Complex trauma sequelae: Mycobacterium goodii and Priestia endophytica Hardware infection in a patient with Ehlers-Danlos syndrome

Abstract

A 26-year-old man with Ehlers-Danlos syndrome, recurrent otitis externa, and chronic otitis media sustained a left lower extremity amputation and open femur fracture with internal hardware fixation after a motor vehicle collision in Arizona. He presented to the emergency department at our institution with severe left leg pain and purulent discharge despite receiving two unidentified antibiotics upon discharge. Evaluations revealed an abscess and malunion of the femur. Initial cultures yielded scant Priestia endophytica, leading to daptomycin treatment. His condition worsened until Gram-positive bacilli identified as Mycobacterium goodii, a rare nosocomial mycobacterial species, were found. Significant improvement occurred with appropriate antibiotics. This case highlights the challenges in diagnosing and managing M. goodii infections in immunocompromised patients with orthopedic complications and notes P. endophytica as a previously unreported, possibly opportunistic human pathogen.

Introduction

Ehlers-Danlos Syndrome (EDS) comprises a group of inherited connective tissue disorders characterized by varying degrees of skin hyperextensibility, joint hypermobility, and tissue fragility [1]. These disorders result from defects in the structure, production, or processing of collagen or related proteins, which are essential components of connective tissue [2]. EDS may increase the risk of infections and allergic disorders and is potentially associated with immune deficiencies [3]. The convergence of EDS, innate immunity dysfunction, and the aftermath of a motor vehicle collision leading to below-the-knee amputation (BKA) and hardware fixation presents a distinctive clinical challenge. Here, we present a case that delineates the intricate management complexities inherent in such a multifaceted presentation, specifically focusing on the emergence of Mycobacterium goodii and Priestia endophytica infections, the latter being an organism not previously identified as a human pathogen.

Case presentation

A 26-year-old man with EDS presented after a motor vehicle collision in Arizona resulting in significant trauma and soil-contaminated wounds to his left lower extremity and underwent BKA and femoral intramedullary nail placement. After a three-week hospitalization, he was discharged with two unspecified antibiotics.

Approximately one week after discharge, the patient presented to the emergency department at our institution with severe left leg pain and purulent drainage from an anterior thigh surgical incision (Fig. 1A; Table 1). He was hospitalized and underwent surgical debridement after a two-week delay due to unexpected circumstances. The area of debridement measured approximately 44 cm × 15 cm × 2 cm with extensive purulence. Notably, antibiotics were not administered prior to this surgical intervention.

Fig. 1

(A) Wound at the admission. (B) 5^th debridement. (C) Pos-operative wound dehiscence. (D) Two weeks after wound dehiscence and antibiotic switch

Table 1 Blood test results at the time of admission

Intraoperative tissue cultures collected during surgical debridement yielded grey-white, gamma-hemolytic colonies with a ground glass appearance, accompanied by long Gram-positive bacilli on Gram stain (Fig. 1). Initially, Bacillus anthracis was considered and was excluded by molecular testing conducted by the Houston Health Department. Thereafter, our laboratory performed further analysis using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) (Bruker, Billerica MA) and sequencing of the 16S rDNA gene on both isolates from two tissue cultures collected from the first debridement and before initiation of antibiotics, which identified the organism as Priestia endophytica (NCBI GenBank accession # PP533212, 1459 base pairs, 100% query coverage, and 100% identity with OP437686), previously known as Bacillus endophyticus [4].

Post-operatively, the patient received vancomycin and later daptomycin due to suboptimal vancomycin levels. As P. endophytica was the only organism isolated from tissue samples from his first debridement, daptomycin was continued and later transitioned to doxycycline based on susceptibility testing (Table 2) and extrapolation of the efficacy of doxycycline from Bacillus species. Subsequent surgical interventions involved incision and drainage procedures every 2–4 days for approximately 3 weeks, culminating in a bone graft placement and permanent intramedullary nail placement (Fig. 1B). The post-operative course was complicated by wound dehiscence (Fig. 1C).

During hospitalization, aerobic, anaerobic, fungal, and acid-fast bacilli (AFB) cultures were collected as a standard-of-care protocol on the first, fourth, and eleventh debridement. Including the first debridement, all AFB cultures eventually were identified as Mycobacterium goodii. P. endophytica was not isolated again after initial debridement and targeted antibiotic therapy.

Empiric trimethoprim/sulfamethoxazole (TMP/SMX) was initiated for the treatment of M. goodii, as it is typically susceptible to SMX. Doxycycline was continued for P. endophytica, and as a second agent for empiric treatment of M. goodii. Remarkably, the patient’s wound began to heal promptly upon initiating combination antimicrobial therapy (Fig. 1D). The susceptibility profile obtained from ARUP Laboratories (Salt Lake City, UT) (Table 2) confirmed that this isolate of M. goodii was susceptible to both TMP/SMX and doxycycline. Therefore, this targeted antibiotic regimen was continued throughout the rest of his hospitalization and on discharge. The patient recovered well without any complications at the 3-month follow-up, with a plan to continue treatment for 6–12 months depending on clinical progress. As there are no clinical practice guidelines to direct the specific treatment of M. goodii infections, we chose a prolonged duration based on clinical experience, extrapolating evidence from recommendations for tissue and skeletal infections caused by related nontuberculous mycobacteria (NTM) [5].

Table 2 Antimicrobial susceptibility for Priestia Endophytica and Mycobacterium goodii

Throughout his hospitalization, the patient’s known history of EDS, poorly healing wounds, and frequent need for debridement of infected tissues prompted the investigation into possible immune dysfunction. Laboratory findings (Table 3) were remarkable for diminished percent and absolute natural killer (NK) cells (CD16 + and CD56+), suggestive of innate cell-mediated immune system dysfunction. Further immunologic investigations are ongoing to determine the significance of this lymphocytopenia and its potential contribution to the infection.

Table 3 T and B natural killer cells panel results

Discussion

P. endophytica was recovered from the hardware infection, along with M. goodii in this patient. P. endophytica, a Gram-positive, rod-shaped, spore-forming bacterium in the family Bacillaceae [4], was previously known as Bacillus endophyticus (https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=135735). Originally isolated from plant tissue, particularly cotton, P. endophytica has been explored for its potential role in enhancing crop productivity [6, 7]. It is characterized as an endophytic bacterium that colonizes the internal tissues of plants without causing disease [8]. The identification of P. endophytica as a pathogen in human infections is unprecedented [9].

Macroscopically and microscopically, P. endophytica closely resembles Bacillus anthracis, the causative agent of anthrax, posing challenges in differentiation. On Sheep Blood agar (SBA), P. endophytica colonies exhibited a white or grey-white, non-hemolytic appearance with irregular edges and a ground-glass appearance. Additionally, comma-shaped projections from the colony edge produced “Medusa-head” colonies (Fig. 2A). Gram staining (Fig. 2B) revealed endospore-forming, box-shaped rods of P. endophytica arranged in short to long chains. Lekota et al. [10], through whole-genome shotgun sequencing, demonstrated the absence of B. anthracis-related plasmids or virulence genes in P. endophytica genomes. Due to the similarity between P. endophytica and B. anthracis and the latter’s classification as a biosafety level 3 (BSL-3) agent, molecular methods are typically utilized to rule out B. anthracis before further identification using MALDI-TOF MS or other manipulations in a clinical sentinel laboratory.

Fig. 2

(A) Isolate of Priestia endophytica on Sheep Blood agar. (B) Gram-stain of Priestia endophytica (1000×)

In our case, while the possibility of environmental contamination cannot be completely ruled out, the isolation of P. endophytica from intraoperative cultures, particularly in two out of three initial surgical tissue samples collected before antibiotic administration, along with the clinical presentation strongly suggests its involvement in the infection. However, it is also possible that an additional pathogen, undetected by culture, contributed to the infection and responded to the antibiotics administered. Ideally, 16S rRNA amplification and sequencing should have been performed on the original samples to confirm the absence of other contributing pathogens, which is a limitation of this study. Despite this, our report represents the first documented instance of P. endophytica  potentially causing infection in humans.

M. goodii was the second uncommon organism isolated from our patient, contributing to the complexity of the infection. M. goodii is characterized as a rapid grower, acid-fast mycobacterium, forming smooth to mucoid, off-white to cream-colored colonies. These colonies may be nonpigmented or late pigmented [11]. It is quite ubiquitous in the environment and can be found in soil, dust, and drinking water [5, 12]. As a pathogen, M. goodii has been primarily associated with posttraumatic wound infections, particularly those following open fractures and associated osteomyelitis [11, 13]. Additionally, reports indicate its involvement in infections associated with surgical implants over the past two decades [14,15,16]. Our case adds to this body of evidence, representing another instance of M. goodii infection following traumatic injury with wound contamination, and subsequent implantation of a foreign body. M. goodii typically displays susceptibility to amikacin, ethambutol, and sulfamethoxazole [11]. It exhibits intermediate susceptibility to ciprofloxacin, doxycycline, and tobramycin, with variable susceptibility to cefmetazole, cefoxitin, and clarithromycin. However, it is resistant to isoniazid and rifampin [11]. This susceptibility profile is not consistent with empiric therapy with clarithromycin and rifampin, commonly used for other rapidly growing NTM. Given the potential for treatment failure associated with monotherapy regimens utilizing TMP/SMX or doxycycline [15], a combination of TMP/SMX and doxycycline was administered to our patient to minimize the risk of recurrence or development of resistance.

Notably, our patient has EDS, a group of inherited disorders that affect the connective tissues in the body, primarily the skin, joints, and blood vessel walls (https://rarediseases.org/rare-diseases/ehlers-danlos-syndrome/). EDS encompasses several subtypes, each linked to mutations in different genes involved in collagen or other connective tissue component production [17]. However, the specific gene mutation underlying our patient’s condition is unknown. Nevertheless, individuals with EDS may present compromised immune function as demonstrated in our patient on his lower natural killer cell count or other underlying health conditions that could predispose them to infections [18]. Therefore, it was not unexpected to encounter uncommon pathogens like M. goodii as the causative agent of severe necrosis and purulence at the surgical site. Additionally, it is plausible for a bacterium typically associated with plants to play a role in this patient’s infection. It is also worth mentioning that the Food and Drug Administration (FDA) recommends avoiding fluoroquinolone antibiotics if a patient has EDS because of an association of this class of medication with the occurrence of aneurysm. This individualized approach emphasizes the importance of considering the specific characteristics of M. goodii infections, the patient’s underlying conditions, and adapting treatment strategies accordingly.

Given the patient’s immunodeficiency, careful consideration was given to its potential impact on treatment response and the risk of recurrent infections. Recognizing the influence of underlying health conditions, such as EDS, is essential in devising appropriate treatment strategies and managing complications effectively. Further investigation into the genetic basis of the patient’s EDS subtype may provide valuable insights into their susceptibility to infections and guide future treatment approaches if necessary.

Conclusion

This case report underscores the identification of two infrequently encountered microbes, P. endophytica and M. goodii, as the potential culprits behind post-trauma hardware infection and abscess in a patient with EDS. Infections caused by M. goodii, although rare, can complicate traumatic orthopedic injuries, especially in patients with EDS and immune dysfunction. Successful management in this case required timely diagnosis, susceptibility-guided antibiotic therapy, and surgical intervention. The case emphasizes the importance of considering atypical pathogens in complex clinical scenarios and tailoring therapeutic strategies accordingly. Furthermore, the use of modern diagnostic tools facilitates the recognition of previously unrecognized pathogens, highlighting the potential emergence of new infectious organisms. This report contributes to our understanding of managing challenging infections and emphasizes the need for continued vigilance and research in infectious diseases.