Concept: Otitis media
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
- Published over 8 years ago
Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%-9% in randomized trials and 17%-23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3-5 years before 7vCRM introduction (mean change, -15%; range, +14% to -24%) and continued to decline afterward (mean, -19%; range, +7% to -48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM.
The development of minimally invasive procedures such as the balloon dilation Eustachian tuboplasty (BET) is an alternative to the grommet tympanum membrane. BET is applied in the cases where, after elimination of all factors influencing the ET and middle ear functioning, no sufficient improvement is observed. The aim of this study was to present the therapeutic benefits of the BET method in the treatment of ETD caused by disorders in the middle ear ventilation. The BET procedure was offered to four patients (3 men and 1 woman) after subjective, physical, otorhinolaryngological and audiometric examinations including pure tone audiometry, tympanometry and pressure-swallow test. As the method was novel, preinterventional CT angiography of the carotid arteries was performed in all patients. Any complications were noticed during and after the procedure (bleeding or damage of regional mucosa) in any patients. Our clinical studies assessed the feasibility and safety of the BET during a short-term period-only a 6-week observation. Although patients revealed a significant improvement of ET score, longer long-term studies are necessary to determine whether this method will demonstrate lasting benefits and safety in the treatment of chronic Eustachian tube dysfunction. In other investigations, improvement was found to be time dependent.
Human Infection with Shewanella putrefaciens and S. algae: Report of 16 Cases in Martinique and Review of the Literature
- The American journal of tropical medicine and hygiene
- Published over 7 years ago
Shewanella spp. are saprophytic bacteria that are part of the marine microflora in warm climates and are rarely pathogenic. However, Shewanella spp. infections are being increasingly reported, and there has been no comprehensive review of the literature describing these infections. This article reports 16 cases of Shewanella spp. infections in Martinique since 1997 and reviews another 239 cases reported in the literature since 1973. Patients experienced soft tissue infections, ear infection, or abdominal and biliary tract infections. A skin or mucosal portal of entry was found for 53% of the patients and exposure to the marine environment was reported for 44%; 79% of patients had an underlying condition. Bacteriema were frequent (28%). Most (87%) patients recovered, although ear infections can become chronic. Death occurred in 13% of the patients. Most Shewanella spp. isolates are susceptible to cefotaxime (95%), piperacillin and tazobactam (98%), gentamicin (99%), and ciprofloxacin (94%).
Background Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media. Methods We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms. Results Children who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P<0.001). Conclusions Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107 .).
Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population.
Otitis media is the most common reason U.S. children receive antibiotics. The requisite 7- to 10-day course of oral antibiotics can be challenging to deliver in children, entails potential systemic toxicity, and encourages selection of antimicrobial-resistant bacteria. We developed a drug delivery system that, when applied once to the tympanic membrane through the external auditory canal, delivers an entire course of antimicrobial therapy to the middle ear. A pentablock copolymer poloxamer 407-polybutylphosphoester (P407-PBP) was designed to flow easily during application and then to form a mechanically strong hydrogel on the tympanic membrane. U.S. Food and Drug Administration-approved chemical permeation enhancers within the hydrogel assisted flux of the antibiotic ciprofloxacin across the membrane. This drug delivery system completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in 10 of 10 chinchillas, whereas only 62.5% of animals receiving 1% ciprofloxacin alone had cleared the infection by day 7. The hydrogel system was biocompatible in the ear, and ciprofloxacin was undetectable systemically (in blood), confirming local drug delivery and activity. This fast-gelling hydrogel could improve compliance, minimize side effects, and prevent systemic distribution of antibiotics in one of the most common pediatric illnesses, possibly minimizing the development of antibiotic resistance.
About 150 human rhinovirus serotypes are responsible for more than 50 % of recurrent upper respiratory infections. Despite having similar 3D structures, some bind members of the low-density lipoprotein receptor family, some ICAM-1, and some use CDHR3 for host cell infection. This is also reflected in the pathways exploited for cellular entry. We found that even rhinovirus serotypes binding the same receptor can travel along different endocytic pathways and release their RNA genome into the cytosol at different locations. How this may account for distinct immune responses elicited by various rhinoviruses and the observed symptoms of the common cold is briefly discussed.
Otitis media (OM) is the most common childhood bacterial infection, and leading cause of conductive hearing loss. Nontypeable Haemophilus influenzae (NTHi) is a major bacterial pathogen for OM. OM characterized by the presence of overactive inflammatory responses is due to the aberrant production of inflammatory mediators including C-X-C motif chemokine ligand 5 (CXCL5). The molecular mechanism underlying induction of CXCL5 by NTHi is unknown. Here we show that NTHi up-regulates CXCL5 expression by activating IKKβ-IκBα and p38 MAPK pathways via NF-κB nuclear translocation-dependent and -independent mechanism in middle ear epithelial cells. Current therapies for OM are ineffective due to the emergence of antibiotic-resistant NTHi strains and risk of side effects with prolonged use of immunosuppressant drugs. In this study, we show that curcumin, derived from Curcuma longa plant, long known for its medicinal properties, inhibited NTHi-induced CXCL5 expression in vitro and in vivo. Curcumin suppressed CXCL5 expression by direct inhibition of IKKβ phosphorylation, and inhibition of p38 MAPK via induction of negative regulator MKP-1. Thus, identification of curcumin as a potential therapeutic for treating OM is of particular translational significance due to the attractiveness of targeting overactive inflammation without significant adverse effects.
The aim of this study was to quantify the excess cases of pediatric and maternal disease, death, and costs attributable to suboptimal breastfeeding rates in the United States. Using the current literature on the associations between breastfeeding and health outcomes for nine pediatric and five maternal diseases, we created Monte Carlo simulations modeling a hypothetical cohort of U.S. women followed from age 15 to age 70 years and their children from birth to age 20 years. We examined disease outcomes using (a) 2012 breastfeeding rates and (b) assuming that 90% of infants were breastfed according to medical recommendations. We measured annual excess cases, deaths, and associated costs, in 2014 dollars, using a 2% discount rate. Annual excess deaths attributable to suboptimal breastfeeding total 3,340 (95% confidence interval [1,886 to 4,785]), 78% of which are maternal due to myocardial infarction (n = 986), breast cancer (n = 838), and diabetes (n = 473). Excess pediatric deaths total 721, mostly due to Sudden Infant Death Syndrome (n = 492) and necrotizing enterocolitis (n = 190). Medical costs total $3.0 billion, 79% of which are maternal. Costs of premature death total $14.2 billion. The number of women needed to breastfeed as medically recommended to prevent an infant gastrointestinal infection is 0.8; acute otitis media, 3; hospitalization for lower respiratory tract infection, 95; maternal hypertension, 55; diabetes, 162; and myocardial infarction, 235. For every 597 women who optimally breastfeed, one maternal or child death is prevented. Policies to increase optimal breastfeeding could result in substantial public health gains. Breastfeeding has a larger impact on women’s health than previously appreciated.
Acute otitis media (AOM) is among the most common pediatric diseases, and the most frequent reason for antibiotic treatment in children. Risk of AOM is dependent on environmental and host factors, as well as a significant genetic component. We identify genome-wide significance at a locus on 6q25.3 (rs2932989, Pmeta=2.15 × 10(-09)), and show that the associated variants are correlated with the methylation status of the FNDC1 gene (cg05678571, P=1.43 × 10(-06)), and further show it is an eQTL for FNDC1 (P=9.3 × 10(-05)). The mouse homologue, Fndc1, is expressed in middle ear tissue and its expression is upregulated upon lipopolysaccharide treatment. In this first GWAS of AOM and the largest OM genetic study to date, we identify the first genome-wide significant locus associated with AOM.