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Rapid susceptibility testing of Mycobacterium tuberculosis by the Mycobacteria Growth Indicator Tube (MGIT AST SIRE).

OBJECTIVE: To evaluate the reliability of the Mycobacteria Growth Indicator Tube (MGIT AST) for susceptibility testing of Mycobacterium tuberculosis. METHODS: Seventy strains of M. tuberculosis were tested for susceptibility to streptomycin, isoniazid, rifampicin and ethambutol by comparing MGIT AST results to those obtained by the method of proportion (MOP) on Lowenstein-Jensen (LJ) and Middlebrook 7H10 media. The 7H10 MOP was considered the method of reference. RESULTS: The turnaround time for MGIT AST was 6.2 days (5-10 days) and for MOP it was 18-21 days. With rifampicin, MGIT AST agreed for all isolates with both MOP. For streptomycin, MGIT AST and 7H10 MOP agreed for 64 isolates (91.4%); 61 were susceptible and three resistant. LJ MOP and 7H10 MOP agreed for 64 isolates (92.2%); 62 were susceptible and three resistant. With isoniazid, both MOP agreed for all isolates, while MGIT AST and 7H10 MOP had two discrepancies. For ethambutol, MGIT AST and 7H10 MOP were concordant for 66 isolates; 65 were susceptible and one resistant. Both MOP were concordant for 67 isolates; 66 were susceptible and one resistant. CONCLUSIONS: Based on these results, MGIT AST is a time-saving method and can be used as an alternative to the BACTEC System. MGIT AST is reliable as far as rifampicin and isoniazid are concerned; however, additional studies are needed for streptomycin and ethambutol.

Drug Resistance, Microbial↗

In vitro and in vivo susceptibility of atypical mycobacteria to various drugs.

In vitro sensitivities to various drugs of a total of 106 strains of atypical mycobacteria were studied in modified Dubos Tween albumin liquid medium. Eight triple-drug combinations of antituberculous drugs were also evaluated in vitro for their potentiated activities. Minimal to moderate potentiation was demonstrated in the majority of the combination. From the results, the triple-drug combination--including rifampin, one of three aminoglycosides (streptomycin, kanamycin, viomycin), and either ethionamide or ethambutol--might be recommended for Mycobacterium kansasii infections. Against Mycobacterium avium-intracellulare infections, rifampin-kanamycin-ethionamide or rifampin-kanamycin-ethambutol might be the choice if we were to select any triple-drug regimen. None of the triple-drug regimens thus far tested on M. avium-intracellulare were active enough to recommend fully for clinical use. In vivo experimental chemotherapy of murine infection with Mycobacterium intracellulare (TMC 1469) on a five-drug regimen, kanamycin-rifampin-cycloserine-ethambutol-ethionamide, showed a moderate therapeutic effect but the infection was not eradicated.

Animals↗

Evaluation of the activity of a number of antimicrobial agents against mycobacteria within mouse macrophages by a radiometric method.

[3H]-uridine was incorporated by Mycobacterium bovis BCG with increasing intensity as the incubation period was increased. Rifampicin and isoniazid inhibited incorporation of the label rapidly. Similar inhibition was seen with M. tuberculosis H37Rv and several clinical isolates of M. tuberculosis both in axenic medium and inside macrophages. Ofloxacin and ciprofloxacin were both inhibitory but clofazimine was not. The combination of rifampicin with either isoniazid or ethambutol produced enhanced killing, but the combination of ethambutol and isoniazid was not synergic. Mycobacterium avium-intracellulare isolates from AIDS patients were less susceptible to rifampicin and were unaffected by isoniazid, ethambutol, clofazimine, ofloxacin and ciprofloxacin. The results obtained by inhibition of [3H]-uridine incorporation by intracellular mycobacteria correlated with conventional in-vitro MICs and was reproducible and rapid; a definitive result was obtainable within seven days.

Animals↗

Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies.

Acquired Immunodeficiency Syndrome↗

In vitro antimicrobial activity of benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex, determined by the radiometric method.

MICs of a newly developed benzoxazinorifamycin derivative, KRM-1648, for Mycobacterium avium complex (MAC) were determined by the BACTEC 460 TB system and compared with those of other known antimicrobial agents. The radiometric method gave a fast, accurate, and reproducible MIC for each antimicrobial agent. MICs of KRM-1648 for 30 strains of MAC (10 strains each of M. avium isolated from AIDS and non-AIDS patients and of Mycobacterium intracellulare isolated from non-AIDS patients) were measured. The MICs, ranging from 0.004 to 0.0625 microgram/ml, were the lowest of all tested drugs, including rifampin, rifabutin, streptomycin, kanamycin, isoniazid, ethambutol, ofloxacin, ciprofloxacin, sparfloxacin, and clarithromycin. The MICs were 2 to 512 and 1 to 32 times lower than those of rifampin and rifabutin, respectively. With rifampin and ethambutol, there were some differences between the MICs for M. avium isolated from AIDS patients (American) and those for M. avium from non-AIDS patients (Japanese). Moreover, appreciable differences between the MICs of some drugs against M. avium and M. intracellulare isolated from non-AIDS patients were found. Many strains of M. avium were more susceptible to ofloxacin than M. intracellulare, but, conversely, M. avium was more resistant to rifampin, streptomycin, ethambutol, and clarithromycin than M. intracellulare.

Acquired Immunodeficiency Syndrome↗

Potential drug targets for Mycobacterium avium defined by radiometric drug-inhibitor combination techniques.

Previously established radiometric techniques were used to assess the effectiveness of combined antimicrobial drug-inhibitory drug (drug-inhibitor) treatment on two clinical isolates of the Mycobacterium avium complex representing three colony variants: smooth opaque (dome) (SmO), smooth transparent (SmT), and rough (Rg). All variants were identified as members of the M. avium complex; however, only the SmT colony type of strain 373 possessed characteristic serovar-specific glycopeptidolipid (GPL) antigens. MICs, determined radiometrically, of drugs with the potential to inhibit the biosynthesis of GPL antigens or other cell envelope constituents were similar for all strains. These drugs included cerulenin, N-carbamyl-DL-phenylalanine, N-carbamyl-L-isoleucine, trans-cinnamic acid, ethambutol, 1-fluoro-1-deoxy-beta-D-glucose, 2-deoxy-D-glucose, and m-fluoro-phenylalanine. The MICs of the antimicrobial drugs amikacin, sparfloxacin, and clarithromycin varied, but overall the MICs for the SmO variant were the lowest. Radiometric assessment of drug-inhibitor combinations by using established x/y determinations revealed enhanced activity when either ethambutol or cerulenin were used in combination with all antimicrobial agents for all variants except the Rg variant of strain 424, for which ethambutol was not effective. Enhanced activity with amino acid analogs was observed with the Rg colony variants of strains 373 and 424. Two potential sites for drug targeting were identified: fatty acid synthesis, for all strains assayed, and peptide biosynthesis, particularly for Rg colony variants that possess previously identified phenylalanine-containing lipopeptides as potential targets for future drug development.

Cerulenin↗

Conventional and radiometric drug susceptibility testing of Mycobacterium tuberculosis complex.

A recently developed method of drug susceptibility testing of Mycobacterium tuberculosis which measures the evolution of labeled CO2 from [1-14C]palmitic acid (BACTEC 460 system) was compared to three conventional methods. The proportion method of drug susceptibility testing was the standard against which all test results were compared. Indirect drug susceptibility to isoniazid, streptomycin, rifampin, and ethambutol of 245 isolates belonging to the M. tuberculosis complex was determined. In 95% of the cases, results obtained by the radiometric method were available within 1 week, as opposed to 3 to 6 weeks needed in conventional methodology. Overall agreement was 96.4%. Specificity values ranged from 0.98 to 1.0; sensitivity values of 1.0 for rifampin, 0.96 for streptomycin, 0.91 for isoniazid, and 0.18 for ethambutol were obtained. The specificity of the absolute concentration and resistance ratio drug susceptibility testing methods were 0.99 and 1.0, respectively. The sensitivity of the former was higher than that of the radiometric method (0.99 verus 0.92), whereas that of the latter was lower (0.88 verus 0.96). Further testing indicated that the low sensitivity determined for ethambutol may be due to the choice of the critical concentration used, rather than to a shortcoming of the procedure. The radiometric method thus does not significantly differ in reliability from conventional methods of drug susceptibility testing of M. tuberculosis.

Antitubercular Agents↗

Evaluation of automated BACTEC MGIT 960 system for testing susceptibility of Mycobacterium tuberculosis to four major antituberculous drugs: comparison with the radiometric BACTEC 460TB method and the agar plate method of proportion.

We evaluated the performance of BACTEC MGIT 960 for automated testing of the susceptibility of 133 strains of Mycobacterium tuberculosis to streptomycin, isoniazid, rifampin, and ethambutol. The BACTEC MGIT 960 results were compared with those obtained with the radiometric BACTEC 460TB system, and when there was disagreement, the method of proportion on agar plates was used as a reference method. Strains resistant to the critical concentration of streptomycin, isoniazid, or ethambutol were also tested with a second, higher concentration. The overall agreement between the two systems was 96.7%, and the 18 discrepancies were resolved in favor of BACTEC 460TB in 11 cases and in favor of BACTEC MGIT 960 in 7, a difference which was not statistically significant. Apart from the assay's low specificity for ethambutol, which was low for the radiometric assay as well, good sensitivity and specificity values characterized BACTEC MGIT 960. The average time required for completion of the test was 2.5 days shorter with BACTEC 460TB. In conclusion, BACTEC MGIT 960 appears to be a suitable replacement for the radiometric method of antimicrobial susceptibility testing of M. tuberculosis. The problem of frequent contamination of BACTEC MGIT 960 tests needs to be quickly resolved; in fact, 14 strains had to be reprocessed because of contamination.

Antitubercular Agents↗

Para-aminosalicylic acid-induced hypoglycaemia in a patient with diabetic nephropathy.

A 62-year-old Indian with diabetic nephropathy controlled with metformin, developed miliary tuberculosis for which he was treated with rifampicin, isoniazid and ethambutol. Soon afterwards he developed cholestatic hepatitis and visual disturbance. Rifampicin and ethambutol were stopped. Streptomycin caused vertigo and had to be stopped. The introduction of para-aminosalicylic acid (PAS) led to hypoglycaemic coma. Metformin was stopped. Hypoglycaemic coma recurred. PAS was stopped and the patient's blood glucose concentrations became normal. Treatment with isoniazid and ethambutol led to total recovery from pulmonary tuberculosis. The induction of hypoglycaemia with PAS in this patient suggests a potential role for PAS in the treatment of diabetes mellitus.

Aminosalicylic Acid↗

Intralaboratory comparison of drug susceptibility testing of Mycobacterium tuberculosis by BACTEC and conventional methodology.

The BACTEC radiometric method of drug susceptibility testing of Mycobacterium tuberculosis is a reliable and rapid diagnostic tool in clinical mycobacteriology. However, large scale comparative studies have also shown that the level of agreement with standard methodology was less satisfactory with strains resistant to ethambutol and streptomycin than with strains resistant to rifampin and to isoniazid. Since disagreement with drug resistance strains is far more frequent than with drug susceptible strains, it was felt that only the comparison of a large number of resistant strains would be needed to further refine this new technique. The analysis of BACTEC-derived data for isoniazid and rifampin shows that the level of agreement with conventional methodology falls well within accepted limits. Statistical analysis of the radiometric versus conventional comparisons shows no significant differences between the two methods in the case of isoniazid, rifampin, and ethambutol (3 mg/L). Streptomycin and two other ethambutol concentrations tested showed lower levels of agreement and significant statistical differences with conventional methodology.

Anti-Bacterial Agents↗

Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention.

Treatment of Tuberculosis. 1. A 6-mo regimen consisting of isoniazid, rifampin, and pyrazinamide given for 2 mo followed by isoniazid and rifampin for 4 mo is the preferred treatment for patients with fully susceptible organisms who adhere to treatment. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should be included in the initial regimen until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (i.e., there is less than 4% primary resistance to isoniazid in the community, and the patient has had no previous treatment with antituberculosis medications, is not from a country with a high prevalence of drug resistance, and has no known exposure to a drug-resistant case). This four-drug, 6-mo regimen is effective even when the infecting organism is resistant to INH. This recommendation applies to both HIV-infected and uninfected persons. However, in the presence of HIV infection it is critically important to assess the clinical and bacteriologic response. If there is evidence of a slow or suboptimal response, therapy should be prolonged as judged on a case by case basis. 2. Alternatively, a 9-mo regimen of isoniazid and rifampin is acceptable for persons who cannot or should not take pyrazinamide. Ethambutol (or streptomycin in children too young to be monitored for visual acuity) should also be included until the results of drug susceptibility studies are available, unless there is little possibility of drug resistance (see Section 1 above). If INH resistance is demonstrated, rifampin and ethambutol should be continued for a minimum of 12 mo. 3. Consideration should be given to treating all patients with directly observed therapy (DOT). 4. Multiple-drug-resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended. 5. Children should be managed in essentially the same ways as adults using appropriately adjusted doses of the drugs. This document addresses specific important differences between the management of adults and children. 6. Extrapulmonary tuberculosis should be managed according to the principles and with the drug regimens outlined for pulmonary tuberculosis, except for children who have miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis who should receive a minimum of 12 mo of therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Killing by antimycobacterial agents of AIDS-derived strains of Mycobacterium avium complex inside cells of the mouse macrophage cell line J774.

The murine macrophage continuous cell line J774 was used to measure the ability of antimicrobial agents, either singly or in combination, to kill intracellular Mycobacterium avium complex. All of 14 strains of M. avium complex, isolated from patients with AIDS, grew inside J774 cells during an incubation period of 7 days. The susceptibility of macrophage-ingested M. avium complex to antimicrobial agents was determined by comparing the number of colony-forming units (cfu) of M. avium complex inside untreated macrophages at the time of drug addition with the number of cfu present in macrophages after treatment with drugs for 7 days. Simultaneous experiments were carried out in broth medium without macrophages in order to compare killing of free mycobacteria with killing of macrophage-ingested mycobacteria. Antimicrobial agents (rifampin, rifabutin [Ansamycin], ethambutol, ciprofloxacin, clofazimine, isoniazid, and amikacin) were tested using concentrations that are achievable in the serum of patients. Among drugs known to penetrate macrophages, there was 96.2% agreement in susceptibility test results between the broth experiments and the J774 experiments when single drugs were tested, but only 74% agreement when combinations of drugs were tested. Killing of M. avium complex inside J774 cells by any single drug was uncommon. However, killing in J774 cells occurred against 10 of 11 (91%) strains with the combination of rifabutin + ethambutol + ciprofloxacin and against all of seven strains tested with the combination of rifabutin + ethambutol + amikacin. Interpretive criteria of in vitro susceptibility data need to be developed so that these interpretations correlate with a predictable clinical response in patients.

Acquired Immunodeficiency Syndrome↗

Clinical trial of two short-course (6-month) regimens and a standard regimen (12-month) chemotherapy in retreatment of pulmonary tuberculosis in Pakistan. Results 18 months after completion of treatment (Lahore Tuberculosis Study).

This study compared the efficacy and tolerability of two 6-month daily regimens of isoniazid and rifampin in combination with either pyrazinamide or ethambutol (RHZ and RHE regimens) against a standard daily regimen of streptomycin, isoniazid, and ethambutol (SHE regimen) given for 6 months followed by isoniazid and ethambutol for an additional 6 months. Only previously treated sputum positive patients suffering from active pulmonary tuberculosis were entered into the study. Three hundred and fifty-eight patients were admitted to the study and 267 (75%) completed chemotherapy. Eighty-five percent of RHZ-regimen and 82% of RHE-regimen patients achieved sputum culture negativity compared to 55% of patients in SHE regimen. Successfully treated patients were followed up for 18 months, and among these, all 3 treatment regimens showed broadly similar levels of culture negativity at the end of the follow-up period. Final therapeutic outcome was based on sputum culture results obtained throughout the follow-up period, and no statistically significant difference in relapse rate was noticed in the 3 regimens. Severe drug intolerance necessitated discontinuation of therapy in only 2 patients.

Antitubercular Agents↗

First-line drug-resistant tuberculosis among children under 15 years in Ethiopia: insights from phenotypic and whole-genome sequencing approaches.

BACKGROUND: Childhood drug-resistant tuberculosis is often underdiagnosed and inadequately characterized due to the paucibacillary nature of the disease. This study aimed to assess resistance to first-line anti-tuberculosis drugs in children using phenotypic drug susceptibility testing and whole-genome sequencing. METHODS: A retrospective-prospective study was conducted on culture-confirmed childhood tuberculosis cases in Ethiopia (2017–2023). Phenotypic drug susceptibility testing was performed on 110 Mycobacterium tuberculosis complex isolates. Whole-genome sequencing was completed for 85 of these isolates, which were analyzed using the TB-Profiler and MTBSeq pipelines. We assessed the sensitivity, specificity, predictive values, and kappa agreement of whole-genome sequencing compared with phenotypic drug susceptibility testing. RESULTS: Phenotypic resistance to at least one first-line anti-TB drug was observed in 26/110 (23.6%) of the examined isolates, with isoniazid resistance being the most frequent, 23/110 (20.9%), followed by rifampicin resistance, 18/110 (16.4%). TB-Profiler showed almost perfect agreement with phenotypic drug susceptibility testing for rifampicin (sensitivity 94.4%, kappa = 0.96) and isoniazid (sensitivity 91.3%, kappa = 0.91), whereas MTBSeq showed slightly lower performance. Both pipelines demonstrated moderate to weak agreement with phenotypic drug susceptibility testing for detecting resistance to ethambutol, pyrazinamide, and streptomycin. The most frequently observed resistance mutations among phenotypically resistant isolates were rpoB (Ser450Leu), katG (S315Thr), embB (Met306Ile), and pncA (C-11 A > G) for rifampicin, isoniazid, ethambutol, and pyrazinamide, respectively. Discrepancies between genotypic and phenotypic drug susceptibility testing were observed across all first-line anti-TB drug-resistant isolates, particularly for ethambutol and pyrazinamide. CONCLUSION: We found a high prevalence of isoniazid resistance, along with rifampicin resistance, underscoring the need for early detection in vulnerable groups. Whole-genome sequencing showed good accuracy for these drugs, with TB-Profiler performing best. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗

Mycobacterium avium complex infection. Pharmacokinetic and pharmacodynamic considerations that may improve clinical outcomes.

Mycobacterium avium complex (MAC) is an infrequent pulmonary pathogen in immunocompetent hosts. In patients with AIDS, MAC causes disseminated infection (DMAC) in up to 50% of those with CD4+ counts less than 100 cells/mm3. A significant portion of the total body burden of MAC is found inside macrophages, and the distribution of organisms has implications for drug therapy. Clarithromycin, azithromycin, and rifabutin all appear to enter these cells well; rifampicin (rifampin), ethambutol, ciprofloxacin, and other agents also appear to enter these cells. MAC susceptibility is probably best tested using the radiometric method (BACTEC). Susceptibility break-points have been proposed for the various anti-MAC agents; however, solid clinical correlations have been achieved only for clarithromycin. Further research is required to establish break-points for the other agents. Based on current data, azithromycin and clarithromycin appear to be key drugs in the treatment of MAC, while rifabutin has been used more often than rifampicin in studies involving patients with AIDS. Among the drugs traditionally used for M. tuberculosis (TB), ethambutol, rifampicin and streptomycin are perhaps the most useful for MAC. Amikacin and clofazimine may also be useful. The limited data available on AIDS patients with MAC, plus additional data from AIDS patients with TB, suggest that malabsorption of the oral antimycobacterial drugs is common. Some drugs (rifampicin and ethambutol) appear to be particularly affected. Because most of the studies of DMAC have not evaluated the pharmacokinetics of the drugs, questions of drug efficacy cannot be separated from questions of biovailability. This significant oversight in study design should be eliminated from future investigations. Patient-specific susceptibility data combined with therapeutic drug monitoring and dosage individualisation is one way to identify problems with drug therapy and to overcome them. Because many of the drugs used in patients with AIDS affect the metabolism of concurrently used drugs, therapeutic drug monitoring is a valuable asset for untangling multiple drug interactions. Since drug therapy is the only aspect of a mycobacterial infection within our control, the better we control the drug therapy, the better our patients should do.

AIDS-Related Opportunistic Infections↗

Tuberculosis in neonates and infants: epidemiology, pathogenesis, clinical manifestations, diagnosis, and management issues.

Tuberculosis is one of the leading infectious causes of death and as such represents a major global health problem. Infants may develop congenital tuberculosis from an infectious mother or, most commonly, they may acquire postnatal disease by contact with an infectious adult source. Important epidemiologic, pathogenetic, and clinical data regarding the management of infantile disease are reviewed. Diagnostic evaluation includes tuberculin skin tests, chest radiography and other imaging studies, smears and cultures, examination of the cerebrospinal fluid, and polymerase chain reaction, as well as the more recent interferon-gamma assay. Pregnant women with a positive Mantoux skin test but normal chest x-ray should either start chemoprophylaxis during gestation or after delivery depending on the likelihood of being recently infected, their risk of progression to disease, as well as their clinical evidence of disease. Pregnant women with a positive Mantoux skin test and chest x-ray or symptoms indicative of active disease should be treated with non-teratogenic agents during gestation; all household contacts should also be screened. When tuberculosis is suspected around delivery, the mother should be assessed by chest x-ray and sputum smear; separation of mother and offspring is indicated only if the mother is non-adherent to medical treatment, needs to be hospitalized, or when drug-resistant tuberculosis is involved. According to the American Academy of Pediatrics, treatment of latent infection is highly effective with isoniazid administration for 9 months. This regimen may be extended to 12 months for immunocompromised patients. When drug resistance is suspected, combination therapies, which usually consist of isoniazid with rifampin (rifampicin), are administered until the results of susceptibility tests become available. Organisms resistant to isoniazid only may be treated with rifampin alone for a total of 6-9 months. All infants with tuberculosis disease should be started on four agents (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) until drug susceptibility is assessed. For susceptible intrathoracic tuberculosis, isoniazid, rifampin, and pyrazinamide are administered for a total of 2 months, at which point pyrazinamide is withdrawn and the other two agents are continued for another 4-10 months depending on the severity of the disease. The same regimen may be applied in extrapulmonary tuberculosis with the exception of skeletal, miliary, and CNS disease, which require daily administration of isoniazid, rifampin, pyrazinamide, and streptomycin for 1-2 months, followed by isoniazid and rifampin daily or twice weekly for another 10 months. When drug-resistant tuberculosis is suspected, a regimen of isoniazid, rifampin, and pyrazinamide plus either streptomycin or ethambutol should be initially prescribed, until the results of susceptibility tests become available. HIV-seropositive infants with pulmonary tuberculosis should receive isoniazid, rifampin, pyrazinamide, and ethambutol or an aminoglycoside for 2 months, followed by isoniazid and rifampin for a total of at least 12 months. Apart from conventional antimycobacterial agents, novel therapeutic modalities, which stimulate the host immune system such as interleukin-2 (IL-2), IL-12, interferon-gamma, and tumor necrosis factor antagonists have been tested with promising results.

Adult↗

[A case of pneumonia caused by Mycobacterium avium complex successfully treated with clarithromycin].

We reported on a 79-year-old woman with pneumonia caused by Mycobacterium avium complex (MAC). She was admitted with fever, general fatigue, and cough. A chest X-ray film showed infiltrative shadows in the right lung field. In spite of administration of conventional antibiotics, the infiltrative shadows enlarged. A chest CT scan revealed areas of consolidation and ground glass opacities. Bronchoalveolar lavage (BAL) examination revealed an increased number of lymphocytes. Transbronchial lung biopsy revealed many granulomatous regions with giant cells. Mycobacterium intracellulare was found in the culture of BAL fluid and identified by PCR. Treatment was started with rifampicin, ethambutol, and clarithromycin. However, rifampicin and ethambutol were soon discontinued because of severe anorexia. Her symptoms and the radiographic appearance markedly improved following treatment of clarithromycin alone. Subsequently small doses of rifampicin and ethambutol were restarted because her general condition was much improved. These findings suggest that clarithromycin is an effective and tolerable agent for elderly patients with MAC.

Aged↗

[Comparative study of 3 tests for susceptibility of Mycobacterium tuberculosis to first-line antituberculous drugs].

Treatment of tuberculosis requires a multidrug regimen for a prolonged period of time (6-12 months), which leads to a high level of noncompliance with therapy. This lack of compliance has led to an increase in drug-resistant strains of Mycobacterium tuberculosis. Rapid drug susceptibility tests are needed to assess effective chemotherapy regimens. In the present study, the reliability of ESP Myco System II(R) and E-test(R) for determining the susceptibility of 82 clinical isolates of M. tuberculosis to rifampin, isoniazid, streptomycin and ethambutol was evaluated by comparing results to those of the multiple proportion method as a reference. ESP Myco System II(R) is a nonradioactive, totally automated, continuously monitored system designed to detect grown mycobacteria. E-test(R) is a well-described method of susceptibility testing which provides data on minimal inhibitory concentration. The susceptibility results of both methods were available within 9 days, while those of the proportion method required 28 days. Levels of agreement between ESP Myco System II(R) and the proportion method for the clinical isolates analyzed were 100% for rifampin, isoniazid and ethambutol. Only one discrepancy was found for streptomycin. For the E-test(R), the results were less favorable. ESP Myco System II(R) was shown to be a rapid and reliable method for testing susceptibility of M. tuberculosis isolates. Nevertheless, E-test(R) provided low specificity for streptomycin and ethambutol. Further studies to test the reliability of the E-test(R) are necessary.

Antitubercular Agents↗