Advances in Infectious Diseases, 2013, 3, 253-256
Published Online December 2013 (http://www.scirp.org/journal/aid)
http://dx.doi.org/10.4236/aid.2013.34038
Open Access AID
253
Fatal Pulmonary Mycobacterium Celatum Infection in an
Immunocompetent Patient. An Eight-Year Follow-Up of
the First Case, a Review of the Literature and a Report of
Beta-2 Microglobulin as a Potential Indicator of Disease
Severity*
S. Rustscheff, J. Darelid
Department of Internal Medicine, Värnamo General hospital and Department of Infectious diseases, Ryhov County hospital,
Jönköping, Sweden.
Received October 4th, 2013; revised November 3rd, 2013; accepted November 10th, 2013
Copyright © 2013 S. Rustscheff, J. Darelid. This is an open access article distributed under the Creative Commons Attribution Li-
cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Setting: Swedish cou nty hospital. Objective: Pulmonary M. celatum infection h as been previously described only twice
in an immunocompetent individual with no pre-existing chest disease. We describe the first Swedish case report of un-
usual drug-related complications and review the literature. Discussion: Atypical mycobacteriosis is often difficult to
treat. We describe a fatal case of m celatum pneumonia in a previously healthy patient, unusual side effects encountered
during her treatment and also the report of the utility of beta-2-microglobulin as a way to measure disease activity in my-
cobacterial infections. Conclusions: M. celatum may cause fatal pneumonia in previously healthy individuals. Treating
the disease may be fraught with difficulty and th ere is a risk for very severe side effects, all of which must be weighed
before taking the decision to treat this disease.
Keywords: Mycobacterium Celatum; Immunocompenent
1. Introduction
Mycobacterium celatum was discovered in 1993 [1]. It
belongs to the Runyon group of nonchromogens and has
biochemical characteristics similar to M. xenopii and M.
avium intracellulare. Mycolic acid liquid chromatogram-
phy (HPLC) or 16S rRNA sequencing was often per-
formed for proper identification. However, modern as-
says utilizing reverse hybrid ization is av ailable no wada ys.
It is a pathogen of various animals such as the domestic
ferret [2] and the white-tailed trogon [3] and may also be
found in clinically healthy aqua rium fish [4].
The first human cases described by Tortoli and Pier-
simoni [5] were found among AIDS victims and a grand
total of 28 patients have been reported since 1994. Infec-
tions in immunocompetent patients seem to be exceed-
ingly rare. The first report of a localized lymp hadenitis in
a previously healthy boy, came in 1994 [6] and a second
in a 22-month-old infant was in 2004 [7]. The first case of
pulmonary infection in an immunocompetent individual
was detected post mortem in a patient treated for suspect-
ed tuberculosis [8]. The second case was described from
Maastricht in 1999, where a 61-year-old male was pre-
sented with a history of three years of we ight loss, co ugh,
malaise and had a cavity in the right upper lobe. This
case was also misdiagnosed as M. tuberculosis due to a
false positive AMTD test [9]. The next case described in
Italy was a 63-year-old HIV negative lady who, however,
had suffered from pulmonary tuberculosis at the age of
16 and, in addition, had developed bronchiectases [10].
We would like to describe the first fatal case of m cela-
tum pneumonia in an immunocompetent individual with
no predisposing chest pathology.
*This paper has received support in the form of an unrestricted grant o
f
four weeks of paid research leave to dr Stefan Rustscheff, a part o
f
which has been used to write this paper. This paper is deemed not to
need ethical approval from the ethics committee of Linköping Univer-
sity hospital, as it is a retro spective review of a clinical case.

Fatal Pulmonary Mycobacterium Celatum Infection in an Immunocompetent Patient.
An Eight-Year Follow-Up of the First Case, a Review of the Literature and a Report
254
of Beta-2 Microglobulin as a Potential Indicator of Disease Severity
2. Case Report
A 77-year-old unmarried former wet-nurse and ship’s
stewardess was in 2001 referred from her private practi-
tioner to a chest clinic in southern Sweden. She was a
native of Sweden but had lived in the United States for
decades as well. She was a lifelong non-smoker.
She presented with a non-productive cough and 10 kg
weight loss. Her chest X-ray showed extensive interstitial
infiltrates in the right lung, discrete infiltrates in the left,
and a cavitation of the right ap ex lung. A ventricular lav-
age was threefold negative on PCR for M. tuberculosis as
was culture on Löwenstein-Jensens medium and the
BACTEC 460 Radiometric system. Four sputum samples
were negative on direct microscopy and PCR against M.
tuberculosis. Her PPD was nevertheless 15 mm. A bron-
choscopy, a ventricular lavage and a sputum sample in
2002 yielded a NTM species both on Bactec and Löwen-
stein-Jensens medium which was identified as Mycobac-
terium avium-intracellulare by the Accuprobe kit. The
strain unfortunately died before sensitivity tests could be
performed. Nevertheless, ex juvantibus treatment was in-
stituted.
Her initial ESR (sedimentation) was 77. She was put
on Rifampin 450 mg, Isoniazid 300 mg and ethambutol
800 mg and followed. Her cough disappeared but due to
rapidly progressive loss of vision, ethambutol was dis-
continued after 11 months of treatment. A central retinal
vein thrombosis was found to be the cause of the loss of
vision. A new bronchoscopy 2003 yielded a mycobacte-
rium sensitive to clarithromycin, amikacin and ethambu-
tol but resistant to ciprofloxacin and rifampicin. This
turned out to be the first Swedish isolate of M. celatum. It
was classified at Karolinska University using 16s rRNA
sequencing.
A re-bronchoscopy 2004 yielded the same result, now
using gas chromatography at the mycobacterial research
laboratory, Lund University (Kristina Persson, BmA,
pers.comm). The growth of M. celatum was considered
to be a commensal. The patient had been losing weight
constantly since 2001, going from 61 kg to 44 kg. This
was attributed to chewing difficulties due to a concomi-
tant trigeminal neuralgia. Her chest x-ray never showed
resolution of the infiltrates and her ESR rose to 81. No
treatment was instituted.
The patient moved to our area in 2005. She was re-
ferred to us from the first hospital for follow-up. She had
an ESR of 90 and a dry cough. Her chest X-ray in May
2005 showed the same picture as in 2004 with right-sided
perihilar fibrotic infiltrates and volu me loss. A new bron-
chos copy was performed and yielded M. celatum, sensi-
tive to amikacin, ofloxacin, clarithromycin and etham-
butol. The strain was classified through reverse hybridi-
zation by the commercial kit “Genotype CM/AS” (Hain
Diagnostics) at Karolinska University. It was also suc-
cessfully cultured on Löwenstein-Jensens medium and
Bactec. Treatment was now instituted with amikacin 500
mg twice weekly, ethambutol and clarithromycin, 1 g per
diem and moxifloxacin 400 mg for two months, with the
intention to reduce ethambutol to 600 mg and discon-
tinue amikacin thereafter, for a total treatment regime of
at least 18 months.
We followed the patient and noted a reduction in ESR
from 90 to 44 and a weight gain to 50 kg. Unfortunately
in January 2006 the patient suffered another retinal vein
thrombosis in her healthy eye and was now clinically
amaurotic. Ethambutol was discontinued in november
2006 because the patient still had some peripheral vision
left and we did not want to risk it if ethambutol happened
to be the cause of her retinal thromboses. Unfortunately,
this decision soon led to a relapse in her pulmonary dis-
ease in april 2007.
She rose in ESR to 89 and developed new patchy infil-
trates on her chest X-ray. A decision was taken to sup-
plement her treatment with amikacin 500 mg twice
weekly again. 3 months afterwards we saw a resolution
of the infiltrates and a return to previous levels in ESR,
42. She remained culture negative. Her cough disappear-
ed and, in spite of her amaurosis she felt much better
than before institution of treatment for her mycobacterial
disease. We could not rule out that her recurrent retinal
thromboses might be a side effect from ethambutol and
she was kept off this drug. In spring 2008 she unfortu-
nately suffered a relapse, making it necessary for us to
reinstate treatment with ethambutol, moxifloxacin and
amikacin in the same dosag e as previously tolerated. This
time, however, the patient developed severe hearing loss
after having had carbamazepine prescribed by another
source for trigeminal neuralgia. Unfortunately, the hear-
ing loss was only partially reversible and the patient was
now dependent on a hearing aid, as well as being amau-
rotic! All antimycobacterial drugs were discontinued in
february 2009. Her ESR varied between 50 and 94 dur-
ing 2009, while her chest X-ray showed a progressively
floccular subhilar infiltrate with an atelectasis until Sep-
tember, when she was admitted with respiratory insuffi-
ciency and an SaO2 of 83%. This X-ray actually showed
partial resolution of the infiltrates but also oedema and
cardiomegaly. She had a 40 mm Hg right ventricular
pressure on her echocardiography, a creatinine level of
113 mmol/l, normal ultrasoun d examinations of her legs,
a D dimer of 2.69 (limit 0.25) and a ventilation perfusion
scintigraphy showing at least an intermediate likelihood
of pulmonary embolism. Treatment with tinzaparin
20,000 E/ml, 0.7 ml·s·c daily was institu ted for 6 months .
The patient could yet again be discharged without sup-
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Fatal Pulmonary Mycobacterium Celatum Infection in an Immunocompetent Patient.
An Eight-Year Follow-Up of the First Case, a Review of the Literature and a Report 255
of Beta-2 Microglobulin as a Potential Indicator of Disease Severity
plemental oxygen.
In august 2010 the patient returned to us, now again
with a respiratory insufficiency and a fast atrial fibrilla-
tion. She was reinstituted on tinzaparin and also received
loracarbef and furosemide. Sputum samples grew proteus
mirabilis and treatment was changed to ciprofloxacin.
Her ESR was only 32 and her CRP 36. Her x-ray showed
progressive infiltrates in her right lower lobe. Neverthe-
less she regained her respiratory sufficiency and was
discharged on September 13th with an alleviated cough in
order to wait for the results of the mycobacterial samples.
She was found dead in her sleep at her home on Sep-
tember 14th, 2010. Her sister refused an autopsy.
During the whole eight-year period we followed her
beta-2 microglobulin serum levels. She had a reasonable
kidney function for her age, with a creatinine clearance
of 40 - 45 and no other known reasons for an elevated
level of beta-2 microglobulin. Her levels before institu-
tion of treatment were 4.1 mg/l (ref 0.6 - 2.4). Treatment
resulted in a rapid drop to 2.7 mg/l. In april 2007, con-
comitant with her exacerbation, levels rose to 3.8 mg/l.
They then went dow n with treatment and hovered around
2.7 mg/l until autumn 2008, when she had another exac-
erbation and a concomitant rise to 5.4 mg/l. On treatment
levels declined to 2.9 mg/l and have on discontinuation
of all therapy risen again to 3.9 mg/l in summer, 2009.
Unfortunately, no beta-2-microglobulin samples were
measured on her last admission to our ward.
3. Discussion
Atypical mycobacteria may be found as commensals in
the bronchial tree, but a surprising number of them are
pathogens in a true sense. Treatment may be prolonged
and very difficult.
A decision to treat non-tuberculous mycobacteria rests
on repeated cultures of the same Specimen, or culture
positive cases with progressive disease and no other
known cause.
We know that M celatum may be misclassified as M
tuberculosis with the Amplified M tuberculosis direct test
[11]. We have been able to grow M. celatum on three
occasions and the patient has responded to treatment,
relapsed twice after amikacin was withdrawn, improved
on its reinstitution, and, finally, succumbing to the dis-
ease when treatment was withheld. We cannot rule out
that this patient first suffered from a mycobacterium
avium-intracellulare infection but we deem it highly un-
likely that this p athogen would be so easily treated th at it
would disappear after just six months of chemotherapy,
never to return, especially when this patient immediately
afterwards g ot col o ni zed by M. celatum.
4. Conclusions
We deem that it is the first Swedish case of a Mycobacte-
rium celatum infection, the first fatal case in a previously
healthy individual, and th e third case in the world of pul-
monary infection in an immunocompetent patient with no
previous lung disease, confirming that M. celatum is a
true pathogen in man. The PPD test was strong ly positive.
Cultures, direct smears and PCR assays have been nega-
tive for M. tuberculosis. We therefore suggest that the
PPD may cross-react with M. celatum. A negative Quan-
tiferon Go ld test has b een performed in 2009. W e postu-
late that central retinal vein thrombosis might be a rare
side effect of etha mbutol.
Unfortunately, the ototoxic effect of aminoglycosides
is well known and may occur more frequently in the eld-
erly, when treatment is prolonged and when other oto-
toxic drugs are added. We therefore advise the utmost
caution when adding potentially ototoxic and/or nephro-
genic drugs to an aminoglycoside-containing regimen,
even if the aminoglycoside is given in a low total weekly
dose. We would also like to point out the dangers of
withholding treatment altogether in these infection s .
Finally, we would like to draw attention to beta-2 mi-
croglobulin, which is said to be synthetised in granulo-
mata. There is an excellent paper published on beta-2 mi-
croglobulin levels in tuberculosis p atients [12]. We tenta-
tively postulate that this test could be of potential value
in monitoring the course of non-tuberculous mycobacte-
rial diseases.
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Fatal Pulmonary Mycobacterium Celatum Infection in an Immunocompetent Patient.
An Eight-Year Follow-Up of the First Case, a Review of the Literature and a Report
of Beta-2 Microglobulin as a Potential Indicator of Disease Severity
Open Access AID
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