Short-term antibiotic therapy for the most common bacterial respiratory infections in infants and children.

Overuse and misuse of antibiotics have strongly accelerated the progressive increase in bacterial antimicrobial resistance (AMR). The evidence that antimicrobial selective pressure was greater the longer the antibiotic therapy was continued has led some experts to reconsider duration of antibiotic therapy testing the use of short-term drug administration. If as effective as long-term therapy, short-term therapy could have been an easy measure to limit AMR emergence. In the present narrative review, whether present knowledge on short-term therapy of acute streptococcal pharyngitis (ASF), acute otitis media (AOM) and mild to moderate community-acquired pneumonia (CAP) allows systematic use of short-term therapy in infants and children with these diseases is discussed. Literature analysis showed that reducing the duration of antibiotic therapy for some of the most common pediatric respiratory infections could be a valid measure to contain the antibiotic abuse and the consequent impact on the emergence of AMR. Several data seem to indicate that this type of intervention is possible, as short-term therapy has been found as effective as the traditionally recommended long-term therapy in some cases of ASF, AOM and mild to moderate CAP. However, further studies are needed to better characterize infants and children who can have benefit with short-term antibiotic therapy in common bacterial respiratory infections.

Antibiotic Prophylaxis for the Prevention of Urinary Tract Infections in Children: Guideline and Recommendations from the Emilia-Romagna Pediatric Urinary Tract Infections (UTI-Ped-ER) Study Group.

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk.

Epidemiology of Respiratory Infections during the COVID-19 Pandemic.

To face the COVID-19 outbreak, a wide range of non-pharmaceutical interventions (NPIs) aimed at limiting the spread of the virus in communities, such as mask-wearing, hand hygiene, social distancing, travel restrictions, and school closures, were introduced in most countries. Thereafter, a significant reduction of new asymptomatic and symptomatic COVID-19 cases occurred, although there were differences between countries according to the type and duration of the NPIs. In addition, the COVID-19 pandemic has been accompanied by significant variations in the global incidence of diseases due to the most common non-SARS-CoV-2 respiratory viruses and some bacteria. In this narrative review, the epidemiology of the most common non-SARS-CoV-2 respiratory infections during the COVID-19 pandemic is detailed. Moreover, factors that could have had a role in modifying the traditional circulation of respiratory pathogens are discussed. A literature analysis shows that NPIs were the most important cause of the general reduction in the incidence of influenza and respiratory syncytial virus infection in the first year of the pandemic, although the different sensitivity of each virus to NPIs, the type and duration of measures used, as well as the interference among viruses may have played a role in modulating viral circulation. Reasons for the increase in the incidences of Streptococcus pneumoniae and group A Streptococcus infections seem strictly linked to immunity debt and the role played by NPIs in reducing viral infections and limiting bacterial superimposed infections. These results highlight the importance of NPIs during pandemics, the need to monitor the circulation of infectious agents that cause diseases similar to those caused by pandemic agents, and the need to make efforts to improve coverage with available vaccines.

Impact of Age and Sex Interaction on Post-Acute Sequelae of COVID-19: An Italian Cohort Study on Adults and Children.

Identifying factors predisposing individuals to post-acute sequelae of COVID-19 (PASC) would allow for the timely treatment of those vulnerable. Attention on the role of sex and age is growing, but published studies have shown mixed results. Our objective was to estimate the effect modification of age on sex as a risk factor for PASC. We analyzed data from two longitudinal prospective cohort studies on adult and pediatric subjects positive to SARS-CoV-2 infection that were enrolled between May 2021 and September 2022. Age classes (≤5, 6-11, 12-50, >50 years) were based on the potential role of sex hormones on inflammatory/immune and autoimmune processes. A total of 452 adults and 925 children were analyzed: 46% were female and 42% were adults. After a median follow-up of 7.8 months (IQR: 5.0 to 9.0), 62% of children and 85% of adults reported at least one symptom. Sex and age alone were not significantly associated to PASC, but their interaction was statistically significant (p-value = 0.024): the risk was higher for males aged 0-5 (females vs. males HR: 0.64, 95% CI: 0.45-0.91, p = 0.012) and for females aged 12-50 (HR: 1.39, 95% CI: 1.04-1.86, p = 0.025), especially those in the cardiovascular, neurological, gastrointestinal and sleep categories. Further research on PASC with regard to sex and age is warranted.

Current and emerging pharmacotherapy for respiratory syncytial virus (RSV) infection in infants.

INTRODUCTION: Respiratory syncytial virus (RSV) is a common respiratory virus with a huge impact on patients, the healthcare system, and society worldwide. Very few effective chances of prevention and treatment of RSV infection are available. AREAS COVERED: In this paper, knowledge on RSV characteristics and current stage of development of new pharmacological measures against this virus are discussed. EXPERT OPINION: In recent years, the structure of RSV was explored in depth and several pharmacologic measures potentially effective for prevention and treatment of RSV infection and disease were identified. These new measures have the aim to overcome the limitations of palivizumab and ribavirin. Strategies to protect infants through immunization of pregnant women and/or the use of more effective monoclonal antibodies were developed. At the same time, it was defined which vaccines could be administered to unprimed infants to avoid the risk of enhanced respiratory disease and which vaccines could be effective in older patients and in subjects with reduced immune system efficiency. Finally, a great number of new antiviral drugs targeting the RSV proteins that allow RSV entering host cells or regulate virus replication were produced. Although further studies are needed, some preparations seem effective and safe, making the future of RSV infection prevention and treatment less gloomy.

Multidrug-resistant tuberculosis in children: Are the same therapy options available worldwide?

The spread of drug-resistant tuberculosis (TB) encouraged the development of new medicines and the reappraisal of old drugs rarely used in recent years. Providing access for children with drug-resistant TB to appropriate treatments is a cornerstone of strategies to reduce the burden of TB worldwide. Aim of this perspective was to describe the availability of child-friendly medicines to treat drug-resistant TB at the global level. We showed that the development of child-friendly formulations of second-line drugs should be encouraged to promote adherence to recommended treatment regimens and consequently to increase the success rate and to prevent the development of additional mycobacterial resistances. This is even more crucial, considering the long duration of antitubercular therapies. Importantly, companies and policy makers are called to more efforts in facilitating their prompt availability in every contest because drug-resistant pediatric TB is a worldwide medical problem.

Treatment options for children with multi-drug resistant tuberculosis.

INTRODUCTION: According to the latest report from the World Health Organization (WHO), approximately 10.0 million people fell ill with tuberculosis (TB) in 2020, 12% of which were children aged under 15 years. There is very few experience on treatment of multi-drug resistant (MDR)-TB in pediatrics. AREAS COVERED: The aim of this review is to analyze and summarize therapeutic options available for children experiencing MDR-TB. We also focused on management of MDR-TB prophylaxis. EXPERT OPINION: The therapeutic management of children with MDR-TB or MDR-TB contacts is complicated by a lack of knowledge, and the fact that many potentially useful drugs are not registered for pediatric use and there are no formulations suitable for children in the first years of life. Furthermore, most of the available drugs are burdened by major adverse events that need to be taken into account, particularly in the case of prolonged therapy. A close follow-up with a standardized timeline and a comprehensive assessment of clinical, laboratory, microbiologic and radiologic data is extremely important in these patients. Due to the complexity of their management, pediatric patients with confirmed or suspected MDR-TB should always be referred to a specialized center.

Update on COVID-19 Therapy in Pediatric Age.

With the extension of the COVID-19 pandemic, the large use of COVID-19 vaccines among adults and the emergence of SARS-CoV-2 variants means that the epidemiology of COVID-19 in pediatrics, particularly among younger children, has substantially changed. The prevalence of pediatric COVID-19 significantly increased, several severe cases among children were reported, and long-COVID in pediatric age was frequently observed. The main aim of this paper is to discuss which types of treatment are presently available for pediatric patients with COVID-19, which of them are authorized for the first years of life, and which are the most important limitations of COVID-19 therapy in pediatric age. Four different antivirals, remdesivir (RVD), the combination nirmatrelvir plus ritonavir (Paxlovid), molnupiravir (MPV), and the monoclonal antibody bebtelovimab (BEB), are presently approved or authorized for emergency use for COVID-19 treatment by most of the national health authorities, although with limitations according to the clinical relevance of disease and patient's characteristics. Analyses in the literature show that MPV cannot be used in pediatric age for the risk of adverse events regarding bone growth. The other antivirals can be used, at least in older children, and RDV can be used in all children except in neonates. However, careful research on pharmacokinetic and clinical data specifically collected in neonates and children are urgently needed for the appropriate management of pediatric COVID-19.

Autoimmune encephalitis after herpes simplex encephalitis: A still undefined condition.

Herpes simplex encephalitis (HSE) is one of the most common sporadic viral encephalitis. Generally, HSE is characterized by a monophasic short course, although in some patients neurological relapses or worsening of deficits can develop some weeks later, when viral therapy has been discontinued and signs and symptoms of the central nervous system (CNS) damage seem to have stabilized. The second HSE stage is generally identified as autoimmune encephalitis after HSE (AEaHSE). Aim of this paper is to discuss which are the present knowledge in this regard. Literature analysis showed that AEaHSE exists, it is more common in younger children and it has different clinical manifestations according to age. All the patients with AEaHSE are positive for one or more neuronal cell-surface and synaptic antibodies, mainly anti-NMDAR antibodies, and the earlier the appearance of the antibodies the greater the risk of AEaHSE development. This means that a careful monitoring of antibody production starting from anti-NMDAR antibodies in all HSE cases could lead to the early identification of AEaHSE and the prompt administration of a potentially effective therapy. Further studies are needed to clarify which are the main pathogenetic mechanisms, whether there are differences in risk of development and clinical course of AEaHSE according to the type of antibody production, why response to immunosuppressive therapy significantly varies and whether administration of steroids to patients with HSE during the first phase of disease can play a role for reducing the risk of AEaHSE development.

Management of Pediatric Urinary Tract Infections: A Delphi Study.

Urinary tract infection (UTI) is one of the most common infectious diseases in the pediatric population and represents a major cause of antibiotic consumption and hospitalization in children. Considering the ongoing controversies on the management of pediatric UTI and the challenges due to increasing antimicrobial resistance, the aim of the present study was to evaluate the level of agreement on UTI management in pediatric age in Emilia-Romagna Region, Italy, and to assess on the basis of recent studies whether there is the need to change current recommendations used by primary care pediatricians, hospital pediatricians, and pediatric surgeons in everyday clinical practice to possibly improve outcomes. This consensus provides clear and shared indications on UTI management in pediatric age, based on the most updated literature. This work represents, in our opinion, the most complete and up-to-date collection of statements on procedures to follow for pediatric UTI, in order to guide physicians in the management of the patient, standardize approaches, and avoid abuse and misuse of antibiotics. Undoubtedly, more randomized and controlled trials are needed in the pediatric population to better define the best therapeutic management in cases with antimicrobial resistance and real usefulness of long-term antibiotic prophylaxis.

Antimicrobial Prophylaxis for Urologic Procedures in Paediatric Patients: A RAND/UCLA Appropriateness Method Consensus Study in Italy.

The main aim of surgical antimicrobial prophylaxis (SAP) in urologic procedures is to prevent bacteraemia, surgical site infections (SSIs), and postoperative urinary tract infections (ppUTIs). Guidelines for SAP in paediatric urology are lacking. Only some aspects of this complex topic have been studied, and the use of antibiotic prophylaxis prior to surgical procedures seems to be more often linked to institutional schools of thought or experts' opinions than to rules dictated by studies demonstrating the most correct and preferred management. Therefore, the aim of this Consensus document realized using the RAND/UCLA appropriateness method is to provide clinicians with a series of recommendations on SAP for the prevention of bacteraemia, SSIs, and ppUTIs after urologic imaging and surgical procedures in paediatric patients. Despite the few available studies, experts agree on some basilar concepts related to SAP for urologic procedures in paediatric patients. Before any urological procedure is conducted, UTI must be excluded. Clean procedures do not require SAP, with the exception of prosthetic device implantation and groin and perineal incisions where the SSI risk may be increased. In contrast, SAP is needed in clean-contaminated procedures. Studies have also suggested the safety of eliminating SAP in paediatric hernia repair and orchiopexy. To limit the emergence of resistance, every effort to reduce and rationalize antibiotic consumption for SAP must be made. Increased use of antibiotic stewardship can be greatly effective in this regard.

Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections.

With the spread of antibiotic resistance in pediatric urinary tract infections (UTIs), more patients are likely to be started empirically on antibiotics to which pathogens are later found to be resistant (discordant therapy). However, in-vivo effectiveness may be different from in-vitro susceptibility. Aims of this study were to describe clinical outcomes of discordant empirical treatments in pediatric UTIs and to investigate risk factors associated to treatment failure. This observational, retrospective study was conducted on children hospitalized for febrile UTIs with positive urine culture and started on discordant empirical therapy. Failure rates of discordant treatments and associated risk factors were investigated. A total of 142/1600 (8.9%) patients were treated with inadequate empirical antibiotics. Clinical failure was observed in 67/142 (47.2%) patients, with no fatal events. Higher failure rates were observed for combinations of penicillin and beta-lactamase inhibitors (57.1%). Significant risk factors for failure of discordant treatment were history of recurrent UTIs (95% CI: 1.13-9.98, OR: 3.23, p < 0.05), recent use of antibiotics (95% CI: 1.46-21.82, OR: 5.02, p < 0.01), infections caused by Pseudomonas aeruginosa (95% CI: 1.85-62.10, OR: 7.30, p < 0.05), and empirical treatment with combinations of penicillin and beta-lactamase inhibitors (95% CI: 0.94-4.03, OR: 1.94, p = 0.05). This study showed that discordant empirical treatments may still be effective in more than half of pediatric UTIs. Clinical effectiveness varies between different discordant antibiotics in pediatric UTIs, and patients presenting risk factors for treatment failure may need a differentiated empirical approach.

Antibiotic Resistance in Paediatric Febrile Urinary Tract Infections.

Febrile urinary tract infection (UTI) is currently considered the most frequent cause of serious bacterial illness in children in the first 2 years of life. UTI in paediatrics can irreversibly damage the renal parenchyma and lead to chronic renal insufficiency and related problems. To avoid this risk, an early effective antibiotic treatment is essential. Moreover, prompt treatment is mandatory to improve the clinical condition of the patient, prevent bacteraemia, and avoid the risk of bacterial localization in other body sites. However, antibiotic resistance for UTI-related bacterial pathogens continuously increases, making recommendations rapidly outdated and the definition of the best empiric antibiotic therapy more difficult. Variation in pathogen susceptibility to antibiotics is essential for the choice of an effective therapy. Moreover, proper identification of cases at increased risk of difficult-to-treat UTIs can reduce the risk of ineffective therapy. In this review, the problem of emerging antibiotic resistance among pathogens associated with the development of paediatric febrile UTIs and the best potential solutions to ensure the most effective therapy are discussed. Literature analysis showed that the emergence of antibiotic resistance is an unavoidable phenomenon closely correlated with the use of antibiotics themselves. To limit the emergence of resistance, every effort to reduce and rationalise antibiotic consumption must be made. An increased use of antibiotic stewardship can be greatly effective in this regard.

Update on Viral Infections Involving the Central Nervous System in Pediatric Patients.

Infections of the central nervous system (CNS) are mainly caused by viruses, and these infections can be life-threatening in pediatric patients. Although the prognosis of CNS infections is often favorable, mortality and long-term sequelae can occur. The aims of this narrative review were to describe the specific microbiological and clinical features of the most frequent pathogens and to provide an update on the diagnostic approaches and treatment strategies for viral CNS infections in children. A literature analysis showed that the most common pathogens worldwide are enteroviruses, arboviruses, parechoviruses, and herpesviruses, with variable prevalence rates in different countries. Lumbar puncture (LP) should be performed as soon as possible when CNS infection is suspected, and cerebrospinal fluid (CSF) samples should always be sent for polymerase chain reaction (PCR) analysis. Due to the lack of specific therapies, the management of viral CNS infections is mainly based on supportive care, and empiric treatment against herpes simplex virus (HSV) infection should be started as soon as possible. Some researchers have questioned the role of acyclovir as an empiric antiviral in older children due to the low incidence of HSV infection in this population and observed that HSV encephalitis may be clinically recognizable beyond neonatal age. However, the real benefit-risk ratio of selective approaches is unclear, and further studies are needed to define appropriate indications for empiric acyclovir. Research is needed to find specific therapies for emerging pathogens. Moreover, the appropriate timing of monitoring neurological development, performing neuroimaging evaluations and investigating the effectiveness of rehabilitation during follow-up should be evaluated with long-term studies.

Update on Acute Bone and Joint Infections in Paediatrics: A Narrative Review on the Most Recent Evidence-Based Recommendations and Appropriate Antinfective Therapy.

Acute bone and joint infections (BJIs) in children may clinically occur as osteomyelitis (OM) or septic arthritis (SA). In clinical practice, one-third of cases present a combination of both conditions. BJIs are usually caused by the haematogenous dissemination of septic emboli carried to the terminal blood vessels of bone and joints from distant infectious processes during transient bacteraemia. Early diagnosis is the cornerstone for the successful management of BJI, but it is still a challenge for paediatricians, particularly due to its nonspecific clinical presentation and to the poor specificity of the laboratory and imaging first-line tests that are available in emergency departments. Moreover, microbiological diagnosis is often difficult to achieve with common blood cultures, and further investigations require invasive procedures. The aim of this narrative review is to provide the most recent evidence-based recommendations on appropriate antinfective therapy in BJI in children. We conducted a review of recent literature by examining the MEDLINE (Medical Literature Analysis and Retrieval System Online) database using the search engines PubMed and Google Scholar. The keywords used were "osteomyelitis", OR "bone infection", OR "septic arthritis", AND "p(a)ediatric" OR "children". When BJI diagnosis is clinically suspected or radiologically confirmed, empiric antibiotic therapy should be started as soon as possible. The choice of empiric antimicrobial therapy is based on the most likely causative pathogens according to patient age, immunisation status, underlying disease, and other clinical and epidemiological considerations, including the local prevalence of virulent pathogens, antibiotic bioavailability and bone penetration. Empiric antibiotic treatment consists of a short intravenous cycle based on anti-staphylococcal penicillin or a cephalosporin in children aged over 3 months with the addition of gentamicin in infants aged under 3 months. An oral regimen may be an option depending on the bioavailability of antibiotic chosen and clinical and laboratory data. Strict clinical and laboratory follow-up should be scheduled for the following 3-5 weeks. Further studies on the optimal therapeutic approach are needed in order to understand the best first-line regimen, the utility of biomarkers for the definition of therapy duration and treatment of complications.

Allergy in total knee replacement surgery: Is it a real problem?

Total knee arthroplasty is a common procedure, with extremely good clinical results. Despite this success, it produces 20% unsatisfactory results. Among the causes of these failures is metal hypersensitivity. Metal sensitization is higher in patients with a knee arthroplasty than in the general population and is even higher in patients undergoing revision surgery. However, a clear correlation between metal sensitization and symptomatic knee after surgery has not been ascertained. Surely, patients with a clear history of metal allergy must be carefully examined through dermatological and laboratory testing before surgery. There is no globally accepted diagnostic algorithm or laboratory test to diagnose metal hypersensitivity or metal reactions. The patch test is the most common test to determine metal hypersensitivity, though presenting some limitations. Several laboratory assays have been developed, with a higher sensitivity compared to patch testing, yet their clinical availability is not widespread, due to high costs and technical complexity. Symptoms of a reaction to metal implants present across a wide spectrum, ranging from pain and cutaneous dermatitis to aseptic loosening of the arthroplasty. However, although cutaneous and systemic hypersensitivity reactions to metals have arisen, thereby increasing concern after joint arthroplasties, allergies against implant materials remain quite rare and not a well-known problem. The aim of the following paper is to provide an overview on diagnosis and management of metal hypersensitivity in patients who undergo a total knee arthroplasty in order clarify its real importance.

Teriparatide anabolic therapy as potential treatment of type II dens non-union fractures.

Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type II fractures are the most common fracture pattern in elderly patients. Treatment (rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type II odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid non-union successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.