Role of systemic immune-inflammatory index and systemic inflammatory response index in predicting the diagnosis of necrotizing pneumonia in children.

BACKGROUND: Necrotizing pneumonia (NP) is a rare serious complication of community-acquired pneumonia (CAP) in children, which is characterized by a protracted course of the disease and a prolonged hospital stay. This study aimed to assess the role of systemic immune-inflammatory index and systemic inflammatory response index in predicting early lung necrotization in children with CAP. METHODS: This study included all children hospitalized in Pediatric Pulmonology Unit, Tanta University, Egypt, with CAP between the ages of two months and 18 years. Systemic inflammatory indices, including the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI), were calculated on patients' admission. RESULTS: The study involved a total of 228 children, 42 patients had NP, 46 patients had parapneumonic effusion, and 140 patients had non-complicated CAP. Patients with NP were substantially younger (p = 0.002), stayed in the hospital longer (p < 0.001), had a longer duration of symptoms before hospital admission (p < 0.001), and had fever for a longer duration than those in the other groups (p < 0.001). Regarding the inflammatory ratios, patients with NP had significantly higher MLR, PLR, SII, and SIRI than those in the other groups (p = 0.020, p = 0.007, p = 0.001, p = 0.037, respectively). ROC curve analysis showed that the combined SII + SIRI + D-dimer showed the highest AUC with a good specificity in predicting the diagnosis of NP. CONCLUSIONS: SII, SIRI, and D-dimer may be beneficial biomarkers for predicting the occurrence of NP in children when performed on patients' admission. In addition, it was found for the first time that combined SII + SIRI + D-dimer had a good sensitivity and specificity in the diagnosis of NP.

Necrotising pneumonia caused by Curvularia hawaiiensis (syn. Bipolaris hawaiiensis) and Mycobacterium tuberculosis coinfection in a patient with ascariasis: a case report and review.

INTRODUCTION: Curvularia hawaiiensis (formerly Bipolaris hawaiiensis) is a plant pathogen often isolated from soil and vegetative material. However, only a few cases of opportunistic invasive infections in humans have been described. CASE: A 16-year-old female patient without comorbidities was admitted to the emergency department because of fever and chest pain. We described the first coinfection of Curvularia hawaiiensis and Mycobacterium tuberculosis necrotising pneumonia. DISCUSSION: Multiple infections can alter immune responses. However, immunosuppression is the most critical risk factor for infection with species of the genus Curvularia. Therefore, it is crucial to carefully examine patients with tuberculosis, as they may rarely be coinfected with unusual fungi.

A challenging high-risk surgery for necrotizing pneumonia in a right bilobed lung.

BACKGROUND: Necrotizing pneumonia is rare in children and is one of the most serious complications of a lung infection caused by antibiotic failure. We present a 12-year-old leukopenic child with a long-lasting lung infection, presenting as having a lung hydatid cyst, but diagnosing with necrotizing pneumonia in the right bilobed lung. Failure to medical treatment and ongoing leukopenia justified surgical intervention with positive results. CASE PRESENTATION: The patient was referred to our teaching hospital's pediatric surgery department. He had previously been diagnosed with intestinal tuberculosis (TB) and received anti-TB treatment. On referral to our hospital, the patient was suffering from restlessness, frequent coughing, fever, vomiting, and diarrhea. Following the completion of the clinical work-up, a blood test revealed leukopenia (white blood cell count of 2100/microliter), a normal platelet count, and a lesion in the right lung. Computerized tomography scanning (CT-Scan) image reported a lung hydatid cyst. In the pediatrics ward, a broad-spectrum antibiotics regimen with triple-antibiotic therapy (linezolid, vancomycin, and metronidazole) was instituted and continued for a week with no response, but worsening of the condition. In the pediatric surgery ward, our decision for surgical intervention was due to the failure of medical treatment because of a pulmonary lesion. Our team performed right lung upper lobe anterior segment wedge resection due to necrotizing pneumonia and followed the patient 45 days post-operation with a reasonable result. CONCLUSION: Living in remote rural areas with low resources and inaccessibility to proper and specialized diagnostic and treatment centers will all contribute to an improper diagnosis and treatment of lung infection. In total, all of these will increase the morbidity and mortality due to lung necrosis in the pediatric population, regardless of their age. In low-resource facilities, high-risk patients can benefit from surgical intervention to control the ongoing infection process.

Pathogenic infection characteristics and risk factors for bovine respiratory disease complex based on the detection of lung pathogens in dead cattle in Northeast China.

Bovine respiratory disease complex (BRDC) involves multiple pathogens, shows diverse lung lesions, and is a major concern in calves. Pathogens from 160 lung samples of dead cattle from 81 cattle farms in Northeast China from 2016 to 2021 were collected to characterize the molecular epidemiology and risk factors of BRDC and to assess the major pathogens involved in bovine suppurative or caseous necrotizing pneumonia. The BRDC was diagnosed by autopsy, pathogen isolation, PCR, or reverse transcription-PCR detection, and gene sequencing. More than 18 species of pathogens, including 491 strains of respiratory pathogens, were detected. The positivity rate of bacteria in the 160 lung samples was 31.77%, including Trueperella pyogenes (9.37%), Pasteurella multocida (8.35%), Histophilus somni (4.48%), Mannheimia haemolytica (2.44%), and other bacteria (7.13%). The positivity rate of Mycoplasma spp. was 38.9%, including M. bovis (7.74%), M. dispar (11.61%), M. bovirhinis (7.94%), M. alkalescens (6.11%), M. arginini (0.81%), and undetermined species (4.68%). Six species of viruses were detected with a positivity rate of 29.33%, including bovine herpesvirus-1 (BoHV-1; 13.25%), bovine respiratory syncytial virus (BRSV; 5.50%), bovine viral diarrhea virus (BVDV; 4.89%), bovine parainfluenza virus type-3 (BPIV-3; 4.28%), bovine parainfluenza virus type-5 (1.22%), and bovine coronavirus (2.24%). Mixed infections among bacteria (73.75%), viruses (50%), and M. bovis (23.75%) were the major features of BRDC in these cattle herds. The risk analysis for multi-pathogen co-infection indicated that BoHV-1 and H. somni; BVDV and M. bovis, P. multocida, T. pyogenes, or Mann. haemolytica; BPIV-3 and M. bovis; BRSV and M. bovis, P. multocida, or T. pyogenes; P. multocida and T. pyogenes; and M. bovis and T. pyogenes or H. somni showed co-infection trends. A survey on molecular epidemiology indicated that the occurrence rate of currently prevalent pathogens in BRDC was 46.15% (6/13) for BoHV-1.2b and 53.85% (7/13) for BoHV-1.2c, 53.3% (8/15) for BVDV-1b and 46.7% (7/15) for BVDV-1d, 29.41% (5/17) for BPIV-3a and 70.59% (12/17) for BPIV-3c, 100% (2/2) for BRSV gene subgroup IX, 91.67% (33/36) for P. multocida serotype A, and 8.33% (3/36) for P. multocida serotype D. Our research discovered new subgenotypes for BoHV-1.2c, BRSV gene subgroup IX, and P. multocida serotype D in China's cattle herds. In the BRDC cases, bovine suppurative or caseous necrotizing pneumonia was highly related to BVDV [odds ratio (OR) = 4.18; 95% confidence interval (95% CI): 1.6-10.7], M. bovis (OR = 2.35; 95% CI: 1.1-4.9), H. somni (OR = 8.2; 95% CI: 2.6-25.5), and T. pyogenes (OR = 13.92; 95% CI: 5.8-33.3). The risk factor analysis found that dairy calves <3 mo and beef calves >3 mo (OR = 5.39; 95% CI: 2.7-10.7) were more susceptible to BRDC. Beef cattle were more susceptible to bovine suppurative or caseous necrotizing pneumonia than dairy cattle (OR = 2.32; 95% CI: 1.2-4.4). These epidemiological data and the new pathogen subgenotypes will be helpful in formulating strategies of control and prevention, developing new vaccines, improving clinical differential diagnosis by necropsy, predicting the most likely pathogen, and justifying antimicrobial use.

Is abdominal pain after an injury just an injury? Case report of rare aspiration pneumonia with lung gangrene and peritoneal response in a 5-year-old child.

Although pneumonia presents a relatively common diagnosis, it does not always present with classic clinical symptoms, nor does it follow a regular course without complications. The presented case describes a rare case of aspiration necrotizing pneumonia, which despite intensive therapy, progressed to lung gangrene and required a lung lobectomy. Another peculiarity is that the correct diagnosis was established only after the onset of abdominal pain, surprisingly by a trauma surgeon. This case emphasizes the necessity of a thorough general examination and draws attention to a rare, but conservatively intractable necrotizing pneumonia complicated by lung gangrene.

Neonatal Manifestations of Chronic Granulomatous Disease: MAS/HLH and Necrotizing Pneumonia as Unusual Phenotypes and Review of the Literature.

Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI), characterized by a deficient phagocyte killing due to the inability of NADPH oxidase to produce reactive oxygen species in the phagosome. Patients with CGD suffer from severe and recurrent infections and chronic inflammatory disorders. Onset of CGD has been rarely reported in neonates and only as single case reports or small case series. We report here the cases of three newborns from two different kindreds, presenting with novel infectious and inflammatory phenotypes associated with CGD. A girl with CYBA deficiency presented with necrotizing pneumonia, requiring a prolonged antibiotic treatment and resulting in fibrotic pulmonary changes. From the second kindred, the first of two brothers developed a fatal Burkholderia multivorans sepsis and died at 24 days of life. His younger brother had a diagnosis of CYBB deficiency and presented with Macrophage Activation Syndrome/Hemophagocytic Lympho-Histiocytosis (MAS/HLH) without any infection, that could be controlled with steroids. We further report the findings of a review of the literature and show that the spectrum of microorganisms causing infections in neonates with CGD is similar to that of older patients, but the clinical manifestations are more diverse, especially those related to the inflammatory syndromes. Our findings extend the spectrum of the clinical presentation of CGD to include unusual neonatal phenotypes. The recognition of the very early, potentially life-threatening manifestations of CGD is crucial for a prompt diagnosis, improvement of survival and reduction of the risk of long-term sequelae.

Septicaemia with deep venous thrombosis and necrotising pneumonia caused by acute community-acquired methicillin-resistant Staphylococcus aureus in an infant with a three-year follow-up: a case report.

BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a common pathogen that usually causes bacteraemia, osteomyelitis, as well as skin and soft tissue infections. However, deep venous thrombosis (DVT) and necrotising pneumonia are rare in infants. CASE PRESENTATION: We report the case of a one-month-five-day-old girl who was hospitalised for DVT and necrotising pneumonia due to septicaemia associated with Staphylococcus aureus. She recovered after treatment with intravenous antibiotics and multiple anticoagulant therapy, but DVT persisted at the three-year follow-up. Collateral circulation around the DVT was well-formed. Post thrombotic syndrome was not observed. CONCLUSIONS: Staphylococcus aureus complicated by DVT and necrotising pneumonia is rare and can be successfully treated.

[Analysis of clinical features and risk factors of necrotizing pneumonia in children].

OBJECTIVE: To investigate the clinical characteristics and risk factor analysis of necrotizing pneumonia in children. METHODS: A retrospective study was used to analyze the case data of 218 children with severe pneumonia hospitalized in the Department of Respiratory Medicine, Children's Hospital of Capital Institute of Pediatrics from January 2016 to January 2020, and they were divided into 96 cases in the necrotizing pneumonia group (NP group) and 122 cases in the non-necrotizing pneumonia group (NNP group) according to whether necrosis of the lung occurred. The differences in clinical characteristics (malnutrition, fever duration, hospitalization time, imaging performance, treatment and regression follow-up), laboratory tests [leukocytes, neutrophil ratio, platelet (PLT), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and lactate dehydrogenase (LDH)] and bronchoscopic performance between the two groups were compared, and Logistic regression analysis of clinical risk factors associated with necrotizing pneumonia was performed to further determine the maximum diagnostic value of each index by subject operating characteristic curve (ROC). The critical value of each index was further determined by the ROC. RESULTS: The differences in age, gender, pathogenic classification, and bronchoscopic presentation between the two groups of children were not statistically significant (P>0.05); whereas the imaging uptake time of the children in the NP group was higher than that in the NNP group (P < 0.05). The differences in malnutrition, fever duration, length of stay, white blood cell count, neutrophil ratio, CRP, PCT, and D-dimer were statistically significant between the two groups (P < 0.05). The imaging uptake time was lower in children under 6 years of age than in those over 6 years of age, and the imaging uptake time for bronchoalveolar lavage within 10 d of disease duration was lower than that for those over 10 d; the imaging uptake time was significantly longer in the mixed infection group than that in the single pathogen infection group. Logistic regression analysis of the two groups revealed that the duration of fever, hospital stay, CRP, PCT, and D-dimer were risk factors for secondary pulmonary necrosis (P < 0.001, P < 0.001, P < 0.001, P=0.013, P=0.001, respectively). The ROC curves for fever duration, CRP, PCT, and D-dimer were plotted and found to have diagnostic value for predicting the occurrence of pulmonary necrosis when fever duration >11.5 d, CRP >48.35 mg/L, and D-dimer > 4.25 mg/L [area under ROC curve (AUC)=0.909, 0.836, and 0.747, all P < 0.001]. CONCLUSION: Children with necrotizing pneumonia have a longer heat course and hospital stay, and the imaging uptake time of mixed pathogenic infections is significantly longer than that of single pathogenic infections. Children with necrotizing pneumonia under 6 years of age have more advantageous efficacy of electronic bronchoscopic alveolar lavage within 10 d of disease duration compared with children in the group over 6 years of age and children in the group with disease duration >10 d. Inflammatory indexes CRP, PCT, and D-dimer are significantly higher. The heat course, CRP, PCT, and D-dimer are risk factors for secondary lung necrosis in severe pneumonia. Heat course >11.5 d, CRP >48.35 mg/L, and D-dimer >4.25 mg/L have high predictive value for the diagnosis of necrotizing pneumonia.

Histopathological and virological features of lung, heart and liver percutaneous tissue core biopsy in patients with COVID-19: A clinicopathological case series.

INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.

Retrospective analysis of necrotizing pneumonia in children between 2015-2019.

INTRODUCTION: An increased incidence rate of cases of complicated pneumonia, reaching up to the stage of necrotizing pneumonia was observed at University Hospital Brno in the past period. The aim of this study was to perform a single-center retrospective analysis of patients with acquired inflammatory lung disease requiring surgical treatment, comprising a long-term follow-up group. METHODS: Patients hospitalized for community-acquired pneumonia and surgically treated in the years 2015-2019 were analyzed. The rates of necessary chest drainages, decortications and lung resections in relation to the whole group and individual years were monitored. Clinical and X-ray examinations were performed one year after hospitalization and the prognosis was determined for individual types of required treatments. The age, gender and etiological agents were also monitored. RESULTS: A total of 688 patients were included in the study with the incidence rising until 2018 and decreasing slightly in 2019. A statistically significantly higher number of community-acquired pneumonias and complications was recorded between 2017 and 2018 (p.

Differences of clinical features and prognosis between Mycoplasma pneumoniae necrotizing pneumonia and non-Mycoplasma pneumoniae necrotizing pneumonia in children.

BACKGROUND: In the past few years, Mycoplasma pneumoniae (Shi et al. Lancet 390:946-958, 2017) infection has been reported more in China. However, there are few studies on the clinical characteristics and prognosis of necrotizing pneumonia (NP) (Griffiths et al. Nature 583:615-619, 2020) caused by different pathogens. METHODS: A retrospective analysis was performed, including 31 children with a clinical diagnosis of NP in the hospital from January 1, 2013 to January 31, 2020. A total of 11 children with MPNP were included in the observation group and the other 20 children with other pathogens were included in the control group. The clinical manifestations, laboratory data, imaging findings, treatments and outcomes were analyzed. RESULTS: The proportion of dyspnea cases was significantly higher in the non-Mycoplasma pneumoniae necrotizing pneumonia (N-MPNP) group than that in the Mycoplasma pneumoniae necrotizing pneumonia (MPNP) group (P = 0.02).The LDH level of all patients in the MPNP group was higher than the normal value, with a median value of 805.0 U/L, which was significantly higher than those in the N-MPNP group (414.0 [299.9-540.6] U/L; Z = - 2.518; P = 0.012). The white blood cells (WBCs) count of the N-MPNP group was 17.8 (11.1-21.7) × 109/L, which was significantly higher than that of the MPNP group (10.2 [6.3-14.1] × 109/L; P < 0.05). The mean time of pulmonary necrosis in the MPNP group was 20.9 ± 6.9 days, which was higher than that of the N-MPNP group (16.8 ± 6.1 days; t = 3.101; P = 0.004). The incidence of pleural effusion in the N-MPNP group (19 patients, 95%) was significantly higher than that in the MPNP group (six patients, 54.55%) (P = 0.013). Among them, two patients received bronchoscopy lavage at a maximum four times, and the cases of plastic bronchitis were seen only in the MPNP group (3 cases; P = 0.037).The length of stay was 18 (10-22) days in the MPNP group and 23.5 (13.5-47) days in the N-MPNP group and no significant difference was observed between the two groups (Z = - 1.923, P = - 0.055). CONCLUSIONS: 1. MP infection is the most common infection in children with NP in the Suzhou area. There is no gender and age difference between MPNP and N-MPNP, but the bacterial infection was mainly observed in the N-MPNP group. 2. Children in the N-MPNP group have more severe clinical symptoms, were more prone to shortness of breath, had a longer hospital stay, and had earlier imaging manifestations of necrosis, whereas children in the MPNP group were more likely to have plastic bronchitis. The level of WBC and LDH and the nature of pleural effusion can be used to identify MPNP and N-MPNP to some extent. 3. The prognosis of MPNP was better than that of N-MPNP. There were no death cases. Pleural thickening, pulmonary fibrosis, and bronchiectasis were the most common sequelae. Compared with N-MPNP, the recovery time of lung imaging in MPNP was shorter.

D-dimer: The Risk Factor and Predictive Indicator of Necrotizing Pneumonia in Children.

BACKGROUND: Necrotizing pneumonia (NP) is a severe complication of community-acquired pneumonia in children. This article assesses the risk factors and the diagnostic value of D-dimer for NP in children. METHODS: The selected patients with lobar pneumonia were divided into two groups, namely: the NP group and the pneumonia only group. This article conducted a comparative study in the differences between the two groups. The authors identified the independent factors of NP with the assistance of multivariate logistic regression analysis upon the completion of the univariate analysis. The authors applied the receiver operating characteristic (ROC) curve for the purpose of discovering the indicators with the most predictive abilities of NP. RESULTS: Three risk factors were observed to be independently associated with the development of NP: Total duration of fever (OR 1.406, 95% CI 1.264 - 1.834), WBC counts (OR 2.662, 95% CI 1.592 - 3.981), and D-dimer (OR 2.878, 95% CI 1.671 - 4.902). D-dimer levels present with higher accuracy in terms of predicting the development of NP than the other two, with a value that is under the ROC of 0.886 (95% CI, 0.815 - 0.958). CONCLUSIONS: Significantly higher D-dimer levels are observed in children with NP. D-dimer could be considered as one of the most important risk factors and predictive indicators of NP.

Characteristics and Outcomes of Children With Necrotizing Pneumonia.

OBJECTIVES: In this study, we describe the characteristics and outcomes of pediatric necrotizing pneumonia in the United States. DESIGN AND SETTING: A retrospective analysis of the Healthcare Cost and Utilization Project 2016 Kids Inpatient Database was performed. The Kids Inpatient Database is a large deidentified hospital discharge database of pediatric patients in the United States. PATIENTS: The database was filtered using International Classification of Diseases, 10th Edition code J85.0 to identify necrotizing pneumonia in children 28 days to 20 years old. INTERVENTIONS: Children with necrotizing pneumonia with and without bacterial isolation and with and without complex chronic conditions were compared. Sample weighting was employed to produce national estimates. MEASUREMENTS AND MAIN RESULTS: Of the 2,296,220 discharges, 746 patients had necrotizing pneumonia (prevalence: 3.2/10,000 discharges). In patients with necrotizing pneumonia, 46.6% required chest tubes, 6.1% underwent video-assisted thoracoscopic surgery, and 27.6% were mechanically ventilated. Pneumothorax was identified in 16.7% and pyothorax in 27.4%. The overall mortality rate was 4.1% (n = 31). Bacterial isolation was documented in 40.9%. The leading organisms identified in patients without a complex chronic condition were Streptococcus pneumoniae (12.6%) and Staphylococcus aureus (9.2%) and in patients with a complex chronic condition were S. aureus (13.4%) and Pseudomonas aeruginosa (12.8%). Patients with bacterial isolation were significantly more likely to develop pneumothorax (odds ratio, 2.6; CI, 1.6-4.2) or septic shock (odds ratio, 3.2; CI, 1.9-5.4) and require a chest tube (odds ratio, 2.5; CI, 1.7-3.5) or mechanical ventilation (odds ratio, 2.3; CI, 1.5-3.3) than patients without bacterial isolation. CONCLUSIONS: Bacterial etiology of necrotizing pneumonia in children varied with the presence or absence of a complex chronic condition. Bacterial isolation is associated with increased invasive procedures and complications. The mortality rate is higher in children with complex chronic conditions. This study provides national data on necrotizing pneumonia among hospitalized children.

Unusual case of necrotizing pneumonia caused by Fusobacterium nucleatum complicating influenza a virus infection.

We report a rare case of Fusobacterium nucleatum necrotizing pneumonia following an influenza viral infection. This rare bacterial lung infection can have severe complications such as respiratory failure and septic shock, so early recognition and treatment are necessary.

[Acute Necrotizing Pneumonia in Blue Tits - Implications for Pulmonology in Dialogue with Veterinary Medicine]. / Akut nekrotisierende Pneumonie bei Blaumeisen.

At the beginning of March 2020, observations of an increasing number of dead blue tits increased. The sick tits suffered among others from respiratory symptoms. The reason for the mass extinction initially remained unclear. By the beginning of May, around 18,000 reports of suspected blue tit deaths with around 33,000 affected birds had been received. The maximum was almost 1,300 reports on April 10th. The number of reports decreased again during the following weeks. According to estimates, about 1,7 million blue tits died in Germany during this time.In a large number of the tits examined, the bacterium Suttonella ornithocola was detected in the lungs.Since the pathogen causes pneumonia, transmission via aerosol or through contact with infected secretions is to be assumed.Autopsies showed lung congestion, bloody intestinal contents and poor nutritional status. Histologically, mild to moderate acute necrotizing pneumonia was found. Since Suttonella ornithocola was also found in the parenchyma of the large organs, an additional acute sepsis can be assumed. Suttonella ornithocola could also be an intestinal pathogen, since Suttonella ornithocola was found in the intestine in addition to bloody intestinal contents, but at the same time no recognized intestinal pathogens were detected. The faeco-oral route of infection is therefore also possible.

Efficacy of Active Immunization With Attenuated α-Hemolysin and Panton-Valentine Leukocidin in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia.

Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

Protective Efficacy of Monoclonal Antibodies Neutralizing Alpha-Hemolysin and Bicomponent Leukocidins in a Rabbit Model of Staphylococcus aureus Necrotizing Pneumonia.

Staphylococcus aureus is a major human pathogen that causes a wide range of infections by producing an arsenal of cytotoxins. We found that passive immunization with either a monoclonal antibody (MAb) neutralizing alpha-hemolysin or a broadly cross-reactive MAb neutralizing Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysins HlgAB and HlgCB conferred only partial protection, whereas the combination of those two MAbs conferred significant protection in a rabbit model of necrotizing pneumonia caused by the USA300 methicillin-resistant S. aureus epidemic clone.

NLRP6 negatively regulates pulmonary host defense in Gram-positive bacterial infection through modulating neutrophil recruitment and function.

Gram-positive bacteria, including Staphylococcus aureus are endemic in the U.S., which cause life-threatening necrotizing pneumonia. Neutrophils are known to be critical for clearance of S. aureus infection from the lungs and extrapulmonary organs. Therefore, we investigated whether the NLRP6 inflammasome regulates neutrophil-dependent host immunity during pulmonary S. aureus infection. Unlike their wild-type (WT) counterparts, NLRP6 knockout (KO) mice were protected against pulmonary S. aureus infection as evidenced by their higher survival rate and lower bacterial burden in the lungs and extrapulmonary organs. In addition, NLRP6 KO mice displayed increased neutrophil recruitment following infection, and when neutrophils were depleted the protective effect was lost. Furthermore, neutrophils from the KO mice demonstrated enhanced intracellular bacterial killing and increased NADPH oxidase-dependent ROS production. Intriguingly, we found higher NK cell-mediated IFN-γ production in KO mouse lungs, and treatment with IFN-γ was found to enhance the bactericidal ability of WT and KO neutrophils. The NLRP6 KO mice also displayed decreased pyroptosis and necroptosis in the lungs following infection. Blocking of pyroptosis and necroptosis in WT mice resulted in increased survival, reduced bacterial burden in the lungs, and attenuated cytokine production. Taken together, these novel findings show that NLRP6 serves as a negative regulator of neutrophil-mediated host defense during Gram-positive bacterial infection in the lungs through regulating both neutrophil influx and function. These results also suggest that blocking NLRP6 to augment neutrophil-associated bacterial clearance should be considered as a potential therapeutic intervention strategy for treatment of S. aureus pneumonia.

The clinical characteristics and risk factors for necrotizing pneumonia caused by Mycoplasma pneumoniae in children.

BACKGROUND: The incidence of necrotizing pneumonia (NP) caused by Mycoplasma pneumoniae (MP) is increasing. We analyzed the clinical characteristics and the risk factors for NP caused by MP. METHODS: A retrospective observational study was conducted in 37 patients with NP caused by MP (NP group) and 74 patients diagnosed with lobar M. pneumoniae pneumonia with no necrosis (control group) who were admitted to our hospital between January 2013 and December 2017. The clinical manifestations, laboratory data, imaging findings, treatments and outcomes were analyzed. RESULTS: The proportion of females, the incidence of pleural effusion, fever duration, hospitalization days, white blood cell count, neutrophil ratio, D-dimer level and use of other types of antibiotics were higher in the NP group than in the control group (P < 0.05). The control group exhibited a greater use of low molecular weight heparin (LMWH) than the NP group (P < 0.05). According to the multivariate logistic regression analysis, a white blood cell count > 12.3 × 109/L (Odds ratio, OR = 6.412), a neutrophil ratio > 73.9% (OR = 6.081) and D-dimer level > 1367.5 ng/mL (OR = 8.501) were risk factors for pulmonary necrosis caused by MP. Furthermore, the use of LMWH (OR = 0.074) reduced the risk of pulmonary necrosis. CONCLUSIONS: NP is a rare complication of severe Mycoplasma pneumoniae pneumonia (SMPP), and although the clinical course is longer than common MP infection, the necrotic area is absorbed gradually. In patients with SMPP presenting with lobar consolidation, a white blood cell count > 12.3 × 109/L, a neutrophil ratio > 73.9% and D-dimer level > 1367.5 ng/mL are risk factors for pulmonary necrosis, and the use of LMWH reduces the risk of pulmonary necrosis.

Staphylococcus Aureus Panton-Valentine Leukocidin causing hip osteomyelitis, thrombophlebitis and necrotizing pneumonia in an immuocompetent child.

Panton-Valentine leukocidin (PVL) represents an important virulence factor for many strains of Staphylococcus aureus. PVL is an esotoxin causing leucocyte destruction and tissue necrosis. We report on a case of osteomyelitis involving the hip joint with thromblophlebitis complicated by necrotizing pneumonia and life-threatening septic shock. The child required advance respiratory support for 14 days with circulatory support for 7 days in ICU (intensive care unit), surgical draninage via arthrotomy of hip joint and second-line antibiotic treatment for 1 month. Among a wide literature, in Europe over half of Panton-Valentine St. Aureus (PVL-SA) is MSSA. Investigations for PVL are not always available determining an under-recognition of the episodes. Data on prevalence of PVL-SA in Italy are scarce. With this clinical report, we emphasize the recognition of clinical features that must lead to suspect PVL-SA osteomyelitis in children, providing their adequate management.