DISEASE MANAGEMENT

The use of antibacterials in paediatric patients with acute otitis media depends on patient age and disease severity Table I. Factors affecting the development and outcome of acute otitis media (AOM) in children[1] Anatomical and physiological parameters Eustachian tubes are relatively short in children aged <2 y and in patients with cleft palate and Down’s syndrome, which results in shorter distances for bacteria to travel to produce infection Opening mechanism of eustachian tube may be impaired in some infants and young children Ciliary function of the respiratory muscosal cells may be impaired during viral infections or as a result of bacterial toxins Immunological factors Susceptibility to AOM may be associated with major immunodeficiency diseases Children prone to AOM have lower IgG2 levels relative to otherwise healthy children Children with recurrent AOM secrete low levels of nasopharyngeal inflammatory cytokines Bacteriological factors Treatment failure rates are higher in children aged <18–24 mo than in older children, which may be related to the different incidences of resistant pathogens in patients with AOM among various age groups Patient ages that correlate with the peak incidence of AOM caused by Moraxella catarrhalis, Streptococcus pneumoniae and Haemophilus influenzae are 6, 12 and 19 mo, respectively Children aged <7 mo have a much higher frequency of both penicillin-resistant S. pneumoniae and β-lactamase-producing Gramnegative organisms than those aged >48 mo S. pneumoniae is more likely than M. catarrhalis or H. influenzae to persist in the middle-ear fluid of untreated or inappropriately treated patients with AOM and to cause sequelae and complications AOM caused by S. pneumoniae is associated with higher fever and more severe tympanic membrane findings than AOM caused by M. catarrhalis or H. influenzae H. influenzae is clearly associated with recurrent AOM Outcome in AOM Spontaneous resolution of AOM is common Benefits of antibacterial treatment are greatest in children aged <2 y Rate of spontaneous resolution depends on the causative organism (e.g. spontaneous cure rates for AOM caused by S. pneumoniae, H. influenzae and M. catarrhalis are 20%, 50% and 70–80%, respectively)

Acute otitis media (AOM) is one of the most common childhood infections. The 2004 American Academy of Pediatrics and American Academy of Family Physicians guidelines on AOM suggest that treatment should be based on the age of the patient, severity of the illness and certainty of the diagnosis. Antibacterial therapy is recommended in some paediatric patients with AOM, while an observational strategy (‘watchful waiting’) without the immediate use of antibacterials is appropriate in other patients.

Very common in children One of the most common childhood infections, acute otitis media (AOM) is a leading cause of visits to physicians, antibacterial therapy and surgery in paediatric patients in many countries.[1-4] The main bacteriological agents responsible for AOM infection are Streptococcus pneumoniae, non-typable Haemophilus influenzae, Moraxella catarrhalis and group A streptococci.[1,4] Approximately 80% of AOM infections occur in children,[2] with the highest incidence observed in children aged 6–9 months.[1] By the age of 1 year, ≈75% of

children will have experienced at least one AOM episode and 17% would have had at least three episodes of AOM.

Vairous factors affect risk and outcome Several risk factors for the development of AOM have been identified, including age, male sex, ethnicity, sibling history of recurrent ear infections, winter, low socioeconomic status, smoke and air pollutants, lack of breast feeding and day-care attendance.[1] There are a variety of anatomical and other factors that affect the development and outcome of AOM in children (table I). Of note, there is evidence that pneumococcal vaccines may be useful in reducing the colonisation of S. pneumoniae, leading to a drop in antibacterial resistance and modest reduction in AOM incidence.[2,5] However, an increase in AOM caused by nonvaccine serotypes and H. influenzae has been reported.[2]

Symptoms have rapid onset Typical symptoms of AOM include middle-ear effusion along with a rapid onset of persistent severe ear pain, fever, nausea, vomiting, conductive hearing loss and, in 1172-0360/08/0001-0013/$48.00 © 2008 Adis Data Information BV. All rights reserved.

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young patients, diarrhoea.[2] There is often a degree of uncertainty with regard to the diagnosis of AOM, especially in infants and young children. According to the 2004 evidence-based American Academy of Pediatrics and American Academy of Family Physicians (AAP/AAFP) clinical practice guidelines on the treatment of AOM,[5] a diagnosis of AOM is certain only if all of the following criteria are met: • rapid onset of symptoms; • presence of middle-ear effusion (e.g. bulging of the tympanic membrane, limited or absent mobility of the tympanic membrane, air-fluid level behind the tympanic membrane or otorrhoea); • signs and symptoms of middle-ear inflammation (e.g. distinct erythema of the tympanic membrane or discomfort clearly referable to the ear that results in interference with or precluded normal activity or sleep).

Important to treat pain As AOM is commonly associated with pain, pain should be assessed and appropriate treatment recommended.[5] Paracetamol (acetaminophen) and ibuprofen offer effective analgesia for mild to moderate pain. For severe pain, narcotic analgesia (e.g. codeine) may be required. Topical agents containing benzocaine may also be considered as adjunctive therapy.[5]

Antibacterials are the standard of care In many countries, the standard of care for the treatment of AOM is antibacterials.[1] The primary goal of AOM treatment is to eliminate the causative organism from middle-ear fluid, thus improving clinical outcomes and decreasing the number of AOM recurrences.[1,6] Although the high rate of spontaneous recovery means that only 20–30% of all cases of AOM require antibacterial therapy, most patients receive antibacterial therapy because of the difficulty in identifying the small proportion of patients who would benefit from such a treatment.[1,2] If pathogens are not eradicated by appropriate antibacterial therapy, the disease may be prolonged resulting in such complications as hearing loss, behavioural problems, and poor linguistic and school performance.[4,7]

Identify the best agent The evolution of resistant-pathogens has forced therapists to reconsider the available drug choices for patients with AOM.[1,3] Results of studies employing the ‘in vivo sensitivity test’ have shown that:[1] • high-dose amoxicillin is the best oral β-lactam for the eradication of penicillin-resistant S. pneumoniae; • macrolides (including azithromycin and clarithromycin) are not effective against H. influenzae and macrolideresistant S. pneumoniae; Drugs Ther Perspect 2008; Vol. 24, No. 1

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•

one dose of intramuscular ceftriaxone is effective against H. influenzae and pencillin-susceptible S. pneumoniae, but three doses are necessary to be effective against pencillin-nonsusceptible S. pneumoniae; cotrimoxazole (trimethoprim/sulfamethoxazole) is no longer a valuable option in the empirical treatment of AOM as it lacks efficacy against H. influenzae and S. pneumoniae.

Amoxicillin appropriate for many The recommended antibacterials for the treatment of AOM in paediatric patients with or without penicillin allergy are provided in table II. High-dose amoxicillin or amoxicillin/clavulanic acid (depending on disease severity) are the drugs of choice for empirical first-line treatment of AOM in patients without penicillin allergy (table II). The standard duration of antibacterial therapy with amoxicillin is 10 days.[1,3,5] A shorter duration of therapy has the potential advantages of lower costs, reductions in adverse events, better patient adherence and decreased chances of development of resistant pathogens.[4] However, the major drawback is possible loss of efficacy,[8] which is an important factor to be considered when looking at reducing treatment period. Treatment for 5–7 days is recommended only in patients aged >6 years with mild or moderate disease.[5]

Antibacterials or watchful waiting? The AAP/AAFP guidelines for the treatment of AOM in paediatric patients are presented in the Patient care guidelines.[5] Treatment is based on the age of the patient, severity of the illness and certainty of the diagnosis. Antibacterial therapy is recommended in some patient groups and an observational strategy (‘watchful waiting’) without the immediate use of antibacterials is appropriate in other patients.

Some patients require antibacterials To summarize the guidelines,[5] antibacterials should be prescribed to patients with AOM aged: • <6 months (regardless of the certainty of diagnosis or severity of the disease); • 6 months to 2 years if the disease is certain (regardless of the severity) or severe (regardless of certainty of the diagnosis); • >2 years only if illness is severe and the diagnosis is certain. Watch other patients… Watchful waiting for 48–72 hours without the use of antibacterials is an option in patients with AOM aged:[5] • ≥6 months to 2 years with both non-severe illness (mild otalgia or fever <39°C) and uncertain diagnosis;

Table II. Antibacterial options in the treatment of acute otitis media in paediatric patients (pts) aged 2 mo to 12 y based on the 2004 American Academy of Pediatrics and American Academy of Family Physicians guidelines[5] Pt group

First-line therapya non-severe

Without penicillin allergy

illnessc

Amoxicillin 80–90 mg/kg/d

Second-line therapyb severe

illnessd

Amoxicillin 90 mg/kg/d + clavulanic acid 6.4 mg/kg/d

non-severe illnessc

severe illnessd

Amoxicillin 90 mg/kg/d + clavulanic acid 6.4 mg/kg/d

Ceftriaxone 50 mg/kg/d ×3d

With penicillin allergy Type I hypersensitivity

Azithromycin 10 mg/kg/d × Ceftriaxone 50 mg/kg/d 1 d, then 5 mg/kg/d × 4 d × 1 or 3 d Clarithromycin 15 mg/kg/d

Clindamycin 15 mg/kg/d

Tympanocentesis Clindamycin 15 mg/kg/d

Non-type I

Cefdinir 14 mg/kg/d Cefuroxime 30 mg/kg/d Cefpodoxime 10 mg/kg/d

Ceftriaxone 50 mg/kg/d ×3d

Tympanocentesis Clindamycin 15 mg/kg/d

Ceftriaxone 50 mg/kg/d × 1 or 3 d

a At diagnosis in pts being treated initially with antibacterial agents and in pts with clinically defined treatment failure at 48–72 h after initial management with observation option. b In pts with clinically defined treatment failure at 48–72 h after initial management with antibacterial agents. c Mild otalgia and temperature <39°C in the past 24 h. d Moderate to severe otalgia and temperature ≥39°C.

•

≥2 years with non-severe illness (regardless of certainty of diagnosis).

…but only if follow-up is ensured Watchful waiting is an option only if follow-up is ensured and antibacterial therapy will be initiated if symptoms persist or worsen.[5] The caregiver should be informed of the degree of diagnostic certainty and the clinician should consider the caregiver’s preference for treatment. Although antibacterial therapy at the initial visit may shorten symptoms by 1 day in 5–14% of children, watchful waiting avoids the adverse effects associated with some therapy and helps prevent the development of antibacterial resistance.[3,5] Option is not without controversy

Of note, the recommendation for watchful waiting is controversial, as some opinion leaders are not convinced that the available data support this strategy.[9] However, available data indicate that early antibacterial therapy is particularly beneficial in patients with severe disease and in those aged <2 years (table I).[1] As the guidelines recommend that watchful waiting should be considered only in children with minimal symptoms or in those aged ≥2 years, the recommendations are consistent with the current literature.[1]

References 1. Leibovitz E. Acute otitis media in children aged less than 2 years: drug treatment issues. Pediatr Drugs 2006; 8 (6): 337-46 2. Leibovitz E. Acute otitis media in pediatric medicine: current issues in epidemiology, diagnosis, and management. Pediatr Drugs 2003; 5 Suppl. 1: 1-12 3. Johnson CE, Belman S. The role of antibacterial therapy of acute otitis media in promoting drug resistance. Paediatric Drug 2001; 3 (9): 639-47 4. Ovetchkine P, Cohen R. Shortened course of antibacterial therapy for acute otitis media. Pediatr Drugs 2003; 5 (2): 133-40 5. American Academy of Pediatrics Subcommittee on Management of Acute Otitis Media. Diagnosis and management of acute otitis media. Pediatrics 2004; 113 (5): 1451-65 6. Dowell SF, Marcy MS, Phillips WR, et al. Otitis media: principles of judicious use of antimicrobial agents. Pediatrics 1998; 101: 165-71 7. Teele DW, Klein JO, Chase C, et al. Otitis media in infancy and intellectual ability, school achievement, speech, and language at age 7 years. J Infect Dis 1990; 162 (3): 546-9 8. Paradise JL. Short course antimicrobial treatment for acute otitis media: not best for infants and young children. JAMA 1997; 278 (20): 1640-2 9. Wald E. Acute otitis media: more trouble with the evidence. Pediatr Infect Dis J 2003; 22 (2): 103-4

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Child aged 2 mo to 12 y presents with AOM Diagnosis is certain if all of the following are present: x Rapid onset of signs and symptoms x Signs of middle-ear effusion x Signs and symptoms of middle-ear inflammation

Determine severity of illness based on symptoms x Severe illness: moderate to severe otalgia and temperature t39˚C x Non-severe illness: mild otalgia and temperature <39˚C in the past 24 h

Age t6 mo to 2 y

Age <6 mo

Certain diagnosis

Uncertain diagnosis

Certain diagnosis

Non-severe illness

Amoxicillin

Uncertain diagnosis

Severe illness

Initiate antibacterial therapy

No

Severe illness

Age t2 y

Uncertain diagnosis

Non-severe illness

Watchful waiting an appropriate option (i.e. follow-up ensured)?

Amoxicillin/ clavulanic acid

Yes

Certain diagnosis

Non-severe illness

Severe illness

Initiate antibacterial therapy (see left-hand side of algorithm)

Yes Symptoms persist or worsen?

No Yes Patient follow-up as appropriate

Response to treatment at 48–72 h?

No Diagnosis of AOM confirmed after reassessment?

No Assess for other causes of illness and manage appropriately

Yes Change antibacterial therapy

Non-severe illness

Severe illness

Amoxicillin/clavulanic acid

Parenteral ceftriaxone

¤Adis Data Information BV 2008

Suggested treatment of acute otitis media (AOM) in children without penicillin allergy[5]

Drugs Ther Perspect 2008; Vol. 24, No. 1