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PubMed1997

Genetic characterization of multidrug-resistant Mycobacterium bovis strains from a hospital outbreak involving human immunodeficiency virus-positive patients.

Nineteen multidrug-resistant (MDR) Mycobacterium complex strains isolated in a nosocomial outbreak were characterized at the molecular level. The strains were microbiologically characterized as Mycobacterium bovis. The mpt40 sequence was not present in chromosomal DNA from these strains, supporting the fact that they were M. bovis. All of the isolates were resistant to isoniazid, rifampin, pyrazinamide, ethambutol, streptomycin, para-aminosalicylic acid, clarithromycin, cycloserine, ethionamide, ofloxacin, capreomycin, and amikacin. By performing the standardized IS6110 fingerprinting by restriction fragment length polymorphism (RFLP) analysis, we were able to differentiate two groups (groups A and B) containing two (16 isolates) and three (3 isolates) IS6110 copies, respectively. These strains were typed by spoligotyping, developed to distinguish M. bovis strains and also to distinguish them from M. tuberculosis strains (J. Kamerbeek et al., J. Clin. Microbiol. 35:907-914, 1997). All the strains were confirmed to be M. bovis. In addition, spoligotyping showed a difference in only 1 of 43 spacers between RFLP groups A and B. The rpo beta region of several strains representative of each identified group was cloned and sequenced, and identical mutations (Ser-531 to Leu) responsible for the rifampin resistance phenotype were found. To our knowledge, this is the first characterization at the molecular level of an MDR M. bovis strain responsible for a nosocomial outbreak.

AIDS-Related Opportunistic Infections↗
PubMed1999

Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial drugs by using the radiometric BACTEC 460 technique and the proportion method with solid media.

In a large multicenter study involving six major study sites in the United States, Canada, and Europe, the susceptibilities of 272 Mycobacterium tuberculosis strains to classical second-line antituberculosis (anti-TB) drugs (capreomycin, cycloserine, ethionamide, and kanamycin) and newer compounds (amikacin, clofazimine, ofloxacin, and rifabutin) were determined by the radiometric BACTEC 460 procedure and the conventional proportion method on Middlebrook 7H10 agar. Previously established critical concentrations for classical second-line anti-TB drugs were compared with several concentrations in liquid medium to establish equivalence. MICs of newer compounds determined in liquid medium were either the same or up to four times lower than those determined in agar medium. After establishing critical concentrations (breakpoints) in the extended testing of clinical isolates, we obtained an excellent overall correlation between the two systems, with no errors with amikacin, kanamycin, and ofloxacin and very few major or very major errors with the other drugs; however, for cycloserine, no breakpoint concentration could be recommended due to repeatedly inconsistent results by both methods. Based on these data we conclude that the BACTEC 460 procedure is a simple and rapid method requiring 4 to 8 days on average to generate accurate antimicrobial susceptibility testing (AST) results for eight anti-TB drugs other than those considered primary ones. These data not only fill a major gap of knowledge regarding the critical test concentrations of secondary anti-TB drugs but also provide a baseline for future evaluations of M. tuberculosis AST with the more recently developed, nonradiometric broth-based culture systems.

Anti-Bacterial Agents↗
PubMed2002

Characterization of Mycobacterium tuberculosis complex isolates from the cerebrospinal fluid of meningitis patients at six fever hospitals in Egypt.

Mycobacterium tuberculosis complex isolates from cerebrospinal fluid of 67 meningitis patients were obtained from six fever hospitals in Egypt. One M. bovis and 66 M. tuberculosis isolates were identified by PCR-restriction fragment length polymorphism (RFLP) analysis of oxyR. Among the M. tuberculosis isolates, 53 unique strain types (with 3 to 16 copies of IS6110) were found by RFLP analyses. Nine clusters (eight with two isolates each and one with six isolates) were also found. Thirty-six spoligotypes, including at least 10 that have been previously reported from other countries, were also observed. Forty-one (62.1%) of the isolates were in spoligotype clusters, and 22 (33%) of the isolates were in RFLP clusters. Fifty-one of the isolates were susceptible in vitro to all of the antituberculosis drugs tested, 11 were monoresistant to capreomycin, rifampin, isoniazid (INH), pyrazinamide, or streptomycin (STR), 4 were resistant to STR and INH, and 1 was resistant to STR, INH, and ethambutol.

Bacterial Proteins↗
PubMed2006

Multicenter laboratory validation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line drugs and newer antimicrobials.

The BACTEC MGIT 960 system, a fully automated, nonradiometric, noninvasive system for detection and drug susceptibility testing of mycobacteria, was evaluated for the ability to test susceptibilities to second-line drugs. In this study, which was carried out in three phases (phase I, mostly susceptible strains; phase II, mostly resistant strains; phase III, final testing of the optimal drug concentrations found in phases I and II), we established the critical concentrations for seven drugs to be tested in the BACTEC MGIT 960 system compared to the BACTEC 460TB system. The critical concentrations for the seven drugs used in the MGIT 960 system are as follows: amikacin, 1.0 microg/ml; capreomycin, 2.5 microg/ml; ethionamide, 5.0 microg/ml; protionamide, 2.5 microg/ml; ofloxacin, 2.0 microg/ml; rifabutin, 0.5 microg/ml; linezolid, 1.0 microg/ml. Our results demonstrate that the BACTEC MGIT 960 system is an accurate method for rapid testing of the susceptibilities of Mycobacterium tuberculosis to second-line drugs.

Antitubercular Agents↗
PubMed2006

Evaluation of MGIT 960-based antimicrobial testing and determination of critical concentrations of first- and second-line antimicrobial drugs with drug-resistant clinical strains of Mycobacterium tuberculosis.

The objectives of this study were to (i) compare agreement of the MGIT 960 system for first-line drugs with a methodology (the resistance ratio method [RRM]) that had been used in clinical trials, relating drug susceptibility to clinical outcome; (ii) compare the performance of the MGIT 960, RRM, and microtiter plate assay (MPA) methodologies for second-line drug testing; and (iii) define critical concentrations for ciprofloxacin and moxifloxacin for liquid-culture-based testing. The large collection of clinical isolates of Mycobacterium tuberculosis (n = 247) used included 176 (71%) multidrug-resistant isolates. The results for MGIT 960 and the RRM for rifampin and isoniazid (n = 200) were in excellent (99 to 100%) agreement for all strains. For streptomycin, 97% of the results at the critical concentration and 92% at high concentration, and for pyrazinamide 92% of results overall, were concordant, but for ethambutol, fewer than 85% (65% for the critical concentration and 84% for the high concentration) of the MGIT-based results were concordant with those for the RRM. The MGIT 960, RRM, and MPA assays (n = 133) correlated well for most second-line drugs tested. For susceptibility to ofloxacin, the MGIT 960 and MPA results were in full agreement. The amikacin and rifabutin results obtained by MGIT 960 agreed with the RRM results in 131 (99%) cases, and for capreomycin, they agreed for 129 of 133 isolates tested (97%). For prothionamide testing, only a limited number of drug-resistant isolates were available for testing and drawing definitive conclusions. We propose critical concentrations of 1.0 microg/ml and 0.125 microg/ml for ciprofloxacin and moxifloxacin, respectively, for liquid-culture-based testing.

Antitubercular Agents↗
PubMed1994

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.

BACKGROUND: The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS: The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS: Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS: Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis.

Adolescent↗
PubMed1998

The safety of antituberculosis medications during breastfeeding.

Most antituberculosis drugs appear to be safe for use with breastfeeding. These agents are excreted in breast milk at relatively small concentrations. No adverse effects have been reported to date. The percentages of the therapeutic dose of antituberculosis agents that potentially may be delivered to the nursing infants range from 0.05% to 28%. Currently isoniazid, rifampin, ethambutol, streptomycin (first-line agents), kanamycin and cycloserine (second-line agents) are the only agents considered by the AAP to be compatible with breastfeeding. Unfortunately, there are still no clear data on the safety of pyrazinamide, ethionamide, and capreomycin during breastfeeding. If the mother chooses to breastfeed, it may be prudent to examine the infant for signs and symptoms of toxicity. In infants requiring treatment with antituberculosis agents, it is important to use therapeutic doses since drug concentrations in breast milk are not adequate as effective therapy for treatment or prevention. However, dosing at the lower end of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid) to decrease the risk of toxicity.

Adult↗
PubMedDate not supplied

A decade surveillance study of Mycobacterium xenopi disease and antimicrobial susceptibility levels in a reference teaching hospital of northern Italy: HIV-associated versus non-HIV-associated infection.

OBJECTIVE AND METHOD: The aim of our survey is to investigate the epidemiology and in vitro antimicrobial susceptibility levels of 35 consecutive Mycobacterium xenopi strains responsible for confirmed disease at a University Hospital from 1993 to 2002 and to identify eventual differences in the in vitro sensitivity profile between the 17 strains isolated from patients with HIV disease and the 18 isolates cultured from non-HIV-infected individuals. RESULTS: The involvement of lower airways accounted for 88.6% of cases; but atypical pulmonary findings, including cavitation and a prominent inflammatory reaction, recently emerged in HIV-infected patients successfully treated with HAART, which raises the possible role of immune reconstitution syndrome in the clinical pathomorphism of this opportunistic disease. When compared with non-HIV-infected patients, patients with HIV disease had a lower mean age and a tendency to suffer from late relapses. The greatest overall in vitro sensitivity rate was registered for capreomycin and protionamide (100% of strains) followed by kanamicin (96.6%), whereas susceptibility rates for the first-line compounds such as ethambutol, isoniazid, and rifampicin were slightly lower (85.7% to 91.4%). No temporal variation in the susceptibility index was seen over the study decade. Non-HIV-infected patients experienced a higher frequency of M. xenopi isolates that proved to be resistant to at least one tested compound compared with HIV-associated episodes, despite the heavy and prolonged exposure of HIV-infected patients to broad spectrum antimicrobials, which included agents effective on atypical mycobacteria. Only one HIV-positive patient developed rifampicin resistance in his third disease recurrence. CONCLUSION: A rapid diagnosis, a reliable differentiation between colonization and disease, and an optimal therapeutic choice for atypical mycobacterial disease (including M. xenopi one) are still serious challenges for clinicians and bacteriologists who treat immunocompromised patients, such as those with HIV disease. In the immunocompromised host, diagnostic difficulties posed by late identification and eventually concurrent opportunistic disorders add their negative effects to therapeutic problems due to the unpredictable in vitro susceptibility profile of atypical mycobacteria, such as M. xenopi.

AIDS-Related Opportunistic Infections↗
PubMed2003

Multidrug-resistant tuberculosis in pregnancy: case report and review of the literature.

A woman at 23 weeks' gestation was treated with rifampin, isoniazid, and ethambutol for cavitary tuberculosis (TB). She did not respond within 3 weeks, and multidrug-resistant (MDR) TB was suspected. Direct plating on susceptibility media was performed immediately. Treatment was initiated with IV capreomycin, levofloxacin, para-aminosalicylic acid, pyrazinamide, cycloserine, and high-dose vitamin B(6) at 26 weeks' gestation. The patient delivered vaginally at week 35. The newborn was not infected. Following delivery, ethionamide was added as a sixth drug, and levofloxacin was replaced with moxifloxacin. The patient's sputum became smear-negative and culture-negative for TB. All reported cases of MDR-TB during pregnancy are reviewed.

Adult↗
PubMed2006

Pulmonary Mycobacterium kansasii infection in Israel, 1999-2004: clinical features, drug susceptibility, and outcome.

BACKGROUND: Mycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in world. However, little is known about its background characteristics or drug sensitivity in nonendemic areas. DESIGN: We assessed the clinical features, radiologic findings, and drug sensitivity associated with M kansasii infection in Israel. METHODS: Patients with a culture-positive diagnosis of M kansasii infection between April 1999 and April 2004 were identified from a clinic database of tuberculosis centers. Mycobacterial cultures were performed with standard methods. Data on patient background and clinical features were collected from the medical files. RESULTS: Mean age (+/- SD) of the 56 patients was 58 +/- 18 years, and 64% were men; 59% had associated lung disease. Fifteen percent were receiving immunosuppressive medications. None had HIV infection. Systemic comorbid diseases were noted in 27%. The most common clinical presentations were chest pain, cough, hemoptysis, fever, and night sweats. Cavitation was noted only in 54%. Older patients had more noncavitary disease than younger patients (p = 0.01, r = 0.35). Lower-lobe predominance was very rare (4%). None of the patients presented with pleural effusion or lymphadenopathy. Only seven patients (11%) underwent bronchoscopy for diagnosis. M kansasii isolates showed the highest sensitivity to rifampin, ethambutol, clarithromycin, and ofloxacin, and the highest resistance to ciprofloxacin and capreomycin. The mean duration of treatment was 21 +/- 7.2 months. There were no disease-related deaths. CONCLUSIONS: M kansasii disease in Israel has no association with HIV, more systemic comorbid diseases and associated lung disease, and fewer cavitations. Following appropriate treatment, patients with M kansasii disease have an excellent prognosis.

Adult↗
PubMedDate not supplied

Clinical pharmacokinetics of the antituberculosis drugs.

The quantitative aspects of the disposition in man of 12 antituberculosis drugs [isoniazid, rifampicin, (rifampin), ethambutol, para-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin and thiacetazone] are reviewed. Isoniazid appears to be the only agent for which plasma concentrations and clearance are related to hereditary differences in acetylator status and for which there is an appreciable 'first-pass' effect. Recent data cast doubt on the suggestion that isoniazid may be more hepatotoxic for rapid as opposed to slow acetylators. Continuous administration of rifampicin leads to induction of enzymes in the liver with a concomitant decrease in maximum plasma concentrations, the time required to achieve this level, elimination half-life, and area under the plasma concentration-time curve (AUC). Coadministration of para-aminosalicylic acid leads to increases in the serum concentrations and elimination half-life of isoniazid. With a few exceptions, the metabolites of the antituberculosis drugs are devoid of antimicrobial activity; the exceptions are 25-desacetylrifampicin which accounts for approximately 80% of the drug's antimicrobial activity in human bile, the acetylated and glycylated metabolites of para-aminosalicylic acid, and the sulphoxide metabolites of ethionamide. The effect of renal impairment is relatively unimportant for the excretion of isoniazid, rifampicin and para-aminosalicylic acid, but the elimination half-life of streptomycin increases to 100 hours when the blood urea nitrogen level is greater than 100mg/100ml, and ototoxicity is strikingly more frequent. In states of malnutrition, such as kwashiorkor, the protein binding of para-aminosalicylic acid decreases from 15% to essentially zero and in the case of ethionamide and streptomycin binding decreases by 6% and 16% respectively. Of the data concerning age-related effects, most notable are the prolonged elimination half-life of isoniazid in neonates (up to 19.8 hours), and the lower peak serum concentrations of rifampicin in children of one-third to one-tenth those of adults following a similar dose on a weight basis. For kanamycin, the maximum plasma concentration varies inversely with age but is not influenced by birthweight; however, the clearance is directly dependent upon birthweight and postnatal age. For the elderly, age is an insignificant factor for the elimination of isoniazid when compared with young adults of similar acetylator status, and the metabolism of rifampicin may be considered globally unaltered in this age group.(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗
PubMed1999

Treatment and prevention of multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDRTB), which is defined as combined resistance to isoniazid and rifampicin, is a 'man-made' disease that is caused by improper treatment, inadequate drug supplies or poor patient supervision. Patients with MDRTB face chronic disability and death, and represent an infectious hazard for the community. Cure rates of 96% have been achieved but require prompt recognition of the disease, rapid accurate susceptibility results, and early administration of an individualised re-treatment regimen. Such regimens are usually based on a quinolone and an injectable agent (i.e. an aminoglycoside or capreomycin) supplemented by other 'second-line' drugs. This therapy is prolonged (e.g. 24 months), expensive, and has multiple adverse effects. Prevention of MDRTB is therefore of paramount importance. The World Health Organization (WHO) has recommended a multifaceted programme, known by the acronym DOTS (directly observed therapy, short-course), that promotes effective treatment of drug-susceptible TB as the prime method of limiting drug resistance. DOTS was part of a successful MDRTB control programme in New York City, which also included treatment of prevalent MDRTB cases, streamlined laboratory testing, effective infection control procedures and wider application of screening and preventive therapy (although the optimal chemotherapy for MDRTB infection remains undefined). Industrialised countries have the resources to treat patients with MDRTB and to mount these extensive control programmes. Unfortunately, MDRTB is also prevalent in Asia, South America and the former Soviet Union. First world countries have a vested interest, as well as a moral responsibility, to assist in controlling MDRTB in these 'hot spots'.

Antitubercular Agents↗
PubMed1988

Mode of action of deoxypheganomycin D on Mycobacterium smegmatis ATCC 607.

Deoxypheganomycin D, a specific inhibitor of mycobacteria, inhibits the growth in vitro of Mycobacterium smegmatis ATCC 607 (M. 607) bacteriostatically at concentrations as high as 7 X 10(-5) M. It shows no cross-resistance to paromomycin, capreomycin, viomycin, streptothricin, kanamycin and streptomycin. Deoxypheganomycin D at 2.8 X 10(-7) M where the cell growth of M. 607 is only partially inhibited does not significantly inhibit DNA, RNA or protein synthesis but leads to marked decrease (13% of control) in [14C]glycerol-derived radioactivity in cell-walls. In the presence of 7 X 10(-6) M deoxypheganomycin D, the influx of leucine but not thymidine is affected while the reverse is true with efflux. The data suggest that the effect of deoxypheganomycin D on M. 607 may be related to both the cell membrane and specific mycobacterial lipid like components of the cell-wall.

Amino Acids↗
PubMed2002

[Pulmonary infection caused by Mycobacterium szulgai: a case report].

We reported a case of pulmonary infection caused by Mycobacterium szulgai (M. szulgai) in an immunocompetent, asymptomatic 55-year-old man without underlying disease. A chest radiograph of an annual health examination revealed a right upper lobe infiltrate with thin-walled cavities, which was not present in the previous year. An acid-fast stain of bronchial washing fluid was positive, and antimycobacterial chemotherapy with isoniazid (400 mg/day), rifampin (450 mg/day), and ethambutol (750 mg/day) was initiated on presumptive diagnosis of the case as tuberculosis. DNA-DNA hybridization of sputum and bronchial washing samples identified M. szulgai as the causative organism. Antimicrobial susceptibility testing indicated that the isolate was sensitive to most common antimycobacterial drugs except capreomycin (CPM) and p-aminosalicylic acid (PAS), and was also sensitive to clarithromycin and fluoroquinolones including ofloxacin, levofloxacin, sparfloxacin, and ciprofloxacin. After 12 months of therapy, a repeat chest radiograph demonstrated improvement of the right upper lobe infiltrate. When M. szulgai is isolated, it almost always represents a true pathogen. Therefore, the detection of even a small number of M. szulgai warrants treatment based on susceptibility testing.

Antitubercular Agents↗
PubMed2002

[A 50-year year history of new drugs in Japan: the developments of antituberculosis drugs and their influences on the epidemiological aspects].

Drugs used in the treatment of tuberculosis (Tb) in Japan are investigated. Especially the chemotherapy for Tb and its influences on epidemiological aspects are discussed. 1. Various drugs were used for Tb patients before the World War II, but none was effective in curing this infectious disease. Creosote and guajacol groups were used frequently to relieve symptoms of pulmonary tuberculosis, but the disease could not cure itself. Because of the sacrifice of young patients, the mortality rate of Tb from 1935 to 1950 was ranked as the worst in Japan. So until the advent of chemotherapeutic drugs, Tb was known as the most formidable fatal plague. 2. Streptomycin (SM), the first effective chemotherapeutic drug, was imported into Japan and widely used from 1947. PAS in 1950 and isoniazid (INH) in 1952 were introduced to Tb therapy. The triple combination therapy of these drugs was considered the most favorable regimen for Tb from the 1950s to the early 1970s. Excellent results were obtained in this period. The mortality rate of Tb had dropped rapidly from its peak to half in 1952 and to a fourth in 1956 (Figs. 2, 3). 3. Several anti-Tb drugs, such as pyrazinamide ethionacide, ethambutol, and some antibiotics (kanamycin, cyloserine, and capreomycin) had been discovered and used in practice. These were not used singly, because of their weak clinical efficacies and severe side effects. They were mostly used to prevent the development of bacillus resistance to SM or INH. In the guidelines of the Japanese Society for Tuberculosis, in 1974. drugs used for Tb could be divided into two major categories: first-line and second-line groups. The second-line drugs included those that prevent a high resistance to the main (first-line) drugs. 4. Rifampicin (RFP), the most valuable drug for Tb, was introduced in therapy in Japan in 1971. RFP has a low incidence of severe side-effects, but because of the rapidity with which resistance may develop, it cannot be used alone. RFP in combination with INH is the most effective therapy for all forms of the disease. The guidelines, newly proposed in 1986 by the Japanese Society for Tuberculosis recommended the short 6-month course of treatment that used combination of RFP and INH. The advent of RFP had contributed to the cure of the individual patient, but it did not effect the mortality or the morbidity rate of Tb. Chemotherapy is the most effective means of suppressing tuberculosis, which was formerly nearly always fatal, but it could not completely eradicate the disease. Preventing the development of resistance to chemotherapeutic drugs might be a special problem.

History, 20th Century↗
PubMed2003

[Multiresistant tuberculosis in the Czech Republic (1999-2001)].

BACKGROUND: Multidrug-resistant (MDR) tuberculosis, defined as a disease caused by Mycobacterium tuberculosis strains, which are resistant to more antituberculous drugs (at least to isoniazid and rifampicin), is a problem frequently discussed in the Czech Republic. Cases of specific disease refractive to causal antituberculous therapy are associated with the risk of the spread of the causative agent among the population. METHODS AND RESULTS: The National Reference Laboratory for Mycobacteria collected 2813 Mycobacterium tuberculosis strains isolated by Czech mycobacteriological laboratories in 1999 to 2001. All strains were tested for susceptibility to basic antituberculous drugs and then the MDR strains were further tested for susceptibility/resistance to other antituberculous and antibacterial drugs. The MDR strains were studied by DNA analysis (DNA fingerprinting restriction analysis, RFLP-Restriction Fragment Length Polymorphism) as well. Thirty-nine patients who had MDR tuberculosis were excretors of 56 Mycobacterium tuberculosis strains. In average, MDR tuberculosis accounted for 1.96% (1.7-2.4) of all cases of bacillary tuberculosis. The most frequent type of the multidrug resistance was that resistant to four basic antituberculous drugs (isoniazid, rifampicin, ethambutol and streptomycin). It was confirmed in 48.2% multidrug resistant strains. CONCLUSIONS: Isepamicin, clofazimin, capreomycin and amikacin are considered to be the most promising antituberculosis drugs. Based on RFLP profiles, 61.5% of strains were placed into 8 clusters while the other strains remained unclustered. No significant differences in geographical distribution and population structure were found between the excretors of clustered strains and those of unclustered strains. Preliminary comparison with restriction profiles of the MDR Mycobacterium tuberculosis strains in the international database suggests the uniqueness of Czech strains showing the profiles not found elsewhere to date.

Czech Republic↗
PubMed2004

A microplate indicator-based method for determining the susceptibility of multidrug-resistant Mycobacterium tuberculosis to antimicrobial agents.

SETTING: Reference Laboratory, Buenos Aires Province Tuberculosis Control Program, Dr Cetrangolo Hospital, Argentina. OBJECTIVE: To obtain a rapid, inexpensive method of determining minimal inhibitory concentrations (MIC) of several drugs acting on multidrug-resistant Mycobacterium tuberculosis (MDR-TB), a colorimetric, microplate-based assay (M-MTT) was developed. DESIGN: One hundred and one clinical isolates were studied. Drugs were placed in a microtiter plate, and several two fold dilutions were made in situ. Kanamycin, capreomycin, ethionamide, para-aminosalicylic acid and clarithromycin were tested in a range concentration of 8.0-0.25 microg/ml, cycloserine 60.0-1.9 microg/ml, clofazimine 3.0-0.10 microg/ml, levofloxacin 4.0-0.13 microg/ml and rifabutin 1.0-0.13 microg/ml. General indicator 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) at 5.0 mg/ml was used for visualising cellular growth and viability. The proportion method with Middlebrook 7H11 was used as the gold standard. RESULTS: MICs by M-MTT were obtained at on average 8 days and correlated with those obtained using the proportion method. In our conditions, the total cost of MIC determination for nine drugs was 5.00 US dollars. CONCLUSION: M-MTT could be used as a simple, rapid, low-cost technology to test the susceptibility of MDR-TB strains to several second-line and alternative drugs, with the objective of orienting future treatment regimens.

Anti-Bacterial Agents↗
PubMed2004

[Pulmonary disease caused by nontuberculous mycobacteria after allogeneic hematopoietic stem cell transplantation--a case report and literature review].

OBJECTIVE: To report a case with pulmonary disease caused by nontuberculous mycobacteria (NTM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a literature review. METHODS: Case report and literature review. RESULTS: A patient with acute non-lymphocytic leukemia was treated by allo-HSCT. Her NTM lung disease developed after HSCT was successfully treated with a 3 antimicrobials combination of clarithromycin, levofloxacin and capreomycin for 10 months. CONCLUSION: NTM infections are infrequent in allo-HSCT recipients and have a good clinical prognosis if correctly treated.

Adult↗