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PubMed1986

Cost savings from alternative treatments for tuberculosis.

The cost effectiveness of short tuberculosis treatment regimes using rifampicin (R) or ethambutol (E) is calculated and compared to long regimes based on thiacetazone and isoniazid (TH). Although rifampicin and ethambutol are more costly per case they are only about one half the cost of the isoniazid based regimes per person effectively treated. This result is primarily derived from higher patient compliance with the short regimes. In addition, ambulatory treatment, where practical, is approximately one third the cost per person effectively treated of regimes using inpatient treatment for the first 2 months. Applied to 1982 data for Botswana, the analysis reveals that treating 80% of patients through ambulatory R and E regimes would have reduced total health expenditures for tuberculosis care by two thirds compared to inpatient regimes based on TH, and the number of people complying and cured would have doubled.

Ambulatory Care↗
PubMed1992

Lymph node tuberculosis: 7-year experience in Veterans General Hospital, Taipei, Taiwan.

We retrospectively studied 71 cases of lymph node tuberculosis confirmed by culture or pathology from 1983 to 1989. Young adults were most frequently involved and the female to male ratio was 3:2. of 71 patients, three-quarters presented with palpable masses and two-thirds were asymptomatic. The cervical nodes were most frequently involved. Roentgenographic evidence of pulmonary tuberculosis was detected in 42% of patients and sputum culture-positive tuberculosis occurred in 7%. Tuberculin skin testing is less useful in our country due to routine BCG vaccination during infancy and early childhood. Selective excisional biopsy in addition to clinical information was necessary for differential diagnosis. 48 patients received regular treatment and were followed up for at least 1 year. Fresh nodes or enlargement of existing nodes developed in 10% of patients during treatment. Residual nodes were present in 10% of patients at the end of 9-month treatment with rifampicin, isoniazid and ethambutol, including prolonged or modified regimens in some individuals. In conclusion, in areas with a high frequency of tuberculous strains presenting a primary resistance to isoniazid, a 9-month regimen of rifampicin, isoniazid and ethambutol is recommended for lymph node tuberculosis.

Adult↗
PubMed1994

High initial and acquired drug resistance in pulmonary tuberculosis in Turkey.

SETTING: Süreyyapasa Center for Chest Diseases and Thoracic Surgery, Istanbul, Turkey between January 1992 and December 1992. OBJECTIVE: To evaluate the prevalances of initial and acquired resistance to antituberculosis drugs in our center. DESIGN: 785 patients with pulmonary tuberculosis (both old = 525/785 and new = 260/785 cases) referred to our center were evaluated with respect to their drug resistance patterns. RESULTS: The overall resistance rate (1 or more drugs) was 35.5%, with initial resistance 26.6% (140 of 525) and acquired resistance 53.4% (139 of 260). Initial resistance to streptomycin was the most frequent (20.6%), followed by rifampicin (10.8%), isoniazid (5.1%) and ethambutol; (4.2%). Initial resistance was noted as 16.4% to 1 drug, 7.7% to 2 drugs, 1.2% to 3 drugs and 1.3% to 4 drugs. Acquired resistance to rifampicin was the most frequent (36.2%) followed by streptomycin 31.9%, and isoniazid 30%. Acquired resistance was found as 18.7% to 1 drug, 19.3% to 2 drugs, 9.6% to 3 drugs and 5.8% to 4 drugs. CONCLUSION: High initial drug resistance in Turkey may well threaten the success rates of antituberculosis treatment and it is therefore mandatory to begin antituberculosis treatment in routine practice in our country with at least 4 first-line drugs, replacing streptomycin with ethambutol due to high resistance to streptomycin. In conclusion there is an urgent need for a nationwide tuberculosis control programme in Turkey, where the treatment of old cases is still challenging, in order to combat the grave situation of high initial and acquired drug resistance.

Adolescent↗
PubMed2004

Rapid, automated, nonradiometric susceptibility testing of Mycobacterium tuberculosis complex to four first-line antituberculous drugs used in standard short-course chemotherapy.

The increasing prevalence of drug-resistant tuberculosis necessitates rapid and accurate susceptibility testing. The nonradiometric BACTEC Mycobacteria Growth Indicator Tube 960 (MGIT) system for susceptibility testing was evaluated on 222 clinical Mycobacterium tuberculosis complex isolates for isoniazid, rifampin, and ethambutol. Fifty-seven of the isolates were tested for pyrazinamide. Results were compared to those of radiometric BACTEC 460 system and discrepancies were resolved by the agar proportion method. We found an overall agreement of 99.0% for isoniazid, 99.5% for rifampin, 98.2% for ethambutol, and 100% for pyrazinamide. After resolution of discrepancies, MGIT yielded no false susceptibility for rifampin and isoniazid. Although turnaround times were comparable, MGIT provides an advantage as inoculation can be done on any weekday as the growth is monitored automatically. The automated MGIT system is a rapid and reliable alternative for susceptibility testing of M. tuberculosis complex to first-line drugs.

Antitubercular Agents↗
PubMed2006

Enhanced susceptibility of multidrug resistant strains of Mycobacterium tuberculosis to granulysin peptides correlates with a reduced fitness phenotype.

Previously it was shown that the antimicrobial protein granulysin possesses potent membranolytic activity against Mycobacterium tuberculosis. Here we demonstrate that granF2 and G13, which are two short synthetic peptides derived from granulysin, inhibited the in vitro growth of clinical isolates of both multidrug resistant and drug susceptible strains of M. tuberculosis. Importantly, a particularly high activity against multidrug resistant M. tuberculosis correlated with a reduced growth rate compared to drug susceptible strains. A synergistic antibacterial effect of granF2 was further observed in combination with ethambutol, a compound with a documented effect on cell wall permeability. This finding suggests that granF2 and ethambutol exert their functions at different levels of the mycobacterial surface. Upon infection of macrophages in vitro, granF2 but not G13 efficiently reduced the intracellular growth of multidrug resistant M. tuberculosis in the presence of the pore-forming protein streptolysin O. The apoptotic function of granF2 apparently promoted destruction of host cells whereby the peptide gained access to and killed intracellular bacteria. Thus, a cost of resistance and a subsequent reduced fitness, measured as decreased growth among multidrug resistant strains of M. tuberculosis, could be associated with increased susceptibility to natural immune defense mechanisms, such as antimicrobial peptides of granulysin. However, a robust cell wall and the membrane of cells still provide physical shelter for the bacteria that may spare sensitive M. tuberculosis stains from being killed.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1997

Flexor tenosynovitis in the hand caused by Mycobacterium malmoense: a case report.

This report analyzes a rare case of flexor tenosynovitis caused by Mycobacterium malmoense. A synovectomy was carried out on the index finger (no other finger was afflicted) of a 66-year-old farmer, followed by antibiotic therapy with ethambutol, rifampin, and clarithromycin. Because of strong side effects, the treatment with ethambutol and rifampicin had to be discontinued after 4 months. There was no recurrence after 14 months, and the patient's finger had a full range of motion.

Aged↗
PubMed2002

In vitro sensitivity of Mycobacterium xenopi to five antibiotics.

We tested 20 strains of Mycobacterium xenopi (M. xenopi) in order to evaluate their in vitro sensitivity to amikacine, clarithromycine, ethambutol, ofloxacine and rifampicin, by establishing minimal inhibitory concentration (MIC) on agar medium. MICs of amikacine, clarithromycine and ofloxacine are low, so that these antibiotics can be used in the treatment of M. xenopi infections. MICs of ethambutol are higher than seric concentrations. Though, its therapeutic use is due to its in vivo ability to enhance penetration of other antibiotics in mycobacteria. Strain sensitivity to rifampicin seems heterogeneous but the small number of tested strains does not entitle the exclusion of rifampicin from the treatment of M. xenopi infections.

Amikacin↗
PubMed2003

The decline of high drug resistance rate of pulmonary Mycobacterium tuberculosis isolates from a southern Taiwan medical centre, 1996-2000.

To investigate the anti-tuberculosis drug resistance pattern of pulmonary tuberculosis isolates in southern Taiwan, we performed a hospital-based surveillance at a southern Taiwan medical centre from 1996 to 2000. The combined drug resistance rates to at least one of four first-line agents (isoniazid, rifampicin, ethambutol, streptomycin) was 52.4%, and to both isoniazid and rifampicin was 11.4%, indicating high resistance rates compared with those reported in the World Health Organization (WHO)/International Union Against Tuberculosis and Lung Disease (IUATLD) global project and in northern Taiwan. The resistance rates to two second-line drugs, cycloserine, and kanamycin, were 75.7 and 23.7%, respectively. A significant decreasing trend in resistance rates to all tested drugs except streptomycin was observed during the 5-year period. The resistance rates in 1996 and 2000 were 43.1 and 16.4% for isoniazid, 23.4 and 9.5% for rifampicin, 23.4 and 12.1% for ethambutol, 92.7 and 50.9% for pyrazinamide. The combined drug resistance rate may not be the most accurate tool as it includes previously treated cases that may inflate the resistance rate and cases without a history of treatment. However, the observation of trends in the susceptibility of pulmonary tuberculosis with the increasing percentages of tuberculosis patients receiving the complete treatment course and the decreasing percentages of cases lost to follow-up in Kaohsiung after the institution of new governmental regulations for case management in 1997, suggest that such intervention programs are useful.

Antitubercular Agents↗
PubMed2005

[Nontuberculous mycobacteria in cystic fibrosis].

Patients with cystic fibrosis are particularly at risk of infection with non-tuberculous mycobacteria (NTM). Prevalence of these infections increases with age to around 15 %. The main species involved are M. abscessus and M. avium, the latter not found in children under 15. Diagnosis relies on clinical, radiological and above all bacteriological criteria defined by the ATS. Identification of the causal species of NTM is essential and requires genetic techniques, some of which are currently evaluated. Treatment depends on the mycobacterial species. For M. avium, combined therapy with rifampicin, clarithromycin and ethambutol must be extended 12 months after negativation. M. abscessus infection is particularly resistant to therapy. Usual treatment is a one month course of intravenous imipenem or cefoxitin plus amikacin followed by oral clarithromycin plus ethambutol for at least 12 months after negativation. In case of local lesions, surgery is an option.

Anti-Bacterial Agents↗
PubMed1995

Impact of the change from an injectable to a fully oral regimen on patient adherence to ambulatory tuberculosis treatment in Dar es Salaam, Tanzania.

OBJECTIVE: To measure the impact on patient adherence to directly observed ambulatory tuberculosis treatment substituting an all-oral treatment regimen for a regimen containing streptomycin. METHODS: The expected and observed attendance of patients during the intensive phase of anti-tuberculosis treatment was measured daily at two out-patient clinics in Dar es Salaam. During the observation period, treatment was changed from a regimen containing streptomycin to an all-oral regimen, and attendance proportions were compared for the three periods during which patients always, sometimes or never received streptomycin during the intensive phase of treatment. RESULTS: In Kinondoni, an average of 98 patients was expected every day, in Ilala 127. No significant difference was observed in attendance in Kinondoni between periods when patients always (median attendance 95.9%) and never (median 95.7%) received streptomycin injections as part of their intensive phase treatment for tuberculosis. In Ilala, no difference was noted in attendance between the period in which patients received streptomycin for at least part of their treatment (median 91.3%) and the period when ethambutol had fully replaced streptomycin (median 91.8%). CONCLUSIONS: In these two districts of Dar es Salaam, patient adherence to a completely oral treatment regimen was indistinguishable from that to a streptomycin-containing regimen. Given the potential of iatrogenic transmission of HIV and the advantages in reduced staff time and drug costs, the results clearly justify the replacement of streptomycin with ethambutol in Tanzania for new patients receiving an ambulatory rifampicin-containing regimen.

Administration, Oral↗
PubMed1999

Therapeutic drug monitoring in patients with cystic fibrosis and mycobacterial disease.

Cystic fibrosis (CF) patients require higher dosages of many antibiotics. The relapse of tuberculosis in one CF patient, and the repeated growth of Mycobacterium avium-intracellulare in another, despite conventional therapy, raised the question of whether the serum levels of the antimycobacterial drugs were adequate. Antimycobacterial drug serum concentrations were assayed in 10 CF patients with pulmonary mycobacterial disease. Serum levels below the proposed target range were seen 2 h after drug intake in the initial four patients treated: for rifampicin in 2/3, ethambutol in 3/4 and for clarithromycin in 2/3 patients, despite standard dosages. Reassays after dose adjustment and assays in six other patients showed that adequate levels were not achieved 4 h after clarithromycin in 3/5, ethambutol in 1/5, ciproflaxacin in 1/2 and ofloxacin in 2/2 patients. The patient with relapse of tuberculosis and the patient with continuous growth of M. avium-intracellulare improved and became culture negative after dose adjustment. Low drug serum levels is one reason for therapy failure in cystic fibrosis patients with mycobacterial disease. Therapeutic drug monitoring is recommended.

Adolescent↗
PubMedDate not supplied

Isolation of drug-resistant tubercle bacilli in cutaneous tuberculosis.

Cutaneous tuberculosis in a teenage boy that did not respond to conventional antitubercular therapy is described. Mycobacterium tuberculosis was recovered on culture and found to be resistant to rifampicin and isoniazid. Gradual regression of the lesions was observed after the addition of streptomycin and ethambutol. Later streptomycin was stopped and the boy was advised to continue ethambutol along with ofloxacin and thioacetazone until complete regression was achieved.

Adolescent↗
PubMed2003

Pulmonary disease caused by Mycobacterium xenopi in HIV-negative patients: five year follow-up of patients receiving standardised treatment.

The literature concerning the management of pulmonary disease caused by Mycobacterium xenopi is scanty and consists of retrospective reports, mostly of small series of patients. Our aim was to document the clinical features and response to treatment of this rare but challenging disease. Patients were treated in a randomised, multi-centre trial with either rifampicin plus ethambutol or rifampicin, ethambutol and isoniazid. Clinical, bacteriological and radiological progress was monitored at set intervals for 5 years. As no differences emerged between the two groups, the results have been combined to provide this prospective survey. Forty-two patients were studied. Mean age was 65 years, three-quarters were male and two-thirds had other lung disease(s). Sputum was positive on direct smear in 62%. Cavitation was present in 81%, mostly large cavities, and disease was extensive in 38%. Despite good clinical response and little toxicity the death rate was high (69%), but less than 10% died primarily because of the M. xenopi disease. The failure of treatment/relapse rate was 12%. Only 11 (26%) were known to be alive at 5 years of whom seven (17%) were known to be cured. There was no correlation between failure of treatment/relapse and in vitro resistance. Better methods of susceptibility testing and more effective regimens are needed, but it is also evident that improved management of concomitant diseases and better general health will play a major part in increasing survival.

Adult↗
PubMed2002

[Osteomyelitis of the tibial head caused by Mycobacterium haemophilium in a patient with AIDS].

HISTORY AND ADMISSION FINDINGS: A 53-year-old man with known HIV infection and AIDS was admitted because of painful swelling at the right knee for 6 weeks. The cause was thought to be osteomyelitis and surgical treatment was planned. INVESTIGATIONS: No causative pathogen was found at curettage and lavage of an abscess at the right medical head of the tibia, but at a subsequent operative revision acid-fast rods were seen and identified as Mycobacterium haemophilum. TREATMENT AND COURSE: A systemic antibiotic, 1 g levofloxacin daily, had been started at the initial abscess operation. 2 weeks later, because swelling of the right knee had recurred with marked local and systemic signs of infection, a second surgical intervention was performed. Afterwards, in view of the histological finding of acid-fast bacteria suggesting tubercular osteomyelitis, the patient was put on combined treatment with 300 mg/d of isoniazid, 1600 mg/d of ethambutol, 2 g/d of pyrazinamide, and 1 g of streptomycin i.m. every other day. After molecular microbiological identification of M. haemophilum the antibiotic treatment was changed to 1600 mg/d of ethambutol, 300 mg/d of rifabutin and 1 g/d of clarithromycin. The operation wound healed well. CONCLUSION: M. haemophilum infection can be lethal in immunodeficient patients if untreated. Although there is no standard treatment, this rare infectious disease responds relatively well to a modified combined tuberculostatic regimen. Special laboratory techniques to identify the specific causative pathogen are therefore of great importance.

AIDS-Related Opportunistic Infections↗
PubMed2005

[Pulmonary infection due to Mycobacterium malmoense].

M. malmoense could be cultivated in sputum samples of a 49-year-old patient with destructive pulmonary disease. The conventional antituberculous therapy (started because initially a presumptive diagnosis of tuberculosis was established) was altered to ethambutol, rifabutin, clarithromycin and ciprofloxacin, followed by a long-time therapy with azithromycin or clarithromycin. But till now it was not possible to eradicate the mycobacteria from the respiratory tract (insufficient compliance, interruptions of the therapy due to side effects, excessive smoking). Infections due to M. malmoense are rare events. Many patients have disposing underlying diseases. In most cases it is a pulmonary infection. The most frequent used antibiotics are rifampicin (or rifabutin), ethambutol and clarithromycin.

Azithromycin↗
PubMed1991

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection.

BACKGROUND AND METHODS: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Acquired Immunodeficiency Syndrome↗
PubMed2000

A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.

Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.

AIDS-Related Opportunistic Infections↗
PubMed2001

A whole blood bactericidal assay for tuberculosis.

The bactericidal activity of orally administered antituberculosis (anti-TB) drugs was determined in a whole blood culture model of intracellular infection in which microbial killing reflects the combined effects of drug and immune mechanisms. Rifampin (Rif) was the most active compound studied and reduced the number of viable bacilli by >4 logs. Isoniazid (INH), 2 quinolones, and pyrazinamide (PZA) showed intermediate levels of activity. Ethambutol exerted only a bacteristatic effect; amoxicillin/clavulanate was inactive. The combination of INH-Rif-PZA showed strong activity against 11 drug-sensitive isolates (mean, -3.8 log) but no activity against 12 multidrug-resistant (MDR) strains. The combination of levofloxacin-PZA-ethambutol had intermediate bactericidal activity against MDR isolates (mean, -1.2 log) but failed to equal that of INH-Rif-PZA against sensitive isolates (P<.001). The whole blood BACTEC method (Becton Dickinson) may be useful for the early clinical evaluation of new anti-TB drugs and in the management of individual patients.

Anti-Infective Agents↗