Respiratory Medicine 139 (2018) 91–100

Contents lists available at ScienceDirect

Respiratory Medicine
journal homepage: www.elsevier.com/locate/rmed

Clinical, radiological and molecular features of Mycobacterium kansasii T

pulmonary disease
Zofia Bakułaa, Justyna Kościuchb, Aleksandra Safianowskab, Małgorzata Proboszczb,
Jacek Bieleckia, Jakko van Ingenc, Rafał Krenkeb, Tomasz Jagielskia,∗
a
Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland
b
Department of Internal Medicine, Pulmonary Diseases & Allergy, Medical University of Warsaw, Warsaw, Poland
c
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands

A R T I C LE I N FO A B S T R A C T

Keywords: Background: Studies concerning sociodemographic, clinical, and laboratory features of Mycobacterium kansasii
Nontuberculous mycobacteria (NTM) pulmonary disease are few and based on small patient cohorts. The objective of the study was to evaluate
Mycobacterium kansasii characteristics of patients from whom M. kansasii respiratory isolates were recovered and to provide a detailed
Mycobacterial lung disease description of M. kansasii disease.
Fibro-cavitary disease
Basic procedures: Retrospective review of electronic medical records of all patients for whom at least one positive
Nodular/bronchiectatic disease
Infiltrative disease
M. kansasii culture was obtained at the Department of Internal Medicine, Pulmonology and Allergology of the
Warsaw Medical University between the year 2000 and 2015. Patients were categorized as having mycobacterial
disease or as isolation cases based on the American Thoracic Society and Infectious Diseases Society of America
(ATS/IDSA) diagnostic criteria.
Main findings: The study comprised of 105 patients (63 females, 42 males, mean age 64.6 ± 17.8 years). Of
these, 86 (81.9%) were diagnosed as having M. kansasii disease. The proportion of positive smear microscopy
was significantly higher in patients with M. kansasii disease compared to M. kansasii isolation (P < 0.001).
There were no statistically significant differences between M. kansasii disease and isolation cases in terms of
clinical symptoms or comorbidities. Patients with M. kansasii disease presented most commonly (43/86, 50%)
fibro-cavitary disease upon radiology. Lesion distribution usually showed bilateral upper lobe involvement.
Among the 191 isolates genotyped, all were identified as M. kansasii type I.
Principal conclusions: The findings from this study support the relaxation of the diagnostic criteria for the de-
finition of M. kansasii disease, set forth by ATS/IDSA. Molecular typing did not differentiate isolates from pa-
tients with true disease from those with isolation only; the role of bacterial virulence factors thus remains
elusive.

1. Introduction
Until the mid-20th century, nontuberculous mycobacteria (NTM)
were considered non-pathogenic, environmental bacteria and the clin-
ical significance of diseases caused by these microorganisms was largely
neglected. In contrast, various NTM diseases have been increasingly
reported in the last decades. This could be attributed to several factors,
including greater clinician awareness, a rising number of susceptible
hosts (old age, comorbidities, immunodeficiencies) and improved di-
agnostic sensitivity [1–3]. To date, over 170 NTM species have been
identified [LPSN database; http://www.bacterio.net/] and almost 30 of
these species have been reported as the cause of pulmonary and ex-
trapulmonary diseases [3].
Mycobacterium kansasii is one of the six most commonly isolated
NTM species across the world. In Poland, the isolation rate of this pa-
thogen is particularly high, exceeding 35% of total NTM isolations,
compared with respective rates of 5% in Europe and 4% globally [2].
Pulmonary disease caused by M. kansasii tends to cluster in specific
geographical locations, with Central Europe being one of the hotspots
[2]. However, since M. kansasii has almost exclusively been recovered
from municipal tap water [4], its distribution in different regions might
be rather attributable to municipal water systems than specific

∗
Corresponding author. Department of Applied Microbiology, Institute of Microbiology, Faculty of Biology, University of Warsaw, I. Miecznikowa 1, 02-096 Warsaw, Poland.
E-mail addresses: zofiabakula@biol.uw.edu.pl (Z. Bakuła), j_kosciuch@o2.pl (J. Kościuch), aleksandra.safianowska@wum.edu.pl (A. Safianowska),
m.proboszcz@wp.pl (M. Proboszcz), jbielecki@biol.uw.edu.pl (J. Bielecki), jakko.van.ingen@rivm.nl (J. van Ingen), rafalkrenke@interia.pl (R. Krenke),
t.jagielski@biol.uw.edu.pl (T. Jagielski).

https://doi.org/10.1016/j.rmed.2018.05.007
Received 22 December 2017; Received in revised form 26 April 2018; Accepted 8 May 2018
Available online 09 May 2018
0954-6111/ © 2018 Elsevier Ltd. All rights reserved.

Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Z. Bakuła et al.
ecological niche. In many countries there is no active surveillance of M.
kansasii (or any other NTM) disease. Thus, the true prevalence of M.
kansasii disease remains largely unknown. The incidence of M. kansasii
disease was estimated at 0.3, 0.6, and 1.5 cases per 100,000 in the UK,
Japan, and Spain, respectively [5–7].
Typically, M. kansasii disease presents as apical fibro-cavitary lung
disease, bearing much clinical resemblance to pulmonary tuberculosis
(TB). The other less frequent pulmonary manifestation is nodular
bronchiectasis. Extrapulmonary manifestations are even rarer and in-
clude lymphadenitis, skin and soft-tissue infections, and disseminated
disease. Like other NTM pulmonary diseases, those due to M. kansasii
are believed to be scarcely contagious with only two surmised cases of
human-to-human transmission described in the literature [8,9].
A definite diagnosis of M. kansasii disease requires three criteria
established by the American Thoracic Society and Infectious Diseases
Society of America (ATS/IDSA), to be fulfilled (i.e. microbiologic,
clinical and radiological) [10]. The ATS/IDSA 2007 document em-
phasizes the necessity for NTM culture positivity of at least two separate
sputa or one bronchoscopy sample, if nodular-bronchiectasis is re-
cognized upon radiology. However, the same document also states that:
“For selected patients treatment decisions can be guided by the pa-
thogenic potential of NTM isolates, especially a virulent NTM species
such as M. kansasii, even if multiple specimens are not positive or
available”. Despite the relatively high pathogenicity of M. kansasii [11],
isolation of this species from respiratory samples may not always in-
dicate NTM disease [10–13]. Variability and non-specificity of clinical
and radiological symptoms make accurate diagnosis of M. kansasii
pulmonary disease even more challenging [14,15].
This study was motivated by the paucity of research into clinical
and molecular aspects of M. kansasii disease. Several retrospective
studies have investigated the disease clinically [12,15–27], yet only a
few have provided the molecular-level identification of the pathogen
[18,20]. Apart from two small studies from the Netherlands and UK
[15,18], a comprehensive investigation into M. kansasii disease from
both clinical and bacteriological perspectives, had never been per-
formed in Europe before.
The objective of this study was to characterize patients with M.
kansasii isolated from respiratory samples in terms of demographic,
clinical, radiological, and bacteriological features. Specifically, the
study was intended to determine the differences between patients with
definite M. kansasii disease and those with M. kansasii isolation only.
2. Methods
2.1. Study design
This was a single center, retrospective study that included patients
treated in the Department of Internal Medicine, Pulmonary Diseases
and Allergy of the Medical University of Warsaw between January 2000
and December 2015.
2.2. Patients
The electronic medical database including data on 11,375 patients
in whom respiratory specimens were tested for mycobacteria was
screened for patients with at least one positive result of mycobacterial
culture. Data of those patients were further reviewed to select those in
whom M. kansasii was found. Thereby, the final study group (n = 105)
was achieved. Their medical records were evaluated to extract pre-
defined clinical, radiological and laboratory data.
2.3. Demographic and clinical data
Two authors independently reviewed medical records to extract the
following data: demographic and social characteristics, clinical char-
acteristics, and the results of microbiological studies. Data collected by
92
Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Respiratory Medicine 139 (2018) 91–100
each author were then compared and verified. Since data on manage-
ment and long-term treatment outcomes were available for only a
minority of patients (due to lack of specific guidelines for NTM patient
management and patients' electronic health record, transfer to other
institutions, lost to follow up, NTM treatment deliberately withheld),
they were excluded from the analysis.
Anemia was identified when hemoglobin levels amounted to less
than 12 g/dL for women and 13 g/dL for men.
As the medical records were anonymized prior to the analysis, the
informed consents of patients were not required. The study was ap-
proved by the local ethics committee of the Medical University of
Warsaw (KB-0/12/2007).
2.4. Radiographic studies
Chest radiographs or computed tomography (CT) images were
available for 100 and 77 patients respectively (each patients had at
least X-ray or CT image) and were reviewed by two authors. In addition,
analysis of written reports of radiographic findings was also included.
In case of inter-observer disagreement, the images were reviewed and
discussed with the senior staff of the Department of Radiology in order
to reach the consensus.
The following radiographic findings were considered to be asso-
ciated with NTM disease: cavities, parenchymal opacifications (in-
filtrates), nodules, bronchiectases, and “tree-in-bud” pattern. Other
pulmonary lesions that were construed as possibly related to pulmonary
NTM disease included disseminated or localized parenchymal fibrotic
lesions and pleural effusion.
Based on radiographic findings, pulmonary M. kansasii disease was
classified into three major categories: fibro-cavitary, infiltrative and
nodular/bronchiectatic disease. Fibro-cavitary disease was diagnosed in
patients with pulmonary parenchymal opacities, and/or cavities and/or
massive fibrotic lesions located in upper lobes or in the apical segments
of the lower lobes. Parenchymal opacifications (infiltrates) with no
cavitations seen upon CT scanning localized in other lung regions (e.g.
in the middle or lower lobes) were classified as infiltrative NTM disease.
Patients with pulmonary nodules and bronchiectasis and patients with
pulmonary nodules yet without bronchiectasis, were diagnosed as
having nodular/bronchiectatic form. Mixed categories that shared the
different characteristics were also distinguished, albeit they were as-
signed to major categories, based on the predominance of signs.
The extent of the lung lesions was considered small when they were
found only in one lobe, moderate – if they occurred in 2–3 lobes, and
large when 4 or more lobes were involved.
2.5. Case definitions
M. kansasii pulmonary disease was diagnosed based on ATS/IDSA
statement [10]. All three criteria (microbiologic, clinical and radi-
ological) had to be met to diagnose definite M. kansasii disease. In line
with the ATS/IDSA guidelines, we allowed diagnosis of M. kansasii
disease in case of only one culture-positive sputum sample. Cases that
did not met ATS/IDSA criteria were considered as M. kansasii isolation.
2.6. M. kansasii isolates
M. kansasii isolates recovered from the study group patients
(n = 105) were identified using high pressure liquid chromatography
(HPLC) methodology [28] and GenoType Mycobacterium CM/AS as-
says (HAIN Lifescience, Nehren, Germany).
Genomic DNA was extracted using an AMPLICOR Respiratory
Specimen Preparation Kit (Roche, Basel, Switzerland). For genotyping
purposes, three independent PCR restriction-enzyme analysis (PCR-
REA) assays were applied, designed for hsp65, rpoB, and tuf genes
[29–31], as well as PCR-sequencing strategy, based on partial (644 bp)
hsp65 gene [32], and partial 432-bp-long internal transcribed spacer
Z. Bakuła et al.
Fig. 1. Flowchart for patient selection. Presented figure shows selection
procedure for the cases of M. kansasii isolation and infection among patients
from the Department of Internal Medicine, Pulmonary Diseases and Allergy,
Medical University of Warsaw (2000–2015). aM. kansasii species identified
before the study at the Department of Internal Medicine, Pulmonary Diseases
and Allergy; bCultures were not deposited or transferred to other medical in-
stitution thus species confirmation could not be performed; cMedical doc-
umentation lacked basic data or was transferred to other medical institution;
d
Samples yielded growth of other NTM and/or M. tuberculosis along with M.
kansasii eOther i.e. one UIP (usual interstitial pneumonia) and one unclassifi-
able pattern.
93
Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Respiratory Medicine 139 (2018) 91–100
(ITS) region [33].
Drug susceptibility profiles of 56 M. kansasii isolates under the study
were reported elsewhere [34].
2.7. Statistical analysis
Data were analyzed with the “R” Statistical Software, ver. 3.2.3 (R
Foundation for Statistical Computing, Vienna, Austria). Data were
presented as mean and standard deviation (SD) or number and per-
centage. To analyze differences between categorical variables χ2 and
Fisher's exact tests were used. For quantitative variables, the Wilcoxon-
Mann-Whitney test was applied. A P value of 0.05 or less was con-
sidered statically significant.
3. Results
A flowchart presenting a process of study group selection is depicted
in Fig. 1. Of 11,371 patients tested for mycobacteria, 843 (7.4%) had at
least one positive culture result. NTM were found in 486 (4.3%) pa-
tients. M. kansasii was the most common NTM, identified in 178/486
(36.6%) patients with NTM isolates. The second and the third most
common NTM isolated from respiratory samples were M. xenopi, and M.
avium, identified in 136 (28%) and 38 (7.8%) patients, respectively.
Since no isolates were preserved for 56 of patients with positive M.
kansasii culture precluding species confirmation, these patients were
excluded from the analysis. Another 17 patients were excluded, because
the clinical records were incomplete (n = 11), or because, in parallel to
M. kansasii, the patients' samples yielded growth of other NTM, namely
M. xenopi (n = 3); M. fortuitum (n = 2), and M. avium (n = 1).
Eventually, the study group comprised of 105 patients, from whom a
total of 191 M. kansasii isolates were recovered (58 patients had one, 26
had two, and 21 had three or more retrievable isolations).
Eighty-six (81.9%) of 105 patients were diagnosed as having M.
kansasii disease. Eleven (12.8%) of these patients had a single positive
culture. Nineteen (18.1%) patients were classified as M. kansasii isola-
tion. None of the patients with M. kansasii isolation met radiological
criterion.
The percentage of patients with positive AFB smear was sig-
nificantly higher in M. kansasii disease compared to M. kansasii isolation
(OR = 9.37, P < 0.001) (Table 1).
3.1. Demographic and socioeconomic data
The characteristics of the study group are shown in Table 1. The
mean age of patients was 64.6 ± 17.8 year (median age, 68 years) and
ranged between 21 and 92 years, with peak prevalence in the 7th
decade of life (Fig. 2). Most (91.4%) of patients were city dwellers. The
mean BMI was 23.5 ± 4.9 for men and 22 ± 4.8 for women. HIV
testing was reported in only 5 patients (all negative), yet none of the
medical records mentioned HIV/AIDS positive status.
3.2. Clinical characteristics
The most common presenting symptom was cough, reported in
76.5% patients. It was followed by dyspnea (54.1%), and general
weakness (50.6%). Majority (89.5%) of patients reporting hemoptysis
presented three or more other symptoms (W = 212, P = 0.028).
Preexisting lung disease was reported in 62 (59%) patients. Nearly
half of patients had a history of either pulmonary TB (30.4%) or NTM
pulmonary disease (20.9%). In more than a third (36.4%) of patients
with earlier NTM pulmonary disease, M. kansasii was the causative
agent of their first episode. These cases were thus considered relapses.
Two (9.1%) patients had M. xenopi pulmonary disease, prior to their M.
kansasii episode. For twelve (54.5%) patients with a past NTM disease,
the Mycobacterium species was not specified. The second most common
underlying pulmonary disease was COPD, diagnosed in 30.5% patients.
Z. Bakuła et al. Respiratory Medicine 139 (2018) 91–100

Table 1
Summarized characteristics of the 105 patients with M. kansasii positive cultures. The only statistically significant difference found between M. kansasii disease
and M. kansasii isolation groups is marked with an asterisk (*).

Categorya M. kansasii cases

Disease (n = 86) Isolation (n = 19) Total (n = 105)

Bacteriological characteristics AFB+b 42 (48.8%)* 2 (10.5%) 44 (41.9%)

Demographic and socioeconomic data Age (yr)c 63.2 ± 18 71.2 ± 15.6 64.6 ± 17.8
Females 54 (62.8%) 9 (47.4%) 63 (60%)
Urban area 78 (90.7%) 18 (94.7%) 96 (91.4%)
Mean BMI (n = 45) 22.5 ± 4.8 23.6 ± 5.3 22.7 ± 4.9
Retired (n = 43) 27 (81.8%) 8 (80%) 35 (81.4%)
Alcohol abuse (n = 79) 10 (14.9%) 2 (16.7%) 12 (15.2%)
Former/current smoker (n = 96)d 53 (65.4%) 12 (80%) 65 (67.7%)

Sign and symptoms Cough Any (n = 85) 55 (74.3%) 10 (90.9%) 65 (76.5%)

Dry (n = 84) 18 (24.6%) 5 (45.4%) 23 (27.4%)
Wet (n = 82) 41 (57.7%) 9 (81.8%) 50 (61%)
Dyspnea (n = 85) 37 (50.7%) 9 (75%) 46 (54.1%)
Weakness (n = 81) 33 (46.5%) 8 (80%) 41 (50.6%)
Weight lost (n = 85) 33 (44%) 2 (20%) 35 (38.8%)
Fever (n = 87) 21 (28%) 4 (33.3%) 25 (28.7%)
Night sweats (n = 83) 19 (26.4%) 3 (27.3%) 22 (26.5%)
Hemoptysis (n = 84) 17 (23.6%) 2 (16.7%) 19 (22.6%)

Comorbidities Any 80 (93%) 18 (94.7%) 98 (93.3%)

Preexisting lung disease 52 (60.5%) 10 (52.6%) 62 (59%)
TB/NTM disease history 44 (51.2%) 5 (26.3%) 49 (46.7%)
COPD 29 (33.7%) 3 (15.8%) 32 (30.5%)
Asthma 5 (5.8%) 0 (0%) 5 (4.8%)
Lung cancer 3 (3.5%) 3 (15.8%) 6 (5.7%)
Pneumoconiosis 1 (1.2%) 0 (0%) 1 (0.9%)
Lung resection 4 (4.6%) 0 (0%) 4 (3.8%)
Thorax deformation 3 (3.5%) 0 (0%) 3 (2.8%)
Anemia 34 (39.5%) 9 (47.4%) 43 (40.9%)
Leukopenia 1 (1.2%) 0 (0%) 1 (0.9%)
Diabetes 15 (17.4%) 4 (21%) 19 (18.1%)
Chronic renal failure 10 (11.6%) 2 (10.5%) 12 (11.4%)
End-stage kidney disease (hemodialysis) 2 (2.3%) 0 (0%) 2 (1.9%)
Gastroesophageal reflux disease 7 (8.1%) 1 (5.2%) 8 (7.6%)
Hiatus hernia 6 (7%) 2 (10.5%) 8 (7.6%)
Immunosuppression 7 (8.1%) 3 (15.8%) 10 (9.5%)
Cancer (other than lung) 6 (7%) 2 (10.5%) 8 (7.6%)
Rheumatoid arthritis 1 (1.2%) 1 (5.2%) 2 (1.9%)
Bronchiectasis (n = 87) 24 (34.2%) 1 (5.9%) 25 (28.7%)
Steroidse 5 (5.8%) 2 (10.5%) 7 (6.7%)
HIV + (n = 5) 0 (0%) 0 (0%) 0 (0%)

a
Data were available for 105 patients, otherwise indicated.
b
AFB+, AFB smears graded more than 1+ (1–9 bacilli in 100 fields) were defined as smear-positive according to the ATS guidelines (Griffith et al., 2007).
c
Mean ± SD.
d
Current or past smoking history available in medical records.
e
Usage of inhaled or oral steroids.

Anemia was the most common coexisting non-pulmonary condition.
It was found in 40.9% patients. The second most frequent non-pul-
monary condition was diabetes, observed in 18.1% patients.
There was no difference between the prevalence of symptoms and
comorbidities in patients with M. kansasii disease as compared to M.
kansasii isolation (P > 0.05).
3.3. Radiological presentation
Radiographic findings in patients with M. kansasii disease are
summarized in Table 2.
The most common radiographic sign was single or multiple pul-
monary infiltrate (parenchymal opacification), present in two-thirds
(65.1%) of patients. Cavities, bronchiectases, nodules, and interstitial
patterns were observed in approximately one-third of patients, each.
Finding of nodules (χ2 = 12.12, P < 0.001), interstitial patterns
(χ = 9.91, P = 0.002) or bronchiectasis (χ2 = 20.57, P < 0.001) was
2
associated with large extent of the lung lesions. In addition, presence of
interstitial pattern (χ2 = 11.43, P = 0.016) was associated with bi-
lateral lung involvement. Nodules occurred more frequently
(χ2 = 16.66, P = 0.007) in the middle lobes whereas bronchiectasis in
this location was significantly rarer (χ2 = 16.14, P = 0.004).
The most common radiographic pattern associated with M. kansasii
disease was fibro-cavitary disease. It was found in half (50%) of pa-
tients, either as a sole radiographic manifestation (95.3%) or conjointly
with other radiographic pattern (4.7%). One-fourth (25.6%) of patients
presented with nodular/bronchiectatic form. Infiltrative type was di-
agnosed in almost one-fourth (22.1%) of patients, and 26.3% of those
presented mixed pattern with nodules, with or without bronchiectasis
(Table 2). Representative CT images for three types of M. kansasii dis-
ease are shown on Fig. 3.
There was a significant predominance of bilateral distribution of
pulmonary lesions (72.1%) (χ2 = 14.11, P < 0.001) and upper lobe
involvement (96.5%) (χ2 = 56.47, P < 0.001). The extent of lung

94

Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Z. Bakuła et al. Respiratory Medicine 139 (2018) 91–100

Fig. 2. Sex and age distribution of patients under the study. The percentage in age ranges for males and females was calculated with categorization into M.
kansasii disease and isolation cases.

Table 2 COPD). In younger patients (< 50 years) cavities occurred more often
Radiological features of the M. kansasii disease cases. (χ2 = 23.2, P < 0.001). Fibro-cavitary form of the disease was diag-
nosed more often in younger patients (< 50 years) than infiltrative and
Category M. kansasii
nodular/bronchiectatic patterns (χ2 = 17.35, P < 0.001).
disease cases
(n = 86)
3.4. Molecular characterization
Type Fibro-cavitary 41 (47.7%)
+infiltrative 1 (1.2%)
+nodular bronchiectasis 1 (1.2%) All isolates (n = 191) were classified as M. kansasii type I using PCR-
Nodular/bronchiectatic 22 (25.6%) REA analysis. Sequencing of the ITS and hsp65 loci was performed for
Infiltrative 14 (16.3%)
105 isolates (one per patient). All isolates exhibited 100% identity, at
+nodules 5 (5.8%)
± bronchiectasis
both loci, when compared with the M. kansasii genotype I reference
UIPa 1 (1.2%) strain (ATCC 12478), thus no intermediate (I/II) or atypical types of M.
Unclassifiable 1 (1.2%) kansasii were identified.
Radiographic Infiltrates 56 (65.1%)
findings Interstitial pattern/fibrosis 30 (34.9%)
Cavities 34 (39.5%) 4. Discussion
Nodules 33 (38.4%)
Bronchiectases 31 (36%)
This is the first European and third worldwide study targeting
Massive fibrotic lesions 13 (15%)
Pleural effusion 7 (8.1%) clinical, radiological, and molecular aspects of the M. kansasii disease
Mediastinal lymphadenopathy (n = 97) 10 (11.6%) and isolation in an ample (> 100) group of patients. A brief overview of
Distribution of Total 24 (27.9%) studies exploring the features of M. kansasii disease in geographically
pulmonary Unilateral Left Total 11 (12.7%) diverse populations is provided in Table 3.
lessionsb U 9 (10.5%)
U+L 2 (2.3%)
The study showed NTM accounting for over half of all acid-fast
Right Total 13 (15.1%) bacilli (AFB) positive cultures, and M. kansasii as the second, after tu-
U 9 (10.5%) bercle bacilli, most common mycobacterium isolated from respiratory
M 1 (1.2%) samples. The species was responsible for more than a fifth of all AFB-
L 1 (1.2%)
positive cultures and almost a third of all NTM isolates. We found that
U+M 2 (2.3%)
Bilateral Total 62 (72.1%) M. kansasii disease mainly affected older patients, nearly half of whom
U 19 (22.1%) were in their seventh decade of life. More than 60% of patients had
U+M 15 (17.4%) preexisting lung diseases, mainly TB, previous NTM pulmonary disease
U+L 7 (8.1%) and COPD. There were no significant differences between patients with
U+M+L 20 (23.3%)
M+L 1 (1.2%)
M. kansasii diseases and isolation cases in terms of comorbidities or
Number of pulmonary lobes with lesions 0 0 (0%) clinical symptoms. M. kansasii disease was associated with bilateral
1 20 (23.2%) distribution of pulmonary lesions (72.1%) and particular predilection to
2 27 (31.4%) upper lobe involvement (96.5%). According to the radiological classi-
3 14 (16.2%)
fication applied, half of the M. kansasii disease patients presented with
4 10 (11.6%)
5 13 (15.1%) fibro-cavitary disease, while the other half developed, at almost equal
frequencies, nodular/bronchiectatic or infiltrative form. Interestingly,
irrespective of the disease manifestation, all M. kansasii isolates were
classified as molecular type I.
The cross-European distribution of M. kansasii is somewhat polar-
ized. The high frequencies of M. kansasii recovery among NTM species
involvement was classified as small, moderate, and high in 20/86
have been reported, apart from Poland, in Slovakia (35%) and the UK
(23.2%), 41/86 (47.7%) and 23/86 (26.7%) patients, respectively.
(11%). Contrarily, low M. kansasii occurrences have been documented
Neither of the diagnosed form was associated with specific symptom
in Denmark (1.48%), Finland (1.16%), Norway (0.94%), and Croatia
or any underlying disease (pulmonary or non-pulmonary, including
(0.5%) [2]. In general, clinically relevant NTM species, including M.

95

Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Z. Bakuła et al.
Fig. 3. Diverse patterns of M. kansasii lung disease, as seen on CT scans. Fibro-cavitary (A), nodular/bronchiectatic (B), and infiltrative form (C).
kansasii, have been more often recovered in areas with mild climate,
high rate of urbanization and dependent on large municipal water
supplies [4,35].
The results of our study reflect the high clinical relevance of M.
kansasii isolations. More than 80% of patients with at least one positive
culture had M. kansasii disease. According to a recent meta-analytical
study on the clinical significance of M. kansasii respiratory tract isola-
tions, our result is close to that from the Netherlands (71%) or UK
(73%), and quite distant from what was obtained in Australia (53%),
South Korea (52%), Croatia (50%), Israel (50%) and Taiwan (44%)
[12]. These differences might be explained by geographic heterogeneity
of M. kansasii isolates or ethnic/sociodemographic differences between
patient groups.
In our study AFB smear positivity was significantly more common in
patients with M. kansasii disease than patients with M. kansasii isolation
(P < 0.001). Thus, a positive result of AFB may strengthen indication
of active M. kansasii disease.
Patients with M. kansasii disease under the study were mostly older
people (mean age 63.2 ± 18). Over half (60.8%) of them suffered from
another lung-related ailment, mostly COPD (33.7%) or prior TB infec-
tion (31.4%). These findings slightly contrast with previous studies in
that the patients with M. kansasii disease were somewhat younger
(mean age, 44–62 years) [12,15–21,24,25,27]. The history of past TB
episode in patients with M. kansasii disease was documented before at a
frequency of 3.1%–32% [12,15,19–21,23–35], whereas COPD was di-
agnosed in 10.9%–65% of such patients [12,17–21,23,24]. Those COPD
and TB histories in M. kansasii patients might be explained by geo-
graphical differences. In TB high-endemic regions, NTM disease is more
associated with TB, while low-endemic TB settings – with COPD.
The most frequent non-pulmonary comorbidity described here was
anemia, diagnosed in 39.5% of patients. The occurrence of anemia in
patients with M. kansasii disease had not previously been reported.
Diabetes has been described as contributing to increased vulner-
ability for developing NTM diseases, including M. kansasii disease. The
incidence of this metabolic disorder among patients with M. kansasii
disease has varied from 1.6 to 13% [12,15,18–21,23–25]. In our study,
18% of patients with M. kansasii disease were diabetics.
Patients with M. kansasii definite disease and patients with M.
kansasii isolation presented similar clinical picture. This may imply that
most of the reported symptoms are related to underlying pulmonary
disorders rather than to M. kansasii disease. Non-specific symptoma-
tology is a hallmark of mycobacterial diseases, and the diagnostic value
of clinical features in the prediction of M. kansasii/NTM disease is ra-
ther poor [21,24].
The predilection of M. kansasii disease for the upper lobes has re-
peatedly been described with 80% up to 97% of patients diagnosed with
this localization [15,16,20,21,26]. Bilateral involvement was reported
here with considerably higher frequency than in other studies (72.1% vs
0–53%) [15–21,23,24,26]. Moreover, the current study does not
96
Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Respiratory Medicine 139 (2018) 91–100
support previously documented right-side predominance of pulmonary
lesions observed in patients with M. kansasii disease [15,26].
Detection of cavities and infiltrates in M. kansasii patients has been
quite diverse, ranging from 25% to 96% [12,15–27] and 12.5%–100%
[18,19,21,22,24–27], respectively. Those broad ranges might be ex-
plained by important advancements in medical imaging on one hand,
and development of methods for microbial identification, on the other.
The present study demonstrates high ratio of infiltrates (65.1%) and
cavities (39.5%). The nodular lesions in M. kansasii disease have been
described in 45.8–79% [12,22,23,25–27] of patients, a frequency which
is somewhat higher than that in our patients (38.4%).
In this study nodules, more frequently than other radiographic
signs, were diagnosed in the middle lobes (P = 0.007). This is in line
with a study of Griffith et al., in which all patients with nodular/
bronchiectatic disease presented middle lobe involvement [36].
The observed frequencies of fibrocavitary (50%) and nodular/bro-
chiectatic (25.6%) disease emulate the relative proportions of these two
patterns among M. kansasii disease patients in previous reports, with
cavitary form reported in ca. 50% [12,20] and nodular/bronchiectatic
in 32% [12].
Of the seven currently recognized M. kansasii subtypes (genotypes,
I-VII), genotype I has predominated among clinical samples, making up
42–100% of M. kansasii clinical isolates, Nevertheless, genotype I has
also been described in non-disease-associated cases [37–44]. This was
confirmed by this study, since all M. kansasii isolates belonged to gen-
otype I. Our multi-locus sequence typing did not allow differentiation
between clinically relevant or irrelevant M. kansasii isolates. New
markers of greater discriminatory power that could be used for an ac-
curate delineation of strain relatedness in epidemiological investiga-
tions, but more importantly that would serve as a proxy for prediction
of M. kansasii disease need to be developed.
In the light of our findings, we opt for relaxation of bacteriological
diagnostic criterion for M. kansasii disease outlined in 2007 ATS/IDSA
statement. The document emphasizes the necessity for culture positivity
of at least two separate sputa or one bronchoscopy sample, if nodular-
bronchiectasis is recognized upon radiology. We suggest to lower the
acceptable threshold for microbiological criterion to only one sputum
positive in culture. In our study group, eleven out of 20 patients (11/20;
55%) who met relaxed microbiologic criterion, met clinical and radi-
ological criteria. Therefore, we believe that relaxed bacteriological
criterion allowed diagnosis of definite M. kansasii disease in those cases.
A need for use of less stringent criteria for NTM species of high re-
levance has already highlighted in a study of Jankovic et al. [45]. A
summarized clinical and radiological characteristic of the study group
with categorization into patients who met strict or relaxed ATS criteria
is provided in Supplementary Tables 1 and 2.
The study has some limitations. Firstly, this was a single center
study which included mainly inhabitants of central Poland, and thence
cannot be considered representative for the whole country. Secondly, as
 Table 3
Clinical, radiological, and molecular characteristics of M. kansasii disease – an overview of previous reports.∗

Category Reference
Z. Bakuła et al.

[16] [17] [46] [15] [36] [19] [18]

Characteristic of Year of publication 1978 1981 1983 1996 2003 2005 2004
the study Country USA USA USA the UK USA USA the Netherlands
Study period 1959–1976 1957–1977 1975–1981 1978–1989 – 1952–1995 1991–2001
(years) (18) (21) (7) (12) (44) (11)
Study groupb ATS – ATS – NI ATS + ATS + ATS + ATS +
S S S S S S
No. of patients 187 184 40 28 18 302 17
Pathogenicityc – – – 84.8% – – –
M. kansasii Id – – – – – – 100%e
Demographic and Mean age 50 50 49 60 58.5 50 50.6
socioeconomic Males 81% 81% 82.5% 75% 55.5% 100% 76%
data Alcohol abuse – – 12.5% 3.5% 39% 56% 11.8%
Smoking history – – – – 61% 73% 81.3%
Sign and Cough – – – – – 84% 88.2%
symptoms Dyspnea – – – – – 32% –
Weight lost – – – – – – 58.8%
Fever/sweats – – – – – – 41.2%
Hemoptysis – – – – – 24% 23.5%
Comorbidities TB/NTM history – – – 17.8% 44% 14% –
COPD – 61% 45% – – 65% 41.2%
Asthma – – – – – 2% –
Lung cancer – – 2.5% – – 6% –
Pneumoconiosis – – 2.5% 3.5% – 2% 5.8%

97
Diabetes – – 2.5% 3.5% – 7% 5.8%
Cancer (other than lung) – – – – – 4% –
CR/CTg CR CR CR CR CR CR CR
Radiographic Cavities 95% 96% 98.5% 75% – 87% 70.5%
findings Infiltrates – – – – – 100% 100%
Nodules – – – – – – –
Bronchiectasis – – – 11% – 2% –
Pleural effusion – 4% – 0% – – –
Cavitary disease – 96% – – 72.2% – –
Nodular disease – – – – 27.8% – –
Distribution of Unilateral 59% 59% – 71% 11.1% 58% 47%
lesions Left – 19% – – – 23% –
Right – 40% – – 100% 35% –
Bilateral 41% 41% – 29% 88.9% 42% 53%
Upper lobes 97% – – 89% 72.3% – –

Reference

For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
[20] [21] [22]a [23] [25] [26]a [24] [12] [27] This study

Characteristic of 2006 2008 2008 2010 2012 2012 2012 2015 2016 2017
the study Israel Israel Japan South Korea Japan Japan Israel South Korea Brazil Poland

Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
1999–2004 1999–2004 1998–2005 1998–2007 2001–2009 1996–2010 2007–2010 2003–2014 2006–2014 (9) 2000–2015
(6) (6) (8) (10) (9) (15) (4) (12) (16)
ATS + ATS + – ATS + ATS + – ATS + ATS + ATS + ATS +
S S S S S S S R
56 62 8 41 29 24 64 54 19 105
Pathogenicityc – – – – – – – 51.9% – 81.9%
(continued on next page)
Respiratory Medicine 139 (2018) 91–100
 Table 3 (continued)

Reference
Z. Bakuła et al.

[20] [21] [22]a [23] [25] [26]a [24] [12] [27] This study

d f
M. kansasii I 90% – – – – – – – – 100%
Demographic and 45 44 65.6 – 57 – 44 62 58 63.2
socioeconomic 64% 66% 0% 81% 86.2% – 64% 72% 52.6% 37.2%
data 6% 6.5% – – – 5% – – 14.9%
39% 42% 37.5% 56% 75.9% – 36% 65% – 65.4%
Sign and 84% 86% – 66% 37.9% – 86% 65% – 74.3%
symptoms – – – 24% 3.5% – – 33% – 50.7%
32% 32% – 5% – – 32% – – 44%
39% 40% – 5% 3.5% – 39% – – 28%
38% 42% – 10% – – 42% 20% – 23.6%
Comorbidities 13% 11% – 32% 10.3% – 3.1% 30% – 31.4%
36% 36% – 32% – – 10.9% 20% – 33.7%
– – – – – – – – – 5.8%
– – – – 6.9% – – – – 3.5%
– – – – – – – – – 1.2%
13% 13% – 5% 6.9% – 1.6% 13% – 17.4%
5% 5% – 22% 10.3% – 0% 9% – 7%
CR/CTg CR CR CR/CT CR/CT CT CT CR CR/CT CT CR/CT
Radiographic 54% 57% 25% 44% 82.8% 91.7% 53.1% 50% 73.7% 39.5%
findings – 34% 12.5% – – – 51.6% – – 65.1%
– – 62.5% 69% 79.3% 45.8% – 70% 68.4% 38.4%
13% 13% – 33% 27.6% – 12.5% 59% 84.2% 36%
0% 0% – 8% 0% – 3.1% – – 8.1%
Cavitary disease 54% – 25% – – – 53% 44% – 50%

98
Nodular disease – – 62.5% – – – – 32% – 25.6%
Distribution of 89% 89% – 49% – 100% 95.3% – – 27.9%
lesions – – – – – 70.8% – – – 12.7%
– – – – – 29.2% – – – 15.1%
11% 11% – 51% – 0% 4.7% – – 72.1%
82% 80% – 37% – 91.6% 60% – – 96.5%

∗
All the studies were retrospective, except [36] and [46].
a
Article in Japanese, abstract available only.
b
Study group comprised of patients who met only microbiological ATS criterion (ATS –) or all three ATS criteria (ATS +), strict (S) or relaxed (R; only one culture-positive sputum sample); NI – not indicated.
c
Percentage of patients with M. kansasii disease out of all patients from whom M. kansasii had been isolated.
d
Percentage of M. kansasii type I isolates.
e
INNO LiPA (Fujirebio, Gandawa, Belgium).
f
AccuProbe (Hologic, Marlborough, USA).
g
Type of radiographic data analyzed in the study i.e. chest radiograph (CR) or computed tomography (CT).

For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
Respiratory Medicine 139 (2018) 91–100
Z. Bakuła et al.
it was a retrospective study, complete data could not be obtained for all
of the categories evaluated. Thirdly, follow-up data on patients with M.
kansasii isolations were not available, including data on the manage-
ment and treatment outcomes.
To conclude, M. kansasii was confirmed to display a high pathogenic
potential; its isolation from even a single respiratory sample, especially
with positive AFB smear result, should raise a clinical suspicion of M.
kansasii disease. Although more than half of M. kansasii diseases de-
veloped in patients with preexisting lung diseases, it can also affect
patients without underlying pulmonary diseases. Nearly half of M.
kansasii disease cases presented fibro-cavitary pattern. There was no
difference between the prevalence of symptoms and comorbidities in
patients with M. kansasii disease as compared to M. kansasii isolation.
Since both disease and isolation M. kansasii isolates were identified as
subtype I, the current genotyping method does not differentiate be-
tween isolates that did and did not cause definite disease.
Funding
This work was supported by the National Centre for Research and
Development LIDER Programme [LIDER/044/457/L-4/12/NCBR/
2013].
Acknowledgments
The authors declare no conflict of interest relevant to the subject of
this article.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://dx.
doi.org/10.1016/j.rmed.2018.05.007.
References
[1] C.L. Daley, Nontuberculous mycobacteria infections, Eur. Respir. Monogr. 52
(2011) 115–129.
[2] W. Hoefsloot, J. van Ingen, C. Andrejak, K. Angeby, R. Bauriaud, P. Bemer,
N. Beylis, M.J. Boeree, J. Cacho, V. Chihota, E. Chimara, G. Churchyard, R. Cias,
R. Daza, C.L. Daley, P.N. Dekhuijzen, D. Domingo, F. Drobniewski, J. Esteban,
M. Fauville-Dufaux, D.B. Folkvardsen, N. Gibbons, E. Gómez-Mampaso,
R. Gonzalez, H. Hoffmann, P.R. Hsueh, A. Indra, T. Jagielski, F. Jamieson,
M. Jankovic, E. Jong, J. Keane, W.J. Koh, B. Lange, S. Leao, R. Macedo,
T. Mannsåker, T.K. Marras, J. Maugein, H.J. Milburn, T. Mlinkó, N. Morcillo,
K. Morimoto, D. Papaventsis, E. Palenque, M. Paez-Peña, C. Piersimoni,
M. Polanová, N. Rastogi, E. Richter, M.J. Ruiz-Serrano, A. Silva, M.P. da Silva,
H. Simsek, N. Szabó, R. Thomson, T. Tórtola Fernandez, E. Tortoli, S.E. Totten,
G. Tyrrell, T. Vasankari, M. Villar, R. Walkiewicz, K.L. Winthrop, D. Wagner, The
geographic diversity of nontuberculous mycobacteria isolated from pulmonary
samples: a NTM-NET collaborative study, Eur. Respir. J. 42 (2013) 1604–1613.
[3] J. van Ingen, Diagnosis of nontuberculous mycobacterial infections, Semin. Respir.
Crit. Care Med. 34 (2013) 103–109.
[4] R. Thomson, C. Tolson, F. Huygens, M. Hargreaves, Strain variation amongst clin-
ical and potable water isolates of M. kansasii using automated repetitive unit PCR,
Int J Med Microbiol. 304 (2014) 484–489.
[5] J.E. Moore, M.E. Kruijshaar, L.P. Ormerod, F. Dobroniewski, I. Abubakar,
Increasing reports of non-tuberculous mycobacteria in England, Wales and
Northern Ireland, 1995-2006, BMC Publ. Health 10 (2010) 612.
[6] M. Santin, F. Alcaide, M.A. Benitez, Salazar, C. Ardanuy, D. Podzamczer, G. Rufi,
J. Dorca, R. Martin, F. Gudiol, Incidence and molecular typing of Mycobacterium
kansasii in a defined geographical area in Catalonia, Spain, Epidemiol. Infect. 132
(2004) 425–432.
[7] H. Namkoong, A. Kurashima, K. Morimoto, Y. Hoshino, N. Hasegawa, M. Ato,
S. Mitarai, Epidemiology of pulmonary nontuberculous mycobacterial disease,
Emerg. Infect. Dis. 22 (2016) 1116–1117.
[8] G.D. Onstad, Familial aggregations of group 1 atypical mycobacterial disease, Am.
Rev. Respir. Dis. 99 (1969) 426–429.
[9] W.M. Ricketts, T.C. O'Shaughnessy, J. van Ingen, Human-to-human transmission of
Mycobacterium kansasii or victims of a shared source? Eur. Respir. J. 44 (2014)
1085–1087.
[10] D.E. Griffith, T. Aksamit, B.A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin,
S.M. Holland, R. Horsburgh, G. Huitt, M.F. Iademarco, N. Iseman, K. Olivier,
S. Ruoss, C.F. von Reyn, R.J. Wallace, K. Winthrop, ATS mycobacterial diseases
subcommittee; American Thoracic society; infectious disease society of America. An
official ATS/IDSA statement: diagnosis, treatment, and prevention of
99
Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Respiratory Medicine 139 (2018) 91–100
nontuberculous mycobacterial diseases, Am. J. Respir. Crit. Care Med. 175 (2007)
367–416.
[11] J. van Ingen, S.A. Bendien, W.C. de Lange, W. Hoefsloot, P.N. Dekhuijzen,
M.J. Boeree, D. van Soolingen, Clinical relevance of non-tuberculous mycobacteria
isolated in the Nijmegen-Arnhem region, The Netherlands, Thorax 64 (2009)
502–506.
[12] S.M. Moon, H.Y. Park, K. Jeon, S.Y. Kim, M.J. Chung, H.J. Huh, C.S. Ki, N.Y. Lee,
S.J. Shin, W.J. Koh, Clinical significance of Mycobacterium kansasii isolates from
respiratory specimens, PLoS One 10 (2015) e0139621.
[13] W.J. Koh, O.J. Kwon, K. Jeon, T.S. Kim, K.S. Lee, Y.K. Park, G.H. Bai, Clinical
significance of nontuberculous mycobacteria isolated from respiratory specimens in
Korea, Chest 129 (2006) 341–348.
[14] M. Nowacka-Mazurek, R. Krenke, H. Grubek-Jaworska, R. Walkiewicz,
A. Safianowska, R. Chazan, Pulmonary mycobacteriosis - the diagnostic challenge.
The authors' experience, Pneumonol. Alergol. Pol. 74 (2006) 84–88.
[15] A.J. Evans, A.J. Crisp, R.B. Hubbard, A. Colville, S.A. Evans, I.D. Johnston,
Pulmonary Mycobacterium kansasii infection: comparison of radiological appear-
ances with pulmonary tuberculosis, Thorax 51 (1996) 1243–1247.
[16] E.E. Christensen, G.W. Dietz, C.H. Ahn, J.S. Chapman, R.C. Murry, G.A. Hurst,
Radiographic manifestations of pulmonary Mycobacterium kansasii infections, AJR
Am. J. Roentgenol. 131 (1978) 985–993.
[17] E.E. Christensen, G.W. Dietz, C.H. Ahn, J.S. Chapman, R.C. Murry, J. Anderson,
G.A. Hurst, Initial roentgenographic manifestations of pulmonary Mycobacterium
tuberculosis, M. kansasii, and M. intracellularis infections, Chest 80 (1981) 132–136.
[18] S.M. Arend, E. Cerdá de Palou, P. de Haas, R. Janssen, M.A. Hoeve, E.M. Verhard,
T.H. Ottenhoff, D. van Soolingen, J.T. van Dissel, Pneumonia caused by
Mycobacterium kansasii in a series of patients without recognised immune defect,
Clin. Microbiol. Infect. 10 (2004) 738–748.
[19] J.R. Zvetina, N. Maliwan, Clinical feature and follow up of 302 patients with
Mycobacterium kansasii pulmonary unfection: a 50 year experience, Postgrad. Med.
81 (2005) 530–533.
[20] D. Shitrit, G.L. Baum, R. Priess, A. Lavy, A.B. Shitrit, M. Raz, S. Dekel, D. Bendayan,
M.R. Kramer, Pulmonary Mycobacterium kansasii infection in Israel, 1999–2004:
clinical features, drug susceptibility, and outcome, Chest 129 (2006) 771–776.
[21] D. Shitrit, N. Peled, J. Bishara, R. Priess, S. Pitlik, Z. Samra, M.R. Kramer, Clinical
and radiological features of Mycobacterium kansasii infection and Mycobacterium
simiae infection, Respir. Med. 102 (2008) 1598–1603.
[22] H. Kamiya, S. Ikushima, T. Sakamoto, K. Morimoto, T. Ando, M. Oritsu, A study on
clinical features of Mycobacterium kansasii pulmonary disease in women, Kekkaku
83 (2008) 73–79.
[23] H.K. Park, W.J. Koh, T.S. Shim, O.J. Kwon, Clinical characteristics and treatment
outcomes of Mycobacterium kansasii lung disease in Korea, Yonsei Med. J. 51 (2010)
552–556.
[24] A. Matveychuk, L. Fuks, R. Priess, I. Hahim, D. Shitrit, Clinical and radiological
features of Mycobacterium kansasii and other NTM infections, Respir. Med. 106
(2012) 1472–1477.
[25] M. Takahashi, H. Tsukamoto, T. Kawamura, Y. Mochizuki, M. Ouchi, S. Inoue,
N. Nitta, K. Murata, Mycobacterium kansasii pulmonary infection: CT findings in 29
cases, Jpn. J. Radiol. 30 (2012) 398–406.
[26] E. Inoue, M. Senoo, N. Nagayama, K. Masuda, H. Matsui, A. Tamura, H. Nagai,
S. Akagawa, E. Toyoda, K. Oota, A comparison of chest radiographs between pa-
tients with pulmonary Mycobacterium kansasii infection and those with
Mycobacterium tuberculosis infection in the initial stage of disease, Kekkaku 88
(2013) 619–623.
[27] R. Mogami, T. Goldeberg, P.G.C. de Marca, 3 de Queiroz Mello FC, Lopes AJ.
Pulmonary infection caused by Mycobacterium kansasii: findings on computed to-
mography of the chest, Radiol. Bras. 49 (2016) 209–213.
[28] W.R. Butler, M.M. Floyd, V. Silcox, G. Cage, E. Desmond, P.S. Duffey, L.S. Guthertz,
W.M. Gross, K.C.J. Jost, L.S. Ramos, L. Thibert, N. Warren, Standardized Method for
HPLC Identification of Mycobacteria. HPLC Users Group in Cooperation with
Centers for Disease Control and Prevention, U.S. Public Health Service, CDC,
Atlanta, 1996.
[29] A. Telenti, F. Marchesi, M. Balz, F. Bally, E.C. Böttger, T. Bodmer, Rapid identifi-
cation of mycobacteria to the species level by polymerase chain reaction and re-
striction enzyme analysis, J. Clin. Microbiol. 31 (1993) 175–178.
[30] B.J. Kim, K.H. Lee, B.N. Park, S.J. Kim, G.H. Bal, S.J. Kim, Y.H. Kook,
Differentiation of mycobacterial species by PCR-restriction analysis of DNA (343
base pairs) of the RNA polymerase gene (rpoB), J. Clin. Microbiol. 39 (2001)
2102–2109.
[31] Z. Bakuła, M. Modrzejewska, A. Safianowska, J. van Ingen, M. Proboszcz,
J. Bielecki, T. Jagielski, Proposal of a new method for subtyping of Mycobacterium
kansasii based upon PCR restriction enzyme analysis of the tuf gene, Diagn.
Microbiol. Infect. Dis. 84 (2016) 318–321.
[32] H. Kim, S.H. Kim, T.S. Shim, PCR restriction fragment length polymorphism ana-
lysis (PRA)-algorithm targeting 644 bp Heat Shock Protein 65 (hsp65) gene for
differentiation of Mycobacterium spp, J. Microbiol. Meth. 62 (2005) 199–209.
[33] T. Iwamoto, H. Saito, Comparative study of two typing methods hsp65 PRA and ITS
sequencing revealed a possible evolutionary link between Mycobacterium kansasii
type I and II isolates, FEMS Microbiol. Lett. 254 (2005) 129–133.
[34] Z. Bakuła, M. Modrzejewska, L. Pennings, M. Proboszcz, A. Safianowska, J. Bielecki,
J. van Ingen, T. Jagielski, Drug susceptibility profiling and genetic determinants of
drug resistance in Mycobacterium kansasii, Antimicrob. Agents Chemother. 62
(2018) e01788-17.
[35] M. Jankovic, M. Samarzija, I. Sabol, M. Jakopovic, V. Katalinic Jankovic, L.J. Zmak,
B. Ticac, A. Marusic, M. Obrovac, J. van Ingen, Geographical distribution and
clinical relevance of nontuberculous mycobacteria in Croatia, Int. J. Tubercul. Lung
Z. Bakuła et al.
Dis. 17 (2013) 836–841.
[36] D.E. Griffith, B.A. Brown-Elliott, R.J. Wallace Jr., Thrice-weekly clarithromycin-
containing regimen for treatment of Mycobacterium kansasii lung disease: results of a
preliminary study, Clin. Infect. Dis. 37 (2003) 1178–1182.
[37] M. Picardeau, G. Prod’hom, L. Raskine, M.P. LePennec, V. Vincent, Genotypic
characterization of five subspecies of Mycobacterium kansasii, J. Clin. Microbiol. 35
(1997) 25–32.
[38] F. Alcaide, I. Richter, C. Bernasconi, B. Springer, C. Hagenau, R. Schulze-Röbbecke,
E. Tortoli, R. Martín, R.C. Böttger, A. Telenti, Heterogeneity and clonality among
isolates of Mycobacterium kansasii: implications for epidemiological and patholo-
gical studies, J. Clin. Microbiol. 35 (1997) 1959–1964.
[39] C. Taillard, G. Greub, R. Weber, E.G. Pfyffer, T. Bodmer, Zimmerli, S. Bassetti,
P. Rohner, J.C. Piffaretti, E. Bernasconi, J. Bille, A. Telenti, G. Prod’hom, Clinical
implications of Mycobacterium kansasii species heterogeneity: swiss National survey,
J. Clin. Microbiol. 41 (2003) 1240–1244.
[40] A. Gaafar, M.J. Unzaga, R. Cisterna, F. Clavo, E. Urra, R. Ayarza, G. Martín,
Evaluation of a modified single-enzyme amplified-fragment length polymorphism
technique for fingerprinting and differentiating of Mycobacterium kansasii type I
isolates, J. Clin. Microbiol. 41 (2003) 3846–3850.
[41] Y. Zhang, L.B. Mann, R.W. Wilson, B.A. Brwon-Elliott, V. Vincent, Y. Iinuma,
100
Downloaded for Anonymous User (n/a) at NTR University of Health Sciences JC from ClinicalKey.com by Elsevier on December 13, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
Respiratory Medicine 139 (2018) 91–100
R.J. Wallace Jr., Molecular analysis of Mycobacterium kansasii isolates from the
United States, J. Clin. Microbiol. 42 (2004) 119–125.
[42] E. Chimara, C.M. Giampaglia, M. Conceição Martins, M.A. De Silva Telles, S.Y. Ueki,
L. Ferrazoli, Molecular characterization of Mycobacterium kansasii isolates in the
state of São Paulo between 1995-1998, Mem. Inst. Oswaldo Cruz 99 (2004)
739–743.
[43] Z. Bakuła, A. Safianowska, M. Nowacka-Mazurek, J. Bielecki, T. Jagielski,
Subtyping of Mycobacterium kansasii by PCR-restriction enzyme analysis of the
hsp65 gene, BioMed Res. Int. (2013) 167954.
[44] G. Kwenda, G.J. Churchyard, C. Thorrold, I. Heron, S. Stevenson, A.G. Duse,
E. Marais, Molecular characterization of clinical and environmental isolates of
Mycobacterium kansasii isolates from South African gold mines, J. Water Health 13
(2015) 190–202.
[45] M. Jankovic, I. Sabol, L. Zmak, V.K. Jankovic, M. Jakopovic, M. Obrovac, B. Ticac,
L.K. Bulat, S.P. Grle, I. Marekovic, M. Samarzija, J. van Ingen, Microbiological
criteria in non-tuberculous mycobacteria pulmonary disease: a tool for diagnosis
and epidemiology, Int. J. Tubercul. Lung Dis. 20 (2016) 934–940.
[46] C.H. Ahn, J.R. Lowell, S.S. Ahn, S.I. Ahn, G.A. Hurst, Short-course chemotherapy for
pulmonary disease caused by Mycobacterium kansasii, Am. Rev. Respir. Dis. 128
(1983) 1048–1050.