Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5-52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures

an observational study

Pulmonary tuberculosis (PTB) results in lung functional impairment and there are no surrogate markers to monitor the extent of lung involvement. We investigated the clinical significance of S100A12 and soluble receptor for advanced glycation end-products (sRAGE) for predicting the extent of lung involvement. We performed an observational study in India with 119 newly diagnosed, treatment naïve, sputum smear positive, HIV-negative PTB patients and 163 healthy controls. All patients were followed-up for six months. Sociodemographic variables and the serum levels of S100A12, sRAGE, esRAGE, HMGB-1, TNF-α, IFN-γ and CRP were measured. Lung involvement in PTB patients was assessed by chest radiography. Compared with healthy controls, PTB patients had increased serum concentrations of S100A12 while sRAGE was decreased. S100A12 was an independent predictor of disease occurrence (OR 1.873, 95%CI 1.212–2.891, p = 0.004). Under DOTS therapy, S100A12 decreased significantly after 4 months whereas CRP significantly decreased after 2 months (p < 0.0001). Importantly, although CRP was also an independent predictor of disease occurrence, only S100A12 was a significant predictor of lung alveolar infiltration (OR 2.60, 95%CI 1.35–5.00, p = 0.004). These results suggest that S100A12 has the potential to assess the extent of alveolar infiltration in PTB

An Observational Study in Hyderabad/India

Background Existing reading schemes for chest X-ray (CXR) used to grade the extent of disease severity at diagnosis in patients with pulmonary tuberculosis (PTB) are often based on numerical scores that summate specific radiographic features. However, since PTB is known to exhibit a wide heterogeneity in pathology, certain features might be differentially associated with clinical parameters of disease severity. Objective We aimed to grade disease severity in PTB patients at diagnosis and after completion of DOTS treatment by developing a reading scheme based on five different radiographic manifestations and analyze their association with the clinical parameters of systemic involvement and infectivity. Methods 141 HIV-negative adults with newly diagnosed sputum smear-positive PTB were enrolled in a prospective observational study in Hyderabad, India. The presence and extent on CXRs of five radiographic manifestations, i.e., lung involvement, alveolar infiltration, cavitation, lymphadenopathy and pleural effusion, were classified using the new reading scheme by using a four-quadrant approach. We evaluated the inter-reader reliability of each manifestation, and its association with BMI and sputum smear positivity at diagnosis. The presence and extent of these radiographic manifestations were further compared with CXRs on completion of DOTS treatment. Results At diagnosis, an average lung area of 51.7% +/- 23.3% was affected by radiographic abnormalities. 94% of the patients had alveolar infiltrates, with 89.4% located in the upper quadrants, suggesting post primary PTB and in 34.8% of patients cavities were found. We further showed that the extent of affected lung area was a negative predictor of BMI (β value -0.035, p 0.019). No significant association of BMI with any of the other CXR features was found. The extent of alveolar infiltrates, along with the presence of cavitation, were strongly associated with sputum smear positivity. The microbiological cure rate in our cohort after 6 months of DOTS treatment was 95%. The extent of the affected lung area in these patients decreased from 56.0% +/- 21.5% to 31.0 +/- 20% and a decrease was also observed in the extent of alveolar infiltrates from 98.4% to 25.8% in at least one quadrant, presence of cavities from 34.8% to 1.6%, lymphadenopathy from 46.8% to 16.1%, and pleural effusion from 19.4% to 6.5%. Conclusions We established a new assessment scheme for grading disease severity in PTB by specifically considering five radiographic manifestations which were differently associated with the BMI and sputum smear positivity, changed to a different extent after 6 months of treatment and exhibited an excellent agreement between radiologists. Our results suggest that this reading scheme might contribute to the estimation of disease severity with respect to differences in disease pathology. Further studies are needed to determine a correlation with short and long-term pulmonary function impairment and whether there would be any benefit in lengthening or modulating therapy based on this CXR severity assessment

Mediastinal mass in an tuberculosis-exposed 2-year old child with neurofibromatosis type 1 – TB or not TB?

A toddler with neurofibromatosis type 1 (NF1) was evaluated for tuberculosis (TB) after exposure. Chest X-ray (CXR) revealed a mediastinal mass indicating lymphadenopathy. However, magnetic resonance imaging showed a large plexiform thoracic neurofibroma. CXR performed for TB screening in NF1 patients cannot clearly differentiate lymphadenopathy from thoracic plexiform neurofibroma. Cross sectional imaging is therefore indicated for classification of mediastinal masses

Specific Chest Radiograph (CXR) features of lung involvement.

<p>(SD) standard deviation.</p><p>Specific Chest Radiograph (CXR) features of lung involvement.</p

Univariable linear regression: association of affected lung area with BMI

<p><b>Model parameters dependent variable BMI: Model 1</b> Constant 17.53 ANOVA 0.008, R² 0.044. <b>Model 2</b> Constant 18.22 ANOVA <0.0001, R² 0.087. <b>Model 3</b> Constant 18.21 ANOVA 0.002, R² 0.076.</p><p>Univariable linear regression: association of affected lung area with BMI</p

Chest Radiograph (CXR) results according to the presence of alveolar infiltrates in the upper or lower lung lobe.

<p>Chest Radiograph (CXR) results according to the presence of alveolar infiltrates in the upper or lower lung lobe.</p

Univariable and multivariable ordinal regression: association of alveolar infiltrates and cavities with number of bacteria in sputum smear.

<p><b>Dependent ordinal variable sputum smear (<1+, 1+, 2+ and 3+). Model 1</b> -2Log 52, Chi² 0.015, Goodness of fit 0.88, Pseudo R² (Cox and snell 0.084 and Nagelkerke 0.091), test of parallel lines 0.021. <b>Model 2</b> -2Log 27.5, Chi² 0.068, Goodness of fit 0.98, Pseudo R² (Cox and snell 0.037 and Nagelkerke 0.040), test of parallel lines 0.971. <b>Model 3</b> -2Log 53, Chi² 0,020, Goodness of fit 0,083, Pseudo R² (Cox and snell 0,067 and Nagelkerke 0,041), test of parallel lines 0,240. <b>Model 4</b> -2Log 158, Chi² 0.08, Goodness of fit 0,012, Pseudo R² (Cox and snell 0.11 and Nagelkerke 0.12), test of parallel lines 0.022. <b>Model 5</b> -2Log 100, Chi² 0.009, Goodness of fit 0,080, Pseudo R² (Cox and snell 0.11 and Nagelkerke 0.12), test of parallel lines 0.075. <b>Reference categories:</b> Sputum smear: 3+, Alveolar infiltrates: No infiltration, Cavities: 2 cavities.</p><p>Univariable and multivariable ordinal regression: association of alveolar infiltrates and cavities with number of bacteria in sputum smear.</p

Univariable logistic regression: association of CXR score based on the affected area of the lung and presence of cavitation with two-month sputum smear.

<p><b>Model parameters: Model 1</b> constant:- 2.22, -2Log likelihood 65.9-Chi² 0.31, Hosmer and lemeshow test <0.0001, R² (Cox 0.007 and Nagelkerke 0.019). <b>Model 2</b> constant:- 3.07, -2Log likelihood 66.7-Chi² 6.37, Hosmer and lemeshow test 0.206, R² (Cox 0.002 and Nagelkerke 0.004). <b>Model 3</b> constant:- 3.77, -2Log likelihood 65-Chi² 1.67, Hosmer and lemeshow test 0.446, R² (Cox 0.013 and Nagelkerke 0.036).</p><p>Univariable logistic regression: association of CXR score based on the affected area of the lung and presence of cavitation with two-month sputum smear.</p