Evaluation of a western blot test as a potential screening tool for occupational exposure to Mycobacterium tuberculosis in health care workers.

Health care workers (HCWs) have a higher than average risk for contracting Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB). No markers of MTB-exposure are available, and TB risk assessment is performed by tuberculin screening, identifying individuals with acquired MTB infection. This study evaluated a western blot (WB) anti-M. bovis A60 complex antibody as a MTB-exposure marker. WB reactivity was evaluated on 127 exposed and 28 non-exposed HCWs from four divisions of the Policlinico Hospital of Modena, and 140 non-exposed bacille Calmette-Guérin-vaccinated controls. Excess of occupational TB risk according to the Occupational Safety and Health Administration (OSHA) was calculated in each division. WB-positivity (%) was: (1) significantly higher in exposed HCWs compared with non-exposed (72% vs 25%, P < 0.00001), (2) highly related (r = 0.99) to OSHA risk excess in all divisions, (3) higher than non-exposed in HCWs with short (< 5 years) MTB-exposure (purified protein derivative [PPD], P > 0.18; WB, P < 0.04). PPD-positivity (%) was higher than controls only in HCWs with longer (> 5 years) MTB-exposure. The study suggests that the WB antibody might represent a more sensitive biological marker of MTB contact among exposed HCWs, related to the level of TB risk and detectable earlier than the PPD skin test, thus providing new tools for TB risk assessment in health care facilities.

Activity of aztreonam in pneumology, Part 2: Influence on phagocytosis and intracellular killing of human alveolar macrophages.

The study aim was to evaluate the activity of aztreonam on phagocytosis and intracellular killing of Staphylococcus aureus ATCC6538 by human alveolar macrophages. Drug concentrations of 1, 10, 25, 100 micrograms/ml were assayed in culture medium. Aztreonam induces dose-dependent phagocytosis up to 25 micrograms/ml concentrations; with a phagocytosis index (PIa) of 1.18 +/- 0.2 at 1 microgram/ml; of 1.27 +/- 0.2 at 10 micrograms/ml; of 1.42 +/- 0.3 at 25 micrograms/ml. No phagocytosis increase or inhibition, with unchanged cell viability compared to controls, is shown at 100 micrograms/ml aztreonam (PI 1.03 +/- 0.3). Intracellular killing acts in a similar way: the killing index (KIa) is 1.27 +/- 0.3 at 1 microgram/ml concentrations; 1.38 +/- 0.3 at 10 micrograms/ml; 1.61 +/- 0.4 at 25 micrograms/ml whereas at 100 micrograms/ml the KIa is 1.03 +/- 0.3. This study shows aztreonam's ability to stimulate macrophages' functional activity against a microorganism (S. aureus) which is not susceptible to its antibacterial activity.

Aztreonam activity in pneumology. Part 1: Clinical activity and pulmonary bioavailability of two different administration regimens.

Twenty-three patients suffering from lower respiratory tract infections caused by Gram-negative germs were treated with aztreonam (AZT) administered according to two different regimens: 17 subjects (Group A) with 2 g i.v. every 12 h and 6 patients (Group B) with 4 g in 100 ml of saline every 24 hours. Group A included 8 cases of superinfected bronchiectasis, 8 purulent bronchitis and 1 gangrene caused by Gram-negative and anaerobic agents. Group B comprised 6 patients with severe bronchiectasis infection. Pseudomonas aeruginosa was isolated from the sputum in 10/23 cases. The treatment was performed for 10 days on the average. The local and systemic tolerability was good. Group B, with higher antibiotic sputum concentrations for at least 12 hours, attained a better response than Group A: with clinical cure in 100% vs 76% cured plus 18% improved patients; therapy lasted 9.5 days for Group B vs 10.8 days for Group A. Moreover, in 14 subjects affected by pulmonary interstitial diseases who underwent diagnostic broncho-alveolar lavage, we dosed AZT in lavage fluids about 1 hour after the injection of a 2 g dose (Group C: 8 cases) or a 4 g dose (Group D: 6 cases). In group D antibiotic concentrations were significantly higher (P less than 0.005) than group C, while all the parameters that usually define the intensity of the alveolar alterations were not significantly different. Therefore, aztreonam administration in a daily monodose seems able to assure higher and longer lasting concentrations at the site of infection.

BAL modifications after antiblastic and immunomodulant therapy in lung cancer.

The bronchoalveolar compartment can be easily investigated with BAL (bronchoalveolar lavage) before and after antiblastic therapy. We studied 50 patients affected by primary lung cancer, of whom 31 served as a control group and 19 were submitted to BAL after chemo- and/or radiotherapy. Data from BAL performed in an unaffected lung area show that antiblastic therapy can produce alterations in the terminal airways without clinical evidence. Chemotherapy causes a significant impairment of the alveolo-capillary barrier. Radiotherapy is able to affect lymphocytes, with a CD4/CD8 reduction. The concomitance of both therapies produces synergistic effects. Immunomodulant therapy with thymostimulin in otherwise untreated lung cancer patients seems able to modify alveolar lymphocyte number and subsets, but these are preliminary data which need further substantiation.

Evaluation of a western blot serum test for the diagnosis of Mycobacterium tuberculosis infection.

This study was designed to evaluate the possibility of monitoring Mycobacterium tuberculosis infection using a serological assay. A discriminant score comprising antigen fractions of 38, 28, 24 and 19 kDa, identified in western blots using the Mycobacterium bovis bacille Calmette-Guérin (BCG) A60 antigen complex was established in a sample of 57 purified protein derivative (PPD)-negative and 47 PPD-positive individuals. It was then tested in a group of 140 subjects undergoing BCG vaccination as a model of tuberculosis complex infection and in a group of human immunodeficiency virus (HIV)-infected individuals as a model of cell-mediated immunodeficiency-related risk of tuberculosis. The discriminant score identified 57 out of 57 (100%) PPD-positives and none (0%) of the 47 PPD-negatives. In the BCG vaccinated subjects, 1.4% tested positive before vaccination and 90% after vaccination. In the HIV-positive subjects, 90% of the PPD-positive and 5% of the PPD-negative subjects had a positive score. This study suggests that the western blot discriminant score is an accurate test to survey M. tuberculosis infection in serum samples.