Lung Lavage Granulocyte Patterns and Clinical Phenotypes in Children with Severe, Therapy-Resistant Asthma.

BACKGROUND: Children with severe asthma have frequent exacerbations despite guidelines-based treatment with high-dose corticosteroids. The importance of refractory lung inflammation and infectious species as factors contributing to poorly controlled asthma in children is poorly understood. OBJECTIVE: To identify prevalent granulocyte patterns and potential pathogens as targets for revised treatment, 126 children with severe asthma underwent clinically indicated bronchoscopy. METHODS: Diagnostic tests included bronchoalveolar lavage (BAL) for cell count and differential, bacterial and viral studies, spirometry, and measurements of blood eosinophils, total IgE, and allergen-specific IgE. Outcomes were compared among 4 BAL granulocyte patterns. RESULTS: Pauci-granulocytic BAL was the most prevalent granulocyte category (52%), and children with pauci-granulocytic BAL had less postbronchodilator airflow limitation, less blood eosinophilia, and less detection of BAL enterovirus compared with children with mixed granulocytic BAL. Children with isolated neutrophilia BAL were differentiated by less blood eosinophilia than those with mixed granulocytic BAL, but greater prevalence of potential bacterial pathogens compared with those with pauci-granulocytic BAL. Children with isolated eosinophilia BAL had features similar to those with mixed granulocytic BAL. Children with mixed granulocytic BAL took more maintenance prednisone, and had greater blood eosinophilia and allergen sensitization compared with those with pauci-granulocytic BAL. CONCLUSIONS: In children with severe, therapy-resistant asthma, BAL granulocyte patterns and infectious species are associated with novel phenotypic features that can inform pathway-specific revisions in treatment. In 32% of children evaluated, BAL revealed corticosteroid-refractory eosinophilic infiltration amenable to anti-TH2 biological therapies, and in 12%, a treatable bacterial pathogen.

Mupirocin for Staphylococcus aureus Decolonization of Infants in Neonatal Intensive Care Units.

: media-1vid110.1542/5849573989001PEDS-VA_2018-1565Video Abstract BACKGROUND AND OBJECTIVES: Staphylococcus aureus (SA) is the second leading cause of late-onset sepsis among infants in the NICU. Because colonization of nasal mucosa and/or skin frequently precedes invasive infection, decolonization strategies, such as mupirocin application, have been attempted to prevent clinical infection, but data supporting this approach in infants are limited. We conducted a phase 2 multicenter, open-label, randomized trial to assess the safety and efficacy of intranasal plus topical mupirocin in eradicating SA colonization in critically ill infants. METHODS: Between April 2014 and May 2016, infants <24 months old in the NICU at 8 study centers underwent serial screening for nasal SA. Colonized infants who met eligibility criteria were randomly assigned to receive 5 days of mupirocin versus no mupirocin to the intranasal, periumbilical, and perianal areas. Mupirocin effects on primary (day 8) and persistent (day 22) decolonization at all three body sites were assessed. RESULTS: A total of 155 infants were randomly assigned. Mupirocin was generally well tolerated, but rashes (usually mild and perianal) occurred significantly more often in treated versus untreated infants. Primary decolonization occurred in 62 of 66 (93.9%) treated infants and 3 of 64 (4.7%) control infants (P < .001). Twenty-one of 46 (45.7%) treated infants were persistently decolonized compared with 1 of 48 (2.1%) controls (P < .001). CONCLUSIONS: Application of mupirocin to multiple body sites was safe and efficacious in eradicating SA carriage among infants in the NICU; however, after 2 to 3 weeks, many infants who remained hospitalized became recolonized.

A Review of the Global Burden, New Diagnostics, and Current Therapeutics for Amebiasis.

Amebiasis, due to the pathogenic parasite Entamoeba histolytica, is a leading cause of diarrhea globally. Largely an infection of impoverished communities in developing countries, amebiasis has emerged as an important infection among returning travelers, immigrants, and men who have sex with men residing in developed countries. Severe cases can be associated with high case fatality. Polymerase chain reaction-based diagnosis is increasingly available but remains underutilized. Nitroimidazoles are currently recommended for treatment, but new drug development to treat parasitic agents is a high priority. Amebiasis should be considered before corticosteroid therapy to decrease complications. There is no effective vaccine, so prevention focuses on sanitation and access to clean water. Further understanding of parasite biology and pathogenesis will advance future targeted therapeutic and preventative strategies.

Zika Virus Infection.

In less than 2 years since entry into the Americas, we have witnessed the emergent spread of Zika virus into large subsets of immunologically naïve human populations and then encountered the devastating effects of microcephaly and brain anomalies that can arise from in utero infection with the virus. Diagnostic evaluation and management of affected infants continues to evolve as our understanding of Zika virus rapidly advances. The development of a safe and effective vaccine holds the potential to attenuate the spread of infection and limit the impact of congenital infection.

Ceftaroline fosamil: a brief clinical review.

Ceftaroline is a novel cephalosporin with a favorable tolerability profile and broad in vitro activity against many resistant Gram-positive and common Gram-negative organisms. Ceftaroline fosamil is the first cephalosporin to be approved by the United States Food and Drug Administration (FDA) for the treatment of adults with acute bacterial skin and soft tissue infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). It is also approved by the FDA for the treatment of adults with community-acquired bacterial pneumonia, including cases caused by Streptococcus pneumoniae (with or without concurrent bacteremia), although there are no data at this time to support the use of ceftaroline fosamil for the treatment of pneumonia caused by MRSA. Ceftaroline fosamil is likewise approved by the European Commission for the treatment of adults with complicated skin and soft tissue infections or community-acquired pneumonia. This review summarizes the pharmacokinetic and microbiologic properties of ceftaroline, as well as the safety and efficacy data that led to its approval by the FDA in 2010 and the European Commission in 2012. Future directions to be addressed are also highlighted.

Burden of disease from cryptosporidiosis.

PURPOSE OF REVIEW: The global significance of cryptosporidiosis is widespread and far-reaching. In this review, we present recent data about strain diversity and the burden of disease, along with developments in therapeutic and preventive strategies. RECENT FINDINGS: Cryptosporidium is an emerging pathogen that disproportionately affects children in developing countries and immunocompromised individuals. Without a diagnostic tool amenable for use in developing countries, the burden of infection and its relationship to growth faltering, malnutrition, and diarrheal mortality remain underappreciated. Disease incidence is also increasing in industrialized countries largely as a result of outbreaks in recreational water facilities. Advances in molecular methods, including subtyping analysis, have yielded new insights into the epidemiology of cryptosporidiosis. However, without practical point-of-care diagnostics, an effective treatment for immunocompromised patients, and a promising vaccine candidate, the ability to reduce the burden of disease in the near future is limited. This is compounded by inadequate coverage with antiretroviral therapy in developing countries, the only current means of managing HIV-infected patients with cryptosporidiosis. SUMMARY: Cryptosporidiosis is one of the most important diarrheal pathogens affecting people worldwide. Effective methods to control and treat cryptosporidiosis among high-risk groups present an ongoing problem in need of attention.

The utility of human challenge studies in vaccine development: lessons learned from cholera.

Experiments in which virulent infectious organisms are administered to healthy adult volunteers with the intent to deliberately induce infection have been practiced for centuries. Many useful applications have developed from these experiments such as the provision of evidence of microbial pathogenicity and the identification of key virulence factors. Challenge studies have also played an important role in the evaluation of preliminary efficacy of potential vaccine candidates. Over the past 40 years, these experimental human challenge studies have found particular utility with regards to the development of both living and nonliving attenuated cholera vaccines. This review highlights some of the important contributions made by these challenge studies to cholera vaccine research.