Smoking and 2-month culture conversion during anti-tuberculosis treatment.

OBJECTIVE: To investigate risk factors for delayed sputum culture conversion to negative during anti-tuberculosis treatment, with an emphasis on smoking. DESIGN: Nested case-control study of adults with non-cavitary, culture-confirmed pulmonary tuberculosis (TB) participating in an anti-tuberculosis treatment trial in Brazil. A case of delayed culture conversion was a patient who remained culture-positive after 2 months of treatment. Odds ratios with 95% confidence intervals were calculated. RESULTS: Fifty-three cases and 240 control patients were analyzed. Smokers had three-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.007) than non-smokers, while smokers and ex-smokers who smoked >20 cigarettes a day had two-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.045). CONCLUSION: Cigarette smoking adversely affects culture conversion during anti-tuberculosis treatment. Support for smoking cessation should be considered to improve outcomes in TB control programs.

Delay in diagnosis of pulmonary tuberculosis at a primary health clinic in Vitoria, Brazil.

SETTING: Primary health clinics in Vitoria, Espirito Santo, Brazil. OBJECTIVE: To identify risk factors associated with patient and health care delays among patients seeking care at primary health clinics. METHODS: A prospective study among tuberculosis (TB) patients diagnosed in Vitoria between 1 January 2003 and 30 December 2007. A questionnaire ascertained the date of onset and duration of TB symptoms and medical records were reviewed. Between-group distributions of delay were compared and multivariate logistic regression was performed. RESULTS: Of 304 patients, 296 (97%) reported at least one TB symptom presenting for the first time to a qualified health service; 244 (80%) reported cough > 3 weeks. Median health care delay was 30 days (range 5-68), and median total delay was 110 days (range 26-784). Multivariate analysis revealed any cough (OR(adj) 7.35, 95%CI 2.40-22.5) and weight at TB diagnosis < 60 kg (OR(adj) 5.92, 95%CI 1.83-19.1) to be associated with patient delay of ≥ 30 days. Factors increasing risk of prolonged delay (≥ 90 days) were age ≥ 30 years (OR(adj) 1.93, 95%CI 1.09-3.43) and chest pain (OR(adj) 2.42, 95%CI 1.29-4.53). CONCLUSION: Improving health care workers' education regarding TB symptoms and implementing active case finding in targeted populations may reduce delays.

Evaluation of low-colony-number counts of Mycobacterium tuberculosis on solid media as a microbiological marker of cross-contamination.

Low-colony-number counts on solid media are considered characteristic of cross-contamination, although they are normally observed in true-positive cultures from some groups of patients. The aim of this study was to evaluate low-yield growth cultures as a microbiological marker for cross-contamination. We evaluated 106 cultures with <15 colonies from 94 patients, and the proportions of false-positive cultures were 0.9% per sample and 1.1% per patient, which indicates that low-yield growth is not a reliable marker of cross-contamination.

Multicentre evaluation of an automated BACTEC 960 system for susceptibility testing of Mycobacterium tuberculosis.

SETTING: Three mycobacteria reference laboratories in the south-eastern part of Brazil. OBJECTIVE: To evaluate the automated Mycobacteria Growth Indicator Tube (MGIT) for drug susceptibility testing of Mycobacterium tuberculosis. DESIGN: Performance of the automated BACTEC MGIT 960 (M960) system for testing M. tuberculosis susceptibility to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB) was evaluated with 95 clinical isolates and compared to the results of the radiometric BACTEC 460TB (B460) system, the proportion method (PM), and the resistance ratio method (RRM). Judicial susceptibility profiles of 88 isolates were defined based on two or more concordant results among B460, PM and RRM, and used as a reference for comparison with M960 results. RESULTS: Agreement rates between M960 and conventional methods were 95.2% with B460, 96.6% with the PM and 93.4% with the RRM. The lowest agreement rates were obtained for SM with the RRM and for EMB with B460. When comparing M960 with judicial susceptibility profiles, the agreement rate was 97.9%. The agreement rates obtained for INH and RMP were 99.2% and for SM and EMB they were 96.2% and 96.9%, respectively. The mean time to reporting the M960 results was 6.9 days. CONCLUSION: M960 offers great improvements when compared to the proportion and resistance ratio methods and would benefit patient treatment.

Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis.

OBJECTIVE: To evaluate the early bactericidal activity (EBA) of the new fluoroquinolones levofloxacin, gatifloxacin and moxifloxacin in patients with pulmonary tuberculosis (PTB). DESIGN: Randomized, open-label trial. Forty adults with newly diagnosed smear-positive PTB (10 per arm) were assigned to receive isoniazid (INH) 300 mg, levofloxacin 1000 mg, gatifloxacin 400 mg, or moxifloxacin 400 mg daily for 7 days. Sputum for quantitative culture was collected for 2 days before and daily during 7 days of monotherapy. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (EBA 0-2) and last 5 days of monotherapy (extended EBA, EBA 2-7). Laboratory staff were blinded to treatment assignment. RESULTS: The EBA 0-2 of INH (0.67 log10 cfu/ml/day) was greater than that of moxifloxacin and gatifloxacin (0.33 and 0.35 log10 cfu/ml/day, respectively), but not of levofloxacin 1000 mg daily (0.45 log10 cfu/ml/day) (P = 0.14). Bactericidal activity between days 2 and 7 was similar for all three fluoroquinolones. In a pooled comparison, the EBA 2-7 of the fluoroquinolones was greater than for INH. CONCLUSION: Moxifloxacin, gatifloxacin, and high-dose levofloxacin have excellent EBA, only slightly less than for INH, and greater extended EBA. These drugs warrant further study in the treatment of drug-susceptible TB.

Biodegradation of polyethylene by the thermophilic bacterium Brevibacillus borstelensis.

AIM: To select a polyethylene-degrading micro-organism and to study the factors affecting its biodegrading activity. METHODS AND RESULTS: A thermophilic bacterium Brevibaccillus borstelensis strain 707 (isolated from soil) utilized branched low-density polyethylene as the sole carbon source and degraded it. Incubation of polyethylene with B. borstelensis (30 days, 50 degrees C) reduced its gravimetric and molecular weights by 11 and 30% respectively. Brevibaccillus borstelensis also degraded polyethylene in the presence of mannitol. Biodegradation of u.v. photo-oxidized polyethylene increased with increasing irradiation time. Fourier Transform Infra-Red (FTIR) analysis of photo-oxidized polyethylene revealed a reduction in carbonyl groups after incubation with the bacteria. CONCLUSIONS: This study demonstrates that polyethylene--considered to be inert--can be biodegraded if the right microbial strain is isolated. Enrichment culture methods were effective for isolating a thermophilic bacterium capable of utilizing polyethylene as the sole carbon and energy source. Maximal biodegradation was obtained in combination with photo-oxidation, which showed that carbonyl residues formed by photo-oxidation play a role in biodegradation. Brevibaccillus borstelensis also degraded the CH2 backbone of nonirradiated polyethylene. SIGNIFICANCE AND IMPACT OF THE STUDY: Biodegradation of polyethylene by a single bacterial strain contributes to our understanding of the process and the factors affecting polyethylene biodegradation.

Mycobacterium tuberculosis bacteremia diagnosed in an HIV-negative patient in Brazil: a rare or an under-reported event?

A case of Mycobacterium tuberculosis bacteremia in an HIV negative immunodepressed patient was described using the BACTEC 460 TB system. This bacterium should be investigated in the blood of immunodepressed non-HIV infected patients with prolonged fever.

Mycobacterium tuberculosis bacteremia diagnosed in an HIV-negative patient in Brazil: a rare or an under-reported event?

A case of Mycobacterium tuberculosis bacteremia in an HIV negative immunodepressed patient was described using the BACTEC 460 TB system. This bacterium should be investigated in the blood of immunodepressed non-HIV infected patients with prolonged fever.

Mycobacteraemia among HIV-1-infected patients in São Paulo, Brazil: 1995 to 1998.

From July 1995 to August 1998, mycobacterial blood cultures were obtained from 1032 HIV-infected patients seen at the Centro de Referência e Treinamento de AIDS (CRTA), Hospital São Paulo (HSP), and Centro de Referência de AIDS de Santos (CRAS). Overall, 179 episodes of mycobacteraemia were detected: 111 (62.0%) at CRTA, 50 (27.9%) at HSP, and 18 (10.1%) at CRAS. The frequency of positive cultures declined sharply from 22.6% in 1995 to 6.9% in 1998, consistent with the decrease in opportunistic infections following the publicly funded distribution of highly active antiretroviral therapy. In 1995, mycobacteraemia was more frequently due to Mycobacterium avium complex (59.2%) than Mycobacterium tuberculosis (28.6%), whereas in 1998 the relative frequencies were reversed (28.6 vs. 64.3% respectively), probably justified by the increased virulence of M. tuberculosis and the greater risk of invasive infection in less-immunocompromised patients, including patients unaware they are infected with HIV.

Protective effect of insulin-like-growth-factor-1 against dopamine-induced neurotoxicity in human and rodent neuronal cultures: possible implications for Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of 70-80% of dopaminergic (DA) neurons in the substantia nigra. High concentrations of DA were suggested to induce oxidative stress and selective neurodegeneration. We evaluated the effect of insulin-like-growth-factor-1 (IGF-1) on DA toxicity in neuronal cultures. IGF-1 (0.5 microg/ml) suppressed cell death induced by exposure to DA (0.3 mM) after 2 and 4 days, in a rat cerebellar culture. Similarly, IGF-1 (0.5 and 1.0 microg/ml) antagonized DA (0.125 and 0.250 mM) neurotoxicity in a human neuroblastoma cell line (SK-N-SH). Flowcytometric analysis of neuroblastoma cells treated with DA (0.5 mM) showed increased apoptosis, which was significantly reduced by IGF-1. The effect of IGF-1 was associated with increased Bcl-2 expression as indicated by flowcytometry and Western blot analysis. We suggest that IGF-1 possesses a neuroprotective effect against DA-induced toxicity, and may have a potential role in the treatment of PD.

Tuberculosis and drug resistance among patients seen at an AIDS Reference Center in São Paulo, Brazil.

OBJECTIVES: To assess the frequency of resistance of Mycobacterium tuberculosis to antituberculosis drugs and the factors associated with it among patients with tuberculosis (TB) and acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: The medical records of TB and AIDS cases diagnosed from 1992 to 1997 in a public service for AIDS care were reviewed. RESULTS: Resistance was diagnosed in 82 (19%) of 431 cases. The mean and median values between the diagnosis of AIDS and the diagnosis of TB were 214.8 days and 70.5 days, respectively. Multidrug-resistant TB (MDR TB) occurred in 11.3% of cases. Of the 186 patients with no previous treatment, 13 (6.9%) presented primary MDR TB. Of the 90 cases with previous treatment, six (6.7%) presented monoresistance to rifampin and 27 (30%) presented MDR TB. The distribution of cases with sensitive and resistant M. tuberculosis strains was homogeneous in terms of the following variables: gender, age, category of exposure to human immunodeficiency virus (HIV), alcoholism, and homelessness. Multivariate analysis showed an association between resistance and the two following variables: previous treatment and duration of AIDS prior to TB exceeding 71 days. The rates of primary multiresistance and of monoresistance to rifampin were higher than those detected in HIV-negative patients in Brazil. CONCLUSIONS: In this patient series, M. tuberculosis resistance was predominantly of the acquired type, and resistance was independently associated with previous treatment for TB and with duration of AIDS prior to TB exceeding 71 days.

Molecular epidemiology of Mycobacterium avium complex isolated from patients with and without AIDS in Brazil and England.

Mycobacterium avium complex (MAC) is ubiquitous throughout the world. It is an opportunistic pathogen in AIDS patients but the number of cases in HIV negative patients is also increasing. The aim of this study was to determine whether patients were being infected with different MAC strains or whether one strain was dominant. DNA obtained from isolates in Brazil and England were compared using pulsed field gel electrophoresis (PFGE). Strains from 22 Brazilian patients clustered into 7 groups but 68/90 patients had a unique strain. In all patients, Brazilian and English, the same strain was isolated repeatedly over time, some over several years. This study shows that it is most likely that Man is infected from the environment and that one strain can survive without change for many years both in the environment and in Man.

Drug resistance of M. tuberculosis isolated from patients with HIV infection seen at an AIDS Reference Center in São Paulo, Brazil.

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

Mycobacterium avium complex (MAC) isolated from AIDS patients and the criteria required for its implication in disease.

Before the AIDS pandemia, the Mycobacterium avium complex (MAC) was responsible in most cases for the pneumopathies that attack patients with basic chronic pulmonary diseases such as emphysema and chronic bronchitis. In 1981, with the advent of the acquired immunodeficiency syndrome (AIDS), MAC started to represent one of the most frequent bacterial diseases among AIDS patients, with the disseminated form of the disease being the major clinical manifestation of the infection. Between January 1989 and February 1991, the Section of Mycobacteria of the Adolfo Lutz Institute, São Paulo, isolated MAC from 103 patients by culturing different sterile and no-sterile processed specimens collected from 2304 patients seen at the AIDS Reference and Training Center and/or Emilio Ribas Infectology Institute. Disseminated disease was diagnosed in 29 of those patients on the basis of MAC isolation from blood and/or bone marrow aspirate. The other 74 patients were divided into categories highly (5), moderately (26) and little suggestive of disease (43) according to the criteria of DAVIDSON (1989). The various criteria for MAC isolation from sterile and non-sterile specimens are discussed.

Mycobacterium avium complex (MAC): an unusual potential pathogen in cerebrospinal fluid of AIDS patients.

Mycobacterium avium complex (MAC) is frequently isolated from patients with late complications of Acquired Immunodeficiency Syndrome (AIDS), especially in North America and Europe. However, its isolation from the central nervous system (CNS) has been seldom reported in these countries. MAC infections in AIDS patients in African and Latin American countries are believed to be uncommon. We report the isolation of MAC from cerebrospinal fluid (CSF) of 11 AIDS patients out of 1723 (0.63%) seen at "Centro de Referência e Treinamento-AIDS", São Paulo and discuss the significance of its isolation.

[Paracoccidioides brasiliensis (Lutz, 1908) isolated by hemoculture in a patient with the acquired immunodeficiency syndrome (AIDS)]. / Paracoccidiodes brasiliensis (Lutz, 1908) isolado por meio de hemocultura em um paciente portador de síndrome de imunodeficiência adquirida (SIDA).

A case of an AIDS patient with positive blood culture for Paracoccidiodes brasiliensis is reported. The patient was a 29-years-old male born in Nova Londrina (Paraná State, Brazil) who presented splenomegaly and fever of unknown origin. Three blood cultures were performed, each one of them for aerobic bacteria, mycobacteria and fungi. Cultures for aerobic bacteria and mycobacteria were negative. However, the yeast phase P. brasiliensis was isolated from two cultures in BHI agar, 20 days after inoculation in Negroni medium. The patient was classified in group V according to the Centers for Disease Control (CDC) criteria for AIDS, due to a Pneumocystis carinii pneumonia. Treatment was discontinued due to an individual decision of the patient on the second dose of amphotericin B. This antibiotic was replaced by ketoconazole in the daily dose of 800 mg. The patient died one year after the isolation of P. brasiliensis on blood culture.