Acute Pediatric Infections Research Articles

Intact FGF23 and Markers of Iron Homeostasis, Inflammation, and Bone Mineral Metabolism in Acute Pediatric Infections.

We intend to evaluate the association of intact Fibroblast Growth Factor 23 (i-FGF23), a phosphaturic hormone that contributes to anemia of inflammation, with markers of iron homeostasis, inflammation, and bone mineral metabolism in acute pediatric infections. Seventy-nine children, aged 1 month-13 years, out of which forty-two were males and thirty-seven females, participated in this study. Children with diseases and nutrient deficiencies causing anemia were excluded. Twenty-six patients had bacterial infections, twenty-six had viral infections, and twenty-seven children served as healthy controls. Complete blood count, markers of inflammation, iron and mineral metabolism, serum hepcidin, and i-FGF23 were compared between the groups. Thirty-nine percent of patients with bacterial infection and twelve percent of patients with viral infection presented characteristics of anemia of inflammation (p < 0.001). Ninety-two percent of patients with bacterial infection and eighty-one percent of patients with viral infection had functional iron deficiency (p < 0.001). Hepcidin was significantly positively correlated with the duration of fever, markers of inflammation, and negatively with iron, mineral metabolism parameters, and i-FGF23. i-FGF23 was positively correlated with iron metabolism parameters and negatively with the duration of fever, markers of inflammation, and hepcidin. Hepcidin levels increase, whereas i-FGF23 levels decrease in acute pediatric infections. Further research is required to understand the role of FGF23 in the hepcidin-ferroportin axis and for hepcidin in the diagnosis of bacterial infections and mineral metabolism.

Decision Challenges for Managing Acute Paediatric Infections: Implications for Antimicrobial Resistance.

Overprescribing of antibiotics in paediatrics accounts for a significant proportion of inappropriate antibiotic use in human healthcare, thereby contributing to the global health emergency of antimicrobial resistance. Antimicrobial stewardship efforts are complicated by the unique social dynamics in paediatric healthcare, with a specific challenge being the prominent role of parents and carers who act as intermediaries between prescribers and paediatric patients. In this Perspective article concentrating on healthcare of the United Kingdom, we describe this complicated interplay of different decision stakeholders (patients, parents and prescribers), outline four dimensions of decision challenges (social, psychological, systemic and specific diagnostic and treatment challenges) and provide a number of theory-based strategies for supporting different stakeholders during the decision process, ultimately with the aim of improving antimicrobial stewardship. Key decision challenges for patients and carers include limited knowledge and experience of managing infections, which were exacerbated during the COVID-19 pandemic and frequently result in health anxiety and inappropriate health-seeking behaviours. Challenges for medical prescribers span societal pressures from prominent patient litigation cases, cognitive biases, and system pressures to specific diagnostic problems (e.g., age limitations of current clinical scoring systems). Strategies for mitigating decision challenges in paediatric infection management will need to include a range of context- and stakeholder-specific actions, including improvements of integrated care and public health education as well as better clinical decision tools and access to evidence-based guidelines.

Role of probiotics and vitamins in maintaining a healthy gut microbiome: recent advances

While the concept of probiotics is not new, science based approaches to developing targeted probiotic products are a renewed interest. Probiotics and the microbiome is now being considered as having a blueprint of good health, unique to every human. Along with the well-known and established health benefits like reduced antibiotic associated diarrhoea and colic symptoms, eczema, necrotising enterocolitis, acute paediatric infections like diahorrea and upper respiratory tract infections; probiotics are now considered as beneficial for maintaining mental well-being as well. This new branch of disease management is now termed as Nutritional neuroscience and these beneficial gut bacteria are referred to as psychobiotics. It is important to identify the specific strains of probiotics and characterize them and conduct randomised controlled trials to establish these benefits. With emerging data related to role of vitamins in modulating the gut microbiome, combining pre and probiotics with micronutrients is likely to result in powerful functional foods boosting host immunity.

1123. Specificity of Diagnosis Codes and Adequacy of Supportive Documentation for Common Acute Pediatric Infections: Implications for Ambulatory Stewardship

BackgroundAssessing the appropriateness of antibiotic prescribing in ambulatory care generally relies on the accuracy of diagnosis codes, which is uncertain. It is also uncertain if documented history and physical findings support antibiotic indications (AI). We completed a retrospective study of pediatric primary care (PPC) encounters to determine: A) if documented findings supported documented AI; and B) whether diagnosis codes captured documented AI (figure).MethodsWe conducted point-prevalence audits of the 9 PPC clinics in our healthcare system, randomly selecting one weekday per month to review all visits between 9/2017 and 4/2018. We included only encounters with antibiotic prescribing. We reviewed clinician notes, orders, laboratory results, and ICD-10 diagnosis codes. We recorded demographics; visit date/location; AI as documented in notes; history, examination, and laboratory findings; and diagnosis codes. We used national guidelines to determine whether documentation supported AI. We calculated the sensitivity of diagnosis codes using documented AI as the gold standard.ResultsThe sample included 452 encounters. The most common AI were acute otitis media (AOM), pharyngitis, and sinusitis. For AOM, 163 of 168 encounters (97.0%) had an appropriate diagnosis code; for pharyngitis, 127 of 138 (92.0%); and for sinusitis, 68 of 75 (90.7%). For AOM, 160 of 168 encounters (95.2%) had adequate documentation of supportive findings. For sinusitis, 44 of 75 encounters had adequate supporting history and/or examination findings (58.7%). For pharyngitis, while 135 of 139 (97.1%) had a positive streptococcal test, 104 of 139 (74.8%) had history and examination findings to support testing.ConclusionBy chart review, we identified each AI and evaluated whether findings supported those AI. The sensitivity of diagnosis codes for AI ranged from 90.7–97.0% for common conditions; this result can inform the design of ambulatory stewardship programs. Only 74.8% of children treated for pharyngitis and 58.7% of children treated for sinusitis had sufficient supporting documentation. Use of discrete data elements alone (Figure 1) may result in overestimates of the proportion of children for whom antibiotics are appropriate. Further research is needed across healthcare settings. Disclosures All authors: No reported disclosures

Prescription practices in acute pediatric infections and their implications on the worldwide antimicrobial resistance

A large proportion of antimicrobial agents are prescribed worldwide for acute respiratory infections, including colds, upper respiratory infections, acute bronchitis, pharyngo-tonsillitis, sinusitis, and acute otitis media [1–9]. Many of these infections are viral in nature, and antimicrobials are of no benefit. However, the widespread and inappropriate utilization of antimicrobials for such viral illnesses is the driving force behind the emergence of infections caused by antimicrobial drug-resistant organisms [10–12]. Antimicrobial drug – resistant strains of communityacquired pathogens, including Streptococcus pneumoniae, Haemophillus influenzae, and Staphylococcusaureus, have emerged as serious global health threats [13– 15]. In the United States the proportion of invasive infections caused by penicillin-nonsusceptible S. pneumoniae increased from 1% in 1992 to 27% in 2000 [10]. Multiple drug resistance of S. pneumoniae has also escalated in frequency as the proportion of S. pneumoniae isolates nonsusceptible to 3 classes of antimicrobial drugs increased from 7% in 1995 to 19% in 2000 [10].

Prescription practices in acute pediatric infections

Optimal medical care requires that patients receive medications appropriate to their clinical needs. To achieve this objective it is essential that irrational patient management practices are ident ...

Global gene expression profiling identifies new therapeutic targets in acute Kawasaki disease.

BackgroundGlobal gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD.MethodsTo gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes.ResultsThe overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target.ConclusionOur study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0102-6) contains supplementary material, which is available to authorized users.

Feline Immunodeficiency Virus Depletes Naïve (CD45RA+) CD4+ Lymphocytes from the Blood and Lymph Nodes of Domestic Cats during Acute Pediatric Infection.

Feline immunodeficiency virus (FIV) is an immunosuppressive lentivirus of domestic cats that serves as an animal model for the pathogenesis of CD4+ lymphopenia and thymus dysfunction in HIV infected humans. During most cases of adult and pediatric HIV infection, naïve CD4+ T lymphocytes recognized by the expression of the RA isoform of the leukocyte common antigen (CD45RA) are infected at a lower level than memory CD4+ T− lymphocytes; however, children with rapidly progressive disease due to thymic insufficiency harbor high levels of HIV within the CD45RA+ subpopulation. In FIV infected cats, the fate of naïve CD4 lymphocytes is unknown due to the lack of specific markers. Recently, a mAb (755) was reported to recognize the feline homologue to CD45RA, allowing the enumeration of naïve CD4 and CD8 lymphocytes in cats. The purpose of this study was to characterize the fate of CD4+CD45RA+ blood cells eight weeks after FIV infection. One-day-old kittens (n=6) were infected with virions either from a wild type clone (JSY3) or mutant ORF-A clone at equivalent reverse transcriptase units and compared to historical control data. Eight weeks after inoculation, the percentages of CD4+ and CD8+ cells belonging to the CD45RA+ subpopulation were measured by two-color flow cytometry. Both FIV inocula were associated with a reduction in total CD4+ lymphocytes from a median of 13% in controls to 8% in infected cats (P=0.004), contributing to a reduction in the CD4:CD8 ratio from 2.45 in controls to 0.76 in infected cats (P=0.007). The decline in CD4+ lymphocytes was attributable to a disproportionate loss of CD4+CD45RA+ cells: 69% of CD4+ cells were CD45RA+ in controls, as compared to 7% in FIV infected cats (P=0.004). In contrast, naïve CD8+ lymphocytes did not change significantly with FIV infection (67% of CD8+ cells were CD45RA+ in FIV infected cats as compared to 80% in controls). The distribution of CD45RA+ cells in the lymph nodes of FIV infected cats mirrored those in the blood. Together, these data suggest that acute FIV infection results in a rapid depletion of naïve CD4 lymphocytes throughout the blood and secondary lymphoid tissues, while proportions of naïve CD8 lymphocytes remain unchanged. CD4+CD45RA+ cells may be depleted during pediatric FIV infection through lytic infection or a transition to a memory phenotype lacking CD45RA.

Fundamental and clinical studies on T-1982 (cefbuperzone), a new cephamycin antibiotic, in the field of pediatrics

Studies on T-1982 (cefbuperazone), a new cephamycin antibiotic, were carried out in the field of pediatrics, and the following results were obtained. 1. Peak MIC of T-1982 against S. pyogenes (group A) lately isolated was 0.39 micrograms/ml, and the drug was active even against highly resistant strains of macrolides, lincomycin, tetracycline and chloramphenicol. 2. Peak MICs of T-1982 were 0.78 microgram/ml against B. pertussis, 0.2 microgram/ml against E. coli and less than or equal to 0.05 microgram/ml against K. oxytoca, and the drug was also active against ampicillin-resistant bacteria. 3. Serum levels and urinary excretions of T-1982 were investigated in 6 cases. When given at a dose of 20-28 mg/kg by 1 hour intravenous drip infusion, serum concentrations of T-1982 attained the peak level of 63.5-75.9 micrograms/ml at the end of administration and sustained the level of 0.9-2.6 micrograms/ml at 6 hours, the serum half-life (T 1/2) ranging 70-82 minutes. Approximately 20-72% of the dose were excreted in the active form into urine within 6 hours. 4. Twenty-seven cases of acute pediatric infections were treated with T-1982 mainly by intravenous drip infusion, and satisfactory clinical results were obtained in all the cases of angina lacunaris, bronchitis, bronchopneumonia, pertussis, sepsis caused by Serratia and acute urinary tract infections caused by ampicillin-resistant E. coli. The efficacy rate was 96.3%. In this study the drug was administered chiefly at a daily dose of 50-70 mg/kg 2-3 times a day for 2-12 days. 5. Gram-positive cocci (S. aureus, S. pneumoniae, S. pyogenes) and Gram-negative rods (H. influenzae, H. parainfluenzae P. vulgaris, B. pertussis, S. marcescens, E. coli) were eradicated by the treatment with T-1982. 6. No noticeable side effects were observed, except for temporary increase of eosinophil in 2 cases and slight elevation of GOT in 1 case.

Experience with clindamycin-2-palmitate in some acute pediatric infections (author's transl)

Experience with clindamycin-2-palmitate in some acute pediatric infections (author's transl)