Septic Arthritis Due to Cellulosimicrobium cellulans

Abstract

Cellulosimicrobium cellulans has been reported as a rare cause of human pathogenesis. Infections mainly occur in immunocompromised patients and very often are associated with a foreign body. We report the first case of septic arthritis caused by C. cellulans in an immunocompetent patient. Our patient suffered a penetrating palm tree thorn injury to his left knee 8 weeks before admission. Although no foreign objects were found, they were suspected because previous reports suggest a frequent association with this microorganism, and open debridament was performed. Removal of foreign bodies related to this organism must be considered a high-priority treatment in these patients to achieve a complete recovery.

CASE REPORT

An 81-year-old man was admitted to our department with a 6-day history of pain, loss of motion, erythema, and swelling in his left knee. His past medical history was significant for gout, mild mitral regurgitation, hypertension, and moderate chronic renal insufficiency, and 8 weeks previously he had been admitted to our department with septic arthritis of the same knee caused by Pantoea agglomerans after suffering a penetrating injury to his left knee with a palm tree thorn, with good response to treatment with intravenous ceftriaxone (1 g per day for 15 days) and levofloxacin (250 mg per day for 15 days).

Physical examination showed an afebrile patient with a painful, warm, swollen, and tender left knee. Limitation of active and passive range of motion were also noted. Otherwise, the examination was unremarkable. Laboratory tests showed an elevated serum C-reactive protein (CRP) level (17 mg/dl; normal, <0.5) with a normal blood cell count. Arthrocentesis yielded 30 ml of yellowish fluid. Direct microscopic examination of the synovial fluid revealed many leukocytes, and crystal analysis with compensated polarized light was negative. Gram stain was negative, and empirical treatment with levofloxacin was started intravenously (500-mg initial dose and then 250 mg every 24 h, with creatinine clearance of 40 ml/min because of renal failure,). Three days after admission, a Gram-positive rod grew in synovial cultures and was subsequently identified as Cellulosimicrobium cellulans. Identification was initially made by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) (Bruker Daltonics) and later confirmed by a semiautomatic culture system (Vitek-II). The microorganism recovered was fully susceptible to vancomycin (MIC, 1 μg/ml) and linezolid (MIC, 1 μg/ml) and showed intermediate susceptibility to tetracyclines (MIC, 4 μg/ml) and levofloxacin (MIC, 3 μg/ml). The isolate was interpreted as a contaminant, so we continued therapy with levofloxacin.

Three days later, due to the persistence of symptoms, the high levels of CRP (23.49 mg/dl), and a high erythrocyte sedimentation rate (ESR) (99 mm/h; normal, <13 mm/h), a new arthrocentesis was performed, and C. cellulans was again isolated. Linezolid was added based on the lack of response to treatment and suspicion of antibiotic-resistant Gram-positive coccal infection as a causative agent, especially methicillin-resistant Staphylococcus aureus (MRSA). However, the arthritis symptoms worsened, and a new joint fluid aspiration was performed 7 days after admission, showing this organism in the synovial cultures. The susceptibility pattern was unchanged with respect to the first pattern isolated. A 16S rRNA sequencing was carried out, which confirmed the pathogen as C. cellulans (GenBank accession no. JN695266). A new laboratory evaluation showed persistence of raised CRP levels (22.51 mg/dl) and high d-dimer levels (4.55 mg/liter; normal, <0.5 mg/liter).

A color Doppler ultrasound of the left leg was negative, and magnetic resonance imaging of the left knee showed a 20- by 1.7- by 3.2-cm abscess along the inner portion of the lower thigh, located from the outer surface of the gracilis muscle to the internal lateral ligament and articular capsule of the knee, and another abscess posterior to the superior tibio-fibular joint 18 mm in diameter, bone erosions, a Baker′s cyst, and synovitis (Fig. 1). An ultrasound examination confirmed the presence of both abscesses, but foreign bodies were not found. Treatment with levofloxacin was stopped, and we added oral rifampin to the linezolid regimen. The patient subsequently underwent surgery with debridement and drainage of the abscesses.

Fig. 1.

Magnetic resonance imaging of the left knee. (a) Axial T2-weighted fat-suppressed image shows a 20- by 1.7- by 3.2-cm abscess along the inner portion of the lower thigh (narrow arrow), bone erosions, and synovitis. (b) A coronal T1-weighted image shows the same abscess (narrow arrow) and another abscess posterior to the superior tibio-fibular joint, which is 18 mm in diameter (large arrow).

After surgery, we saw an important reduction of CRP (from 22.51 mg/dl to 3.15 mg/dl) and ESR levels (from 99 mm/h to 21 mm/h) and improvement of arthritis symptoms and general condition, and the patient was discharged to complete a 6-week antibiotic regimen with rifampin and linezolid. At the follow-up visits 3 and 6 months later, our patient was symptom free, and the acute-phase reactants were negative.

Septic arthritis is defined as a joint infection caused by pathogenic inoculation of the joint either directly or more commonly by hematogenous spread (11). Plant thorn penetration after injury and the presence of the remaining part of the thorn as a foreign body have been described as a rare cause of microorganism inoculation and, subsequently, septic arthritis (3). In these cases Pantoea agglomerans, a Gram-negative bacterium, is the microorganism most frequently isolated from synovial fluid specimens and blood cultures (3, 20). Other bacteria, such as Serratia fonticola, have been also associated with this mechanism of infection (6).

We report the first case described of septic arthritis caused by Cellulosimicrobium cellulans (equivalent name, Oerskovia xanthineolytica) in an immunocompetent patient after a palm tree thorn injury.

The genus Cellulosimicrobium is composed of three species, namely, C. cellulans, C. funkei, and C. terreum. Cellulosimicrobium species are non-acid-fast, catalase-positive, Gram-positive bacilli. This genus belongs to the suborder Micrococcineae, order Actinomycetales, and class Actinobacteria (1, 16, 17, 24).

C. cellulans is an uncommon human pathogen that has been rarely associated with human infection. The organism inhabits soil, grass cuttings, water, decaying plant material, and brewery sewage (1, 24). It has mostly been reported in immunocompromised hosts and associated with the presence of foreign bodies, including plant thorns (19). Isolation of this organism from sterile fluids as synovial fluid should be interpreted with caution.

There have been 27 case reports published so far describing infection due to Cellulosimicrobium, including bacteremia, peritonitis, meningitis, endocarditis, gangrenous colecistitis, keratitis, pyonephrosis, soft tissue infection, and association with bone marrow transplantation (4, 5, 13, 16). Prosthetic joint infection and pyogenic flexor tenosynovitis, both foreign-body-associated infections, have also been reported (13, 16), but a case of septic arthritis due this microorganisms has never been described. In most of the cases already reported involving C. cellulans (14 of 21 cases), infection was secondary to a medical device, and removal of the device was required for resolution of the infection in the majority of them (4, 7, 9, 10, 14, 16, 18, 19, 21). In the other two cases, infection was related to an invasive procedure, such as cholangio-pancreatic endoscopy and steroid injections (16). Our patient reported that 8 weeks prior to admission, he had been injured by a palm tree thorn on the medial side of his left knee. The patient was then also admitted to our department for further investigation, and P. agglomerans was isolated in synovial fluid, with a complete resolution after 2 weeks of successful antibiotic therapy. The possible presence of a foreign body seems to be related to the first episode of arthritis after the palm tree thorn injury. We believe that C. cellulans might have been present since the moment of the injury but the relatively nonvirulent and smoldering course of this pathogen (7, 13) and the use of levofloxacin to treat the P. agglomerans infection could have delayed the presence of symptoms for 8 weeks after pathogen inoculation. Involvement of direct intra-articular inoculation during arthrocentesis after careful aseptic treatment and any source other than a foreign body were considered highly unlikely.

Although antibiotic susceptibility testing demonstrated intermediate susceptibility to levofloxacin, because of the high penetration of levofloxacin in joint fluid exceeding serum levels, we believe the inadequate response to therapy was due to biofilm formation of foreign-body-associated infection (15, 22). However, we cannot rule out that persistence of the clinical picture was secondary to a delay in the initiation of appropriate therapy. In addition to susceptibility pattern, the absence of previous reports of arthritis caused by this microorganism prompted us to consider C. cellulans as a contaminant and that the pathogen responsible for the infection was P. agglomerans.

Two cases of C. cellulans infection of previously healthy patients have been reported (2, 19); however, C. cellulans has been described as an opportunistic pathogen in humans and as a cause of infection in immunocompromised patients in the context of HIV infection, tumor-induced immunosuppression, and posttransplant patients (4, 8, 19).

Furthermore, several patients presented with end-stage renal disease as the most frequent underlying condition (14). Our patient was not immunocompromised, but he related a history of moderate chronic renal insufficiency.

C. cellulans has been reported as resistant to erythromycin and other macrolides (7, 18) but is considered susceptible to vancomycin in vitro, which is the therapy of choice in most of the cases reported. However, removal or early debridement has been indispensable in most of the cases when infection was related to a foreign body (7, 10). In 9 of the 14 cases related to foreign bodies, monotherapy or a prolonged course of combined antibiotic therapy was not enough to eradicate the pathogen completely (16), and patients only improved after the foreign body had been removed. This lack of antibiotic efficacy has been associated with inadequate penetrance of the infected area, which inhibits but not does not eradicate the microorganism (4, 12).

In our case, although no foreign objects were found, they were highly suspected as this microorganism has often been associated with foreign-body-associated infection and resolution was not achieved until debridement and drainage of the abscess were performed. Association of prolonged course of combined antibiotic therapy with linezolid and rifampin was needed for a complete resolution of the infection, after the patient was showing no improvement with levofloxacin and linezolid after antibiotic susceptibility testing. The association of rifampin to other antibiotic has been described in three cases with good response (10, 16, 23).

To our knowledge, our patient represents the first documented case of septic arthritis due to C. cellulans, a pathogen opportunistic for humans with increasing relevance in the last years. Furthermore, if a history of previous penetrating skin injury is reported by the patient and this microorganism is isolated from sterile fluids, the presence of foreign bodies must be investigated and a prolonged course of combined antibiotic therapy must be started after a comprehensive microbiologic evaluation. The presence of a foreign body requires removal, and early invasive surgical debridement is essential in cases where a foreign body is not found. Prompt intervention in these cases improves the prognosis and maximizes the possibility of cure, reducing the long-term functional problems associated with arthritis.