Italian consensus on the therapeutic management of uncomplicated acute hematogenous osteomyelitis in children.
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ABSTRACT: Background
Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient's age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection.Methods
A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study.Results
Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment.Conclusions
The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.
SUBMITTER: Krzysztofiak A
PROVIDER: S-EPMC8403408 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundClinicians cannot reliably predict complications of acute hematogenous osteomyelitis (AHO).MethodsConsecutive cases of AHO from 2 pediatric centers in the United States were analyzed retrospectively to develop clinical tools from data obtained within 96 hours of hospitalization to predict acute and chronic complications of AHO. Two novel composite prediction scores derived from multivariable logistic regression modeling were compared with a previously published severity of illness (SOI) score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using area under the receiver operating characteristic curve analyses.ResultsThe causative organisms were identified in 73% of 261 cases. Bacteremia (45%), abscesses (38%), and associated suppurative arthritis (23%) were relatively common. Acute or chronic complications occurred in 24% and 11% of patients, respectively. Multivariable logistic regression identified bone abscess (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0-5.2]), fever > 48 hours (OR, 2.7 [95% CI, 1.2-6.0]), suppurative arthritis (OR, 3.2 [95% CI, 1.3-7.5]), disseminated disease (OR, 4.6 [95% CI, 1.5-14.3]), and delayed source control (OR, 5.1 [95% CI, 1.4-19.0]) as strong predictors of acute complications. In a separate model, CRP ≥ 100 mg/L at 2-4 days after antibiotics (OR, 2.7 [95% CI, 1.0-7.3]), disseminated disease (OR, 3.3 [95% CI, 1.1-10.0]), and requirement for bone debridement (OR, 6.7 [95% CI, 2.1-21.0]) strongly predicted chronic morbidity. These variables were combined to create weighted composite prediction scores for acute (A-SCORE) and chronic (C-SCORE) osteomyelitis, which were superior to SOI, CRP, and ESR and had negative predictive values > 90%.ConclusionsTwo novel composite clinical scores were superior to existing tools to predict complications of pediatric AHO.
| S-EPMC7904074 | biostudies-literature
Project description:Background:Children with acute hematogenous osteomyelitis (AHO) have a broad spectrum of illness ranging from mild to severe. The purpose of this study is to evaluate the impact of genomic variation of Staphylococcus aureus on clinical phenotype of affected children and determine which virulence genes correlate with severity of illness. Methods:De novo whole genome sequencing was conducted for a strain of Community Acquired Methicillin Resistant Staphylococcus aureus (CA-MRSA), using PacBio Hierarchical Genome Assembly Process (HGAP) from 6 Single Molecule Real Time (SMRT) Cells, as a reference for DNA library assembly of 71 Staphylococcus aureus isolates from children with AHO. Virulence gene annotation was based on exhaustive literature review and genomic data in NCBI for Staphylococcus aureus. Clinical phenotype was assessed using a validated severity score. Kruskal-Wallis rank sum test determined association between clinical severity and virulence gene presence using False Discovery Rate (FDR), significance <0.01. Results:PacBio produced an assembled genome of 2,898,306 bp and 2054 Open Reading Frames (ORFs). Annotation confirmed 201 virulence genes. Statistical analysis of gene presence by clinical severity found 40 genes significantly associated with severity of illness (FDR ?0.009). MRSA isolates encoded a significantly greater number of virulence genes than did MSSA (p < 0.0001). Phylogenetic analysis by maximum likelihood (PAML) demonstrated the relatedness of genomic distance to clinical phenotype. Conclusions:The Staphylococcus aureus genome contains virulence genes which are significantly associated with severity of illness in children with osteomyelitis. This study introduces a novel reference strain and detailed annotation of Staphylococcus aureus virulence genes. While this study does not address bacterial gene expression, a platform is created for future transcriptome investigations to elucidate the complex mechanisms involved in childhood osteomyelitis.
| S-EPMC6039886 | biostudies-literature
Project description:AimsThis study aims to evaluate the diagnostic value of blood metagenomic next-generation sequencing (mNGS) in detecting pathogens from patients clinically diagnosed as acute hematogenous osteomyelitis (AHO).MethodsThis retrospective study enrolled 66 patients with AHO. The test results of mNGS and bacterial culture on different samples, including blood and puncture fluid samples, from patients with AHO were compared to explore the diagnostic value of blood mNGS. Besides, this study also explored the efficacy of blood mNGS in decision making for antibiotic administration and analyzed the factors associated with the positive result of blood mNGS.ResultsThe most common causative pathogens were Staphylococcus and Streptococcus. The sensitivity of blood mNGS (77.3%) was higher than that of blood culture (42.4%) (P<0.001), while the turnaround time of blood mNGS (2.1 ± 0.4 d) is much less than that of blood culture (6.0 ± 2.1 d) (P<0.001). Besides, the sensitivity of blood mNGS tests (77.3%) was slightly lower than that of puncture fluid mNGS (89.4%). Furthermore, detection comparison at pathogen level unravels that blood mNGS might be suitable for diagnosing AHO caused by common pathogens, while puncture fluid mNGS could be considered as preferred examination in diagnosing AHO caused by uncommon pathogens. Finally, three independent factors associated with the true positive result of blood mNGS in patients with AHO were identified, including Gram-positive pathogens (OR=24.4, 95% CI = 1.4-421.0 for Staphylococcus; OR=14.9, 95%CI= 1.6-136.1 for other Gram-positive bacteria), body temperature at sampling time (OR=8.2, 95% CI = 0.6-107.3 for body temperature of >38.5°C; OR=17.2, 95% CI = 2.0-149.1 for patients who were chilling), and no use of antibiotics before sampling (OR=8.9, 95% CI =1.4-59.0).ConclusionThis is the first report on evaluating and emphasizing the importance of blood mNGS in diagnosing AHO. Blood sample might be an alternative sample for puncture fluid for mNGS, and its extensive application in diagnosing AHO could be expected.
| S-EPMC9911542 | biostudies-literature
Project description:BACKGROUND:Acute hematogenous osteomyelitis (AHO) occurs primarily in children and is believed to evolve from bacteremia followed by localization of infection to the metaphysis of bones. Currently, there is no consensus on the route and duration of antimicrobial therapy to treat AHO. METHODS:We conducted a systematic review of a short versus long course of treatment for AHO due primarily to Staphylococcus aureus in children aged 3 months to 16 years. We searched Medline, Embase and the Cochrane trials registry for controlled trials. Clinical cure rate at 6 months was the primary outcome variable, and groups receiving less than 7 days of intravenous therapy were compared with groups receiving one week or longer of intravenous antimicrobials. RESULTS:12 eligible prospective studies, one of which was randomized, were identified. The overall cure rate at 6 months for the short course of intravenous therapy was 95.2% (95% CI = 90.4 - 97.7) compared to 98.8% (95% CI = 93.6, 99.8) for the longer course of therapy. There was no significant difference in the duration of oral therapy between the two groups. CONCLUSIONS:Given the potential increased morbidity and cost associated with longer courses of intravenous therapy, this finding should be confirmed through a randomized controlled equivalence trial
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Project description:BackgroundThe rate of chronic drooling in children older than 4 years is 0.5%, but it rises to 60% in those with neurological disorders. Physical and psychosocial consequences lead to a reduction in the quality of Life (QoL) of affected patients; however, the problem remains under-recognized and under-treated. We conducted an Italian consensus through a modified Delphi survey to discuss the current treatment paradigm of drooling in pediatric patients with neurological disorders.MethodsAfter reviewing the literature, a board of 10 experts defined some statements to be administered to a multidisciplinary panel through an online encrypted platform. The answers to the questions were based on a 1-5 Likert scale (1 = strongly disagree; 5 = strongly agree). The scores were grouped into 1-2 (disagreement) and 4-5 (agreement), while 3 was discarded. The consensus was reached when the sum of the disagreement or agreement was ≥75%.ResultsFifteen statements covered three main topics, namely clinical manifestations and QoL, quantification of drooling, and treatment strategies. All statements reached consensus (≥75% agreement). The 55 Italian experts agreed that drooling should be assessed in all children with complex needs, having a major impact on the QoL. Attention should be paid to investigating posterior hypersalivation, which is often neglected but may lead to important clinical consequences. Given that the severity of drooling fluctuates over time, its management should be guided by the patients' current needs. Furthermore, the relative lack of validated and universal scales for drooling quantification limits the evaluation of the response to treatment. Finally, the shared therapeutic paradigm is progressive, with conservative treatments preceding the pharmacological ones and reserving surgery only for selected cases.ConclusionThis study demonstrates the pivotal importance of a multidisciplinary approach to the management of drooling. National experts agree that progressive treatment can reduce the incidence of complications, improve the QoL of patients and caregivers, and save healthcare resources. Finally, this study highlights how the therapeutic strategy should be reconsidered over time according to the available drugs on the market, the progression of symptoms, and the patients' needs.
| S-EPMC9297577 | biostudies-literature
Project description:BackgroundCurrent guidelines recommend assessing and relieving pain in all children and in all instances; yet, in clinical practice, management is frequently suboptimal. We investigated the attitude of Italian family pediatricians towards the evaluation and treatment of different types of acute pain in children aged 7-12 years.MethodsThis is a cross-sectional study based on a 17-question survey accessible online from October 2017 to October 2018. Responders had to describe cases of children suffering from any type of acute pain among headache, sore throat, musculoskeletal/post-traumatic pain, and earache. Children's characteristics, pain assessment modalities and therapeutic approaches were queried. The following tests were used: Z-proportion to evaluate the distribution of categorical data; chi-squared and Kruskall-Wallis to explore data heterogeneity across groups; Mann-Whitney for head-to-head comparisons.ResultsOverall, 929 pediatricians presented 6335 cases uniformly distributed across the types examined. Pain was more frequently of moderate intensity (42.2%, P < 0.001) and short duration (within some days: 98.4%, P < 0.001). Only 50.1% of responders used an algometric scale to measure pain and 60.5% always prescribed a treatment. In children with mild-moderate pain (N = 4438), the most commonly used first-line non-opioids were ibuprofen (53.3%) and acetaminophen (44.4%). Importantly, a non-recommended dosage was prescribed in only 5.3% of acetaminophen-treated cases (overdosing). Among the misconceptions emerged, there were the following: i) ibuprofen and acetaminophen have different efficacy and safety profiles (when choosing the non-opioid, effectiveness weighted more for ibuprofen [79.7% vs 74.3%, P < 0.001] and tolerability for acetaminophen [74.0% vs 55.4%, P < 0.001]); ii) ibuprofen must be taken after meals to prevent gastric toxicities (52.5%); ibuprofen and acetaminophen can be used combined/alternated for persisting mild-moderate pain (16.1%). In case of moderate-severe pain not completely controlled by opioids, ibuprofen and acetaminophen were the most used add-on medications, with ibuprofen being much more prescribed than acetaminophen (65.2% vs 23.7%, respectively) overall and in all pain types.ConclusionsSeveral gaps exist between the current practice of pain assessment and treatment and recommendations. Further efforts are needed to raise awareness and improve education on the possible exposure of the child to short- and long-term consequences in case of suboptimal pain management.
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Project description:BackgroundPhenylketonuria (PKU) is a rare inherited metabolic disorder caused by defects in the phenylalanine-hydroxylase gene (PAH), the enzyme catalyzing the conversion of phenylalanine to tyrosine. PAH impairment causes phenylalanine accumulation in the blood and brain, with a broad spectrum of pathophysiological and neurological consequences for patients. Prevalence of disease varies, with peaks in some regions and countries, including Italy. A recent expert survey described the real-life of clinical practice for PKU in Italy, revealing inhomogeneities in disease management, particularly concerning approach to pharmacotherapy with sapropterin hydrochloride, analogous of the natural PAH co-factor, allowing disease control in a subset of patients. Therefore, the purpose of this paper is to continue the work initiated with the expert survey paper, to provide national guidances aiming to harmonize and optimize patient care at a national level.ParticipantsThe Consensus Group, convened by 10 Steering Committee members, consisted of a multidisciplinary crowd of 46 experts in the management of PKU in Italy.Consensus processThe Steering Committee met in a series of virtual meeting in order to discuss on clinical focuses to be developed and analyzed in guidance statements, on the basis of expert practice based evidence, large systematic literature review previously performed in the expert survey paper, and evidence based consensus published. Statements were re-discussed and refined during consensus conferences in the widest audience of experts, and finally submitted to the whole consensus group for a modified-Delphi voting.ResultsSeventy three statements, divided in two main clinical areas, PKU management and Pharmacotherapy, achieved large consensus in a multidisciplinary group of expert in different aspects of disease. Importantly, these statements involve guidances for the use of sapropterin dihydrochloride, still not sufficiently implemented in Italy, and a set of good practice to approach the use of novel enzyme replacement treatment pegvaliase.ConclusionsThis evidence-based consensus provides a minimum set of guidances for disease management to be implemented in all PKU centers. Moreover, these guidances represent the first statement for sapropterin dihydrochloride use, implementation and standardization in Italy, and a guide for approaching pegvaliase treatment at a national level on a consistent basis.
| S-EPMC8594187 | biostudies-literature
Project description:Osteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused by Staphylococcus aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or implantation of foreign material and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized the resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistant S. aureus isolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over 5 weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in the trabecular bone volume fraction but little effect on bone cortices. Histological assessment revealed differences in the precise focus of musculoskeletal infection, with various mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole-genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, this USA100 isolate showed a distinct predilection for septic arthritis compared to the other isolates tested, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.
| S-EPMC8445171 | biostudies-literature
Project description:INTRODUCTION:This article presents an overview of a prospective randomised controlled non-inferiority study designed to evaluate the safety and effectiveness of non-operative management (NOM) with operative management in children with acute uncomplicated appendicitis (AUA). Here, we present the study protocol for this APRES study, a multicentre Australian study. The rationale and details of future analysis, in particular, non-inferiority calculations, cost-effectiveness, feasibility and acceptability of each intervention. DESIGN:A multicentre, prospective randomised controlled clinical trial, conducted in 2 Australian tertiary paediatric hospitals. PARTICIPANTS:Children who meet the inclusion criteria of an age between 5 and 15?years and a clinical diagnosis of AUA will be invited to participate, and after consent will be randomised via a computer-based program into treatment groups. The study started in June 2016, and the target recruitment is 220 patients. INTERVENTIONS:Children in the control group will be treated with prophylactic antibiotics and appendicectomy, and those in the intervention group will be treated with antibiotic therapy alone. Primary outcome measures include unplanned or unnecessary operation and complications at 30?days. Secondary outcomes include longer term complications within 1 year, length of stay, time off work and school analgesic requirements and cost. ANALYSIS:Data analyses will be on the intention-to-treat principle using non-inferiority analysis. Analysis will include the Pearson ?2 test for categorical variables and independent sample t-test or Mann-Whitney test for continuous variables. Non-inferiority for NOM will be tested using 1-sided Wald tests with an ? level of 0.05. ETHICS AND DISSEMINATION:The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospital Network. In addition, results will be reported through academic journals, seminars and conference presentations. TRIAL REGISTRATION NUMBERS:NCT02795793; ACTRN12616000788471.
| S-EPMC5223693 | biostudies-literature
Project description:BackgroundGuidance on the recommended durations of antibiotic therapy, the use of oral antibiotic therapy, and the need for repeat blood cultures remain incomplete for gram-negative bloodstream infections. We convened a panel of infectious diseases specialists to develop a consensus definition of uncomplicated gram-negative bloodstream infections to assist clinicians with management decisions.MethodsPanelists, who were all blinded to the identity of other members of the panel, used a modified Delphi technique to develop a list of statements describing preferred management approaches for uncomplicated gram-negative bloodstream infections. Panelists provided level of agreement and feedback on consensus statements generated and refined them from the first round of open-ended questions through 3 subsequent rounds.ResultsThirteen infectious diseases specialists (7 physicians and 6 pharmacists) from across the United States participated in the consensus process. A definition of uncomplicated gram-negative bloodstream infection was developed. Considerations cited by panelists in determining if a bloodstream infection was uncomplicated included host immune status, response to therapy, organism identified, source of the bacteremia, and source control measures. For patients meeting this definition, panelists largely agreed that a duration of therapy of ~7 days, transitioning to oral antibiotic therapy, and forgoing repeat blood cultures, was reasonable.ConclusionsIn the absence of professional guidelines for the management of uncomplicated gram-negative bloodstream infections, the consensus statements developed by a panel of infectious diseases specialists can provide guidance to practitioners for a common clinical scenario.
| S-EPMC8561258 | biostudies-literature