Non-vertebral Mycobacterium avium complex osteomyelitis in an immunocompetent patient

Abstract

Mycobacterium avium complex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients. In this case, we describe the presentation of an otherwise healthy man in his 50s presenting with months of malaise and severe hip pain, with aspiration initially yielding no bacteria and presumed fastidious infection. He was treated with irrigation and debridement, surgical stabilisation of the femoral neck and conventional broad-spectrum antibiotics with final cultures diagnostic of MAC osteomyelitis. This case serves to demonstrate the importance of clinical suspicion and appropriate workup of this unusual case of MAC hip osteomyelitis in an otherwise immunocompetent patient.

Background

Mycobacterium avium complex (MAC) is a ubiquitous soil pathogen that is an uncommon cause of diseases in immunocompetent patients.¹ Clinically, MAC are typically seen in (1) opportunistic infections patients with AIDS, (2) non-tuberculous lung infection in a patient with pre-existing pulmonary disease, (3) disseminated MAC infection in immunocompromised hosts and (4) focal extrapulmonary MAC infections. Disseminated MAC infections are primarily diagnosed in patients with cancer on chronic steroids or undergoing chemotherapy and in patients with underlying immunosuppression.² Osteomyelitis, as a localised presentation, is most commonly vertebral: between 1982 and 2016, 16 cases of vertebral MAC-associated osteomyelitis have been reported in immunocompetent patients.³ To our knowledge, MAC osteomyelitis of the extremity is exceedingly rare and has not been previously reported.

Case presentation

A male in his 50s presented with 7 months of insidious onset progressive right hip pain without prior trauma, surgery or known risk factors for being immunocompromised. In addition to severe groin pain, he reported malaise, night sweats and an unintentional 60-lb weight loss over 6 months with recent dental work for tooth abscesses. He was referred to the Orthopaedic Surgery department for his continued hip pain and concern for an insufficiency (stress) fracture on AP pelvic x-rays.

Investigations

On presentation, his physical exam revealed pain with hip motion and soft tissue swelling to the lateral side of the hip with palpable lymphadenopathy along the right inguinal crease. Laboratory values were significant for a serum white blood cell count of 13.3×10(9) g/L, serum C-reactive protein of 16.76 mg/dL and erythrocyte sedimentation rate of 80 mm/hour. Haematologic work-up was consistent with microcytic anaemia (haemoglobin, 9.9 g/dL; haematoctrit, 31.5%; and mean corpuscular volume, 79.7 fL). Plain radiographs demonstrated a destructive lesion of the proximal femur (figure 1). MRI demonstrated a T1-weighted post-contrast isointense (figure 2A) and a T2-weighted hyperintense (figure 2B) peripherally contrast-enhancing lesion within the soft tissue of the proximal hip consistent with a large abscess measuring 19 cm. There was also evidence of a marrow-replacing process of the proximal femur in continuity with soft tissue lesions suggesting osteomyelitis with a sinus tract. The patient underwent hip aspiration, which demonstrated brown, turbid fluid. Cytology of the aspirate demonstrated neutrophils and histiocytes without evidence of malignant cells. Gram stain was negative, and there was no growth from the aerobic, anaerobic, acid-fast or fungal cultures at 4 days. No antibiotics had been administered to the patient before the hip aspiration and collection of specimens for culture. Following aspiration, the patient was initiated on empiric antibiotics consisting of vancomycin of 1250 mg/12 hours and piperacillin-tazobactam of 3.375 g/6 hour.

Figure 1.

Plain radiograph demonstrating a destructive lesion of the proximal femur.

Figure 2.

MRI demonstrating a T1-weighted post-contrast isointense (A) and a T2-weighted hyperintense (B) peripherally contrast-enhancing lesion within the soft tissue of the proximal hip consistent with a large abscess measuring 19 cm.

Histopathology of the tissue sample revealed lymphohistiocytic inflammation consistent with giant cells and poorly formed granulomas with no evidence of malignancy. After 72 hours without bacterial growth on hip aspirate cultures, an echocardiogram was performed to evaluate for subacute bacterial endocarditis and revealed a 3 mm sessile myxomatous mass of the anterior leaflet of the mitral valve. CT chest demonstrated multiple pulmonary abscesses, perhaps the result of septic emboli originating from a cardiac source. He was then transitioned from piperacillin-tazobactam to ceftriaxone 2 g to target oral flora. Further evaluation for endocarditis did not reveal abnormalities (ophthalmologic, CT abdomen/pelvis, blood cultures). Due to concerns about immunosuppression, the patient underwent a work-up including purified protein derivative placement, QuantiFERON gold and HIV testing – all of which were negative.

Differential diagnosis

A patient presenting with months of fevers, chills, night sweats, unintentional weight loss and insidious onset progressively worsening hip pain, in the absence of an alternative diagnosis, prompts work-up to rule out malignancy, osteonecrosis or infectious source. Classically, these symptoms are associated with tuberculosis infection, though less likely in immunocompetent patients.⁴ Bone pain with constitutional symptoms also serves as the first sign of primary malignancy or more often in adult patients aged over 40 years, malignant metastatic disease.

Treatment

The patient was taken to the operating room for debridement and irrigation for a presumed fastidious organism based on the imaging and negative culture results. A posterior approach was used to access the fluid collection and sinus, which were extracapsular. Intraoperatively, gross purulence was noted throughout the soft tissues and extending into the proximal femur. After debridement and irrigation, hip capsulotomy was performed, and no purulence was noted. Prophylactic fixation of the femoral neck with a dynamic hip screw was performed to prevent collapse due to the size of the defect (figure 3). Calcium sulfate with a ratio of 3 g vancomycin and 3.6 g tobramycin was packed into the defect, and separate beads were placed in the soft tissues with closure over a drain. Postoperatively, the patient was continued on intravenous vancomycin and ceftriaxone 2 g pending culture results from the send-out laboratory.

Figure 3.

Postoperative radiographs after prophylactic fixation of the femoral neck with a dynamic hip screw.

At this time, the patient reported that he had undergone multiple tooth extractions for tooth abscesses, before the initial onset of his presenting symptoms, raising concern for potential seeding of oral flora. Several days later, he transitioned to moxifloxacin 400 mg instead of vancomycin and ceftriaxone due to elevated creatinine levels and concerns for acute kidney failure.

Outcome and follow-up

During the patient’s hospital stay, 6 days postoperatively, his preoperative aspiration cultures were sent to LabCorp grew acid-fast bacilli (AFB). 17 days postoperatively, his operative cultures also grew AFB. These results were originally observed as contaminants due to a previous decrease in inflammatory markers on the treatment with ceftriaxone and vancomycin. However, on postoperative day 22, further speciation of these cultures via a DNA probe was consistent with MAC. At this time, the patient was initiated on empiric treatment of MAC infection under the guidance of the Infectious Disease physician to include 500 mg of azithromycin, 1300 mg of ethambutol, and 600 mg of rifampin daily. Moxifloxacin was also continued for coverage of odontogenic pathogens. The planned treatment course was anticipated to be 3 to 6 months. In retrospect, routine antibiotic coverage (ceftriaxone, vancomycin, piperacillin-tazobactam) and the operative beads (impregnated with vancomycin and tobramycin) would have had no impact on the treatment of MAC infection.

Further laboratory testing revealed intermediate sensitivity to moxifloxacin but susceptible to amikacin, rifampin and azithromycin. Moxifloxacin was discontinued, and rifampin, azithromycin and ethambutol were continued. Due to previous concerns of acute kidney injury, amikacin was not preferred. At subsequent follow-ups, the patient reported great improvement in his hip pain and tolerated the treatment regimen. Following the completion of his course of antibiotics, the patient was doing well with plans to move out of state.

Discussion

Non-tuberculous mycobacterial infections in immunocompetent patients are rare with few case reports in the literature. Infection is typically acquired through inhalation or inoculation. Often, non-tuberculous mycobacterial infections are not considered until the late stages of the disease course, especially when presenting in immunocompetent patients.¹ In this patient, hip aspiration only resulted in the detection of AFB after 10 days; however, it was not until treatment failure that the correct treatment was started due to the rarity of this presentation.

The delay in MAC infection diagnosis is complicated by challenges growing the bacteria in culture, namely, its slow-growing nature, quoted to be as long as 6 weeks.⁴ Challenges with speciation have been reported in the literature with mycobacteria culture sensitivity rates being less than 50%.⁵ Additionally, this is complicated by non-specific histological findings of granulomatous tissue and macrophage inflammation often in the setting of low bacterial loads. Doumas et al demonstrated the challenges with diagnosing mycobacterial infections, in their case report where they diagnosed an 18-year-old male with MAC osteomyelitis with PCR after microscopy and culture failed to reveal any organism. Numerous surgical biopsies of granulomatous lesions were negative for MAC.³

The pathophysiology of musculoskeletal infection is thought to include haematogenous inoculation from surgical procedures, penetrating injury or steroid injections. None of these risk factors were present in this patient, apart from the reported history of dental procedures, making the diagnosis even more challenging. The time to diagnosis is often delayed; the median time to diagnosis of MAC infection is 2 years.⁶

There is a paucity of case reports on MAC osteomyelitis in the literature. Jones et al discussed a case of a 43-year-old man who developed medial ankle swelling that progressed for over 3 months until joint fluid aspirate culture grew MAC. A review of the patient’s medical history revealed a penetrating injury from a mud-coated stick at age 8 years, suggesting a possible source of inoculation. He also sustained a chainsaw injury to the same ankle 13 years before the presentation. After the diagnosis, he underwent surgical debridement, drainage, arthrodesis and 18 months of antibiotic treatment. Despite a significant work-up, the patient was found to have a competent immune system with no explanation for the MAC infection.⁷

A 2014 article by Yano et al described the case of an immunocompetent 67-year-old with chronic wrist swelling, previously diagnosed with rheumatoid arthritis, who was ultimately diagnosed with Mycobacterium intracellulare. She presented with swelling and discharges from a right wrist fistula and underwent radical surgical debridement and anti-tuberculous drugs for 1 year with no recurrence at 3 years.⁸

Yi et al detailed the presentation and treatment of non-tuberculous mycobacteria in a 51-year-old female patient who underwent 3 years of extensive treatment for presumed plantar fasciitis and was ultimately diagnosed with calcaneal osteomyelitis. A physical exam demonstrated heat, swelling and tenderness. Subsequent MRI findings revealed cortical destruction at the right medial calcaneal tubercle. After the diagnosis, the patient underwent partial calcanectomy and packing with calcium sulfate absorbable beads impregnated with vancomycin and tobramycin. HIV serology and cellular and humoral immunity revealed no signs of immunodeficiency. Medical therapy included a prolonged course of several antibiotics.⁹

Currently, there is no consensus on the diagnostic and treatment protocol for bone infections caused by MAC. In this patient, surgical debridement, placement of a dynamic hip screw and treatment with antituberculous antibiotics resolved the infection and the patient’s return to full activity. Our patient demonstrates that MAC infections should be considered in patients presenting with atypical progressive hip pain associated with fevers, chills, night sweats and weight loss.

This case highlights the importance of broad culturing, especially with a clinical picture concerning for a fastidious organism. Failure of conventional treatment warrants additional consideration for atypical organisms, even in patients without traditional risk factors.

Learning points.

• Osteomyelitis caused by Mycobacterium avium complex (MAC) most commonly occurs in immunocompromised patients in the vertebrae.

• In a patient with atypical progressive hip pain associated with fevers, chills, night sweats and weight loss, MAC osteomyelitis should be considered.

• MAC infections can be hard to diagnose as it is slow-growing and hard to culture.

Ethics statements

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