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PubMed2002

Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999.

BACKGROUND: The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. METHODS: The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. RESULTS: There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. CONCLUSION: Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.

AIDS-Related Opportunistic Infections↗
PubMed2005

Rates of drug resistance and risk factor analysis in civilian and prison patients with tuberculosis in Samara Region, Russia.

BACKGROUND: Tuberculosis (TB) and HIV rates continue to escalate in Russia, but true rates for drug resistance, especially multidrug resistant tuberculosis (MDR TB), are unknown. A study was conducted with the aims of identifying first line drug resistance, both in the civilian and prison sectors, for new and previously treated cases; and risk factors for the development of drug resistance. METHODS: A cross sectional survey was undertaken of 600 patients (309 civilians, 291 prisoners) with bacteriologically confirmed pulmonary TB over a 1 year period during 2001-2 in Samara Oblast, Russia. RESULTS: The prevalence of isoniazid, rifampicin, streptomycin, ethambutol and pyrazinamide resistance in new TB cases (civilian and prison patients) was 38.0%, 25.2%, 34.6%, 14.7%, and 7.2%, respectively. The prevalence of MDR TB was 22.7%, 19.8%, and 37.3% in all new cases, new civilian cases, and new prison cases, respectively, with an overall prevalence of 45.5% and 55.3% in previously treated cases. Factors associated with resistance included previous TB treatment for more than 4 weeks, smoking (for isoniazid resistance), the presence of cavitations on the chest radiograph, and imprisonment. HIV was not associated with resistance in all patients. The rates of resistance were significantly higher in prisoners, with rate ratios (RR) of 1.9 (95% CI 1.1 to 3.2) for MDR TB, 1.9 (95% CI 1.1 to 3.2) for rifampicin, and 1.6 (95% CI 1.0 to 2.6) for isoniazid. CONCLUSIONS: Rates of first line drug resistance are high, particularly in prisoners and previously treated cases. TB control programmes should initially focus on standardised treatment to maximise cure, combined with measures to reduce institutional TB spread (particularly in prisons) coupled with early diagnosis of MDR TB to reduce the spread and development of resistance.

Adult↗
PubMed1994

Mycobacterium kansasii pulmonary infection: a prospective study of the results of nine months of treatment with rifampicin and ethambutol. Research Committee, British Thoracic Society.

BACKGROUND: Pulmonary disease caused by Mycobacterium kansasii is reported in approximately 50 new patients in Britain annually. Rifampicin and ethambutol are effective in vitro but the optimal duration of treatment, and whether isoniazid should also be given, are uncertain. The British Thoracic Society has conducted a prospective, multicentre study of the treatment of this condition with rifampicin and ethambutol given for nine months. METHODS: One hundred and seventy three patients with two or more positive cultures and radiological evidence of disease were recruited via the Mycobacterium Reference Unit (PHLS) in Cardiff from 113 physicians in England, Scotland, and Wales. Rifampicin and ethambutol were given for nine months, other antituberculosis drugs being discontinued once the culture was identified as M kansasii. Patients were reviewed, sputum cultured, and chest radiographs performed before, during, and at regular intervals for 51 months after chemotherapy. RESULTS: The mean (SD) age was 55.5 (11.7) years, 73% were men, and 50% had other lung problems. Cavitation was seen in 88%, bilateral shadowing in 48%, and three or more lung zones were affected in 46%. All cultures were sensitive to rifampicin and ethambutol but resistant to isoniazid and pyrazinamide. One patient who took chemotherapy irregularly still had positive cultures at seven and eight months. Fifteen patients developed positive cultures after the end of chemotherapy; factors which might account for the relapse were identified in eight. Reinfection rather than relapse was suspected in three of the 15. Radiographic improvement stabilised within three years in 80%. CONCLUSIONS: M kansasii pulmonary infection responds well to nine months of treatment with rifampicin and ethambutol but patients who contract this disease have a high mortality rate from other causes. Isoniazid does not appear to be a necessary part of the regimen.

Adolescent↗
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↗
PubMed1995

Hepatotoxicity caused by the combined action of isoniazid and rifampicin.

A 35 year old black Somalian woman with miliary tuberculosis developed hepatotoxicity after a few days of treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol. After withdrawal of all drugs the liver profile returned to normal and remained so after challenge with isoniazid. Hepatotoxicity recurred when rifampicin was added, but it was well tolerated when reintroduced without isoniazid.

Adult↗
PubMed1996

Evaluation of a directly observed six months fully intermittent treatment regimen for tuberculosis in patients suspected of poor compliance.

BACKGROUND: Although a priority for tuberculosis control is to achieve the maximum cure rate, compliance with chemotherapy in specific high risk groups (homeless, intravenous drug abusers, chronic alcoholics) is usually poor. METHODS: From January 1990 to December 1994 102 patients with tuberculosis (96 pulmonary, six extrapulmonary) who were poorly compliant with treatment were treated with a six month fully intermittent (twice weekly) directly observed regimen. They comprised 71 homeless subjects, 50 chronic alcoholics, 23 intravenous drug abusers, nine infected with HIV, and 11 who had previously abandoned a daily antituberculosis regimen; 53 had more than one of these risk factors. Treatment included isoniazid and rifampicin for six months and pyrazinamide during the first two months. Patients who failed to take their medication on two consecutive occasions were actively sought by telephone or by personal search. RESULTS: After two months of treatment 95 of the 102 patients had taken their medication regularly and 90 of them had negative cultures. Four of the remaining patients had negative cultures after three months. At the end of the six months 87 patients had completed treatment and were considered cured. Only 15 patients abandoned the treatment (13 of whom had more than one risk factor). Only three relapses occurred in the 102 patients at one year follow up and in the 88 patients followed for two years. Two patients required a change of treatment due to major side effects. Although intravenous drug abuse was the only predictor of non-compliance in the multivariate analysis, if the available variables in the second month of treatment were analysed, current poor compliance and abandonment of treatment in the past were found to be significantly associated with non-compliance. CONCLUSIONS: This study shows the efficacy of this intermittent regimen and the effectiveness of a directly observed treatment programme.

Adolescent↗
PubMed1997

Reversible cystic disease associated with pulmonary tuberculosis: radiologic findings.

PURPOSE: The authors describe radiologic findings of cystic lung disease associated with pulmonary tuberculosis. MATERIALS AND METHODS: Three immunocompetent women with pulmonary tuberculosis were seen with acute respiratory failure and diffuse bilateral pulmonary opacity depicted at admission chest radiography. The women did not have acquired immunodeficiency syndrome, or AIDS. They were aged 26, 27, and 52 years. RESULTS: Follow-up radiography and computed tomography showed multiple air-filled cystic lesions in both lungs, which disappeared almost completely after antituberculous chemotherapy (isoniazid, rifampin, ethambutol hydrochloride, and pyrazinamide). CONCLUSION: Pulmonary tuberculosis manifested with reversible multiple cystic lung disease in three immunocompetent patients.

Adult↗
PubMed1979

Uric acid transport in brush border membrane vesicles isolated from rabbit kidney.

The transport of uric acid was studied in brush border membrane vesicles isolated from rabbit kidney. The uptake of uric acid by the vesicles was osmotically sensitive and occurred in the absence of significant uric acid degradation. Under the conditions used to evaluate transport, urate binding to the membranes represented only 10--15% of the total uptake. The initial rate of uptake was linear over the concentration range 0.04--8 mM urate. Uptake of urage was Na+ gradient independent. It was dependent on external pH and temperature with Q10 near 3. The urate uptake was inhibited reversibly by p-chloromercuribenzoate. Probenecid, ouabain, cyclic adenosine 3',5'--monophosphate, and its dibutyryl derivative had no appreciable effects. Pyrazinoic acid and pyrazinamide stimulated urate uptake. Experiments performed with osmotically shocked vesicles demonstrated that this stimulatory effect resulted from increased binding of urate to the membranes. These results indicate that in several ways urate transport in vesicles resembles that observed with more physiologically intact preparations.

Animals↗
PubMed1999

Renal Transport of Urate in Humans.

The theory of the "four-component model" of urate excretion in humans is reevaluated, considering that a decrease in urate excretion induced by drugs like pyrazinamide or by endogenous compounds like lactate and ketone bodies might be a result of stimulation of urate reabsorption and not, as previously considered, of inhibition of urate secretion.

Journal Article↗
PubMedDate not supplied

Multidrug-resistant tuberculosis: long term follow-up of 40 non-HIV-infected patients.

BACKGROUND: There has been a steady increase in referrals of patients with multidrug-resistant tuberculosis (MDR-TB) who are human immunodeficiency virus (HIV) negative. Between 1986 and 1999, 40 patients were admitted to the authors' institution, eight of whom were admitted between January and June 1999. The management of such individuals is difficult. Although they are a clinically and epidemiologically important group of patients, few reports detail their management. OBJECTIVES: To review the demographics, clinical management and long term outcome of 40 non-HIV-infected individuals with MDR-TB referred to the only specialized TB inpatient service in Ontario. PATIENTS AND METHODS: Clinical hospital records were reviewed. RESULTS: Twenty-one men and 19 women (mean age 41+/-18 years) were admitted between January 1986 and June 1999 with MDR-TB and negative serology for HIV. Thirty-eight patients (95%) were born outside of Canada. Twenty-six patients (65%) had a history of previous TB. All were symptomatic with productive cough and positive sputum smears for acid-fast bacilli. There was a delay of 4.5 months between the initial diagnosis of TB and the recognition of the presence of MDR-TB. Four patients (10%) had TB resistant to isoniazid and rifampin only. Over 50% of patients had TB with additional resistance to streptomycin, and over 40% had additional resistance to ethambutol. Coexisting resistance was also found in significant numbers for pyrazinamide, ethionamide, para-aminosalicylic acid and cycloserine. Bacteriological conversion was achieved in 34 patients (85%). Six patients underwent surgical resection for localized lung disease. Twenty-four patients completed treatment and have remained free of disease for 33+/-25 months. All five patients (12%) who died had longstanding disease before their referral. CONCLUSIONS: MDR-TB is most frequently seen among immigrants with a previous history of TB, especially if they come from countries in which TB is highly prevalent. Outcome can be improved by a more timely recognition of MDR-TB.

Adult↗
PubMed2006

[Anti-tuberculosis drug resistance of Mycobacterium tuberculosis in the area of the Hospital de Sagunto from 1999 to 2004].

OBJECTIVES: This study aimed to know the drug resistance patterns of Mycobacterium tuberculosis, specifically primary drug resistance to isoniazid, in the area of the Hospital de Sagunto and to study the clinical characteristics and the risk factors associated with them. MATERIAL AND METHODS: Patients included were those who were diagnosed of tuberculosis and whose M. tuberculosis strains were isolated in culture of a clinical sample and in whom a susceptibility test against the first line anti-tuberculosis drugs was performed from January 1999 to December 2004. Risk factors and clinical characteristics of the patients were gathered from the case- history. RESULTS: The total number of strains isolated was 77 and the global rate of resistance was 14.1%. Rate of primary drug resistance was 12.1%, and acquired 27%. No multidrug resistant case was detected. Primary drug resistance was 3% to isoniazid, 3% to rifampin, 3% to pyrazinamid, 4.5% to ethambutol and 3% to streptomycin. Acquired drug resistance was 9.1% against isoniazid and 27% against streptomicin, no resistance against the other drugs tested being found. CONCLUSIONS: The low level of primary drug resistance against isoniazid allows us to start treatment with three-drug regimes in new cases of native population. In our hospital area, the risk factors associated with drug resistances were smoking habit and alcoholism. Although all patients with drug resistance presented pulmonary disease, the differences were not statistically significant. However, the higher rate of pleural effusion in patients with drug resistance was statistically significant.

Adult↗
PubMed2002

Rapidly progressive glomerulonephritis due to rifampicin therapy.

A 60-year-old man was treated with rifampicin, isoniazid, ethambutol and pyrazinamide for pulmonary tuberculosis. Acute renal failure developed 1 month after re-administration of rifampicin following 1 month's interruption of treatment. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis. This is, to our knowledge, the fourth case of rapidly progressive crescentic glomerulonephritis associated with rifampicin treatment, which responded to methylprednisolone pulse therapy followed by oral steroid therapy.

Antibiotics, Antitubercular↗
PubMed1999

Quinolones and multidrug-resistant tuberculosis.

The prevalence of initial resistance of multidrug-resistant tuberculosis (MDR-TB) to at least isoniazid (INH) and rifampicin (RFP) in Thailand during the period 1993-1997 is reported; in this era, trends for INH + RFP + streptomycin (SM) and ethambutol (EMB), INH + RFP + SM or EMB and MDR-TB were stable. The prevalence of acquired MDR-TB is on a slight downward trend, with the latest level at 22.6%. Recommended management of MDR-TB is outlined and advantages and disadvantages of these guidelines discussed. The role of ofloxacin in MDR-TB is presented, with results from a study performed by the Thailand CDC showing that the percentage of strains resistant to ofloxacin was 4.3%, and to ciprofloxacin was 8.3%. The resistance to both ofloxacin and ciprofloxacin was very low at 1.4%. The percentage of cross-resistance between these fluoroquinolones was also low; 33% resistant to ofloxacin were also resistant to ciprofloxacin and only 17% of those resistant to ciprofloxacin were also resistant to ofloxacin. Results from a clinical trial evaluating ofloxacin with other drugs for MDR-TB are also reported. The regimen comprised ofloxacin 600 mg/day, pyrazinamide (PZA), two to three months of kanamycin (KM) or amikacin (AMK), para-aminosalicylic acid (PAS) plus EMB or thiacetazone. Drugs were given for 18 months. Follow-up was every three months for two years. Preliminary results revealed that the percentage of acquired MDR-TB resistant to specific agents was as follows: 36% resistant to INH and RFP, 23% resistant to INH, RFP plus EMB, 27% resistant to INH, RFP and SM, and 14% resistant to all four of these agents (INH + RFP + SM + EMB). All isolates were sensitive to ofloxacin. At one month of treatment, sputum culture conversion was approximately 25%, climbing to 93% by nine months of treatment. Treatment with ofloxacin in a combined regimen achieved a success rate of 78%. The role of quinolones in preventing TB in MDR-TB contacts is also discussed.

Anti-Infective Agents↗
PubMed2000

Sensitivity of BCG to modern antibiotics.

The viability of bacillus Calmette-Guérin (BCG) in intravesical instillation therapy has been demonstrated to be crucial for the prevention of bladder tumour recurrence. The aim of the present study was to determine the effects of modern antibacterial chemotherapeutics on BCG viability, particularly cycloserine, which has been recommended in the treatment of BCG-induced sepsis. The minimal inhibitory concentrations (MICs) of 32 antibacterial drugs potentially effective against the Connaught BCG strain were measured in vitro by the radiometric BACTEC 460TB method. The MICs were compared with the drug concentrations achievable in blood and urine. Susceptibility testing of cycloserine was performed with three different strains (Connaught, Tice and RIVM), using the modified proportion method, as defined in the German guidelines for anti-tuberculosis drug testing. The Connaught BCG strain was highly susceptible to fluoroquinolones, but was resistant to beta-lactams, macrolides (except clarithromycin), and some aminoglycosides. It was also sensitive to doxycycline and gentamicin at dosages that typically occur in the urine of patients after a normal dose. Connaught BCG was susceptible to all the tuberculostatic drugs tested, except for pyrazinamide. All the BCG strains analysed were resistant to cycloserine. During intravesical BCG instillation therapy, simultaneous administration of fluoroquinolones, doxycycline or gentamicin should be avoided. In cases of severe systemic complications, or if one of the antituberculosis drugs is not tolerated, fluoroquinolones may be used. Cycloserine is no longer recommended for the early treatment of BCG sepsis.

Administration, Intravesical↗
PubMedDate not supplied

Pulmonary infection due to Mycobacterium szulgai.

A 75-year-old man was admitted with cough, purulent sputum, fatigue and weight loss of 10 kg of some months' duration. His chest radiograph showed poorly defined opacities in the right lung. Eleven years before admission an epidermoid carcinoma of the right lung had been diagnosed and a right bilobar resection had been performed. The patient remained asymptomatic for 8 years. Cultures of 4 consecutive sputum samples were positive for mycobacteria that were identified as Mycobacterium szulgai by gas chromatography. A 6-month regimen of rifampin, isoniazid and pyrazinamide resulted in complete eradication of the mycobacterium. M. szulgai is an unusual pathogen in humans. In the English literature, only 35 cases of pulmonary disease have been reported. Its clinical and radiological characteristics are similar to tuberculosis but in contrast to the rest of the non-tuberculous mycobacteria, M. szulgai has shown in vitro and in vivo susceptibility to most primary antituberculosis drugs.

Aged↗
PubMedDate not supplied

Perinatally acquired tuberculosis in a neonate. a case report.

OBJECTIVES: To report a case of perinatal tuberculosis that appeared on the 21st day of life of an infant born to a mother with latent tuberculosis. CLINICAL PRESENTATION AND INTERVENTION: A preterm male infant was born by spontaneous vertex delivery at 33 weeks gestational age to a 33-year-old primiparous Philippine woman. The infant was well until the 21st day of life when he developed recurrent episodes of cyanosis and bradycardia. A chest radiograph showed infiltrates which were thought to be bacterial in origin. Blood, urine, and cerebrospinal fluid cultures were normal. Tracheal aspirate revealed acid-fast bacilli by Ziehl-Neelsen stain, later confirmed to be MYCOBACTERIUM TUBERCULOSIS by culture in Lowenstein-Jensen medium. The mother was later diagnosed as a case of tuberculosis with symptoms, signs and radiologic manifestation of hilar lymphadenopathy with mild pleural effusion and positive tuberculin skin test. Both infant and mother were treated with intravenous isoniazid, intravenous rifampicin, oral pyrazinamide, and intravenous pyridoxine. Both recovered. CONCLUSION: A preterm male infant perinatally acquired tuberculosis, most likely by inhalation of the bacteria during delivery. Both infant and mother responded well to antituberculous treatment.

Humans↗
PubMed1989

Tuberculous peritonitis complicating long-term peritoneal dialysis. Report of 5 cases and review of the literature.

The characteristics of 5 patients who developed tuberculous peritonitis while receiving long-term peritoneal dialysis (PD) are presented. There were 2 males and 3 females. 3 patients were on intermittent and 2 were on continuous ambulatory peritoneal dialysis when tuberculous peritonitis was first diagnosed. None of the patients had recently received immunosuppression therapy or were diabetics. The clinical presentations were similar to other forms of peritonitis complicating PD except for a more insidious onset. As extraperitoneal involvement and peritoneal lymphocytosis were rarely present, the diagnosis was mainly dependent on the direct demonstration of Mycobacterium tuberculosis with smear (1 patient) and culture (4 patients). In 1 patient with a pleuroperitoneal communication, the diagnosis was made by pleural biopsy and a positive response to antituberculous therapy. All patients responded to treatment with a combination of three antituberculous drugs which included streptomycin, isoniazid, rifampicin and pyrazinamide. Two patients were transferred to hemodialysis. In 3 patients, peritoneal dialysis was continued. Peritoneal clearance and ultrafiltration capacity were unchanged for up to 16 months after treatment in 2 patients who continued peritoneal dialysis but was reduced by 30 and 50%, respectively, in the remaining patient. Only 1 patient died, but her death was not directly related to tuberculous peritonitis. It was concluded that with a high index of suspicion and early institution of treatment, tuberculous peritonitis complicating PD can be successfully treated with low mortality and without compromising the dialysis capacity of the peritoneal membrane.

Adult↗
PubMed1994

Tuberculosis of the spine (Pott's disease) in patients with end-stage renal disease.

Extrapulmonary tuberculosis is more common in end-stage renal disease than in normal subjects, and it frequently poses both diagnostic and therapeutic challenges. We describe 2 dialysis patients with tuberculosis of the spine (Pott's disease). The 1st patient presented with back and left hip pain, low-grade fever, left-quadriceps weakness, hypoesthesia of the left thigh, and hypoactive left-knee jerk. X-rays of the spine showed only osteophytes. Magnetic resonance imaging showed increased signal intensity of L3 with focal expansion into the spinal canal. A computerized tomography guided biopsy revealed granulomas, and Ziehl-Neelsen stain was positive. Therapy with rifampin, isoniazid, ethambutol, and pyrazinamide caused peripheral neuropathy and optic neuritis. The 2nd patient developed bilateral proximal thigh pain and weakness that progressed to paraplegia. Magnetic resonance imaging showed destructive lesion of L3-5, involving both psoas muscles, prevertebral space, and neural foramina. Ziehl-Neelsen stain of the biopsy specimen was negative, but culture was positive for Mycobacterium tuberculosis. Paraplegia improved only partially after 1 year of therapy. Pott's disease should be suspected in end-stage renal disease patients with back pain and/or neuromuscular complaints, particularly in those who immigrated from Asian and Latin-American countries. Treatment of tuberculosis in dialysis patients may cause significant morbidity.

Adult↗