Simultaneous intravenous and intramiddle-ear dosing to determine cefditoren influx and efflux clearances in middle ear fluid in freely moving chinchillas.

This study was conducted to determine cefditoren (CDTR) transport kinetics between plasma and middle ear fluid (MEF) by characterizing influx (CLin) and efflux (CLout) clearances expressed in terms of unbound concentrations and their ratio. Simultaneous intravenous bolus and intramiddle-ear dose were administered to two groups of chinchillas: normal control and infected. In vivo microdialysis was employed to determine protein-unbound CDTR levels in MEF.

Quality control and the identification of vaccine responders using ELISA-derived antibody data.

First vaccines are traditionally licensed after showing favourable results from phase III efficacy trials. Subsequent competing vaccines, however, have been licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Focusing on pneumococcal vaccines where optical densities are measured and serum antibody concentrations are 'estimated' (from a statistical model) using an immunoglobulin (IgG) enzyme-linked immunosorbent assay (ELISA), the focus of this paper will centre on two highly related issues: the determination of an upper limit for quality control used in the assay methodology (let us call it the maximum tolerated limit or MTL) and the identification of vaccine responders.

Pneumococcal conjugate vaccines as maternal and infant immunogens: challenges of maternal recruitment.

Maternal pneumococcal immunization may be a strategy for the prevention of pneumococcal disease during the first months of life before infant-administered pneumococcal conjugate vaccine (PCV) becomes protective. Preparatory to a Phase III efficacy trial to investigate this strategy for preventing early infant otitis media (OM), we are conducting a Phase I-II randomized, double-masked trial to determine if maternal 9-valent PCV immunization alters active antibody production in infants who are immunized with PCV-7 and to compare local and systemic adverse events among women immunized with PCV-9 or placebo. A pilot study was conducted in 1997 in a Minneapolis-St.

Chronic otitis media with effusion sequelae in children treated with tubes.

Objective: To determine incidence and prevalence of middle ear sequelae and abnormal tympanometry results among children with chronic otitis media with effusion (OME) who received standard treatment with tympanostomy tubes.

Design: Prospective cohort study.

Setting: Community clinic and academic medical center.

Analysis by cDNA microarrays of altered gene expression in middle ears of rats following pneumococcal infection.

Objective: Streptococcus pneumoniae is the most common pathogen in otitis media. Infection of the middle ear with S. pneumoniae potentiates development of thick effusion in the middle ear which frequently causes hearing loss and communication disorders in children.

Maternal pneumococcal conjugate immunization protects infant chinchillas in the pneumococcal otitis media model.

Infant immunization with pneumococcal polysaccharide-protein conjugate vaccines (PCVs) is unlikely to elicit protective serum antibody concentrations during the first 4-6 months of life, when recurrent pneumococcal otitis media (POM) often begins. We therefore investigated a maternal pneumococcal immunization strategy to prevent early infant POM. Pregnant chinchillas (dams) received injections of heptavalent PCV or saline.

Induction of mucous cell metaplasia in the middle ear of rats using a three-step method: an improved model for otitis media with mucoid effusion.

Otitis media with mucoid effusion, characterized by mucous cell metaplasia in the middle ear cleft and thick fluid accumulation in the middle ear cavity, is a common otological disease that frequently affects young children. Multiple factors are involved in the development of this disease, especially middle ear infection and Eustachian tube dysfunction. In this study, in order to induce otitis media with effusion in rats, we introduced a three-step method, namely inoculation of Streptococcus pneumoniae at 10(7) colony-forming units (CFU)/ear or Haemophilus influenzae at 5 x 10(7) CFU/ear into the middle ear cavity twice at 2-week intervals, followed by Eustachian tube obstruction (ETO) for 4 and 8 weeks.

Microdialysis studies of the middle ear distribution kinetics of amoxicillin in the awake chinchilla.

This work was performed to develop an experimental animal model for the study of antibiotic drug distribution into middle ear fluid (MEF) and to evaluate its relevance and significance to the clinical treatment of otitis media (OM). Chinchillas were assigned to normal or infected ear groups after Eustachian tube obstruction (ETO) or direct trans-bullar inoculation with type 3 Streptococcus pneumoniae. Following survival surgery to implant microdialysis (MD) probes in the jugular vein and middle ear (ME), amoxicillin was given intravenously (iv) as a bolus or infusion.

A multi-laboratory evaluation of an enzyme-linked immunoassay quantitating human antibodies to Streptococcus pneumoniae polysaccharides.

An enzyme-linked immunoassay (EIA) is described and evaluated which quantitates human antibodies to serotype specific S. pneumoniae polysaccharide (PnPs) in human sera. Based on the observations previously described by Koskela (1), native PnPs are used as coating antigens and sera are absorbed with a soluble pneumococcal absorbant material containing C-polysaccharide (CPs) to ensure measurement of serotype specific anti-PnPs antibodies.

Low cord blood pneumococcal antibody concentrations predict more episodes of otitis media.

Objective: To determine if cord blood anticapsular polysaccharide pneumococcal IgG antibody concentration was related to the number of otitis media (OM) and acute OM episodes during the first year of life.

Design: Prospective study following infants from birth to 24 months.

Setting: Health maintenance organization.

Otitis media prevention: non-vaccine prophylaxis.

Preventing recurrent acute otitis media (AOM) is a goal of child health care. The objective is to reduce the frequency of pain and fever, shorten the duration of hearing loss, reduce the costs of physician visits, surgery and drugs, reduce parent anxiety, and prevent long term sequelae. Preventive approaches include understanding individual and familial risk factors, avoidance of environmental risk factors, antibiotic drug prophylaxis, polyvalent pneumococcal vaccination, myringotomy with tympanostomy tubes, and adenoidectomy.

Low cord blood type 14 pneumococcal IgG1 but not IgG2 antibody predicts early infant otitis media.

Type-specific IgG1 and IgG2 antibodies to Streptococcus pneumoniae capsular polysaccharides 14 and 19F were measured in cord blood samples from 425 neonates, to determine which antibody subclass was most strongly associated with otitis media (OM) during the first 6 months of life (early OM). Early OM was significantly associated with type 14 IgG1 antibody in the lowest antibody quartile (P=.055) but not with type 19F IgG1 antibody or with either IgG2 antibody.

An analytical model applied to a multicenter pneumococcal enzyme-linked immunosorbent assay study.

Pneumococcal conjugate vaccines will eventually be licensed after favorable results from phase III efficacy trials. After licensure of a conjugate vaccine for invasive pneumococcal disease in infants, new conjugate vaccines will likely be licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Analytical methods must therefore be developed, evaluated, and validated to compare immunogenicity results accurately within and between laboratories for different vaccines.

Update of microbial problems in pediatric otorhinolaryngology: plenary session.

The bacteria to consider in upper respiratory tract infections in children are pneumococci, Haemophilus influenzae, group A streptococci and Moraxella catarrhalis.

Prospective study of tympanic membrane retraction, hearing loss, and multifrequency tympanometry.

Tympanic membrane retraction is a significant sequela of OME and has been linked clinically to atelectasis, ossicular erosion, and cholesteatoma. We investigated important factors for prediction of tympanic membrane retraction in a prospective study of 112 children. After 4 to 6 years of follow-up, 12% of ears had pars tensa retraction without atrophy, and 28% had various degrees of retraction with atrophy.

Acute otitis media: management and surveillance in an era of pneumococcal resistance. Drug-Resistant Streptococcus Pneumoniae Therapeutic Working Group.

Experts in the management of otitis media and the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group were convened by the Centers for Disease Control and Prevention to respond to changes in antimicrobial susceptibility among pneumococci. The objective was to provide consensus recommendations for the management of acute otitis media (AOM) and for the surveillance of drug-resistant Streptococcus pneumoniae. After summarizing published and unpublished data from the scientific literature and the experience of the panel members, the group concluded that oral amoxicillin should remain the first-line antimicrobial agent for treating AOM.

Epidemiology of otitis media onset by six months of age.

Objective: Although early otitis media (OM) onset predicts later recurrent and chronic OM, little research has been directed at illuminating the role of prenatal exposures in early OM. This prospective study examined prenatal, innate, and early environmental exposures associated with acute otitis media (AOM) onset and recurrent OM (ROM) by age 6 months.

Design And Methods: Prospective study of 596 infants from a health maintenance organization followed from birth to 6 months.

Otitis media: the chinchilla model.

Streptococcus pneumoniae infection and disease have been modeled in several animal species including infant and adult mice, infant and adult rats, infant Rhesus monkeys, and adolescent and adult chinchillas. Most are models of sepsis arising from intravenous or intraperitoneal inoculation of bacteria, and a few were designed to study disease arising from intranasal infection. Chinchillas provide the only animal model of middle ear pneumococcal infection in which the disease can be produced by very small inocula injected into the middle ear (ME) or intranasally, and in which the disease remains localized to the ME in most cases.

Pneumococcus activation of the 5-lipoxygenase pathway and production of glycoproteins in the middle ear of rats.

Pneumococcal otitis media is associated with the production of potent inflammatory mediators (leukotrienes), but the mechanism by which pneumococcus induces production of leukotrienes in the middle ear is poorly understood. In this study, up-regulation of 2 genes that govern the lipoxygenase pathway, cPLA2 and 5-LOX, was observed in rats following inoculation of pneumococcus into the middle ear cavity. Expression of cPLA2 was low, and 5-LOX gene expression was not detected in control animals.

Middle ear fluid cytokine and inflammatory cell kinetics in the chinchilla otitis media model.

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1beta, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-alpha) are recognized as being important local mediators in acute inflammation.

Chronic otitis media with effusion.

Chronic OME, which arises from a complex series of inflammatory events in the middle ear, affects approximately 5% to 30% of children. The mean duration of MEE is 16 to 20 weeks during the first 2 years of life. This condition is diagnosed best with pneumatic otoscopy and tympanometry.