Infectious endocarditis and vertebral osteomyelitis caused by Moraxella catarrhalis

Abstract

Moraxella catarrhalis frequently colonises the oropharynges of healthy individuals. Disease is usually limited to the oropharynx, upper airways and lower airways in patients with predisposing conditions. The pathogen rarely causes more invasive disease. We present the case of a 65-year-old woman with Crohn’s disease on azathioprine, who was diagnosed with native valve M. catarrhalis endocarditis and vertebral osteomyelitis several weeks after an upper respiratory tract infection. She presented to hospital with 5 weeks of worsening malaise, nausea, relapsing fevers, weight loss, acute-on-chronic exacerbation of lower back pain and diffuse myalgia. Transoesophageal echocardiogram showed a 12 mm vegetation on her mitral valve, contrast-enhanced MRI was consistent with L4 osteomyelitis and blood cultures were persistently positive for M. catarrhalis. She was initially treated with ceftriaxone 2 g intravenously daily, and although her symptoms initially resolved, she experienced a relapse of osteomyelitis with L3 extension a few weeks after treatment discontinuation.

Background

Moraxella catarrhalis is a micro-organism that frequently colonises the oropharynx, seen in up to 78% of healthy children¹ and in about 4% of healthy adults.² It is most frequently associated with middle ear infections and upper respiratory tract infections in children.² In adults, it is an important cause of pneumonia in patients with chronic lung disease² and in those who are immunocompromised.³ It is very rarely known to cause invasive infections such as septic arthritis or endocarditis,² and only one case of vertebral osteomyelitis caused by M. catarrhalis alone has been published to date.⁴ Typically, invasive infections with M. catarrhalis have occurred in patients who are immunocompromised.³

This case highlights an unusual presentation of invasive M. catarrhalis infection and serves as an important reminder of several key clinical lessons for managing patients with suspected infectious endocarditis (IE), especially in cases where the presentation is insidious and the diagnosis may initially be overlooked.

The pathogens most commonly isolated in patients who have IE with native heart valves are Staphylococcus aureus, Viridans group streptococci and enterococci.⁵ IE can be notoriously difficult to diagnose⁵; no organism is identified on blood culture in up to 31% of cases,⁶ and between 30% and 40% of positive cultures are false-positives due primarily to contamination by skin microflora.⁷ IE has been associated with metastatic infection in up to 59% of cases.^{8 9} The incidence of bone and joint infections as a complication of IE varies: in the case of S. aureus and viridans streptococci, rates have been reported between approximately 6%^{10 11} and 15%,¹² while for enterococcal endocarditis, osteoarticular manifestations are rare.¹³ Larger vegetation size, mitral valve involvement and S. aureus infection have been associated with significantly higher rates of bacterial emboli.^{14 15}

Case presentation

A 65-year-old woman presented to the emergency department with a 5-week history of progressive fatigue, diffuse myalgia, persistent nausea, intermittent daily high-grade fever, night sweats and weight loss of 4 kg. She also reported an acute deterioration of long-standing lower back pain without neurological sequelae. She did not experience skin rashes or nail changes, oral ulcers, peripheral joint pain, chest pain or any changes in bowel or urinary habits. Prior to the onset of her symptoms, she experienced an upper respiratory tract infection that was assumed to be viral and treated symptomatically without antibiotics.

On initial examination, she was febrile (T_MAX=38.8°C). Cardiac exam revealed a grade 3/6 systolic murmur in the aortic area and a grade 2/6 systolic murmur near the apex. Head-and-neck, respiratory, abdominal and musculoskeletal examination was normal. Lumbar pain limited the assessment of range of motion of the spine. There was no spinal or paraspinal tenderness on palpation, the straight leg raise test was negative and she had normal power in the lower extremities with no saddle anaesthesia. Examination of the fingernails revealed two small, vertical, red-brown streaks under the nail of the left index finger, possibly representing splinter haemorrhages (figure 1). The rest of the physical examination was unremarkable, including funduscopy.

Figure 1.

Two possible splinter haemorrhages on patient’s left index finger.

Her medical history included Crohn’s disease treated with Azathioprine 200 mg per os daily, lichen planus and thrombophilia with superior sagittal sinus thrombosis during pregnancy, superior mesenteric vein thrombosis, portal vein thrombosis and partial retinal artery occlusion, treated with rivaroxaban 20 mg daily. Finally, she had a history of chronic lower back pain related to T12 and L2 vertebral compression fractures secondary to osteoporosis. Aside from the azathioprine and rivaroxaban, she was only taking Tylenol #3 at the time of admission. Her family history was unremarkable, and she denied using tobacco products and consuming ethanol or recreational drugs.

Investigations

Initial laboratory investigations revealed macrocytic anaemia (haemoglobin 101 mg/dL and mean corpuscular volume of 106 fL), leukocytopaenia with lymphopaenia (3.39 and 0.54×10⁹/L, respectively), and elevated inflammatory markers (C reactive protein 121.6 mg/L and Erythrocyte Sedimentation Rate 130 mm/hour). Two separate initial blood cultures drawn at the time of admission demonstrated no bacterial growth. However, she remained febrile in hospital so additional blood cultures were collected 2 days, 3 days and 4 days after admission. On each day, 1 of 2, 1 of 2 and 1 of 4 cultures grew M. catarrhalis, respectively. Antibiotic sensitivities showed production of beta-lactamase, with sensitivity to amoxicillin-clavulanate, ceftriaxone and trimethoprim-sulfamethoxazole, but resistance to ampicillin. Treatment with ceftriaxone was started on the fourth day after admission. Antinuclear antibodies, C3, C4 and rheumatoid factor were normal.

Initial transthoracic echocardiogram (TTE) visualised a small independently mobile structure attached to the mitral valve leaflet on the atrial side, suggesting a possible vegetation. A follow-up transoesophageal echocardiogram (TOE) revealed mild aortic regurgitation, mild to moderate mitral regurgitation and a 9 mm × 12 mm echogenic multilobed mass, attached to the posterior leaflet on the atrial side of the mitral valve (figure 2). Mitral valve leaflets were noted to be thickened, and the posterior mitral annulus thickened with layered echogenic materials.

Figure 2.

Transoesophageal echocardiogram image demonstrating a 9 mm × 12 mm echogenic multilobed mass attached to the posterior leaflet on the atrial side of the mitral valve.

Because she complained of significant worsening of her chronic lower back pain that temporally coincided with her other symptoms, a lumbar spine MRI was ordered with and without gadolinium contrast. This revealed osseous oedema involving the upper two-thirds of the L4 vertebral body with abnormal enhancement extending into the subjacent anterior prevertebral soft tissue and deep fibres of the right psoas muscle (figure 3).

Figure 3.

Top: T1 lumbar MRI without contrast, sagittal view. Osseous oedema involving the upper two-thirds of the L4 vertebral body with abnormal enhancement extending into the subjacent anterior prevertebral soft tissue visible. Bottom: T1 lumbar MRI with gadolinium contrast, axial view, L4 level. Similar interpretation with the addition of abnormal enhancement extending into the subjacent anterior prevertebral soft tissue and deep fibres of the right psoas muscle.

Differential diagnosis

The patient presented with subacute onset of non-specific systemic symptoms and no clear focus of abnormality. The differential diagnosis for this presentation includes inflammatory conditions (such as connective tissue diseases or extraintestinal manifestations related to Crohn’s disease), malignancy (haematological or solid organ) and infectious processes, particularly viral infections (such as HIV seroconversion, Epstein-Barr virus or cytomegalovirus infection) or subacute bacterial infections (such as endocarditis, osteomyelitis or occult abscesses). Given the patient’s history of thrombophilia, venous or arterial thrombosis is also in the differential diagnosis.

Treatment

Although she was febrile, the patient displayed no other signs of sepsis, and therefore she was not treated with empiric antibiotics initially. When blood cultures grew M. catarrhalis, the infectious disease service was consulted, and ceftriaxone 2 g daily intravenously was initiated. This high dose was chosen because of the suspicion for endocarditis. The patient received a peripherally inserted central venous catheter after repeated blood cultures were negative to complete an 8-week course of antibiotics.

Outcome and follow-up

The patient improved significantly over the course of her hospital stay, with her constitutional symptoms subsiding almost entirely, and all symptoms (aside from her back pain) disappearing completely shortly after discharge. Unfortunately, her back pain improved only minimally, and she required one subsequent brief hospitalisation to address pain control. At the end of her treatment, a repeat TOE was performed, noting the disappearance of the previously mentioned mitral vegetation. However, after a brief symptom-free period, 3 months after her initial diagnosis, her symptoms returned and lumbar pain worsened yet again. A repeat MRI was performed to evaluate for reinfection or relapse. This demonstrated ongoing osteomyelitis and suggested progression of her infection, with increased abnormal signal in the L3-L4 disk space as well as on the inferior endplate of L3 (figure 4). Repeat blood cultures again grew M. catarrhalis. Recurrence of bacteraemia and vertebral osteomyelitis in patients who complete at least 8 weeks of antibiotics occurs rarely (in as few as 2% of cases).¹⁶ In such cases, a bone biopsy could be considered to establish definitive diagnosis. However, given that the suspicion for recurrent haematogenous vertebral osteomyelitis was high based on imaging and blood culture results, and in the interest of avoiding an invasive test, a clinical diagnosis of recurrent osteomyelitis was made and a new 3-month course of treatment with doxycycline 100 mg orally twice daily was started. After 3 weeks of treatment, blood CRP decreased from 36.0 mg/L to 4.5 mg/L, which remained low throughout her treatment and at 4-month follow-up. The patient experienced significant clinical improvement after treatment without further relapse.

Figure 4.

T1 lumbar MRI without contrast, sagittal view, 3 months postdischarge. A loss of T4 vertebral height and increased abnormal signal in the L3-L4 disk space as well as on the inferior endplate of L3 are visible.

Discussion

We report a case of M. catarrhalis bacteraemia associated with endocarditis and vertebral osteomyelitis with persistent infection despite prolonged treatment. To our knowledge, this is the first reported case of concurrent endocarditis and vertebral osteomyelitis secondary to M. catarrhalis and the first report of relapsed infection after appropriate therapy. Although M. catarrhalis is a common commensal organism, bacteraemia is rare. A literature review found only 61 cases of M. catarrhalis bacteraemia published until 1998 in English and Scandinavian literature.¹⁷ Most (54%) of the cases of bacteraemia were related to respiratory tract infection and only five cases (8%) had endocarditis. An additional five cases of M. catarrhalis endocarditis have subsequently been reported.^18–22 Immunosuppression and valvular abnormalities, including prosthetic valves, appear to be important risk factors for M. catarrhalis endocarditis. Osteomyelitis appears to be an even rarer complication of M. catarrhalis infection. Three cases of acute mastoiditis in paediatric patients have been reported,^23–25 most likely from direct contiguous spread secondary to upper respiratory tract infection or otitis media. Vertebral osteomyelitis was only reported in two cases, one of which was a polymicrobial infection.^{4 26} Given the patient’s history of Crohn’s disease and therapy with the immunomodulatory agent, azathioprine, immunocompromise may have played a role in predisposing her to this infection.

Over 90% of clinical isolates of M. catarrhalis produce beta-lactamase enzymes and up to 50% demonstrate resistance to trimethoprim-sulfamethoxazole.^{27 28} Third generation cephalosporins are recommended as first-line empirical therapy.²²

Our patient experienced persistent infection despite a prolonged course of appropriate antibiotic therapy, which is unusual in the setting of invasive M. catarrhalis disease. Of the patients who recovered after being diagnosed with M. catarrhalis bacteraemia, described in the aforementioned literature review, none experienced relapse.¹⁷ Of the five cases of endocarditis we identified post-1998, four recovered completely and one died of septic shock 40 days after initial admission but with negative blood cultures and possibly unrelated to the initial diagnosis.²¹

This case highlights several important clinical lessons for managing patients with suspected endocarditis. The first is a reminder of the potentially insidious and non-specific presentation of endocarditis, particularly in immunocompromised patients or involving unusual pathogens. Second, empiric antibiotics should not be administered until blood culture results are obtained if the patient is clinically stable. Several sets of blood cultures were required in order to make the diagnosis in our patient, and early antibiotics would have risked sterilising the results and delaying diagnosis further. Third, multiple blood cultures are often needed to diagnose IE, particularly when the infectious agent is unusual, as in this case. Fourth, transoesophageal echocardiography is often needed to make the diagnosis of endocarditis because transthoracic echocardiography is poorly sensitive (40%–66% for TTE vs 90%–100% for TOE).⁵ Fifth, in patients with endocarditis, it is important to seriously consider that any new complaints of pain could represent metastatic sites of infection. In this case, our patient’s pain might have been attributed to her chronic issues. However, the severity and timing of her symptoms led us to request contrast-enhanced imaging, and she was found to have vertebral osteomyelitis. Clinicians caring for patients with endocarditis should have a high index of suspicion for haematogenous spread of infection to remote sites, as these may occur in more than half of cases.^{8 9} Finally, it may be important to continue clinical surveillance after completing the initial course of antibiotics, as our patient experienced recurrence of symptoms and progression of her infection despite appropriate therapy.

Patient’s perspective.

Everything started with a sore throat and then for about 2 weeks, I started to have chills and night sweats. I would feel really really cold at night where I needed 2–3 blankets, after which I would sweat until morning. I went to my doctor and he said it was just a nasty virus, so I just let it go on for another 3 weeks. Then I went back, he took one look at me and said ‘you should be in the hospital’. Around that time, I was in a lot of pain. My back was hurting whenever I would get up, sit on the toilet, etc, and all of my joints were stiff. After I was discharged, my heart was racing intermittently, and I had to come back to the hospital. I was sent home with a Holter monitor, which thankfully was okay. Shortly thereafter, my back pain and other symptoms returned. So, I booked an appointment with the infectious disease doctor who confirmed my suspicion that the infection didn’t go away. I was started on a new antibiotic and I feel like my original infection is much better now, but I’m experiencing very unpleasant symptoms. Overall, this experience has been debilitating, and I just don’t feel like myself anymore.

Learning points.

• Moraxella catarrhalis colonisation of the oropharynx is common in healthy children and adults. Although they are rare, invasive infections including endocarditis and osteomyelitis can occur.

• M.catarrhalis isolates often produce beta-lactamase enzymes, and the first-line empirical antibiotic for invasive infections are often third generation cephalosporins.

• In the setting of suspected endocarditis in a stable patient, antibiotics should not be administered prior to drawing blood cultures, and multiple repeat cultures may be needed to achieve a diagnosis, particularly for atypical organisms, like Moraxella.

• Metastatic infections are common in patients with endocarditis, thus new pain or focal symptoms should prompt investigation for bacterial seeding of that site.