Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections.

Bacterial infections are re-emerging as substantial threats to global health due to the limited selection of antibiotics that are capable of overcoming antibiotic-resistant strains. By deterring such mutations whilst minimizing the need to develop new pathogen-specific antibiotics, immunotherapy offers a broad-spectrum therapeutic solution against bacterial infections. In particular, pathology resulting from excessive immune response (i.e. fibrosis, necrosis, exudation, breath impediment) contributes significantly to negative disease outcome. Herein, we present a nanoparticle that is targeted to activated macrophages and loaded with siRNA against the Irf5 gene. This formulation is able to induce >80% gene silencing in activated macrophages in vivo, and it inhibits the excessive inflammatory response, generating a significantly improved therapeutic outcome in mouse models of bacterial infection. The versatility of the approach is demonstrated using mice with antibiotic-resistant Gram-positive (methicillin-resistant Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) muscle and lung infections, respectively. Effective depletion of the Irf5 gene in macrophages is found to significantly improve the therapeutic outcome of infected mice, regardless of the bacteria strain and type.

Neumonía estafilocócica complicada en un paciente pediátrico: a propósito de un caso clínico / Stafilocócica pneumony complicated in a pediatric patient: on the purpose of a clinical case

La neumonía es definida por la Organización Mundial de Salud (OMS) como una infección respiratoria aguda que afecta a los alvéolos pulmonares, dificultando la respiración y absorción de oxígeno afectando a la población infantil. Por eso se propuso analizar la neumonía estafilocócica complicada con enfoque clínico, radiológico y tratamiento en el paciente pediátrico para establecer elementos que ayuden a la elaboración de protocolos de diagnóstico y tratamiento. Se realizó un estudio de tipo documental, observacional y analítico mediante la entrevista directa con el paciente y familiares y el análisis clínico de los signos y síntomas presentados por el paciente. Mediante la valoración clínico, radiológico y oportuno tratamiento en el paciente pediátrico con neumonía estafilocócica complicada, se logró establecer elementos que podrán ayudar a la elaboración de un protocolo de diagnóstico y tratamiento de dicha patología(AU)

Pneumonia is defined by the World Health Organization (WHO) as an acute respiratory infection that affects the pulmonary alveoli, making it difficult to breathe and absorb oxygen, affecting the child population. Therefore, it was proposed to analyze complicated staphylococcal pneumonia with a clinical, radiological and treatment approach in the pediatric patient to establish elements that help to develop diagnostic and treatment protocols. A documentary, observational and analytical study was conducted through a direct interview with the patient and family members and the clinical analysis of the signs and symptoms presented by the patient. By means of the clinical, radiological evaluation and timely treatment in the pediatric patient with complicated staphylococcal pneumonia, it was possible to establish elements that may help to elaborate a protocol for the diagnosis and treatment of said pathology(AU)

Oral administration of Lactobacillus acidophilus alleviates exacerbations in Pseudomonas aeruginosa and Staphylococcus aureus pulmonary infections.

Staphylococcus aureus and Pseudomonas aeruginosa are largely the cause of morbidity and mortality in both hospital and community settings. These pathogens remain the important cause of pulmonary infections in patients with cystic fibrosis with a worldwide prevalence. Although, antibiotics are efficient measures of treating bacterial lung infections, the occurrence of antibiotic resistant bacteria has been encouraging the researchers to explore novel therapeutic approaches. It has been discovered that certain lactic acid bacteria possess protective effects against bacterial and viral respiratory infections. The aim of present study was to investigate the capability of orally administered L. acidophilus to ameliorate S. aureus and P. aeruginosa pulmonary infections. Animals were exposed to aerosol of pathogenic suspension. After 24 hours of infection, L. acidophilus treatment was administered orally for 7 consecutive days. Evaluation of tissue bacteriology, histopathology and serum cytokinomics were performed. In parallel, human alveolar A549 cells were utilized to determine possible role of probiotic on pulmonary infections. Oral administration of L. acidophilus significantly (P<0.05) alleviate lung bacterial load and severity of infection as depicted by our histopathological studies. Results obtained from cytokinomics revealed that pro-inflammatory cytokines induced due to lung infection were suppressed in oral probiotic treatment groups. In addition, treatment with L. acidophilus induced murine lung anti inflammatory, IL-10 cytokine level. Current work suggests that orally administered L. acidophilus in mice is able to attenuate S. aureus and P. aeruginosa induced lung cytotoxicity by modulation of host immune response.

Mesenchymal stem cells significantly improved treatment effects of Linezolid on severe pneumonia in a rabbit model.

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

Childhood pneumonia in low-and-middle-income countries: An update.

OBJECTIVES: To review epidemiology, aetiology and management of childhood pneumonia in low-and-middle-income countries. DESIGN: Review of published English literature between 2013 and 2019. RESULTS: Pneumonia remains a major cause of morbidity and mortality. Risk factors include young age, malnutrition, immunosuppression, tobacco smoke or air pollution exposure. Better methods for specimen collection and molecular diagnostics have improved microbiological diagnosis, indicating that pneumonia results from several organisms interacting. Induced sputum increases microbiologic yield for Bordetella pertussis or Mycobacterium tuberculosis, which has been associated with pneumonia in high TB prevalence areas. The proportion of cases due to Streptococcus pneumoniae and Haemophilus influenzae b has declined with new conjugate vaccines; Staphylococcus aureus and H. influenzae non-type b are the commonest bacterial pathogens; viruses are the most common pathogens. Effective interventions comprise antibiotics, oxygen and non-invasive ventilation. New vaccines have reduced severity and incidence of disease, but disparities exist in uptake. CONCLUSION: Morbidity and mortality from childhood pneumonia has decreased but a considerable preventable burden remains. Widespread implementation of available, effective interventions and development of novel strategies are needed.

Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus.

The incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system's response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia.

Parenteral irons versus transfused red blood cells for treatment of anemia during canine experimental bacterial pneumonia.

BACKGROUND: No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy. STUDY DESIGN AND METHODS: Purpose-bred beagles (n = 42) with experimental Staphylococcus aureus pneumonia rendered anemic were randomized to be transfused RBCs stored for 7 days or one of two IV iron preparations (7 mg/kg), iron sucrose, a widely used preparation, or ferumoxytol, a newer formulation that blunts circulating iron levels. RESULTS: Both irons increased the alveolar-arterial oxygen gradient at 24 to 48 hours (p = 0.02-0.001), worsened shock at 16 hours (p = 0.02-0.003, respectively), and reduced survival (transfusion 56%; iron sucrose 8%, p = 0.01; ferumoxytol 9%, p = 0.04). Compared to fresh RBC transfusion, plasma iron measured by non-transferrin-bound iron levels increased with iron sucrose at 7, 10, 13, 16, 24, and 48 hours (p = 0.04 to p < 0.0001) and ferumoxytol at 7, 24, and 48 hours (p = 0.04 to p = 0.004). No significant differences in cardiac filling pressures or performance, hemoglobin (Hb), or cell-free Hb were observed. CONCLUSIONS: During canine experimental bacterial pneumonia, treatment of mild anemia with IV iron significantly increased free iron levels, shock, lung injury, and mortality compared to transfusion of fresh RBCs. This was true for iron preparations that do or do not blunt circulating free iron level elevations. These findings suggest that treatment of anemia with IV iron during infection should be undertaken with caution.

Lentiviral Vector Gene Therapy Protects XCGD Mice From Acute Staphylococcus aureus Pneumonia and Inflammatory Response.

Chronic granulomatous disease (CGD) is a primary immunodeficiency due to a deficiency in one of the subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD patients are characterized by an increased susceptibility to bacterial and fungal infections, and to granuloma formation due to the excessive inflammatory responses. Several gene therapy approaches with lentiviral vectors have been proposed but there is a lack of in vivo data on the ability to control infections and inflammation. We set up a mouse model of acute infection that closely mimic the airway infection in CGD patients. It involved an intratracheal injection of a methicillin-sensitive reference strain of S. aureus. Gene therapy, with hematopoietic stem cells transduced with regulated lentiviral vectors, restored the functional activity of NADPH oxidase complex (with 20-98% of dihydrorhodamine positive granulocytes and monocytes) and saved mice from death caused by S. aureus, significantly reducing the bacterial load and lung damage, similarly to WT mice even at low vector copy number. When challenged, gene therapy-treated XCGD mice showed correction of proinflammatory cytokines and chemokine imbalance at levels that were comparable to WT. Examined together, our results support the clinical development of gene therapy protocols using lentiviral vectors for the protection against infections and inflammation.

Successful treatment of Panton-Valentine leukocidin-expressing Staphylococcus aureus-associated pneumonia co-infected with influenza using extracorporeal membrane oxygenation.

BACKGROUND: Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and lung necrosis. Managing respiratory failure and acute respiratory distress syndrome secondary to PVL-expressing Staphylococcus aureus pneumonia and its associated lung necrosis with mechanical ventilation is challenging. We report a patient with life-threatening PVL-expressing S. aureus-associated pneumonia who was rescued using extracorporeal membrane oxygenation (ECMO). CASE REPORT: We examined the case of a woman who presented to our Emergency Department with septic shock due to PVL-expressing S. aureus-associated pneumonia. A 27-year-old Filipino woman was transferred to our hospital due to severe dyspnea, hemosputum, and high-grade fever. She had a medical history of osteosarcoma of the leg and hyperthyroidism. On arrival, her vital signs indicated septic shock, with a white blood cell count of 3.5×10(3)/µl. Because a Gram stain of her sputum indicated SA, therapy with antibiotics, including meropenem and vancomycin, was started. Hypoxemia necessitated intubation and ventilation. Because the patient's PaO2/FiO2 remained less than 60 mmHg and her blood pressure was unstable despite aggressive conventional management, venoarterial ECMO was administered approximately 11 h after her arrival. The ECMO circuit was changed to veno-venous ECMO on day 7 and the patient was successfully weaned off ECMO after 12 days of treatment. She was discharged from the hospital 104 days after admission. CONCLUSION: This case demonstrates that early induction of ECMO support can be a reasonable therapeutic option for PVL-S. aureus-associated pneumonia. This patient's successful outcome might be attributable to early establishment of ECMO to prevent ventilation-induced lung injury.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia.

In a randomized controlled blinded trial, 2-year-old purpose-bred beagles (n = 24), with Staphylococcus aureus pneumonia, were exchanged-transfused with either 7- or 42-day-old washed or unwashed canine universal donor blood (80 mL/kg in 4 divided doses). Washing red cells (RBC) before transfusion had a significantly different effect on canine survival, multiple organ injury, plasma iron, and cell-free hemoglobin (CFH) levels depending on the age of stored blood (all, P < .05 for interactions). Washing older units of blood improved survival rates, shock score, lung injury, cardiac performance and liver function, and reduced levels of non-transferrin bound iron and plasma labile iron. In contrast, washing fresh blood worsened all these same clinical parameters and increased CFH levels. Our data indicate that transfusion of fresh blood, which results in less hemolysis, CFH, and iron release, is less toxic than transfusion of older blood in critically ill infected subjects. However, washing older blood prevented elevations in plasma circulating iron and improved survival and multiple organ injury in animals with an established pulmonary infection. Our data suggest that fresh blood should not be washed routinely because, in a setting of established infection, washed RBC are prone to release CFH and result in worsened clinical outcomes.

Immunity to Staphylococcus aureus secreted proteins protects rabbits from serious illnesses.

Staphylococcus aureus causes significant illnesses throughout the world, including toxic shock syndrome (TSS), pneumonia, and infective endocarditis. Major contributors to S. aureus illnesses are secreted virulence factors it produces, including superantigens and cytolysins. This study investigates the use of superantigens and cytolysins as staphylococcal vaccine candidates. Importantly, 20% of humans and 50% of rabbits in our TSS model cannot generate antibody responses to native superantigens. We generated three TSST-1 mutants; G31S/S32P, H135A, and Q136A. All rabbits administered these TSST-1 toxoids generated strong antibody responses (titers>10,000) that neutralized native TSST-1 in TSS models, both in vitro and in vivo. These TSST-1 mutants lacked detectable residual toxicity. Additionally, the TSST-1 mutants exhibited intrinsic adjuvant activity, increasing antibody responses to a second staphylococcal antigen (ß-toxin). This effect may be due to TSST-1 mutants binding to the immune co-stimulatory molecule CD40. The superantigens TSST-1 and SEC and the cytolysin α-toxin are known to contribute to staphylococcal pneumonia. Immunization of rabbits against these secreted toxins provided complete protection from highly lethal challenge with a USA200 S. aureus strain producing all three exotoxins; USA200 strains are common causes of staphylococcal infections. The same three exotoxins plus the cytolysins ß-toxin and γ-toxin contribute to infective endocarditis and sepsis caused by USA200 strains. Immunization against these five exotoxins protected rabbits from infective endocarditis and lethal sepsis. These data suggest that immunization against toxoid proteins of S. aureus exotoxins protects from serious illnesses, and concurrently superantigen toxoid mutants provide endogenous adjuvant activity.

[Necrotizing community-acquired Staphylococcus aureus pneumonia]. / Pneumopathie aiguë nécrosante à Staphylocoque doré sécréteur de la toxine de Panton-Valentine.

Acute necrotizing pneumonia due to Panton-Valentine secreting Staphylococcus aureus was identified as a clinical entity by Gilet et al., in 2002. This severe acute necrotizing pneumonia occurring in previously healthy children and adolescents can lead to a rapid fatal outcome even if quickly diagnosed and treated. We report the case of a healthy 10-year-old girl presenting with hemorrhagic necrotizing pneumonia and septic shock. Bacteriological cultures yielded methicillin-susceptible Staphylococcus aureus. The course of the disease was characterized by recurrent uncontrolled hemoptysia leading to refractory hypoxemia. The details of the hospital stay are presented. We discuss the clinical features of the disease and describe recent epidemiologic data and Panton-Valentine toxin research results as well as primary hospital care and treatment.

An evaluation of the emerging vaccines and immunotherapy against staphylococcal pneumonia in children.

BACKGROUND: Staphylococcus aureus is a commensal of human skin and nares. It is also one of the leading nosocomial pathogens in both developed and developing countries and is responsible for a wide range of life threatening infections, especially in patients who are immunocompromised, post-surgery, undergoing haemodialysis and those who are treated with catheters and ventilators. Over the past two decades, the incidence of nosocomial staphylococcal infections has increased dramatically. Currently there are at least seven vaccine and immunotherapy candidates against S. aureus in the developmental phase targeting both active and passive immunization. METHODS: We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against Staphylococcus aureus relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies) to participate. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. RESULTS: The panel of experts expressed low levels of optimism (score around or below 50%) on the criteria of answerability, efficacy, maximum disease burden reduction potential, low cost of production, low cost of implementation and affordability; moderate levels of optimism (scores around 60 to 80%) that these vaccines could be developed at a low cost, and thus on the deliverability, sustainability and impact on equity; and high levels of optimism (scores above 80%) regarding acceptable of such a product to both the end-users and health workers. While assessing the candidates for passive immunization against S.aureus, the experts were poorly optimistic regarding low production cost, low implementation cost, efficacy, deliverability, sustainability, affordability and equity; moderately optimistic regarding answerability and acceptability to health workers and end-users. They were of the opinion that these interventions would have only a modest impact (3 to 5%) on the burden of childhood pneumonia. . CONCLUSION: In order to provide an effective vaccine against S. aureus, a number of unresolved issues in vaccine development relating to optimal antigenic target identification, criteria for acceptable efficacy, identification of target population, commercial development limitations, optimal timing of immunization strategy, storage, cold chain requirements and cost need to be addressed properly. There is still a great deal unknown about the complex interaction between S. aureus and the human host. However, given the nature of S. aureus and the lessons learned from the recent failure of two emerging vaccines, it is clear that a multi-component vaccine is essential. Combating only one virulence factor is not sufficient in the human host but finding the right combination of factors will be very challenging.

Surgical treatment for chronic type A aortic dissection and aortic regurgitation in a patient with a tracheostoma.

We successfully performed aortic root replacement and partial aortic arch replacement by a T-shaped sternotomy at the second intercostal space in a patient who had undergone tracheotomy for respiratory insufficiency and cardiac failure caused by methicillin-resistant Staphylococcus aureus pneumonia during preservation treatment of chronic type A aortic dissection and aortic regurgitation.

Clinical and economic outcomes in patients with community-acquired Staphylococcus aureus pneumonia.

BACKGROUND: While the clinical and economic consequences of S. aureus pneumonia in healthcare settings have been well documented, much less is known about community-acquired S. aureus pneumonia (CAP). METHODS: We retrospectively identified all patients admitted to a large US urban teaching hospital between January 2005 and May 2008 with pneumonia and positive blood or respiratory cultures for S. aureus within 48 hours of admission. Patients with suspected healthcare-associated pneumonia (HCAP) were excluded from the study sample, using established criteria (eg, recent hospitalization, admission from nursing home, hemodialysis). Patients were designated as having methicillin-resistant (MRSA) or methicillin-susceptible (MSSA) CAP based on initial S. aureus isolates. Initial therapy was designated "appropriate" vs. "inappropriate" based on expected susceptibility of the organism to the regimen received. RESULTS: We identified a total of 128 CAP patients with S. aureus isolates; mean (standard deviation [SD]) age was 60 (17) years. A total of 55 patients (43%) had initial cultures positive for MRSA. Patients with MRSA CAP were more likely to receive inappropriate initial therapy (24 [44%] vs. 13 [18%] for MSSA; P = 0.002). Approximately 25% of all patients underwent surgery for pneumonia, 69% received mechanical ventilation, 79% were admitted to intensive care unit (ICU), and 24% died in hospital. Mean (SD) length of stay was 17.0 (15.7) days, and total hospital charges averaged $127,922 ($154,605) per patient; there were no significant differences between patients with MRSA vs. MSSA CAP. CONCLUSION: Outcomes are poor, hospital stays are long, and costs of care are high in patients with S. aureus CAP, and do not differ between those with MRSA vs. MSSA.

Necrotizing pneumonia in children submitted to thoracoscopy due to pleural empyema: incidence, treatment and clinical evolution.

OBJECTIVE: To assess the incidence of necrotizing pneumonia (NP) in children submitted to thoracoscopy, comparing patients with and without NP in terms of the presentation and clinical evolution. METHODS: A retrospective study of children with pleural empyema submitted to thoracoscopy. Thoracoscopy was performed in patients not previously submitted to thoracic drainage and in whom there was evidence of loculated effusion or pneumothorax, as well as in those previously submitted to thoracic drainage and in whom there was persistent pneumothorax or fever with purulent discharge. On the basis of the thoracoscopy findings, patients were distributed into two groups: those with NP (NP group) and those without (no-NP group). RESULTS: The study sample comprised 52 patients. Of the 24 patients with NP, 19 (79%) had undergone thoracic drainage prior to thoracoscopy, 11 (46%) presented with pneumothorax, and 16 (67%) developed bronchopleural fistula. In the NP group, the median drainage time and the median length of hospital stay were 18 and 19 days, respectively. Of the 28 patients without NP, 10 (36%) had undergone thoracic drainage prior to thoracoscopy, 9 (32%) presented pneumothorax, and 5 (18%) developed bronchopleural fistula. In the no-NP group, the median drainage time and the median length of hospital stay were 6 and 10 days, respectively. CONCLUSIONS: Pneumothorax should raise the suspicion of NP. Early thoracoscopy can be a valuable treatment option for NP in children because it hastens recovery in comparison with the medical treatment alone and avoids extensive late thoracotomy lung resections.

Pneumonia necrosante em crianças submetidas à toracoscopia por empiema pleural: incidência, tratamento e evolução clínica / Necrotizing pneumonia in children submitted to thoracoscopy due to pleural empyema: incidence, treatment and clinical evolution

OBJETIVO: Analisar a incidência de pneumonia necrosante (PN) em crianças submetidas a toracoscopia e comparar pacientes com e sem PN em relação às diferentes apresentações e evolução clínica. MÉTODOS: Estudo retrospectivo de crianças portadoras de empiema e submetidas a toracoscopia. A toracoscopia foi realizada em pacientes não submetidos a drenagem torácica prévia e evidência de derrame septado ou pneumotórax, assim como naqueles submetidos previamente a drenagem torácica e pneumotórax persistente ou febre e secreção purulenta. Baseado na presença de PN durante a toracoscopia, os pacientes foram divididos em dois grupos: com PN e sem PN. RESULTADOS: Participaram do estudo 52 pacientes. Dos 24 pacientes com PN, 19 (79 por cento) foram submetidos a drenagem torácica anterior à toracoscopia, 11 (46 por cento) apresentaram pneumotórax, e 16 (67 por cento) evoluíram com fístula broncopleural. Neste grupo, as medianas do tempo de drenagem e de hospitalização foram, respectivamente, 18 e 19 dias. Dos 28 pacientes sem PN, 10 (36 por cento) foram submetidos a drenagem torácica anterior à toracoscopia, 9 (32 por cento) apresentaram pneumotórax, e 5 (18 por cento) evoluíram com fístula broncopleural. Neste grupo, as medianas do tempo médio de drenagem e de hospitalização foram, respectivamente, 6 e 10 dias. CONCLUSÕES: A PN deve ser suspeitada na presença de pneumotórax. A toracoscopia precoce pode ser uma opção terapêutica de grande valor na PN da infância, pois acelera a recuperação quando comparada ao tratamento médico isolado e evita ressecções pulmonares extensas da toracotomia tardia.

OBJECTIVE: To assess the incidence of necrotizing pneumonia (NP) in children submitted to thoracoscopy, comparing patients with and without NP in terms of the presentation and clinical evolution. METHODS: A retrospective study of children with pleural empyema submitted to thoracoscopy. Thoracoscopy was performed in patients not previously submitted to thoracic drainage and in whom there was evidence of loculated effusion or pneumothorax, as well as in those previously submitted to thoracic drainage and in whom there was persistent pneumothorax or fever with purulent discharge. On the basis of the thoracoscopy findings, patients were distributed into two groups: those with NP (NP group) and those without (no-NP group). RESULTS: The study sample comprised 52 patients. Of the 24 patients with NP, 19 (79 percent) had undergone thoracic drainage prior to thoracoscopy, 11 (46 percent) presented with pneumothorax, and 16 (67 percent) developed bronchopleural fistula. In the NP group, the median drainage time and the median length of hospital stay were 18 and 19 days, respectively. Of the 28 patients without NP, 10 (36 percent) had undergone thoracic drainage prior to thoracoscopy, 9 (32 percent) presented pneumothorax, and 5 (18 percent) developed bronchopleural fistula. In the no-NP group, the median drainage time and the median length of hospital stay were 6 and 10 days, respectively. CONCLUSIONS: Pneumothorax should raise the suspicion of NP. Early thoracoscopy can be a valuable treatment option for NP in children because it hastens recovery in comparison with the medical treatment alone and avoids extensive late thoracotomy lung resections.

[Two cases of severe necrotizing pneumonia caused by community-acquired methicillin-resistant Staphylococcus aureus].

We present 2 cases with severe necrotizing pneumonia due to community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection. The patients were a 89-year-old man and a male student of 15 years of age. Chest X-rays and CT scans demonstrated multiple consolidations with cavitary lesions showing necrotizing pneumonia. MRSA strains were isolated from the sputum cultures on admission in these patients who did not have any established risk factors for MRSA infections such as history of hospitalization, surgery, hemodialysis, the presence of a permanent indwelling catheter or percutaneous medical device, and residence in a long-term care facility. These patients thus satisfied the international criteria for CA-MRSA presented by the Centers for Disease Control and Prevention (CDC). Unfortunately, the first case died of CA-MRSA pneumonia in spite of intensive treatments including anti-MRSA antibiotics. Unlike the severe CA-MRSA cases in western countries, Panton-Valentine leukocidin (PVL) genes were not detected in the present cases, suggesting that factors other than PVL had a significant effect on the severity of necrotizing pneumonia. To the best of our knowledge, this is the first report of severe necrotizing pneumonia caused by CA-MRSA in Japan.