Adrian Rendon

Global Phylogeny of Mycobacterium tuberculosis Based on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of Other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set

We analyzed a global collection of Mycobacterium tuberculosis strains using 212 single nucleotide polymorphism (SNP) markers. SNP nucleotide diversity was high (average across all SNPs, 0.19), and 96% of the SNP locus pairs were in complete linkage disequilibrium. Cluster analyses identified six deeply branching, phylogenetically distinct SNP cluster groups (SCGs) and five subgroups. The SCGs were strongly associated with the geographical origin of the M. tuberculosis samples and the birthplace of the human hosts. The most ancestral cluster (SCG-1) predominated in patients from the Indian subcontinent, while SCG-1 and another ancestral cluster (SCG-2) predominated in patients from East Asia, suggesting that M. tuberculosis first arose in the Indian subcontinent and spread worldwide through East Asia. Restricted SCG diversity and the prevalence of less ancestral SCGs in indigenous populations in Uganda and Mexico suggested a more recent introduction of M. tuberculosis into these regions. The East African Indian and Beijing spoligotypes were concordant with SCG-1 and SCG-2, respectively; X and Central Asian spoligotypes were also associated with one SCG or subgroup combination. Other clades had less consistent associations with SCGs. Mycobacterial interspersed repetitive unit (MIRU) analysis provided less robust phylogenetic information, and only 6 of the 12 MIRU microsatellite loci were highly differentiated between SCGs as measured by GST. Finally, an algorithm was devised to identify two minimal sets of either 45 or 6 SNPs that could be used in future investigations to enable global collaborations for studies on evolution, strain differentiation, and biological differences of M. tuberculosis.

Safety, Tolerance, and Efficacy of Posaconazole Therapy in Patients with Nonmeningeal Disseminated or Chronic Pulmonary Coccidioidomycosis

BACKGROUND Coccidioidomycosis can be difficult to treat with available therapies, particularly in patients with progressive or disseminated disease. Posaconazole is a new azole antifungal with potent activity against Coccidioides species, the causative agent of coccidioidomycosis. METHODS Twenty patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis were enrolled in a multicenter trial to study the safety and tolerability of posaconazole therapy, with efficacy as a secondary end point. Patients received posaconazole (400 mg/day) in capsule formulation for up to 6 months. Safety was evaluated on the basis of the occurrence of adverse events. A satisfactory efficacy response was defined as a >or=50% reduction in the Mycoses Study Group score from baseline. RESULTS Seventeen (85%) of 20 patients had a satisfactory response to treatment. The median duration of treatment was 173 days. Paired baseline and end-of-treatment culture results for Coccidioides species were available for 4 patients, all of whom converted from being positive to being negative for Coccidioides species. Relapse was experienced by 3 of 9 patients who did not receive antifungal therapy during the follow-up period. In general, posaconazole therapy was well tolerated, with 12 of 20 patients reporting adverse events that were possibly or probably related to treatment. The most common adverse events were dry mouth (in 5 patients [25%]) and headache (in 3 patients [15%]). CONCLUSIONS Courses of posaconazole therapy that were up to 6 months in duration were well tolerated in patients with coccidioidomycosis. Although this study was limited by the number of patients enrolled, it clearly demonstrates that posaconazole shows promise in the treatment of patients with coccidioidomycosis and warrants additional investigation in a full-scale clinical trial.

In Vitro Activities of DA-7157 and DA-7218 against Mycobacterium tuberculosis and Nocardia brasiliensis

ABSTRACT The in vitro activities of DA-7157, a novel oxazolidinone, against clinical isolates of Nocardia brasiliensis and Mycobacterium tuberculosis were determined. Equal MIC50s and MIC90s (0.25 and 0.5 μg/ml, respectively) were found for susceptible and multidrug-resistant isolates of M. tuberculosis. The N. brasiliensis isolates showed an MIC90 of 1 μg/ml and an MIC50 of 1 μg/ml. The DA-7157 prodrug, DA-7218, exhibited similar MICs for M. tuberculosis but fivefold-higher MICs for N. brasiliensis.

Isavuconazole Treatment of Cryptococcosis and Dimorphic Mycoses

Isavuconazole (ISAV) is a novel water-soluble triazole with potential advantages over existing agents. In a cohort of patients with cryptococcosis and endemic mycoses ISAV was well tolerated, exhibited a favorable safety profile, and demonstrated clinical activity against these endemic fungi.

Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis

BackgroundCommunity-acquired pneumonia (CAP) is considered the most important cause of death from infectious disease in developed countries. Severity assessment scores partially address the difficulties in identifying high-risk patients. A lack of specific and valid pathophysiologic severity markers affect early and effective sepsis therapy. HMGB-1, sRAGE and RAGE have been involved in sepsis and their potential as severity markers has been proposed. The aim of this study was to evaluate HMGB-1, RAGE and sRAGE levels in patients with CAP-associated sepsis and determine their possible association with clinical outcome.MethodWe evaluated 33 patients with CAP-associated sepsis admitted to the emergency room and followed in the medical wards. Severity assessment scores (CURB-65, PSI, APACHE II, SOFA) and serologic markers (HMGB-1, RAGE, sRAGE) were evaluated on admission.ResultsThirty patients with a diagnosis of CAP-associated sepsis were enrolled in the study within 24 hours after admission. Fourteen (46.6%) had pandemic (H1N1) influenza A virus, 2 (6.6%) had seasonal influenza A and 14 other diagnoses. Of the patients in the study group, 16 (53.3%) had a fatal outcome. ARDS was observed in 17 (56.6%) and a total of 22 patients had severe sepsis on admission (73%). The SOFA score showed the greatest difference between surviving and non-surviving groups (P = .003) with similar results in ARDS patients (P = .005). sRAGE levels tended to be higher in non-surviving (P = .058) and ARDS patients (P = .058). Logistic regression modeling demonstrated that SOFA (P = .013) and sRAGE (P = .05) were the only variables that modified the probability of a fatal outcome.ConclusionThe association of elevated sRAGE with a fatal outcome suggests that it may have an independent causal effect in CAP. SOFA scores were the only clinical factor with the ability to identify surviving and ARDS patients.

Mycobacterium tuberculosis Spoligotypes in Monterrey, Mexico

ABSTRACT Although tuberculosis is still a public health problem in Mexico, there is little information about the genetic characteristics of the isolates. In the present study, we analyzed by spoligotyping 180 Mycobacterium tuberculosis clinical isolates from the urban area of Monterrey, Mexico, including drug-susceptible and drug-resistant isolates. The spoligotype patterns were compared with those in the international SITVIT2 spoligotyping database. Four isolates presented spoligotype patterns not found in the database (orphan types); the rest were distributed among 44 spoligo international types (SITs). SIT53 (clade T1) and SIT119 (clade X1) were predominant and included 43 (23.8%) and 28 (15.5%) of the isolates, respectively. In order to determine if there was a dominant spoligotype in the group of multidrug-resistant isolates, 37 of them were analyzed by IS6110-based restriction fragment length polymorphism assays, and scarce clustering of strains with more than five bands was observed. Fourteen isolates of this multidrug-resistant group presented four bands or less and were distributed in four SITs: SIT53 (n = 8), SIT92 (n = 3), SIT70 (n = 2), and SIT3038 (n = 1). When the molecular detection of mutations in the katG and rpoB genes were analyzed in these isolates with low copy numbers of IS6110, only two isolates shared the same IS6110, spoligotyping, and mutations patterns. When the distribution of the spoligotypes was analyzed by age cohort, SIT119 was predominantly found in patients 0 to 20 years old, especially in males, accounting for up to 40% of the isolates. In contrast, SIT53 was more prevalent in older females. This analysis demonstrates the variability of M. tuberculosis isolates in Monterrey and the partial dominance of SIT53 and SIT119 in that area of Mexico.

Panorama actual en el diagnóstico de la tuberculosis cutánea

Pulmonary and cutaneous tuberculosis are caused by Mycobacterium tuberculosis. According to data from the World Health Organization, there are around 8 million new cases per year. The incidence of cutaneous tuberculosis has risen in parallel with that of pulmonary tuberculosis, and coinfection by M tuberculosis and human immunodeficiency virus is considered to be one of the main causes. Current diagnostic methods for pulmonary and extrapulmonary tuberculosis are far from perfect, leading to a delay in starting appropriate therapy. We present a review of these diagnostic methods and of their use in the cutaneous forms. In conclusion, histopathologic findings and isolation of M tuberculosis in cultures of biopsy material or by polymerase chain reaction are the most useful diagnostic tools in cutaneous tuberculosis.

current Panorama in the Diagnosis of cutaneous Tuberculosis

Pulmonary and cutaneous tuberculosis are caused by Mycobacterium tuberculosis. According to data from the World Health Organization, there are around 8 million new cases per year.The incidence of cutaneous tuberculosis has risen in parallel with that of pulmonary tuberculosis, and coinfection by M tuberculosis and human immunodeficiency virus is considered to be one of the main causes. Current diagnostic methods for pulmonary and extrapulmonary tuberculosis are far from perfect, leading to a delay in starting appropriate therapy.We present a review of these diagnostic methods and of their use in the cutaneous forms. In conclusion,histopathologic findings and isolation of M tuberculosis in cultures of biopsy material or by polymerase chain reaction are the most useful diagnostic tools in cutaneous tuberculosis.

Chronic obstructive pulmonary disease case finding in Mexico in an at-risk population.

OBJECTIVE To apply a case-finding strategy in Mexico to identify chronic airway obstruction among individuals with risk factors and/or symptoms compatible with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS Individuals aged ≥ 40 years with known risk factors and/or symptoms compatible with COPD were referred for an interview and spirometry. RESULTS Of 2293 subjects included, 472 (20.6%) had a post-bronchodilator forced expiratory volume in one second/forced vital capacity ratio of <70% (for Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages II-IV, prevalence was 17.1%). Those with airflow obstruction had smoked more cigarettes for more years than subjects without (19 vs. 13 cigarettes/day, P < 0.001, and 32 vs. 23 years, P < 0.001); they also had a more frequent history of exposure to biomass smoke (23.3% vs. 18.3%, P = 0.002). Females were exposed to biomass smoke for more years (24 vs. 19 years; P < 0.0001) and more hours per day than males (6.2 vs. 5.1; P < 0.001). In multiple logistic regression analysis, increasing age, male sex, ever smoking, pack-years of smoking and years of exposure to biomass smoke were significantly associated with COPD prevalence. CONCLUSIONS Airflow obstruction was identified in one in five of Mexican individuals with risk factors and/or COPD symptoms. Exposure to biomass smoke was significantly associated with the presence of airflow obstruction.

In Vitro Susceptibility of Mycobacterium tuberculosis Clinical Isolates to Garenoxacin and DA-7867

ABSTRACT The in vitro activities of DA-7867, a novel oxazolidinone, and garenoxacin (BMS-284756) were compared to those of linezolid in 67 susceptible and drug-resistant clinical isolates of Mycobacterium tuberculosis. DA-7867 was the most active drug with an MIC90 of 0.125 μg/ml, compared to the MIC90s of 4 μg/ml of garenoxacin and 2 μg/ml of linezolid.