Acute glomerulonephritis with concurrent suspected bacterial pneumonia - is it the tip of the iceberg?

BACKGROUND: Post infectious glomerulonephritis is the most common glomerulopathy in children, occurring several weeks after nephritogenic streptococcal throat or skin infection. Reports of acute glomerulonephritis (AGN) occurring during active bacterial pneumonia in children are rare. The aim of this study was to evaluate the incidence of AGN concurrent with bacterial pneumonia in children. METHODS: We reviewed records of all children admitted with a diagnosis of pneumonia to the pediatric department in a single tertiary medical center between January 2015 and April 2023. Patients with bacterial pneumonia and concurrent glomerulonephritis were included. RESULTS: Eleven (0.98%) of 1,123 patients with bacterial pneumonia had concurrent AGN. All were males with a median age of 2.7 years (range 1-13). Mean time from bacterial pneumonia onset to acute glomerulonephritis symptoms was 2.7 ± 1.5 days. Five (45%) patients had evidence of pneumococcal infection. Hypertension was found in 10 (91%) patients. Mean trough eGFR was 43.5 ± 21.4 ml/min/1.73 m2 (range 11-73). Ten patients (91%) had low C3 levels. Median urinary protein-to-creatinine ratio was 2.5 mg/mg (IQR 2.15-14.75). All patients fully recovered. Microscopic hematuria was the last finding to normalize after a median of 29.5 days (IQR 17.25-38). CONCLUSION: AGN during bacterial pneumonia may be more frequent than previously recognized. Kidney prognosis was excellent in all patients. Prospective studies are needed to evaluate the impact of this condition.

Treatable traits and challenges in the clinical management of non-tuberculous mycobacteria lung disease in people with cystic fibrosis.

INTRODUCTION: Over the last ten years an increasing prevalence and incidence of non-tuberculous mycobacteria (NTM) has been reported among patients with cystic fibrosis (CF) Viviani (J Cyst Fibros, 15(5):619-623, 2016). NTM pulmonary disease has been associated with negative clinical outcomes and often requires pharmacological treatment. Although specific guidelines help clinicians in the process of diagnosis and clinical management, the focus on the multidimensional assessment of concomitant problems is still scarce. MAIN BODY: This review aims to identify the treatable traits of NTM pulmonary disease in people with CF and discuss the importance of a multidisciplinary approach in order to detect and manage all the clinical and behavioral aspects of the disease. The multidisciplinary complexity of NTM pulmonary disease in CF requires careful management of respiratory and extra-respiratory, including control of comorbidities, drug interactions and behavioral factors as adherence to therapies. CONCLUSIONS: The treatable trait strategy can help to optimize clinical management through systematic assessment of all the aspects of the disease, providing a holistic treatment for such a multi-systemic and complex condition.

Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

Seroprevalence of community-acquired atypical bacterial pneumonia among adult COVID-19 patients from a single center in Al Madinah Al Munawarah, Saudi Arabia: A retrospective cohort study.

OBJECTIVES: To investigate the seroprevalence of the community-acquired bacterial that causes atypical pneumonia among confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) patients. METHODS: In this cohort study, we retrospectively investigated the seroprevalence of Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila among randomly selected 189 confirmed COVID-19 patients at their time of hospital presentation via commercial immunoglobulin M (IgM) antibodies against these bacteria. We also carried out quantitative measurements of procalcitonin in patients' serum. RESULTS: The seropositivity for L. pneumophila was 12.6%, with significant distribution among patientsolder than 50 years (χ2 test, p=0.009), while those of M. pneumoniae was 6.3% and C. pneumoniae was 2.1%, indicating an overall co-infection rate of 21% among COVID-19 patients. No significant difference (χ2 test, p=0.628) in the distribution of bacterial co-infections existed between male and female patients. Procalcitonin positivity was confirmed amongst 5% of co-infected patients. CONCLUSION: Our study documented the seroprevalence of community-acquired bacteria co-infection among COVID-19 patients. In this study, procalcitonin was an inconclusive biomarker for non-severe bacterial co-infections among COVID-19 patients. Consideration and proper detection of community-acquired bacterial co-infection may minimize misdiagnosis during the current pandemic and positively reflect disease management and prognosis.

Decreasing Incidence and Determinants of Bacterial Pneumonia in People With HIV: The Swiss HIV Cohort Study.

BACKGROUND: Bacterial pneumonia is a leading reason for hospitalization among people with HIV (PWH); however, evidence regarding its drivers in the era of potent antiretroviral therapy is limited. METHODS: We assessed risk factors for bacterial pneumonia in the Swiss HIV Cohort Study using marginal models. We further assessed the relationship between risk factors and changes in bacterial pneumonia incidence using mediation analysis. RESULTS: We included 12927 PWH with follow-ups between 2008 and 2018. These patients had 985 bacterial pneumonia events during a follow-up of 100779 person-years. Bacterial pneumonia incidence significantly decreased from 13.2 cases/1000 person-years in 2008 to 6.8 cases/1000 person-years in 2018. Older age, lower education level, intravenous drug use, smoking, lower CD4-cell count, higher HIV load, and prior pneumonia were significantly associated with higher bacterial pneumonia incidence. Notably, CD4 cell counts 350-499 cells/µL were significantly associated with an increased risk compared to CD4 ≥ 500 cells/µL (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01-1.89). Decreasing incidence over the last decade can be explained by increased CD4-cell counts and viral suppression and decreased smoking frequency. CONCLUSIONS: Improvements in cascade of care of HIV and decrease in smoking may have mediated a substantial decrease in bacterial pneumonia incidence.

Aspectos epidemiológicos, clínicos y microbiológicos en pacientes menores de 5 años con neumonía bacteriana / Epidemiological, clinical and microbiologic aspects in patients under 5 years with bacterial pneumonia

Introducción: Las infecciones respiratorias agudas abarcan entre 20 y 40 % del total de todas las hospitalizaciones y 20 - 34 % de las muertes en menores de 5 años de edad, fundamentalmente a expensas de neumonía. Objetivo: Describir aspectos epidemiológicos, clínicos y microbiológicos en pacientes menores de 5 años con neumonía bacteriana. Métodos: Se realizó un estudio descriptivo y transversal de 39 pacientes con neumonía y aislamientos bacterianos en hemocultivos, líquido pleural y/o exudados nasofaringeos, ingresados en el Hospital Infantil Docente Sur Antonio María Béguez Cesar de Santiago de Cuba, desde enero de 2018 hasta diciembre de 2019. Se analizaron variables de interés, tales como edad, sexo, factores de riesgo, sintomatología y cultivos microbiológicos. Se utilizaron la frecuencia absoluta y el porcentaje como medidas de resumen. Resultados: Prevalecieron los pacientes entre 1 - 4 años de edad, el sexo femenino y los hemocultivos con estafilococos coagulasa negativo, así como neumococos, estos últimos también aislados en exudados nasofaríngeos. Los factores de riesgo más frecuentes fueron infección respiratoria aguda previa, uso anticipado de antibióticos, asistencia a círculo infantil, supresión precoz de lactancia materna, fiebre, tos, tiraje y alteraciones del murmullo vesicular. Predominaron la insuficiencia respiratoria aguda y el derrame pleural como complicaciones. Se notificó más gravedad en los lactantes y ocurrieron 2 decesos, para una letalidad de 1,47 %. Conclusiones: La conjunción de factores de riesgo detectados, la baja positividad de los cultivos, la identificación de bacterias prevalentes en hemocultivos y el descenso de la letalidad resultaron de interés en el estudio.

Introduction: Acute respiratory infections take in between 20 and 40 % of all the hospitalizations and 20 - 34% of deaths in children under 5 years, fundamentally at the expense of pneumonia. Objective: To describe epidemiologic, clinical and microbiologic aspects in patients under 5 years with bacterial pneumonia. Methods: A descriptive and cross-sectional study of 39 patients with pneumonia and bacterial isolations in hemocultures, pleural fluid and/or nasopharyngeal swabs was carried out. They were admitted to Antonio María Béguez Cesar Southern Teaching Children Hospital in Santiago de Cuba, from January, 2018 to December, 2019. Variables of interest were analyzed, such as age, sex, risk factors, symptomatology and microbiologic cultures. The absolute frequency and the percentage as summary measures were used. Results: There was a prevalence of patients among 1 - 4 years, female sex and the hemocultures with negative coagulase staphylococcu, as well as pneumococus, these last ones also isolated in nasopharingeal swabs. The most frequent risk factors were previous acute respiratory infection, premature use of antibiotics, attendance to day care center, early suppression of breastfeeding, fever, cough, tirage and changes of the vesicular breath sound. The acute respiratory failure and pleural effusion as complications prevailed. More seriousness was notified in infants and there were 2 deaths, for a letality of 1.47 %. Conclusions: The combination of detected risk factors, low positivity of the cultures, identification of bacterias prevalents in hemocultures and the decrease of letality was of interest in the study.

Chronic infection with Chlamydia pneumoniae in asthma: a type-2 low infection related phenotype.

BACKGROUND: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria. METHOD: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae. RESULTS: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV1/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations. CONCLUSION: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation.

Incidence and risk factors for respiratory tract bacterial colonization and infection in lung transplant recipients.

To evaluate incidence of and risk factors for respiratory bacterial colonization and infections within 30 days from lung transplantation (LT). We retrospectively analyzed microbiological and clinical data from 94 patients transplanted for indications other than cystic fibrosis, focusing on the occurrence of bacterial respiratory colonization or infection during 1 month of follow-up after LT. Thirty-three percent of patients developed lower respiratory bacterial colonization. Bilateral LT and chronic heart diseases were independently associated to a higher risk of overall bacterial colonization. Peptic diseases conferred a higher risk of multi-drug resistant (MDR) colonization, while longer duration of aerosol prophylaxis was associated with a lower risk. Overall, 35% of lung recipients developed bacterial pneumonia. COPD (when compared to idiopathic pulmonary fibrosis, IPF) and higher BMI were associated to a lower risk of bacterial infection. A higher risk of MDR infection was observed in IPF and in patients with pre-transplant colonization and infections. The risk of post-LT respiratory infections could be stratified by considering several factors (indication for LT, type of LT, presence of certain comorbidities, and microbiologic assessment before LT). A wider use of early nebulized therapies could be useful to prevent MDR colonization, thus potentially lowering infectious risk.

Statewide Seasonal Variations of Infections Within the Intensive Care Unit Among the Trauma Population.

BACKGROUND: Infections within intensive care unit (ICU) are a persistent problem among the critically ill. Viral pneumonias have already been established as having a season variations. We attempt to evaluate the seasonal variations of pneumonia among the traumatically injured and the critically ill. MATERIALS AND METHODS: A retrospective cohort study among traumatized patients admitted from 1997 to 2017 to an ICU within the state of Florida was performed who were diagnosed with pneumonia. A multivariate regression analysis was performed to adjust for confounders. Time periods were divided into seasons: summer, winter, spring, and fall. A subset analysis of geriatric patients (>65 years) was also performed. RESULTS: A total of 869 553 patients were identified. The most common viral infection was influenza with adenovirus the least. The most common bacterial pneumonia was Staphylococcus aureus with Bordetella pertussis the least. Pneumonias had a seasonal variation. Compared to summer, winter had a higher likelihood of pneumonia overall (Adjusted Odds Ratio (AOR)1.13). This was seen in the spring (AOR 1.04) but not in fall (AOR 1.00). Viral infections were more pronounced (AOR 3.79) in all other seasons, while bacterial showed increased likelihood during winter (AOR 1.05). In geriatrics, pneumonia was again more likely in the winter (AOR 1.22) with both viral and bacterial infections being more pronounced during winter (AOR 4.79, AOR 1.09). DISCUSSION: Pneumonias are seen more frequently within the ICU during the winter for the traumatized patient. This held true with the critically ill geriatric population as well. This effect was observed in both viral and bacterial pneumonias.

Clinical and microbiological characteristics of adults with hospital-acquired pneumonia: a 10-year prospective observational study in China.

Hospital-acquired pneumonia (HAP) is a significant nosocomial infection; data on the distribution and antimicrobial resistance profiles of HAP in China are limited. We included 2827 adult patients with HAP from the Chinese Antimicrobial Resistance Surveillance of Nosocomial Infections network admitted in 15 Chinese teaching hospitals between 2007 and 2016. Clinical data and antimicrobial susceptibility of isolated pathogens were obtained from the medical records and central laboratory, respectively. Multivariable logistic regression was performed to determine the risk factors for mortality and multidrug resistance (MDR). A total of 386 (13.7%) patients died in the hospital, while 1181 (41.8%) developed ventilator-associated pneumonia (VAP). Active immunosuppressant therapy (OR 1.915 (95% CI 1.475-2.487)), solid tumor (OR 1.860 (95% CI 1.410-2.452)), coma (OR 1.783 (95% CI 1.364-2.333)), clinical pulmonary infection score ≥7 (OR 1.743 (95% CI 1.373-2.212)), intensive care unit stay (OR 1.652 (95% CI 1.292-2.111)), age ≥65 years (OR 1.621 (95% CI 1.282-2.049)), and tracheal cannula insertion (OR 1.613 (95% CI 1.169-2.224)) were independent risk factors for in-hospital mortality. Liver cirrhosis (OR 3.120 (95% CI 1.436-6.780)) and six other variables were independent predictors of MDR. Acinetobacter baumannii (25.6%), Pseudomonas aeruginosa (20.1%), Klebsiella pneumoniae (15.4%), and Staphylococcus aureus (12.6%) were the most common pathogens (MDR prevalence 64.9%). Isolates from VAP patients showed more A. baumannii and less K. pneumoniae and E. coli strains (p < 0.001, respectively) than those from patients without VAP. The proportion of methicillin-resistant S. aureus strains decreased; that of carbapenem-resistant A. baumannii and Enterobacterales strains increased. There had been changes in the antibiotic resistance profiles of HAP pathogens in China. Risk factors for mortality and MDR are important for the selection of antimicrobials for HAP in China.

Patrones imagenológicos en pacientes menores de 5 años con diagnóstico de neumonía bacteriana / Imaging patterns in patients under 5 years with diagnosis of bacterial pneumonia

Introducción: La radiografía de tórax constituye el mejor método de diagnóstico para la confirmación clínica de la neumonía, aunque existen discrepancias en relación con su causalidad. Objetivo: Describir los patrones imagenológicos según variables clínicas, epidemiológicas y microbiológicas en pacientes menores de 5 años ingresados por neumonía bacteriana. Métodos: Se realizó un estudio descriptivo, prospectivo y transversal de 84 pacientes con diagnóstico de neumonía y aislamiento bacteriano en hemocultivos y/o líquido pleural. Como variables analizadas figuraron: edad, sexo, factores de riesgo, manifestaciones clínicas, así como resultados de los estudios imagenológicos de tórax y de los cultivos microbiológicos. Como medidas de resumen se utilizaron la frecuencia absoluta y el porcentaje. Resultados: En la serie predominaron la consolidación alveolar (57,1 %), el grupo de 1-4 años y el sexo masculino, así como también el uso de tratamiento antimicrobiano previo al ingreso, la supresión precoz de lactancia materna y la presencia de fumadores en casa como principales factores de riesgo. La fiebre, la tos, la taquipnea, el tiraje, la rinorrea y los estertores húmedos resultaron ser las manifestaciones clínicas más frecuentes y prevaleció el neumococo en pacientes con patrón de condensación alveolar (64,6 %). Conclusiones: El patrón de consolidación alveolar estuvo relacionado con causa predominantemente neumocócica, con múltiples factores de riesgo y con síntomas típicos de neumonía bacteriana.

Introduction: Chest radiography is the best diagnostic method for clinical confirmation of pneumonia, although there are discrepancies in its relation to causation. Objective: To describe imaging patterns according to clinical, epidemiological, and microbiological variables, in patients under five years of age admitted for bacterial pneumonia. Methods: descriptive, prospective, and cross-sectional study of 84 patients diagnosed with pneumonia and bacterial isolation in blood cultures and / or pleural fluid. Variables of interest were operationalized, with frequency, and percentage calculations being performed. Results: alveolar consolidation (57.1 %) prevailed in preschoolers, male sex, with previous antimicrobial treatment, early suppression of breastfeeding, and smoking at home. Fever, cough, tachypnea, retraction, rhinorrhea, and wet rales were the most frequent symptoms. Pneumococcus prevailed (64.6 %) in patients with alveolar condensation pattern. Conclusions: the pattern of alveolar consolidation was consistent with pneumococcal causality predominantly; with multiple risk factors and typical clinical presentation of bacterial pneumonia.

Complicated pneumonia in children.

Complicated community-acquired pneumonia in a previously well child is a severe illness characterised by combinations of local complications (eg, parapneumonic effusion, empyema, necrotising pneumonia, and lung abscess) and systemic complications (eg, bacteraemia, metastatic infection, multiorgan failure, acute respiratory distress syndrome, disseminated intravascular coagulation, and, rarely, death). Complicated community-acquired pneumonia should be suspected in any child with pneumonia not responding to appropriate antibiotic treatment within 48-72 h. Common causative organisms are Streptococcus pneumoniae and Staphylococcus aureus. Patients have initial imaging with chest radiography and ultrasound, which can also be used to assess the lung parenchyma, to identify pleural fluid; CT scanning is not usually indicated. Complicated pneumonia is treated with a prolonged course of intravenous antibiotics, and then oral antibiotics. The initial choice of antibiotic is guided by local microbiological knowledge and by subsequent positive cultures and molecular testing, including on pleural fluid if a drainage procedure is done. Information from pleural space imaging and drainage should guide the decision on whether to administer intrapleural fibrinolytics. Most patients are treated by drainage and more extensive surgery is rarely needed; in any event, in low-income and middle-income countries, resources for extensive surgeries are scarce. The clinical course of complicated community-acquired pneumonia can be prolonged, especially when patients have necrotising pneumonia, but complete recovery is the usual outcome.

Management of Fever in Infants and Young Children.

Despite dramatic reductions in the rates of bacteremia and meningitis since the 1980s, febrile illness in children younger than 36 months continues to be a concern with potentially serious consequences. Factors that suggest serious infection include age younger than one month, poor arousability, petechial rash, delayed capillary refill, increased respiratory effort, and overall physician assessment. Urinary tract infections are the most common serious bacterial infection in children younger than three years, so evaluation for such infections should be performed in those with unexplained fever. Abnormal white blood cell counts have poor sensitivity for invasive bacterial infections; procalcitonin and C-reactive protein levels, when available, are more informative. Chest radiography is rarely recommended for children older than 28 days in the absence of localizing signs. Lumbar puncture is not recommended for children older than three months without localizing signs; it may also be considered for those from one to three months of age with abnormal laboratory test results. Protocols such as Step-by-Step, Laboratory Score, or the Rochester algorithms may be helpful in identifying low-risk patients. Rapid influenza testing and tests for coronavirus disease 2019 (COVID-19) may be of value when those diseases are circulating. When empiric treatment is appropriate, suggested antibiotics include ceftriaxone or cefotaxime for infants one to three months of age and ampicillin with gentamicin or with cefotaxime for neonates. For children three months to three years of age, azithromycin or amoxicillin is recommended if pneumonia is suspected; for urinary infections, suggested antibiotics are cefixime, amoxicillin/clavulanate, or trimethoprim/sulfamethoxazole. Choice of antibiotics should reflect local patterns of microbial resistance.

Respiratory outcomes of metformin use in patients with type 2 diabetes and chronic obstructive pulmonary disease.

Few studies investigated the respiratory outcomes of metformin use in patients with coexistent type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD). We want to compare the long-term respiratory endpoints of metformin use and nonuse in patients with T2DM and COPD. This retrospective cohort study enrolled patients with T2DM and COPD from Taiwan's National Health Insurance Program between January 1, 2000, and December 31, 2012. Main outcomes were hospitalized bacterial pneumonia, hospitalization for COPD, noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation (IMV), and lung cancer. In total, 20,644 propensity score-matched metformin users and nonusers were assessed. The adjusted hazard ratios (95% confidence intervals) of metformin use relative to nonuse for bacterial pneumonia, hospitalization for COPD, NIPPV, IMV, and lung cancer were 1.17 (1.11-1.23), 1.34 (1.26-1.43), 0.99 (0.89-1.10), 1.10 (1.03-1.17), and 1.12 (0.96-1.30). Metformin use also exhibited significant dose-response relationship with respect to the risks of bacterial pneumonia, hospitalization for COPD and IMV. Consistent results were found in the sensitivity test. This nationwide cohort study demonstrated that in patients with T2DM and COPD, metformin use was associated with higher risks of pneumonia, hospitalization for COPD, and IMV. If patients with COPD use metformin, vigilance with regard to their pulmonary condition may be required.

Clinical diagnostic application of metagenomic next-generation sequencing in children with severe nonresponding pneumonia.

Pneumonia is one of the most important causes of morbidity and mortality in children. Identification and characterization of pathogens that cause infections are crucial for accurate treatment and accelerated recovery. However, in most cases, the causative agent cannot be identified, which is partly due to the limited spectrum of pathogens covered by current diagnostics based on nucleic acid amplification. Therefore, in this study, we explored the application of metagenomic next-generation sequencing (mNGS) for the diagnosis of children with severe pneumonia. From April to July 2017, 32 hospitalized children with severe nonresponding pneumonia in Shenzhen Children's Hospital were included in this study. Blood tests were conducted immediately after hospitalization to assess cell counts and inflammatory markers, oropharyngeal swabs were collected to identify common pathogens by qPCR and culture. After bronchoscopy, bronchoalveolar lavage fluid (BALF) samples were collected for further pathogen identification using standardized diagnostic tests and mNGS. Blood tests were normal in 3 of the 32 children. In 9 oropharyngeal swabs, bacterial pathogens were detected, in 5 of these Mycoplasma pneumoniae was detected. Adenovirus was detected in 5 BALF samples, using the Direct Immunofluorescence Assay (DFA). In 15 cases, no common pathogens were found in BALF samples, using the current standard diagnostic tests, while in all 32 BALFs, pathogens were identified using mNGS, including adenovirus, Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, cytomegalovirus and bocavirus. This study shows that, with mNGS, the sensitivity of detection of the causative pathogens in children with severe nonresponding pneumonia is significantly improved. In addition, mNGS gives more strain specific information, helps to identify new pathogens and could potentially help to trace and control outbreaks. In this study, we have shown that it is possible to have the results within 24 hours, making the application of mNGS feasible for clinical diagnostics.

Clinical features, therapy and outcome of patients hospitalized or not for nursing-home acquired pneumonia.

BACKGROUND: nursing home-acquired pneumonia (NHAP), is among the main causes of hospitalization and mortality of frail elderly patients. Aim of this study was analysis of patients residing in long-term care facilities (LTCF) and developing pneumonia to reach a better knowledge of criteria for hospitalization and outcomes. MATERIALS/METHODS: this is a prospective, observational study in which patients residing in 3 LTCFs (metropolitan area of Rome, Italy) and developing pneumonia, hospitalized or treated in LTCF, were recruited and followed up from January 2017 to June 2019. Primary endpoint was 30-day mortality, secondary endpoint was analysis of risk factors associated with hospitalization. RESULTS: Overall, 146 episodes of NHAP were enrolled in the study: 57 patients were treated in LTCF, while 89 patients were hospitalized. Overall incidence rates of NHAP varied from 2.6 to 7.5 per 1000 residents. Methicillin-resistant Staphylococcus aureus was the most frequently isolated pathogen (25%), and in 28 (55%) patients was documented a MDR pathogen. For hospitalized patients was reported a higher 30-day mortality (43.8% Vs 7%, p < 0.001). Multivariate analysis showed that severe pneumonia, neoplasm, chronic hepatitis, antibiotic monotherapy, and malnutrition were independent risk factors for hospitalization from LTCF. MDR pathogen, severe pneumonia, COPD, and moderate to severe renal disease were independently associated with death at 30 days. CONCLUSION: frail elderly patients in LTCF have a high risk of MDR etiology with a higher risk to receive an inadequate antibiotic therapy and a fatal outcome. These results point to the need for increased provision of acute care and strategies in LTCF.

Incidence of common opportunistic infections among HIV-infected children on ART at Debre Markos referral hospital, Northwest Ethiopia: a retrospective cohort study.

BACKGROUND: Opportunistic infections (OIs) are the leading cause of morbidity and mortality among children living with human immunodeficiency virus (HIV). For better treatments and interventions, current and up-to-date information concerning occurrence of opportunistic infections in HIV-infected children is crucial. However, studies regarding the incidence of common opportunistic infections in HIV-infected children in Ethiopia are very limited. Hence, this study aimed to determine the incidence of opportunistic infections among HIV-infected children on antiretroviral therapy (ART) at Debre Markos Referral Hospital. METHODS: A facility-based retrospective cohort study was undertaken at Debre Markos Referral Hospital for the period of January 1, 2005 to March 31, 2019. A total of 408 HIV-infected children receiving ART were included. Data from HIV-infected children charts were extracted using a data extraction form adapted from ART entry and follow-up forms. Data were entered using Epi-data™ Version 3.1 and analyzed using Stata™ Version 14. The Kaplan Meier survival curve was used to estimate the opportunistic infections free survival time. Both bi-variable and multivariable Cox proportional hazard models were fitted to identify the predictors of opportunistic infections. RESULTS: This study included the records of 408 HIV-infected children-initiated ART between the periods of January 1, 2005 to March 31, 2019. The overall incidence rate of opportunistic infections during the follow-up time was 9.7 (95% CI: 8.13, 11.48) per 100 child-years of observation. Tuberculosis at 29.8% was the most commonly encountered OI at follow-up. Children presenting with advanced disease stage (III and IV) (AHR: 1.8, 95% CI: 1.2, 2.7), having "fair" or "poor" ART adherence (AHR: 2.6, 95% CI: 1.8, 3.8), not taking OI prophylaxis (AHR:1.6, 95% CI: 1.1, 2.4), and CD4 count or % below the threshold (AHR:1.7, 95% CI: 1.1, 2.6) were at a higher risk of developing opportunistic infections. CONCLUSIONS: In this study, the incidence rate of opportunistic infections among HIV-infected children remained high. Concerning predictors, such as advanced disease stage (III and IV), CD4 count or % below the threshold, "fair" or "poor" ART adherence, and not taking past OI prophylaxis were found to be significantly associated with OIs.

Influence of Preoperative Oropharyngeal Microflora on the Occurrence of Postoperative Pneumonia and Survival in Patients Undergoing Esophagectomy for Esophageal Cancer.

OBJECTIVE: The aim of this study was to clarify the correlation between oropharyngeal microflora and postoperative complications as well as long-term survival after esophagectomy. BACKGROUND: Although the oral cavity is known to be a potential reservoir for pathogens, the influence of abnormal oropharyngeal microflora on the outcomes of patients undergoing esophagectomy remains unknown. METHODS: This study included 675 patients who underwent esophagectomy between 2007 and 2014. Saliva samples from the oropharynx were collected 2 days before the operation. There were 442 patients with indigenous flora (Ind group) and 233 with allopatric flora. Among the patients with allopatric flora, 140 had antibiotic-sensitive microbes only (Allo-S group) while 93 had different types of antibiotic-resistant microbes (Allo-R group). We investigated the correlation between the types of oropharyngeal microflora and the incidence of postoperative complications as well as long-term outcomes. RESULTS: Sixteen microbes could be cultivated from the saliva samples. The incidence of postoperative pneumonia in the Allo-S and Allo-R groups was significantly higher than in the Ind group (P < 0.001). In addition, acute respiratory distress syndrome was more often observed in the Allo-R group than in the other groups (P = 0.002). A significantly higher rate of antibiotic use and longer hospital stays were observed in the Allo-R group compared with the Ind group. Multivariate logistic regression analysis revealed that the presence of allopatric antibiotic-resistant microbes in the oropharynx was an independent risk factor for postoperative pneumonia (odds ratio, 3.93; 95% confidence interval, 2.41-6.42). The overall survival was significantly poorer in the Allo-R group than in the other groups. CONCLUSIONS: Preoperative oropharyngeal culture is a simple and low-cost method that can predict both the occurrence of postoperative pneumonia and poor prognosis after esophagectomy.

A multicentre analysis of Nocardia pneumonia in Spain: 2010-2016.

OBJECTIVE: To analyse all cases of Nocardia pneumonia occurring between 2010 and 2016 in five Spanish hospitals. METHODS: This was a retrospective observational analysis of clinical and microbiological data collected from 55 cases of Nocardia pneumonia. RESULTS: There were one to 20 cases per hospital and six to nine cases per year. Chronic obstructive pulmonary disease, bronchiectasis, and asthma were the main predisposing underlying respiratory conditions. Thirty-four patients were receiving systemic and/or inhaled corticosteroids prior to infection, eight had neoplasia, and six had haematological malignancies. Clinical and radiological findings were common to pneumonia of other infectious aetiologies, except for the frequent presence of nodules and cavitation. Overall, the 1-year mortality was high (38.2%), and mortality was directly related to the pulmonary disease in 15 patients (27.3%). The most frequently identified species were N. cyriacigeorgica (n=21), N. abscessus (n=8), and N. farcinica (n=5). All Nocardia isolates were susceptible to linezolid and all but two were susceptible to amikacin and trimethoprim-sulfamethoxazole. CONCLUSIONS: Nocardia pneumonia-associated mortality remains high, probably because of the debilitated status of patients in whom this pathogen is able to cause pulmonary infection.

Hafnia alvei pneumonia: a rare cause of infection in the multimorbid or immunocompromised.

Hafnia alvei is a rare, poorly understood commensal bacterium which has, on occasion, been shown to infect humans. We present two cases. The first patient presented with a 1-week history of dyspnoea, pleurisy and a productive cough, and the second with a prodrome of fatigue and night sweats. The former had a history of severe chronic obstructive pulmonary disease and the latter had a history of Crohn's disease. Both patients had underlying comorbidities and immunosuppression, but differed in presentation, radiological findings and recovery. This case series aims to remind readers of the broad differential of pathogens that can lead to disease in the immunocompromised and that one should not dismiss atypical cultured bacteria as commensal too hastily.