Acute otitis externa (AOE) is a common but preventable ear condition. Clinical guidelines issued in 2006 recommended topical treatments for uncomplicated AOE, but systemic antimicrobials appear to be commonly prescribed. The objective of this analysis was to describe pre- and postguideline prescribing patterns by clinician specialty and antimicrobial type and assess trends over time.Retrospective longitudinal analysis of a large insurance database.Outpatient departments in the United States.Initial outpatient visits in 2004 to 2010 for AOE (excluding visits with complicating conditions) were extracted from an insurance database. Prescription drug claims were linked and categorized by clinician specialty and antimicrobial type.The analysis included 907,261 initial outpatient visits. Use of systemic antimicrobials declined by 4.9% (95% confidence interval [CI], 4.1%, 5.7%) from 36.5% of initial visits in 2004 to 32.1% in 2010. Use of systemic antimicrobials varied by specialty. Systemic antimicrobials were prescribed in 47.1% of 2010 emergency department (ED) visits (-6.9% from 2004, 95% CI -12.3, -1.5), 25.9% of otolaryngologist visits (-1.6%, 95% CI -5.6, 2.4), and 20.4% of pediatrician visits (-6.6%, 95% CI -8.8, -4.4). Penicillins were prescribed most frequently (42.3% of systemic prescriptions in 2010), followed by cephalosporins (19.8%), erythromycin/macrolides (17.4%), and quinolones (11.1%). Opioids were prescribed in 26.4% of ED visits and 9% of outpatient visits.Use of systemic antimicrobials declined over time, but one-third of 2010 visits resulted in systemic antimicrobials, despite exclusion of visits with complicating factors. Use of systemic antimicrobials varied by specialty. Further educational efforts and outreach to other specialties might be warranted.

Acute mastoiditis is a potential complication of acute otitis media (AOM), with Streptococcus pneumoniae historically the most common pathogen isolated. Following the release of the 7-valent pneumococcal conjugate vaccine in 2000, a marked decline in invasive pneumococcal disease and a smaller reduction in pneumococcal AOM were observed, but data regarding its impact on acute mastoiditis are limited. With the recent introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), it is anticipated that pneumococcal AOM and invasive disease will further diminish. We report a case of acute mastoiditis from a multidrug-resistant serotype 19A S. pneumoniae in an immunocompetent child who had received three PCV13 vaccinations.

Acute otitis media (AOM) is a polymicrobial disease, which usually occurs as a complication of viral upper respiratory tract infection (URI). While respiratory viruses alone may cause viral AOM, they increase the risk of bacterial middle ear infection and worsen clinical outcomes of bacterial AOM. URI viruses alter Eustachian tube (ET) function via decreased mucociliary action, altered mucus secretion and increased expression of inflammatory mediators among other mechanisms. Transient reduction in protective functions of the ET allows colonizing bacteria of the nasopharynx to ascend into the middle ear and cause AOM. Advances in research help us to better understand the host responses to viral URI, the mechanisms of viral-bacterial interactions in the nasopharynx and the development of AOM. In this review, we present current knowledge regarding viral-bacterial interactions in the pathogenesis and clinical course of AOM. We focus on the common respiratory viruses and their established role in AOM.

A prospective clinical cohort study was established to investigate the humoral immune response in middle ear fluids (MEF) and serum against bacterial surface proteins in children suffering from recurrent acute otitis media (rAOM) and chronic otitis media with effusion (COME), using Luminex xMAP technology. The association between the humoral immune response and the presence of Moraxella catarrhalis and Streptococcus pneumoniae in the nasopharynx and middle ear was also studied. The levels of antigen-specific IgG, IgA, and IgM showed extensive interindividual variation. No significant differences in anti-M. catarrhalis and anti-S. pneumoniae serum and MEF median fluorescence intensity (MFI) values (anti-M. catarrhalis and antipneumococcal IgG levels) were observed between the rAOM or COME groups for all antigens tested. No significant differences were observed for M. catarrhalis and S. pneumoniae colonization and serum IgG levels against the Moraxella and pneumococcal antigens. Similar to the antibody response in serum, no significant differences in IgG, IgA, and IgM levels in MEF were observed for all M. catarrhalis and S. pneumoniae antigens between OM M. catarrhalis- or S. pneumoniae-positive and OM M. catarrhalis- or S. pneumonia-negative children suffering from either rAOM or COME. Finally, results indicated a strong correlation between antigen-specific serum and MEF IgG levels. We observed no significant in vivo expressed anti-M. catarrhalis or anti-S. pneumoniae humoral immune responses using a range of putative vaccine candidate proteins. Other factors, such as Eustachian tube dysfunction, viral load, and genetic and environmental factors, may play a more important role in the pathogenesis of OM and in particular in the development of rAOM or COME.

The bactericidal antibody response to three nontypeable Haemophilus influenzae (NTHi) outer membrane proteins (D, P6, and OMP26) was studied in 24 otitis-prone children (aged 7-28 months) after an acute otitis media (AOM) caused by NTHi. The study was carried out to understand the contribution of antigen-specific bactericidal antibody responses in the class of children who are most vulnerable to recurrent otitis media infections. Levels of protein D (P = 0.005) and P6 (P = 0.026) but not OMP26 antibodies were higher in bactericidal sera compared with nonbactericidal sera. For five (24%) and 16 (76%) of 21 bactericidal sera tested, removal of anti-protein D and P6 antibody, respectively, resulted in a two- to fourfold drop in bactericidal antibody. Antibodies to OMP26 did not make any contribution to the overall bactericidal activity in any serum samples. Eleven of 21 sera (52%) had bactericidal activity against a heterologous NTHi (86-028 NP) strain but the titers were significantly lower (P < 0.05) as compared to the homologous strains. Future studies of protein D, P6, OMP26, and other potential NTHi vaccine antigens should include studies of bactericidal antibody in children who are otitis prone as a possible correlate of protection.

Increases in colonization with serotypes of Streptococcus pneumoniae not contained within the 7-valent pneumococcal conjugate vaccine (PCV) have been reported among children following introduction. Serotype 6C has emerged as prevalent in nasopharyngeal colonization and acute otitis media (AOM), though it is uncommonly recovered from children with invasive pneumococcal disease. Vaccine serotypes within PCV7 have been replaced by nonvaccine serotypes without significant changes in the overall carriage rate. We hypothesize 1) that serotypes vary in their ability to evade host defenses and establish AOM following colonization and 2) the observed reduction in pneumococcal otitis results from a reduced disease potential by some 'replacement serotypes'. We compared the capacity of S. pneumoniae serotypes 6C and 19A to produce experimental otitis media (EOM) in a chinchilla model. The proportion of chinchillas that developed culture positive EOM and density of middle ear infection was evaluated. EOM was found in 28/82 (34%) ears challenged with 6C compared to 13/18(72.2%) with 19A [p = 0.0003]. When disease due to 6C did occur, it was characterized by low-density infection. Our findings demonstrate that challenge with serotype 6C results in EOM less frequently than 19A. These data support the need for greater knowledge regarding differences among serotypes to produce AOM.

The temporal bone may be affected by a variety of systemic pathology because the disease nature, location, and extent determine the symptoms. Middle ear and mastoid infections may be the initial clinical manifestation of autoimmune and acquired immunodeficiency disorders. Rituximab, an anti-CD20 chimeric antibody, has become increasingly popular as a therapeutic agent for patients with a wide range of autoimmune disorders refractory to standard treatments. Normal levels of immunoglobulin levels are usually maintained during and after rituximab therapy, and clinical trials to date have shown no statistically significant increase of serious infections among patients with autoimmune diseases being treated with rituximab (Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, et al, for the REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at 24 weeks. Arthritis Rheum. 2006;54:2793-2806. Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350:2572-2581). However, there have been several reports of opportunistic infections associated with rituximab (Kelesidis T, Daikos G, et al. Does rituximab increase the incidence of infectious complications? A narrative review. Int J Infect Dis 2011;15:e2-e16. Teichmann LL, Woenckhaus M, Vogel C, et al. Fatal Pneumocystis pneumonia following rituximab administration for rheumatoid arthritis. Rheumatology 2008;47:1256-1257), as well as cases of it accelerating the presentation of hypogammaglobulinemia (Diwakar L, Gorrie S, et al. Does rituximab aggravate pre-existing hypogammaglobulinaemia? J Clin Pathol 2010;63:275-277). Humoral immune defects can cause persistent acute and serous otitis media, with the development of chronic suppurative otitis media refractory to medical and surgical therapy (Sasaki CT, Askenase P, Dwyer J, et al. Chronic ear infection in the immunodeficient patient. Arch Otolaryngol 1981;107:82). Here, we describe the first presentation, diagnostic workup, and treatment with intravenous immunoglobulin of chronic bilateral otomastoiditis in the setting of rituximab-induced hypogammaglobulinemia.

The spectrum of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) represents a large burden on healthcare systems around the world. Meningitis, bacteraemia, community-acquired pneumonia (CAP), and acute otitis media (AOM) are vaccine-preventable infectious diseases that can have severe consequences. The health economic model presented here is intended to estimate the clinical and economic impact of vaccinating birth cohorts in Canada and the UK with the 10-valent, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared with the newly licensed 13-valent pneumococcal conjugate vaccine (PCV-13).The model described herein is a Markov cohort model built to simulate the epidemiological burden of pneumococcal- and NTHi-related diseases within birth cohorts in the UK and Canada. Base-case assumptions include estimates of vaccine efficacy and NTHi infection rates that are based on published literature.The model predicts that the two vaccines will provide a broadly similar impact on all-cause invasive disease and CAP under base-case assumptions. However, PHiD-CV is expected to provide a substantially greater reduction in AOM compared with PCV-13, offering additional savings of Canadian $9.0 million and £4.9 million in discounted direct medical costs in Canada and the UK, respectively.The main limitations of the study are the difficulties in modelling indirect vaccine effects (herd effect and serotype replacement), the absence of PHiD-CV- and PCV-13-specific efficacy data and a lack of comprehensive NTHi surveillance data. Additional limitations relate to the fact that the transmission dynamics of pneumococcal serotypes have not been modelled, nor has antibiotic resistance been accounted for in this paper.This cost-effectiveness analysis suggests that, in Canada and the UK, PHiD-CV's potential to protect against NTHi infections could provide a greater impact on overall disease burden than the additional serotypes contained in PCV-13.

The objective of the study was to estimate the possible association of maternal diseases with the risk of isolated ear congenital abnormalities (IECA) including mainly microtia and anotia in their children. Incidence of acute and prevalence of chronic maternal diseases in the mothers with IECA and in the mothers of their matched controls and all controls without any defects, in addition in the mothers of malformed controls with other isolated defects was compared in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. Of 354 cases with IECA, 32 had mothers with high fever related influenza-common cold during the critical period of IECA and it resulted in a higher risk of IECA in their live-born infants (adjusted OR with 95% CI: 4.3, 1.9-7.4) compared with their matched controls. However, the early and effective antifever treatment in these pregnant women prevented them from the IECA. In addition there was an association of maternal otitis media with higher risk of complex defects of middle and external ears (OR with 95% CI: 5.2, 1.6-28.3), however, this association was based on 4 cases only. In conclusion high fever related influenza-common cold with secondary complications may play a role in the origin of IECA, but is preventable with the early and effective antifever treatment of these pregnant women.

Otitis media is an infectious, inflammatory process involving the middle ear space. Chronic inflammation is associated with fibrosis, scarring and osteogenesis within the middle ear, which may contribute to subsequent hearing loss and increase the difficulty of treatment.Heat-killed Streptococcus pneumoniae was injected into the middle ears of 8-12 week old Balb/c mice. Control mice were treated with PBS middle ear injections. Middle ears were harvested at 1, 3, 5 and 7 days following injection (n=8 for each time point). The middle ears were processed using standard RT-PCR techniques. Up- and down-regulation of mRNA expression of various members of the Bone Morphogenetic Protein (BMP), Fibroblast Growth Factor (FGF) and Matrix Metalloproteinase (MMP) families was quantified and compared to PBS treated controls (n=8 for each time point).Significant upregulation of MMP2, MMP3 and MMP9 was observed at varying time points (p<0.05). Significant downregulation of BMP3, BMP4, BMP5 BMP6 and BMP8a was seen at varying time points (p<0.05). Significant downregulation of FGF3, FGF6, FGF10 and FGFr1 was observed at varying time points (p<0.05). No significant expression of BMP8b, BMP9, BMP10, FGF5, FGF8, MMP1a, MMP7 and MMP14 was detected within the middle ear.Inflammation within the middle ear following injection of bacterial products results in changes in the regulation of several tissue remodeling cytokines and proteinases in the mouse model. Further understanding of these molecular processes may allow for the development of treatment modalities aimed at preventing middle ear tissue remodeling.