Researcher in Developmental & Behavioral Neuroanatomy
April 08, 2009
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
Otitis-related bacteria with antibiotic resistance (eg, 48, 51, 67)
Viruses associated with otitis media (eg, 18,51; not in order of prevalence)
Herpes simplex virus (HSV)
Respiratory syncytial virus (RSV)
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)
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.
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."
2. The growing burden of antimicrobial resistance.
Hawkey PM. J Antimicrob Chemother. 2008 Sep;62 Suppl 1:i1-9.
3. Community factors in the development of antibiotic resistance.
Larson E. Annu Rev Public Health. 2007;28:435-47.
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)
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.
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.
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]
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.
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]
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]
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]
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]
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.
17. Naturopathic treatment for ear pain in children.
Sarrell EM et al. Pediatrics. 2003 May;111(5 Pt 1):e574-9. [free online
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]
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]
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.
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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