RESUMO
In the modern era, infections of the lung are typically managed medically. However, all pulmonary hydatid cysts require surgery with rare exceptions, and bacterial abscesses require surgery if they are complicated, resistant to treatment, and/or large. Surgical treatment of these pulmonary conditions requires clinical knowledge of tests for causative organisms, perioperative antimicrobial therapies, options for surgical management, and postoperative care.
Assuntos
Equinococose Pulmonar , Abscesso Pulmonar , Equinococose Pulmonar/complicações , Equinococose Pulmonar/diagnóstico , Equinococose Pulmonar/cirurgia , Humanos , Pulmão , Abscesso Pulmonar/diagnóstico , Abscesso Pulmonar/terapiaRESUMO
Phage lysins are promising new therapeutics against multidrug-resistant bacteria. These so-called enzybiotics offer, amongst their most notable advantages, high target specificity and low resistance development. Moreover, there are numerous recent and ongoing studies aimed at demonstrating the efficacy and safety of endolysins in animal models or even in clinical trials. Nonetheless, as is the case for other antimicrobials, it is important to assess potential strategies that may broaden their potential applications or improve their stability. Encapsulation, for instance, has given very good results for some antibiotics. This study sought to evaluate the feasibility of encapsulating an endolysin against the opportunistic human pathogen Staphylococcus aureus, one of the most problematic bacteria in the context of the current antibiotic resistance crisis. Endolysin LysRODI has antimicrobial activity against many S. aureus strains from different sources, including methicillin-resistant S. aureus (MRSA) isolates. Here, this protein was encapsulated in pH-sensitive liposomes with an efficacy of approximately 47%, retaining its activity after being released from the nanocapsules. Additionally, the encapsulated endolysin effectively reduced S. aureus cell counts by > 2log units in both planktonic cultures and biofilms upon incubation at pH 5. These results demonstrate the viability of LysRODI encapsulation in liposomes for its targeted delivery under mild acidic conditions.
RESUMO
Phage lytic proteins are promising antimicrobials that could complement conventional antibiotics and help to combat multi-drug resistant bacteria that cause important human and animal infections. Here, we report the characterization of endolysin LysRODI (encoded by staphylophage phiIPLA-RODI) and its application as a prophylactic mastitis treatment. The main properties of LysRODI were compared with those of endolysin LysA72 (encoded by staphylophage phiIPLA35) and the chimeric protein CHAPSH3b (derived from the virion-associated peptidoglycan hydrolase HydH5 and lysostaphin). Time-kill experiments performed with Staphylococcus aureus and Staphylococcus epidermidis demonstrated that the killing rate of LysRODI and CHAPSH3b is higher than that of LysA72 (0.1 µM protein removed 107 CFU/ml of S. aureus in 30 min). Of note, all proteins failed to select resistant mutants as bacterial exposure to sub-lethal concentrations of the proteins did not alter the MIC values. Additionally, LysRODI and CHAPSH3b were non-toxic in a zebrafish embryo model at concentrations near the MIC (0.5 and 0.7 µM, respectively). Moreover, these two proteins significantly reduced mortality in a zebrafish model of systemic infection. In contrast to LysRODI, the efficacy of CHAPSH3b was dose-dependent in zebrafish, requiring higher-dose treatments to achieve the maximum survival rate. For this reason, LysRODI was selected for further analysis in mice, demonstrating great efficacy to prevent mammary infections by S. aureus and S. epidermidis. Our findings strongly support the use of phage lytic proteins as a new strategy to prevent staphylococcal mastitis.
RESUMO
The history of dairy farming goes back thousands of years, evolving from a traditional small-scale production to the industrialized manufacturing of fermented dairy products. Commercialization of milk and its derived products has been very important not only as a source of nourishment but also as an economic resource. However, the dairy industry has encountered several problems that have to be overcome to ensure the quality and safety of the final products, as well as to avoid economic losses. Within this context, it is interesting to highlight the role played by bacteriophages, or phages, viruses that infect bacteria. Indeed, bacteriophages were originally regarded as a nuisance, being responsible for fermentation failure and economic losses when infecting lactic acid bacteria, but are now considered promising antimicrobials to fight milk-borne pathogens without contributing to the increase in antibiotic resistance.
RESUMO
BACKGROUND: While most patients with tuberculosis (TB) can be successfully treated using short-course medical chemotherapy, thoracic surgery is an important adjunctive strategy for many patients with drug-resistant disease. The need for physical, technical and financial resources presents a potential challenge to implementing surgery as a component of treatment for multidrug-resistant TB (MDR-TB) in resource-poor settings. However, a cohort of patients with severe MDR-TB in Lima, Peru underwent surgery as part of their treatment. METHODS: 121 patients underwent pulmonary surgery for drug-resistant tuberculosis between May 1999 and January 2004. Surgery was performed by a team of thoracic surgeons under the Ministry of Health. Patient demographic data, clinical characteristics, surgical procedures and surgical outcomes were studied. RESULTS: Most of the patients had failed multiple TB regimens and were resistant to a median of seven drugs. The median time of follow-up after surgery was 33 months. 79.3% of patients were culture-positive before surgery, and sustained culture-negative status among survivors was achieved in 74.8% of patients. 63% of those followed up for at least 6 months after surgery were either cured or probably cured. Postoperative complications, observed in 22.6% of patients, were associated with preoperative haemoptysis, vital capacity <50% and low forced expiratory volume in 1 s. CONCLUSIONS: This is one of the largest cohorts with MDR-TB to be treated with surgery, and the first from a resource-poor country. Although surgery is not often considered an option for patients in resource-poor settings, the findings of this study support the argument that adjunctive surgery should be considered an integral component of MDR-TB treatment programmes, even in poor countries such as Peru.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/cirurgia , Adolescente , Adulto , Idoso , Antituberculosos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Complicações Pós-Operatórias/mortalidade , Estudos Prospectivos , Tuberculose Resistente a Múltiplos Medicamentos/mortalidadeRESUMO
El tratamiento de la tuberculosis pulmonar (TB) es esencialmente farmacológico, pero debido a la aparición de resistenciaa drogas, el tratamiento se ha dificultado. En ese contexto la cirugía pulmonar es una importante estrategia coadyuvantepara el tratamiento de la tuberculosis multidrogo resistente (TB MDR). Objetivo. Describir las características clínicas,resultados y complicaciones en una serie de 304 pacientes con TB MDR sometidos a terapia quirúrgica. Materiales y métodos. Entre mayo de 1999 y enero del 2007 un total de 336 intervenciones quirúrgicas fueron realizadas en 304 pacientes, pertenecientes al Programa Nacional de Control de la Tuberculosis, los cuales fueron operados por un equipoquirúrgico del Ministerio de salud, en el Hospital Nacional Hipólito Unanue y en un Centro Privado de Lima. Resultados. Lamayoría de casos fueron de sexo masculino (60 por ciento) y el promedio de edad fue 28 años. Los pacientes tuvieron resistencia a una mediana de 5 drogas. Las lesiones cavitarias fueron las más frecuentes (91.8 por ciento) y la lobectomía fue el procedimiento quirúrgico más utilizado (68.4 por ciento). La morbilidad postoperatoria ocurrió en 12,8 por ciento de los casos y la mortalidad post-operatoria fue de 2 por ciento. Los pacientes fueron seguidos hasta 79,3 meses y la curación fue alcanzada en el 77,2 por ciento de los casos. Conclusiones. La cirugía pulmonar coadyuvante es una alternativa efectiva para la curación en pacientes con TB MDR. Esta estrategia debe ser incluida como parte de los programas de tratamiento de la TB MDR.
Treatment for pulmonary tuberculosis (TB) is drug-based but the emergence of drug-resistance has decreased itstherapeutic efficacy. Pulmonary surgery is an important beneficial adjuvant strategy for MDR TB treatment in this context.Objectives. To describe the clinical characteristics results and complications in a series of 304 patients with MDR TBsubmitted to surgical therapy. Material and methods. Between May of 1999 and January of 2007 a total of 336 surgicalinterventions were performed on 304 patients from the National Program of TB Control who, were operated by a surgicalteam of the Ministry of Health in the Hipolito Unanue National Hospital and in a Private Center in Lima. Results. Mostcases were male (60 per cent) and the mean age was 28 years. Patients were resistant to a median of 5 drugs. Cavitarylesions were the most common (91.8 per cent) and lobectomy was the most commonly performed surgical procedure (68.4 per cent). Postoperative morbidity and mortality occurred in 12.8 per cent and 2 per cent respectively. Patients were followed post-operatively for a maximum time of 79.3 months and healing was reached in the 77.2 per cent of cases. Conclusions. Pulmonary adjuvantsurgery on MDR TB patients is an effective alternative for cure. This strategy should be included as part of treatmentprograms for MDR TB.