Selecting antibiotics for acute otitis media - is it important?

Wai-Kin Lee 李偉健, Betty W Y Young 楊允賢

HK Pract 2005;27:380-382

Summary

A 28-month old boy was hospitalised because of meningitis caused by penicillin non-susceptible Streptococcus pneumoniae and was later found to suffer from a unilateral profound hearing deficit. In the two to three weeks before his hospitalisation, he had received at least five different courses of antimicrobials for otitis media. This is different to the recommendation made by the American Academy of Pediatrics. It is necessary to realise and remember the importance in the selection of an optimal antibiotic with an optimal dosage to treat certain community-acquired respiratory tract infections.

摘要

一個28個月大的男孩，因抗青黴素的肺炎鏈球菌 引發的腦膜炎入院， 隨後發現患兒有單側的嚴重聽力障礙。入院前 2-3周， 患兒曾因中耳炎而接受了5個以上不同療程的抗菌劑治療。 這有不符合美國兒科學會 所推薦的治療原則。認識到選擇一種最佳抗生素， 並以最佳劑量來治療社區的呼吸道感染，是非常重要的。

Introduction

Acute otitis media (AOM) is one of the most common childhood respiratory tract infections. In one review, it was shown that about 17% to 30% of children younger than one year old had two or more episodes of this infection and 50% of children younger than three years old had at least one episode.¹ Streptococcus pneumoniae was isolated from the middle-ear fluid in about 25% to 50% of the affected children.² There has been a global concern about antibiotic resistant strains of this organism. In this paper, we report a case of meningitis caused by penicillin intermediate S. pneumoniae in a child who had been treated with multiple antimicrobials for otitis media before hospitalisation.

Case report

The patient was a 28-month old boy, who was admitted to our hospital in December 2003 because of fever and irritability of two days duration. He had been unwell for three weeks prior to his admission. He initially presented to a private paediatrician after 2 days of fever (highest 103^oF). He had no obvious respiratory symptoms other than the fever. He was told that he had acute otitis media in the right ear and was given an antibiotic for treatment. Fever persisted after one week of the antibiotic despite he remained active and playful and had good appetite. Different courses of oral antibiotics followed which were given sequentially, namely cefaclor, azithromycin and then ceftributen. In the second week of the illness, he was managed by a private otorhinolaryngologist, who prescribed a 1 week course of amoxicillin-clavulanate. The daily dose of amoxicillin was 20mg/kg. He appeared to have shown improvement in the third week with no further recordable temperature rise. However, towards the end of the third week, the child appeared clinically to be less active, became more irritable with vomiting and had a return of fever. He was then commenced on intravenous cloxacillin and cefuroxime in a private hospital. The child was subsequently admitted into our hospital because of further deterioration in his clinical condition.

The patient was the first child of the family. He had a normal spontaneous full term delivery. Birth weight was 3.27kg with no perinatal complication. He had no past history of any severe infection. He had received the routine immunisations as recommended in Hong Kong as well as a full course of Haemophilus influenzae type B vaccines. However, he did not receive a pneumococcal vaccination. His development was described to be normal except for a mild expressive speech delay. His parents and 13-month old sister were all healthy. The parents were not consanguineous.

Physical examination at admission showed that his body temperature was 37.8^oC. He was drowsy but could open his eyes spontaneously and obey verbal command. He had poor peripheral circulation, a tachycardia of 167 heart beats/min and BP of 112/77 mmHg. His respiratory rate was 20/min and SaO₂ was 100% in room air. Pupils were equal in size measuring 3mm and reactive to light. Fundoscopy examination was normal. He had neck rigidity and brisk deep tendon reflexes of all four limbs. Plantar reflexes were down-going. The right tympanic membrane was congested and bulging whereas the left side was normal. There was no periauricular swelling or tenderness.

Lumbar puncture was performed after initial stabilisation with oxygen and intravenous fluid therapy. The opening pressure was elevated (46cmH₂O). The cerebrospinal fluid (CSF) was clear to the naked eye. The microscopy showed a white cell count of 42/mm³ (99% polymorphs) and gram positive cocci was present. CSF protein was elevated (3.18g/L) and CSF glucose was markedly decreased (0.2mmol/L) (blood glucose was 6.8mmol/L). Rapid antigen test was positive for S. pneumoniae. Cefotaxime was commenced. His cardiovascular status was soon stabilised after admission. His alertness also improved, with the temperature rise subsiding over the following several days. A right myringotomy was performed the next day. Cultures of the right middle ear fluid (after commencement of antibiotic) and blood were negative. The CSF culture was however, confirmed to be positive for S. pneumoniae with the minimal inhibitory concentration (MIC) for penicillin of 0.3mg/L. The organism was reported to be cefotaxime sensitive.

During his hospital stay, he had one episode of convulsion lasting for about one minute. Phenytoin prophylaxis was therefore started, with good effect.

He, however, despite his improvements had a recurrent fever afterwards. The microscopy, biochemistry and culture of his CSF were all back to normal. The fever was subsequently shown to be associated with a diarrhoea episode. The stool specimen taken was positive for rotavirus.

Upon discharge after 4 weeks in hospital, he was active and playful again and his oral feeding was normal. However, his hearing was found to be profoundly impaired on the right side (sensorineural) as shown by audiometry and brainstem auditory evoked potential. He was followed up in the hospital outpatient clinic where he still showed some speech delay but no other neurological deficit.

Discussion

The Alexander Project was an international antimicrobial susceptibility surveillance study of bacterial pathogens causing community-acquired lower respiratory tract infections. S. pneumoniae was classified according to the susceptibility to penicillin (susceptible, MIC < 0.06mg/L; intermediate, MIC < 0.12-1mg/L; and resistant, MIC > 2mg/L).³ The Alexander Project demonstrated a high prevalence of penicillin non-susceptible S. pneumoniae in many parts of the world (worldwide average: 31.7%) including Hong Kong (73.6%). The percentage of this pathogen being resistant to other antimicrobials such as cefaclor, cefuroxime, erythromycin, clarithromycin and azithromycin was also high in Hong Kong: 85.5%, 69.9%, 80.3%, 80.3% and 80.8% respectively.⁴

In a review of pharmacokinetics and pharmacodynamics of antimicrobials in otitis media, Craig WA and Andes D (1996) illustrated that the bacteriological cure was related to the percentage of time that the serum levels of the antimicrobials exceed the MIC₉₀ (time above MIC). Bacterial killing occurred when the time above MIC was 40-50% of the dosing interval. Maximum killing was observed when the time above MIC was more than 60-70%. For penicillin-intermediate S. pneumoniae, the times above MIC were for amoxicillin (40mg/kg/day three times a day) 59-83%, for cefaclor (40mg/kg/day three times a day) 0% and cefuroxime (250mg twice daily) 33-53%.

For penicillin-resistant S. pneumoniae, the times above MIC for amoxicillin, cefaclor and cefuroxime in the same dosage regime were 46-59%, 0% and 0-23% respectively.⁵ It can be concluded that amoxicillin in appropriate doses were possibly more effective than the other two antimicrobials in the eradication of S. pneumoniae in otitis media.

There are many medications that are proven to be clinically effective for AOM. The American Academy of Pediatrics recommends amoxicillin as the first-line therapy, based on its general effectiveness when used in sufficient doses as well as for its safety, low cost, acceptable taste and narrow microbiologic spectrum. When amoxicillin was used, the dose of 80-90mg/kg/day was recommended, based on the extrapolation from microbiologic studies and expert opinion. The amoxicillin-clavulanate combination was suggested for patients who have severe illness and in those for whom additional coverage for b-lactamase-positive Haemophilus influenzae and Moraxella catarrhalis is desired.²

The cause of meningitis and hearing loss in our patient with treated AOM was probably multiple but uncertain. Hearing loss is one of the known common complications and sequelae of otitis media and can be conductive, sensorineural or both. Permanent sensorineural hearing loss, as a result of otitis media, is most likely the result of the spread of infection or products of inflammation. Intracranial complications such as meningitis is rare in the antibiotic era although the exact incidence of meningitis after an event of acute otitis media is unknown.⁶ Inflammation of the cochlea and the auditory nerve could cause reversible or permanent deafness in 5-30% of children with bacterial meningitis.⁷

It is uncertain whether there are some antibiotics that have been proven to be superior to others in the prevention of complications such as meningitis due to AOM or in the prevention of complications such as hearing loss due to meningitis. Data suggested that there is a possible benefit for the use of dexamethasone in meningitis due to S. pneumoniae. It is suggested that this "should be considered" for meningitis due to S. pneumoniae in infants and children six weeks of age and older but not for patients with "partially treated" meningitis.⁸

There is still another concern and that is resistance of S. pneumoniae to third generation cephalosporins.⁴ Therapy with third generation cephalosporin alone for pneumococcal meningitis may not be effective. It is advised to add vancomycin to the third generation cephalosporin when S. pneumoniae is suspected on the basis that CSF smears taken in some regions show there is high prevalence of the pathogen being resistant both to penicillin and cephalosporins.⁷

Conclusions

Selecting an optimal antibiotic with optimal dosage is important in treating common infections such as acute otitis media in children. In view of the high prevalence of penicillin non-susceptible S. pneumoniae in Hong Kong, an appropriate local recommendation is useful for primary care physicians as well as other specialists, who would come to manage children with otitis media, other respiratory tract infections and/or meningitis.

Key messages

1. S. pneumoniae is one of the common bacterial aetiologies causing acute otitis media in children.
2. In Hong Kong, the prevalence of penicillin non-suspectible S. pneumoniae is high.
3. The American Academy of Pediatrics recommended amoxicillin 80-90mg/kg/day with or without its combination with clavulanate as first-line therapy for acute otitis media.