Alternative Therapies for Otitis Media

Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
April 08, 2009

Introduction:

          Since the 1950s, antibiotic  resistance has been recognized as a problem (1-3). Ironically, some  of the scientists who first identified antibiotic processes had  warned decades previously that overuse would lead to resistant  bacteria (4). More recently, news reports and medical articles have  described "flesh-eating bacteria" and amputations related to  methicillin-resistant Staphylococcus aureus (6; MRSA). Furthermore,  antibiotic resistant microbes including MRSA have been identified  in children with persistent otitis (eg, 7-8, see also 9-10).

          The increasing prevalence of  resistant microbes has prompted various medical organizations to  offer guidelines wherein antibiotics are to be used far less in  pediatric otitis (eg, 11-14). The need to reduce the use of  antibiotics has led to consideration and preliminary evaluation of  alternative therapies which might be helpful in treatment of otitis  and respiratory infections which can exacerbate otitis (eg, 15-19).  Indeed, some therapeutics within complimentary and alternative  medicine (CAM) have been found to be efficacious (cites below).

 

  Some quotes from peer-reviewed journals:

 

  "Acute otitis media (AOM) is the most common cause of physicians'  office visits for children ages 1-4 years in the United States...  Some of these children develop hearing deficits resulting in poor  school performance and often require surgical procedures to improve  middle ear drainage. Moreover, children with recurrent AOM require  frequent use of antibiotics, making AOM the most common reasons for  antibiotic prescription in the United States... As a result, AOM  treatment has also contributed to the rapid emergence of multi-drug  resistant bacteria. Direct and indirect costs of AOM are estimated  to exceed 4 billion dollars per year in the United States..."  (15).

 

  "Bacteria that antibiotics have controlled in the past are  increasingly developing resistance to these drugs. Today, virtually  all important bacterial infections in the United States and  throughout the world are becoming resistant...  The overuse of  antimicrobials is beginning to be discouraged as scientific  evidence is emerging to support the use of other therapies. In  pediatric practice an emphasis on accurate diagnoses, control of  environmental risk factors, and utilization of complementary and  alternative medicine (CAM) therapies could reduce antibiotic  prescribing. Antibiotic resistance poses a growing threat to  health. CAM therapies may provide a safer, more effective treatment  for many acute infections of childhood." (16)

 

                            Patients who were given [naturopathic] ear drops alone had a better  response than patients who were given ear drops together with  amoxicillin. (17)

 

  "Viral infection of the upper respiratory tract results in  congestion of the nasal and nasopharyngeal mucosa. Congestion in  and around the nasopharyngeal orifice of the Eustachian tube leads  to dysfunction of the tube, which is considered the most important  factor in the development of AOM..." (18)

 

  "A combination of echinacea, propolis, and ascorbic acid decreased  the number of URTI [upper respiratory tract infection] episodes,  the duration of symptoms, and the number of days of illness (p <  0.001)." (19)

 

                            The quotes represent a rationale supported by peer-reviewed medical  literature: Otitis is common and can be severe. Antibiotic  resistance (AR) has become a major problem. Many children have  antibiotic-resistant bacteria in MEF and/or in nasopharynx. In  response to AR, guidelines about using antibiotics for otitis have  changed. Among advances in otitis media, there is increasing  appreciation for the role of respiratory infections. CAM has been  proposed as a way to prevent or alleviate ROM, AOM, and respiratory  infections; and, although a range of results is reported, many  alternative therapies have been found helpful.

 

                            As we consider CAM therapuetics in relation to otitis media and  otitis-associated respiratory infections, we shall also consider  factors associated with otitis, eg, gastro intestinal pathology,  hypersensitivity to specific foods, suboptimal nutrient status, day  care for infants, tobacco smoke, and air pollution.

 

                            A major purpose of this document is to present citations related to  various CAM therapies that may be helpful for some individuals.  However, a caveat is in order. Although the following information  is based upon published medical literature, otitis media can have  severe ramifications. These include but are not limited to impaired  hearing and meningitis. There is much variation between individuals  in regard to symptoms, recurrence, and outcomes. A qualified health  practitioner is a valuable partner when a parent has a child with  acute or recurrent otitis media.

   

                            The following topics are considered: nutrient levels, supplements,  herbs with microbial or anti-inflammatory properties, and  environmental factors such as tobacco smoke, air pollution, and  excessive oxidative stress. Another way to address recurrent or  acute otitis and related respiratory infections is to consider  pathogens associated with otitis and with respiratory infections,  inflammation that exacerbates otitis, and circumstances which  elevate oxidative stress. Each domain can be addressed via CAM.

 

  CAM therapies helpful in some cases of otitis

 

                            Glutathione is helpful in many cases of otitis (20).

 

                            Garlic is bactericidal and may be helpful (21), although garlic may  induce respiratory symptoms in some individuals (22).

 

                            Echinacea may produce a rash and, in some individuals, may reduce  the rate or severity of otitis-associated recurrent upper  respiratory infections (URTIs) in some children (23-24).

 

                            A combination of echinacea, bee propolis, and vitamin C has been  found helpful in minimizing effects of otitis-associated  respiratory infections (25; see also 26). 

 

                            Cow's Milk Allergy is associated with recurrent otitis media  (26b).

 

                            Naturopathic Herbal Extract Ear Drops (NHED) were more effective in  treating otitis media ear pain than were antibiotics (17).

 

                            Vitamin C studies have described mixed findings, including  subgroups of younger children who had "shorter and less severe  episodes" of otitis-associated URTIs (27-28, discussed in 29).  Vitamin C and other antioxidant nutrients were found low in a group  of children with otitis and tonsillitis (cites below).

 

  Nutrients related to otitis, immunity, and URTIs

 

                            Immunity, nutrients, and nutritional status have functional,  important interactions (eg, 30-31).

 

  "high prenatal dietary vitamin C intake was significantly inversely  related to early AOM" (31, see also 32)

 

  "Oxidants and antioxidants played a significant role in the  pathogenesis of otitis media with effusion in children. These  children are under significant oxidative stress." (33)

 

  "The organism maintains defense systems including nonenzymatic  antioxidants such as Vitamins A, E and C and reduced glutathione  (GSH) against reactive oxygen species (ROS). In the present study,  lipid peroxidation status and nonenzymatic antioxidant capacity  were investigated in children with AOM and AT [acute  tonsillitis]... All of the antioxidant vitamins such as  beta-carotene, retinol, Vitamin E, and Vitamin C levels were  observed to be significantly decreased in the both patient  groups... GSH levels were also decreased in the patient groups. MDA  levels were found to be higher in children with AOM and AT than in  the healthy control subjects." (34)

 

  Factors related to otitis and to respiratory infections

 

                            Tobacco smoke, air pollution, and household mold increase the  likelihood of otitis in children (35-37). Day care increases the  rate at which an infant or toddler is exposed to pathogens  associated with otitis and with respiratory infections (38-39).

 

  Oxidative stress in otitis and UTRIs

 

  "Oxidative stress is caused by an imbalance between the production  of reactive oxygen and a biological system's ability to readily  detoxify the reactive intermediates or easily repair the resulting  damage." (40)  Elevated oxidative stress and lower levels of  antioxidant nutrients are found in otitis and tonsillitis (27,  33-34). Elevated oxidative stress is associated with autism and  with ADHD (41-44; 45-47). Antioxidant nutrients may reduce elevated  oxidative stress in some and perhaps many individuals (eg, 42).  However, no crystal clear rules apply.

 

                            Peer-reviewed literature about using supplements to alleviate  oxidative stress shows mixed results. There is no overwhelming  conclusion that supplements can reduce elevated oxidative stress in  all situations, even as there are studies which show that nutrients  having antioxidant functions are low in various human pathologies.  Indeed, in some subgroups (schizophrenia, autism), positive effects  from using vitamin supplements to reduce elevated levels of  oxidative stress has been reported (42 and cites therein).   Nutrients found helpful include vitamin C, carnosine, vitamin B6,  magnesium, zinc, selenium, and glutathione (42).

 

                            Precaution: excessive intake of biologically necessary nutrients  can induce adverse effects. Some health-care providers use lab  tests as a basis for recommending a specific nutrient-protocol for  a given child.

 

  Other nutrients, other herbs

 

                            Otitis media can be bacterial, viral, or a combination of viral and  bacterial (15). PCR has identified fungi in many case of otitis  (49). Many herbs have antibacterial or antiviral properties. Not  all have been tested in regard to pediatric otitis media.  Therefore, the following comments and citations should be  considered suggestions for research - in the context that overuse  of antibiotics and the prevalence of antibiotic-resistant strains  has prompted searches for CAM therapeutics which are both  efficacious and safe.

 

                            Bacteria associated with otitis media (18, 50, 67):

      Haemophilus influenzae non-type b

      Moraxella catarrhalis

      Peptostreptococcus species

      Pseudomonas aeruginosa

      Streptococcus pneumoniae

      Streptococcus pyogenes

      Staphylococcus aureus

 

                            Otitis-related bacteria with antibiotic resistance (eg, 48, 51,  67)

      Haemophilus influenzae

      Moraxella catarrhalis

      Pseudomonas aeruginosa

      Staphylococcus aureus

      Streptococcus pneumonia

      Streptococcus pyogenes

 

                            Viruses associated with otitis media (eg, 18,51; not in order of  prevalence)

      Cytomegalovirus (CMV)

      Enterovirus

      Herpes simplex virus (HSV)

      Influenza

      Parainfluenza viruses

      Respiratory syncytial virus (RSV)

      Rhinovirus

 

                            Many cases of recurrent or acute otitis media (ROM, AOM) have  combinations (i) of bacterial and viruses, (ii) of several  bacteria, or (iii) of several viruses (eg, 15, 18).

 

  Additional antimicrobial herbs that merit research: The  following list is preliminary and is intended to suggest directions  for research regarding CAM treatments for otitis media and for  related respiratory infections. Each herb listed here has either  antimicrobial and/or anti-inflammatory properties or may boost the  immune system. The list presented here is not intended to be  complete. When parents have a child with ROM or AOM, consulting a  qualified health-care practitioner is recommended.

 

     Astragalus membranaceus & other species (eg,  52-54)

     Cinnamomi cortex & other specis (cinnamon;  58-60)

     Glycyrrhiza glabra (licorice; 61-64)

     Olea europaea (olive leaf; 65-66)

     Origanum compactum, Origanum vulgare (oregano;  68-70)

     Uncaria tomentosa, Uncaria guianensis (cat's claw;  55-57)

 

                            Conclusion:

         This e-document calls attention to  complementary and alternative medicine findings that have  documented or implied relevance to otitis media (especially ROM and  AOM) and to otitis-related respiratory infections. Some peer  reviewed studies have concluded that various CAM therapies are  helpful in treating otitis media or otitis-associated respiratory  infections. The mechanisms by which these CAM-related therapies are  efficacious may not yet have been firmly established. Possible  mechanisms include anti-pathogen, anti-inflammatory, and  immune-boosting effects. Antioxidant effects are also relevant.  Indeed, some nutrients have anti-oxidant significance and, if  suboptimal within a specific child, can boost immunity.  Furthermore, the more that otitis-associated environmental  exposures can be avoided, the better the child's likelihood of not  progressing to recurrent or acute otitis.  Perhaps before many  years have passed, clinically oriented researchers will have  explored some of the anti-microbial herbs presented in this  preliminary document.

 

 

  References:

 

                            1. "The overuse of antibiotics like penicillin and erythromycin  which used to be one-time miracle cures were associated with  emerging resistance since the 1950s."

  http://en.wikipedia.org/wiki/Antibiotic#Antibiotic_resistance

 

                            2. The growing burden of antimicrobial resistance.

                            Hawkey PM.  J Antimicrob Chemother. 2008 Sep;62 Suppl  1:i1-9.

  http://jac.oxfordjournals.org/cgi/content/full/62/suppl_1/i1

 

                            3. Community factors in the development of antibiotic  resistance.

                            Larson E.  Annu Rev Public Health. 2007;28:435-47.

  http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.publhealth.28.021406.144020

 

                            4. The Antibiotic Paradox: How the Misuse of Antibiotics Destroys  Their Curative Powers.

                            Stuart B. Levy; Da Capo Press, 2002.

 

                            5. Methicillin resistant Staphylococcus aureus (MRSA)

  http://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus

 

                            6. MRSA in lower limb amputation and the role of antibiotic  prophylaxis.

                            Richards T et al.  J Cardiovasc Surg (Torino). 2005  Feb;46(1):37-41.

 

                            AIM: Methicillin Resistant Staphylococcus Aureus (MRSA)  colonisation is reported in 3-20% of vascular patients. Many  develop infective complications. MRSA is associated with poor  prognosis. Aim of the study is to assess MRSA in lower limb  amputation and efficacy of antibiotic prophylaxis. METHODS:  Prospective study of lower limb amputation. MRSA screen and wound  swabs were taken at operation. Antibiotic prophylaxis included  teicoplanin (400 mg) 1 dose at operation. RESULTS: Twenty-five  patients underwent 33 primary amputations. At operation 15 legs  (45%) were colonised with MRSA and 18 legs (58%) had active wound  infection; MRSA (4) and other (14). Following surgery 3 patients  died. Twenty-two legs (76%) had primary healing. Infection  developed in 7 stumps (24%), MRSA (5) and Pseudomonas (2). Stump  infection increased time to wound healing (p<0.0001). MRSA stump  infection increased revision amputation (p=0.009) and duration of  hospital stay (p<0.0074). MRSA wound infection at operation  increased the risk of MRSA stump infection (p=0.007). Non-MRSA  wound infection at operation was not associated with a worse  outcome. No patient colonised with MRSA at operation developed  postoperative MRSA stump infection. CONCLUSIONS: MRSA is more  prevalent that previously reported. MRSA infection has a poor  prognosis. Prophylaxis may be effective for patients colonised with  MRSA.

 

                            7. Methicillin-resistant Staphylococcus aureus: pediatric  otitis.

                            Santos F et al.  Arch Otolaryngol Head Neck Surg. 2000  Nov;126(11):1383-5.

  http://archotol.ama-assn.org/cgi/content/full/126/11/1383

 

                            BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a  potentially lethal organism in pediatric patients. MRSA is an  uncommon otologic pathogen that requires special diagnostic and  therapeutic intervention. METHODS: Three pediatric patients with  community-acquired MRSA otologic infections were identified during  1999. SETTING: Tertiary care ear institution. RESULTS: All patients  required intravenous antibiotic therapy to achieve resolution of  the infections. CONCLUSIONS: MRSA in children can be community  acquired and can cause otitis externa, otitis media with otorrhea,  or acute mastoiditis; intravenous therapy that includes vancomycin  is necessary for resolution.

 

                            8. Methicillin-resistant Staphylococcus aureus otorrhea after  tympanostomy tube placement.

                            Coticchia JM, Dohar JE.  Arch Otolaryngol Head Neck Surg. 2005  Oct;131(10):868-73.

  http://archotol.ama-assn.org/cgi/content/full/131/10/868

 

                            OBJECTIVE: To compare a retrospective cohort of nonhospitalized  children with methicillin-resistant Staphylococcus aureus (MRSA)  otorrhea with those with methicillin-sensitive S aureus (MSSA)  otorrhea to determine the risk factors predisposing to MRSA  otorrhea and the treatments used. DESIGN: Retrospective  case-controlled series. SETTING: Tertiary pediatric care facility.  PATIENTS: Seventeen children with MRSA otorrhea after bilateral  myringotomy with tympanostomy tube insertion (BM&T) and 19 age-  and sex-matched control subjects who demonstrated MSSA otorrhea.  The average age at culture in MRSA patients was 52 months; in MSSA  patients, 54 months. There were 8 boys and 3 girls in the MRSA  group and 8 boys and 4 girls in the MSSA group. INTERVENTIONS:  Oral, topical, and intravenous antimicrobial agents. MAIN OUTCOME  MEASURES: Antibiotic exposure and history of otitis media and  routine antibiotic administration (topical, oral, or intravenous).  RESULTS: The following findings were statistically significant (P  < or = .06, Mann-Whitney test): (1) longer duration of  antibiotic treatment after BM&T for patients with MRSA vs those  with MSSA; (2) increased number of episodes of acute otitis media  before BM&T in patients with MRSA vs those with MSSA; and (3)  increased number of courses of antibiotics after BM&T in  patients with MRSA vs those with MSSA. CONCLUSIONS:  Methicillin-resistant S aureus otorrhea is commonly seen as a  community-acquired infection in otherwise healthy pediatric  outpatients. Risk factors for development of MRSA otorrhea include  the number of episodes of acute otitis media before BM&T and  number of treatment courses and duration of antibiotic therapy  after BM&T.

 

                            9. Microbial interactions during upper respiratory tract  infections.

                            Pettigrew MM et al. Emerg Infect Dis. 2008 Oct;14(10):1584-91.  [free online]

  http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2609881&blobtype=pdf

 

                            Streptococcus pneumoniae, Haemophilus influenzae, Moraxella  catarrhalis, and Staphylococcus aureus often colonize the  nasopharynx. Children are susceptible to bacterial infections  during or soon after upper respiratory tract infection (URI). We  describe colonization with these 4 bacteria species alone or in  combination during URI. Data were from a prospective cohort of  healthy children 6 to 36 months of age followed up for 1 year.  Analyses of 968 swabs from 212 children indicated that S.  pneumoniae colonization is negatively associated with colonization  by H. influenzae. Competitive interactions shifted when H.  influenzae and M. catarrhalis colonized together. In this  situation, the likelihood of colonization with all 3 species is  higher. Negative associations were identified between S. pneumoniae  and S. aureus and between H. influenzae and S. aureus.  Polymicrobial interactions differed by number and species of  bacteria present. Antimicrobial therapy and vaccination strategies  targeting specific bacterial species may alter the flora in  unforeseen ways.

 

                            10. Rates of antimicrobial resistance among common bacterial  pathogens causing respiratory, blood, urine, and skin and soft  tissue infections in pediatric patients.

                            Jones ME et al.  Eur J Clin Microbiol Infect Dis. 2004  Jun;23(6):445-55.

  http://www.springerlink.com/content/4keva25dt73m92lc/

 

                            Antimicrobial resistance patterns among the principal bacterial  pathogens from infections of the respiratory tract, blood, skin and  soft tissue, and urinary tract of pediatric patients from the USA,  Canada, Germany, France, and Italy were studied using the The  Surveillance Network (TSN) database. Among Streptococcus pneumoniae  isolates from respiratory tract infections, the prevalence of  high-level penicillin resistance (MIC>/=2 microg/ml) ranged from  1.1 (Italy) to 36.2% (USA); erythromycin resistance was higher,  ranging from 13.4 (Germany) to 63.8% (France). The prevalence of  beta-lactamase-positive Haemophilus influenzae among isolates from  lower respiratory tract infections ranged from <10 (Italy and  Germany) to 38.4% (USA). Among isolates from blood and skin and  soft tissue infections, the prevalence of methicillin-resistant  Staphylococcus aureus (MRSA) ranged from 7.2% (Canada and Germany)  to 27.3% (Italy). The prevalence of Escherichia coli and Klebsiella  pneumoniae with putative extended-spectrum beta-lactamases among  isolates from blood, urinary tract, and skin and soft tissue  infections ranged from 0 (Germany and France) to 29.6% (Italy).  With the exception of pseudomonal infections or infections with  MRSA, amoxicillin-clavulanate retained moderate activity, whilst  ceftriaxone and cefepime were the most effective broad-spectrum  injectable agents. Meropenem was the most effective agent against  Pseudomonas aeruginosa with <5% resistance. Low levels of  resistance, along with acceptable safety profiles and the  availability of convenient oral formulations, continue to support  the use of ceftriaxone, cefepime, amoxicillin-clavulanate, and  meropenem as viable options for the treatment of infections in  pediatric patients.

 

                            11. New guidelines on acute otitis media: an overview of their key  principles for practice.

                            Marcy SM.  Cleve Clin J Med. 2004 Jun;71 Suppl 4:S3-9. [free  online]

  http://www.ccjm.org/content/71/Suppl_4/S3.long

 

                            12. Clinical practice guideline: Otitis media with effusion.

                            Rosenfeld RM et al.

                            Otolaryngol Head Neck Surg. 2004 May;130(5 Suppl):S95-118.

 

                            The clinical practice guideline on otitis media with effusion (OME)  provides evidence-based recommendations on diagnosing and managing  OME in children. This is an update of the 1994 clinical practice  guideline "Otitis Media With Effusion in Young Children," which was  developed by the Agency for Healthcare Policy and Research (now the  Agency for Healthcare Research and Quality). In contrast to the  earlier guideline, which was limited to children aged 1 to 3 years  with no craniofacial or neurologic abnormalities or sensory  deficits, the updated guideline applies to children aged 2 months  through 12 years with or without developmental disabilities or  underlying conditions that predispose to OME and its sequelae. The  American Academy of Pediatrics, American Academy of Family  Physicians, and American Academy of Otolaryngology-Head and Neck  Surgery selected a subcommittee composed of experts in the fields  of primary care, otolaryngology, infectious diseases, epidemiology,  hearing, speech and language, and advanced practice nursing to  revise the OME guideline. The subcommittee made a strong  recommendation that clinicians use pneumatic otoscopy as the  primary diagnostic method and distinguish OME from acute otitis  media (AOM). The subcommittee made recommendations that clinicians  should (1) document the laterality, duration of effusion, and  presence and severity of associated symptoms at each assessment of  the child with OME; (2) distinguish the child with OME who is at  risk for speech, language, or learning problems from other children  with OME and more promptly evaluate hearing, speech, language, and  need for intervention in children at risk; and (3) manage the child  with OME who is not at risk with watchful waiting for 3 months from  the date of effusion onset (if known), or from the date of  diagnosis (if onset is unknown). The subcommittee also made  recommendations that (4) hearing testing be conducted when OME  persists for 3 months or longer, or at any time that language  delay, learning problems, or a significant hearing loss is  suspected in a child with OME; (5) children with persistent OME who  are not at risk should be reexamined at 3- to 6-month intervals  until the effusion is no longer present, significant hearing loss  is identified, or structural abnormalities of the eardrum or middle  ear are suspected; and (6) when a child becomes a surgical  candidate, tympanostomy tube insertion is the preferred initial  procedure. Adenoidectomy should not be performed unless a distinct  indication exists (nasal obstruction, chronic adenoiditis); repeat  surgery consists of adenoidectomy plus myringotomy, with or without  tube insertion. Tonsillectomy alone or myringotomy alone should not  be used to treat OME. The subcommittee made negative  recommendations that (1) population-based screening programs for  OME not be performed in healthy, asymptomatic children and (2)  antihistamines and decongestants are ineffective for OME and should  not be used for treatment; antimicrobials and corticosteroids do  not have long-term efficacy and should not be used for routine  management. The subcommittee gave as options that (1) tympanometry  can be used to confirm the diagnosis of OME and (2) when children  with OME are referred by the primary clinician for evaluation by an  otolaryngologist, audiologist, or speech-language pathologist, the  referring clinician should document the effusion duration and  specific reason for referral (evaluation, surgery), and provide  additional relevant information such as history of AOM and  developmental status of the child. The subcommittee made no  recommendations for (1) complementary and alternative medicine as a  treatment for OME based on a lack of scientific evidence  documenting efficacy and (2) allergy management as a treatment for  OME based on insufficient evidence of therapeutic efficacy or a  causal relationship between allergy and OME. Last, the panel  compiled a list of research needs based on limitations of the  evidence reviewed. The purpose of this guideline is to inform  clinicians of evidence-based methods to identify methods to  identify, monitor, and manage OME in children aged 2 months through  12 years. The guideline may not apply to children older than 12  years because OME is uncommon and the natural history is likely to  differ from younger children who experience rapid developmental  change. The target population includes children with or without  developmental disabilities or underlying conditions that predispose  to OME and its sequelae. The guideline is intended for use by  providers of health care to children, including primary care and  specialist physicians, nurses and nurse practitioners, physician  assistants, audiologists, speech-language pathologists, and child  development specialists. The guideline is applicable to any setting  in which children with OME would be identified, monitored, or  managed. This guideline is not intended as a sole source of  guidance in evaluating children with OME. Rather, it is designed to  assist primary care and other clinicians by providing an  evidence-based framework for decision-making strategies. It is not  intended to replace clinical judgment or establish a protocol for  all children with this condition, and may not provide the only  appropriate approach to diagnosing and managing this problem.

 

                            13. Nonsevere acute otitis media: a clinical trial comparing  outcomes of watchful waiting versus immediate antibiotic  treatment.

                            McCormick DP, Chonmaitree T et al.  Pediatrics. 2005  Jun;115(6):1455-65. [Free online]

  http://pediatrics.aappublications.org/cgi/content/full/115/6/1455

 

                            OBJECTIVE: The widespread use of antibiotics for treatment of acute  otitis media (AOM) has resulted in the emergence of  multidrug-resistant pathogens that are difficult to treat. However,  it has been shown that most children with nonsevere AOM recover  without ABX. The objective of this study was to evaluate the  safety, efficacy, acceptability, and costs of a non-ABX  intervention for children with nonsevere AOM. METHODOLOGY: Children  6 months to 12 years old with AOM were screened by using a novel  AOM-severity screening index. Parents of children with nonsevere  AOM received an educational intervention, and their children were  randomized to receive either immediate antibiotics (ABX;  amoxicillin plus symptom medication) or watchful waiting (WW;  symptom medication only). The investigators, but not the parents,  were blinded to enrollment status. Primary outcomes included parent  satisfaction with AOM care, resolution of symptoms, AOM  failure/recurrence, and nasopharyngeal carriage of Streptococcus  pneumoniae strains resistant to ABX. Secondary outcomes included  medication-related adverse events, serious adverse events,  unanticipated AOM-related office and emergency department visits  and telephone calls, the child's absence from day care or school  resulting from AOM, the parent's absence from school or work  because of their child's AOM, and costs of treatment. Subjects were  defined as failing (days 0-12) or recurring (days 13-30) if they  experienced a higher AOM-severity score on reexamination. RESULTS:  A total of 223 subjects were recruited: 73% were nonwhite, 57% were  <2 years old, 47% attended day care, 82% had experienced prior  AOM, and 83% had not been fully immunized with heptavalent  pneumococcal vaccine. One hundred twelve were randomized to ABX,  and 111 were randomized to WW. Ninety-four percent of the subjects  were followed to the 30-day end point. Parent satisfaction with AOM  care was not different between the 2 treatment groups at either day  12 or 30. Compared with WW, symptom scores on days 1 to 10 resolved  faster in subjects treated with immediate ABX. At day 12, among the  immediate-ABX group, 69% of tympanic membranes and 25% of  tympanograms were normal, compared with 51% of normal tympanic  membranes and 10% of normal tympanograms in the WW group. Parents  of children in the ABX group gave their children fewer doses of  pain medication than did parents of children in the WW group.  Subjects in the ABX group experienced 16% fewer failures than  subjects in the WW group. Of the children in the WW group, 66%  completed the study without needing ABX. Immediate ABX resulted in  eradication of S pneumoniae carriage in the majority of children,  but S pneumoniae strains cultured from children in the ABX group at  day 12 were more likely to be multidrug-resistant than strains from  children in the WW group. More ABX-related adverse events were  noted in the ABX group, compared with the WW group. No serious  AOM-related adverse events were observed in either group. Office  and emergency department visits, phone calls, and days of  work/school missed were not different between groups. Prescriptions  for ABX were reduced by 73% in the WW group compared with the ABX  group. Costs of ABX averaged $47.41 per subject in the ABX group  and $11.43 in the WW group. CONCLUSIONS: Sixty-six percent of  subjects in the WW group completed the study without ABX. Parent  satisfaction was the same between groups regardless of treatment.  Compared with WW, immediate ABX treatment was associated with  decreased numbers of treatment failures and improved symptom  control but increased ABX-related adverse events and a higher  percent carriage of multidrug-resistant S pneumoniae strains in the  nasopharynx at the day-12 visit. Key factors in implementing a WW  strategy were (a) a method to classify AOM severity; (b) parent  education; (c) management of AOM symptoms; (d) access to follow-up  care; and (e) use of an effective ABX regimen, when needed. When  these caveats are observed, WW may be an acceptable alternative to  immediate ABX for some children with nonsevere AOM.

 

                            14. Age inconsistency in the American Academy of Pediatrics  guidelines for acute otitis media.

                            Meropol SB, Glick HA, Asch DA.  Pediatrics. 2008  Apr;121(4):657-68.  [free online]

  http://pediatrics.aappublications.org/cgi/content/full/121/4/657

 

                            15. Role of respiratory syncytial virus in acute otitis media:  implications for vaccine development.

                            Patel JA et al.  Vaccine. 2007 Feb 19;25(9):1683-9. [free  online]

  http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1828634&blobtype=pdf

 

                            We summarize herein the results of various virologic studies of  acute otitis media (AOM) conducted at our site over a 10-year  period. Among 566 children with AOM, respiratory syncytial virus  (RSV) was the most common virus identified in either middle ear  fluid or nasal wash; it was found in 16% of all children and 38% of  virus-positive children. Seventy-one percent of the children with  RSV were 1 year of age or older, which was significantly older than  all other viruses combined (P=0.045). RSV infection was associated  with the common bacterial pathogens causing AOM. Past efforts to  develop vaccines for RSV have emphasized prevention of lower  respiratory tract infection in infants, which is a more serious  problem but less common than AOM. Our results suggest that RSV  vaccines that work only against infection in older children may  have value in preventing AOM, the most common pediatric  disease.

 

 

                            16. Can CAM therapies help reduce antibiotic resistance?

                            MacKay D Altern Med Rev. 2003 Feb;8(1):28-42.

  http://www.thorne.com/media/cam_therapies_8-1.pdf

 

                            17. Naturopathic treatment for ear pain in children.

                            Sarrell EM et al.  Pediatrics. 2003 May;111(5 Pt  1):e574-9.  [free online

  http://pediatrics.aappublications.org/cgi/content/full/111/5/e574

 

                            18. Importance of respiratory viruses in acute otitis media.

                            Heikkinen T, Chonmaitree T. Clin Microbiol Rev. 2003 16(2):230-41.  [free online, important review]

  http://cmr.asm.org/cgi/reprint/16/2/230

 

                            Acute otitis media is usually considered a simple bacterial  infection that is treated with antibiotics. However, ample evidence  derived from studies ranging from animal experiments to extensive  clinical trials supports a crucial role for respiratory viruses in  the etiology and pathogenesis of acute otitis media. Viral  infection of the upper respiratory mucosa initiates the whole  cascade of events that finally leads to the development of acute  otitis media as a complication. The pathogenesis of acute otitis  media involves a complex interplay between viruses, bacteria, and  the host's inflammatory response. In a substantial number of  children, viruses can be found in the middle-ear fluid either alone  or together with bacteria, and recent studies indicate that at  least some viruses actively invade the middle ear. Viruses appear  to enhance the inflammatory process in the middle ear, and they may  significantly impair the resolution of otitis media. Prevention of  the predisposing viral infection by vaccination against the major  viruses would probably be the most effective way to prevent acute  otitis media. Alternatively, early treatment of the viral infection  with specific antiviral agents would also be effective in reducing  the occurrence of acute otitis media.

 

                            19. Complementary and alternative medicine for  upper-respiratory-tract infection in children

                            Carr RR, Nahata MC.  Am J Health Syst Pharm. 2006 Jan  1;63(1):33-9.

 

                            20. Management of chronic otitis media with effusion: the role of  glutathione.

                            Testa B et al.  Laryngoscope. 2001 Aug;111(8):1486-9.

 

                            BACKGROUND: The inflammatory cells documented in chronic otitis  media with effusion (OME) spontaneously release oxidants which can  induce middle ear (ME) epithelial cell damage. Glutathione (GSH), a  major extracellular antioxidant in humans, plays a central role in  antioxidant defense. PURPOSE: To evaluate the effects of GSH  treatment on chronic otitis media with effusion (OME). SUBJECTS AND  INTERVENTION: Sixty children with chronic OME were enrolled, 30 of  whom were randomly assigned to the treatment group and 30 to the  placebo group. Patients in the treatment group received 600 mg  glutathione in 4 mL saline per day subdivided into five 2-minute  administrations given by nasal aerosol every 3 or 4 waking hours  for 2 weeks. Patients in the control group received 4 mL saline per  day following the same procedure as for GSH treatment. RESULTS:  Three months after therapy improvement had occurred in 66.6% of  patients in the GSH-treated group and in 8% of the control subjects  (P <.01). CONCLUSION: On the basis of these results, GSH  treatment could be considered for the nonsurgical management of  chronic OME.

 

                            21. Management of acute otitis media in an era of increasing  antibiotic resistance.

                            Klein JO.  Int J Pediatr Otorhinolaryngol. 1999 Oct 5;49 Suppl  1:S15-7.

 

                            Development of resistance to available antimicrobial agents has  been identified in every decade since the introduction of the  sulfonamides in the 1930s. Current concerns for management of acute  otitis media (AOM) are multi-drug resistant Streptococcus  pneumoniae and beta-lactamase producing Haemophilus influenzae and  Moraxella catarrhalis. In the USA, amoxicillin remains the drug for  choice for AOM. Increasing the current dose to 80 mg/kg/day in two  doses provides increased concentrations of drug in serum and middle  ear fluid and captures additional resistant strains of S.  pneumoniae. For children who fail initial therapy with amoxicillin  an expert panel convened by the Centers for Disease Control and  Prevention suggested amoxicillin-clavulanate, cefuroxime axetil or  intramuscular ceftriaxone. To protect the therapeutic advantage of  antimicrobial agents used for AOM, it is important to promote  judicious use of antimicrobial agents and avoid uses if it is  likely that viral infections are the likely cause of the disease,  to implement programs for parent education and to increase the  accuracy of diagnosis of AOM. Conjugate polysaccharide pneumococcal  vaccines are currently in clinical trial; early results indicate  protective levels of antibody can be achieved with a three dosage  schedule beginning at 2 months of age. Finally, alternative  medicine remedies may be of value for some infectious diseases  including AOM; garlic extract is bactericidal for the major  bacterial pathogens of AOM but is heat- and acid-labile and loose  activity when cooked or taken by mouth.

 

                            22. Cross-reactions between respiratory and food allergens.

                            de Blay F, Pauli G, Bessot JC.  Allergy Proc. 1991  Sep-Oct;12(5):313-7.

 

                            Cross-reactions between inhaled and food allergens are usually  attributed to pollen hypersensitivity associated with fruit and  vegetable allergy. However, other allergens are involved in these  types of cross-reactions. In a few cases, there is a complete  similarity between the inhaled and food allergens (garlic,  crustacea proteins). More frequently, partial similarity has been  demonstrated: whole inhaled allergens are included in ingested  substances. Moreover, immunological techniques can demonstrate  common antigenic epitopes in organic substances without any  apparent relationship. This has been demonstrated by  RAST-inhibition and/or immunoblot techniques, using sera from  patients cross-sensitized to (1) pollens and fruits or vegetables  or (2) avian sera and eggs. Respiratory sensitization always seems  to precede food allergy symptoms.

 

                            23.  Efficacy and safety of echinacea in treating upper  respiratory tract infections in children: a randomized controlled  trial.

                            Taylor JA et al.  JAMA. 2003 Dec 3;290(21):2824-30. [free  online]

  http://jama.ama-assn.org/cgi/content/full/290/21/2824

 

                            CONTEXT: Echinacea is a widely used herbal remedy for treatment of  upper respiratory tract infections (URIs). However, there are few  data on the efficacy and safety of echinacea in treating URIs in  children. OBJECTIVES: To determine if Echinacea purpurea is  effective in reducing the duration and/or severity of URI symptoms  in children and to assess its safety in this population. DESIGN,  SETTING, AND PARTICIPANTS: Randomized, double-blind,  placebo-controlled trial of healthy children 2 to 11 years old  recruited from a regional practice-based network and an alternative  medical center in 4-month periods from 2000 through 2002.  INTERVENTIONS: Study patients were randomized to receive either  echinacea or placebo for up to 3 URIs over a 4-month period. Study  medication was begun at the onset of symptoms and continued  throughout the URI, for a maximum of 10 days. MAIN OUTCOME  MEASURES: Primary outcomes were duration and severity of symptoms  and adverse events recorded by parents; secondary outcomes included  peak severity of symptoms, number of days of peak severity, number  of days of fever, and a global assessment of severity of symptoms  by parents of study children. RESULTS: Data were analyzed on 707  URIs that occurred in 407 children, including 337 URIs treated with  echinacea and 370 with placebo. There were 79 children who  completed their study period without having a URI. The median  duration of URIs was 9 days (95% confidence interval, 8-10 days);  there was no difference in duration between URIs treated with  echinacea or placebo (P =.89). There was also no difference in the  overall estimate of severity of URI symptoms between the 2  treatment groups (median, 33 in both groups; P =.69). In addition,  there were no statistically significant differences between the 2  groups for peak severity of symptoms (P =.68), number of days of  peak symptoms (1.60 in the echinacea group and 1.64 in the placebo  group; P =.97), number of days of fever (0.81 in the echinacea  group vs 0.64 in the placebo group; P =.09), or parental global  assessment of severity of the URI (P =.67). Overall, there was no  difference in the rate of adverse events reported in the 2  treatment groups; however, rash occurred during 7.1% of the URIs  treated with echinacea and 2.7% of those treated with placebo (P  =.008). CONCLUSIONS: Echinacea purpurea, as dosed in this study,  was not effective in treating URI symptoms in patients 2 to 11  years old, and its use was associated with an increased risk of  rash.

 

                            24.  Echinacea purpurea for prevention of upper respiratory  tract infections in children.

                            Weber W et al. J Altern Complement Med. 2005 Dec;11(6):1021-6.

  http://www.liebertonline.com/doi/abs/10.1089/acm.2005.11.1021

 

                            OBJECTIVE: The aim of this study was to determine whether Echinacea  purpurea given to children for the treatment of acute upper  respiratory tract infection (URI) was effective in reducing the  risk of subsequent URI. DESIGN: This was

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