]. Actinomyces spp. often are isolated in polymicrobial infections where they are a commensal organism, clouding the clinical relevance of their isolation, especially via sensitive modalities (e.g., MALDI-TOF). However, a recent study determined Actinomyces spp. to be a clinically relevant isolate from wound cultures [14].

The management of Actinomyces spp.-based NSTIs is similar to that for infections caused by other pathogens and consists of empiric antibiotics, hemodynamic support, and early surgical debridement. Historically, antibiotic therapy in the absence of debridement has been associated with a mortality rate approaching 100% [15]. Intuitively, the time to surgical intervention correlates with death. McHenry et al. demonstrated that the average time to operation in nonsurvivors was 90 hours vs. 25 hours in survivors [16]. Further studies have demonstrated significant improvements in the mortality rate in patients receiving surgical care within six hours of presentation [17,18]. With the strength of evidence in support of early surgical intervention, clinicians must maintain high suspicion for NSTI. In this case, the presentation of the NSTI was unrecognized during the first 24 hours of the hospital stay with subsequent rapid clinical deterioration. Clearly, clinical suspicion should prompt surgical evaluation. Similarly, debridement should be started at the facility where the diagnosis was suspected, and patient optimization should include timely surgery.

Actinomyces spp. still are a penicillin-sensitive group of organisms. In contrast, variable patterns of resistance to metronidazole and clindamycin exist [19,20]. Penicillin G or amoxicillin is considered the drug of choice. In this case, standard empiric coverage for the NSTI included vancomycin and piperacillin/tazobactam, which resulted in rapid clinical improvement after surgical intervention.

Conclusion

We describe a rare case of NSTI caused by Actinomyces turicensis. Surgical intervention and antimicrobial therapy treated the infection effectively. The case illustrates the value of enhanced pathogen identification via rapid diagnostics (i.e., MALDI-TOF) supporting a future role in aiding early identification and guiding treatment of underlying pathogens, including rare organisms. This case points out that, although infections are rare, Actinomyces spp. may be pathogens and should not always be disregarded as contaminants.