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Levofloxacin is a broad-spectrum fluoroquinolone antibiotic with activity against many pathogens that cause bacterial infections in children, including penicillin-resistant pneumococci. To provide dosing guidance for children, 3 single-dose, multicenter pharmacokinetic studies were conducted in 85 children in 5 age groups: 6 months to <2 years, 2 to <5 years, 5 to <10 years, 10 to <12 years, and 12 to 16 years. Each child received a single 7-mg/kg dose of levofloxacin (not to exceed 500 mg) intravenously or orally. Plasma and urine samples were collected through 24 hours after dose. Pharmacokinetic parameters were estimated and compared among the 5 age groups and to previously collected adult data. Levofloxacin absorption (as indicated by C(max) and t(max)) and distribution in children are not age dependent and are comparable to those in adults. Levofloxacin elimination (reflected by t1/2 and clearance), however, is age dependent. Children younger than 5 years of age clear levofloxacin nearly twice as fast (intravenous dose, 0.32+/-0.08 L/h/kg; oral dose, 0.28+/-0.05 L/h/kg) as adults and, as a result, have the total systemic exposure (area under the plasma drug concentration-time curve) approximately one half that of adults. The levofloxacin area under the plasma drug concentration-time curve (dose normalized) in children receiving a single dose of the oral liquid formulation is comparable to that in children receiving the intravenous formulation. To provide compatible levofloxacin exposures associated with clinical effectiveness and safety in adults, children > or =5 years need a daily dose of 10 mg/kg, whereas children 6 months to <5 years should receive 10 mg/kg every 12 hours. [ABSTRACT FROM AUTHOR]

Sustained-release (SR) bupropion (Zyban) is approved as a smoking cessation aid for adults. Since smoking often begins in adolescence, we determined the single-dose pharmacokinetics of bupropion SR in 75 adolescent subjects ranging from 13 to 18 years old. Subjects self-reported their smoking status. Urinary cotinine concentration was used to verify smoking status. Thirty-seven subjects (18 males, 19 females) were classified as cigarette smokers and 38 were nonsmokers (19 males, 19 females). Fasted subjects received one tablet (150 mg) of bupropion SR, and plasma samples were collected before (0) and 1/2, 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours after dosing. Plasma samples were analyzed for bupropion and its three major metabolites (hydroxybupropion and the aminoalcohol isomers, erythrohydrobupropion plus threohydrobupropion, expressed as a composite) by solid-phase extraction, followed by LC/MS/MS. Factorial analysis of variance (ANOVA) was used to evaluate the effects of smoking and gender on pharmacokinetic parameters. Smokers and nonsmokers differed significantly (p < 0.05) in age and urinary cotinine (p < 0.01) concentration but did not differ significantly in mean weight, height, body surface area, or body mass index. The pharmacokinetic (PK) parameters for bupropion and hydroxybupropion did not differ between smokers and nonsmokers, but differences were found between male and female subjects. Mean values for area under the plasma concentration versus time curve (AUC0-->infinity), volume of distribution (Vd beta) normalized to body weight, maximum plasma concentration (Cmax), and elimination half-life (t1/2 beta) for bupropion were significantly (p < 0.05) greater in females than males, while clearance of bupropion normalized to body weight (CL/f) did not differ between males and females. Females also exhibited significantly (p < 0.05) larger values for hydroxybupropion mean AUC0-->infinity and Cmax than males. The mean ratio of hydroxybupropion to bupropion AUC for adolescents was approximately 4 to 5, which is lower than that previously reported for adults. In conclusion, smoking status does not affect the single-dose pharmacokinetics of bupropion SR in adolescents. However, females differ from males in several potentially important PK parameters for bupropion and its major metabolite, hydroxybupropion. [ABSTRACT FROM AUTHOR]

Objective: Pregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women., Methods: A phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age., Results: In pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19-related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low., Conclusion: CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age., Trial Registration Number: NCT04425629., Competing Interests: Competing interests: TDN, MT, SG, SA, JC, AW, JX, JDD, SCI, CP, DA, DS, BK, ATD, RB, GPG, EC, NB and PD are employees and stockholders at Regeneron Pharmaceuticals, Inc. ATH is a Regeneron employee/stockholder and former Pfizer employee and current stockholder. KCT, JDH and GAH are Regeneron employees and stockholders, and have a patent pending, which has been licensed and receiving royalties, with Regeneron. JAB is a site PI for Regeneron Pharmaceuticals, Inc. multicentred clinical trials, Enanta multicentred clinical trials and Pfizer multicentred clinical trials; a sub-investigator for Novavax multicentred clinical trials; and an advisory board/panel member for Avalere, Pfizer, Moderna, Sobi and Valneva., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Invasive meningococcal disease (IMD) is rare but associated with high morbidity and mortality. In the United States, the most vulnerable age groups are infants and adolescents/young adults, and the most common type of IMD is caused by serogroup B (MenB). MenB is preventable among adolescents and young adults with the use of two licensed vaccines, MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc, Collegeville, PA) and MenB-4C (Bexsero®; GSK Vaccines, Srl, Italy). Because the effectiveness of MenB vaccination is dependent on broad vaccine coverage across circulating disease-causing strains, we reviewed the available clinical and real-world evidence regarding breadth of coverage of the two licensed vaccines in adolescents and young adults in the United States. Both vaccines protect against various MenB strains. More controlled data regarding breadth of coverage across MenB strains are available for MenB-FHbp compared with MenB-4C, whereas more observational data regarding US outbreak strain susceptibility are available for MenB-4C.

Although significant progress has been made in reducing the incidence of invasive pneumococcal disease (IPD) in children, IPD remains a continued threat. Since the introduction of pneumococcal conjugate vaccines (PCVs), rates of IPD and non-IPD have substantially decreased. However, serotype replacement reversed some of the benefits of PCV7 and, more recently, PCV13. Several replacement serotypes are antibiotic resistant, which is a cause of concern for providers. The introduction of the higher-valency conjugate vaccines PCV15 and PCV20 is expected to provide greater serotype coverage; unfortunately, these vaccines do not include some of the recently emerged serotypes. Recommendations for the use of the 23-valent polysaccharide vaccine in high-risk populations may be modified because of the effectiveness of the newer PCVs. Pediatricians must be aware of the new vaccine strategies for the prevention of IPD and the manifestations of IPD so that prompt empirical therapy can be initiated when treatment is required. [ Pediatr Ann . 2023;52(3):e96-e101.] .

Background: In the phase 1-2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern., Methods: In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated., Results: Covid-19-related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P = 0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody-positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was -0.71 log 10 copies per milliliter (95% confidence interval [CI], -0.90 to -0.53) in the 1200-mg group and -0.86 log 10 copies per milliliter (95% CI, -1.00 to -0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups., Conclusions: REGEN-COV reduced the risk of Covid-19-related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.)., (Copyright © 2021 Massachusetts Medical Society.)

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its 'oxidative immune-metabolic' physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Vaccines are one of the greatest public health achievements, protecting children and adults against numerous infectious diseases; however, the complex, rigorous process of vaccine development is unknown to many. A candidate vaccine undergoes extensive evaluation of safety and efficacy to meet licensure requirements before recommendations for use become policy. This time-consuming process involves an intricate collaboration among academia, public and private organizations, and federal agencies to ensure that safety is prioritized in every step. Vaccine safety continues to be monitored after licensure through a robust system. Yet, vaccine hesitancy remains a major challenge, especially now with the coronavirus disease 2019 (COVID-19) pandemic and concerns about the speed with which candidate vaccines are being developed. This article reviews the vaccine development process and the systems in place to ensure safety and effectiveness. A better understanding of these topics is necessary to address concerns and improve public acceptance of all vaccines, particularly COVID-19 vaccines. [Pediatr Ann. 2020;49(12):e509-e515.]., (Copyright 2020, SLACK Incorporated.)

Background: Group B Streptococcus (GBS) remains a significant cause of neonatal infection, but the maternal risk factors for GBS colonization remain poorly defined. We hypothesized that there may be an association between antibiotic exposure during pregnancy and GBS colonization and/or the presence of inducible clindamycin resistance (iCLI-R) in GBS isolates from GBS-colonized pregnant women., Methods: A retrospective cohort study was performed at Louisiana State University Health Sciences Center - Shreveport including demographic and clinical data from 1513 pregnant women who were screened for GBS between July 1, 2009 and December 31, 2010., Results: Among 526 (34.8%) women who screened positive for GBS, 124 (23.6%) carried GBS strains with iCLI-R (GBS-iCLI-R). While antibiotic exposure, race, sexually-transmitted infection (STI) in pregnancy, GBS colonization in prior pregnancy and BMI were identified as risk factors for GBS colonization in univariate analyses, the only independent risk factors for GBS colonization were African-American race (AOR = 2.142; 95% CI = 2.092-3.861) and STI during pregnancy (AOR = 1.309; 95% CI = 1.035-1.653). Independent risk factors for GBS-iCLI-R among women colonized with GBS were non-African-American race (AOR = 2.13; 95% CI = 1.20-3.78) and younger age (AOR = 0.94; 95% CI = 0.91-0.98). Among GBS-colonized women with an STI in the current pregnancy, the only independent risk factor for iCLI-R was Chlamydia trachomatis infection (AOR = 4.31; 95% CI = 1.78-10.41)., Conclusions: This study identified novel associations for GBS colonization and colonization with GBS-iCLI-R. Prospective studies will improve our understanding of the epidemiology of GBS colonization during pregnancy and the role of antibiotic exposure in alterations of the maternal microbiome.

Successful intervention for inborn errors of metabolism (IEMs) is a triumph of modern medicine. For many of these conditions, medical foods are the cornerstone of therapy and the only effective interventions preventing disability or death. Medical foods are designed for patients with limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foods or nutrients, whereby dietary management cannot be achieved by modification of the normal diet alone. In the United States today, access to medical foods is not ensured for many individuals who are affected despite their proven efficacy in the treatment of IEMs, their universal use as the mainstay of IEM management, the endorsement of their use by professional medical organizations, and the obvious desire of families for effective care. Medical foods are not sufficiently covered by many health insurance plans in the United States and, without insurance coverage, many families cannot afford their high cost. In this review, we outline the history of medical foods, define their medical necessity, discuss the barriers to access and reimbursement resulting from the regulatory status of medical foods, and summarize previous efforts to improve access. The Advisory Committee on Heritable Disorders in Newborns and Children asserts that it is time to provide stable and affordable access to the effective management required for optimal outcomes through the life span of patients affected with IEMs. Medical foods as defined by the US Food and Drug Administration should be covered as required medical benefits for persons of all ages diagnosed with an IEM., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Aims: 25-Hydroxyvitamin D [25(OH)VD] deficiency/inadequacy is a major public health issue affecting more than 1 billion people worldwide. A convincing association exists between low levels of circulating 25(OH)VD and the poor health outcomes associated with chronic diseases. However, high supraphysiological doses of VD are needed to achieve the required 25(OH)VD levels in the blood, because many subjects respond poorly to supplementation., Results: This study reports a link between 25(OH)VD deficiency and a reduction in glutathione (GSH) in obese adolescents. The improvement in GSH status that results from cosupplementation with VD and l-cysteine (LC; a GSH precursor) significantly reduced oxidative stress in a mouse model of 25(OH)VD deficiency. It also positively upregulated VD regulatory genes (VDBP/VD-25-hydroxylase/VDR) in the liver and glucose metabolism genes (PGC-1α/VDR/GLUT-4) in muscle, boosted 25(OH)VD, and reduced inflammation and insulin resistance (IR) levels in the blood compared with supplementation with VD alone. In vitro GSH deficiency caused increased oxidative stress and downregulation of VDBP/VD-25-hydroxylase/VDR and upregulation of CYP24a1 in hepatocytes and downregulation of PGC-1α/VDR/GLUT-4 in myotubes. This study demonstrates that improvement in the GSH status exerts beneficial effects on the blood levels of 25(OH)VD, as well as on the inflammation and IR in a VD-deficient mouse model. Thus, the VD supplements widely consumed by the public are unlikely to be successful unless the GSH status is also corrected., Innovation: These studies demonstrate a previously undiscovered mechanism by which GSH status positively upregulates the bioavailability of 25(OH)VD., Conclusion: Supplementation with a combination of VD and LC or GSH precursor, rather than supplementation with VD alone, is beneficial and helps achieve more successful VD supplementation. Antioxid. Redox Signal. 00, 000-000.

Purpose of Review: This review describes the impact of recommendations for routine immunization of infants and children against hepatitis A and hepatitis B, the changing epidemiology of these infections, and the remaining challenges to controlling or eliminating these diseases in the United States., Recent Findings: Rates of hepatitis A and B have significantly declined because of childhood vaccination programs and long-term protection provided by infant immunization. However, hepatitis A immunization rates remain lower than other vaccines, and outbreaks continue to occur in part due to a growing number of susceptible adults. The Advisory Committee on Immunization Practice has updated pre and postexposure prophylaxis and travel recommendations for hepatitis A prevention in young infants, as well as recommendations to reduce ongoing perinatal transmission of hepatitis B., Summary: Pediatric healthcare providers should continue to immunize all infants against hepatitis A and B and ensure that no child outgrows the pediatric practice without being vaccinated. To address hepatitis A, providers should be aware of new recommendations for unimmunized travelers, use vaccines to prevent and control outbreaks, and ensure postexposure prophylaxis. Universal vaccination of infants against hepatitis B should begin before hospital discharge. The prevention of perinatal transmission is critical for control and possible eradication of hepatitis B.

Purpose of Review: Maternal vaccination is a well-tolerated and effective way to protect mothers, their developing fetuses, and their young infants from infectious diseases. Although influenza vaccine and diphtheria, tetanus, and acellular pertussis (Tdap) vaccine are recommended for all pregnant women, uptake rates in the United States remain low. This review will focus on the rationale, scientific evidence, and perceptions of vaccination during pregnancy., Recent Findings: Recent studies show that administration of influenza and Tdap vaccines during pregnancy is well tolerated and provides protection to the pregnant woman, her fetus, and young infant. Studies have shown that many pregnant women look to their obstetricians to guide their prenatal care. A strong provider recommendation remains the greatest impetus to increase vaccine uptake. Both healthcare providers and expectant mothers should continue to be educated on the importance and safety of the influenza and Tdap vaccines during pregnancy., Summary: Providers play a central role in advising patients and their families about the importance of maternal vaccination. The strong recommendation of providers and the availability of maternal vaccines in OB/GYN offices are keys to improve vaccine uptake. Attention must be paid to further development of intervention techniques that address unique barriers such as vaccine cost, storage concerns, and misinformation about vaccine safety.

Purpose of Review: As healthcare-associated influenza is a serious public health concern, this review examines legal and ethical arguments supporting mandatory influenza vaccination policies for healthcare personnel, implementation issues and evidence of effectiveness., Recent Findings: Spread of influenza from healthcare personnel to patients can result in severe harm or death. Although most healthcare personnel believe that they should be vaccinated against seasonal influenza, the Centers for Disease Control and Prevention (CDC) report that only 79% of personnel were vaccinated during the 2015-2016 season. Vaccination rates were as low as 44.9% in institutions that did not promote or offer the vaccine, compared with rates of more than 90% in institutions with mandatory vaccination policies. Policies that mandate influenza vaccination for healthcare personnel have legal and ethical justifications. Implementing such policies require multipronged approaches that include education efforts, easy access to vaccines, vaccine promotion, leadership support and consistent communication emphasizing patient safety., Summary: Mandatory influenza vaccination for healthcare personnel is a necessary step in protecting patients. Patients who interact with healthcare personnel are often at an elevated risk of complications from influenza. Vaccination is the best available strategy for protecting against influenza and evidence shows that institutional policies and state laws can effectively increase healthcare personnel vaccination rates, decreasing the risk of transmission in healthcare settings. There are legal and ethical precedents for institutional mandatory influenza policies and state laws, although successful implementation requires addressing both administrative and attitudinal barriers.

Summary: We describe the case of a 24-year-old male with hyper-IgE syndrome (HIES) which was diagnosed at 4 years of age and died from a very rare cardiac complication. He had typical clinical and laboratory manifestations of HIES, including total serum IgE as high as > 100,000 IU/mL. Stem cell transplantation was not available. During the 20-year follow-up, he suffered numerous various infections of the skin and deep organs, partial lung resection, as well as multiple bone fractures. At age 24, he developed acute decompensated heart failure associated with elevated serum troponin I and brain natriuretic protein. Two-dimensional echocardiogram revealed global hypokinesis of the left ventricle with estimated ejection fraction 20-25%, and catheterization revealed ectasia of multiple coronary arteries. Endomyocardial biopsy showed lymphocytic myocarditis, focal necrosis, mild fibrosis, and myxoid degeneration, but cultures were negative. The patient improved on corticosteroid therapy and was discharged on heart failure therapy and external defibrillator. Six weeks later, he developed supraventricular tachycardia and persistent global hypokinesis and was treated with amiodarone. A trial of intravenous immunoglobulin was initiated and was repeated as outpatient every four weeks for four times. However, his cardiac function did not improve and he developed severe hypotension and pulseless electrical activity arrest. Resuscitation was unsuccessful. To the best of our knowledge, this is the first reported case of HIES complicated with lymphocytic myocarditis. Both immunologists and cardiologists need to be aware of such a complication and practice caution in using immunosuppressants when the patient's immune status is markedly compromised.

With the expansion of the adolescent immunization schedule during the past decade, immunization rates notably vary by vaccine and by state. Addressing barriers to improving adolescent vaccination rates is a priority. Every visit can be viewed as an opportunity to update and complete an adolescent's immunizations. It is essential to continue to focus and refine the appropriate techniques in approaching the adolescent patient and parent in the office setting. Health care providers must continuously strive to educate their patients and develop skills that can help parents and adolescents overcome vaccine hesitancy. Research on strategies to achieve higher vaccination rates is ongoing, and it is important to increase the knowledge and implementation of these strategies. This clinical report focuses on increasing adherence to the universally recommended vaccines in the annual adolescent immunization schedule of the American Academy of Pediatrics, the American Academy of Family Physicians, the Centers for Disease Control and Prevention, and the American Congress of Obstetricians and Gynecologists. This will be accomplished by (1) examining strategies that heighten confidence in immunizations and address patient and parental concerns to promote adolescent immunization and (2) exploring how best to approach the adolescent and family to improve immunization rates., (Copyright © 2017 by the American Academy of Pediatrics.)

The adolescent period heralds the pediatric patient's transition into adulthood. It is a time of dynamic development during which effective preventive care measures can promote safe behaviors and the development of lifelong health habits. One of the foundations of preventive adolescent health care is timely vaccination, and every visit can be viewed as an opportunity to update and complete an adolescent's immunizations.In the past decade, the adolescent immunization schedule has expanded to include 2 doses of quadrivalent meningococcal conjugate vaccine, 1 dose of tetanus, diphtheria, acellular pertussis, absorbed vaccine, 2 or 3 doses of human papillomavirus vaccine, depending on the child's age, and an annual influenza vaccine. In addition, during adolescent visits, health care providers can determine whether catch-up vaccination is needed to meet early childhood recommendations for hepatitis B; hepatitis A; measles, mumps, rubella; poliovirus; and varicella vaccines. New serogroup B meningococcal vaccines are now available for those at increased risk for meningococcal disease; in addition, these serogroup B meningococcal vaccines received a Category B recommendation for healthy adolescents, where individual counseling and risk-benefit evaluation based on health care provider judgements and patient preferences are indicated. This clinical report focuses on the epidemiology of adolescent vaccine-preventable diseases by reviewing the rationale for the annual universally recommended adolescent immunization schedule of the American Academy of Pediatrics, the American Academy of Family Physicians, the Centers for Disease Control and Prevention, and the American Congress of Obstetricians and Gynecologists. In addition, the barriers that negatively influence adherence to this current adolescent immunization schedule will be highlighted., (Copyright © 2017 by the American Academy of Pediatrics.)

Purpose of Review: This article provides a clinically relevant review and analysis of the latest research and recommendations regarding human papillomavirus (HPV) vaccine., Recent Findings: Although studies have found that bivalent and quadrivalent HPV vaccines are well tolerated and effective, high-risk HPV types not included in these vaccines are responsible for a significant burden of disease worldwide. Clinical trials have found that the recently licensed 9-valent vaccine, which includes five additional high-risk HPV types, is well tolerated and efficacious. This vaccine was added to the Advisory Committee on Immunization Practices HPV vaccination recommendations in 2015. A two-dose series in girls and boys 9-14 years old with a 6- or 12-month interval between doses has been shown to result in antibody titers noninferior to those measured after the three-dose series in women 16-26 years old. The Food and Drug Administration is considering these data., Summary: Recent publications highlight the safety and effectiveness of HPV vaccines, the licensure of the 9-valent HPV vaccine, and the revision of HPV vaccine recommendations.

Purpose of Review: This article provides a clinically relevant review and analysis of the latest research regarding barriers to human papillomavirus (HPV) vaccination and strategic efforts to promote this vaccine., Recent Findings: HPV vaccines are safe, effective, and could prevent the majority of HPV-attributable cancers, if vaccination coverage is high. However, uptake of HPV vaccine lags behind other vaccines recommended for 11 to 12-year olds. A lack of provider recommendation has consistently been found to be a key barrier to increasing vaccination rates. Lack of knowledge about the vaccine among parents coupled with an overestimation of parental vaccine hesitancy among providers also hinder vaccine uptake. Strongly recommending the vaccine as a safe, routine immunization that prevents cancer, and coadministering it with tetanus, diphtheria, and acellular pertussis vaccine and quadrivalent meningococcal conjugate vaccine, enhance vaccine uptake. In some cases, reminder and recall systems result in additional increases in vaccination rates., Summary: Recent publications reveal new information about the implementation of HPV vaccines. Provider recommendation is a key approach, as is offering it routinely at the same time as other universally recommended adolescent immunizations. With the integration of these concepts into the clinical setting, adolescents can be better protected against HPV and its associated diseases.

On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.

Purpose of Review: To provide a clinically relevant synopsis of the latest research and recommendations regarding adolescent immunizations., Recent Findings: Immunization is an important and effective strategy for preventing morbidity and mortality in adolescents. Although there has been progress in recent years, coverage rates in the US remain suboptimal, particularly for the human papillomavirus vaccine. Much work has been done to better understand and address the barriers to adolescent immunization, so that all teens may be protected against serious vaccine-preventable diseases. In addition, several recent studies have focused on the effectiveness of current adolescent vaccines and the development of new vaccines to protect against additional types of human papillomavirus and serotype B Neisseria meningitidis. Decreased pertussis vaccine effectiveness has led to new recommendations for pregnant women, including adolescents, to protect them and their young infants. The present review highlights selected literature on acellular pertussis, meningococcal, and human papillomavirus vaccines. Research findings on various strategies to improve adolescent vaccine uptake are also discussed in this review., Summary: Research on adolescent immunizations and their delivery continues to have an impact on clinical practice and will shape future guidelines. Through this work, we can learn how best to protect adolescents against vaccine-preventable diseases.

During its February 2015 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended 9-valent human papillomavirus (HPV) vaccine (9vHPV) (Gardasil 9, Merck and Co., Inc.) as one of three HPV vaccines that can be used for routine vaccination. HPV vaccine is recommended for routine vaccination at age 11 or 12 years. ACIP also recommends vaccination for females aged 13 through 26 years and males aged 13 through 21 years not vaccinated previously. Vaccination is also recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously. 9vHPV is a noninfectious, virus-like particle (VLP) vaccine. Similar to quadrivalent HPV vaccine (4vHPV), 9vHPV contains HPV 6, 11, 16, and 18 VLPs. In addition, 9vHPV contains HPV 31, 33, 45, 52, and 58 VLPs. 9vHPV was approved by the Food and Drug Administration (FDA) on December 10, 2014, for use in females aged 9 through 26 years and males aged 9 through 15 years. For these recommendations, ACIP reviewed additional data on 9vHPV in males aged 16 through 26 years. 9vHPV and 4vHPV are licensed for use in females and males. Bivalent HPV vaccine (2vHPV), which contains HPV 16, 18 VLPs, is licensed for use in females. This report summarizes evidence considered by ACIP in recommending 9vHPV as one of three HPV vaccines that can be used for vaccination and provides recommendations for vaccine use.

Background: The treatment of symptomatic congenital cytomegalovirus (CMV) disease with intravenous ganciclovir for 6 weeks has been shown to improve audiologic outcomes at 6 months, but the benefits wane over time., Methods: We conducted a randomized, placebo-controlled trial of valganciclovir therapy in neonates with symptomatic congenital CMV disease, comparing 6 months of therapy with 6 weeks of therapy. The primary end point was the change in hearing in the better ear ("best-ear" hearing) from baseline to 6 months. Secondary end points included the change in hearing from baseline to follow-up at 12 and 24 months and neurodevelopmental outcomes, with each end point adjusted for central nervous system involvement at baseline., Results: A total of 96 neonates underwent randomization, of whom 86 had follow-up data at 6 months that could be evaluated. Best-ear hearing at 6 months was similar in the 6-month group and the 6-week group (2 and 3 participants, respectively, had improvement; 36 and 37 had no change; and 5 and 3 had worsening; P=0.41). Total-ear hearing (hearing in one or both ears that could be evaluated) was more likely to be improved or to remain normal at 12 months in the 6-month group than in the 6-week group (73% vs. 57%, P=0.01). The benefit in total-ear hearing was maintained at 24 months (77% vs. 64%, P=0.04). At 24 months, the 6-month group, as compared with the 6-week group, had better neurodevelopmental scores on the Bayley Scales of Infant and Toddler Development, third edition, on the language-composite component (P=0.004) and on the receptive-communication scale (P=0.003). Grade 3 or 4 neutropenia occurred in 19% of the participants during the first 6 weeks. During the next 4.5 months of the study, grade 3 or 4 neutropenia occurred in 21% of the participants in the 6-month group and in 27% of those in the 6-week group (P=0.64)., Conclusions: Treating symptomatic congenital CMV disease with valganciclovir for 6 months, as compared with 6 weeks, did not improve hearing in the short term but appeared to improve hearing and developmental outcomes modestly in the longer term. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00466817.).

This report summarizes the epidemiology of human papillomavirus (HPV) and associated diseases, describes the licensed HPV vaccines, provides updated data from clinical trials and postlicensure safety studies, and compiles recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of HPV vaccines. Persistent infection with oncogenic HPV types can cause cervical cancer in women as well as other anogenital and oropharyngeal cancers in women and men. HPV also causes genital warts. Two HPV vaccines are licensed in the United States. Both are composed of type-specific HPV L1 protein, the major capsid protein of HPV. Expression of the L1 protein using recombinant DNA technology produces noninfectious virus-like particles (VLPs). Quadrivalent HPV vaccine (HPV4) contains four HPV type-specific VLPs prepared from the L1 proteins of HPV 6, 11, 16, and 18. Bivalent HPV vaccine (HPV2) contains two HPV type-specific VLPs prepared from the L1 proteins of HPV 16 and 18. Both vaccines are administered in a 3-dose series. ACIP recommends routine vaccination with HPV4 or HPV2 for females aged 11 or 12 years and with HPV4 for males aged 11 or 12 years. Vaccination also is recommended for females aged 13 through 26 years and for males aged 13 through 21 years who were not vaccinated previously. Males aged 22 through 26 years may be vaccinated. ACIP recommends vaccination of men who have sex with men and immunocompromised persons (including those with HIV infection) through age 26 years if not previously vaccinated. As a compendium of all current recommendations for use of HPV vaccines, information in this report is intended for use by clinicians, vaccination providers, public health officials, and immunization program personnel as a resource. ACIP recommendations are reviewed periodically and are revised as indicated when new information and data become available.

Purpose of Review: To provide a clinically relevant summary of the latest research and recommendations regarding childhood and adolescent immunizations., Recent Findings: Childhood vaccination has dramatically reduced pediatric morbidity and mortality in the United States. Recent research on childhood and adolescent immunizations has focused on expanding the use of current vaccines for additional subpopulations as well as the development of new vaccines. In particular, data confirming the safety and immunogenicity of vaccines in various groups of children have shaped national guidelines. Furthermore, studies on vaccine uptake, cost-effectiveness, and impact of vaccination have reinforced the importance of adhering to these guidelines. More work needs to be done by providers and parents to increase vaccination coverage rates to better protect children and adolescents from these serious diseases. In this article, selected recent publications and recommendations on the following vaccines are reviewed: influenza, meningococcal conjugate, childhood and adolescent/adult formulations of diphtheria and tetanus toxoids and acellular pertussis, pneumococcal conjugate, and human papillomavirus., Summary: Research on childhood and adolescent vaccinations continues to shape future guidelines. Through this work, we can learn how to optimize the protection of all children and adolescents against vaccine-preventable diseases.

Purpose: The US Secretary of Health and Human Services provides guidance to state newborn screening programs about which conditions should be included in screening (i.e., the "Recommended Uniform Screening Panel"). This guidance is informed by evidence-based recommendations from the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. This report describes the Advisory Committee's revised decision-making process for considering conditions nominated to the panel., Methods: An expert panel meeting was held in April 2012 to revise the decision matrix, which helps to guide the recommendation process. In January 2013, the Advisory Committee voted to adopt the revised decision matrix., Results: The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominated conditions., Conclusion: The revised decision matrix will bring increased quality, transparency, and consistency to the process of modifying the recommended uniform screening panel and will now allow formal evaluation of the challenges that state newborn screening programs face in adopting screening for new conditions.

Purpose of Review: To provide a clinically relevant synopsis of recent research findings as well as updated recommendations from the American Academy of Pediatrics (AAP) and Advisory Committee on Immunization Practices (ACIP) regarding adolescent immunizations., Recent Findings: Coverage rates for the adolescent vaccinations continue to lag behind those of the childhood vaccinations, despite their importance. Recent research has focused on the reasons for suboptimal adolescent vaccination rates as well as strategies for improvement. By more fully understanding the barriers to immunization, efforts can be implemented to address these concerns and to ensure that all eligible adolescents receive their vaccinations. In addition, much work has focused on the duration of protection induced by childhood and adolescent vaccinations and the need for booster doses in older adolescents. Because immunity has been found to wane after vaccination, these booster doses can serve to more fully protect adolescents. This article reviews selected recent publications on human papillomavirus, meningococcal conjugate, and tetanus and diphtheria toxoids and acellular pertussis vaccines., Summary: Adolescent vaccinations will continue to be studied and this research will serve to shape future recommendations. Through this work, we can learn the best methods to optimize the protection of all adolescents against these very serious diseases.

Purpose of Review: To provide a clinically relevant synopsis of recent research findings as well as updated guidelines from the American Academy of Pediatrics and Advisory Committee on Immunization Practices regarding child and adolescent immunizations., Recent Findings: Childhood vaccinations have served to dramatically reduce pediatric morbidity and mortality in the USA. Much of the recent research has focused on the improvement of current vaccines as well as on the development of new vaccines. By improving the safety, efficacy and immunogenicity of vaccinations, children can be more fully protected. Additionally, recommendations have broadened as vaccinations have been proven well tolerated and effective for a growing number of subpopulations. Although more groups of children are now included in vaccination recommendations, efforts must continue to ensure that all eligible children receive their vaccinations. This article reviews selected recent publications on influenza, human papillomavirus, the childhood and adolescent/adult formulations of diphtheria and tetanus toxoids and acellular pertussis, meningococcal conjugate and pneumococcal vaccines. The relationship between febrile seizures and childhood immunizations is explored., Summary: The research on childhood and adolescent vaccinations is continuously growing and will serve to shape future recommendations. Through their findings, we can learn how to optimize the protection of all children and adolescents against these very serious diseases.

Background: Infants of diabetic mothers (IDMs) are at increased risk for metabolic complications. Type 1 and some type 2 diabetic patients have elevated levels of the ketone bodies acetoacetate (AA) and β-hydroxybutyrate (BHB)., Objective: The aim of this study was to examine how hyperketonemia in diabetic mothers affects markers of inflammation and oxidative stress in their offspring., Methods: Blood was obtained from 23 diabetic mothers and 13 healthy mothers and their infants' umbilical cords at delivery. Interleukin-8, monocyte chemotactic protein-1 (MCP-1) and protein carbonyl (protein oxidation) levels were determined by ELISA. U937 human monocyte cell culture was used to examine the effect of AA and BHB on secretion of MCP-1., Results: There was a significant increase in the levels of AA in cord blood of IDMs compared with cord blood of infants of healthy mothers. A significant increase in the levels of protein oxidation (p < 0.05) and MCP-1 levels (p < 0.05) was observed in the cord blood of IDMs. The level of MCP-1 correlated significantly (r = 0.51, p = 0.01) with the concentration of AA in the IDMs. In further experiments with cultured monocytes treated with exogenous AA (0-4 mM), a significant increase in MCP-1 secretion was observed in AA- but not BHB-treated monocytes., Conclusion: Blood levels of AA and MCP-1 are elevated in IDMs, which may contribute to the development of the metabolic complications seen in IDMs., (Copyright © 2012 S. Karger AG, Basel.)

Sinus of Valsalva aneurysm is a rare, catastrophic complication of endocarditis. We report an unusual case of ruptured sinus of Valsalva aneurysm associated with endocarditis that was caused by Streptococcus pneumoniae serotype 21. The patient, a 12-year-old girl, underwent surgical repair of the aneurysm and was given intravenous antibiotics for 6 weeks. She was doing well at the 6-week follow-up visit. This case is unusual because of the patient's young age at presentation, the absence of predisposing factors, and the isolation of a nonvaccine serotype 21, which revealed the epidemiologic changes of invasive pneumococcal disease. To our knowledge, this is the first reported case of endocarditis caused by this S. pneumoniae serotype.

Objectives: To pilot-test a visual aid developed to help counsel pregnant women., Methods: After agreeing to participate, pregnant women at >28 weeks of gestation were assigned randomly to counseling with or without a visual aid. The visual aid contained pictures, graphics, and short messages about delivery room resuscitation, chances of survival, anticipated neonatal course, and long-term neurodevelopmental disabilities. A neonatal fellow performed counseling with a standardized script for an anticipated delivery at 23 weeks of gestation. In precounseling and postcounseling sessions, women were given a structured interview to assess their knowledge of chances of survival and disability and attitudes toward resuscitation., Results: Of the 89 women who participated, 76% were black and 59% read below a 9th-grade level. Compared with the no-visual aid group, women in the visual aid group recalled more disabilities and predicted longer neonatal stays (P = .01). For both groups, mothers' perceptions of the chances of survival were lower after counseling; the decrease was greater in the visual aid group (P = .03). The majority of women in each group opted for resuscitation, which was not affected by counseling. In multivariate analyses, use of the visual aid was a significant independent factor in explaining before/after differences in survival chances and recall of a long NICU stay and number of disabilities; higher literacy levels also were significant for recalling the number of disabilities., Conclusions: Use of a visual aid improved mothers' knowledge and showed promise as a decision aid for counseling at the threshold of viability.

Purpose of Review: To provide a clinically relevant synopsis of research findings regarding childhood and adolescent vaccines., Recent Findings: Much research confirms the safety, immunogenicity, and efficacy of specific vaccines as well as the positive impact on overall morbidity and mortality. Prevention and control strategies involve the expansion of vaccine recommendations to include more individuals and/or more vaccine doses. In addition, the role of universal infant vaccination, the advantages of even partial immunization, and the documented benefits of recently introduced vaccines are explored. The material in this review includes important areas of clinical practice improvement, such as awareness of interim recommendations or monitoring of vaccine failures. Literature on hepatitis B, rotavirus, Haemophilus influenzae type b conjugate, and pneumococcal vaccines is included in this first of two articles., Summary: New research on childhood and adolescent vaccines is anticipated to shape the practice of pediatric providers. Research will continue to provide the science to optimize protection and to promote the health and well being of all children and adolescents.

We report a case of failure of clindamycin therapy due to inducible clindamycin resistance. We surveyed and found that only 52% of reporting hospitals in the state of Louisiana were performing the D test for inducible clindamycin resistance according to guidelines recommended by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards).

Purpose of Review: To provide a clinically relevant synopsis of research findings regarding childhood and adolescent vaccines., Recent Findings: Vaccine coverage is relatively static or improving for the vaccines included in the 2010 annual harmonized immunization schedules. Providers should be reviewing patients' immunization records at each visit to take advantage of any opportunity to administer indicated, age-appropriate vaccines. There have been infectious disease outbreaks among highly immunized populations, although unvaccinated or undervaccinated individuals continue to play large roles in the spread of disease. Infants, many of whom are too young to be vaccinated, continue to bear a large disease burden, which underscores the importance of cocooning and, in some cases, vaccination of pregnant women. Influenza, measles, mumps, and rubella, varicella, hepatitis A, meningococcal conjugate, human papillomavirus, diphtheria and tetanus toxoids and acellular pertussis, and tetanus and diphtheria toxoids and acellular pertussis vaccines are reviewed in this second of two articles., Summary: New research on childhood and adolescent vaccines is anticipated to shape the practice of pediatric providers. Research will continue to provide the science to optimize protection and to promote the health and well being of all children and adolescents.

Purpose: Retinopathy of Prematurity (ROP) is a vasoproliferative disorder affecting preterm infants leading to visual impairment. ROP is more common in Caucasians than African Americans. Very low birth weight infants have immature retinas and are susceptible to ROP. Because of differences in individual responses to the treatment, various genetic factors have been looked into to understand the etiology of ROP. Endothelial nitric oxide (eNO) serves as a vasodilator, relaxes smooth muscle, prevents platelet aggregation, and facilitates improved blood flow and vascular tonicity. Mutant eNO synthase (eNOS) genotypes result in reduced nitric oxide levels by decreasing enzyme activity. Since eNO affects vasculature and ROP is a vascular disease, the present investigation was aimed at studying the association of genotypes with ROP., Methods: Two eNOS gene single nucleotide polymorphisms (SNPs) (T-786C, and G894T) were studied by microplate-Restriction Fragment Length Polymorphism Polymerase Chain Reaction (RFLP PCR) method. Genotypes were studied in 146 premature infants., Results: The present data showed significant differences in the baseline gene frequencies between Caucasians and African Americans. ROP patients displayed 3-fold higher frequencies of mutant -786C and 894T alleles in both ethnicities compared to respective controls., Conclusions: The present data suggest ethnic stratification of genotypes. Mutant -786C and 894T alleles are significant risk factors in the development of ROP, and suggest a strong association between eNOS polymorphisms and the disease. It is interesting to know if a larger dataset of ROP patients can confirm our initial findings.

Head lice infestation is associated with limited morbidity but causes a high level of anxiety among parents of school-aged children. Since the 2002 clinical report on head lice was published by the American Academy of Pediatrics, patterns of resistance to products available over-the-counter and by prescription have changed, and additional mechanical means of removing head lice have been explored. This revised clinical report clarifies current diagnosis and treatment protocols and provides guidance for the management of children with head lice in the school setting.

The 2006 mumps resurgence in the United States raised questions about the appropriate isolation period for people with mumps. To determine the scientific basis for isolation recommendations, we conducted a literature review and considered isolation of virus and virus load in saliva and respiratory secretions as factors that were related to mumps transmission risk. Although mumps virus has been isolated from 7 days before through 8 days after parotitis onset, the highest percentage of positive isolations and the highest virus loads occur closest to parotitis onset and decrease rapidly thereafter. Most transmission likely occurs before and within 5 days of parotitis onset. Transmission can occur during the prodromal phase and with subclinical infections. Updated guidance, released in 2007-2008, changed the mumps isolation period from 9 to 5 days. It is now recommended that mumps patients be isolated and standard and droplet precautions be followed for 5 days after parotitis onset.

Hydrogen sulfide (H(2)S) is emerging as a physiological neuromodulator as well as a smooth muscle relaxant. We submit the first evidence that blood H(2)S levels are significantly lower in fasting blood obtained from type 2 diabetes patients compared with age-matched healthy subjects, and in streptozotocin-treated diabetic rats compared with control Sprague-Dawley rats. We further observed that supplementation with H(2)S or an endogenous precursor of H(2)S (l-cysteine) in culture medium prevents IL-8 and MCP-1 secretion in high-glucose-treated human U937 monocytes. These first observations led to the hypothesis that lower blood H(2)S levels may contribute to the vascular inflammation seen in diabetes.