Association Between Uropathogenic Escherichia coli Virulence Genes and Severity of Infection and Resistance to Antibiotics.

Purpose: Urinary tract infection (UTI) is the most frequent bacterial infection. Some uropathogenic Escherichia coli (UPEC) genes have been associated with disease severity and antibiotic resistance. The aim was to determine the association of nine UPEC virulence genes with UTI severity and antibiotic resistance of strains collected from adults with community-acquired UTI. Patients and Methods: A case-control study (1:3) (38 urosepsis/pyelonephritis and 114 cystitis/urethritis) was conducted. The fimH, sfa/foc, cvaC, hlyA, iroN, fyuA, ireA, iutA, and aer (the last five are siderophore genes) virulence genes were determined by PCR. The information of antibiotic susceptibility pattern of the strains was collected from medical records. This pattern was determined using an automated system for antimicrobial susceptibility testing. Multidrug-resistant (MDR) was defined as resistance to three or more antibiotic families. Results: fimH was the most frequently detected virulence gene (94.7%), and sfa/foc was the least frequently detected (9.2%); 55.3% (83/150) of the strains were MDR. The evaluated genes were not associated with UTI severity. Associations were found between the presence of hlyA and carbapenem resistance (Odds ratio [OR] = 7.58, 95% confidence interval [CI], 1.50-35.42), iutA and fluoroquinolone resistance (OR = 2.35, 95% CI, 1.15-4.84, and aer (OR = 2.8, 95% CI, 1.20-6.48) and iutA (OR = 2.95, 95% CI, 1.33-6.69) with penicillin resistance. In addition, iutA was the only gene associated with MDR (OR = 2.09, 95% CI,1.03-4.26). Conclusion: There was no association among virulence genes and UTI severity. Three of the five iron uptake genes were associated with resistance to at least one antibiotic family. Regarding the other four non-siderophore genes, only hlyA was associated with antibiotic resistance to carbapenems. It is essential to continue studying bacterial genetic characteristics that cause the generation of pathogenic and multidrug-resistant phenotypes of UPEC strains.

Immunomodulation and Antioxidant Activities as Possible Trypanocidal and Cardioprotective Mechanisms of Major Terpenes from Lippia alba Essential Oils in an Experimental Model of Chronic Chagas Disease.

In the late phase of Trypanosoma cruzi infection, parasite persistence and an exaggerated immune response accompanied by oxidative stress play a crucial role in the genesis of Chronic Chagasic Cardiomyopathy (CCC). Current treatments (Benznidazole (BNZ) and Nifurtimox) can effect only the elimination of the parasite, but are ineffective for late stage treatment and for preventing heart damage and disease progression. In vivo trypanocidal and cardioprotective activity has been reported for Lippia alba essential oils (EOs), ascribed to their two major terpenes, limonene and caryophyllene oxide. To investigate the role of antioxidant and immunomodulatory mechanisms behind these properties, chronic-T. cruzi-infected rats were treated with oral synergistic mixtures of the aforementioned EOs. For this purpose, the EOs were optimized through limonene-enrichment fractioning and by the addition of exogenous caryophyllene oxide (LIMOX) and used alone or in combined therapy with subtherapeutic doses of BNZ (LIMOXBNZ). Clinical, toxicity, inflammatory, oxidative, and parasitological (qPCR) parameters were assessed in cardiac tissue. These therapies demonstrated meaningful antioxidant and immunomodulatory activity on markers involved in CCC pathogenesis (IFN-γ, TNF-α, IL-4, IL-10, and iNOS), which could explain their significant trypanocidal properties and their noteworthy role in preventing, and even reversing, the progression of cardiac damage in chronic Chagas disease.

Circulating Trypanosoma cruzi load and major cardiovascular outcomes in patients with chronic Chagas cardiomyopathy: a prospective cohort study.

OBJECTIVES: To analyse the effect of parasite load assessed by quantitative reverse transcription PCR (RT-qPCR) in serum on the prognosis of patients with chronic Chagas cardiomyopathy (CCM) after a 2-year follow-up. METHODS: Prospective cohort study conducted between 2015 and 2017. One hundred patients with CCM were included. Basal parasitaemia levels of Trypanosoma cruzi (T. cruzi) were measured using a quantitative polymerase chain reaction (qPCR) test. The primary composite outcome (CO) was all-cause mortality, cardiac transplantation and implantation of a left ventricular assist device. Secondary outcomes were the baseline levels of serum biomarkers and echocardiographic variables. RESULTS: After a 2 years of follow-up, the primary CO rate was 16%. A positive qPCR was not associated with a higher risk of the CO. However, when parasitaemia was evaluated by comparing tertiles (tertile 1: undetectable parasitaemia, tertile 2: low parasitaemia and tertile 3: high parasitaemia), a higher risk of the CO (HR 3.66; 95% CI 1.11-12.21) was evidenced in tertile 2. Moreover, patients in tertile 2 had significantly higher levels of high-sensitivity troponin T and cystatin C and more frequently exhibited an ejection fraction <50%. CONCLUSION: Low parasitaemia was associated with severity markers of myocardial injury and a higher risk of the composite outcome when compared with undetectable parasitaemia. This finding could be hypothetically explained by a more vigorous immune response in patients with low parasitaemia that could decrease T. cruzi load more efficiently, but be associated with increased myocardial damage. Additional studies with a larger number of patients and cytokine measurement are required to support this hypothesis.

OBJECTIFS: Analyser l'effet de la charge parasitaire évaluée par PCR quantitative de transcription inverse (RT-qPCR) dans le sérum sur le pronostic des patients atteints de cardiomyopathie chronique de Chagas (CCM) après un suivi de deux ans. MÉTHODES: Etude de cohorte prospective menée entre 2015 et 2017. Une centaine de patients atteints de CCM ont été inclus. Les niveaux de parasitémie basale de Trypanosoma cruzi (T. cruzi) ont été mesurés en utilisant un test de réaction en chaîne de la polymérase quantitative (qPCR). Le principal résultat composite (RC) était la mortalité toutes causes, la transplantation cardiaque et l'implantation d'un dispositif d'assistance ventriculaire gauche. Les critères secondaires étaient les niveaux de base des biomarqueurs sériques et des variables échocardiographiques. RÉSULTATS: Après 2 ans de suivi, le taux de RC primaire était de 16%. Une qPCR positive n'était pas associée à un risque plus élevé de RC. Cependant, lorsque la parasitémie était évaluée en comparant les tertiles (tertile 1: parasitémie indétectable, tertile 2: parasitémie faible et tertile 3: parasitémie élevée), un risque plus élevé de RC (HR: 3,66; IC95%: 1,11-12,21) a été mis en évidence dans le tertile 2. De plus, les patients du tertile 2 avaient des niveaux significativement plus élevés de troponine T et de cystatine-C à haute sensibilité et présentaient plus fréquemment une fraction d'éjection <50%. CONCLUSION: Une faible parasitémie était associée à des marqueurs de sévérité des lésions myocardiques et à un risque plus élevé de résultat composite par rapport à une parasitémie indétectable. Cette découverte pourrait être hypothétiquement expliquée par une réponse immunitaire plus vigoureuse chez les patients présentant une faible parasitémie qui pourrait diminuer la charge de T. cruzi plus efficacement mais être associée à une augmentation des lésions myocardiques. Des études supplémentaires avec un plus grand nombre de patients et une mesure des cytokines sont nécessaires pour étayer cette hypothèse.

Acute Chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia.

BACKGROUND: Outbreaks of acute Chagas disease associated with oral transmission are easily detected nowadays with trained health personnel in areas of low endemicity, or in which the vector transmission has been interrupted. Given the biological and genetic diversity of Trypanosoma cruzi, the high morbidity, mortality, and the observed therapeutic failure, new characteristics of these outbreaks need to be addressed at different levels, both in Trypanosoma cruzi as in patient response. The aim of this work was to evaluate the patient's features involved in six outbreaks of acute Chagas disease which occurred in Santander, Colombia, and the characteristics of Trypanosoma cruzi clones isolated from these patients, to establish the potential relationship between the etiologic agent features with host behavior. METHODS: The clinical, pathological and epidemiological aspects of outbreaks were analyzed. In addition, Trypanosoma cruzi clones were biologically characterized both in vitro and in vivo, and the susceptibility to the classical trypanocidal drugs nifurtimox and benznidazole was evaluated. Trypanosoma cruzi clones were genotyped by means of mini-exon intergenic spacer and cytochrome b genes sequencing. RESULTS: All clones were DTU I, and based on the mini-exon intergenic spacer, belong to two genotypes: G2 related with sub-urban, and G11 with rural outbreaks. Girón outbreak clones with higher susceptibility to drugs presented G2 genotype and C/T transition in Cyt b. The outbreaks affected mainly young population (±25.9 years), and the mortality rate was 10 %. The cardiac tissue showed intense inflammatory infiltrate, myocardial necrosis and abundant amastigote nests. However, although the gastrointestinal tissue was congestive, no inflammation or parasites were observed. CONCLUSIONS: Although all clones belong to DTU I, two intra-DTU genotypes were found with the sequencing of the mini-exon intergenic spacer, however there is no strict correlation between genetic groups, the cycles of the parasite or the clinical forms of the disease. Trypanosoma cruzi clones from Girón with higher sensitivity to nifurtimox presented a particular G2 genotype and C/T transition in Cyt b. When the diagnosis was early, the patients responded well to antichagasic treatment, which highlights the importance of diagnosis and treatment early to prevent fatal outcomes associated with these acute episodes.

Infecciones por Staphylococcus aureus meticilino resistente en niños en Bucaramanga Colombia / Methicillin-resistant Staphylococcus aureus infections in children in Bucaramanga Colombia

Introducción: La emergencia de infecciones, en niños, por Staphylococcus aureus meticilino resistente adquirido en comunidad (SAMR-AC) en niños constituye un problema de salud pública en varios países del mundo, sin embargo, en nuestro país hay pocos reportes sobre las características clínicas, factores de riesgo y características moleculares. Materiales y métodos: Estudio descriptivo que comparó el comportamiento clínico y epidemiológico de las infecciones por S. aureus meticilino resistente y S. aureus meticilino sensible. Se detectaron los genes mecA, lukS-PV y lukF-PV por amplificación y se determinó la resistencia a antimicrobianos. Resultados: De las 39 infecciones por S. aureus entre enero de 2008 y junio de 2009, el 60% fueron por S. aureus meticilino resistente, con mayor proporción de lactantes y uso previo de antibióticos en el grupo meticilino resistente. Predominó la localización Osteoarticular (54%) seguida de piel y tejidos blandos (41%). En los meticilino resistentes el gen mecA y lukS-PV y lukF-PV se detectaron en el 93% y 86% respectivamente. En el grupo meticilino resistentes y leucocidina de Panton Valentine positiva fueron más frecuentes los abscesos subcutáneos, una mayor respuesta inflamatoria y susceptibilidad a la mayoría de los antibióticos. Conclusión: Reportamos la presencia de infecciones por SAMR – AC (LPV +, con susceptibilidad a la mayoría de los antibióticos) en nuestro medio, con abscesos como foco clínico predominante y una mayor respuesta inflamatoria.

Introduction: The emergence of the infection by community-acquired methicillin-resistant S. aureus, in children, is a public health problem in many countries of the world, however, in Colombia, local dates about the clinical features, risk factors and molecular characteristic are scarce. Materials and methods: This descriptive study compared the clinical and epidemiological behavior of infections by methicillin-resistant S. aureus and methicillin suceptible S. aureus. The gen mecA and lukS-PV y lukF-PV were detected by amplification and antibiotic sensitivity was determinated. Results:From January 2008 to June de 2009, 39 infections caused by S. aureus were diagnosed, 60% by methicillin-resistant S. aureus. In the group methicillin-resistant, there were more proportion of infants and previous use of antibiotics. The most frequents location of the infection were: Osteoarticular (54%) and Skin and soft tissue (41%). The gen mecA and lukSPV y lukF-PV were detected in 93% and 86% of the methicillin-resistant S. aureus. Soft tissue abscess, an inflammatory response enhanced and sensitivity to the most of the antibiotics were most frequent in the group methicillin-resistant and Panton-Valentine leuokocidin (PVL) positive. Conclusions: We report the presence of infections by MRSA – AC, PVL + and sensitivity to the most of antibiotics, in our media. The most frequent features are the presence of soft tissue abscesses and an inflammatory response enhanced.