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.

COVID-19 Vaccine Cardiac Complications: A Case Series on Implications of Marijuana in Adolescents With Myopericarditis.

We report on two critically ill pediatric patients, aged 16 and 18 years, presenting with acute myopericarditis at a tertiary-care center in New Jersey, United States. Both patients had their severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations, tested negative for SARS-CoV-2, and shared only significant history of asthma. Clinical presentations were similar to acute onset chest pain that worsened with deep inspiration. One patient reported a history of vaping and escalating marijuana use several hours preceding presentation. Both patients had elevated troponin on admission and had ST-segment elevation on electrocardiogram (EKG), thus prompting admission to the pediatric intensive care unit (PICU) for cardiac monitoring. Myopericarditis has multiple etiologies and is a newly described rare complication of the SARS-CoV-2 vaccine. It can also occur as a complication of vaping and frequent marijuana drug use. Our paper highlights the importance of a detailed social and drug history in adolescents presenting with chest pain. The clinical characterization is necessary to promote better case definitions and the design of targeted interventions for this vulnerable group.

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.

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.

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.

Sexual Behavior and Knowledge among Adolescents with Perinatally Acquired Human Immunodeficiency Virus Infection Compared to HIV-Uninfected Adolescents at an Urban Tertiary Center in New Jersey.

Background. Sexual behaviors and knowledge among PHIV-infected (PHIV(+)) adolescents in comparison with HIV-uninfected youths are not well understood and continue to be studied actively. Objective. To compare sexual behavior and sexual knowledge of PHIV(+) and HIV-uninfected adolescents at an urban, tertiary-care center in New Jersey. Study Design. Modified Centers for Disease Control and Prevention (CDC) Youth Risk Behavior Surveillance questionnaire was administered to PHIV(+) and HIV-uninfected adolescents to assess and compare sexual behavior and knowledge over a 1-year-period. Results. Twenty-seven PHIV(+) and 100 HIV-uninfected adolescents were studied; 59% PHIV(+) and 52% HIV-uninfected adolescents were sexually active. A significantly higher proportion of PHIV(+) adolescents compared to HIV-uninfected adolescents reported ≥1 occasion of unprotected penetrative sex (p < 0.0001) and reported multiple (>4) sexual partners (p = 0.037). Significantly more PHIV(+) males reported receptive anal intercourse (p < 0.001). About 1/3 of adolescents in both groups were unaware that sexual abstinence can prevent HIV transmission and >80% adolescents in both groups did not consider multiple sexual partners a risk factor for HIV transmission. Only 25% PHIV(+) adolescents reported disclosing their seropositive status to their first sexual partners. Conclusions. High risk sexual behaviors were significantly more prevalent among PHIV(+) youths; however both groups demonstrated considerable gaps in sexual knowledge. There is an urgent need for heightening awareness about risky behaviors, interventions for prevention, and reproductive health promotion among adolescents.

Impact of routine methicillin-resistant Staphylococcus aureus (MRSA) surveillance and cohorting on MRSA-related bloodstream infection in neonatal intensive care unit.

OBJECTIVE: To study the impact of methicillin-resistant Staphylococcus aureus (MRSA) surveillance on the incidence of MRSA-related bloodstream infection (BSI) in neonatal intensive care unit (NICU) and to evaluate cost-effectiveness of MRSA surveillance. STUDY DESIGN: MRSA surveillance policy was introduced in our NICU in April 2008. Pre-MRSA surveillance period (P1, April 2006-March 2008) was compared with the surveillance period (P2, April 2008-April 2010) for MRSA-related BSI (MRSA BSI). RESULTS: During P1 and P2, 1,576 and 1,512 neonates were enrolled. Of these, 3.8/1,000 and 5.3/1,000 developed MRSA BSI, respectively. During P2, 100% MRSA-related BSI occurred in MRSA-colonized neonates, as compared with zero in noncolonized group (p < 0.0001). Overall, 7 (30%) of the 23 neonates colonized during hospitalization developed MRSA BSI as compared with 1 of the 31 (3%) neonates colonized at admission (p = 0.007). Direct screening cost was $208 per patient. Since 28 neonates had to be screened to detect one colonization, $5,824 estimated per detection, excluding indirect costs. CONCLUSIONS: MRSA surveillance may protect non-MRSA colonized neonates from becoming colonized. This is of considerable importance because the acquisition of colonization during hospitalization was associated with a 10-fold increase in risk of developing MRSA BSI. Cost-effectiveness of MRSA surveillance remains debatable and further studies are needed to delineate cost-benefit ratio.

Cardiac mechanics in patients with human immunodeficiency virus: a study of systolic myocardial deformation in children and young adults.

Human immunodeficiency virus (HIV) infection causes dysfunction of different organ systems. Myocardial diastolic dysfunction has been reported previously in an adult HIV population. Our aim was to study myocardial strain in children and young adults infected by HIV who have apparently normal ejection fraction. Forty HIV-infected patients (mean age 20.6 ± 1.5 years) with normal ejection fraction and 55 matched normal controls (mean age 17 ± 1.5 years) were studied by two-dimensional echocardiogram. The images were stored then exported to velocity vector imaging software for analysis. Measures considered were left-ventricular peak global systolic strain (LV S) and strain rate (LV SR) as well as right-ventricular peak global systolic strain (RV S) and strain rate (RV SR). Circumferential measures of the left ventricle included the following: LV circumferential peak global systolic strain (LV circ S), strain rate (LV circ SR), radial velocity (LV rad vel), and rotational velocity (LV rot vel) at the level of the mitral valve. Statistical significance was set at p < 0.05. The means of all longitudinal deformation parameters were significantly lower in HIV patients compared with normal controls: LV S (-14.15 vs. -19.31), LV SR (-0.88 vs. -1.30), RV S (-19.58 vs. -25.09), and RV SR (-1.34 vs. -2.13), respectively (p < 0.05). LV rot vel was lower in patients compared with controls (43.23 vs. 51.71, p = 0.025). LV circ S, LV circ SR, and LV rad vel showed no significant difference between the two groups (p ≥ 0.05). HIV infection affects longitudinal systolic cardiac strain and strain rate in children and young adults. Normal ejection fraction might be attributed to preserved circumferential myocardial deformation. Strain and strain rate may help identify HIV patients at high risk for cardiac dysfunction and allow early detection of silent myocardial depression.

Maternal sepsis, chorioamnionitis, and congenital Candida kefyr infection in premature twins.

This is the first reported case of maternal sepsis and placental transmission of Candida kefyr to premature fraternal twins. The mother consumed organic dairy products regularly throughout her pregnancy and developed sepsis with chorioamnionitis caused by C. kefyr. The twins developed respiratory distress at birth. The placenta, fetal membranes, and umbilical cords showed numerous colonies of yeasts, subsequently identified as C. kefyr. C. kefyr sepsis in preterm neonates should be considered when there is a significant maternal history of organic dairy product consumption during pregnancy.

Malignancy in perinatally human immunodeficiency virus-infected children in the United States.

OBJECTIVES: To determine the incidence of and factors associated with malignancy in perinatally human immunodeficiency virus (HIV)-infected children in the United States. METHODS: Included were 2969 children followed in the Pediatric AIDS Clinical Trials Group (PACTG) 219/219C cohort from 1993 through 2003. Cancer incidence by sex, race, age, histology and highly active antiretroviral therapy (HAART) era (pre-HAART, 1993-1997; HAART, 1998-2003) was estimated, and the standardized incidence ratio contrasting infected and uninfected children was determined. Poisson regression was used to further investigate the relation between HAART use (> or =3 drugs of > or =2 classes, 1 of which was a protease inhibitor), CD4% and cancer. RESULTS: There were 37 cancers (17 prevalent and 20 incident) diagnosed in 2969 children for a prevalence of 0.6% [95% confidence interval (CI), 0.3, 0.9] and an incidence of 1.56/1000 person-years (95% CI 0.95, 2.41). Compared with uninfected children, the standardized incidence ratio was 10.08 (95% CI 5.87, 16.14). Incidence did not significantly differ by sex, race, age or HAART era. Of the cases, 35% were immunocompetent (CD4 > or =25%), 25% were moderately immunosuppressed (15%< or = CD4 < or =24%) and 40% were severely immunosuppressed (CD4 <15%) at diagnosis. In multivariate regression, the cancer rate was 3.09 (95% CI 1.22, 7.85) times higher in children with < or =2 years of HAART use than in children with >2 years of HAART and 3.20 (95% CI 1.32, 7.76) times higher in children with CD4 <15% at cohort enrollment than in children with CD4 > or =15%. CONCLUSION: Cancer incidence in this U.S. pediatric cohort was lower than that of European cohorts but was markedly higher than that of HIV-uninfected children. Cancer incidence was highest in children who were severely immunosuppressed and in children who received HAART for < or =2 years.