Corynebacterium striatum as a rare cause of septic arthritis in a native joint: A case report and review of the literature

Abstract

Septic arthritis commonly occurs due to gram-positive cocci and usually presents as acute monoarticular swelling and tenderness, often associated with systemic signs of sepsis. In rare scenarios, Corynebacterium striatum, a gram-positive bacillus, can cause septic arthritis. We present a rare case of native joint septic arthritis caused by C. striatum in an immunocompetent patient. A 74-year-old man with history of ESRD receiving HD presented with hematuria. He was found to have anemia and pyuria and was admitted for management of hematuria and UTI with ceftriaxone. Five days later, he developed new persistent fever and worsening leukocytosis, while receiving antibiotics. Examination revealed right knee swelling, erythema, and tenderness, with decreased range of motion. X-ray showed joint effusion for which he underwent right knee arthrocentesis and aspiration. Synovial fluid culture grew C. striatum, initially disregarded as a contaminant. Repeat cultures again grew C. striatum. He was treated with IV vancomycin and oral colchicine along with arthroscopic irrigation and debridement, and discharged on a 4-week course of vancomycin. C. striatum is typically a considered pathogen in immunocompromised individuals; however, emerging reports describe its role in infections among immunocompetent hosts. While C. striatum remains a rare cause of native joint septic arthritis, its isolation in multiple specimens in the appropriate clinical context should prompt clinicians to consider a true infection rather than contamination. Prompt identification and appropriate management is key to improving patient outcomes. Susceptibility testing helps guide targeted treatment for this emerging pathogen with increasing multi-drug resistance.

Background

Septic arthritis is most commonly caused by Gram-positive cocci such as Staphylococcus and Streptococcus species, and usually presents as acute monoarticular swelling and tenderness, often associated with systemic signs of sepsis [1]. Corynebacterium striatum is an emerging cause of invasive infections, generally in immunocompromised patients [2]; it is an exceedingly rare cause of septic arthritis. To our knowledge, there are only 8 previously reported cases of native joint septic arthritis to date in which C. striatum is the causative pathogen [3], [4], [5], [6], [7], [8], [9], [10]. Of these, there are only 3 instances of acute septic arthritis caused by C. striatum involving a native knee [4], [7], [8]. In this report, we present a rare and interesting case of C. striatum joint infection in an immunocompetent individual. This represents the fourth documented case of acute C. striatum septic arthritis involving a native knee joint. In addition, we provide a brief overview of septic arthritis, and review the existing literature on C. striatum septic arthritis.

Case

A 74-year-old man presented to the emergency department (ED) from his nursing home with hematuria. His medical history was notable for end-stage renal disease (ESRD) necessitating hemodialysis (HD) via a right internal jugular (IJ) venous tunneled dialysis catheter, prior HD catheter associated Klebsiella bacteremia, hypertension, dementia, and benign prostatic hyperplasia. There was no history of injection drug use, recent hospitalization, malignancy, or recent trauma.

Upon admission, he was afebrile with unremarkable vital signs. Physical exam revealed conjunctival pallor and gross hematuria. Initial laboratory diagnostics showed hemoglobin 8.9 gm/dL [reference range 12.5–16.5 gm/dL], normal white blood cell (WBC) count of 9.5 k/uL [reference range 4–10.8 k/uL], and limited urinalysis with pyuria, bacteriuria and hematuria.

He was admitted to the hospital for management of complicated urinary tract infection (UTI) and acute blood-loss anemia. Intravenous (IV) ceftriaxone was initiated, and a Foley catheter was placed. Non-contrast computed tomography (CT) of the pelvis demonstrated bladder wall thickening and clot volume of approximately 120 ml. Cystoscopy with prostatic fulguration and clot evacuation was performed; his hematuria resolved within the next 4 days, and the Foley catheter was successfully removed. Urine culture grew Klebsiella pneumoniae; he was continued on ceftriaxone.

Five days after presentation, the patient developed new persistent fever and worsening leukocytosis (up to 18.7 k/uL), while receiving antibiotics. Examination revealed right knee swelling, erythema, and tenderness, with decreased range of motion; there were no open wounds noted. The right IJ tunneled dialysis catheter site was clean, dry and without erythema or tenderness. Ferritin level was 614.5 ng/ml [reference range 28–365 ng/ml] and C-reactive protein was 281 mg/L [reference range 0–3 mg/L]. Repeat blood cultures remained negative. Contrast-enhanced abdominopelvic CT showed cystitis but was otherwise unremarkable. Right knee x-ray showed osteophyte formation with extensive degenerative changes and associated joint effusion (Fig. 1). The patient underwent right knee arthrocentesis with aspiration of turbid fluid; synovial fluid analysis showed 49,460 WBCs/mm³ with 97 % neutrophils and was positive for uric acid and calcium pyrophosphate crystals. Synovial fluid culture grew Corynebacterium striatum within 44 h, which was initially disregarded as a contaminant. Given uncertainty of septic arthritis vs crystal arthropathy, the patient was continued on ceftriaxone, and underwent a repeat right knee arthrocentesis the following day. The second synovial fluid sample was analyzed, revealing 31,850 WBCs/mm³ and re-demonstration of calcium pyrophosphate crystals. Furthermore, the second set of synovial fluid also grew C. striatum, with approximately 33 h to positivity. The two consecutive synovial fluid cultures demonstrating C. striatum growth sealed the diagnosis of septic arthritis caused by this pathogen, and the relatively short time to positivity in both samples suggested a substantial burden of infection, and may reflect a more aggressive strain. Antimicrobial susceptibility testing was performed on the second aspirate isolate, which revealed resistance to penicillin, meropenem, clindamycin, ceftriaxone, doxycycline and trimethoprim-sulfamethoxazole, and susceptibility to linezolid, vancomycin and gentamicin. By this time, the patient had completed a 7-day course of ceftriaxone for his complicated Klebsiella UTI.

Fig. 1.

Plain film radiograph of the right knee revealing osteophyte formation with extensive degenerative changes and associated joint effusion.

He was initiated on IV vancomycin and oral colchicine for the management of C. striatum septic arthritis with concomitant calcium pyrophosphate deposition disease (CPPD). Right knee arthroscopic exploration revealed extensive synovitis, diffuse arthritic changes, and degenerative medial and lateral meniscal tears. Arthroscopic irrigation with debridement, synovectomy and meniscal debridement were performed. He was continued on vancomycin with resolution of fever and leukocytosis, with eventual clinical improvement of the right knee. He was discharged to subacute rehabilitation in stable condition and continued on a 4-week course of vancomycin. He was seen by orthopedics two weeks after discharge and was noted to be improving as expected. He had an unrelated brief hospitalization seven months later at which time he did not have any septic complications.

Discussion and review of the literature

Corynebacterium striatum is a non-diphtheritic, facultative anaerobic, Gram-positive bacillus, which is a commensal of humans as part of the normal flora of the skin and oropharynx [2]. It is often regarded as a contaminant when isolated in clinical specimens, but has been known to cause invasive infections such as infective endocarditis (IE), central-line associated bacteremia, and pneumonia [11], particularly in immunocompromised individuals. In recent decades, C. striatum has been noted to be an emerging opportunistic nosocomial pathogen, often resistant to several antibiotics including quinolones and penicillin, but usually susceptible to vancomycin, linezolid and daptomycin [12], [13]. IE is the most common manifestation of C. striatum infection [9]. C. striatum has also been implicated in prosthetic joint infections [13], [14], but is an infrequent cause of septic arthritis in native joints.

Bacterial septic arthritis most commonly occurs via hematogenous seeding of the synovial membrane; other mechanisms include direct inoculation of bacteria into the joint space, and local spread [15]. Bacteria settle in the synovial tissue which lacks a restricting basement membrane, allowing easy spread into the synovial fluid which triggers a purulent joint [16]. The mechanism by which our patient developed C. striatum septic arthritis is unclear. A possibility includes daily blood draws from his indwelling HD line leading to transient C. striatum bacteremia. This could have resulted in hematogenous seeding of the patient’s right knee synovium.

Risk factors for septic arthritis include advanced age, preexisting joint disease, recent bacteremia, immunosuppression, diabetes, malignancy, cirrhosis, renal disease, injection drug use, intraarticular corticosteroids, recent injury or surgical procedure, and prosthetic joint [17], [18]. Our patient’s right knee radiograph and arthroscopic findings indicated severe degenerative changes consistent with osteoarthritis. This, likely in conjunction with concomitant CPPD, predisposed him to develop septic arthritis, possibly in the setting of transient bacteremia. Additionally, ESRD is another risk factor. The diagnosis of septic arthritis is established definitively with a positive synovial fluid Gram-stain or culture [16], as in our case. Synovial fluid with > 50,000 WBCs/mm³, most of which are neutrophils, indicates a diagnosis of septic arthritis. The likelihood of septic arthritis increases with increasing synovial fluid WBC count, and when the percentage of neutrophils is > 90 % [16]. Treatment involves needle, arthroscopic or open joint drainage, and intravenous antibiotics. Considering that C. striatum appears to be a multi-drug resistant pathogen, antibiotic susceptibility testing is a key tool in guiding management of invasive infections. Diagnosing true C. striatum septic arthritis is challenging due to its frequent classification as a contaminant. In our case, isolation from two separate joint aspirates supports its clinical significance. While susceptibility testing was performed on only one isolate, the clinical context of the repeat isolation from a sterile site in a symptomatic patient suggests that both cultures represent the same strain and a true infection. Ideally, susceptibility testing should be performed on both isolates.

A literature search using PubMed revealed 7 reported cases of acute C. striatum septic arthritis from 1998 to 2023 [3], [4], [6], [7], [8], [9], [10], most of which were related to trauma or degenerative joint disease. A summary of these cases is presented in Table 1. There are only 3 previously described cases of acute C. striatum septic arthritis in a native knee joint [4], [7], [8]. In 2006, Scholle et al. described a case of native knee C. striatum septic arthritis following a fall in a patient with osteoarthritis and recent arthrocentesis 20 days prior to presentation, which was treated with arthroscopic irrigation and vancomycin [8]. Similar to the aforementioned case, Westblade et al. presented a case in 2014 of C. striatum septic arthritis of the knee in a patient who had sustained a fall and had arthrocentesis 4 days prior; treatment with arthroscopic knee irrigation and 4 weeks of vancomycin successfully cleared the infection [7]. In 2018, Molina Collada et al. reported a case of acute C. striatum septic arthritis of the knee, in an 84-year-old man with a history of left nephrectomy, who had existing CPPD and had undergone arthrocentesis 5 months prior; he was managed with surgical knee lavage and antibiotics. Vancomycin was not trialed due to the patient only having one kidney. Initial treatment with linezolid first, and then teicoplanin were unsuccessful. Finally, a single dose of dalbavancin cleared the infection [4].

Table 1.

Summary of published cases of C. striatum septic arthritis.

Authors of Report	Year of publication	Affected joint	Chronicity	Age (years)/Sex	Risk factors	Treatment	Outcome
Cone et al [10].	1998	Elbow	Acute	51/M	Injury*** of affected extremity	I&D; vancomycin, then ciprofloxacin (total 4-week course)	Resolution
Boltin et al [9].	2008	Shoulder	Acute	80/F	Age, immunosuppression	Vancomycin	Septic complications, Death
Feced Olmos et al [6].	2013	Shoulder	Acute	59/F	Intra-articular steroids	Ceftriaxone × 1 month	Resolution
Roy et al [3].	2016	Shoulder	Acute	77/M	Age, immunosuppression, age, ESRD on HD	Arthroscopic debridement; vancomycin × 4 weeks	Resolution
Scholle et al [8].	2006	Knee	Acute	87/M	Age, recent fall, osteoarthritis, recent arthrocentesis	Arthroscopic irrigation; vancomycin × 2 weeks	Resolution
Westblade et al [7].	2014	Knee	Acute	84/M	Age, diabetes, recent fall, recent arthrocentesis	Arthroscopic irrigation; vancomycin × 4 weeks	Resolution
Molina Collada et al [4].	2018	Knee	Acute	84/M	Age, CPPD, recent arthrocentesis	Surgical washout; single dose of dalbavancin	Resolution
Hollnagel et al [5].	2020	Knee	Chronic	78/M	Age, diabetes, history of malignancy, intra-articular steroids	Surgical irrigation and debridement; IV daptomycin × 6 weeks	Resolution

^***Scalpel laceration; I&D - incision and drainage; ESRD - end stage renal disease; HD - hemodialysis; CPPD - calcium pyrophosphate deposition disease; IV - intravenous.

We encountered one case report of chronic C. striatum septic arthritis of the knee [5]. In 2020, Hollnagel et al. detailed a case of chronic C. striatum septic arthritis of the knee in a patient who had knee pain for 3 years, and intraarticular steroid injection 2 months prior to presentation. There was no history of prolonged hospitalization, knee trauma or instrumentation; they proposed that the patient’s diabetes and history of prostate cancer likely placed him in an overall immunocompromised state. The patient underwent a successful treatment regimen consisting of open irrigation and debridement, complete synovectomy, and a six-week course of intravenous daptomycin [5].

Several common themes can be identified in the cases described in Table 1, and in our patient. In addition to immunosuppression and advanced age, some of the cases identify trauma, intra-articular steroids and recent arthrocentesis as risk factors for C. striatum septic arthritis. It is worth noting that in the case described by Boltin et al., the patient does not seem to have undergone joint drainage in conjunction with antibiotics; the patient ultimately developed worsening septic complications and passed away [9]. Although our sample size is small, we can extrapolate that since patients survived in all other cases with reasonable response, procedural joint drainage is a crucial part of managing C. striatum septic arthritis. Given that C. striatum has demonstrated multi-drug resistance (as seen in our case, with the organism demonstrating susceptibility only to vancomycin, linezolid and gentamicin), most prior cases were treated with vancomycin, with one case presenting the use of a novel antibiotic such as dalbavancin with success. In some cases, alternative antibiotics were used due to allergy, intolerance, or side-effects. Vancomycin has been typically used for C. striatum bone and joint infections [2], [14]. A French case series and literature review included 11 patients & 12 infections, and reported successful use of amoxicillin in combination with rifampin for C. striatum bone and joint infections including septic arthritis of native joints, prosthetic joint infections and osteomyelitis [14]. It is worth noting that this study used breakpoints provided by the European Committee for Antimicrobial Susceptibility Testing (EUCAST), whereas the Clinical and Laboratory Standards Institute (CLSI) does not currently provide interpretive criteria for the MIC of amoxicillin for C. striatum. Most laboratories in the United States extrapolate from penicillin susceptibility. A recent study from the Mayo Clinic analyzing 1925 Corynebacterium isolates (over 680 of which were C. striatum) found that penicillin susceptibility declined over time from 47.5 % to 20.6 % as of 2023; notably linezolid and vancomycin remained universally effective [19]. Another systematic review of antibiotic susceptibilities concluded that C. striatum was always susceptible to vancomycin, with linezolid, teicoplanin and daptomycin being reasonable alternatives in severe infections; mild infections may be treated with amoxicillin-clavulanate if susceptibility testing aligns [2]. There is concern for emerging resistance of C. striatum to daptomycin [14]. These findings emphasize the importance of antimicrobial susceptibility testing for C. striatum when isolated in 2 or more synovial fluid samples, with testing expanded to include common oral antibiotics such as amoxicillin when possible.

Conclusion

C. striatum is an emerging cause of invasive infections in immunocompromised patients, with increasing reports of pathogenicity in immunocompetent individuals as well. It has been reported to cause prosthetic joint infections, and is a rare cause of native joint septic arthritis. Risk factors for C. striatum septic arthritis include immunosuppression, arthrocentesis, intra-articular steroids, renal disease, and existing degenerative joint disease. Treatment should always include joint drainage. C. striatum appears to possess multi-drug resistance, and most prior cases of bone and joint infections with this pathogen have described success with the use of vancomycin in addition to procedural intervention. There have been reports of successful treatment of C. striatum septic arthritis with vancomycin, ceftriaxone, daptomycin and dalbavancin. Recent systematic reviews have revealed some susceptibility to amoxicillin, which could be a viable treatment option in mild infections. Given the rarity of C. striatum septic arthritis, standardized treatment guidelines are lacking. Further research is warranted on the best antimicrobial management strategies for C. striatum bone and joint infections including native joint septic arthritis. In the interim, routine use of antibiotic susceptibility testing for C. striatum when there is reasonable suspicion for pathogenicity could prove to be useful to help guide targeted treatment for this emerging pathogen with increasing multi-drug resistance.

CRediT authorship contribution statement

Kaushik Kumar: Writing – review & editing. Sakthi Gautham: Writing – review & editing, Writing – original draft. Shiavax J. Rao: Writing – review & editing, Supervision.

Ethical approval

N/A.

Consent Statement

Written informed consent was obtained from the patient/next of kin for publication of this case report and accompanying images.

Funding Statement

No funding was received for this research.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.