Positive Mycobacterium Tuberculosis Research Articles

Tuberculosis in liver transplant recipients: A systematic review and meta-analysis of individual patient data

Mycobacterium tuberculosis (MTB) causes substantial morbidity and mortality in liver transplant recipients. We examined the efficacy of isoniazid latent Mycobacterium tuberculosis infection (LTBI) treatment in liver transplant recipients and reviewed systematically all cases of active MTB infection in this population. We found 7 studies that evaluated LTBI treatment and 139 cases of active MTB infection in liver transplant recipients. Isoniazid LTBI treatment was associated with reduced MTB reactivation in transplant patients with latent MTB risk factors (0.0% versus 8.2%, P = 0.02), and isoniazid-related hepatotoxicity occurred in 6% of treated patients, with no reported deaths. The prevalence of active MTB infection in transplant recipients was 1.3%. Nearly half of all recipients with active MTB infection had an identifiable pretransplant MTB risk factor. Among recipients who developed active MTB infection, extrapulmonary involvement was common (67%), including multiorgan disease (27%). The short-term mortality rate was 31%. Surviving patients were more likely to have received 3 or more drugs for MTB induction therapy (P = 0.003) and to have been diagnosed within 1 month of symptom onset (P = 0.01) and were less likely to have multiorgan disease (P = 0.01) or to have experienced episodes of acute transplant rejection (P = 0.02). Compared with the general population, liver transplant recipients have an 18-fold increase in the prevalence of active MTB infection and a 4-fold increase in the case-fatality rate. For high-risk transplant candidates, isoniazid appears safe and is probably effective at reducing MTB reactivation. All liver transplant candidates should receive a tuberculin skin test, and isoniazid LTBI treatment should be given to patients with a positive skin test result or MTB pretransplant risk factors, barring a specific contraindication. Liver Transpl 15:894-906, 2009. (c) 2009 AASLD.

Theoretical basis for reducing time-lines to the determination of positive Mycobacterium tuberculosis cultures using thymidylate kinase (TMK) assays.

BackgroundIn vitro culture of pathogens on growth media forms a "pillar" for both infectious disease diagnosis and drug sensitivity profiling. Conventional cultures of Mycobacterium tuberculosis (M.tb) on Lowenstein Jensen (LJ) medium, however, take over two months to yield observable growth, thereby delaying diagnosis and appropriate intervention. Since DNA duplication during interphase precedes microbial division, "para-DNA synthesis assays" could be used to predict impending microbial growth. Mycobacterial thymidylate kinase (TMKmyc) is a phosphotransferase critical for the synthesis of the thymidine triphosphate precursor necessary for M.tb DNA synthesis. Assays based on high-affinity detection of secretory TMKmyc levels in culture using specific antibodies are considered. The aim of this study was to define algorithms for predicting positive TB cultures using antibody-based assays of TMKmyc levels in vitro.Methods and resultsSystems and chemical biology were used to derive parallel correlation of "M.tb growth curves" with "TMKmyc curves" theoretically in four different scenarios, showing that changes in TMKmyc levels in culture would in each case be predictive of M.tb growth through a simple quadratic curvature, |tmk| = at2+ bt + c, consistent with the "S" pattern of microbial growth curves. Two drug resistance profiling scenarios are offered: isoniazid (INH) resistance and sensitivity. In the INH resistance scenario, it is shown that despite the presence of optimal doses of INH in LJ to stop M.tb proliferation, bacilli grow and the resulting phenotypic growth changes in colonies/units are predictable through the TMKmyc assay. According to our current model, the areas under TMKmyc curves (AUC, calculated as the integral ∫(at2+ bt + c)dt or ~1/3 at3+ 1/2 bt2+ct) could directly reveal the extent of prevailing drug resistance and thereby aid decisions about the usefulness of a resisted drug in devising "salvage combinations" within resource-limited settings, where second line TB chemotherapy options are limited.ConclusionTMKmyc assays may be useful for reducing the time-lines to positive identification of Mycobacterium tuberculosis (M.tb) cultures, thereby accelerating disease diagnosis and drug resistance profiling. Incorporating "chemiluminiscent or fluorescent" strategies may enable "photo-detection of TMKmyc changes" and hence automation of the entire assay.

Direct real-time PCR examination for Mycobacterium tuberculosis in respiratory samples can be cost effective

Aim: To assess whether the use of direct realtime polymerase chain reaction (PCR) on smear-positive sputa can be cost-effective, by speciating mycobacteria earlier than current methods and thereby preventing unnecessary screening tests as part of the contact tracing process. Methods: A retrospective study of all patients with smear-positive sputa in a Liverpool teaching hospital between 2004 and 2007. All the PCRs performed on these patients were reviewed and compared them with their mycobacterial culture results. Unit costs for PCR, chest X-ray (CXR), tuberculin skin test (TST), interferon-gamma (IFN-γ) and medical/nursing time were conservatively estimated at £50, £11, £10, £40 and £30 respectively. The total PCR costs were compared with the costs of unnecessary follow up of patients, negative for Mycobacterium tuberculosis (MTB) by PCR, subsequently confirmed to be MTB culture negative. Results: 203 smear-positive patients underwent direct PCR testing. 126 (62%) patients grew Mycobacterium tuberculosis (MTB), 74 (37%) had environmental mycobacterial infection (EMI) and 3 (1%) were culture negative. Of the 126 patients’ culture positive MTB patients, 123 were PCR positive and 3 PCR negative. Of the 77 patients that were culture negative for MTB, 75 were PCR negative and 2 PCR positive The sensitivity, specificity, positive and negative predictive values for direct PCR versus MTB culture were 98%, 96%, 98% and 97% respectively. Total costs of all PCRs performed amounted to £10,150. The cost of contact procedures for PCR-negative and MTB culturenegative index cases was estimated at £19,650. This equated to a total saving of £9,500 in contact tracing costs. Conclusions: Direct PCR examination testing of smear-positive patients can be cost-effective in areas where there is a high incidence of EMI.

Molecular genotyping and epidemiology of Mycobacterium tuberculosis isolates obtained from inmates of correctional institutions of Campinas, Southeast Brazil

The objective of this study was to investigate the possible transmission of tuberculosis among 39 inmates with positive Mycobacterium tuberculosis smears in four correctional institutions located in Campinas City, SP, Brazil over a 19-month period. Fifty-one M. tuberculosis isolates from these inmates were characterized according to the number of IS6110 insertion elements present in their genomic DNA. The number of insertion elements in M. tuberculosis isolates varied from two to twelve. The dendrogram of similarity resulted in the grouping the isolates in six main clusters. These results, associated to epidemiological data, suggested the transmission of tuberculosis among inmates of the same and different institutions inmates. Univariate analysis of epidemiological data (total delay for beginning of treatment, previous treatment, and HIV status) and clustering occurrence showed that only 'previous treatment' (OR = 7.65, p = 0.032) was associated with the possible transmission of tuberculosis in the studied prisons.

Isolation and identification of a new antibacterial entity from the Antarctic cyanobacterium Nostoc CCC 537

The present study was aimed at the isolation, purification and structural elucidation of an antibacterial entity/lead molecule from the Antarctic cyanobacterium Nostoc CCC 537. A methanolic extract of the cyanobacterium was bioassayed with Enterobacter aerogenes as a target. The extract was purified by TLC, and the most active band was subjected to HPLC. The fraction (retention time 15.7 min) designated as the active principle was antibacterial towards Gram positive Mycobacterium tuberculosis H37Rv, Staphylococcus aureus ATCC 25923, Gram negative Salmonella typhi MTCC 3216, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25992, Enterobacter aerogenes MTCC 2822 and multi-drug resistant strains of Escherichia coli GS 2003/01, 02, 03. Based on UV, IR, 1H NMR, EIMS, and ESIMS data, the structure of the active principle is proposed as 4-[(5-carboxy-2-hydroxy)-benzyl]-1,10-dihydroxy-3,4,7,11,11-pentamethyloctahydrocyclopenta naphthalene (Mr 428, Mp 243–249°C). This intracellular biomolecule is similar to anthraquinone and indane derivatives of a diterpenoid. The rate of production of the active principle currently corresponds to 1.70 mg g−1 biomass dry weight. The inherent property of Nostoc sp. to synthesise niche-specific biomolecules/lead molecules may be exploited for future drug development.

Improved Recovery ofMycobacterium tuberculosisFrom Children Using the Microscopic Observation Drug Susceptibility Method

The diagnosis of pulmonary tuberculosis presents challenges in children, because symptoms are nonspecific, sputa are not accessible, and Mycobacterium tuberculosis cultures and smears often are negative. The Microscopic Observation Drug Susceptibility technique is a simple, inexpensive method for Mycobacterium tuberculosis isolation with superior speed and sensitivity over Lowenstein-Jensen culture in studies of adults with pulmonary tuberculosis. The objective of this study was to determine whether Microscopic Observation Drug Susceptibility culture can improve the sensitivity and the speed of Mycobacterium tuberculosis recovery among Peruvian children with symptoms suggestive of pulmonary tuberculosis. Two specimens of each type (gastric aspirate, nasopharyngeal aspirate, and stool specimens) were collected from each patient, examined by auramine stain, and cultured by Microscopic Observation Drug Susceptibility and Lowenstein-Jensen techniques. Patients (n = 165) were enrolled between April 2002 and February 2004 at the Instituto de Salud del Niño, the major pediatric hospital in Lima, Peru. Inclusion criteria were age < or = 12 years, Stegen-Toledo clinical score > or = 5 points, and absence of antituberculous therapy. The main outcome measurements were (1) proportion of specimens that were culture positive by Microscopic Observation Drug Susceptibility versus Lowenstein-Jensen and (2) days required for positive culture result, stratified by specimen type and auramine stain result. Fifteen (9%) patients had at least 1 positive Mycobacterium tuberculosis culture (from stool in 3 cases, nasopharyngeal aspirate in 8 cases, and gastric aspirate in 15 cases). Thirty-eight culture-positive specimens were obtained (22 gastric aspirate, 12 nasopharyngeal aspirates, and 4 stools). Microscopic Observation Drug Susceptibility provided significantly more positive cultures than Lowenstein-Jensen (33 of 38 specimens culture positive by Microscopic Observation Drug Susceptibility vs 21 of 38 by Lowenstein-Jensen). This was attributed to enhanced recovery of Mycobacterium tuberculosis from auramine-negative specimens (19 of 23 by Microscopic Observation Drug Susceptibility vs 9 of 23 by Lowenstein-Jensen), in contrast to similar detection rates for the 2 tests with auramine-positive samples. Similar results were found for analyses that were limited to gastric aspirates. Isolation was faster by Microscopic Observation Drug Susceptibility than Lowenstein-Jensen. Isolation of Mycobacterium tuberculosis from children with suspected pulmonary tuberculosis by Microscopic Observation Drug Susceptibility demonstrated greater yield and faster recovery than by Lowenstein-Jensen method, significantly improving local capabilities to detect pediatric tuberculosis in resource-poor settings.

Assessing the Performance of Overseas Tuberculosis Screening Programs

Tuberculosis cases in foreign-born persons account for more than 50% of all tuberculosis cases in the United States. The Institute of Medicine has recommended enhancing overseas screening as one measure to support tuberculosis elimination efforts. We assessed the ability of overseas tuberculosis screening (chest radiograph followed by 3 acid-fast bacilli sputum smears for persons with abnormal chest radiographs [suggestive of active tuberculosis]) to detect pulmonary tuberculosis disease among US-bound immigrants with abnormal chest radiographs. During October 1998 to October 1999, 14 098 US immigrant visa applicants were screened overseas in Vietnam. Adult applicants with abnormal chest radiographs were enrolled to assess screening test characteristics among this group using mycobacterial culture as the gold standard for pulmonary tuberculosis disease diagnosis. Risk factors for pulmonary tuberculosis disease were also evaluated. Among 1179 adult applicants with abnormal chest radiographs, 82 (7.0%) had positive acid-fast bacilli smear results, and 183 (15.5%) had positive Mycobacterium tuberculosis culture results (pulmonary tuberculosis disease). The sensitivity, specificity, and positive and negative predictive values of serial acid-fast bacilli screening among this group were 34.4% (63/183), 98.1% (977/996), 76.8% (63/82), and 89.1% (977/1097), respectively. Risk factors for pulmonary tuberculosis disease included younger age (18-34 years), no history of tuberculosis or treatment, reported symptoms, and cavitation or consolidation on chest radiograph. The ability of current overseas screening to detect tuberculosis among immigrants with abnormal chest radiographs is low. Improved diagnostic methods, enhanced screening measures, and postmigration follow-up are essential to control tuberculosis among immigrants and support US and global tuberculosis elimination.

Comparison of bronchoscopy and gastric washings in the investigation of smear-negative pulmonary tuberculosis.

This study compares the utility of gastric washings (GWs) and bronchoscopy in the diagnosis of smear-negative pulmonary tuberculosis (TB). The aim of the study was to identify which investigation or combination of investigations provided the greatest yield of positive Mycobacterium tuberculosis cultures of samples from patients with smear-negative pulmonary TB. We retrospectively analyzed the medical records of 180 patients with smear-negative pulmonary TB. The positive culture yield for bronchoalveolar lavage fluid (62 [34%] of 180 patients) was significantly greater than that for specimens from 3 GWs (32 [21%] of 149 patients) (P=.02). Combining GW and bronchoscopy increased the positive culture yield: bronchoscopy combined with 2 GWs resulted in a positive culture rate of 38%. Bronchoscopy is superior to GW in the diagnosis of smear-negative pulmonary TB; however, the combination of bronchoscopy and 2 GWs should be regarded as optimal for the diagnosis of smear-negative pulmonary TB.

Sputum induction problems identified through genetic fingerprinting.

To identify the contamination source of a cluster of eight positive Mycobacterium tuberculosis isolates from one laboratory session. Spoligotyping was performed on M. tuberculosis isolates processed during one laboratory session. Laboratory and sputum induction protocols and records were reviewed. Sputum induction staff were interviewed. An environmental assessment of the sputum induction booth was performed. Spoligotyping identified a unique strain of susceptible M. tuberculosis from five induced sputa collected at Clinic A on the same day. Three specimens processed concurrently from other clinics had spoligotypes different from each other and from the cluster strain. A laboratory investigation revealed no procedural lapses. Sputum induction records from Clinic A indicated that patient 1 in the sputum induction booth had prior culture-confirmed tuberculosis. Patient 2 had a history of a drug-resistant strain. Patient 3 had completed tuberculosis treatment, with positive cultures 7 months earlier. Patients 4 and 5 were new to the clinic and had no subsequent positive M. tuberculosis specimens. The sputum induction booth was working within normal parameters. Sputum induction that day was overseen by a new employee with limited training and no supervision. A review of the sputum induction protocol identified ambiguity regarding care of the ultrasonic nebulizer between patients, which may have led to reuse of the discarded nebulizer solution from patient 1. A break in the sputum induction protocol may have contributed to contamination of patient specimens. Sputum induction is complicated, mandating adequate staff training and supervision and patient preparation. Spoligotyping identified a potential source of M. tuberculosis contamination.

Progressive rise of Mycobacterium tuberculosis resistance to rifampicin and streptomycin in Riyadh, Saudi Arabia.

The aim of this study was to investigate, for the first time, the factors associated with resistance to antituberculous drugs in Saudi Arabia, and to follow the long-term trends in drug resistance. A retrospective study of patients with positive Mycobacterium tuberculosis recorded at the Riyadh Tuberculosis Center in 1990 was undertaken. The resistance figures from the same centre for the period July 1996 to June 1997 were reviewed for comparison. Resistance was significantly higher in those previously treated (71%) than in those who denied previous treatment (34%). There was a trend towards association of resistance with cavitatory, multilobar, and acid fast bacilli-positive cases. Nationality (Saudis, Yemenis, others) had no significant effect on resistance. The Riyadh Region now has the same high prevalence of rifampicin resistance as previously reported in the Western Region of the Kingdom. The figures on resistance for the years 1986-88, 1990, and 1996-97 were: isoniazid 19.5/13.8/11.1%, rifampicin 10/20.7/24.6%, streptomycin 5/22/27.4%, ethambutol 3.7/3.9/1.8%, respectively. The reduction in isoniazid and ethambutol resistance coincided with a rise in resistance to rifampicin and streptomycin. We speculate that this resulted from the fact that isoniazid and ethambutol are restricted only to the treatment of tuberculosis and cannot, by law, be dispensed by general practitioners or private pharmacies. Rifampicin and streptomycin, however, are widely used for brucellosis; an endemic disease in Saudi Arabia where up to 12 weeks of rifampicin therapy is recommended. There has been a significant increase in rifampicin and streptomycin resistance in Saudi Arabia over the last 10 years. Possible causes include poor compliance and wide use of these two drugs for non-tuberculosis conditions. These findings could jeopardize the benefits of the directly observed therapy short course policy which is being implemented in Saudi Arabia. Consideration should be given to prohibiting the routine use of rifampicin for the treatment of brucellosis.

Pulmonary tuberculosis in children in a developing country.

We evaluated the clinical and epidemiologic characteristics of Peruvian children presenting with pulmonary tuberculosis (PTB) to determine whether features predictive of confirmed PTB could be identified. This was a cross-sectional study of 135 children (mean age: 6.8 years) presenting to the Hospital del Niño in Lima, Peru, with presumptive diagnosis of PTB. Clinical, epidemiologic, and laboratory findings were compared between 3 groups of pediatric patients with a presumptive diagnosis of PTB: those with positive Mycobacterium tuberculosis (MTB) cultures, those likely to have PTB based on clinical criteria but with negative cultures, and those who did not meet clinical diagnostic criteria or have positive cultures. A total of 50 (37%) patients were diagnosed with definitive PTB based on positive sputum culture. Another 55 (47%) patients were classified as having probable PTB based on meeting at least 2 of the following criteria: cough lasting for at least 2 weeks, typical chest radiograph changes, purified protein derivative (PPD) >/=10 mm, or history of tuberculosis family contact. Patients with definitive or probable PTB were significantly older than patients without clinical PTB, and those with symptomatic disease were significantly older than those with asymptomatic disease. Patients with PTB diagnosed by culture were significantly more likely than those diagnosed using clinical criteria to have cough lasting >/=2 weeks, fever, and a PPD >/=10 mm. The typical presentation of PTB in Peruvian children includes symptoms of active pulmonary disease similar to those seen in adults. This presentation differs significantly from that reported in developed countries, where many children have minimal or no symptoms at the time of presentation. The diagnostic criteria for pediatric PTB must be modified in hyperendemic developing country environments where features may differ from those described in the United States. The triad of cough lasting >/=2 weeks, fever, and a PPD >/=10 mm was highly predictive for culture-positive PTB among children in this low-income Peruvian population.

Factores de riesgo asociados a pacientes tuberculosos con microscopía del esputo positiva

The main factor responsible for producing new cases of tuberculosis by exogen transmission is the existence of Mycobacterium tuberculosis in the sputum of tuberculosis patients. The objective of this study was to determine the risk factors associated to positive smear tuberculosis cases in Lleida (Spain). We studied new cases of tuberculosis over the period 1992-1998. The variables considered were: age, gender, coinfection with HIV, injection drug use (IDU), consumption of alcohol, existence of caverns in thorax X-ray, and laboratory results of direct smear examination. We calculated the incidence rates for 100,000 persons-year. The association between the dependent variable case of tuberculosis with positive Mycobacterium tuberculosis smear and the remaining independent variables were assessed obtaining odds ratios (OR) and 95% confidence intervals (CI) (crude cOR and adjusted aOR by non conditional logistic regression). We detected 905 new cases of tuberculosis. The rates in the period 1992-1998 decreased from 38.8 to 30.8. 44.9% of cases (n = 406) presented a positive direct smear. There was a positive association between the risk of being a positive smear patient and having caverns in thorax x-ray (aOR = 6.8; 95% CI, 4.8-95), being male (aOR = 1.8; 95% CI, 1.3-2.6) and consuming alcohol (aOR = 1.6; 95% CI,1.1-2.3) and this risk was significant lower in those under 15 years old (aOR = 0.2; 95% CI, 0.1-0.5), and coinfection with HIV (aOR = 0.5; 95% CI, 0.3-0.9). HIV infection implies a reduced impact in endemecity of tuberculosis. Study of contacts and the implementation of directly observed treatment must be considered not only for coinfected HIV cases and IDU but also for adult males, especially those who consume alcohol, particularly when they have caverns.

Cross-contamination with Mycobacterium tuberculosis: an epidemiological and laboratory investigation.

To investigate possible cross-contamination of laboratory specimens, as suggested by an increased incidence of newly diagnosed patients with tuberculosis, many of whom had all negative smears for acid-fast bacilli and only one positive Mycobacterium tuberculosis culture referred to as "negative smears, one positive" or NSOP. Medical-record reviews were performed for all patients with NSOP results diagnosed at this facility within a 9-month period. Laboratory logbooks were reviewed for all isolates processed; DNA fingerprinting was performed on available isolates. Of 80 patients with NSOP results, 45 (56%) were found to have false-positive cultures resulting from laboratory contamination with H37Ra, an avirulent stock strain of Mycobacterium tuberculosis. Laboratory cross-contamination resulted in the false diagnosis of tuberculosis in at least 45 individuals. Use of the Mycobacteria Growth Indicator Tube may have contributed to these contamination incidents by detecting small numbers of contaminating mycobacteria that may not have been detected with less sensitive media.

Cross-Contamination with Mycobacterium tuberculosis: An Epidemiological and Laboratory Investigation

OBJECTIVE: To investigate possible cross-contamination of laboratory specimens, as suggested by an increased incidence of newly diagnosed patients with tuberculosis, many of whom had all negative smears for acid-fast bacilli and only one positive Mycobacterium tuberculosis culture referred to as “negative smears, one positive” or NSOP. METHODS: Medical-record reviews were performed for all patients with NSOP results diagnosed at this facility within a 9-month period. Laboratory logbooks were reviewed for all isolates processed; DNA fingerprinting was performed on available isolates. RESULTS: Of 80 patients with NSOP results, 45 (56%) were found to have false-positive cultures resulting from laboratory contamination with H37Ra, an avirulent stock strain of Mycobacterium tuberculosis . CONCLUSION: Laboratory cross-contamination resulted in the false diagnosis of tuberculosis in at least 45 individuals. Use of the Mycobacteria Growth Indicator Tube may have contributed to these contamination incidents by detecting small numbers of contaminating mycobacteria that may not have been detected with less sensitive media.

Mycobacterium tuberculosis specimen contamination revisited: the role of laboratory environmental control in a pseudo-outbreak.

To investigate suspected pseudo-outbreaks of Mycobacterium tuberculosis (MTB) during August 1994 and July 1995 among patients who did not have clinical findings consistent with tuberculosis. Retrospective and prospective surveys of all clinical and laboratory data using standard epidemiological tools and DNA fingerprinting. A university-affiliated community hospital. Those with positive MTB cultures during periods when we noted that the number of MTB positive cultures greatly outnumbered the usual monthly average (retrospective analysis, 1994) and patients with positive MTB cultures without clinical findings consistent with tuberculosis (prospective survey, 1995). Epidemiological and molecular studies revealed specimen cross-contamination in the laboratory due to a faulty exhaust hood. Improvement in laboratory ventilation and change of the implicated hood prevented further specimen contamination. The identification of positive MTB cultures from patients without clinical evidence of tuberculosis should be a signal to suspect laboratory contamination and implement control measures. These should include a thorough epidemiological investigation, DNA fingerprint analysis, and an environmental inspection.

Comparison of characteristics of patients and treatment outcome for pulmonary non-tuberculous mycobacterial infection and pulmonary tuberculosis.

Patients with non-tuberculous mycobacteria are usually started on conventional antituberculous triple therapy once acid fast bacilli are detected, before the exact type of mycobacteria has been identified. The ability to identify the characteristics of patients with tuberculous and non-tuberculous mycobacteria may be helpful in identifying before treatment those patients more likely to have non-tuberculous infection. A retrospective study was conducted of all patients in one unit in whom non-tuberculous mycobacteria were identified in sputum or bronchoalveolar washings in the period 1987-93. The pattern of drug resistance was determined from laboratory records, and all case notes and chest radiographs were reviewed to identify the underlying disease and treatment outcome. All cases were compared with a matched control group of patients with culture positive Mycobacterium tuberculosis diagnosed during the same period. In the period studied there were 70 non-tuberculous and 221 tuberculous isolates. The non-tuberculous bacteria were typed as follows: M xenopi 23 (33%), M kansasii 19 (27%), M fortuitum 14 (20%), others 14 (20%). Of those with non-tuberculous mycobacteria, 83% were white subjects compared with 47% for tuberculosis. Patients with non-tuberculous mycobacteria were older than those with tuberculosis. Pre-existing lung disease or AIDS was present in 81% of patients with non-tuberculous mycobacteria and in 17% of patients with tuberculosis. Sensitivity to rifampicin and ethambutol was seen in 95% of M xenopi and 96% of M kansasii isolates. Relapse occurred in 60% of cases infected with M xenopi, 20% infected with M kansasii, and in 7% of cases with tuberculosis. In the population studied non-tuberculous mycobacteria occurred most frequently in elderly white subjects with pre-existing lung disease. If mycobacteria are detected in this group, consideration should be given to the possibility of non-tuberculous infection before embarking on treatment. A combination containing rifampicin and ethambutol is effective. The relapse rate for infection with M xenopi is high and prospective studies of the effect of the above combination of antituberculosis drugs are needed.

Pleural Tuberculosis and HIV Infection

Human immunodeficiency virus infection changes the clinical presentation of tuberculosis infection with atypical radiographs and more common extra-pulmonary involvement. We retrospectively studied pleural tuberculosis in HIV-positive patients over a 5-year period. We identified 70 patients with pleural tuberculosis by positive Mycobacterium tuberculosis cultures of pleural fluid and/or pleural tissue, including 43 HIV-positive and 27 HIV-negative patients. The HIV-positive patients were significantly younger (mean age, 38 +/- 1 years in HIV-positive vs 52 +/- 3 years in HIV-negative patients, p < 0.05). There were more intravenous drug abusers in the HIV-positive group (74 vs 30 percent, p < 0.01). The HIV-positive group had significantly fewer positive tuberculin skin tests (41 percent vs 76 percent, p < 0.03). Both groups had similar pleural fluid cellularity and pleural biopsy histologic conditions, but the HIV-positive patients demonstrated significantly more acid-fast bacteria identifiable in pleural tissue (69 percent vs 21 percent, p < 0.01), and a higher incidence of positive M tuberculosis cultures of sputum (53 percent vs 23 percent, p = 0.02). Pleural tuberculosis in HIV-positive patients presented more often as a manifestation of a greater burden of microorganisms and impaired host response.