Pyogenic spondylodiscitis in HIV-positive patients under antiretroviral therapy: A case series

Abstract

Background: The incidence of pyogenic spondylodiscitis has been increasing in countries of Europe and North America, probably due to an increasing number of persons with risk factors for this infection. It is unclear whether HIV infection in the era of antiretroviral therapy (ART) increases the risk for spondylodiscitis. Method: We present 7 cases of pyogenic spondylodiscitis of the cervical, thoracic, and lumbar spine in six individuals living with HIV under ART with suppressed viral load. Results: All patients presented with severe non-radicular pain and elevated inflammatory markers. Diagnosis was confirmed by magnetic resonance imaging (MRI) scan and isolation of the pathogen. Staphylococcus aureus was the causative pathogen in five patients. One patient suffered from an infection with Klebsiella pneumoniae followed by a mixed infection with Cutibacterium acnes and Bacillus circulans 18 months later. All patients needed surgical intervention, and the mean duration of antibiotic treatment was 17 weeks (range 12–26). Five patients recovered fully, including two persons who also suffered from endocarditis. One patient died from multi-organ failure. Conclusion: Spondylodiscitis may be seen more frequently in persons living with HIV as they grow older and suffer from comorbidities which put them at risk for this infection. HIV physicians should be aware of the infection and its risk factors.

Keywords

Pyogenic spondylodiscitis epidural abscess HIV Klebsiella pneumoniae Staphylococcus aureus Cutibacterium acnes

Introduction

Pyogenic spondylodiscitis is a rare inflammation of the disc and the adjacent vertebral bodies. It is usually caused by haematogenous spread of infection from a distant focus, although in many cases the primary focus cannot be identified. Rarely, infection can spread from adjacent soft tissue infection or as a complication of surgery or injections into the disc space. The last decades have seen an increase in the incidence of spondylodiscitis in countries such as USA,¹ Germany,² France,³ and Denmark.⁴ This might be due to better diagnostic tools as well as to the growing number of individuals with risk factors for this infection. These include older age, polymorbidity, immunocompromised state, diabetes mellitus, intravenous drug use, a history of medical procedures or bacterial infection.⁵ HIV infection has also been regarded a risk factor,⁶ but previous case series included patients without viral suppression in the early years of the HIV epidemic^7–10 or cases with mycobacterial infections in countries where tuberculosis is endemic.¹¹ Whether people living with HIV in the era of modern ART with suppressed viral load and normal CD4+T cell count have an increased risk for vertebral osteomyelitis and discitis is not clear. Here we describe 7 cases of bacterial spondylodiscitis in six patients under ART with their HIV-1 viral load below the limit of detection.

Methods

We present the details of 7 cases of spondylodiscitis seen in a single-centre cohort of adults living with HIV between 2017 and 2021. Data were collected by review of patient records. All cases were confirmed by clinical history, MRI imaging and identification of the causative pathogen. We describe demographic characteristics, clinical and laboratory findings including CD4+T cell count and HIV-1 viral load at the time of diagnosis of spondylodiscitis as well as risk factors, history, treatment, and long-term follow-up of the cases (until May 2023).

Results

Patient characteristics

Between 2000 and 2021, 1060 adults living with HIV-1 were cared for at the HIV department of Innsbruck University Hospital in Austria. A comprehensive database is maintained prospectively for all patients in care and comprises 8819 person-years of follow-up during the observation period. Between 2000 and 2016 no cases of spondylodiscitis were recorded, whereas between 2017 and 2021 seven cases of spondylodiscitis of the cervical, thoracic, or lumbar spine were diagnosed in six patients. The demographic and clinical characteristics of these cases are shown in the table. The mean age at diagnosis was 54 years (range 38–74), four patients were male, two were female. All were virologically suppressed under long-term ART, the mean CD4+T cell count was 567/µl (range 111–1059). Three patients had serious comorbidities (end stage renal disease, liver cirrhosis, acute hepatitis C).

Presentation and outcome of spondylodiscitis cases

The details of the individual cases are presented in the Table 1. Severe non-radicular pain was the presenting symptom in all cases. Five patients reported fever. Three patients presented with transient neurological deficits. Serum inflammatory markers (CRP, ESR) were elevated in all cases, with the highest values seen in the two patients who also suffered from endocarditis. The causative pathogen was identified in all cases from blood and/or tissue. Staphylococcus aureus was found in five patients, in one of these cases the isolates were methicillin-resistant. One patient presented with two distinct episodes of spondylodiscitis of the lumbar spine: Klebsiella pneumoniae was found in the first episode in 2017 and a mixed anaerobic infection (Cutibacterium acnes, Bacillus circulans) in the following episode in 2019. MRI scans confirmed the diagnosis in all cases, showing abnormal signal intensity in disc space and adjacent vertebral bodies. Figures 1 and 2 show MRI pictures of the cervical and lumbar spine of two patients. All seven infections needed surgical intervention in the course of the disease. In four cases epidural abscesses of the cervical spine were present and surgically drained, in three patients infection of the paravertebral soft tissue was described. One of the two patients with endocarditis needed mitral valve replacement. His electrocardiogram (ECG) showed an ST elevation in the leads V1 and V2 which returned to normal after recovery. Antibiotic treatment was given according to the results of antibiotic resistance testing and the preference of the managing physician. The details of antibiotic treatment in the individual cases are shown in the appendix. In the five patients who survived, the mean duration of hospital stay was 51 days (range 10-86), and the mean duration of antibiotic treatment was 17 weeks (range 12–26). The outcome was complete recovery in four patients. Patient 5 developed a second episode of spondylodiscitis due to different bacteria 18 months later, from which he also recovered. One patient suffered from septicaemia and multi-organ failure and died 50 days after admission to hospital.

Figure 1.

Sagittal T2 MR image shows abnormal signal intensity in the disc space C5-7 with increased signal intensity in the vertebral bodies C5-7 (a). Sagittal T1 (b) and sagittal T1 postcontrast MR image (c) show abnormal enhancement of the C5-7 vertebral bodies. Epidural abscess formation is seen from C5-7 with compression of the thecal sac.

Figure 2.

Abnormal signal intensity in the disc space L4-5 in the sagittal T2 MR image (a). Sagittal T1 (b) and sagittal T1 postcontrast MR image (c) reveal an increased enhancement of the L4-5 vertebral bodies. From the disc level cranially ascending epidural abscess with resulting severe spinal canal stenosis.

Table 1.

Demographic and clinical characteristics of 7 episodes of pyogenic spondylodiscitis in 6 HIV-infected patients under ART with undetectable viral load

	Patient 1 (MD)	Patient 2 (CR)	Patient 3 (KO)	Patient 4 (GH)	Patient 5 (MR)		Patient 6 (ID)
Age/sex	38/male	52/female	56/female	74/male	54/male	75/male	49/male
HIV transmission	MSM	IVDU	IVDU	MSM	MSM		IVDU
Year of HIV diagnosis	2001	1985	1985	1997	2008		2007
CD4 nadir (cells/μl)	120	174	3	86	393		372
Time on ART	8 years	27 years	24 years	22 years	6 years	7 years	12 years
Comorbidity/relevant history	End Stage Renal Disease (dialysis)	Liver Cirrhosis (HCV); active IVDU	Pneumonia/Pyothora x (surgery 30.7.18)	None	Acute Hepatitis C	None	None
Date of diagnosis of spondylodiscitis	04.06.2019	19.10.2018	17.10.2018	02.04.2020	25.07.2017	12.02.2019	27.08.2021
Location	C3/4/5 + epidural abscess	C6/7 + epidural abscess	Th9/10/11 + paravertebral infection	L4/5 + paravertebral infection	L4/5 + epidural abscess	L3/4	C6/7 + + paravertebral and epidural abscess
Pathogen (cultured from)	MSSA (blood, tissue)	MRSA (blood, tissue)	MSSA (blood)	MSSR (blood)	Klebsiella pneumonia (blood, tissue)	Cutibacterium acnes; Bacillus circulans (tissue)	MSSA (blood, tissue)
Duration of symptoms before diagnosis / MRT	7 days	3 days	10 days	28 days	5 days	unclear (chronic pain)	19 days
Pain (non-radicular)	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Fever (>38°C)	Yes	Yes	Yes	Yes	Yes	No	No
Neurologic deficit	Yes	Yes	Yes	No	No	No	No
WBC (neutrophils) G/L	15.5 (13.9)	4.8 (4.2)	7.7 (6.5)	14.9 (13.3)	11.5 (8.9)	5.7	9.9 (7.8)
CRP mg/d	36.9	28.5	6.55	19.6	12.97	5.07	15.69
ESR mm/h	75	69	42	59	22	20	Not done
CD4 (CD4/CD8 ratio) at diagnosis of spondylodiscitis	414 (0.46)	246 (0.56)	111 (0.22)	554 (1.31)	710 (0.76)	875 (0.96)	1059 (0,76)
Surgery of the spine (date)	5.6.19; 26.6.19; 6.7.19	23.11.18	30.10.18	9.4.20	18.8.17	13.2.19	30.08.21
Signs of endocarditis on echocardiography	Yes (mitral valve) Surgery 7.8.19	Yes (aortic valve) No surgery	Not investigated	Not investigated	No	No	No
Duration antibiotics	26 weeks	12 weeks	17 weeks	7 weeks (until death)	13 weeks	22 weeks	15 weeks
Duration hospital stay	86 days	82 days	30 days	50 days (until death)	35 days	10 days	62 days
Outcome	Healed	Healed	Healed	Multiple-organ failure. Death	Healed	Healed	Healed
Comment				Patient refused intensive care	New infection 18 months later

Discussion

It is not clear whether living with HIV put our patients at higher risk of spondylodiscitis, as all of them had been on ART with their viral load below the limit of detection at the time of diagnosis of spondylodiscitis. Only one of our patients had a CD4 count below 200, but five had risk factors in addition to HIV: end stage renal disease, liver cirrhosis, active intravenous drug use, recent infection and surgery, and advanced age. It has been suggested that the increase of pyogenic spondylodiscitis seen in industrialized countries is due to an increasing proportion of individuals with risk factors for this infection.⁵ We think that increasing age of people living with HIV and comorbidities rather than the HIV infection itself put them at higher risk. Further epidemiological studies are needed to define the risk.

The most common cause of pyogenic infection of the spine is Staphylococcus aureus, which accounts for about half of cases in industrialized countries^3,10,12–14 and is frequently associated with complications and a mortality up to 30%.¹⁵ In five of our patients Staphylococcus aureus could be isolated, and they all presented with a febrile illness. Two of these patients also suffered from endocarditis and one of them needed mitral valve replacement. We do not know whether the endocarditis preceded the spondylodiscitis or vice versa. Two patients did not have transoesophageal echocardiography, so valvular disease cannot be ruled out with certainty; it could have been present in Patient four who died from multi-organ failure. A review reported infectious endocarditis in 31% of patients with pyogenic vertebral osteomyelitis.¹⁶ It is warranted to evaluate patients (especially those with valvular disease or new onset cardiac symptoms) for concurrent infectious endocarditis.^16,17 The antibiotic treatment might be the same, but these individuals will need antimicrobial prophylaxis to prevent subsequent endocarditis when indicated. One of the five Staphylococcus aureus infections in our patients was due to methicillin-resistant strains (MRSA). Similarly, less than 20% of isolated Staphylococcus aureus in a German cohort of spondylodiscitis were methicillin-resistant.¹⁵ In contrast, in a cohort of American patients with native vertebral osteomyelitis a much higher proportion of isolates were methicillin-resistant.¹⁴ Empirical treatment should have activity against MRSA until culture results are available.

One of our patients with spondylodiscitis due to Staphylococcus aureus died; the other infections resolved completely and showed no relapses in the long term follow up. Recently, a German group of researchers suggested a score for evaluation of mortality risk on hospital admission, the Hamburg Spondylodiscitis Assessment Score.¹⁸ It takes age, C-reactive protein, kidney function, and pathogen into account. When retrospectively applying the score to our patients, the one who died was indeed classified as at a very high risk for mortality. One other patient (Patient 1) was predicted as high risk: he needed three spinal surgeries, a mitral valve replacement, received antibiotics for 26 weeks, and stayed in hospital for 86 days. The remaining cases with a low mortality risk score required less time on antibiotics or in hospital care. Implementing the Hamburg score could help clinicians to identify patients at high risk of mortality or complications already at the time of hospital admission.

Patient 5, a man who has sex with men (MSM), presented twice with uncommon infections of the lumbar discs: Klebsiella pneumoniae was cultured from both blood and disc L4/5 during his first episode of spondylodiscitis. There are few case reports of Klebsiella pneumoniae causing spondylodiscitis, for example in association with urinary tract infection¹⁹ or liver abscess²⁰ in Asian populations, where hypervirulent Klebsiella pneumonia could cause more metastatic spread of infection.²¹ In our patient the infection was spontaneous, which has recently also been described in a Japanese and a Thai male.^22,23 Bacterial translocation across the intestinal mucosa has been suggested as possible entry mechanism. Sexual practices with anal intercourse (and possibly concomitant drug use) could have played a role in our patient, as he also acquired hepatitis C during this time. Eighteen months later he suffered from a second episode of spondylodiscitis (L3/4) due to a mixed anaerobic infection with Cutibacterium acnes and Bacillus circulans. Cutibacterium acnes is a low-virulence and slow-growing skin commensal bacterium which can cause post-operative orthopaedic infections.²⁴ As it was grown from five tissue samples we consider it a relevant infection rather than just a contamination. We cannot rule out that this infection is associated with the spine surgery 18 months previously and had been lingering for a long time. In a report of 29 cases of spondylodiscitis due to Cutibacterium acnes, 28 cases had undergone spinal surgery with a mean delay of 34 months between intervention and infection²⁵ and most of these patients were afebrile like our case. The median time to diagnosis was 4.7 months; similarly, our patient complained about back ache for many months. Among nine cases of anaerobic spondylodiscitis reported from Taiwan only two have had previous spinal surgery, but all were to some degree immunocompromised.²⁶ Bacillus circulans is a common contaminant in health-care settings and can cause endophthalmitis after eye surgery or injury.^27,28 In our case, it was found in only one of the five tissue samples (together with Cutibacterium acnes) and might not have been of significance for the spinal infection. However, infection with more than one pathogen has been reported before, for example in Germany in 12 of 134 intra-operative specimens¹⁵ and in three of 15 people living with HIV with spondylodiscitis.¹⁰ Low virulence anaerobic bacteria might be present in discs without causing symptoms: a meta-analysis of bacterial cultures from discectomies for degenerative disease reported bacteria in 25% of discs, with Cutibacterium acnes accounting for over half of these cultures.²⁹

In the literature there are few reports of other rare causes of pyogenic spondylodiscitis in patients living with HIV, for example Candida dubliniensis³⁰ and Campylobacter fetus.³¹ Clusters of extraintestinal infections with enteric pathogens such as Campylobacter and Shigella have been reported in MSM.^32,33 If sexual transmission of such pathogens is ongoing, there could be more cases of rare presentations like spondylodiscitis in the future.

In our cohort, we have not seen cases of mycobacterial infections of the spine, which are the most common cause of spondylodiscitis in countries where tuberculosis is endemic.¹¹ In contrast to our observations, there were cases of opportunistic mycobacterial spine infections in cohorts of people living with HIV reported from Holland⁹ and Germany¹⁰ (four of 10 and six of 16 cases, respectively). Five of our 6 patients were Austrian by descent. The immigrants in our HIV cohort tend to be younger and might lack some of the additional risk factors for spondylodiscitis.

In four of our cases the correct diagnosis was made within 10 days of symptom onset, which is probably due to the acute onset of symptoms and the rapid availability of medical care and MRT imaging in our setting. In other retrospective cohorts the delay between symptom onset and hospital admission was typically several weeks to months, which could also be influenced by the different spectrum of pathogens involved. Despite the short delay between symptom onset and diagnosis our patients presented with advanced disease, suggesting a longer overall duration of the disease process. All patients were seriously ill, needed surgical intervention, and many weeks of inpatient care and antibiotic treatment. Non-radicular pain in the spine should give rise to suspicion of spondylodiscitis, particularly in the presence of fever and laboratory abnormalities.

Conclusion

Spondylodiscitis is a rare infectious complication, which might be seen more frequently in individuals living with HIV as they are age and suffer from comorbidities which put them at risk. In patients with severe non-radicular pain, fever, and/or elevated serum inflammatory markers (CRP, ESR) spondylodiscitis is an important differential diagnosis. Magnetic resonance imaging (MRI) and/or 18F-fluorodeoxyglucose (FDG) PET/CT are the most sensitive diagnostic methods. Awareness of the condition and its risk factors will help with faster diagnosis and better outcome.

Supplemental Material

Supplemental Material - Pyogenic spondylodiscitis in HIV-positive patients under antiretroviral therapy: A case series

Supplemental Material for Pyogenic spondylodiscitis in HIV-positive patients under antiretroviral therapy: A case series by Maria Kitchen, Irina Gasslitter, Martin Gisinger, Johannes Deeg, Armin Rieger, and Mario Sarcletti in International Journal of STD & AIDS

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Medizinische Universitat Innsbruck; Drittmittel.

ORCID iD

Maria Kitchen

Supplemental Material

Supplemental material for this article is available online

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