The cocktail infection: anaerobic and aerobic co-Infections in tubercular vertebral osteomyelitis

Introduction

Anaerobic organisms have been known to have an association with dental infections, bacteremia, endocarditis and soft tissue infections.¹ However, anaerobic isolation from bone and joint infections are relatively rare. This could be attributed to the fastidious nature of the organism which makes isolation from the bone and joint infections cumbersome.¹

The most common organisms implicated in anaerobic osteomyelitis are Bacteroides, Fusobacterium, Peptostreptococcus and Clostridium species. Predisposing factors include children, contiguous spread of infection, vascular disease and complicated fractures.² Sparse literature has been found on reports of anaerobic osteomyelitis. There is no literature reported on anaerobic osteomyelitis complicating Tuberculosis of spine/Tubercular vertebral osteomyelitis (Pott’s spine). However, our cases highlight the rare isolation of gram-negative anaerobes (Prevotella, Bacteroides, Peptoniphilus) from Tubercular vertebral osteomyelitis (TVO) in immunocompetent adults diagnosed with tuberculosis of spine.

Materials/Methods

Two cases of infectious spondylodiscitis have been presented in this case series.

Consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patients.

Case report

Case 1

A 22-year-old poorly built (body mass index: 16 kg/m²) lady from rural South India who was pursuing her undergraduate degree, presented with complaints of low back ache of one-month duration. It was insidious in onset and gradually radiated to the right gluteal region. She was able to walk only a few steps with a limp. There was no bowel or bladder disturbance. She preferred to keep her right hip flexed to about 30 degrees in supine position. The backache was associated with high grade fever with chills and rigors. There was no history of tuberculosis in her family or her community. She had no significant history suggestive of immunosuppression. She had no known co-morbidities. There was no significant genetic history given by the patient.

On examination, she was febrile (102° F) with a pulse rate of 98 beats/minute. There was midline and right paraspinal tenderness from L3 to sacral region. Neurological examination of lower limbs was unremarkable. There was no focal neurological deficit.

Lab investigations showed that she was anaemic (Haemoglobin of 8 g/dl). Her total counts were 13600/mm³ (predominantly neutrophilia). The ESR was elevated (88 mm/hour) and CRP (261mg/L). The renal function tests were within normal limits, while serum albumin was only 1.9 mg/dl. Blood and urine cultures were sterile. Her chest x-ray showed no evidence of tuberculosis.

A radiograph revealed mild lumbar scoliosis to the left side and bulky psoas muscle in the right side (Figure 1a and b).

Figure 1. a: Radiograph of Spine (AP view). Arrow indicating bulky psoas muscle. b: Radiograph of Spine (lateral view). c: MRI (T2 flair) transverse section lumbar spine. Arrow indicating Abscess with air-fluid level. d: MRI lumbar spine. Saggital section. Arrow indicating right psoas abscess. e: MRI lumbar spine (T2/STIR) showing post-contrast enhancement in L5-S1 disc and adjacent end plates. f: Radiograph of spine (lateral) before and after treatment.

MRI spine revealed features suggestive of spondylodiscitis of L5-S1, spondylitis of L4 with abscesses adjacent to L4, L5, S1, S2 and S3 vertebra in the right side. There was also air-fluid level in the abscess (Figure 1c and d). The spondylodiscitis can be appreciated in the Figure 1e which shows post-contrast enhancement in L5-S1 vertebral discs. Figure 1f shows the radiographs before treatment and after treatment for comparison.

In view of the psoas abscess and radiological evidence of spondylodiscitis, she underwent surgery involving decompression of L5 vertebra and exploration of L5-S1 space with drainage of the abscess. Intra-operatively foul-smelling gas escaped from the abscess. The L5-S1 disc also had purulent collection. Pus was sent for CBNAAT (cartridge based nucleic acid amplification test) for tuberculosis, aerobic and anaerobic cultures. Material from L5-S1 disc was sent for histopathology.

On the third hospital day CBNAAT report was suggestive of Mycobacterium tuberculosis she was started on anti-tubercular therapy (ATT). The next day the aerobic culture grew Escherichia coli whereas anaerobic culture grew Bacteroids fragilis and Peptoniphilus asachrolyticus. In addition, she was also started on injection Piperazillin-Tazobactem and oral tinidazole for 10 days. There was wound dehiscence on tenth postoperative day.

The repeat culture from the pus drained grew only E. coli with similar sensitivity though the growth was scanty. We continued antitubercular drugs and added Injection Amikacin and Imipenem (as per the culture sensitivity report) for a total of three weeks. She was taken up for secondary suturing during this period. Patient was discharged subsequently. On follow-up at one month, her symptoms had improved and her anemia had improved to 9.5 gm%. She had also gained 1.6 kgs in weight. Repeat radiographs and MRI were done at the three-month follow-up and showed resolution of the abscesses. Patient was adherent and tolerated the anti-tubercular medications well. She was continued on ATT for 18 months. She did not have any ATT related complications and was compliant with the treatment throughout the follow-up.

Case 2

A 54-year-old man from an urban district of South India, a tailor by occupation, came with complaints of insidious onset of neck pain of about three weeks duration. The pain was gradually progressive over the past 10 days. The pain would aggravate on movements of the neck, but there was no radiculopathy. There was also associated fever with chills and rigors. He reported significant weight loss in the recent past. There was no history of medical co-morbidites. There was no relevant psycho-social or genetic history obtained from the patient.

On examination, neck appeared short and kyphotic. There was midline tenderness from C4-C7 region. Movements of the neck was grossly restricted due to pain and spasm. He was unable to flex his neck without significant pain. The elbow flexion was MRC Grade 4/5 on both sides. There was no sensory deficits and reflexes were normal. He was anaemic (Hb 10 g/dl) with neutrophilia. ESR was moderately elevated at 68 mm/hour. His chest radiograph was normal.

In an X-ray of the cervical spine, we noted increased prevertebral soft tissue shadow and erosion of vertebral end plates at C4-5 level with gross kyphosis. Air-fluid levels were also seen in the prevertebral soft tissue shadow (Figure 2a and b).

Figure 2. a: Radiograph cervical spine (lateral). b: Radiograph cervical spine (AP view). Arrow indicationg soft tissue shadow with air-fluid levels. c: MRI cervical spine (saggital view). d: MRI cervical spine (transverse view). Arrows indicating parapharyngeal collection with C4-5 spondylodiscitis. e: Cervical spine AP view. Post-operative radiographs. f: Cervial Spine lateral view. Post-operative radiographs.

MRI of the cervical spine confirmed spondylodiscitis of C4-C5 with cord compression. Multiple collections in parapharyngeal space communicating with the pre-vertebral space were also seen along with air-fluid levels (Figure 2c and d)

By this time the blood culture grew Streptococcus constellatus and he was started on Injection ceftriaxone (2gm q24h) as per sensitivity report. His urine culture was sterile and Brucella agglutination test was negative.

He underwent anterior cervical decompression, by C5 corpectomy and fusion (Figure 2e and f). A distinct foul-smelling odour was noted intra-operatively and around 100 ml of pus was drained. The C4 and C5 vertebrae were completely destroyed with surrounding caseous material. Pus was sent for aerobic and anaerobic cultures and the caseating tissue was sent for histopathology. Patient tolerated the procedure well.

The aerobic bacterial culture from the pus grew Streptococcus constellatus with similar sensitivity as that of his blood culture. Anaerobic culture grew Prevotella sps. The CBNAAT report was positive for Mycobacterium tuberculosis. Histopathology confirmed granulation tissue with epitheloid cells and Langhans giant cells suggestive of tubercular osteomyelitis.

He was started on Antitubercular therapy and Injection Metronidazole (500 mg q8h for two weeks) in addition to Injection Ceftriaxone (two weeks). The wound healed well. Anti-tubercular treatment was initiated and the patient was followed up on OPD basis. He was compliant with treatment and took the ATT for a total of 15 months. Improvement in anemia and ESR, weight gain as well as radiological improvement was noted in this patient on follow-up.

Discussion

Anaerobic osteomyelitis was first reported in 1884 by Von Langenbeck in case of vertebral osteomyelitis.³ Decades later, Taylor and Davies noted the presence of anaerobic organisms within sequestra in 55% of patients with chronic osteomyelitis.⁴ It was found that these anaerobic organisms were more frequently isolated from the inside of the sequestra and were usually mixed isolates i.e two or more anaerobic isolates were isolated. The chronicity of the osteomyelitis was directly proportional to the frequency of anerobic isolates found.

In a retrospective study done on osteomyelitis by Lewis et al., it was found that 39 percent of patients with osteomyelitis had anaerobic infections.¹ This serves to prove that anaerobes play a much larger role in osteomyelitis than known previously. It is likely that these infections are less reported due to poor awareness of their prevalence and the cumbersome methods of isolation.

However, these organisms were found as a part of the mixed flora which included gram positive cocci, gram negative bacilli and other anaerobes. This is consistent with the pattern of mixed infections reported in our case report. Our first patient was found to have anaerobic Prevotella infection from epidural abscess with associated Streptococcus bacteremia in a chronic tubercular vertebral osteomyelitis. Our second case was also found to have a combination of anaerobes comprising of Bacteroides, Peptoniphilus (Peptotreptococcus) and Clostridium with gram-negative Pseudomonas aeruginosa isolated from a psoas abscess secondary to a chronic tubercular vertebral osteomyelitis.

The predisposing factors contributing to anaerobic osteomyelitis usually include children, diabetes mellitus, oral infections or procedures, upper respiratory tract infections, trauma, peripheral neuropathy and complicated fractures.² It is interesting to note that both our patients had no pre morbidities to predispose them to anaerobic osteomyelitis.

In a review by Raff and Melo of a large series of 193 anaerobic osteomyeltits cases collected from the world literature published between 1936 to 1976, it was the found that the most common anaerobe implicated in osteomyelitis was Bacteroides followed by Peptostreptococcus and Fusobacterium.⁵ This trend was confirmed by a study by Ziment et al. who found the most common isolate being Bacteroides followed by Peptostreptococcus and Fusobacterium.⁶ This similar trend of occurrence was noted in a large study done on 134 cases of pyogenic osteomyelitis by Haider et al. between 1992 to 1993.⁷ This trend agrees with our case of anaerobic osteomyelitis which showed a mixed anaerobic isolate of Bacteroides with Peptostreptococcus and Clostridium.

A review of literature on available data on anaerobic osteomyelitis with Prevotella isolates shows only nine cases reported till date.^8–16 Among this only one case reports secondary Prevotella infection on chronic tubercular vertebral osteomyelitis. A summary of the data available on Anaerobic osteomyelitis with prevotella isolates are shown in Table 1.

A literature search was done to identify other published reports of anaerobic infections complicating tubercular vertebral osteomyelitis. However, we found only one case report by Salavert M et al who reported a combination of Prevotella and Candida infection in an intravenous drug abuser diagnosed with tubercular vertebral osteomyelitis in 1997.¹⁷

Both our cases did not show any evidence of hematogenous osteomyelitis. This finding concurs with evidence found by in a review study on 61 cases of anaerobic osteomyelitis of long bones¹⁸ where 29.5% of the cases were hematogenous and 32.8% were exogenous osteomyelitis. The study by Lewis et al. also shows a preponderance towards exogenous osteomyelitis.¹ In both our cases we could not ascertain how these polyorganisms could infect the spine.

Management of anaerobic osteomyelitis includes a two-pronged approach with adequate drainage of purulent material and parenteral administration of antibiotics for at least four to eight weeks.¹⁹ The antibiotics were decided according to the sensitivity pattern noted on culture. 

Strengths and limitations: The strength of this case series is the similar clinical presentation of both the cases and the presence of aerobic and anaerobic infections in both of them. However, we were unable to follow up the second case beyond two months as he opted for care under a local orthopaedician due to travel constraints. This was one of the limitations of our case series. As a result of this adherence and tolerance of the treatment could not be assessed in the second case.

Conclusion

Though tubercular vertebral osteomyelitis is usually a diagnosis in itself, it should not hinder us from considering secondary infections (both aerobic and anaerobic) complicating the osteomyelitis. Further, the presence of air-fluid levels on imaging studies and the presence of foul smell during operative exploration of the spine must arouse the suspicion of an anaerobic co-infection. Isolation and treatment of these organisms are crucial as they may hamper the clinical outcome of the primary TVO. Therefore, the cocktail of organisms, both aerobic and anaerobic isolated in these cases highlights the importance of suspecting, isolating and treating these lurking organisms in cases of tuberculosis of spine.