Catherine S. Lachenauer

Serotypes VI and VIII Predominate among Group B Streptococci Isolated from Pregnant Japanese Women

Infection by group B streptococcus (GBS) is an important cause of bacterial disease in neonates, pregnant women, and nonpregnant adults. Whereas serotypes Ia, Ib, II, III, and V are most commonly associated with colonization and disease in the United States, strains of other serotypes have been isolated from patients in Japan. By use of an inhibition ELISA, the serotypes of 73 vaginal colonizing GBS strains isolated from healthy pregnant Japanese women were investigated. Twenty-six (35.6%) were type VIII, 18 (24.7%) were type VI, and the remaining 29 were distributed among more traditional serotypes. Strains were also tested by immunoblot for the presence of GBS surface proteins. Fifty-three (72.6%) of the 73 strains expressed one or more laddering GBS proteins. These data show that type VI and VIII GBS strains are common vaginal isolates in pregnant Japanese women and that one or more laddering proteins are present in most GBS strains.

Results from a Prospective, International, Epidemiologic Study of Invasive Candidiasis in Children and Neonates

Background: Candida species are the third most common cause of pediatric health care–associated bloodstream infection in the United States and Europe. To our knowledge, this report from the International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis. Methods: From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis. Results: Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes. Conclusions: We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.

The alpha C protein mediates internalization of group B Streptococcus within human cervical epithelial cells

Group B Streptococcus (GBS) is the leading cause of bacterial chorioamnionitis and neonatal pneumonia, sepsis, and meningitis. Deletion of the alpha C protein gene (bca) attenuates the virulence of GBS in an animal model; significant survival differences in the first 24 h of infection suggest a pathogenic role for the alpha C protein early in the infection process. We examined the role of alpha C protein in the association between GBS and mucosal surfaces using a human cervical epithelial cell line, ME180. Fluorescent and confocal microscopy and flow cytometry demonstrated that 9‐repeat alpha C protein binds to the surface of ME180 cells. Isolated N‐terminal region of this protein also binds to these cells and competitively inhibits binding of the full protein. Wild‐type GBS strain A909 and the bca‐null isogenic mutant JL2053 bound similarly to the surface of ME180 cells. However, A909 entered these cells threefold more. Internalization of A909 was inhibited with 2‐ and 9‐repeat alpha C and with N‐terminal region alone but not by repeat region‐specific peptide. Translocation across polarized ME180 membranes was fivefold greater for A909 than for JL2053. These findings suggest a role for the alpha C protein in interaction with epithelial surfaces and initiation of infection.

Quantitative Determination of Immunoglobulin G Specific for Group B Streptococcal β C Protein in Human Maternal Serum

The beta C protein of group B streptococci (GBS) elicits antibody that is protective against GBS challenge in animals and is considered to be a potential component of a GBS conjugate vaccine. We developed a quantitative enzyme-linked immunosorbent assay to measure beta-specific serum immunoglobulin G (IgG) levels and used it to compare beta-specific IgG in a group of mothers of neonates with invasive type Ib/beta GBS disease and a group of mothers colonized with Ib/beta strains whose neonates remained well. beta-Specific IgG concentrations from these 2 groups were similar. To investigate differences in beta-specific antibody in animals and humans, protein fragments were generated that corresponded to major regions within the beta C protein. A single major region was predominantly recognized in human and rabbit serum samples. Thus, in contrast to immunized animals, no relationship was seen between levels of naturally acquired human beta-specific IgG and protection from neonatal disease. This difference was not explained by a major difference in epitope specificity.

The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy.

RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 1993–2006 for transplant recipients, and 2000–2005 for patients with cancer. RSV was the most common respiratory virus identified. There were 17 (10% of all patients) deaths overall, of which 12 were at least partly attributed to the presence of a RVI. In multivariate models, LRT symptoms in the absence of upper respiratory symptoms on presentation (OR 10.2 [2.3, 45.7], p = 0.002) and adenoviral infection (OR 3.7 [1.1, 12.6], p = 0.034) were significantly associated with poor outcome, defined as death or disability related to RVI. All of the deaths occurred in patients who had received either solid organ or HSCT. There were no infections resulting in death or disability in the cancer chemotherapy group.

Group B Streptococcus Bacteremia Elicits β C Protein-Specific IgMand IgG in Humans

Group B Streptococcus (GBS) beta C protein elicits protective antibodies in experimental animals, making beta C protein an attractive component of a human GBS glycoconjugate vaccine. We determined whether natural exposure to beta C protein elicits antibodies in humans. Geometric mean concentrations (in micrograms per milliliter) of beta C-specific immunoglobulin (Ig) M and IgG as determined by enzyme-linked immunosorbent assay were similar in serum from 16 colonized (0.82 and 0.76, respectively) and 48 age-matched noncolonized (0.96 and 0.74, respectively) pregnant women. Serum from 3 women with beta C GBS bacteremia had significantly higher levels of IgM (6.0) and IgG (52.9) (P=.01 and 0.01, respectively). Invasive disease but not colonization elicits beta C-specific IgM and IgG.

Cloning and Expression in Escherichia coli of a Protective Surface Protein from Type V Group B Streptococci

This report describes a trypsin-resistant laddering protein purified from a type V strain, a serotype of important emerging clinical significance. This protein is present in a majority of type V clinical strains, elicits protective antibody in an animal model, and is cross-reactive with the alpha C protein and R1. The gene encoding this protein has been cloned; preliminary nucleotide sequence analysis reveals significant homology, though not identity, with the alpha C protein gene. These data support the hypothesis that there exists a family of related but distinct GBS surface proteins which may play a role in immunity to GBS infection.

Fatal Disseminated candida Lusitaniae Infection In An Infant With Chronic Granulomatous Disease

A 3-month-old boy born to a mother carrying an X-linked form of chronic granulomatous disease presented with persistent fever and hepatosplenomegaly. The diagnosis was confirmed as a gp91phox defect by genetic analysis, and the patient was managed with broad spectrum antibacterial agents, gamma-interferon and later amphotericin B. A liver biopsy revealed granulomata with budding yeast forms, and cultures of blood and urine grew Candida lusitaniae. The patient died 26 days after admission.

Does Clarithromycin Cause Hearing Loss? A 12-Year Review of Clarithromycin Therapy for Nontuberculous Mycobacterial Lymphadenitis in Children

Objective(s): The objective was to describe the characteristics of hearing losses documented in patients treated with clarithromycin alone for nontuberculous mycobacterial NTM lymphadenitis in a pediatric tertiary care center over a 12-year period. Methods: An institutional review board (IRB) approval was obtained. A database search was performed using the ICD-10 diagnosis codes 31.0, 31.1, and 31.8 between January 2004 and January 2017. A REDCap database was created to record variables. Patients were included if they received clarithromycin alone and had, at the minimum, a baseline audiology assessment, and 1 further evaluation during treatment. Fisher’s exact test was used to analyze categorical variables, and Wilcoxon rank sum test was used to analyze continuous variables. Results: A total of 167 patients with cervicofacial NTM were identified. Of them, 42 patients fulfilled inclusion criteria. Three children (7%) developed a hearing loss (HL) between 25 and 63 days after starting treatment. HL was unilateral in 2 children. HL persisted in 1 child following cessation of treatment. However, this patient had Rubinstein Taybi syndrome, limiting our ability to attribute the HL solely to clarithromycin. Conclusion: We noted a 7% hearing loss rate in our series. Confounding issues, such as 1 patient with a syndrome potentially contributing to HL, and limitations to this study, including retrospective design and loss to follow-up, temper our ability to conclude that clarithromycin was the sole cause of these HL. However, enough supporting data for a role in clarithromycin causing HL exist that testing should be considered for patients undergoing long-term clarithromycin treatment.

Group B streptococci.

Publisher Summary The original Lancefield group B streptococcal reference strains are isolated chiefly from cases of bovine mastitis, but human disease caused by group B streptococci (GBS) have emerged as an important cause of neonatal disease, surpassing Escherichia coli as the leading cause of serious infections. GBS are non-motile, facultative anaerobic Gram-positive cocci that form small, grey-white colonies on solid medium and chains or diplococci in broth. Definitive identification of GBS depends upon demonstration of the group B carbohydrate antigen by immunological methods. More recently, while co-ordinated prevention strategies have been partially successful in reducing the impact of neonatal disease, invasive GBS disease in non-pregnant adults has been increasingly recognized. Ongoing investigative efforts are directed to elucidating the patho physiology and optimizing the prevention of GBS disease. Other biochemical characteristics of GBS include the failure to hydrolyze bile esculin agar, the ability to sodium hippurate broth, and the production of an orange pigment during anaerobic growth.