Short communication J. Altclas A. Lescano C. Salgueira A. Di Martino V. Brennan R. Campestri V. Ritacco D. Palmero
Key words: multidrug-resistant tuberculosis; bone marrow transplantation; transplant; tuberculosis
Multidrug-resistant tuberculosis in bone marrow transplant recipient
Abstract: Multidrug-resistant tuberculosis (TB) is an increasing problem worldwide, however only three cases have been previously described in transplant recipients, especially involving lung and heart transplant.We describe a case of multidrug-resistant TB in an allogenic bone marrow transplant recipient with good response to second-line therapy.
Authors’ a⁄liations:
J. Altclas1, A. Lescano1, C. Salgueira1, A. Di Martino2, V. Brennan1, R. Campestri3, V. Ritacco4, D. Palmero5 1
The incidence of tuberculosis (TB) has increased substantially worldwide. In organ transplant recipients, this incidence has been found to be signi¢cantly higher than in the general population (1). Although a higher incidence is expected in allogenic bone marrow transplant (ABMT) recipients, a low rate has been reported (0.1^2.2%) (2^4). Surprisingly, the incidence in bone marrow transplantation (BMT) is also lower than in other organ transplant recipients (1- 4). On the other hand, multidrug-resistantTB (MDR-TB) has emerged as a
Department of Infectious Diseases, Sanatorio Mitre, Buenos Aires, Argentina,
2 Department of Microbiology, Sanatorio Mitre, Buenos Aires, Argentina, 3 Department of Hematology, Sanatorio Mitre, Buenos Aires, Argentina, 4 National Institute of Infectious Diseases ‘‘Carlos G. Malbra¤n,’’ Buenos Aires, Argentina, 5 Hospital Francisco J. Muniz, Buenos Aires, Argentina
global problem and has been associated with incomplete or inadequate treatment, nosocomial outbreaks, and human immunode¢ciency virus (HIV). In Argentina, at least two institutional outbreaks have been reported in HIV and non-HIV patients (5^7 ). In spite of these occurrences, few cases have been reported in transplant recipients (8^10).We describe the case of a patient who developed primary and sporadic MDR-TB fol-
Correspondence to: Javier Altclas Bartolome¤ Mitre 2553 (C1039AAO) Buenos Aires Argentina Tel/Fax: 1 54 11 49547070 ext 494 e-mail:
[email protected]
lowing ABMT with good response to speci¢c therapy.
Case report A 56 -year-old female underwent ABMT for non-Hodgkin lymphoma in Received 30 December 2004, accepted for publication 3 March 2005 Copyright & Blackwell Munksgaard 2005 Transplant Infectious Disease . ISSN 1398 -2273 Transpl Infect Dis 2005: 7: 45^46 Printed in Denmark. All rights reserved
November 1999, and was admitted on day 1 300 post transplant with alveolar in¢ltrate in the right upper lobe. She was receiving meprednisone 40 mg daily for chronic graft-versus-host disease (GVHD) grade III. She had no personal or familial history of TB. Pre-transplant tuberculin skin 45
Altclas et al: Multidrug-resistant TB in BMT
test, chest x-ray, and HIV testing were negative. A bronchoalveolar
tional facilities (5 - 6). Nosocomial transmission of AIDS-related MDR-
lavage (BAL) was performed. Cultures for bacteria and fungi were
TB has been documented in Argentina (6 -7 ). In the report of Ritacco
negative. Ziehl-Neelsen stain showed acid-fast bacilli. Weight-
et al. (6), a single M. tuberculosis strain (named M strain) was found to
adjusted treatment with rifampin 450 mg, isoniazid 300 mg, ethambutol
a¡ect 92% of patients with a highly resistant pattern and history of hos-
1200 mg, and pyrazinamide 1125 mg once daily was started.
pital exposure.
W|th subsequent growth of Mycobacterium tuberculosis in BAL sample
To our knowledge, only three cases of MDR-TB have been reported in
cultures, and considering the deteriorating clinical condition of the pa-
solid organ transplant recipients (8^10). In one fatal case, a heart trans-
tient, drug-resistant TB was suspected. Empirical treatment was
plant, the patient had risk of exposure to resistant strains because he had
switched to cycloserine 500 mg, ethionamide 750 mg, levo£oxacin
a history of prolonged imprisonment 10 years before transplantation and
500 mg, and ethambutol 1200 mg daily. Following this adjustment, clini-
the result of a drug susceptibility test showed resistance to rifampin and
cal improvement was observed. The M. tuberculosis strain genotyping
isoniazid, with susceptibility to other ¢rst-line drugs (8). In the second
via IS- 6110 restriction fragment length polymorphism (RFLP) revealed
case, a double-lung transplant, the patient most likely acquired MDR-TB
it was not related to any other outbreak strain studied in our country.The
from the donor because of the early onset of illness and because the or-
susceptibility test, using World Health Organization standard recom-
gan was obtained from a high-risk donor. She was thereafter successfully
mendations, showed resistance to rifampin, isoniazid, ethambutol, pyra-
treated with second-line drugs (9). In the third case, a heart-lung trans-
zinamide, streptomycin, rifabutin, and ethionamide and susceptibility
plant, the patient acquired infection from the donor and because of con-
to cycloserine, kanamycin, para-aminosalicylic acid (PAS), capreomycin,
comitant medical therapy, he required a pulmonary resection as adjunct
amikacin, cipro£oxacin, o£oxacin, and clofazimine. On this basis, treat-
treatment for his disease (10). An exhaustive examination revealed that
ment was switched to cycloserine 500 mg, levo£oxacin 500 mg, PAS 10 g
our patient did not have personal or familial history of TB nor was she
daily, and kanamycin 1 g three times a week. She was discharged with
exposed to any anti-tuberculous drugs. This case is remarkable because
clinical and radiological improvement and a negative sputum culture
it appears to be a primary MDR-TB.The patient strain was also unique in
for acid-fast bacilli. She completed 18 months of treatment. Periodic con-
the Malbran Institute RFLP database. Consequently, this situation may
trols showed no relapse after 4 years of follow-up.
re£ect an unusual and dangerous sporadic transmission of a multidrugresistant strain to an immunocompromised host other than an AIDS patient.The treatment of MDR-TB is more complicated with a worse clinical
Discussion
prognosis than susceptible TB, because of prolonged therapy, drug toxicity, and the scarce therapeutic options available. Treatment must there-
MDR-TB is de¢ned by its resistance to rifampin and isoniazid, drugs
fore be individualized according to in vitro susceptibility data.
considered essential for therapy. The mortality of TB has been reported
As shown by our report, MDR-TB represents a concerning issue in the
to be higher in both HIV and non-HIV patients. Several MDR-TB out-
management of TB in immunocompromised hosts other than AIDS
breaks have been reported particularly a¡ecting hospitals and correc-
patients.
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