Objective: To determine the minimum inhibitory concentrations (MICs) of parenteral penicillin and moxifloxacin against Streptococcus pneumoniae strains isolated at a hospital center. Methods: In-vitro, prospective study involving 100 S. pneumoniae isolates collected from patients who had been treated, between October of 2008 and July of 2010, at the Hospital das Clínicas complex of the University of São Paulo School of Medicine, located in the city of São Paulo, Brazil. The isolates were obtained from respiratory tract cultures or blood samples unrelated to meningeal infections, and they were tested for penicillin and moxifloxacin susceptibility by E-test. The MIC category interpretations were based on updated standards. Results: All isolates were fully susceptible to parenteral penicillin (MIC ≤ 2 µg/mL), and, consequently, they were also susceptible to amoxicillin, ampicillin, third/fourth generation cephalosporins, and ertapenem. Of the S. pneumoniae strains, 99% were also susceptible to moxifloxacin, and only one strain showed an MIC = 1.5 µg/mL (intermediate). Conclusions: Our results showed high susceptibility rates to parenteral penicillin and moxifloxacin among S. pneumoniae isolates unrelated to meningitis, which differs from international reports. Reports on penicillin resistance should be based on updated breakpoints for non-meningitis isolates in order to guide the selection of an antimicrobial therapy and to improve the prediction of the clinical outcomes.

Keywords: Drug resistance; Penicillin G; Pneumococcal infections; Streptococcus pneumoniae; Respiratory tract infections. Drug resistance; Penicillin G; Pneumococcal infections; Streptococcus pneumoniae; Respiratory tract infections.

Background: Streptococcus pneumoniae is the most common etiologic agent of community-acquired respiratory infections. In recent years, S. pneumoniae resistance to antimicrobial agents has increased. Minimum inhibitory concentration (MIC) is routinely used to determine resistance. Polymerase chain reaction (PCR) detects the genes responsible for Streptococcus pneumoniae resistance to penicillin within approximately 8 hours. Objective: To compare the PCR and MIC methods in determining Streptococcus pneumoniae resistance to penicillin. Method: A total of 153 Streptococcus pneumoniae samples, isolated from various anatomical sites, were evaluated in order to detect mutations in the genes encoding pbp1a, pbp2a and pbp2x, which are responsible for Streptococcus pneumoniae penicillin resistance. A correlation was found between mutations and penicillin MIP, as determined by the agar diffusion method. Results: Overal Streptococcus pneumoniae resistance to penicillin was 22.8% (16.3% intermediate resistance and 6.5% high resistance). In a statistically significant finding, we observed no mutations in the penicillin-sensitive samples and only one mutation, typically in the gene encoding pbp2x, among the samples with intermediate resistance, whereas mutations in all three genes studied were observed in the high-resistance samples. Conclusion: For determining Streptococcus pneumoniae resistance to penicillin, PCR is a rapid method of detection that could well be used in clinical practice.

Keywords: Streptococcus pneumoniae. Penicillin resistance. Polymerase chain reaction/methods.

Streptococcus pneumoniae resistance to penicillin was studied in two hospitals in Caxias do Sul, Rio Grande do Sul, Brazil, between May 1998 and November 2001. From the 176 strains of invasive Streptococcus pneumoniae that were identified, 2.28% (CI 0.62-5.74) presented intermediate resistance, and 3.42% (CI 1.26-7.31) presented high-level resistance. Conclusion was that the use of penicillin in Caxias do Sul was still justified as treatment of pneumococcal pneumonia, differently from other centers where the penicillin was replaced by other antibiotics. These results confirm the statement of IDSA (Infectious Diseases Society of America) guideline for the management of community-acquired pneumonia in adults, that the choice of antimicrobial drug to treat pneumococcal pneumonia should be guided by local or regional prevalence of resistance to penicillin.

Objective: The aim of this study was to determine the prevalence of macrolide-resistant S. pneumoniae and to identify its phenotypic and genotypic characteristics. Methods: Strains of S. pneumoniae isolated in the city of Porto Alegre between May 2002 and August 2004 from samples collected from different anatomical sites were analyzed. For the agar diffusion test, disks of erythromycin, clarithromycin, azithromycin and clindamycin were used. The minimum inhibitory concentrations of erythromycin were determined for macrolide-resistant isolates by the agar dilution method. Macrolide-resistant isolates were phenotyped by agar diffusion test and genotyped by polymerase chain reaction. Results: A total of 229 pneumococcal strains were evaluated, 12 (5.2%) of which were macrolide-resistant. Among the 12 resistant strains, 9 (75%) presented the MLSB phenotype, and 3 (25%) presented the M phenotype. Polymerase chain reaction testing indicated that 8 MLSB phenotype isolates harbored the ermB gene only, whereas the mefE gene was present in all 3 M phenotype isolates. One MLSB phenotype isolate presented both genes. Conclusion: In Porto Alegre, the S. pneumoniae resistance to macrolides is still low since such resistance is due primarily to the presence of the ermB gene expressing the MLSB phenotype.

Objective: To evaluate the available evidence comparing the use of the bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen for 6 months with that of standard-of-care regimens for patients with multidrug-resistant or rifampin-resistant tuberculosis (MDR/RR-TB). Methods: This was a systematic review of clinical trials comparing the use of the BPaLM regimen with the standard of care in patients with MDR/RR-TB. The main outcome measure was an unfavorable endpoint (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, and recurrence), and secondary outcome measures included adverse events and serious adverse events. We searched the MEDLINE, EMBASE, Google Scholar, LILACS, and ClinicalTrials.gov databases, from their inception to January 31, 2024, with no limitation as to language or year of publication. The risk of bias was assessed by using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation approach. Results: A total of 3,668 studies were retrieved; only one (a randomized clinical trial) met the inclusion criteria and was included. In patients with MDR/RR-TB, treatment with the BPaLM regimen, when compared with the standard of care, reduced the risk of an unfavorable outcome (composite, number needed to treat [NNT] = 7); early treatment discontinuation (NNT = 8); adverse events and discontinuation (NNT = 12); and serious adverse events (NNT = 5). Conclusions: This systematic review of the use of BPaLM in patients with MDR/RR-TB, although it included only one study, showed that BPaLM is more effective than is the standard of care and has a better safety profile. That has major implications for guidelines on the treatment of MDR/RR-TB.

Keywords: Tuberculosis, multidrug-resistant; Antitubercular agents; Diarylquinolines; Linezolid; Moxifloxacin; Nitroimidazoles.

Objective: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. Methods: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. Results: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53‑6.65). Conclusions: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

Keywords: Lung neoplasms; Polymorphism, genetic; Metabolism.

Background: Knowledge of the rates of drug resistance is one of the pillars of tuberculosis control program evaluation. Data from low-resource countries are scarce and results are delayed due to the techniques employed. There is therefore an urgent need for evaluation of faster and less onerous testing methods. Objective: To compare the performance of rapid colorimetric assays for phenotyping that employ oxidationreduction indicators to determine the susceptibility profile of Mycobacterium tuberculosis with the gold-standard proportion method on Lowenstein-Jensen Medium. Method: We analyzed 166 M. tuberculosis strains of known susceptibility. Minimal inhibition concentrations for isoniazid and rifampicin were determined in microplates, using a liquid medium and Alamar Blue and tetrazolium bromide indicators. To measure agreement the Kappa value was used. Cutoff values between sensitive and resistant strains were defined as 0.2µg/mL and 1.0µg/mL for isoniazid and rifampicin, respectively. Results: There was 100% concordance between Alamar Blue and tetrazolium bromide methods in the determination of minimal inhibition concentrations. Agreement between the colorimetric method and the Lowenstein-Jensen was 95% for isoniazid and rifampicin. Using the colorimetric method, results were obtained within 7 days, in contrast to the 28 days required for the conventional method. Conclusions: Assays to determine minimal inhibition concentrations in liquid medium and employing oxidationreduction indicators proved to be rapid and inexpensive. This method has the potential to become a faster, alternative method for determining susceptibility of M. tuberculosis strains in developing countries.

Keywords: Mycobacterium tubercolis. Disease susceptibility. Isoniazid/therapeutic use. Rifampin/therapeutic use.

Objective: To determine the prevalence and the characteristics of Mycoplasma pneumoniae-related community-acquired pneumonia (CAP) and parapneumonic pleural effusion (PPE) in children and adolescents. Methods: This was a retrospective observational study involving 121 patients with CAP/PPE hospitalized in a tertiary referral hospital between 2000 and 2008, divided into six groups according to the etiologic agent (G1 to G6, respectively): M. pneumoniae with or without co-infection, in 44 patients (group 1); etiologic agents other than M. pneumoniae, in 77 (group 2); M. pneumoniae without co-infection, in 34 (group 3); Streptococcus pneumoniae, in 36 (group 4); Staphylococcus aureus, in 31 (group 5); and M. pneumoniae/S. pneumoniae co-infection, in 9 (group 6). Results: In comparison with group 2, group 1 showed higher frequencies of females, dry cough, and previous use of beta-lactam antibiotics; longer duration of symptoms prior to admission; and lower frequencies of use of mechanical ventilation and chest tube drainage. In comparison with groups 4 and 5, group 3 showed higher frequencies of previous use of beta-lactam antibiotics and dry cough; longer duration of symptoms prior to admission; a lower frequency of use of chest tube drainage; a higher mean age and a lower frequency of nausea/vomiting (versus group 4 only); and a lower frequency of use of mechanical ventilation (versus group 5 only). M. pneumoniae/S. pneumoniae co-infection increased the duration of symptoms prior to admission. Conclusions: In this sample, the prevalence of M. pneumoniae-related CAP/PPE was 12.75%. Although the disease was milder than that caused by other microorganisms, its course was longer. Our data suggest that M. pneumoniae-related CAP/PPE in children and adolescents should be more thoroughly investigated in Brazil.

Keywords: Pleural effusion; Empyema, pleural; Pneumonia; Mycoplasma pneumoniae.

Objective: In the antibiotic era, purulent pericarditis is a rare entity. However, there are still reports of cases of the disease, which is associated with high mortality, and most such cases are attributed to delayed diagnosis. Approximately 40-50% of all cases of purulent pericarditis are caused by Gram-positive bacteria, Streptococcus pneumoniae in particular. Methods: We report four cases of pneumococcal pneumonia complicated by pericarditis, with different clinical features and levels of severity. Results: In three of the four cases, the main complication was cardiac tamponade. Microbiological screening (urinary antigen testing and pleural fluid culture) confirmed the diagnosis of severe pneumococcal pneumonia complicated by purulent pericarditis. Conclusions: In cases of pneumococcal pneumonia complicated by pericarditis, early diagnosis is of paramount importance to avoid severe hemodynamic compromise. The complications of acute pericarditis appear early in the clinical course of the infection. The most serious complications are cardiac tamponade and its consequences. Antibiotic therapy combined with pericardiocentesis drastically reduces the mortality associated with purulent pericarditis.

Keywords: Pneumonia, pneumococcal/complications; Pneumonia, pneumococcal/mortality; Pericarditis/therapy; Cardiac tamponade; Streptococcus pneumoniae/pathogenicity.

Background: Host genetic factors may play a role in the susceptibility to active tuberculosis (TB), and several polymorphisms in different cytokine coding genes have been described and associated with diseases to date. Objectives: To investigate whether polymorphisms within the promoter region of the TNF-á (-238/-308) coding genes are associated to the occurrence of active TB. Methods: SNPs within the TNF-á gene were analyzed by PCR-RFLP among two groups of individuals: patients with TB (n = 234, and patients non TB (n = 113). Results: In this study, the presence of the -238A allele was associated with susceptibility to TB disease occurrence and severity (p = 0,00002; OR = 0,15; IC = 0,06-0,36. On the contrary, the -308A allele was associated with protection to the occurrence of another pulmonary diseases. Conclusions: These results suggest the importance of genetics studies on TB occurrence. Further studies are needed pursuing a better understanding of the human pathogenesis of M. tb.

Keywords: Tuberculosis/genetics. Polymorphism, single nucleotide/genetics. Tumor necrosis factor/genetics. Alleles. Genotype. Lung diseases.

This was a cross-sectional study aimed at determining the association between exposure to tobacco displays at the point of sale and susceptibility to smoking in schoolchildren in the 14- to 17-year age bracket. Of the participating students, 69.0%, 21.3%, and 9.7% were classified as never smokers, experimenters, and smokers, respectively. Of the participants who were classified as being exposed to smoking, 18.9% were susceptible to smoking. Of the participants who were classified as being unexposed to smoking, 12.9% were susceptible to smoking (OR = 1.56; 95% CI: 1.04 -2.35; p = 0.029). Exposure to point-of-sale tobacco displays is associated with smoking susceptibility in Brazilian adolescents.

Objective: To evaluate how pulmonologists view the impact that asthma and COPD has on their patients, as well as how they treat these diseases. Methods: Survey including 227 pulmonologists participating in the VI Brazilian Congress on Asthma, II Brazilian Congress on COPD and II Brazilian Congress on Smoking, all of which were held in 2007. Results: According to the answers given by the pulmonologists, COPD is a public health problem of equal or greater importance than asthma, and COPD causes various disruptions in the lives of patients and their family members. When prescribing an inhalation device, pulmonologists feel that simplicity of use is more important than is the cost. There was a slight preference for the Aeroliser® and Diskus® systems. The budesonide-formoterol combination was the therapeutic regimen most often cited for the continued treatment of symptomatic asthma, whereas tiotropium bromide was the most often cited medication for the treatment of COPD. Selection of the therapeutic regimen for asthma and COPD is primarily influenced by the results of therapeutic trials published in the literature. Conclusions: The opinions of pulmonologists on the topics under study are in concordance with data in the specialized literature.

Keywords: Questionnaires; Asthma; Pulmonary disease, chronic obstructive; Physician's practice patterns; Brazil.

The objective of this study was to review the literature and to discuss epidemiological and physiopathological aspects and therapeutical implications of an unified approach to allergic rhinosinusitis and asthma. The bibliographic survey was based on the information provided by the following databases: Medline, MD Consult, Highwire, Medscape, LILACS and through direct search over thirty years, using the terms allergic rhinitis and asthma. Fifty-five original articles were selected in the no systematically review addressing the issue of clinical association between allergic rhinusinusitis and asthma. It is noteworthy that in the late years, with the use of specific topical medications for the lower airways or else, to the upper airways, the therapeutical approach has been distinct. However, numerous epidemiological surveys, immunopatological and clinical studies demonstrate the inter-relationship between asthma and allergic rhinossinusitis, characterized by: i) allergic rhinitis is associated to asthma and constitute an independent risk factor for its occurrence; ii) the immunopathological characteristics of allergic rhinitis and asthma are similar; iii) allergic rhinitis and asthma are manifestations of a systemic disease; iv) control of rhinitis favors asthma control. taking into consideration the close inter-relationship between allergic rhinitis and asthma, the approach to diagnosis, treatment and prophylaxis of these illnesses should be integrated. Therapeutical options that allow for the simultaneous control of asthma and allergic rhinitis offer advantages related both to costs and tolerability.

Keywords: Asthma/epidemiology; Asthma/physiopathology; Asthma/drug therapy; Sinusitis/epidemiology; Sinusitis/drug therapy; Sinusitis/physiopathology; Rhinitis, allergic, perennial

Objective: To determine the sensitivity of the scoring system proposed by the Brazilian National Ministry of Health in 2002 for the diagnosis of tuberculosis in children and adolescents suspected of having the disease. Methods: This was a retrospective study of 316 children and adolescents (0-14 years of age) diagnosed with pulmonary tuberculosis between 1997 and 2007 at the Brazilian Institute for Tuberculosis Research, located in the city of Salvador, Brazil. After reviewing the medical charts and chest X-rays of the patients, we calculated the tuberculosis scores. Results: The majority of the subjects (80.4%) had a history of close household contact with an AFB-positive adult within the last two years. The tuberculin test was negative in 11 subjects (3.5%). According to the scoring system, 251 (79.4%) were very likely to have tuberculosis (score, ≥ 40), 63 (19.9%) were moderately likely to have tuberculosis (score, 30-35), and 2 (0.7%) were unlikely to have tuberculosis (score, ≤ 25). When a cut-off score of 30 was used, the sensitivity of this scoring system was 99.3%. Conclusions: In our sample, the sensitivity of this scoring system was high when the selected cut-off score was employed. If a cut-off score of 40 had been used, 20% of the subjects would not have been treated. Therefore, scores between 30 and 35 are critical for diagnostic confirmation. Judicious clinical evaluation should prevail in the decision of treating these patients. When the cut-off score of 30 is used, 30% of individuals with other pathologies will be treated for tuberculosis. This highlights the need for improved diagnostic methods for tuberculosis.

Keywords: Tuberculosis/diagnosis; Epidemiology; Diagnostic techniques and procedures.

Background: The primary work-related lung disease in Brazil is silicosis. Its pathogenic agent is the dust of crystalline free silica (SiO2; silicon dioxide). The inflammatory process of silicosis is not yet well understood. Objective: To analyze, through immunologic laboratory evaluation, including nonspecific and specific immunity, the profile of IgG, IgM, IgA, C3, C4 and autoantibodies in the serum of workers, with or without silicosis, exposed to silica. Methods: Fifty-eight male workers were studied. All had been exposed to silica. Immunologic, radiologic and functional evaluations were made. The immunoglobulins IgG, IgA, and IgM, the complement system components C3 and C4, and the autoantibodies were assessed. Results: Chest X-rays were normal in 20 of the 58 workers and compatible with silicosis in 38. Among the 38 who were positive, IgG values were, on average, higher than in the group with normal X-rays (p < 0.05). There were no significant differences in average values of IgA, IgM, C3 or C4 (p > 0.05). The percentage of autoantibody positivity was higher in the silicosis group than in the group with normal X-rays. Conclusion: The increased levels of IgG in patients with silicosis constitutes an important discovery. It may represent continuity of the granulomatous reaction, even when the individual is no longer being exposed to silica. However, further studies are necessary in order to increase understanding of the mechanism involved in the silicosis immunologic process.

Keywords: Lung diseases. Silicosis. Occupational diseases. Immunoglobulins

Objective: To assess airway hyperresponsiveness to 4.5% hypertonic saline solution in comparison to that obtained through challenge with other bronchoconstriction agents and in relation to patient allergic sensitization. Methods: A cross-sectional, experimental study was conducted, initially involving 85 subjects. After exclusions, the final sample consisted of 62 patients, divided into two groups: a study group of those with asthma (n = 45) and a control group of those with no asthma or allergies (n = 17). Hypertonic saline was nebulized using an ultrasonic nebulizer and administered successively for 0.5, 1, 2, 4 and 8 minutes until a drop in forced expiratory volume in one second of = 15% was achieved in relation to the baseline value. The level of specific immunoglobulin E to Dermatophagoides pteronyssinus level was determined by ImmunoCAP assay and was considered positive when > 0.35 kU/L. Results: In the 36 asthma group subjects presenting a response, the mean drop in forced expiratory volume in one second after hypertonic saline nebulization was 27.4%. None of control group subjects (immunoglobulin E < 0.35 kU/L) presented a positive response to hypertonic saline. The mean forced expiratory volume in one second for control group subjects was 9%. The results of a bronchial provocation test were negative in 9 of the asthma group subjects. The frequency of bronchial provocation test positivity was higher in the subjects presenting elevated levels of specific immunoglobulin E, indicating that there is a relationship between bronchial hyperresponsiveness and the level of specific immunoglobulin E. The sensitivity and specificity of the test were 80% and 92%, respectively. Conclusion: Bronchial provocation with hypertonic saline presents satisfactory sensitivity and specificity. Therefore, in addition to being a low cost procedure that requires very little equipment, it is a useful means of assessing hyperresponsiveness in children and adolescents.

Keywords: Bronchial provocation tests; Bronchial hyperreactivity; Saline solution, hypertonic; Administration, inhalation;