Open Journal of Respiratory Diseases, 2013, 3, 107-112
http://dx.doi.org/10.4236/ojrd.2013.32016 Published Online May 2013 (http://www.scirp.org/journal/ojrd)
Clinical Analysis of Pulmonary Nontuberculous
Mycobacterial Disease Diagnosed as Coincidental
Pulmonary Infection Due to Mycobacterium Species*
Yoshihiro Kobashi#, Keiji Mouri, Yasushi Obase, Shigeki Kato, Mikio Oka
Department of Respiratory Medicine, Kawasaki Medical School, Kurashiki, Japan
Received April 3, 2013; revised April 28, 2013; accepted May 8, 2013
Copyright © 2013 Yoshihiro Kobashi et al. 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
Objectives: We analyzed the clinical characteristics of patients with pulmonary mycobacterial disease diagnosed as
coincidental pulmonary infection due to Mycobacterium species. Materials and Methods: One hundred sixty patients
satisfied the diagnostic criteria of nontuberculous mycobacterial disease proposed by American Thoracic Society during
the last seven years. Six patients (3.8%) were coincidental pulmonary infection due to two Mycobacterium species. We
investigated the background, laboratory findings, microbiological findings, radiological findings, treatment and progno-
sis. Results: There were six patients, 3 males and 3 females, with a mean age of 71.7 years. The causative microorgan-
isms of coincidental pulmonary infection consisted of Mycobacterium avium + Mycobacterium intracellulare in two
patients, Mycobacterium avium + Mycobacterium kansasii in one, Mycobacterium intracellulare + Mycobacterium che-
lonae in one, Mycobacterium intracellulare + Mycobacterium abscessus in one, and Mycobacterium intracellulare +
Mycobacterium tuberculosis in one. Regarding the radiological findings, the distribution of the lesion was frequently
shown in both the right middle and left lingula lobes, but the extent of the lesion was limited within the unilateral lung
field. Centrilobular small nodules with bronchiectasis were recognized in all patients and cavities or infiltration shad-
ows were recognized in half of them on chest computed tomography. A definite diagnosis was obtained by bronchoal-
veolar lavage fluid in four patients and expectorated sputum in two. Combined chemotherapy was performed for two
patients and that for pulmonary tuberculosis in one. Conclusions: Coincidental pulmonary infection due to Myco-
bactterium species occurred at a low percentage. Although most patients were elderly with underlying disease and
clinical features were compatible with pulmonary Mycobacterium a vium complex disease, the prognosis was compara-
tively good with and without treatment.
Keywords: Coincidental Pulmonary Infection; Mycobacterium Species
1. Introduction
Since the American Thoracic Society (ATS) proposed
the diagnostic guidelines of pulmonary nontuberculous
mycobacterial (NTM) disease in 2007 [1], the number of
patients with pulmonary NTM disease has been increas-
ing in Japan [2]. Of many causative microorganisms of
pulmonary NTM disease, Mycobacterium avium is the
most common pathogen, Mycobacterium intracellulare is
the second, and Mycobacterium kansasii is the third one
in Japan. Among the microbiological diagnostic criteria
of pulmonary NTM disease, if positive culture results
from at least two separate expectorated sputum samples
or positive culture results from at least one bronchial
wash or lavage are obtained, we can confirm a definite
diagnosis of pulmonary NTM disease in combination
with clinical findings.
Recently, because bronchoscopy has been frequently
performed to obtain a definite diagnosis of pulmonary
NTM disease and its diagnostic usefulness was reported
[3,4], we sometimes discover coincidental pulmonary
infection due to Mycobacterium species. There are few
reports about the clinical characteristics of coincidental
pulmonary infection due to Mycobacterium species as far
as we investigated. Therefore, we clarified the clinical
characteristics of patients with coincidental pulmonary
infection due to Mycobacterium species during the last
seven years in this study.
*The authors declare that they have no conflict of interest (COI).
#Corresponding author.
C
opyright © 2013 SciRes. OJRD

Y. KOBASHI ET AL.
108
2. Materials and Methods
This study was approved by the institutional review
board (Ethical Committee of Kawasaki Medical School).
Informed consent from each patient was not required
because all data were collected retrospectively. We se-
lected one hundred and sixty patients who satisfied the
diagnostic criteria of NTM disease proposed by ATS [5]
in our hospital between January 2005 and December
2011. Among these patients, six patients (3.8%) had co-
incidental pulmonary infection due to two Mycobacte-
rium species. We investigated the backgrounds, labora-
tory findings, microbiological findings, radiological find-
ings, diagnostic methods, treatment and prognosis of
these patients and the remaining patients with pulmonary
NTM disease (154 patients) in this study.
All data from patients were drawn from charts, which
included age, sex, smoking history and past medical his-
tory. Laboratory findings such as total protein or albumin
showing nutritional condition purified protein derivatives
(PPD) or QuantiFERON (QFT) and microbiological find-
ings such as causative microorganisms or drug sensi-
tivity tests using the Broth MIC method (Kyokuto Phar-
maceutical Industrial Co. Ltd.), as well as the results of
smear and culture tests for acid-fast bacilli, were re-
viewed. Radiological findings, such as portion, extension
of lesion 1) within one-third of the unilateral lung field; 2)
within the unilateral lung field; 3) over the unilateral lung
field) for pulmonary NTM disease, bronchiectatic change,
cavity, centrilobular small nodules, and infiltration shad-
ows, were also reviewed. All radiological findings were
evaluated on computed tomography (CT) scans of the
chest by one pulmologist and one radiologist. In terms of
treatment, the medication for pulmonary NTM disease
was reviewed. Long-term follow-up was evaluated for
these patients to investigate the prognosis.
3. Results
The clinical findings of the patients with coincidental
pulmonary infection due to Mycobacterium species are
shown in Table 1. Six patients (3.8%) had coincidental
pulmonary infection due to two Mycobacterium species,
including Mycobacterium avium complex (MAC). The
mean age of the six patients was 71.7 years and there
were three males and three females. Two patients had a
smoking history. All patients had underlying diseases
and one of six patients received immunosuppressive
treatment.
Regarding the laboratory findings, nutritional condi-
tions such as total protein or albumin were preserved
except in one patient. PPD was positive for two patients
tested and QFT was negative for all five patients tested.
The causative microorganisms in patients with coinci-
dental pulmonary infection due to Mycobacterium spe-
cies consisted of Mycobacterium avium + Mycobacte-
rium intracellulare in 2 patients, Mycobacterium avium +
Mycobacterium kansasii in 1, Mycobacterium intracellu-
Table 1. Clinical findings of the patients with coincidental pulmonar y infe c tion due to Mycobacterium species.
Laboratory findings Drug-sensitivity test
Case Age Sex Smoking
history
Past
history TP
(g/dl)
Alb
(g/dl) PPD QFT (ZU/l)
Causative
microorganisms SMEBKMINH RFP LVFX CAMTMAMK
1 61 M (+)
Bronchial
asthma
Gastric ulcer
Glaucoma
7.3 4.6 00
10 10

0.21
M. avium
+
M. kansasii
32
>128
4
16
64
>128
N.D.
N.D.
8
2
1
>32
2
32
2
8
>16
>16
2 68 F (−) Breast
Ca(ope) 6.7 4.1 N.D. <0.05
M. avium
+
M. intracellulare
16
>128
>128
>128
64
128
>32
>32
4
8
8
8
1
2
>16
>16
16
>16
3 72 F (−) Gastric
Ca(ope) 8 3.7 N.D. <0.05
M. intracellulare
+
M. chelonae
16
16
>128
64
64
32
32
>32
0.5
8
4
2
1
0.125
16
8
8
>16
4 84 M (−)
Gastric
Ca(ope)
Unstable
angina
7.9 4.1 00
20 15

<0.05
M. intracellulare
+
M. abscessus
8
>128
>128
>128
64
32
32
>32
2
>32
4
16
0.5
32
>16
>16
8
>16
5 70 F (−)
RA(Steroid)
Basedow
disease
6.4↓ 3.4↓ N.D. N.D.
M. tuberculosis
+
M. intracellulare
10
8
2.5
4
20
8
1
32
40
0.25 2 0.25 44
6 75 M (+) COPD 7 4 N.D. <0.05
M. avium
+
M. intracellulare
32
4
>128
8
64
32
N.D.
N.D.
4
0.125
32
1
4
0.5
>16
16
>16
4
TP: Total protein; Alb: Albumin; PPD: Purified protein delivatives; QFT: QuantiFERON; SM: Streptomycin; EB: Ethambutol; KM: Kanamycin; INH: Isoni-
azid; RFP: Rifampicin; LVFX: Levofloxacin; CAM: Clarithromycin; TH: Thionamide; AMK: Amikacin; RA: Rheumatoid arthritis; COPD: Chronic obstruc-
ive pulmonary disease. t

Y. KOBASHI ET AL. 109
lare + Mycobacterium chelonae in 1, Mycobacterium
intracellulare + Mycobacterium abscessus in 1, and My-
cobacterium tuberculosis + Mycobacterium intracellu-
lare in 1, respectively. The results of drug sensitivity
tests for several antibiotics are shown in Table 1. Al-
though the minimum inhibitory concentration (MIC)
showed higher concentrations of most antibiotics for
Mycobacterium kansasii and Mycobacterium abscessus,
it was preserved at lower concentrations of clarithromy-
cin (CAM) for isolated MAC in most patients. The diag-
nostic methods used bronchoscopic specimens in four
patients and expectorated sputum in two.
Concerning the radiological findings (Table 2), lesions
due to pulmonary NTM disease existed within the uni-
lateral lung field and bilaterally in all patients. All pa-
tients had centrilobular small nodules with bronchiectasis
and three of six patients showed multiple cavitary lesions
or infiltration shadows. These radiological findings re-
sembled those of pulmonary MAC disease.
Anti-mycobacterium species treatment was prescribed
for three patients after the diagnosis of pulmonary my-
cobacterial disease. The clinical effect was good for these
three patients with an improvement in clinical symptoms
and radiological findings. There were no complications
with pulmonary NTM disease and the prognosis was
comparatively good (all patients survived from one to
seven years after a definite diagnosis).
The clinical findings of the patients with the remaining
patients with pulmonary NTM disease (154 patients) are
shown in Table 3. The mean age of these patients were
younger and the frequency of patients with underlying
disease was lower compared to those with coincidental
pulmonary infection. The causative microorganisms in
the remaining patients with pulmonary NTM disease
consisted of M. avium in 73 patients, M. intacellulare in
60, M. kansasii in 14, and others in 7, respectively. Con-
cerning the treatment, combined chemotherapy including
antituberculous drugs was performed for half of these
patients. The mortality rate was comparatively low and
most of these patients died of other complications or un-
derlying diseases.
4. Discussion
Since bronchoscopy has been frequently performed to
obtain a definite diagnosis of pulmonary NTM disease,
the number of patients with this disease has been in-
creasing and the usefulness of bronchoscopy has been
reported [3,4]. In this study, the frequency of coinciden-
tal infection due to Mycobacterium species was a low
percentage (3.8%: 6/160) and two species including
MAC were identified in all patients. In a previous report,
Jarand et al. indicated that over half of patients with My-
cobacterium abscessus pulmonary disease (55%) had
coexistent, or a history of, pulmonary MAC disease [5].
They investigated the frequency of only coincident pul-
monary infection due to both Mycobacterium abscessus
and MAC and there are few epidemiological studies on
coincidental pulmonary infection due to different several
Mycobacterium species.
Regarding the background of patients with coinciden-
tal pulmonary infection due to Mycobacterium species,
Table 2. Clinical findings of the patients with coincidental pulmonar y infe c tion due to Mycobacterium species.
Radiological findings
Case
Portion Extent of
lesion※ Cavity Bronchiectatic
change
Centriliobular
small nodules
Infiltration
shadow
Diagnostic
methods Treatment Clinical effect Complication Prognosis
1 Bilateral 2 (+) (+) (+) (+)
BALF
(Smear(+),
Culture(+))
RFP + EB + CAM
+ S
(6 months)
Good (−) Survival
(1 year)
2 Bilateral 1 (−) (+) (+) (−)
BALF
(Smear(−),
Culture(+))
(−) (−) Survival
(7 years)
3 Bilateral 2 (+) (+) (+) (+)
Sputum
(Smear(+),
Culture(+)
CAM + EB + SM +
LVFX
(1 year)
Good (−) Survival
(3 years)
4 Bilateral 2 (+) (+) (+) (+)
BALF
(Smear(+),
Culture(+))
(−) (−) Survival
(3 years)
5 Bilateral 2 (−) (+) (+) (−)
Sputum
(Smear(+),
Culture(+))
INH + RFP + EB
+ PZA (6 months) Good (−) Survival (2 years)
6 Bilateral 2 (−) (+) (+) (−)
BALF
(Smear(+),
Culture(+))
(−) (−) Survival
(1 year)
B
ALF: Bronchoalveolar lavage fluid; ※1: Within one-third of the unilateral lung field; 2: Within the unilateral lung field; 3: Over the unilateral lung field.

Y. KOBASHI ET AL.
110
Table 3. Clinical findings of the patients with pulmonary
NTM disease excluding the patients with coincidental pul-
monary infection due to Mycobacterium species (154 cases).
Age (Mean ± S.D., years) 68.5 ± 10.4
Sex (Male:Female ) 61:93
Smoking history (+) 70 (45%)
Underlying disease (+) 108 (70%)
46 (30%)
Respiratory disease
Non-respiratory disease



62 (40%)
Causativemicroorganisms
M. avium 73 (47%)
M. intracellulare 60 (39%)
M. kansasii 14 (9%)
Others 7 (5%)
Radiological findings
109 (71%)
Bilateral
Portion Unilateral



45 (29%)
60 (39%)
78 (51%)
1
Extension #2
3





16 (10%)
Cavity 95 (62%)
Bronchiectatic change 137 (89%)
Diagnostic methods
Sputum 72 (47%)
BALF 71 (46%)
Others 11 (4%)
Treatment
Combined chemotherapy 80 (52%)
Surgical operation 6 (4%)
Prognosis
Died 18 (12%)
BALF: Bronchoalvelar lavage fluid;
1:Within one-third of unilateral lung field
#2:Within unilateral lung field
3:Over unilateral lung field




elderly patients with underlying diseases such as respira-
tory diseases or malignancies were common, as in pre-
vious reports [6,7], but nutritional conditions were pre-
served except in one case.
The radiological findings of 6 patients with pulmonary
MAC disease such as centrilubular small nodules with
bronchiectatic changes mainly in the right middle lobe or
left lingula segment were a common characteristic. Ra-
diological abnormalities of pulmonary MAC disease
have been classified into the following five patterns on
the basis of chest CT: nodular and bronchiectatic disease,
fibrocavitary disease, solitary nodule disease, hypersen-
sitivity disease, and disseminated disease [1]. Of the five
patterns, nodular and bronchiectatic disease was the most
frequent and fibrocavitary disease was the second most
frequent in previous reports. All patients had MAC as
causative microorganisms of coincidental pulmonary
infection in this study. The radiological findings of My-
cobacterium abscessus or Mycobacterium chelonae pul-
monary disease have been said to resemble those of
MAC pulmonary disease in previous reports [1,5,8]. On
the other hand, the radiological findings of Mycobacte-
rium kansasii pulmonary disease or pulmonary tubercu-
losis had characteristic thin or thick cavities located in
the apical segment [9]. We think that it is difficult to
suggest the causative microorganism from the radiologi-
cal findings in patients with coincidental pulmonary in-
fection due to Mycobacterium species based on this study.
We followed-up patients with pulmonary MAC disease,
and Mycobacterium tuberculosis were also isolated si-
multaneously from one patient (Case 5). She was receiv-
ing immunosuppressive treatment (corticosteroid drugs)
and was in a poor nutritional condition. Because new
lesion appeared in the bilateral upper lobe on periodical
chest CT (Figure 1), the attending physician performed
an acid-fast bacilli examination and, finally, Mycobacte-
rium tuberculosis was detected. Physicians must be care-
ful when treating immunocompromised patients compli-
cated with pulmonary tuberculosis.
(a)
(b)
Figure 1. (Case 5) Coincidental pulmonary infection due to
Mycobacterium intracellulare and Mycobacterium tuberculo-
sis. New lesion with centrilobular small nodules on chest CT
appea r ed i n th e b i l a tera l u p p e r l obe . ( a ) 2 009. 10; (b) 2010.11.

Y. KOBASHI ET AL. 111
Concerning the diagnostic methods, the bronchoscopic
procedure is important to acquire accurate information
about coincidental pulmonary infection due to Mycobac-
terium species. In this study, four of six patients were
given an accurate diagnosis using bronchoalveolar lavage
fluid (BALF). Although bronchoscopy is an invasive
technique, we think it is necessary to consider a differen-
tial diagnosis of pulmonary NTM disease.
Regarding the selection of treatment, ATS/IDSA pro-
posed a guideline for treatment of pulmonary NTM dis-
ease in 2007 [1]. The therapy for pulmonary MAC dis-
ease was recommended as combined chemotherapy in-
cluding a macrolide (clarithromycin (CAM) or azithro-
mycin (AZM)), ethambutol (EB), rifampicin (RFP) ±
aminoglycoside depending on disease status and/or se-
verity. On the other hand, therapy for pulmonary Myco-
bacterium abscessus or Mycobacterium chelonae disease
was recommended as combined chemotherapy consisting
of a macrolide, aminoglycoside, imipenem and cefoxitin
and that for pulmonary Mycobacterium kansasii disease
was combined chemotherapy including isoniazid (INH),
RFP and EB. There is a little difference in the treatment
between Mycobacterium species. Therefore, it is impor-
tant to identify the species in NTM. However, the clinical
effect of combined chemotherapy for pulmonary NTM
disease except for pulmonary Mycobacterium kansasii
disease was not good (clinical symptoms and/or abnor-
mal radiological findings) [10]. There are no guidelines
for initiating or ending treatment or the adaptation of
treatment for elderly patients. Consequently, combined
chemotherapy was performed for three of six patients
because there were mainly elderly patients in this study;
multi-drug chemotherapy including CAM for two pa-
tients and antituberculous treatment for Mycobacterium
tuberculosis for one. The clinical effect due to combined
chemotherapy was good and the prognosis was also good
despite their general condition. We do not think there
was a relationship between coincidental pulmonary in-
fection and clinical effect or prognosis of the subjects in
this study.
There are a few limitations in this study. Firstly, there
were only a few patients with coincidental pulmonary
infection due to Mycobacterium species among patients
with pulmonary mycobacterial disease in one hospital in
a restricted area, so we need to perform a large-scale
study including several hospitals in Japan to get an accu-
rate of coincidental mycobacterial infection. Secondly,
the rate of coincidental mycobacterial infection was lower
than in other reports [5]. This is because the diagnostic
accuracy of the acid-fast bacilli culture was poor in our
laboratory when patients with coincidental infection due
to Mycobacterium species were tested.
In conclusion, the rate of coincidental pulmonary in-
fection due to Mycobacterium species was a low per-
centage and clinical characteristics were similar to those
of pulmonary MAC disease mainly on the radiological
findings. Although most patients were elderly with un-
derlying diseases, the clinical effect and prognosis were
comparatively good.
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