Refractory Acute Otitis Media Research Articles

Is Bilateral Acute Otitis Media Clinically more Refractory than Unilateral Acute Otitis Media?

Objective: To compare the clinical characteristics of bilateral acute otitis media (BAOM) with unilateral acute otitis media (UAOM) in children and to find risk factors of refractory otitis media.Patients and Methods: Four hundred and sixty-six children aged 0 to 14 years old (median age; 1 year old) with AOM were enrolled during January 2010 and June 2011.Diagnosis of acute otitis media, the severity classification by clinical/ontological scores, and treatments were based on Clinical Practical Guidelines for Acute Otitis Media in Children in Japan 2009. Refractory acute otitis media (RAOM) was designated as recurrent acute otitis media with more than 3 episodes in 6 months or more than 4 episodes in 12 months and/or persistent otitis media with a prolonged course of otitis media more than 3 weeks after the treatment. A multivariate logistic regression analysis was used to estimate the risk of BAOM and UAOM presenting with RAOM.Results: One hundred and thirty-seven (29.4%) patients were diagnosed as having RAOM. Two hundred and seventy-eight (60%) patients were diagnosed as having BAOM, 45.3% of whom had RAOM, whereas 11 (5.9%) of 188 patients with UAOM showed a refractory clinical course. One hundred and fifty-four (33%) patients were under 2 years of age and 71.3% of them had RAOM. The odds ratio for BAOM patients (compared with UAOM patients) to present with RAOM was 8.7 (95% confidence interval; 4.4-17.1). The odds ratio for patients under 2 years of age (compared with patients aged 2 or over) to present with RAOM was 7.1 (95% confidence interval; 4.4-11.8).Conclusions: BAOM patients and UAOM patients aged under 2 years of age were significantly associated with an intractable clinical course, and simultaneous occurrence of otitis media and an age under 2 years were apparent risk factors for refractory otitis media.

Microbiology of Acute Mastoiditis and Complicated or Refractory Acute Otitis Media Among Hospitalized Children in the Postvaccination Era

In the post-heptavalent pneumococcal conjugate vaccine era, Streptococcus pneumoniae remains the leading cause of acute mastoiditis and other complicated or refractory acute otitis media among hospitalized children in our settings. Serotype 19A is predominant, invasive and multidrug resistant causing more than half of all mastoiditis cases, two-thirds of cases with subperiosteal abscess and all those requiring mastoidectomy. Continuous surveillance is required.

鼻副鼻腔炎併発は小児急性中耳炎難治化の危険因子である

鼻副鼻腔炎併発は小児急性中耳炎難治化の危険因子である

Ceftriaxone for Refractory Acute Otitis Media

To determine the effect of a clinical practice guideline (CPG) on the use of ceftriaxone for the treatment of refractory acute otitis media (AOM) at a tertiary care pediatric hospital. Charts of all patients aged 3 to 60 months referred from an emergency department to a day treatment center for management of refractory AOM with ceftriaxone were reviewed. Data were collected during two 18-month periods before and after implementation of a CPG developed by a local group of experts. Ceftriaxone was indicated for children with symptomatic AOM despite 48 hours of treatment with high-dosage amoxicillin or amoxicillin-clavulanate (>75 mg/kg per day) or despite receiving 1 of these 2 antibiotics over the previous month. Overall treatment was considered adequate if patients met these indications for ceftriaxone, if at least 3 daily doses had been prescribed, and if all doses were within the 40- to 60-mg/kg range. Thirty-two emergency physicians referred 127 patients to the day treatment center (60 preimplementation and 67 postimplementation of the CPG). The mean (SD) patient ages were 16.7 (7.4) and 19.7 (12.4) months in the preimplementation and postimplementation groups, respectively. Indications for prescription of ceftriaxone were adequate in 16.7% of the preguideline and 22.4% of the postguideline groups (P = 0.4). Physicians were twice as likely to use ceftriaxone adequately after the guideline's implementation, but this result was not statistically significant (crude odds ratio, 2.2; 95% confidence interval, 0.5-9.0). Implementation of a CPG for the treatment of refractory AOM with ceftriaxone did not improve indications for its use.

Efficacy, tolerability, and parent reported outcomes for cefdinir vs. high-dose amoxicillin/clavulanate oral suspension for acute otitis media in young children

ABSTRACTObjectives: To compare efficacy, tolerability, and parental satisfaction of cefdinir and high-dose amoxicillin/clavulanate oral suspensions given to young children with non-refractory acute otitis media (AOM) based on clinical endpoints and outcomes measures.Research design and methods: This was an investigator-blinded, multicenter study in which 318 children 6 months through 6 years of age with a clinical diagnosis of AOM were randomized to receive 10 days of either cefdinir (14 mg/kg divided BID) or high-dose amoxicillin/clavulanate (90/6.4 mg/kg divided BID).Main outcome measures: Investigators evaluated clinical response at an end-of-therapy (EOT) office visit conducted on day 12–15. Outcomes of satisfaction, tolerability, and adherence were also assessed at that visit using an Otitis Parent Questionnaire.Results: The treatment groups were similar at baseline with respect to patient demographics. At the EOT visit, for cefdinir and amoxicillin/clavulanate, respectively, intent-to-treat (ITT) clinical cure rates were 82% (129/158) and 85% (134/158) ( p = 0.547; 95% confidence interval [CI] –11.7 to 5.4) and per-protocol cure rates were 82% (123/150) and 90% (129/143) ( p = 0.045; 95% CI –16.4 to 0.0). This difference was driven primarily by reduced cefdinir response in patients with recurrent AOM (p = 0.010) and those younger than 24 months (p = 0.039). Comparing cefdinir with amoxicillin/clavulanate, parents more often reported significantly better ease of use (89% vs. 57%; p < 0.0001), better taste (85% vs. 39%; p < 0.0001), and better adherence (at least 95% of doses) (82% vs. 61%; p < 0.0001). Diarrhea/loose stools were more common in the amoxicillin/clavulanate group than in the cefdinir group (28% vs. 18%, respectively; p = 0.0341). One patient in the cefdinir group and eight patients in the amoxicillin/clavulanate group withdrew from the study prematurely due to at least one adverse event ( p = 0.0364). Study limitations included assessment of clinical recurrence by telephone call rather than office visit, exclusion of children with refractory AOM, and no assessment of middle ear microbiology.Conclusions: Among young children with non-refractory AOM, cefdinir was as efficacious as high-dose amoxicillin/clavulanate in the ITT group, but somewhat less effective in per-protocol analysis. From the parental perspective, cefdinir was easier to administer, had a better taste, caused less diarrhea, and resulted in higher treatment adherence than high-dose amoxicillin clavulanate.

Pathogen Shifts and Changing Cure Rates for Otitis Media and Tonsillopharyngitis

Pneumococcal conjugate vaccine use has caused a decrease in the incidence of recurrent and refractory acute otitis media in the United States and a shift in the predominant pathogens. Now Haemophilus influenzae is the most commonly isolated organism (about 60% of the total), and more than half the strains make beta-lactamase, rendering them resistant to amoxicillin. Penicillin nonsusceptible pneumococci, the main target of antibiotic therapy in the 1990s, has become a much less common isolate (10%- 25% of the total). These changes impact antibiotic selection for acute otitis media. Penicillin treatment of group A streptococcal tonsillopharyngitis does not meet the minimum United States Food and Drug Administration standards for first-line treatment, which is 85% or greater eradication at the end of therapy. Recent results with amoxicillin suggest its efficacy is also waning. Cephalosporins have the highest bacteriologic and clinical efficacy. This has implications for optimal antibiotic therapy.

Effectiveness of Laser‐Assisted Myringotomy for Otitis Media in Children

To evaluate the effectiveness of OtoScan CO2 laser-assisted myringotomy (OtoLAM ESC/Sharplan) for acute otitis media and chronic otitis media with effusion (COME) in children. Retrospective review of 47 children with refractory acute otitis media (RAOM) or COME more than 3 months in duration in a pediatric otolaryngology practice. Laser-assisted myringotomy was performed on 47 patients (79 ears) using the OtoLAM device. There were 28 children (ages 0.50-3 years) with RAOM and 19 children (ages 0.58-15 years) with COME. A total of 57.4% of procedures were considered treatment failures. Failures occurred in 53.6% of patients with RAOM on average +/-SD 3.89 +/- 2.16 weeks after the procedure and in 63.2% of patients with COME on average +/-SD 7.25 +/- 5.57 weeks after the procedure. Age, sex, microorganism isolated, myringotomy size, wattage, and laterality did not predict outcome. Ventilation tube insertion was performed in 27 (57.4%) patients. Two patients have persistent tympanic membrane perforations at 2 years. Laser-assisted myringotomy in children with RAOM and COME was associated with a high incidence of recurrence or persistence of disease and with perforation of the tympanic membrane. Recommendations for use of the OtoLAM should include discussion of high failure rates and the strong likelihood of subsequent ventilation tube insertion. The OtoLAM remains an option for office-based ventilation of the middle ear for families and patients where general anesthesia is a concern.

Bacteriology of medically refractory acute otitis media in children: a 9-year retrospective study

Objective: To identify the causative organisms for medically refractory acute otitis media (AOM) in children, and to recommend the appropriate antibiotics for these patients. Study design: Retrospective chart review. Methods: The medical records for 671 children (1258 ears) undergoing myringotomies between January 1993 and December 2001 were retrospectively reviewed. “Medically refractory” AOM is defined as AOM requiring emergency myringotomy because of toxicity persisting despite second-phase antibiotics. Of these, 18 children were enrolled in our study, with 25 of the ears affected by medically refractory AOM. Myringotomy was performed for pus drainage, bacterial culture and susceptibility studies in all cases. Clinical factors were analyzed to demonstrate possible relationships with microbiological findings. Results: Bacteria were recovered in specimens taken from 12 ears. The positive culture rate was 48%. Bacteriological studies showed mostly growing gram-positive bacteria, such as coagulase negative staphylococcus, Staphylococcus aureus and Streptococcus pneumoniae (in decreasing order of incidence). The sensitivity rate to pre-myringotomy antibiotics was 85.7%. With the exception of Pseudomonas aeruginosa and two ears with intracranial complications or pneumonia, all other isolated microorganisms were susceptible to first-generation cephalosporins. No statistically significant differences were noted between culture rates and clinical factors. Conclusion: The distribution of organisms in our medically refractory AOM cases differed from that for simple AOM, with gram-positive bacteria having significantly higher rates of incidence. Combining intravenous aminoglycoside with first-generation cephalosporin is considered an inexpensive and effective treatment covering all potential microorganisms. Vancomycin or third-generation cephalosporins are only needed for major complications or other coincident infections extant during the initial presentation.

Treatment and prevention of otitis media.

To review and summarize recent advances in the treatment and prevention of otitis media (OM). A MEDLINE search (1996-March 2000) was performed to identify relevant primary and review articles. References from these articles were also reviewed if deemed important. English-language primary and review articles focusing on the treatment and prevention of acute otitis media (AOM) were included. Studies focusing exclusively on OM with effusion or serous OM and chronic suppurative OM were excluded. Information regarding prevention and drug therapy was reviewed, with an emphasis placed on advances made in the last two years. Recently, an expert panel of the Centers for Disease Control and Prevention recommended use of only three of 16 systemic antibiotics approved by the Food and Drug Administration for treatment of AOM: amoxicillin, cefuroxime axetil, and ceftriaxone. Controversy exists over the importance of key selection factors used by the expert panel in determining which antibiotics to recommend in a two-step treatment algorithm, that is, in vitro data, pharmacodynamic profiles, and necessity for coverage of drug-resistant Streptococcus pneumoniae at all steps of empiric treatment. Additional antibiotic and patient selection factors useful for individualizing therapy include clinical efficacy, adverse effects, frequency and duration of administration, taste, cost, comorbid infections, and ramifications should bacterial resistance develop to the chosen antibiotic. Presumed or past patient/caregiver adherence (especially when antibiotic failure has occurred) is also paramount in selecting antibiotic therapy. A three-step treatment algorithm for refractory AOM that employs amoxicillin, trimethoprim/sulfamethoxazole (TMP/SMX), or high-dose amoxicillin/clavulanate (depending on the prior dose of and adherence to amoxicillin therapy), and ceftriaxone or tympanocentesis at steps 1, 2, and 3, respectively, appears rational and cost-effective. The recent upsurge in antimicrobial resistance is highlighted, and recommendations are presented for the treatment of AOM and prevention of recurrent otitis media (rAOM). Amoxicillin remains the antibiotic of choice for initial empiric treatment of AOM, although the traditional dosage should be increased in patients at risk for drug-resistant S. pneumoniae. In cases refractory to high-dose amoxicillin, TMP/SMX should be prescribed if adherence to prior therapy seemed good or complete, or high-dose amoxicillin/clavulanate if adherence was incomplete or questionable. Ceftriaxone should be reserved as third-line treatment. The increasing prevalence of drug-resistant S. pneumoniae emphasizes the importance of alternative medical approaches for the prevention of OM, as well as judicious antibiotic use in established cases. Removal of modifiable risk factors should be first-line therapy for prevention of rAOM. We support the use of conjugate pneumococcal vaccine per guidelines for prevention of rAOM from the Advisory Committee on Immunization Practice of the Centers for Disease Control and Prevention, with consideration given to influenza vaccine for cases of rAOM that historically worsen during the flu season. Sulfisoxazole prophylaxis should be reserved for children who are immunocompromised, have concurrent disease states exacerbated by AOM, or meet the criteria of rAOM despite conjugate pneumococcal and influenza vaccination. Therapy should be intermittent, beginning at the first sign of an upper respiratory infection, and should continue for 10 days. The invasive nature and risks of anesthesia relegate myringotomy, tympanostomy tubes, and adenoidectomy to last-line therapies for rAOM.

Management of acute otitis media in the 1990s: the decade of resistant pneumococcus.

Acute otitis media (AOM) has become increasingly difficult to treat in the 1990s, the decade of drug-resistant pneumococcus. Throughout the world, drug-resistant strains of this pathogen are being recovered from 20 to 50% of cases of initial untreated AOM, and from 45 to 90% of refractory AOM. Almost as alarming is that beta-lactamase-producing strains of Haemophilus influenzae are currently being isolated in 40 to 50% of cases of AOM in the US. Clinicians can no longer expect 'Pollyanna-like' high rates of clinical resolution for this disease. It is now imperative that they become aware of the regional prevalence of these drug-resistant bacteria and, just as importantly, their patterns of antibacterial resistance. Although some authors would hold that any antibacterial, or even placebo, should be adequate for most cases of AOM, clinical practice appears to suggest otherwise. Amoxicillin, still the first-line therapeutic choice for initial nonrefractory AOM, will often fail. The real dilemma begins when clinicians search for clinical data to select an antibacterial for therapeutic failures--few data are available. Thus, to give optimal treatment to a child who has failed antibacterial therapy--the true actual indication for all second-line antibacterials--they must instead become familiar with the following in vivo and in vitro data: 1. 'In vivo sensitivity data': otherwise known as bacteriological efficacy, in which repeat tympanocentesis is performed in mid-therapy. This reveals the bacterial 'Achilles heel' or weakness for the individual antibacterial agents. 2. Clinical efficacy data: analysis of rates of clinical resolution after therapy in comparative trials which use a single tympanocentesis initially and a 'gold standard' comparator antibacterial. 3. 'Bug to drug' data: comparison of reported middle ear concentrations for each individual antibacterial agent relative to the respective minimum inhibitory concentrations of isolates, particularly drug-resistant pneumococcus and H. influenzae (if possible, obtained from the paediatric respiratory tract). The selection of an antibacterial agent for AOM in any particular case should not be merely a random process. It involves awareness of the pathogens most likely to be observed: with co-infections; after failure with a particular antibacterial (the bacterial 'Achilles heel' of the drug); and at different points in time, whether initially or after therapeutic failures (e.g. first-line versus fourth-line failure).

Chlamydia pneumoniae in acute otitis media.

Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.

Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media.

Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most frequently isolated pathogens in patients with acute otitis media (AOM). Other potential causative pathogens include Streptococcus pyogenes in older children and Chlamydia pneumoniae in younger children. The recent emergence of penicillin-resistant S. pneumoniae and the increasing frequency of beta-lactamase-producing strains of M. catarrhalis and H. influenzae are creating concerns regarding the use of amoxicillin as traditional first line empiric therapy for AOM in younger children. Both the in vitro antibiotic activity against these more resistant causative pathogens and the antibiotic concentrations achieved in middle ear fluid must be considered when selecting antibiotics for treatment of refractory AOM. The newer macrolides, azithromycin and clarithromycin, provide reasonable in vitro coverage against penicillin-resistant S. pneumoniae and beta-lactamase-producing H. influenzae, although azithromycin is more active against the latter. Both drugs also achieve notably higher, sustained concentrations in middle ear fluid than do beta-lactam antibiotics. Thus the newer macrolides represent important new rational alternatives for the management of AOM.

Limit antibiotic prescriptions to bacterial infections

Jan. 19, 1992: The weather outside is biting, frigid and overcast. I renewed the contract with the laboratory last week. For the last three years, the reference laboratory has asked if I still want to check the penicillin susceptibility of every pneumococcal middle-ear isolate: Certainly we9ll be happy to do it for you, doctor. (Snickering. Waste your money.) Julia, our laboratory technician, summoned me to examine the blood agar plate. The bacterial colonies from the middle-ear fluid of an 18-month-old child with refractory acute otitis media were alpha-hemolytic and inhibited by the optochin disk. Obvious pneumococci.