ABSTRACT
Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.
Subject(s)
Angiotensin I , Anti-Bacterial Agents , Mice, Inbred C57BL , Peptide Fragments , Proto-Oncogene Mas , Pseudomonas Infections , Pseudomonas aeruginosa , Receptors, G-Protein-Coupled , Animals , Angiotensin I/metabolism , Pseudomonas aeruginosa/drug effects , Mice , Pseudomonas Infections/drug therapy , Pseudomonas Infections/metabolism , Pseudomonas Infections/microbiology , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Receptors, G-Protein-Coupled/metabolism , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/metabolism , Cytokines/metabolism , Mice, Knockout , Pneumonia/drug therapy , Pneumonia/metabolism , Pneumonia/microbiology , Male , Lung/microbiology , Lung/metabolism , Lung/pathology , Signal Transduction/drug effects , Neutrophil Infiltration/drug effectsABSTRACT
BACKGROUND: During pneumonia, normal alveolar areas coexist adjacently with consolidated areas, and high inspiratory efforts may predispose to lung damage. To date, no study has evaluated different degrees of effort during Biphasic positive airway pressure (BIVENT) on lung and diaphragm damage in experimental pneumonia, though largely used in clinical setting. We aimed to evaluate lung damage, genes associated with ventilator-induced lung injury (VILI) and diaphragmatic injury, and blood bacteria in pressure-support ventilation (PSV), BIVENT with low and high inspiratory efforts in experimental pneumonia. MATERIAL AND METHODS: Twenty-eight male Wistar rats (mean ± SD weight, 333±78g) were submitted Pseudomonas aeruginosa-induced pneumonia. After 24-h, animals were ventilated for 1h in: 1) PSV; 2) BIVENT with low (BIVENTLow-Effort); and 3) BIVENT with high inspiratory effort (BIVENTHigh-Effort). BIVENT was set at Phigh to achieve VT = 6 ml/kg and Plow at 5 cmH2O (n = 7/group). High- and low-effort conditions were obtained through anaesthetic infusion modulation based on neuromuscular drive (P0.1). Lung mechanics, histological damage score, blood bacteria, and expression of genes related to VILI in lung tissue, and inflammation in diaphragm tissue. RESULTS: Transpulmonary peak pressure and histological damage score were higher in BIVENTHigh-Effort compared to BIVENTLow-Effort and PSV [16.1 ± 1.9cmH2O vs 12.8 ± 1.5cmH2O and 12.5 ± 1.6cmH2O, p = 0.015, and p = 0.010; median (interquartile range) 11 (9-13) vs 7 (6-9) and 7 (6-9), p = 0.021, and p = 0.029, respectively]. BIVENTHigh-Effort increased interleukin-6 expression compared to BIVENTLow-Effort (p = 0.035) as well as expressions of cytokine-induced neutrophil chemoattractant-1, amphiregulin, and type III procollagen compared to PSV (p = 0.001, p = 0.001, p = 0.004, respectively). Tumour necrosis factor-α expression in diaphragm tissue and blood bacteria were higher in BIVENTHigh-Effort than BIVENTLow-Effort (p = 0.002, p = 0.009, respectively). CONCLUSION: BIVENT requires careful control of inspiratory effort to avoid lung and diaphragm damage, as well as blood bacteria. P0.1 might be considered a helpful parameter to optimize inspiratory effort.
Subject(s)
Continuous Positive Airway Pressure/adverse effects , Lung/pathology , Pneumonia, Bacterial/therapy , Pseudomonas Infections/therapy , Pseudomonas aeruginosa/isolation & purification , Ventilator-Induced Lung Injury/etiology , Animals , Diaphragm/pathology , Disease Models, Animal , Male , Pneumonia, Bacterial/pathology , Pseudomonas Infections/pathology , Rats, Wistar , Tidal Volume , Ventilator-Induced Lung Injury/pathologyABSTRACT
BACKGROUND: Melioidosis is an infectious disease caused by Burkholderia pseudomallei. In Mexico, the disease is rarely diagnosed in humans and there is no evidence of simultaneous environmental isolation of the pathogen. Here, we describe clinical profiles of fatal cases of melioidosis in two children, in a region without history of that disease. CASE PRESENTATION: About 48 h before onset of symptoms, patients swam in a natural body of water, and thereafter they rapidly developed fatal septicemic illness. Upon necropsy, samples from liver, spleen, lung, cerebrospinal fluid, and bronchial aspirate tissues contained Burkholderia pseudomallei. Environmental samples collected from the locations where the children swam also contained B. pseudomallei. All the clinical and environmental strains showed the same BOX-PCR pattern, suggesting that infection originated from the area where the patients were swimming. CONCLUSIONS: The identification of B. pseudomallei confirmed that melioidosis disease exists in Sonora, Mexico. The presence of B. pseudomallei in the environment may suggest endemicity of the pathogen in the region. This study highlights the importance of strengthening laboratory capacity to prevent and control future melioidosis cases.
Subject(s)
Melioidosis/complications , Pneumonia, Bacterial/etiology , Adolescent , Burkholderia pseudomallei/isolation & purification , Child , Fatal Outcome , Female , Humans , Male , Melioidosis/diagnosis , Melioidosis/pathology , Melioidosis/physiopathology , Mexico , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/physiopathology , Sepsis/microbiology , SwimmingSubject(s)
Coinfection , Coronavirus Infections/pathology , Lung/pathology , Pneumonia, Viral/pathology , Aged, 80 and over , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Cross Infection/microbiology , Cross Infection/pathology , Enterococcus faecalis , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/pathology , Humans , Lung/diagnostic imaging , Male , Pandemics , Pneumonia, Bacterial/pathology , Pneumonia, Viral/complications , SARS-CoV-2ABSTRACT
Sloths are xenarthrans from Central and South America with a highly adapted morphophysiology. Five of the six known species of sloths are found in Brazil, among which Bradypus torquatus (maned three-toed sloth) is considered a vulnerable species by International Union for Conservation of Nature. Nevertheless, knowledge on health and disease of sloths is very scarce, thus this study aimed to describe macroscopic and microscopic findings in 36 Brazilian sloths. The most common findings included iron storage disorder, probable bacterial pneumonia, gastric and intestinal nematode parasitism, and a presumptive diagnosis of systemic mastocytosis.
Subject(s)
Gastrointestinal Diseases/veterinary , Hemochromatosis/veterinary , Mastocytosis, Systemic/veterinary , Nematoda/isolation & purification , Pneumonia, Bacterial/veterinary , Sloths , Animals , Brazil/epidemiology , Gastrointestinal Diseases/parasitology , Gastrointestinal Diseases/pathology , Hemochromatosis/epidemiology , Hemochromatosis/pathology , Mastocytosis, Systemic/diagnosis , Mastocytosis, Systemic/pathology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathologyABSTRACT
In this article, we report a case series of patients with infections caused by Enterobacteriales coresistant to carbapenems and polymyxins who were treated with ceftazidime/avibactam (CAZ-AVI) salvage therapy on a compassionate-use protocol. We enrolled 29 adult patients in 3 centers that had an infection due to a resistant microorganism and for whom the treatments available were considered ineffective, treated them with CAZ-AVI, and assessed clinical and microbiological cure at the end of treatment and all-cause mortality at 14 days and 30 days. The antimicrobial susceptibility profile was determined using broth microdilution, and total genomic DNA was sequenced. Twelve (41.4%) patients had bacteremia, and 48.3% (14/29) of the infections were treated with combination therapy. All strains were producers of KPC-2 and were susceptible to CAZ-AVI (MIC90, 1 µg/ml). Clinical success was high (24/29 [82.7%; 95% confidence interval, 64.2 to 94.2%]), even for the bacteremic cases (75%). The 14-day and 30-day mortality rates were 9/29 (31%) and 15/29 (51.7%), respectively. The 14-day mortality rate for pneumonia was the same as that for bloodstream infections (33.3%) and although not significant, we found that patients with renal impairment that received adjusted doses of CAZ-AVI had high mortality (4/9 [44%]; P = 0.22). We concluded that CAZ-AVI is an option for the treatment of severe infections due to difficult-to-treat drug-resistant Enterobacteriales.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Azabicyclo Compounds/therapeutic use , Bacteremia/drug therapy , Ceftazidime/therapeutic use , Drug Resistance, Multiple, Bacterial/drug effects , Enterobacteriaceae Infections/drug therapy , Pneumonia, Bacterial/drug therapy , Salvage Therapy/methods , Adult , Bacteremia/microbiology , Bacteremia/mortality , Bacteremia/pathology , Carbapenems/therapeutic use , Drug Combinations , Drug Resistance, Multiple, Bacterial/genetics , Enterobacteriaceae/drug effects , Enterobacteriaceae/enzymology , Enterobacteriaceae/growth & development , Enterobacteriaceae/pathogenicity , Enterobacteriaceae Infections/microbiology , Enterobacteriaceae Infections/mortality , Enterobacteriaceae Infections/pathology , Female , Gene Expression , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/mortality , Pneumonia, Bacterial/pathology , Polymyxins/therapeutic use , Prospective Studies , Survival Analysis , beta-Lactamases/genetics , beta-Lactamases/metabolismABSTRACT
The Amazon river dolphin Inia geoffrensis and tucuxi Sotalia fluviatilis are classified as Data Deficient species. Despite very limited knowledge on health and disease aspects of these species, the main threats to their conservation include incidental mortality in fishing gear, population fragmentation, habitat loss and environmental pollution. It is also suggested that underlying diseases may contribute to their mortality rates. Herein, we retrospectively describe gross and microscopic pulmonary lesions in free-ranging I. geoffrensis (n = 24) and S. fluviatilis (n = 28) found dead. Nearly 85% of the examined animals presented some kind of primary lung disease, wherein the main etiological diagnoses were verminous pneumonia by Halocercus brasiliensis (25%), bacterial pneumonia (25%) and a single case of meconium aspiration syndrome (1.9%). An etiology was not determined in 36.5% (19/52) of animals. These results indicate a high incidence of pulmonary pathology in these species, raising concerns about population impacts and potential zoonotic implications in some instances. These data may provide a scientific basis for future medical and conservation efforts focused on Amazonian dolphins.
Subject(s)
Dolphins , Lung Diseases, Parasitic/veterinary , Pneumonia, Aspiration/veterinary , Pneumonia, Bacterial/veterinary , Animals , Brazil , Female , Lung/pathology , Lung Diseases, Parasitic/epidemiology , Lung Diseases, Parasitic/pathology , Male , Pneumonia, Aspiration/epidemiology , Pneumonia, Aspiration/pathology , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/pathology , Retrospective StudiesABSTRACT
Tuberculosis (TB) remains an important cause of mortality and morbidity. The TB vaccine, BCG, is not fully protective against the adult form of the disease and is unable to prevent its transmission although it is still useful against severe childhood TB. Hence, the search for new vaccines is of great interest. In a previous study, we have shown that proteoliposomes obtained from Mycobacterium smegmatis (PLMs) induced cross reactive humoral and cellular response against Mycobacterium tuberculosis (Mtb) antigens. With the objective to evaluate the protective capability of PLMs, a murine model of progressive pulmonary TB was used. Animals immunized with PLMs with and without alum (PLMs/PLMsAL respectively) showed protection compared to non-immunized animals. Mice immunized with PLMsAL induced similar protection as that of BCG. Animals immunized with BCG, PLMs and PLMsAL showed a significant decrease in tissue damage (percentage of pneumonic area/lung) compared to non-immunized animals, with a more prominent effect in BCG vaccinated mice. The protective effect of the administration of PLMs in mice supports its future evaluation as experimental vaccine candidate against Mtb.
Subject(s)
Mycobacterium smegmatis/immunology , Proteolipids/immunology , Tuberculosis Vaccines , Tuberculosis, Pulmonary/prevention & control , Adjuvants, Immunologic , Alum Compounds , Animals , BCG Vaccine , Bacterial Load , Disease Models, Animal , Disease Progression , Male , Mice, Inbred BALB C , Mycobacterium tuberculosis/growth & development , Mycobacterium tuberculosis/isolation & purification , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/prevention & control , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathologyABSTRACT
High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it.
Subject(s)
Diabetes Mellitus, Experimental/metabolism , Glucose/metabolism , Lung/metabolism , Pneumonia, Bacterial/metabolism , Pseudomonas Infections/metabolism , Sodium-Glucose Transporter 1/genetics , Staphylococcal Infections/metabolism , Alloxan , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/microbiology , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/microbiology , Bronchodilator Agents/pharmacology , Colony Count, Microbial , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/genetics , Gene Expression Regulation , Isoproterenol/pharmacology , Lung/drug effects , Lung/microbiology , Lung/pathology , Male , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/growth & development , Phlorhizin/pharmacology , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/genetics , Pneumonia, Bacterial/pathology , Pseudomonas Infections/complications , Pseudomonas Infections/genetics , Pseudomonas Infections/pathology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/growth & development , Rats , Rats, Wistar , Sodium-Glucose Transporter 1/agonists , Sodium-Glucose Transporter 1/antagonists & inhibitors , Sodium-Glucose Transporter 1/metabolism , Staphylococcal Infections/complications , Staphylococcal Infections/genetics , Staphylococcal Infections/pathologyABSTRACT
A northern Gulf of Mexico (GoM) cetacean unusual mortality event (UME) involving primarily bottlenose dolphins (Tursiops truncatus) in Louisiana, Mississippi, and Alabama began in February 2010 and continued into 2014. Overlapping in time and space with this UME was the Deepwater Horizon (DWH) oil spill, which was proposed as a contributing cause of adrenal disease, lung disease, and poor health in live dolphins examined during 2011 in Barataria Bay, Louisiana. To assess potential contributing factors and causes of deaths for stranded UME dolphins from June 2010 through December 2012, lung and adrenal gland tissues were histologically evaluated from 46 fresh dead non-perinatal carcasses that stranded in Louisiana (including 22 from Barataria Bay), Mississippi, and Alabama. UME dolphins were tested for evidence of biotoxicosis, morbillivirus infection, and brucellosis. Results were compared to up to 106 fresh dead stranded dolphins from outside the UME area or prior to the DWH spill. UME dolphins were more likely to have primary bacterial pneumonia (22% compared to 2% in non-UME dolphins, P = .003) and thin adrenal cortices (33% compared to 7% in non-UME dolphins, P = .003). In 70% of UME dolphins with primary bacterial pneumonia, the condition either caused or contributed significantly to death. Brucellosis and morbillivirus infections were detected in 7% and 11% of UME dolphins, respectively, and biotoxin levels were low or below the detection limit, indicating that these were not primary causes of the current UME. The rare, life-threatening, and chronic adrenal gland and lung diseases identified in stranded UME dolphins are consistent with exposure to petroleum compounds as seen in other mammals. Exposure of dolphins to elevated petroleum compounds present in coastal GoM waters during and after the DWH oil spill is proposed as a cause of adrenal and lung disease and as a contributor to increased dolphin deaths.
Subject(s)
Adrenal Gland Diseases/mortality , Adrenal Glands/pathology , Bottle-Nosed Dolphin , Brucellosis/mortality , Lung/pathology , Petroleum Pollution/adverse effects , Pneumonia, Bacterial/mortality , Adrenal Gland Diseases/etiology , Adrenal Gland Diseases/pathology , Animals , Bottle-Nosed Dolphin/microbiology , Bottle-Nosed Dolphin/virology , Brucellosis/etiology , Brucellosis/microbiology , Brucellosis/pathology , Female , Gulf of Mexico , Louisiana , Male , Morbillivirus Infections/etiology , Morbillivirus Infections/mortality , Morbillivirus Infections/pathology , Morbillivirus Infections/virology , Mortality , Pneumonia, Bacterial/etiology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathologyABSTRACT
Community-acquired methicillin-resistant Staphylococcus aureus is the first cause of skin and soft tissue infections, but can also produce severe diseases such as bacteremia, osteomyelitis and necrotizing pneumonia. Some S. aureus lineages have been described in cases of necrotizing pneumonia worldwide, usually in young, previously healthy patients. In this work, we describe a fatal case of necrotizing pneumonia due to community-acquired methicillin-resistant S. aureus clone ST30-SCCmecIVc-spat019-PVL positive in an immunocompetent adult patient.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Pneumonia, Bacterial/microbiology , Staphylococcal Infections/microbiology , Argentina , Community-Acquired Infections/pathology , Fatal Outcome , Humans , Male , Methicillin-Resistant Staphylococcus aureus/classification , Middle Aged , Necrosis , Pneumonia, Bacterial/pathology , Staphylococcal Infections/pathologyABSTRACT
The aim of the present work is to provide a better comprehension of the pneumonia-induced sepsis model through temporal evaluation of several parameters, and thus identify the main factors that determine mortality in this model. Klebsiella pneumoniae was inoculated intratracheally in anesthetized Swiss male mice. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Six, 24 and 48 h after inoculation, animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF-α and IL-1ß levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS-2 expression appeared late after bacteria inoculation, whereas levels of NOS-1 and NOS-3 were unchanged. The high NOS-2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. This study shows that K. pneumoniae inoculation induces a systemic inflammatory response and cardiovascular alterations, which endures at least until 48 h. K. pneumoniae-induced lung infection is a clinically relevant animal model of sepsis and a better understanding of this model may help to increase the knowledge about sepsis pathophysiology.
Subject(s)
Klebsiella Infections/pathology , Klebsiella pneumoniae/immunology , Pneumonia, Bacterial/pathology , Sepsis/pathology , Animals , Bacterial Load , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Disease Models, Animal , Humans , Klebsiella Infections/immunology , Klebsiella Infections/mortality , Leukocytes , Lung/immunology , Lung/metabolism , Male , Mice , Myocardium/immunology , Myocardium/metabolism , Nitrates/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Nitrites/metabolism , Pneumonia, Bacterial/immunology , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/mortality , Sepsis/immunology , Sepsis/microbiology , Sepsis/mortality , Spleen/immunology , Spleen/metabolismABSTRACT
The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC) and avian fecal (A(fecal)) Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic A(fecal) strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.). Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE), terminal deoxynucleotidyl dUTP nick end labeling (TUNEL) for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas.
Subject(s)
Chickens/metabolism , Escherichia coli Infections/metabolism , Escherichia coli Infections/veterinary , Escherichia coli , Lung/metabolism , Macrophages/metabolism , Poultry Diseases/metabolism , Animals , Antibodies, Bacterial/metabolism , Apoptosis , Avian Proteins , Caspase 3/metabolism , Caspase 7/metabolism , Escherichia coli Infections/pathology , Lung/microbiology , Lung/pathology , Macrophages/microbiology , Macrophages/pathology , Pneumonia, Bacterial/metabolism , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial/veterinary , Poultry Diseases/microbiology , Poultry Diseases/pathology , Time FactorsABSTRACT
BACKGROUND: Community-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. METHOD: We 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. RESULTS: Thirty 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. CONCLUSION: The 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.
Subject(s)
Biomarkers/blood , Community-Acquired Infections/pathology , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/pathology , Receptor for Advanced Glycation End Products/blood , Sepsis/pathology , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Community-Acquired Infections/diagnosis , Community-Acquired Infections/mortality , Female , Humans , Influenza A virus , Male , Middle Aged , Pneumonia, Bacterial/mortality , Prognosis , Sepsis/diagnosis , Sepsis/mortalityABSTRACT
Se presentan 4 casos de actinomicosis pulmonar en pacientes mayores de 40 años, 2 de ellos con enfermedad pulmonar obstructiva crónica (EPOC), que mostraron un aumento de la tos productiva, episodios de disnea, hemoptisis y fiebre de larga evolución. En las radiografías de tórax de rutina se observaban imágenes segmentarias de consolidación aérea, sugestivas de cuadros neumónicos no resueltos o neoplasia. La tomografía axial computarizada (TAC) mostró hallazgos similares a los anteriores. Los cultivos de esputo y las pruebas de Mantoux fueron repetidamente negativos. Debido a la mala evolución de los pacientes y a los hallazgos radiológicos, se practicó una punción-aspiración con aguja fina (PAAF) para descartar neoplasia. En la citología se observaron conglomerados tridimensionales, de bordes filamentosos y aspecto algodonoso compatibles con Actinomyces. El tratamiento antibiótico produjo la mejoría del cuadro clínico y el seguimiento demostró la desaparición de las opacidades radiológicas. Actualmente, la actinomicosis pulmonar es infrecuente y la sintomatología inespecífica, por lo que puede confundirse con procesos neoplásicos. Por tanto, en pacientes con factores de riesgo, síntomas de neumonía subaguda e imágenes radiológicas de consolidación del parénquima es aconsejable considerar la posibilidad de actinomicosis pulmonar. Es una enfermedad tratable y su correcto diagnóstico mediante la PAAF evita al paciente pruebas diagnósticas más agresivas, retrasos en el diagnóstico y le permite una cura completa con tratamiento antibiótico.
We present four cases of pulmonary actinomycosis in patients over 40 years of age, two of them with chronic obstructive pulmonary disease (COPD), showing an increase in productive cough, episodes of dyspnea, hemoptysis and long-term fever. Routine chest radiographs revealed segmental air-space consolidation, suggestive of unresolved pneumonia or neoplasm. Computed tomography (CT) scan showed similar findings to the ones previously described. Sputum cultures for mycobacteriae and Mantoux tests were constantly negative. Due to the poor clinical and radiodological outcome of the patients, a fine needle aspiration (FNA) was made to rule out a neoplasm. Tridimensional filamentous colonies of Actinomyces were observed in cytology. Antibiotic treatment resulted in an improvement of symptoms. The follow-up showed a decrease of the consolidation areas. Pulmonary actinomycosis is rare nowadays and clinical symptoms are unspecific and can be confused with a neoplasm process. Therefore, in patients with risk factors, symptoms of subacute pneumonia and radiologic findings of consolidation, it is advisable to consider pulmonary actinomycosis as a diagnostic possibility. It is a treatable disease and its correct diagnosis by FNA, avoids performing invasive diagnostic tests, delays in the diagnosis and allows for a complete cure by antibiotic therapy.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Actinomycosis/diagnosis , Biopsy, Fine-Needle , Pneumonia, Bacterial/diagnosis , Actinomycosis/complications , Actinomycosis/pathology , Actinomycosis , Alcoholism/complications , Diagnosis, Differential , Disease Susceptibility , /complications , Lung Neoplasms/diagnosis , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/pathology , Pneumonia, Bacterial , Pulmonary Disease, Chronic Obstructive/complications , Tomography, X-Ray ComputedABSTRACT
We present four cases of pulmonary actinomycosis in patients over 40 years of age, two of them with chronic obstructive pulmonary disease (COPD), showing an increase in productive cough, episodes of dyspnea, hemoptysis and long-term fever. Routine chest radiographs revealed segmental air-space consolidation, suggestive of unresolved pneumonia or neoplasm. Computed tomography (CT) scan showed similar findings to the ones previously described. Sputum cultures for mycobacteriae and Mantoux tests were constantly negative. Due to the poor clinical and radiodological outcome of the patients, a fine needle aspiration (FNA) was made to rule out a neoplasm. Tridimensional filamentous colonies of Actinomyces were observed in cytology. Antibiotic treatment resulted in an improvement of symptoms. The follow-up showed a decrease of the consolidation areas. Pulmonary actinomycosis is rare nowadays and clinical symptoms are unspecific and can be confused with a neoplasm process. Therefore, in patients with risk factors, symptoms of subacute pneumonia and radiologic findings of consolidation, it is advisable to consider pulmonary actinomycosis as a diagnostic possibility. It is a treatable disease and its correct diagnosis by FNA, avoids performing invasive diagnostic tests, delays in the diagnosis and allows for a complete cure by antibiotic therapy.
Subject(s)
Actinomycosis/diagnosis , Biopsy, Fine-Needle , Pneumonia, Bacterial/diagnosis , Actinomycosis/complications , Actinomycosis/diagnostic imaging , Actinomycosis/pathology , Adult , Aged , Alcoholism/complications , Diabetes Mellitus, Type 2/complications , Diagnosis, Differential , Disease Susceptibility , Female , Humans , Lung Neoplasms/diagnosis , Male , Middle Aged , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/diagnostic imaging , Pneumonia, Bacterial/pathology , Pulmonary Disease, Chronic Obstructive/complications , Tomography, X-Ray ComputedABSTRACT
OBJETIVO: Descrever os resultados do tratamento cirúrgico de crianças com pneumonia necrosante. MÉTODOS: Análise retrospectiva dos prontuários de 20 crianças diagnosticadas com pneumonia necrosante e submetidas ao tratamento cirúrgico nos serviços de cirurgia torácica de dois hospitais na cidade de Manaus (AM) entre março de 1997 e setembro de 2008. Dados referentes a idade, sexo, agente etiológico, motivos da indicação cirúrgica, tipo de ressecção cirúrgica realizada e complicações pós-operatórias foram compilados. RESULTADOS: Dos 20 pacientes analisados, 12 (60 por cento) eram do sexo feminino. A média de idade dos pacientes foi de 30 meses. Os agentes etiológicos mais encontrados foram Staphylococcus aureus, em 5 pacientes (25 por cento), e Klebsiella sp., em 2 (10 por cento). Os motivos de indicação cirúrgica foram sepse, em 16 pacientes (80 por cento), e fístula broncopleural, em 4 (20 por cento). Os tipos de procedimentos cirúrgicos realizados foram lobectomia, em 12 pacientes (60 por cento), segmentectomia, em 7 (35 por cento), e bilobectomia, em 1 (5 por cento). Além desses procedimentos, 8 pacientes (40 por cento) foram submetidos à descorticação pulmonar. As complicações pós-operatórias foram as seguintes: fístula broncopleural, em 4 pacientes (20 por cento); empiema, em 1 (5 por cento); pneumatocele, em 1 (5 por cento); e flebite em membro superior esquerdo, em 1 (5 por cento). Quatro pacientes (20 por cento) morreram. CONCLUSÕES: Pacientes com evidências de necrose pulmonar devem ser considerados para a ressecção cirúrgica, que está indicada em casos graves de sepse, fístula broncopleural de alto débito ou insuficiência respiratória aguda que não respondem ao tratamento clínico.
OBJECTIVE: To describe the results of the surgical treatment of children with necrotizing pneumonia. METHODS: A retrospective analysis of the medical charts of 20 children diagnosed with necrotizing pneumonia and submitted to surgical treatment between March of 1997 and September of 2008 in the thoracic surgery departments of two hospitals in the city of Manaus, Brazil. We compiled data regarding age, gender, etiologic agent, indications for surgery, type of surgical resection performed, and postoperative complications. RESULTS: The mean age of the patients was 30 months. Of the 20 patients studied, 12 (60 percent) were female. The most common etiologic agents were Staphylococcus aureus, in 5 patients (25 percent), and Klebsiella sp., in 2 (10 percent). The indications for surgery were sepsis, in 16 patients (80 percent), and bronchopleural fistula, in 4 (20 percent). The types of surgical procedures performed were lobectomy, in 12 patients (60 percent), segmentectomy, in 7 (35 percent), and bilobectomy, in 1 (5 percent). There were 8 patients (40 percent) who also underwent decortication. The postoperative complications were as follows: bronchopleural fistula, in 4 patients (20 percent); empyema, in 1 (5 percent); pneumatocele, in 1 (5 percent); and phlebitis of the left arm, in 1 (5 percent). Four (20 percent) of the patients died. CONCLUSIONS: Surgical resection should be considered in patients with evidence of pulmonary necrosis. Resection is indicated in cases of severe sepsis, high output bronchopleural fistula, or acute respiratory failure that are refractory to clinical treatment.
Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Lung/pathology , Pneumonia, Bacterial/surgery , Respiratory Tract Diseases/etiology , Thoracic Surgical Procedures/adverse effects , Necrosis , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/pathology , Retrospective Studies , Respiratory Tract Diseases/classification , Thoracic Surgical Procedures/classificationABSTRACT
We report a 58-year-old female presenting with fever and vomiting. The initial laboratory examination disclosed two blood cultures that were positive for Streptococcus Pyogenes. An abdominal CAT scan showed a right basal pneumonia. The patient was treated with antimicrobials and discharged with oral cefadroxil for 21 days. One month after discharge she was asymptomatic and with a normal C reactive protein. Pneumonia is an important differential diagnosis in unknown origin bacteremia caused by Streptococcus Pyogenes. It may have a fulminant evolution and may complicate with abscess and empyema.
Subject(s)
Pneumonia, Bacterial/microbiology , Streptococcus pyogenes/isolation & purification , Diagnosis, Differential , Female , Humans , Middle Aged , Pneumonia, Bacterial/pathologyABSTRACT
We report a 58-year-old female presenting with fever and vomiting. The initial laboratory examination disclosed two blood cultures that were positive for Streptococcus Pyogenes. An abdominal CAT scan showed a right basal pneumonia. The patient was treated with antimicrobials and discharged with oral cefadroxil for 21 days. One month after discharge she was asymptomatic and with a normal C reactive protein. Pneumonia is an important differential diagnosis in unknown origin bacteremia caused by Streptococcus Pyogenes. It may have a fulminant evolution and may complicate with abscess and empyema.