Clinical Infection in Practice 9 (2021) 100064

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Clinical Infection in Practice

journal homepage: www.elsevier.com/locate/clinpr

Case Reports and Series

Mycobacterium microti pulmonary infection with vertebrodiscitis and a

psoas abscess
Anna Wild, Victoria Shivji, Louise Berry, Pradhib Venkatesan ⇑
Department of Infectious Diseases, Nottingham University Hospitals, City Campus, Nottingham NG5 1PB, United Kingdom

a r t i c l e i n f o a b s t r a c t

Article history: Background: Mycobacterium microti is a member of the Mycobacterium tuberculosis complex. It usually
Received 5 October 2020 causes disease in various mammalian hosts, with its name being derived from rodents. It is difficult to
Received in revised form 19 December 2020 process for sensitivities in the laboratory and clinical experience of this organism in human hosts is lim-
Accepted 29 December 2020
ited.
Case report: We report a rare presentation of M. microti tuberculosis in a 40 year old female. She initially
presented with palpitations and breathlessness. A chest X-ray was abnormal and subsequent Computed
Keywords:
tomography (CT) of the chest and biopsy results led to a diagnosis of sarcoidosis. She was commenced on
Mycobacterium microti
Mycobacterium tuberculosis complex
prednisolone and her breathing improved. Nine months later she developed back and leg pain with asso-
Vertebrodiscitis ciated weakness. Spinal Magnetic Resonance Imaging (MRI) revealed vertebrodiscitis of L4/5 with an
Psoas abscess adjacent psoas abscess. Cultures from biopsies were negative. In the meantime her chest deteriorated
Vole and she became productive of green sputum.
Results: Three sputum samples were Acid-Fast Bacilli (AFB) smear positive and M. tuberculosis complex
polymerase chain reaction (PCR) positive. Repeat chest X-ray showed bilateral upper lobe cavitation. It
transpired that the patient lived in a rural area, close to fields and lakes. Her cat brought multiple dead
rodents into the house, including voles. The patient was left to clear up their entrails. Sputum sample
yielded M. microti.
Conclusion: To our knowledge this is the first reported human instance of vertebrodiscitis and a psoas
abscess due to M. microti. Although reportedly less pathogenic than M. tuberculosis, this case illustrates
its indolent and tissue destructive potential and the need for prolonged courses of anti-tuberculous
therapy.
Ó 2021 The Author(s). Published by Elsevier Ltd on behalf of British Infection Association. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Clinical case
One year prior to presentation to our centre, a 40 year old
female, who worked in the gardens of a stately home, developed
palpitations and breathlessness. She was diagnosed with atrioven-
tricular nodal re-entrant tachycardia. She was commenced on biso-
prolol. In the course of cardiac investigations her chest X-ray was
found to be abnormal and a subsequent CT scan showed wide-
spread septal thickening, perilymphatic nodularity, septal beading
and ground glass opacification (Fig. 1). A respiratory work up
included a trans-bronchial biopsy, which showed well-formed,
non-caseating granulomata, with negative stains for acid-fast
bacilli and fungi. Mycobacterial cultures had not been set up for
⇑ Corresponding author.
E-mail addresses: annalouise.wild@nhs.net (A. Wild), victoria.shivji@nhs.net (V.
Shivji), louise.berry@nuh.nhs.uk (L. Berry), pradhib.venkatesan@nuh.nhs.uk (P.
Venkatesan).
the bronchoscopic specimens, but Staphylococcus aureus grew from
bronchial washings, for which she received a course of oral flu-
cloxacillin. A diagnosis of sarcoidosis was made and her breathless-
ness improved on commencement of prednisolone 10 mg per day.
There were no extra-pulmonary features of sarcoidosis.
Nine months later she then developed pains around her right
hip, numbness on her anterior thigh and then over a 3 month per-
iod developed weakness of hip flexion, with associated back pains.
An MRI scan of her spine showed L4-5 vertebrodiscitis with a right
psoas abscess. She was referred to the regional Spinal Centre. Her
C-reactive protein (CRP) was <5 mg/L and her erythrocyte sedi-
mentation rate (ESR) was 22 mm/hour. An HIV test was negative.
A repeat MRI spine is shown in Fig. 2. In addition to the verte-
brodiscitis and psoas abscess, there was abnormal signal in L2
and L5 and a fracture through the superior end-plate of L4. A radi-
ological biopsy was undertaken from the psoas abscess, but con-
ventional, mycobacterial and fungal cultures all proved negative,
as well as a 16 s rRNA polymerase chain reaction (PCR). Brucella

https://doi.org/10.1016/j.clinpr.2021.100064
2590-1702/Ó 2021 The Author(s). Published by Elsevier Ltd on behalf of British Infection Association.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
A. Wild, V. Shivji, L. Berry et al.
Fig. 1. CT chest at time of diagnosis of sarcoidosis.
serology was also negative. When 17 years old, she had been on a
three-week family holiday to India, and other holidays were in Eur-
ope, North America and Japan. She gave no known contact history
with tuberculosis, but had missed having the BCG vaccine at
school.
With on-going back pain, and negative microbiological results
from her psoas abscess samples, she was empirically treated with
a six-week course of flucloxacillin and clindamycin, but no rifam-
picin. Her symptoms were unchanged and by now her CRP ranged
between 44 and 62 mg/L. She was referred back to the Spinal Unit
for an open spinal biopsy and stabilisation. This occurred about one
year after her first referral. The bone biopsy showed non-
inflammatory bone and again conventional, mycobacterial and
fungal cultures all proved negative, as did a 16 s rRNA PCR. How-
ever, by the time of spinal sampling her chest had been worse
for at least four months, with a new productive cough and
Fig. 2. MRI spine showing L4/5 vertebrodiscitis and right psoas abscess.
2
Clinical Infection in Practice 9 (2021) 100064
increased breathlessness. Chest X ray and chest CT scan showed
new bi-apical cavitation. Her sputum was now acid-fast bacilli
smear positive, Mycobacterium tuberculosis complex PCR positive,
with no detectable rifampicin resistance mutations, and by now
her CRPs ranged from 74 to 271 mg/L.
She was commenced on rifampicin, isoniazid, pyrazinamide,
ethambutol and pyridoxine. Through whole genome sequencing
her mycobacterial sample proved to be Mycobacterium microti.
Sequencing implied sensitivity to quinolones, pyrazinamide and
aminoglycosides, but failed to clarify sensitivities to rifampicin,
isoniazid and ethambutol. Moxifloxacin was added to the initial
quadruple regime, but a total of five smear-positive specimens
failed to become liquid culture positive for phenotypic sensitivities
over 8 weeks. Her chest was very slow to settle, but eventually her
sputum production became minimal and her CRP fell to 18 mg/L.
Her antibiotics were continued for 16 months, the duration reflect-
ing her gradual improvement. A CT chest scan at the end of treat-
ment showed extensive residual bi-apical changes, with relative
thinning of her previously very thick cavity walls (Fig. 3). The orig-
inal nodularity in the lower lung fields is not evident. The psoas
abscess resolved on repeat MRI scanning and her neurology grad-
ually improved. The prednisolone dose had been doubled to
20 mg per day while on rifampicin, was then reduced to 10 mg
per day and has gradually been completely weaned. She remains
sputum mycobacterial culture negative 18 months post treatment.
The patient’s home is surrounded by fields and lakes. Her cat
regularly catches and brings into the house a variety of rodents.
These have included voles. Their entrails are cleared up by the
patient and her spouse. The cat remained well.
Discussion
M. microti failed to culture from both respiratory and spinal
samples. We did not prove that this organism was responsible
for the spinal infection, but by exclusion had no other explanation.
A. Wild, V. Shivji, L. Berry et al.
Fig. 3. CT chest scan at the end of treatment.
The psoas abscess did resolve with antibiotics. Without the benefit
of molecular diagnostics and speciation by whole genome
sequencing, we may have treated for conventional M. tuberculosis,
without clear knowledge of sensitivities. However the time course
of evolution seemed indolent for M. tuberculosis. CRPs only rose
later, despite an on-going tissue destructive process.
M. microti is part of the M. tuberculosis complex. Genetically
there are ten reported regions of difference (RD) between M.
microti and M. tuberculosis (Brodin et al., 2002). Importantly RD-1
genes, including those coding for the antigens ESAT-6 and CFP-
10, are absent in M. microti. This has implications for interferon
gamma release assays (IGRA), which cannot therefore be used for
contact tracing, and for pathogenicity. Restoration of RD-1 genes
in a knock-in strain of M. microti rendered it pathogenic in an
immunodeficient mouse model compared with the wild type
(Pym et al., 2002). Nonetheless M. microti is sufficiently pathogenic
to cause infection and disease in a number of hosts. It has been
found in cats (Gunn-Moore et al., 2011a, 2011b), dogs (Deforges
et al., 2004), cattle (Jahans et al., 2004), pigs (Taylor et al., 2006),
wild boar (Chiari et al., 2016), meerkats (Palgrave et al., 2012),
alpacas, llamas (Zanolari et al., 2009); squirrel monkeys (Henrich
et al., 2007), hyrax (Lutze-Wallace et al., 2006), various rodents
(Cavanagh et al., 2002), but the known maintenance host is the
field vole, Microtus agrestis (Kipar et al., 2014). In the United King-
dom there have been large studies on infected cats (Gunn-Moore
et al., 2011a, 2011b; Major et al., 2016). Cutaneous nodular or
ulcerated lesions with regional lymphadenopathy are seen, as well
as pulmonary lesions, hepatosplenomegaly and skeletal lesions.
Infection is probably acquired from rodent sources. In one study
in the United Kingdom 13% of trapped field voles harboured M.
microti (Kipar et al., 2014). These voles had systemic disease most
commonly affecting spleen and liver, but also skin, lymph nodes
and lungs. It is presumed that transmission of infection occurs with
direct contact between animals and devouring.
We are aware of 28 previously published human cases of dis-
ease caused by M. microti – the majority of these were summarised
by Panteix et al. in 2010 (Panteix et al., 2010), with one subsequent
case report in 2020 (Van de Weg et al., 2020). We have reviewed
the available literature. The first report of human infection was
in 1998. Of these cases, 19 had pulmonary disease, with four
reports of extra-pulmonary disease (1 peritoneal, 1 intra-
3
Clinical Infection in Practice 9 (2021) 100064
abdominal, and 2 with osteomyelitis or septic arthritis of the
hip). Disease locus was not described in remaining cases (Kremer
et al., 1998; Geiss et al., 2005; Emmanuel et al., 2007). Symptoms
at presentation were described for 18 patients with weight loss
(13), cough (11), night sweats (7), fever (6) and haemoptysis (2).
Information on chest X-rays is available for 16 cases. Fifteen had
abnormalities, with 12 showing upper lobe infiltration and three
infiltrates elsewhere. Cavitation was present in eight cases. Of four
patients with extra-pulmonary disease, only two had chest X-rays,
of which one was normal and one showed nodular infiltrates.
Exposure to animals was questioned in 20 cases, with four known
exposures – one to mice, one to a domestic pet dog and cat, one to
a raccoon and a dog, and one case lived on a farm.
Of the cases described in the literature, specimen smear-
microscopy was positive in all 23 cases in which it was performed.
Of 19 reported cultures 17 were positive. Culture media were
reported in 15 cases, with seven positive in liquid media only, four
in solid media and four in both liquid and solid media. Time taken
to culture positivity was documented for nine cases and ranged
from 42 to 75 days, with a median of 48 days. This demonstrates
that M. microti is a slow-growing mycobacterium, with most cases
requiring longer than the standard 42 days. The utility of the M.
tuberculosis complex PCR is highlighted by our culture-negative
case. Whilst culture is slow and is not inevitable, susceptibility
testing has proved difficult. Of the 28 cases described in the liter-
ature, 18 did not have drug susceptibility information, or suscepti-
bility testing had failed. Of the remaining 10 cases, five were
sensitive to rifampicin, isoniazid, pyrazinamide and ethambutol.
5 cases were sensitive to rifampicin, isoniazid and ethambutol,
but deemed resistant to pyrazinamide. In six cases sensitivity test-
ing against streptomycin showed susceptibility.
Treatment drug options were known for 19 cases, and all were
treated successfully with a combination of at least three or four
drugs from the standard anti-TB drug combination of rifampicin,
isoniazid, pyrazinamide and ethambutol. Additional drugs were
used in four cases, including ofloxacin, moxifloxacin and clar-
ithromycin. Treatment durations were reported for 17 cases and
ranged from 6 to 48 months, median 24 months. Outcomes were
not known for 5 patients, but three patients died and 20 recovered.
Amongst the three patients who died, two had intra-abdominal
disease, one was a renal transplant recipient and one was HIV pos-
itive. Amongst survivors one had a renal transplant and there were
three others who were HIV positive.
One can ask whether the granulomas seen on trans-bronchial
lung biopsy in our patient were in fact due to sarcoidosis or were
in fact due to mycobacterial infection. If due to mycobacterial
infection, she seemed to have been relatively well for the extent
of nodularity seen on the first CT scan. If due to sarcoidosis this,
plus steroids, may have pre-disposed her to later mycobacterial
infection. However there has been clearance of the nodularity on
her CT scan after antibiotics, and no deterioration in radiology on
withdrawal of steroids.
Diagnosis in this case was aided by the availability of whole
genome sequencing. It may be the first reported human instance
of vertebrodiscitis and a psoas abscess due to M. microti. Although
reportedly less pathogenic than M. tuberculosis this case illustrates
its indolent and tissue destructive potential. She was slow to
recover, but with the antibiotic regime used, remains culture neg-
ative after a prolonged period.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
A. Wild, V. Shivji, L. Berry et al.
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgements
The authors would like to sincerely thank the laboratory staff at
both Nottingham University Hospitals and the national Tuberculo-
sis reference laboratory, along with all the healthcare staff involved
in this patient’s case. We would also like to thank the patient for
giving us their support and consent to publish this case.
Consent
Written informed consent for publication of their clinical details
and clinical images was obtained from the patient. A copy of the
consent form is available for review by the Editor of this journal.
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