Serotype distribution of Streptococcus pneumoniae in north-western Greece and implications for a vaccination programme

Serotypes and antibiotic sensitivities were determined for 338 strains of Streptococcus pneumoniae from children of north-western Greece with invasive pneumococcal disease (IPD), acute otitis media (AOM) and nasopharyngeal carriage. The most common serotypes among the isolates from IPD were 14 and 19F, while 3, 19F, 9V and 14 were the major cause of AOM. In these groups, the heptavalent conjugate vaccine for pneumococci (7vPCV) seems to cover 90.5% of the serotypes isolated from children less than 2 years old. Serotypes 23F and 6B were the most prevalent in carrier strains. Overall, 23.7% of the isolates were penicillin nonsusceptible (PNS), 97% were fully susceptible to cefotaxime, 29% were resistant to erythromycin, 11.2% to co-trimoxazole and 1.2% to clindamycin.     

Co-amoxiclav in recurrent acute otitis media: placebo controlled study.

OBJECTIVE--To determine the efficacy of coamoxiclav in children aged 6 months to 12 years with recurrent acute otitis media. DESIGN--A randomised double blind placebo controlled clinical trial. SETTING--General practice in the Netherlands. PATIENTS--121 children with recurrent acute otitis media, defined by onset of otalgia and otoscopic signs of middle ear infection within four to 52 weeks after the previous attack. Confirmation of diagnosis and randomisation was done by otolaryngologists. INTERVENTION--Oral co-amoxiclav or placebo in weight related doses for seven days. MAIN OUTCOME MEASURE--An irregular clinical course defined as the presence of otalgia or a body temperature greater than or equal to 38 degrees C, or both, after three days. RESULTS--Eleven (16%; 95% confidence interval 9% to 28%) children had an irregular course in the co-amoxiclav group and 10 (19%; 9% to 31%) in the placebo group (difference not significant). Age, dichotomised at 2 years, was the only significant prognostic factor for irregular course of the disease (odds ratio 5.9; 1.8 to 19.1). Among children aged below 2 years, 28% (4/14) in the co-amoxiclav group and 58% (7/12) in the placebo group had irregular courses. For children 2 years and older these percentages were 13% (7/52) and 7% (3/41). CONCLUSION--Children with recurrent acute otitis media are at greater risk of an irregular clinical course of the disease than children with a first episode of acute otitis media. Co-amoxiclav has no significant benefit over placebo in treating children over 2 years with acute otitis media.     

Characterization of Streptococcus pneumoniae isolated from children with otitis media

Streptococcus pneumoniae is the main causative agent of acute otitis media in children. Serotype-based vaccines have provided some protection against otitis media, but not as much as anticipated, demonstrating the need for alternative vaccine options. Pneumococcal otitis media isolates were obtained from children 5 years old or younger from hospitals around Mississippi in the prevaccine era (1999-2000). These isolates were compared by capsular typing, pneumococcal surface protein A (PspA) family typing, antibiotic susceptibility, and DNA fingerprinting. Our study shows that there is great genetic variability among pneumococcal clinical isolates of otitis media, except with regard to PspA. Therefore, efforts focused on the development of a PspA-based pneumococcal vaccine would be well placed.     

Are antibiotics indicated as initial treatment for children with acute otitis media? A meta-analysis.

OBJECTIVE: To determine the effect of antibiotic treatment for acute otitis media in children. DESIGN: Systematic search of the medical literature to identify studies that used antibiotics in randomised controlled trials to treat acute otitis media. Studies were examined blind, and the results of those of satisfactory quality of methodology were pooled. SUBJECTS: Six studies of children aged 7 months to 15 years. MAIN OUTCOME MEASURES: Pain, deafness, and other symptoms related to acute otitis media or antibiotic treatment. RESULTS: 60% of placebo treated children were pain free within 24 hours of presentation, and antibiotics did not influence this. However, at 2-7 days after presentation, by which time only 14% of children in control groups still had pain, early use of antibiotics reduced the risk of pain by 41% (95% confidence interval 14% to 60%). Antibiotics reduced contralateral acute otitis media by 43% (9% to 64%). They seemed to have no influence on subsequent attacks of otitis media or deafness at one month, although there was a trend for improvement of deafness at three months. Antibiotics were associated with a near doubling of the risk of vomiting, diarrhoea, or rashes (odds ratio 1.97 (1.19 to 3.25)). CONCLUSIONS: Early use of antibiotics provides only modest benefit for acute otitis media: to prevent one child from experiencing pain by 2-7 days after presentation, 17 children must be treated with antibiotics early.     

Sulfisoxazole Chemoprophylaxis and Recurrent Otitis Media

Sulfisoxazole, 75 mg per kg per day, was administered for 13 weeks to all children with otitis media recurring at a rate of at least once every other month. The first 26 patients began prophylaxis during the months of January and February of 1979. To compare rates of otitis media with those in children not receiving concurrent prophylaxis during the same season, a matched control was randomly chosen as a child who began prophylaxis on the day nearest that when a study patient completed prophylaxis. The rates of otitis media during this same period were determined as the number of episodes per patient-month. Of the 26 treated patients, 11 had 16 episodes of otitis media in 72 patient-months (0.22 episodes per patient-month), in contrast to the 26 untreated patients who had 63 episodes in the same period (0.88 episodes per patient-month). This 75% reduction in incidence was statistically significant by X² analysis (P<.005). The two groups of children were comparable in age, sex, nursery school attendance, family history of allergy and number of episodes in the three months preceding chemoprophylaxis. These findings support the short-term chemoprophylactic use of sulfisoxazole for recurrent otitis media.     

Effect of recolonisation with "interfering" alpha streptococci on recurrences of acute and secretory otitis media in children: randomised placebo controlled trial

ObjectiveTo study the effect of recolonisation with α streptococci with the ability to inhibit the growth of otopathogens (“interfering” activity) on the recurrence of acute otitis media in susceptible children and the effect on the frequency of secretory otitis media.DesignDouble blind, randomised, placebo controlled study.SettingEar, nose, and throat clinic with three doctors.Participants130 children prone to otitis media aged between 6 months and 6 years, 108 of whom were eligible and followed for 3 months.InterventionsChildren with no recurrences during the last month received phenoxymethylpenicillin (n=22), and those with a recurrence within 1 month received amoxicillin clavulanic acid (n=86), both twice daily for 10 days. These were followed by a streptococcal or placebo solution sprayed into the nose for a further 10 days. At day 60 the same spray was started for another 10 days.ResultsAt 3 months 22 children (42%) given the streptococcal spray were healthy and had a normal tympanic membrane compared with 12 (22%) of those given placebo. This difference was shown separately for recurrences of both acute otitis media and secretory otitis media.ConclusionsSelected bacteria with the ability to inhibit the growth of common otopathogens can be used to protect against recurrent acute otitis media and secretory otitis media in children.     

Virulence of Streptococcus pneumoniae serotype 6C in experimental otitis media

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.     

Anaerobes in the Nasopharynx During Acute Otitis Media Episodes in Infancy

The present study, as a part of our longitudinal study on the development of the nasopharyngeal microflora, investigates the nasopharyngeal carriage of anaerobes during 75 episodes of acute otitis media (AOM) experienced by 34 infants during their first 2 years of life. Special emphasis was put on adequate methods of detecting anaerobic bacteria from carefully collected nasopharyngeal aspirates. During the follow-up period, two-thirds of the infants carried anaerobes in the nasopharynx at least once. Anaerobic species were recovered from 47% of the nasopharyngeal aspirates. Environmental/ecological changes in the nasopharynx during infection favour the growth of anaerobes. Their significance in the pathogenesis of AOM, if any, warrants further study.     

Acute otitis media: clinical course among children who received a short course of high dose antibiotic.

A prospective study was carried out in 274 children aged 3 to 10 years with acute otitis media. They were randomly allocated to one of two treatment regimens: (a) a seven day course of amoxycillin 125 mg three times a day, and (b) a two day course of amoxycillin 750 mg twice a day. They were followed up by symptom diaries and clinical examination. The findings in the 243 children who completed the trial showed that the short course of treatment was as effective as the seven day course in the speed of resolution of symptoms and signs, irrespective of previous history of otitis media or of episodes in which bulging of the eardrums was observed at presentation. A subgroup of 185 children was followed up for one year after entry to the trial. During this period no appreciable differences emerged between the two antibiotic regimens, either in recurrence rate of otitis media or in the frequency of hearing loss at one month and six months after entry to the study. Side effects of treatment were few, and those that could be attributed to antibiotic use occurred with equal frequency in the two treatment groups.     

Parent-Reported Otorrhea in Children with Tympanostomy Tubes: Incidence and Predictors

Purpose

Although common in children with tympanostomy tubes, the current incidence of tympanostomy tube otorrhea (TTO) is uncertain. TTO is generally a sign of otitis media, when middle ear fluid drains through the tube. Predictors for otitis media are therefore suggested to have predictive value for the occurrence of TTO.

Objective

To determine the incidence of TTO and its predictors.

Methods

We performed a cohort study, using a parental web-based questionnaire to retrospectively collect data on TTO episodes and its potential predictors from children younger than 10 years of age with tympanostomy tubes.

Results

Of the 1,184 children included in analyses (total duration of time since tube placement was 768 person years with a mean of 7.8 months per child), 616 children (52%) experienced one or more episodes of TTO. 137 children (12%) had TTO within the calendar month of tube placement. 597 (50%) children had one or more acute TTO episodes (duration <4 weeks) and 46 children (4%) one or more chronic TTO episodes (duration ≥4 weeks). 146 children (12%) experienced recurrent TTO episodes. Accounting for time since tube placement, 67% of children developed one or more TTO episodes in the year following tube placement. Young age, recurrent acute otitis media being the indication for tube placement, a recent history of recurrent upper respiratory tract infections and the presence of older siblings were independently associated with the future occurrence of TTO, and can therefore be seen as predictors for TTO.

Conclusions

Our survey confirms that otorrhea is a common sequela in children with tympanostomy tubes, which occurrence can be predicted by age, medical history and presence of older siblings.     

IgG Responses to Pneumococcal and Haemophilus Influenzae Protein Antigens Are Not Impaired in Children with a History of Recurrent Acute Otitis Media

Background

Vaccines including conserved antigens from Streptococcus pneumoniae and nontypeable Haemophilus influenzae (NTHi) have the potential to reduce the burden of acute otitis media. Little is known about the antibody response to such antigens in young children with recurrent acute otitis media, however, it has been suggested antibody production may be impaired in these children.

Methods

We measured serum IgG levels against 4 pneumococcal (PspA1, PspA 2, CbpA and Ply) and 3 NTHi (P4, P6 and PD) proteins in a cross-sectional study of 172 children under 3 years of age with a history of recurrent acute otitis media (median 7 episodes, requiring ventilation tube insertion) and 63 healthy age-matched controls, using a newly developed multiplex bead assay.

Results

Children with a history of recurrent acute otitis media had significantly higher geometric mean serum IgG levels against NTHi proteins P4, P6 and PD compared with healthy controls, whereas there was no difference in antibody levels against pneumococcal protein antigens. In both children with and without a history of acute otitis media, antibody levels increased with age and were significantly higher in children colonised with S. pneumoniae or NTHi compared with children that were not colonised.

Conclusions

Proteins from S. pneumoniae and NTHi induce serum IgG in children with a history of acute otitis media. The mechanisms in which proteins induce immunity and potential protection requires further investigation but the dogma of impaired antibody responses in children with recurrent acute otitis media should be reconsidered.     

Bacterial otitis media: current vaccine development strategies

Otitis media is the most common reason for children less than 5 years of age to visit a medical practitioner. Whilst the disease rarely results in death, there is significant associated morbidity. The most common complication is loss of hearing at a critical stage of the development of speech, language and cognitive abilities in children. The cause and pathogenesis of otitis media is multifactorial. Among the contributing factors, the single most important are viral and bacterial infections. Infection with respiratory syncytial virus, influenza viruses, para-influenza viruses, enteroviruses and adenovirus are most commonly associated with acute and chronic otitis media. Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis are the most commonly isolated bacteria from the middle ears of children with otitis media. Treatment of otitis media has largely relied on the administration of antimicrobials and surgical intervention. However, attention has recently focused on the development of a vaccine. For a vaccine to be effective against bacterial otitis media, it must, at the very least, contain antigens that induce a protective immune response in the middle ear against the three most common infecting bacteria. Whilst over the past decade there has been significant progress in the development of vaccines against invasive S. pneumoniae disease, these vaccines are less efficacious for otitis media. The search for candidate vaccine antigens for non-typeable H. influenzae are well advanced whilst less progress has been made for M. catarrhalis. No human studies have been conducted for non-typeable H. influenzae or M. catarrhalis and the concept of a tribacterial vaccine remains to be tested in animal models. Only when vaccine antigens are determined and an understanding of the immune responses induced in the middle ear by infection and immunization is gained will the formulation of a tribacterial vaccine against otitis media be possible.     

Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study

The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants.     

Randomized controlled trial of chewing gum for weight loss

The possible effects on body weight of chewing gum on a regular schedule have not been tested in a randomized controlled trial (RCT). We conducted an 8-week RCT in 201 overweight and obese adults to test the hypothesis that receiving printed material on good nutrition and chewing gum for a minimum of 90 min/day (n = 102) would lead to greater weight loss than receiving printed nutrition information only (n = 99). Changes in BMI, waist circumference, and blood pressure were secondary outcomes. Adherence to the gum-chewing protocol in the intervention group was >95%. In the intention-to-treat analysis, there were virtually no changes in weight or BMI in either group between baseline and the end of the intervention at 8 weeks. Waist circumference decreased significantly in the intervention group between baseline and 8 weeks (mean ± SD change = -1.4 ± 5.3 cm; P = 0.0128); however, there was no significant difference in change in waist circumference comparing the groups. Similarly, systolic and diastolic blood pressure decreased significantly in the intervention group between baseline and 8 weeks (-3.0 ± 9.9 mm Hg; P = 0.0032 and -3.2 ± 7.3 mm Hg; P = 0.0001, respectively); however, there were no significant differences in the changes in systolic or diastolic blood pressure between the groups. Analyses including completers only produced essentially the same results. We conclude that chewing gum on a regular schedule for 8 weeks did not facilitate weight loss in these overweight and obese adults.     

Colonization and turnover of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in otitis-prone children

Recurrent otitis media are frequently intractable during childhood. It is unclear whether recurrent otitis media is caused by etiological bacteria colonization or by new infections. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were isolated from the nasopharynx of 7 otitisprone and 2 non-prone children with recurrent otitis media. Plural bacterial species and strains were found in all children while affected by otitis media. The same strain was repeatedly isolated from all otitisprone children even after administration of antibiotics but was not from the non-prone children. Antibiotic susceptibility did not differ significantly among the same repeatedly isolated strains. This pilot study suggests that the etiological bacteria tend to colonize and is hard to eliminate in otitis-prone children.     

Duration and recurrence of otitis media with effusion in children from birth to 3 years: prospective study using monthly otoscopy and tympanometry.

OBJECTIVE: To monitor the natural course of otitis media with effusion. DESIGN: Prospective, longitudinal assessment of the state of the middle ear by otoscopy and tympanometry at monthly intervals from birth to 3 years. SETTING: Domiciliary visits to family homes. SUBJECTS: 95 full term infants born between August 1991 and November 1993. MAIN OUTCOME MEASURES: Observed and simulated data (Monte Carlo) for the duration of single episodes of otitis media with effusion. RESULTS: 17 of the children had unilateral or bilateral otitis media with effusion for more than half of their first three years of life. Thirty three of the 95 children had tympanograms suggestive of otitis media with effusion at more than a third of observations; the remaining 62 had such tympanograms at less than a third of observations. The data of each group were described by a first order Markov model, yielding a mean duration of unilateral effusion episodes of 5-6 weeks in both groups; the mean duration of bilateral effusion was 6 and 10 weeks in the low and high incidence groups, respectively. However, the main difference between the groups was the time spent between episodes of effusion: effusion free periods were, on average, three times longer in the children who experienced less otitis media with effusion. CONCLUSION: Children who are susceptible to otitis media with effusion tend to have more separate episodes of effusion rather than an increased overall duration of episodes. Such children are primarily distinguished by the likelihood with which they acquire the disease than by their ability to recover from it.     

Etiology and rational therapy of severe otitis media purulenta acuta in children]

Etiology and antibiotic susceptibility of the pathogens of otitis media purulenta acuta in children was studied within 2000-2005. A total of 161 children at the age of 1 to 14 years were examined. The middle ear discharge collected during paracentosis (79.5%) or spontaneous perforation of the tympanic membrane (20.5%) was used in the bacteriological tests. The microflora growth in the culture was detected in 80% of the cases. The leading pathogen was Streptococcus pyogenes (47.5%), the part of Streptococcus pneumoniae amounted to 36.6% of all the etiologically significant microflora, the part of Staphylococcus aureus amounted to 6.9% and that of Haemophilus influenzae amounted to 4.0%. The part of the associations of 2 microorganisms equaled 5.0%. The species composion of the pathogens differed from that described in the literature. The isolates of S. pneumoniae and S. pyogenes were characterized by low resistance to macrolides (4.0-6.3%). As for the S. pneumoniae isolates, 97.3% of them was susceptible to penicillin. The results of the etiology study and the pathogen antibiotic susceptibility showed that the drugs of choice for the empirical antibacterial therapy of otitis media purulenta acuta in children should be amoxicillin and 1st generation cepholosporins. When the antibacterial therapy within the first 3 days fails, it is advisable to use protected aminopenicillins or 2nd generation cephalosporins. In case of the drug intolerance, macrolide antibiotics should be used.     

Policies on antibiotics of south east London general practitioners for managing acute otitis media in children.

Questionnaires on antibiotic treatment of acute otitis media in children were sent to the general practitioners who make regular referrals to clinics in the King''s College Hospital group. The most popular first choice of drug was amoxycillin (44%), but 37% of general practitioners said that they often used oral phenoxymethylpenicillin. This drug has relatively low activity against Haemophilus influenzae and many strains of Staphylococcus aureus. It is poorly absorbed from the stomach, does not penetrate the middle ear well, and its use may be one factor in the development of chronic middle ear effusions after acute otitis media. Sixty two per cent of the doctors who replied never treated acute otitis media with intramuscular antibiotics, but 57% used oral loading doses. Ninety seven per cent never treated their patients without antibiotics.     

Clinical streptococci and their sensitivity to enterocins produced by different strains of the species Enterococcus faecium (short communication)

In children, acute otitis media (AOM) is one of the most frequently occurring infections caused by Streptococcus pneumoniae and Str. pyogenes. The standard treatment of AOMis provided by antibiotics; however, an increased resistance of the causative agents to antibiotics requires the need to search for innovations. This study was focused on in vitro testing sensitivity of streptococci isolated from AOM to enterocins produced by 9 different origin strains of E. faecium. Enterocins (Ent) represent ribosomally synthesized proteinaceous substances with antimicrobial activity against Gram-positive and/or Gram-negative bacteria which are produced mostly by strains of the species Enterococcus faecium. Str. pneumoniae were sensitive at least to 1 Ent. Str. pneumoniae SPn 754 was sensitive to 5 Ent. Five Str. pyogenes were sensitive to enterocins. Ent A (P) inhibited the growth of 3 Str. pneumoniae, and 4 Str. pyogenes (activity between 100 and 3,200 AU/ml). Most of Ent inhibited the growth of streptococci tested (100-3,200 AU/ml). Str. pyogenes were more sensitive to Ent than Str. pneumoniae. Although more detailed further studies are required, our results indicate a new possibility for enterocin use.     

唾液的增加加速了含羧甲基壳聚糖口香糖的抗菌效果

目的:本论文采用了含羧甲基壳聚糖的口香糖,咀嚼这种口香糖的机械效果加速了其对口腔细菌的抑制作用,还比较口腔嗽洗液和咀嚼口香糖的抗菌效果,证明了通过咀嚼这种口香糖加速了唾液的分泌.方法:从青岛大学口腔科的老师和学生中选取了12名健康的受试者.在测试前取受试者的唾液测试细菌含量.在测试口香糖的试验中,受试者咀嚼5分钟口香糖然后休息5分钟.在测试口腔嗽洗液时,受试者用10ml嗽洗液漱口30秒后,休息9分30秒.同一天中这些测试步骤在50分钟内连续不断的进行了5次.5次测试后分别在0、30和60min收集被试者的唾液测试细菌含量.在测试唾液分泌的试验中,受试者每天咀嚼三次口香糖持续两天.结果:与使用口腔嗽洗液相比,咀嚼含羧甲基壳聚糖口香糖的受试者,在三个取样时间内口腔细菌的含量基本都明显减少,但是在60分钟的取样时间结果有点差异.咀嚼含羧甲基壳聚糖的口香糖明显提高了唾液的分泌量.结论:咀嚼含羧甲基壳聚糖的口香糖具有明显的抗菌效果.目前的研究结果强有力的证明了:使用像壳聚糖以及其衍生物这样的天然物质,对我们的口腔健康以及生活质量都有很大的帮助.