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Journal of Clinical Microbiology, July 2001, p. 2745-2746, Vol. 39, No. 7
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.7.2745-2746.2001
LETTERS TO THE EDITOR
Clarithromycin Resistance in Mycobacterium abscessus
 |
LETTER |
We read with interest the article by Sanguinetti et al. titled
"Fatal Pulmonary Infection Due to Multidrug-Resistant
Mycobacterium abscessus in a Patient with Cystic
Fibrosis," which appeared in the February 2001 issue
(5). We would like to point out some additional
information relating to the authors' comment, "to our knowledge,
this is the first evidence of true resistance to clarithromycin, which
is considered the most active drug against M. chelonae." First, the case report involves Mycobacterium abscessus, not
M. chelonae. The two names are not synonymous and should not
be used interchangeably (10). The organisms have different
biologies, are readily differentiated in the laboratory, and have
different drug susceptibilities (2, 3, 6, 8). (Essentially
all cases of chronic lung disease caused by rapidly growing
mycobacteria in the setting of cystic fibrosis are due to M. abscessus [3].)
Second, there have been several previous reports of acquired
clarithromycin resistance in isolates of M. abscessus and
the closely related M. chelonae, and the genetics of this
resistance have been well characterized (7, 9, 11). We
would especially call the authors' attention to an article describing
the study of clarithromycin resistance in a series of 800 isolates of
M. chelonae and M. abscessus. Eighteen of 800 clinical isolates (2.3%) submitted for susceptibility testing between
1990 and 1995 were found to be resistant to clarithromycin; 10 of these
isolates were M. abscessus (9). The underlying
conditions most commonly associated with the development of macrolide
resistance in M. abscessus following clarithromycin therapy
were cystic fibrosis (as in the case reported by the authors) and
disseminated cutaneous disease. Sequencing studies of the 23S rRNA gene
revealed that 94% of the clarithromycin-resistant isolates had a
mutation involving the adenine at position 2058 or 2059 (Escherichia coli numbering system). Selected laboratory
mutants resistant to clarithromycin had the same mutations, as have
other species of mycobacteria and bacteria with acquired clarithromycin
resistance (1, 4). The study also revealed that M. chelonae and M. abscessus have only a single copy of
the ribosomal operon in their genome and hence demonstrate
susceptibility to a single point mutation resulting in high-level
(clinical) resistance.
| |
FOOTNOTES |
*
Phone: (903) 877-7685
Fax: (903) 877-7652
E-mail: Barbara.Elliott{at}uthct.edu
| |
REFERENCES |
| 1.
|
Alarcón, T.,
D. Domingo,
N. Prieto, and M. López-Brea.
2000.
PCR using 3'-mismatched primers to detect A2142C mutation in 23S rRNA conferring resistance to clarithromycin in Helicobacter pylori clinical isolates.
J. Clin. Microbiol.
38:923-925[Abstract/Free Full Text].
|
| 2.
|
Brown, B. A.,
R. J. Wallace, Jr.,
G. Onyi,
V. DeRosas, and R. J. Wallace, III.
1992.
Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonae-like organisms.
Antimicrob. Agents Chemother.
36:180-184[Abstract/Free Full Text].
|
| 3.
|
Griffith, D. E.,
W. M. Girard, and R. J. Wallace, Jr.
1993.
Clinical features of pulmonary disease caused by rapidly growing mycobacteria: "Analysis of 154 patients."
Am. Rev. Respir. Dis.
147:1271-1278[Medline].
|
| 4.
|
Pina, M.,
A. Occhialini,
L. Monteiro,
H.-P. Doermann, and F. Mégraud.
1998.
Detection of point mutations associated with resistance of Helicobacter pylori to clarithromycin by hybridization in liquid phase.
J. Clin. Microbiol.
36:3285-3290[Abstract/Free Full Text].
|
| 5.
|
Sanguinetti, M.,
F. Ardito,
E. Fiscarelli,
M. La Sorda,
P. D'Argenio,
G. Ricciotti, and G. Fadda.
2001.
Fatal pulmonary infection due to multidrug-resistant Mycobacterium abscessus in a patient with cystic fibrosis.
J. Clin. Microbiol.
39:816-819[Abstract/Free Full Text].
|
| 6.
|
Swenson, J. M.,
R. J. Wallace, Jr.,
V. A. Silcox, and C. Thornsberry.
1985.
Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae.
Antimicrob. Agents Chemother.
28:807-811[Abstract/Free Full Text].
|
| 7.
|
Tebas, P.,
F. Sultan,
R. J. Wallace, Jr., and V. Fraser.
1995.
Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient.
Clin. Infect. Dis.
20:443-444[Medline].
|
| 8.
|
Wallace, R. J., Jr.,
B. A. Brown, and G. Onyi.
1992.
Skin, soft tissue, and bone infections due to Mycobacterium chelonae subspecies chelonae importance of prior corticosteroid therapy, frequency of disseminated infections, and resistance to oral antimicrobials other than clarithromycin.
J. Infect. Dis.
166:405-412[Medline].
|
| 9.
|
Wallace, R. J., Jr.,
A. Meier,
B. A. Brown,
Y. Zhang,
P. Sander,
G. O. Onyi, and E. C. Böttger.
1996.
Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus.
Antimicrob. Agents Chemother.
40:1676-1681[Abstract].
|
| 10.
|
Wallace, R. J., Jr.,
V. Silcox, and B. A. Brown.
1994.
Taxonomy of rapidly growing mycobacteria.
Clin. Infect. Dis.
18:121-122[Medline].
|
| 11.
|
Wallace, R. J.,
D. Tanner,
P. J. Brennan, and B. A. Brown.
1993.
Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae.
Ann. Int. Med.
119:482-486[Abstract/Free Full Text].
|
| | | | |
Barbara A. Brown-Elliott*
Richard J. Wallace Jr.
Department of Microbiology
The University of Texas Health Center
11937 US Hwy 271
Tyler, TX 75708
|
| |
AUTHORS' REPLY |
We thank Dr. Wallace and Dr. Brown-Elliott for their interest in our
article, and we appreciate their comments, which were occasioned by the
following sentence: "To our knowledge, this is the first
evidence of true resistance to clarithromycin, which is considered the
most active drug against M. chelonae." Regarding the
first comment, M. chelonae is different from M. abscessus; therefore, the use of the term M. chelonae was a mistake, due to the fact that M. abscessus was formerly designated M. chelonae subsp. abscessus. It is known that M. abscessus is the rapidly growing mycobacterial species most
frequently involved in infections of patients with cystic fibrosis
(3, 4), but M. chelonae (1) and
M. fortuitum (2) also cause severe lung disease in these patients. With regard to the second comment, our intention was
to stress the concept that the described case was the first fatal case
of M. abscessus infection in a cystic fibrosis patient being associated with a multidrug resistance pattern (including resistance to clarithromycin). In fact, even though there are some
reports of infections caused by M. chelonae and M. abscessus resistant to clarithromycin, as underlined by Dr.
Wallace and Dr. Brown-Elliott, only infections caused by M. chelonae (5, 7) have been clinically well defined. On
the other hand, while Wallace et al. (6) interestingly
reported the insurgence of clinical resistance to clarithromycin in
rapidly growing mycobacteria, such as M. abscessus and
M. chelonae, isolated from patients with disseminated or
chronic lung disease, no mention of the outcome of disease for any
patient was made. However, in our report we highlighted the fatal
outcome of the M. abscessus infection associated with the
multidrug resistance pattern of the isolate. In conclusion, we
apologize for our inappropriate sentence, recognizing that it should
have read as follows: "To our knowledge, this is the first evidence
of a fatal infection due to a M. abscessus isolate resistant
to several drugs, including clarithromycin, which is considered the
most active drug against rapidly growing mycobacteria."
| |
REFERENCES |
| 1.
|
Boxerbaum, B.
1980.
Isolation of rapidly growing mycobacteria in patients with cystic fibrosis.
J. Pediatr.
961:689-691.
|
| 2.
|
Efthimou, J.,
M. J. Smith,
M. E. Oddson, and J. C. Batten.
1984.
Fatal pulmonary infection with Mycobacterium fortuitum in cystic fibrosis.
Br. J. Dis. Chest
78:229-302.
|
| 3.
|
Griffith, D. E.,
W. M. Girard, and R. J. Wallace, Jr.
1993.
Clinical features of pulmonary disease caused by rapidly growing mycobacteria.
Am. Rev. Respir. Dis.
147:1271-1278.
|
| 4.
|
Olivier, K. N.,
J. R. Yankaskas, and M. R. Knowles.
1996.
Nontuberculous mycobacterial pulmonary disease in cystic fibrosis.
Semin. Respir. Infect.
11:272-284[Medline].
|
| 5.
|
Tebas, P.,
F. Sultan,
R. J. Wallace, Jr., and V. Fraser.
1995.
Rapid development of resistance to clarithromycin following monotherapy for disseminated Mycobacterium chelonae infection in a heart transplant patient.
Clin. Infect. Dis.
20:443-444.
|
| 6.
|
Wallace, R. J., Jr.,
A. Meier,
B. A. Brown,
Y. Zhang,
P. Sander,
G. O. Onyi, and E. C. Böttger.
1996.
Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus.
Antimicrob. Agents Chemother.
40:1676-1681.
|
| 7.
|
Wallace, R. J.,
D. Tanner,
P. J. Brennan, and B. A. Brown.
1993.
Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae.
Ann. Int. Med.
119:482-486.
|
| | | | |
Maurizio Sanguinetti
Giovanni Fadda
Istituto di Microbiologia
Università Cattolica del S. Cuore
L. go F. Vito 1, 00168 Rome, Italy
|
Journal of Clinical Microbiology, July 2001, p. 2745-2746, Vol. 39, No. 7
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.7.2745-2746.2001
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