Overlapping presentation of fungal tubulointerstitial nephritis in an immunosuppressed pediatric patient

With the expanding use of immunosuppressive therapies and broad-spectrum antibiotics, Candida species has become an increasingly important cause of infections, particularly in the presence of anti-tumor necrosis factor-α therapy. We report the case of a 17-year-old female with ulcerative colitis who developed oliguric renal failure following immunosuppressive and nephrotoxic therapy. Although urine cultures and urinary tract imaging were negative in the face of fungemia, renal biopsy was the key to establishing the diagnosis of fungal tubulo-interstitial nephritis as the primary reversible cause of the renal failure

Lobar pneumonia caused by Ralstonia pickettii in a sixty-five-year-old Han Chinese man: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Ralstonia pickettii </it>is a gram-negative, oxidase-positive bacillus and is an emerging pathogen found in infections described in hospital settings. The cases reported in the literature mostly are nosocomial infections due to contaminated blood products, sterile water, saline, treatment fluids and venous catheters. Human infection unrelated to contaminated solutions is rare. We report a case of lobar pneumonia and pulmonary abscess caused by <it>Ralstonia pickettii </it>in an older patient.</p> <p>Case presentation</p> <p>A sixty-five-year old Han Chinese man presented having had cough, expectoration, chest pain and fever lasting for twenty days. His medical history was notable for hypertension over the previous ten years, and the habit of smoking for forty years. A thoracic computed tomography scan supported the diagnosis of right-sided lobar pneumonia. A lung biopsy was done and pathological analysis confirmed lobar pneumonia. Two lung biopsy specimens from separate sites grew <it>Ralstonia pickettii</it>. After six days, a repeat thoracic scan revealed a right-sided abscess. A thoracentesis was performed and the purulent fluid grew <it>Ralstonia pickettii</it>. The chest tube remained inserted to rinse the cavity with sterile sodium chloride. He received an antibiotic course of intravenous cefoperazone sodium-sulbactam sodium for eighteen days and imipenem-cilastatin for twelve days. A repeat chest X-ray revealed resolution of the pulmonary abscess and improvement of pneumonia. He remained afebrile and free of respiratory symptoms after treatments.</p> <p>Conclusion</p> <p>This case demonstrates a <it>Ralstonia pickettii </it>infection in the absence of an obvious nosocomial source. It is possible that such cases will become common in the future. Therefore, further studies are needed to evaluate its sensitivity to common antibiotics.</p

Cytomegalovirus infection in pediatric rheumatic diseases: a review

Human cytomegalovirus (HCMV) is familiar to pediatric rheumatologists mainly as a cause of opportunistic disease in pharmacologically immune suppressed patients. However, HCMV also has a variety of immuno-modulatory effects, through which it may influence the course of rheumatic conditions. In this article we discuss the interplay between HCMV and the immune system, and review the clinical manifestations, diagnosis, and treatment of HCMV infection in children with rheumatic disease

Frequency of oral mucositis and microbiological analysis in children with acute lymphoblastic leukemia treated with 0.12% chlorhexidine gluconate

Tendo em vista o potencial de morbidade das complicações orais em pacientes com leucemia, este estudo avaliou as alterações clínicas e microbiológicas que ocorrem na mucosa bucal de crianças com leucemia linfoblástica aguda (LLA), submetidas à quimioterapia antineoplásica e administração profilática do gluconato de clorexidina 0,12%. A amostra foi constituída de 17 crianças de 2 a 12 anos, as quais foram submetidas a exame clínico da mucosa oral para a detecção de lesões bucais. Além disso, foi coletado material biológico das mucosas labial e jugal para análises microbiológicas. A mucosite oral foi observada em apenas 5 (29,4%) pacientes. A análise microbiológica revelou a presença de um número reduzido de microorganismos potencialmente patogênicos, como estafilococos coagulase-negativos (47%), Candida albicans (35,3%), Klebsiella pneumoniae (5,9%), Escherichia coli enteropatogênica (5,9%) e Stenotrophomonas maltophilia (5,9%). Pacientes com mucosite oral apresentaram uma maior freqüência de estafilococos coagulase-negativos (80%) quando comparados aos pacientes que exibiam mucosa oral normal (33,3%). Em conclusão, os resultados do presente estudo sugerem que o uso profilático do gluconato de clorexidina 0,12% reduz a freqüência de mucosite oral e de patógenos orais em crianças com LLA. Além disso, os presentes achados sugerem uma possível relação entre estafilococos coagulase-negativos e o desenvolvimento de mucosite oral. _________________________________________________________________________________________ ABSTRACT: In view of the morbidity potential of oral complications in patients with leukemia, this study evaluated the clinical and microbiological alterations that occur in the oral mucosa of children with acute lymphoblastic leukemia (ALL) undergoing antineoplastic chemotherapy and prophylactic administration of 0.12% chlorhexidine gluconate. The sample consisted of 17 children aged 2 to 12 years that underwent clinical examination of the oral mucosa for the detection of oral lesions. In addition, biological material was collected from labial and buccal mucosa for microbiological analysis. Oral mucositis was observed in only 5 (29.4%) patients. Microbiological analysis revealed a reduced number of potentially pathogenic microorganisms, such as coagulase-negative staphylococci (47%), Candida albicans (35.3%), Klebsiella pneumoniae (5.9%), enteropathogenic Escherichia coli (5.9%), and Stenotrophomonas maltophilia (5.9%). Patients with oral mucositis showed a higher frequency of coagulase-negative staphylococci (80%) when compared with patients with normal oral mucosa (33.3%). In conclusion, the results of the present study suggest that the prophylactic use of 0.12% chlorhexidine gluconate reduces the frequency of oral mucositis and oral pathogens in children with ALL. In addition, the present findings suggest a possible relationship between coagulase-negative staphylococci and the development of oral mucositis

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Biological Roles of the O-Methyl Phosphoramidate Capsule Modification in Campylobacter jejuni.

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS) of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN) modification present on most C. jejuni isolates. Although the MeOPN structure is rare in nature it has structural similarity to some synthetic pesticides. In this study, we have demonstrated, by whole genome comparisons and high resolution magic angle spinning NMR, that MeOPN modifications are common to several Campylobacter species. Using MeOPN biosynthesis and transferase mutants generated in C. jejuni strain 81-176, we observed that loss of MeOPN from the cell surface correlated with increased invasion of Caco-2 epithelial cells and reduced resistance to killing by human serum. In C. jejuni, the observed serum mediated killing was determined to result primarily from activation of the classical complement pathway. The C. jejuni MeOPN transferase mutant showed similar levels of colonization relative to the wild-type in chickens, but showed a five-fold drop in colonization when co-infected with the wild-type in piglets. In Galleria mellonella waxmoth larvae, the MeOPN transferase mutant was able to kill the insects at wild-type levels. Furthermore, injection of the larvae with MeOPN-linked monosaccharides or CPS purified from the wild-type strain did not result in larval killing, indicating that MeOPN does not have inherent insecticidal activity

Use of the WHO Access, Watch, and Reserve classification to define patterns of hospital antibiotic use (AWaRe): an analysis of paediatric survey data from 56 countries

BACKGROUND: Improving the quality of hospital antibiotic use is a major goal of WHO's global action plan to combat antimicrobial resistance. The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate simple stewardship interventions that are widely applicable globally. We aimed to present data on patterns of paediatric AWaRe antibiotic use that could be used for local and national stewardship interventions. METHODS: 1-day point prevalence survey antibiotic prescription data were combined from two independent global networks: the Global Antimicrobial Resistance, Prescribing, and Efficacy in Neonates and Children and the Global Point Prevalence Survey on Antimicrobial Consumption and Resistance networks. We included hospital inpatients aged younger than 19 years receiving at least one antibiotic on the day of the survey. The WHO AWaRe classification was used to describe overall antibiotic use as assessed by the variation between use of Access, Watch, and Reserve antibiotics, for neonates and children and for the commonest clinical indications. FINDINGS: Of the 23 572 patients included from 56 countries, 18 305 were children (77·7%) and 5267 were neonates (22·3%). Access antibiotic use in children ranged from 7·8% (China) to 61·2% (Slovenia) of all antibiotic prescriptions. The use of Watch antibiotics in children was highest in Iran (77·3%) and lowest in Finland (23·0%). In neonates, Access antibiotic use was highest in Singapore (100·0%) and lowest in China (24·2%). Reserve antibiotic use was low in all countries. Major differences in clinical syndrome-specific patterns of AWaRe antibiotic use in lower respiratory tract infection and neonatal sepsis were observed between WHO regions and countries. INTERPRETATION: There is substantial global variation in the proportion of AWaRe antibiotics used in hospitalised neonates and children. The AWaRe classification could potentially be used as a simple traffic light metric of appropriate antibiotic use. Future efforts should focus on developing and evaluating paediatric antibiotic stewardship programmes on the basis of the AWaRe index. FUNDING: GARPEC was funded by the PENTA Foundation. GARPEC-China data collection was funded by the Sanming Project of Medicine in Shenzhen (SZSM2015120330). bioMérieux provided unrestricted funding support for the Global-PPS