Biofilm Producing Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Humans: Clinical Implications and Management.

Since its initial description in the 1960s, methicillin-resistant Staphylococcus aureus (MRSA) has developed multiple mechanisms for antimicrobial resistance and evading the immune system, including biofilm production. MRSA is now a widespread pathogen, causing a spectrum of infections ranging from superficial skin issues to severe conditions like osteoarticular infections and endocarditis, leading to high morbidity and mortality. Biofilm production is a key aspect of MRSA's ability to invade, spread, and resist antimicrobial treatments. Environmental factors, such as suboptimal antibiotics, pH, temperature, and tissue oxygen levels, enhance biofilm formation. Biofilms are intricate bacterial structures with dense organisms embedded in polysaccharides, promoting their resilience. The process involves stages of attachment, expansion, maturation, and eventually disassembly or dispersion. MRSA's biofilm formation has a complex molecular foundation, involving genes like icaADBC, fnbA, fnbB, clfA, clfB, atl, agr, sarA, sarZ, sigB, sarX, psm, icaR, and srtA. Recognizing pivotal genes for biofilm formation has led to potential therapeutic strategies targeting elemental and enzymatic properties to combat MRSA biofilms. This review provides a practical approach for healthcare practitioners, addressing biofilm pathogenesis, disease spectrum, and management guidelines, including advances in treatment. Effective management involves appropriate antimicrobial therapy, surgical interventions, foreign body removal, and robust infection control practices to curtail spread within healthcare environments.

Epidemiologic Characteristics of Adolescents with COVID-19 Disease with Acute Hypoxemic Respiratory Failure.

We report our experience of COVID-19 disease with hypoxemic respiratory failure among patients aged 12-21 years admitted to the intensive care unit at two tertiary care institutions in Northeastern and Midwestern United States. Our results showed that during the main study period that spanned the initial surge at both geographic locations, adolescents with SARS-COV-2 infection admitted to the ICU with respiratory failure were more likely to be male, black, and morbidly obese and with two or more comorbidities. The majority (79%) were admitted with COVID-19-related pneumonia and 15 developed respiratory failure; two-thirds of patients with respiratory failure (9/15, 60%) required mechanical ventilation (MV). More than two-thirds of patients (11/15, 75%) with respiratory failure were obese with BMI > 30 compared to those without respiratory failure (p < 0.0001), and those with BMI > 40 were 4.3 times more likely to develop respiratory failure than those with normal BMI; 40% of patients with respiratory failure had two or more pre-existing medical comorbidities. Inflammatory markers were 2-20 times higher in patients with respiratory failure (p < 0.05). The majority of patients on MV (7/9) developed complications, including ARDS (acute respiratory distress syndrome), acute renal injury, and cerebral anoxic encephalopathy. Patients with respiratory failure had a significantly longer length of hospital stay than patients without respiratory failure (p < 0.05). The majority of the admitted adolescents in the ICU received steroid treatment. None of the patients died. An additional review of a 6-month postvaccination approval period indicated that the majority of ICU admissions were unvaccinated, obese, black patients and all patients who developed respiratory failure were unvaccinated. Our study highlights and supports the need for maximizing opportunities to address vaccination and healthcare gaps in adolescents as well as promoting public health measures including correct use of masks, effective vaccination campaigns for this age group, and additional passive preventive interventions for COVID-19 disease in adolescents especially with comorbid conditions, and in minority populations.

Smart and connected devices in point-of-care molecular diagnostics: what role can they play in the response to COVID-19?

INTRODUCTION: Coronavirus disease-2019 (COVID-19) has been a huge public health challenge that has led to significant morbidity and mortality across the globe. Given the high prevalence and continued circulation of SARS-CoV-2 infection globally, accurate and rapid point-of-care testing is critical. AREAS COVERED: Knowledge of role of digital technology including smart and connected devices in rapid diagnosis of COVID-19 is an evolving area of scientific investigation. This review discusses the importance of rapid at-home point-of-care testing, highlighting the possible role of smart and connected device-based molecular diagnostics for COVID-19. EXPERT OPINION: Accurate and rapid diagnostic modalities have the potential to improve accessibility and efficiency of diagnosis of symptomatic and asymptomatic patients and could be instrumental in timely implementation of appropriate therapeutic interventions as well as public health measures to mitigate spread of infection. With emerging challenges like newer viral variants, global vaccine shortages and vaccine hesitancy, accurate diagnostic testing with the ability to rapidly identify infection remains critical. Digital technologies are likely to become important tools in future of healthcare and technological advancements may play a crucial role in response to COVID-19 with the goal of ultimately overcoming this pandemic.

Adolescents as partners in the fight against COVID-19.

We report our experience of COVID-19 disease burden among patients aged 0-21 years at two tertiary care institutions in the Northeast and Midwest from New Jersey and Iowa. Our results showed that during the initial surge (March to August 2020) at both geographic locations, majority of COVID-19 disease burden occurred in adolescents and that they were more likely to be hospitalized for COVID-related illnesses, as well as develop severe disease needing intensive care. The study results emphasize the need for providing more targeted interventions toward this group to help prevent disease acquisition and transmission.

Emerging Evidence on Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection: a Systematic Review with Meta-analysis.

With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries (p < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C. Supplementary Information: The online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.

Management and outcomes of patients hospitalized with severe COVID-19 at a tertiary care center in midwestern United States.

Knowledge of treatment regimens and outcomes for novel coronavirus disease 2019 (COVID-19) is evolving. Recent studies have reported mortality rates ranging from 39-50% among hospitalized patients with COVID-19. We report our experience ofmanagement and outcomes of hospitalized patients with COVID-19 at a large tertiary-care center in Midwestern United States. Of 658 patients presenting to our tertiary care center, 217 needed hospitalization, majority (77%) of whom were severely sick requiring admission to the intensive care unit (ICU). All received corticosteroids, and 78% of the patients received tocilizumab. More than two-thirds of the patients received anticoagulation and 80% of patients in the ICU had prone-positioning. The median duration of hospitalization was 12 days (interquartile range, 8 to16), median duration of intensive care unit stay was 7 days (interquartile range, 5 to 9) and requirement of mechanical ventilation was 6 days (interquartile range, 5 to 8) in our cohort. Of the 217 patients, 27 died (12% mortality). The majority of our patients received corticosteroids, tocilizumab, anticoagulation and prone positioning. While higher mortality rates of >30% have been reported in various studies among hospitalized patients with COVID-19, the majority of hospitalized patients in our cohort survived with a low mortality rate. The majority of our patients received corticosteroids, tocilizumab, anticoagulation and prone positioning. While higher mortality rates of >30% have been reported in various studies among hospitalized patients with COVID-19, the majority of hospitalized patients in our cohort survived with a low mortality rate.

A Systematic Review of Multisystem Inflammatory Syndrome in Children Associated With SARS-CoV-2 Infection.

BACKGROUND: Recently, severe manifestations associated with coronavirus disease 2019 (COVID-19) called multisystem inflammatory syndrome in children (MIS-C) have been recognized. Analysis of studies for this novel syndrome is needed for a better understanding of effective management among affected children. METHODS: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020. Observational cross-sectional, cohort, case series, and case reports were included. RESULTS: A total of 328 articles were identified. Sixteen studies with 655 participants (3 months-20 years of age) were included in the final analysis. Most of the children in reported studies presented with fever, gastrointestinal symptoms, and Kawasaki Disease-like symptoms. Sixty-eight percent of the patients required critical care; 40% needed inotropes; 34% received anticoagulation; and 15% required mechanical ventilation. More than two-thirds of the patients received intravenous immunoglobulin and 49% received corticosteroids. Remdesivir and convalescent plasma were the least commonly utilized therapies. Left ventricular dysfunction was reported in 32% of patients. Among patients presenting with KD-like symptoms, 23% developed coronary abnormalities and 26% had circulatory shock. The majority recovered; 11 (1.7%) children died. CONCLUSIONS: This systematic review delineates and summarizes clinical features, management, and outcomes of MIS-C associated with SARS-CoV-2 infection. Although most children required intensive care and immunomodulatory therapies, favorable outcomes were reported in the majority with low-mortality rates.

Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with 2019 Novel Coronavirus (SARS-CoV-2) Infection.

We report three critically ill pediatric patients (aged 6-10 years), presenting with features of multisystem inflammatory syndrome in children (MIS-C) from April 4 to May 10, 2020, to a tertiary-care center in New Jersey, United States. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and were previously healthy. Clinical presentations were similar with fever, abdominal pain, gastrointestinal complaints, and/or rash. One patient had altered mental status with cerebrospinal fluid (CSF) findings consistent with aseptic meningitis. Laboratory values were remarkable for high levels of C-reactive protein, D-dimers, B-type natriuretic peptide (BNP), and troponin in all patients. All had low albumin levels. Evaluation for other infectious etiologies was negative. All of the patients were critically ill, requiring admission to the intensive care unit. All had circulatory shock and needed inotropes. Two patients had respiratory failure requiring advanced respiratory support and one had cardiac dysfunction. All patients received steroids, and two received intravenous immunoglobulin (IVIG). One patient received tocilizumab. None of the children died. MIS-C is a recently recognized pediatric illness spectrum in association with SARS-CoV-2 infection, and clinical characterization is essential for understanding disease mechanisms to inform clinical practice.

It Is Complicated: The Medico-Social Journey of an Undocumented Pregnant Adolescent.

Adolescent pregnancies are a global health problem with over 16 million children born to this age group globally. Adolescent females also represent almost half of all adolescent global migrants. Adolescent pregnancy by itself is associated with poor health care access and morbidities; the additional risk of social insecurity in the case of undocumented adolescent migrants leads to higher risks for the mother and newborn. According to the CDC, adolescents comprise half of all new sexually transmitted diseases (STDs) including reported primary and secondary syphilis. Our case highlights the relationship between social insecurity for the undocumented adolescent migrant and excess risks for preventable mother-to-child transmission of communicable diseases. In formulating preventive measures and policies for the recent rise in sexually transmitted maternal diseases with resultant congenital infections, there is need for health care systems and providers to familiarize themselves with advocacy and other useful resources that will promote health care access for undocumented and other vulnerable adolescents. Additionally, local providers who work in areas with a large population of immigrant adolescents should utilize the untapped resources of these adolescents to develop youth community advocacy projects that link adolescents to health resources, including reproductive health.

Severe Enteritis as the Sole Manifestation of Novel Coronavirus Disease 2019 (COVID-19) in Adolescent Patients.

Enteritis as the only manifestation of novel coronavirus disease 2019 (COVID-19) in adolescents without features of multisystem inflammatory syndrome in children (MIS-C) or a prior history of inflammatory bowel disease (IBD) has not been described. We report two adolescent patients (a 14-year-old male and a 20-year-old pregnant female) presenting to tertiary-care centers in the United States with severe enteritis as the only manifestation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patients were hospitalized with acute abdominal pain and gastrointestinal (GI) bleeding, with no evidence of MIS-C, and were previously healthy with no history of IBD. The patients' nasopharyngeal swabs were positive for SARS-CoV-2 infection by reverse transcription polymerase chain reaction (RT-PCR), and testing for other infectious etiologies was negative. Both patients received intravenous corticosteroids and recovered without short-term complications. None of the patients died. This report highlights the need for keeping a high index of suspicion for SARS-CoV-2 infection in adolescents presenting solely with gastrointestinal manifestations, in the absence of respiratory symptoms or multisystem involvement, for prompt recognition and timely management.

Pediatric Methicillin-Resistant Staphylococcus aureus Osteoarticular Infections.

Osteoarticular infections (OSI) are a significant cause of hospitalizations and morbidity in young children. The pediatric patient with OSI presents unique challenges in diagnosis and management due to higher morbidity, effect on growth plate with associated long-lasting sequelae, and challenges in early identification and management. Methicillin-resistant Staphylococcus aureus (MRSA), first described in the 1960s, has evolved rapidly to emerge as a predominant cause of OSI in children, and therefore empiric treatment for OSI should include an antibiotic effective against MRSA. Characterizing MRSA strains can be done by antimicrobial susceptibility testing, detection of Panton⁻Valentine leukocidin (PVL) gene, staphylococcal cassette chromosome mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Worldwide, community-onset methicillin-resistant staphylococcal disease is widespread and is mainly associated with a PVL-producing clone, ST8/USA300. Many studies have implied a correlation between PVL genes and more severe infection. We review MRSA OSI along with the pertinent aspects of its pathogenesis, clinical spectrum, diagnosis, and current guidelines for management.

Congenital rubella syndrome: A brief review of public health perspectives.

Congenital rubella syndrome (CRS) is one of the most devastating congenital infections and yet the only one which is vaccine preventable and is a public health challenge for clinicians and policymakers across the developing world including India. The clinical manifestations of CRS include growth retardation, cardiac defects, cataracts, and hearing impairment. The World Health Organization (WHO) estimates that worldwide over 100,000 babies are born with CRS every year despite the availability of safe and inexpensive vaccines, thus highlighting the need for broader vaccination coverage programs. This article briefly reviews the importance of CRS, the proposed strategies for prevention by the WHO, and the "Rubella initiative" that Government of India is launching in view of the recognition of CRS as a significant problem in India.

The Role of Antifungals in Pediatric Critical Care Invasive Fungal Infections.

Invasive fungal infections (IFIs) have seen considerable increase in pediatric intensive care units over the past several decades. IFIs are predominantly caused by Candida species, and candidemia is the third most common cause of healthcare-associated bloodstream infections (BSIs) in children. IFIs are opportunistic infections that affect pediatric patients in critical care resulting in significant morbidity and mortality especially in those with a compromised immune system. IFIs are the leading cause of death in children with comorbidities such as immunosuppression, and pediatric ICU admission has been shown to be an independent risk factor for mortality. Management of IFI and fungal sepsis is broad and encompasses several key components that include prompt initiation of therapy and rapid source identification and control. This study reviews important antifungals in the pediatric critical care setting including the pharmacologic properties, antifungal spectrum, adverse effects, and clinical uses of agents belonging to the four major classes of antifungals-the polyenes, azoles, echinocandins, and pyrimidine analogue flucytosine. The polyenes and azoles are the most often used classes of antifungals. The echinocandins are a relatively newer class of antifungal agents that offer excellent Candida activity and are currently recommended as the first-line therapy for invasive candidiasis.

Non-Type b Haemophilus influenzae Invasive Infections in North Dakota and South Dakota, 2013-2015.

Reports of children with non-type b Haemophilus influenzae infection in the United States in recent years have been limited. Here, we report the spectrum and severity of disease associated with invasive non-type b H influenzae infection in 17 patients at 2 tertiary-care children's hospitals over a 2-year period. Meningitis was the most common diagnosis. The majority of the patients had neurologic sequelae, and 1 patient died. The high proportions of hospitalization, intensive care utilization, and neurologic complications reveal that non-type b H influenzae infection was associated with significant morbidity in this pediatric population.