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Clinical course, complications and sequelae of acute otitis media

2000; Lippincott Williams & Wilkins; Volume: 19; Issue: Supplement Linguagem: Inglês

10.1097/00006454-200005001-00007

1532-0987

Charles D. Bluestone,

Respiratory and Cough-Related Research

With the introduction of a new vaccine to prevent pneumococcal infections in infants and children, it is appropriate to review our state of knowledge of the clinical course, complications and sequelae of acute otitis media (AOM) caused by this organism; the pneumococcus is the most common cause of AOM. 1 The following is based not only on our current knowledge of these conditions but also in part on the consensus of experts in the field. First I describe the clinical course of AOM in which the child has been treated with an antimicrobial agent. Thus the clinical course will not truly be the natural history of the disease. Even though today some clinicians suggest withholding antibiotics or practicing selectivity in prescribing these agents in some or even in all children who have AOM, the current recommendation from official organizations is to prescribe a course of an antimicrobial agent that has been demonstrated to be safe and effective. These recommendations are accompanied by the caveat that an acute middle ear infection be diagnosed correctly and distinguished from otitis media with effusion (OME). 2 The usual recommendation is a 10-day course of most of the approved oral antibiotics; amoxicillin remains the initial agent of choice. 3 After detailing the clinical course, I then describe the suppurative complications and sequelae of otitis media (OM) that occur within the temporal bone and intracranial cavity. CLINICAL COURSE After the onset of AOM there are several possible outcomes after the initiation of antimicrobial therapy: (1) relief of the signs and symptoms of the acute infection, such as otalgia and fever, and resolution of the middle ear effusion (MEE) at or near the end of the course of treatment; (2) relief of the signs and symptoms, but persistence of MEE for weeks or months after the treatment ends; (3) persistence or recurrence of the signs and symptoms during the course of antibiotic therapy, which is termed a treatment failure or symptomatic failure; (4) development of a suppurative complication; (5) occurrence of a spontaneous perforation of the tympanic membrane resulting in purulent otorrhea; (6) relief of the signs and symptoms of the acute infection during the course of treatment, but with a relapse within 3 to 4 weeks after the onset of the attack; or (7) symptomatic relief of the acute infection, but a recurrent episode of AOM after the onset of the initial episode; a persistent MEE may or may not be present. A child may have one or more of these possible outcomes, such as a treatment failure followed by a spontaneous perforation and a suppurative complication, e.g. acute mastoiditis with osteitis. Figure 1 shows the possible outcomes after the onset of an attack of AOM. Fig. 1: Possible outcomes after the onset of an attack of acute otitis media. More than one of these outcomes can occur concurrently.Symptom relief vs. treatment failure. After administration of antimicrobial therapy for AOM, the child's symptoms of acute infection (e.g. otalgia, fever) should be relieved within a short period of time; if not it is considered a treatment failure (symptomatic failure). However, the percentage of patients for whom treatments fail is related to several factors, including the duration of time after therapy that results in symptomatic relief. Clinical trials that have evaluated antibiotic vs. placebo have provided important insight into these appropriate end points. As shown by the large clinical trial that evaluated amoxicillin compared with placebo conducted by Kaleida et al., 4 symptom relief within the first 12 to 24 h after the antibiotic treatment for AOM is related to the severity of the episode and the age of the child. The episodes of AOM were determined to be either severe or nonsevere, based on a scoring system that included the severity of otalgia and degree of fever. Twelve hours after initiating amoxicillin to treat severe AOM, 12.1% of infants younger than 2 years did not have relief of symptoms and were treatment failures, whereas only 4.1% of children 2 years and older were treatment failures. When the episodes were considered nonsevere, only 6.5% of the infants failed to have relief of their symptoms 24 h after amoxicillin therapy, compared with 0.5% of older children. Rosenfeld, 5 in his recent review of 7 trials that compared antibiotic (i.e. penicillin, amoxicillin or amoxicillin/clavulanate) with placebo, reported that 38% of subjects who had AOM failed to have relief of symptoms at 24 h, 15.4% at 2 to 3 days, 10.5% at 4 to 7 days and 8.6% at 7 to 14 days. Despite these variations in the rates of treatment failures related to the time after the onset of the illness, the current recommendations call treatment in a child whose symptoms persist unimproved 48 to 72 h after initiating antibiotic therapy a failure. In 1 of our trials in Pittsburgh in which 113 children were initially treated with amoxicillin, 5.7% failed to improve at the 48-h end point, and their treatment was considered a failure. 6 Spontaneous perforation. In a study by Mygind et al. 7 of 72 infants and children treated with penicillin for AOM, 7 (9.7%) developed a spontaneous perforation within 7 days of the onset. However, there were no acute perforations in the trial conducted by Burke et al. 8 in 118 infants and children treated with antibiotics; the diagnosis of AOM in these children was not confirmed. Nevertheless spontaneous perforation occurs and is relatively high in special populations, such as in Native Americans, in Australian Aborigines and in developing countries. 9 Early recurrence vs. relapse. After antibiotic treatment is terminated for an episode of AOM, the patient may develop an early recurrence with a new bacterium or have a relapse due to the same organism within 21 to 30 days after the onset of the attack. To clarify whether these early episodes are recurrent attacks of new infection or a relapse, Carlin et al. 10 evaluated 36 (35%) of 103 infants and children who had a recurrent infection within 1 month of antibiotic treatment for AOM. Initially a tympanocentesis was performed. Of the 36 patients 29 had a repeat tympanocentesis at the time of the early recurrence, and of these 29 patients 13 (44.8%) had no pathogen recovered, 12 (41.4%) had a new infection and only 4 (13.8%) had a relapse with the same organism. Capsular serotyping of pneumococcus in the 6 patients who developed a recurrence caused by this bacterium identified 2 patients with reinfection and 1 with relapse. Thus early recurrence was more commonly caused by a new organism than reinfection with the initial bacterium. Recurrence Our trials that assessed the recurrence rates of AOM after antimicrobial treatment consistently showed that ∼50% of the subjects developed 1 or more new episodes during the next 3 months, but the rate varied related to the age of the child and the degree of severity of the initial episode. In the trial by Mandel et al. 11 in which 10-day amoxicillin therapy was initially administered to 86 infants and children, 54.7% had no recurrence, 34.9% had 1 recurrence and 10.5% had 2 recurrences during the following 90 days after the onset of the episode. This rate occurred in patients with and without MEE after the antibiotic treatment. In the study by Kaleida et al., 12 56% of 80 subjects who were effusion-free and 47% of 47 patients who had effusion at the end of a 10-day course of antibiotics developed a recurrence. Slightly less than one-half of the episodes occurred within 30 days after the onset of the MEE. This trial also showed that the recurrence rate statistically decreased with the advancing age of the child: in subjects below age 2 years, the rate was 55%, compared with 23% in children 2 to 5 years old and only 11% in subjects 6 years and older. Also the recurrence rate from 2 to 6 weeks after the attack is higher when the initial episode is severe than with those that are nonsevere. In the trial by Kaleida et al., 4 the rate was 40.9% in subjects whose initial attack was severe as compared with 27.9% when the episode was nonsevere. In infants and children followed for 1 year after their initial attack of AOM, the rate of recurrence of a new episode is approximately 3, as shown in a trial conducted by Mandel et al. 6 that involved 214 subjects. Similarly this rate is related to the age of the child as shown in the trial conducted by Kaleida et al. 4 in which the rate over 1 year was 3 in subjects <2 years old after both severe and nonsevere episodes, whereas the rate was 1.9 for severe and 1.5 for nonsevere episodes in children 2 years old and older. As shown by a study conducted by Casselbrant et al. 13, in which 198 newborns were prospectively followed from birth to their second birthday, 12.3% developed 3 or more episodes of AOM. Persistent MEE After antibiotic treatment for an episode of AOM, 30 to 70% of infants and children will have a persistent MEE 10 to 14 days later that can last for weeks to months. 4, 5, 11, 12, 14 Without further treatment only 6 to 26% will have an effusion remaining in the middle ear 3 months after the onset of the acute episode. 5, 11, 12, 14, 15Figure 2 shows the progressive resolution of MEE after 10 days of amoxicillin therapy in 93 infants and children in the trial conducted by Mandel et al. 11Fig. 2: Time until clearance of middle ear effusion (MEF) in 93 infants and children initially treated with amoxicillin for acute otitis media. 11Tympanostomy tube placement Two studies were conducted in Pittsburgh in which infants were followed prospectively from birth, or soon after, to their second birthday to determine the incidence of OM. In 1 study Casselbrant et al. 13 reported that of 198 infants, 12 (6%) had 1 operation for myringotomy and tympanostomy tube insertion for chronic OME during the 2 years; 4 also had recurrent AOM. In the other study Paradise et al. 16 followed 2253 infants and found that 1.8% and 4.2% had tympanostomy tube placement during the first and second years of life, respectively. However, because there is currently no consensus on the indications for tympanostomy tube insertion, the rate varies considerably from community to community. Even though controversy persists over the precise indications for this operation, there are current guidelines for infants and young children who develop chronic OME. 17 Despite some weaknesses with these guidelines, they have considerable strengths. 18 INTRATEMPORAL (EXTRACRANIAL) COMPLICATIONS AND SEQUELAE OF OM AND RELATED CONDITIONS During the course of AOM, a complication can develop or a sequela may follow. 19 Some of these conditions, however, may be categorized as both a complication and a sequela, such as hearing loss. Also one complication can cause another one; for example acute mastoid osteitis may cause petrositis or spread to the intracranial cavity. Table 1 shows the terminology and classification of the complications and sequelae of OM. Table 1: Classification of complications and sequelae of otitis media and related conditionsEpidemiology Despite the widespread use of antimicrobial agents to treat AOM for more than 50 years, complications and sequelae of OM are still prevalent and remain potentially life-threatening. Of the suppurative complications of AOM that occur within the temporal bone, mastoiditis and facial paralysis are the most common. In the preantibiotic era the rate of mastoiditis was between 5 and 10% of patients who developed AOM. 20 Following the advent of the administration of antibiotics for AOM in the industrialized countries of the world, this rate has declined and, in turn, the death rate caused by these complications has dramatically decreased. The mortality rates (per 100 000 persons) from OM and mastoiditis between 1936 and 1976 fell from ∼2 to <0.01. 21 One study reported that in 1938 the rate of mastoidectomy as a complication of AOM was 20%, whereas 10 years after the introduction of sulfonamides and penicillin the frequency had fallen to 2.5%, with an almost 90% reduction in the mortality rate during that period. 22 An early study from Finland revealed that of 28 patients who had an intratemporal complication of AOM between 1956 and 1971, all had an acute mastoiditis; 1 patient also developed a facial paralysis and another also had labyrinthitis. 23 In our recent review of 100 infants and children treated for a complication of OM that involved the temporal bone at the Children's Hospital of Pittsburgh between 1980 and 1995, 72% had acute mastoiditis, 22% had an acute onset of a facial paralysis, 5% had acute labyrinthitis and 4% had acute petrositis (Table 2). 24Table 2: Intratemporal complications in 100 infants and children at the Children's Hospital of Pittsburgh, 1980 to 1995 24However, in developing nations, these complications persist at relatively high rates because of the lack of adequate primary care. From studies in developing countries the rate in some communities was as high as 33% for perforation of the tympanic membrane, 6% for otorrhea and 5% for mastoiditis. 25 During one 8-year period (1983 to 1990) a medical center in northern Thailand treated 77 patients with an intratemporal complication of OM: 45% had a facial paralysis; 42% had an acute mastoiditis; and 26% had labyrinthitis (several patients had more than 1 complication). 26 Complications Complications of AOM that occur in the temporal bone are perforation of the tympanic membrane, mastoiditis, facial paralysis, labyrinthitis and external otitis. Because hearing loss occurs concurrently in most cases of AOM, it can be considered a complication, but it can also be considered a sequela to such conditions as adhesive OM or fixation or disarticulation of the ossicles. Disturbances in vestibular, balance and motor functions can also be a complication of OM, because the presence of an MEE can affect these functions. Also there is now evidence that balance dysfunction may be a sequela of OM, even when MEE is absent. Perforation of the tympanic membrane. After hearing loss an acute perforation of the tympanic membrane is the most common complication of AOM. However, as shown in Figure 1, a perforation can occur as part of the clinical course and was more frequently encountered before the widespread use of antimicrobial therapy. When an attack of AOM is complicated by a perforation (usually accompanied by otorrhea), one of four outcomes is possible: (1) resolution of the AOM and healing of the tympanic membrane defect; (2) resolution of the AOM, but the perforation becomes chronic; (3) the perforation and OM persist into the chronic stage, that is, chronic suppurative OM; or (4) a suppurative complication of OM develops. 9 A chronic perforation occurs when an acute perforation of the tympanic membrane fails to heal after 3 months or longer. It may be present with or without OM; the former condition may or may not be associated with otorrhea. A chronic perforation usually does not heal spontaneously. The middle ear is susceptible to AOM, however, and subsequently to chronic suppurative OM when a chronic perforation is present. This can result from contamination of the middle ear through the external auditory canal or by reflux of nasopharyngeal secretions into the middle ear. 27 The initial bacteria causing the AOM and otorrhea are usually the same as those that cause AOM when the tympanic membrane is intact. In a study of 178 infants and children who developed AOM and otorrhea through a tympanostomy tube, Streptococcus pneumoniae was isolated in 21%, Pseudomonas aeruginosa in 20%, Haemophilus influenzae in 16% and Moraxella catarrhalis in 9%. 28 Even though this study involved children who had tympanostomy tubes in place, these are most likely the same type of bacteria, with the exception of Pseudomonas, that cause AOM when a perforation of the tympanic membrane is present;Pseudomonas most likely enters the middle ear through a nonintact tympanic membrane. A tympanoplasty to repair a tympanic membrane perforation is usually recommended, and this operation is the most common major surgical procedure performed on children's ears worldwide; tympanostomy tube placement is the most common minor surgical procedure. Chronic suppurative OM usually follows an episode of AOM in which an acute spontaneous perforation with otorrhea occurred that progressed to the chronic stage. It can also be associated with a cholesteatoma. Mastoiditis is invariably a part of the pathologic process. Even though Pseudomonas is the most commonly isolated organism, 1 study of 51 infants and children (80 ears) revealed that S. pneumoniae was isolated in 9% of ears;P. aeruginosa was isolated in 70%. 29 Mastoiditis. Mastoiditis can be either acute, subacute or chronic. Acute mastoiditis has the following stages: acute mastoiditis without periosteitis/osteitis; acute mastoiditis with periosteitis; and acute mastoid osteitis with or without subperiosteal abscess. 27 Subacute mastoiditis has also been termed masked mastoiditis because the mastoid infection may not be obvious, but it may be the cause of another suppurative complication within the temporal bone, e.g. labyrinthitis, or an intracranial complication. Chronic mastoiditis is part of the pathology of chronic suppurative OM but can also be present without a perforation of the tympanic membrane. Acute infection from the mastoid can spread into the petrosal cells of the mastoid apex, which is called acute petrositis. Acute mastoiditis without periosteitis/osteitis is the natural extension and part of the pathologic process of acute middle ear infection. Periosteitis and osteitis are absent. If a computed tomographic (CT) scan would be obtained on all patients who have an episode of AOM, most, if not all, would have evidence of mastoid involvement, but this stage of acute mastoiditis is not a complication of OM. It can nevertheless be misinterpreted as a complication of OM, especially when CT scans are obtained for other reasons during an episode of OM, e.g. after head trauma. Specific signs or symptoms of mastoid infection such as protrusion of the pinna, postauricular swelling, tenderness, otalgia or erythema are not present in this most common type of mastoiditis. This stage of mastoiditis can either resolve (most common) or progress into a true complication of OM, i.e. acute mastoiditis with periosteitis, which can progress into acute mastoid osteitis. Acute mastoiditis with periosteitis can develop when infection within the mastoid spreads to the periosteum covering the mastoid process. The route of infection from the mastoid cells to the periosteum is by venous channels, usually the mastoid emissary vein. Acute mastoiditis with periosteitis is characterized by erythema, mild swelling and tenderness in the postauricular area. The pinna may or may not be displaced inferiorly and anteriorly, with loss of the postauricular crease; infrequently there is sagging of the posterior external auditory canal. 24 The erythema of the postauricular area in this stage of acute mastoiditis should not be confused with the presence of a subperiosteal abscess, which is a manifestation of acute mastoid osteitis. At the Children's Hospital of Pittsburgh between 1980 and 1995, 72 infants and children developed acute mastoiditis, but only 18 (25%) required a mastoidectomy; the remaining 54 (75%) did not. 24 The children who received a mastoidectomy in this retrospective chart review most likely had osteitis, whereas those who did not receive surgery had only periosteitis. Acute mastoid osteitis has also been termed acute coalescent mastoiditis , but the pathologic process is osteitis; a subperiosteal abscess may or may not be present (Fig. 3). When infection within the mastoid gas cell system progresses, rarefying osteitis can cause destruction of the bony trabeculae that separate the mastoid cells. The postauricular area is usually involved but mastoid osteitis can occur without evidence of postauricular involvement. The signs and symptoms are similar to those described above for acute mastoiditis with periosteitis, but a subperiosteal abscess is usually present when acute mastoid osteitis is present. In the absence of a subperiosteal abscess, a CT scan is frequently helpful in diagnosing osteitis of the mastoid. Table 3 shows the bacteriologic findings from 65 infants and children who developed acute mastoiditis with periosteitis or acute mastoid osteitis in the Pittsburgh study. S. pneumoniae was the most common organism isolated. 24Fig. 3: CT scan of a 7-week-old male infant who developed acute otitis media in the right ear that progressed into an acute mastoiditis with osteitis and subperiosteal abscess (arrow). Cortical mastoidectomy and tympanostomy tube placement was performed, at which time cultures from the middle ear and mastoid revealed S. pneumoniae, susceptible to penicillin. The child had an uneventful recovery after the surgery and intravenous antibiotic therapy.Table 3: Bacteriology of effusions, otorrhea and mastoids in 65 infants and children with acute mastoiditis at the Children's Hospital of Pittsburgh, 1980 to 1995 24Facial paralysis. Facial paralysis most commonly occurs in children during an episode of AOM because of exposure of the facial nerve from a congenital bony dehiscence in its tympanic portion within the middle ear. It also can occur as a complication of acute mastoiditis with osteitis or chronic suppurative OM. 30 In the preantibiotic era facial paralysis was estimated to occur in 0.5% of patients with AOM; the current rate is 0.005%, as reported in a recent study from Denmark. 31 In the Pittsburgh review of 22 infants and children who had acute facial paralysis associated with OM (or related infections), the paralysis occurred most frequently in children age 6 years and younger; 50% were younger than age 4 years (see Table 2). 24 Approximately 10% of these infants and children had pneumococcus isolated from the middle ear or mastoid, or both. A variety of other organisms were cultured, such as P. aeruginosa and H. influenzae. Labyrinthitis. Labyrinthitis results when infection spreads from the middle ear or mastoid gas cells, or both, into the inner ear. Labyrinthitis may also be caused by meningitis, which may or may not be a complication of OM. As demonstrated by the patient described in Figure 4, AOM can spread to the inner ear through a preformed pathway, such as a perilymphatic fistula, which is a congenital defect between the middle ear and the labyrinth. This child survived the acute suppurative labyrinthitis, but another child, recently treated at our Children's Hospital, who had a Mondini dysplasia of the inner ear, developed AOM, suppurative labyrinthitis and meningitis and died. S. pneumoniae was cultured from both the middle ear and the cerebrospinal fluid. 32 Progressive or fluctuating sensorineural hearing loss, which occurs during an attack of AOM, is commonly caused by this malformation. 33, 34 However, labyrinthitis can occur even without an abnormal communication between the middle and inner ear, especially when the OM is untreated, as might happen in developing countries. 26Fig. 4: Magnetic resonance image of left acute suppurative labyrinthitis (arrow) as a complication of the first attack of acute otitis media in a 18-month-old male child who had a preexisting congenital perilymphatic/cerebrospinal fluid fistula of the labyrinthine windows. The child presented with left otorrhea, fever, vertigo and dehydration 5 days after the onset of the acute otitis media;P. aeruginosa was isolated from the otorrhea. Labyrinthectomy on the left ear and bilateral tympanostomy tube placement as an emergency procedure was performed with no further progression of the infection. The child had no further hearing loss or suppurative complication over the ensuing 3-year follow-up period. 24External otitis. AOM with perforation and otorrhea or chronic suppurative OM can cause an infection of the external auditory canal termed external otitis, or infectious eczematoid external otitis. An infection in the mastoid may also erode the bone of the ear canal or the postauricular area, resulting in dermatitis. The skin of the ear canal is erythematous, edematous and filled with purulent drainage, and yellow-crusted plaques may be present. The organisms involved are usually the same as those found in a middle ear-mastoid infection, but the flora of the external canal usually contribute to the infectious process. Hearing loss. Hearing loss is the most common complication and sequela of OM and can be conductive, sensorineural or both. When conductive the loss may be either transient or permanent. When sensorineural the impairment is usually permanent. Fluctuating or persistent conductive hearing loss is present in most children who have MEE caused by AOM. When a MEE is present, there is an average loss of 27 dB, but the loss can be as much as 60 dB. 35 The hearing usually returns to normal thresholds when the MEE resolves. Permanent conductive hearing loss can occur, however, as a result of recurrent acute or chronic inflammation due to adhesive OM or ossicular discontinuity or fixation. Although a debated subject, hearing loss caused by chronic and recurrent middle ear disease may be associated with delay or impairment of speech, language and cognition in young children, which may or may not affect performance in school. 36, 37 Permanent sensorineural hearing loss, as a complication of OM, is most likely the result of the spread of infection, or products of inflammation, through the round window membrane into the labyrinth. 38–40 In an animal experiment Morizono et al. 41 inoculated pneumococcus into the middle ear with resultant penetration into the labyrinth. Vestibular, balance and motor dysfunctions. The most common cause of vestibular disturbance in children is OM. 42 Many parents of infants and children report balance problems, such as clumsiness, when a MEE is present. We now have evidence from studies of labyrinthine function in children with and without MEE to confirm that the vestibular system is adversely affected, and, after tympanostomy tube placement, these dysfunctions return to more normal values. 43–45 Also tests of motor proficiency have been demonstrated to be abnormal in children when MEE is present. 46–48 It is likely that pressure from the MEE on the round and oval windows is the pathogenesis of these findings, but a low grade labyrinthitis is also possible. Most recently a study revealed that children who had a past history of OM, but no MEE present at the time of the vestibular testing, also had abnormal function, which indicates there may be some residual effect of OM on the labyrinth (ML Casselbrant, unpublished data, 1999). Sequelae After AOM or related conditions, sequelae, such as adhesive OM, tympanosclerosis or ossicular fixation or discontinuity, can occur. Cholesteatoma can be a sequela of OM but is also commonly secondary to atelectasis of the middle ear in which a retraction pocket is present. 49 When caused by OM invagination of epithelium from the margins of perforation into the middle ear (and mastoid) is frequently the pathogenesis. INTRACRANIAL COMPLICATIONS OF OM There are seven intracranial suppurative complications of OM (see Table 1). These complications may not only be directly caused by OM but also be the result of one or more of the otitic intratemporal complications, such as mastoiditis, petrositis or labyrinthitis, or by another suppurative complication of OM that occurs within the intracranial cavity. 50 Epidemiology Before the antibiotic era intracranial complications of OM were a common occurrence that frequently resulted in death. In a 1935 study of 3225 patients who had mastoiditis, 6% developed an intracranial complication and of these cases 76% died. 51 After antibiotics for treating OM became available, the incidence of a fatal outcome due to these complications fell dramatically. Lund 52 reported the mortality rate from intracranial complications was 36% between 1939 and 1949 (pre- and early antibiotic era), decreased to 6% between 1950 and 1960 and that there were no deaths from 1961 to 1971. A study from Finland in the 1950s demonstrated the impressive effect of antibiotics on the rate of these complications. Of 629 patients in that study who had AOM, 176 were treated with penicillin and 453 received no antimicrobial agent. There were no complications in the penicillin-treated group, but there were 9 patients in the untreated group who developed complications: 7 had mastoiditis; 1 had meningitis; and 1 patient died as the result of otogenic sinus thrombosis and brain abscess. 53 Today with the widespread use of antibiotics, intracranial complications are less common in the industrialized nations of the world, but they still occur and remain life-threatening. Between 1980 and 1997 at the Children's Hospital of Pittsburgh, 37 infants and children were treated for a suppurative intracranial complication of OM (Table 4). 54 The average age of the children in the Pittsburgh study was 2 years when meningitis developed and 6.5 years when nonmeningitic complications occurred. Of the 37 patients 20 (54%) had meningitis and all had AOM with or without acute mastoiditis with osteitis; 2 of these patients died. In an earlier study from the Children's Hospital of Boston, Friedman et al. 55 reported that between 1981 and 1984, 92 patients had an intracranial infection associated with acute middle ear disease; 84 (91%) of the children had meningitis and 8 (9%) had nonmeningitic involvement; there were 3 deaths. In a recent review from the Netherlands 21 children and adults were treated for an intracranial complication of OM at the University Hospital of Groningen from 1993 to 1996. 56 Of these 21 patients 12 (57%) had meningitis and 9 (43%) had nonmeningitic complications; 1 patient died from multiple brain abscesses. Between 1970 and 1990, 28 children were treated for an intracranial complication of OM in an Israeli medical center, and 3 of these patients died from meningitis, lateral sinus thrombosis or brain abscess. 57Table 4: Distribution of 48 suppurative intracranial complications of otitis media* in 37 children at the Children's Hospital of Pittsburgh, 1980 to 1997 54In contrast to the relatively low rate of these complications in developed countries, the rate remains high in the developing nations of the world. Of 181 South African patients with intracranial complications of OM treated by Singh and Maharaj between 1985 and 1990 (74% of whom were age 20 or younger), 51% had a brain abscess and only 12% had meningitis. 58 One medical center in Thailand reported that between 1983 and 1990, 43 children and adults had an intracranial complication of OM and 8 (18%) died, primarily from brain abscess. 26 Microbiology As shown in our study in Pittsburgh, in the 37 infants and children who developed an intracranial complication of OM, H. influenzae and S. pneumoniae were the most common organisms isolated from the middle ear, mastoid or both (Table 5). 54 Of the 20 patients with meningitis 12 (60%) had H. influenzae isolated, of which 11 were type b and 1 was nontypable; 11 (55%) were S. pneumoniae, of which 1 was penicillin-resistant; these bacteria were also the most frequently isolated from the cerebrospinal fluid. Of the 17 patients who had nonmeningitic complications, S. pneumoniae was isolated in 2 (12%). Figure 5 shows the CT scan of the brain of a child who was recently treated at our hospital since we reported the series cited above. This patient developed a brain abscess resulting from AOM and mastoid osteitis, in which pneumococcus was isolated from both the middle ear and the brain abscess. Table 5: Bacterial isolates from middle ear and mastoid cultures from 37 infants and children who had intracranial complications of otitis media treated at the Children's Hospital of Pittsburgh, 1980 to 1997 54Fig. 5: CT scan of a 10-year-old boy showing a right cerebellar brain abscess (arrows) as a complication of right acute mastoiditis with otitis media. The child had a 3-week history of headache and vertigo 1 day after the onset of fever and presented with increasing lethargy, vertigo, slurred speech, nausea and head-tilting to the left. Examination revealed ataxia, nystagmus, mild confusion and right-sided weakness but no otalgia or otorrhea. Otoscopic examination revealed left middle ear effusion, which was confirmed by tympanocentesis. The brain abscess was drained, and cortical mastoidectomy and tympanostomy tube insertion was performed. Purulent material was found within the mastoid at the time of mastoid surgery and culture of the abscess revealed S. pneumoniae, susceptible to penicillin. The child made a complete recovery, without any sequelae, after the brain and mastoid surgery and intravenous antimicrobial therapy.Potential impact of a pneumococcal vaccine A new vaccine to prevent AOM caused by S. pneumoniae, the most common causative organism, should not only decrease episodes caused by this bacterium but also possibly reduce the overall recurrence rates. This in turn will hopefully decrease the rate of tympanostomy tube placement. In addition because the pneumococcus is commonly isolated from chronic MEE, 1 for which tympanostomy tubes are also inserted, operations for this indication should likewise decrease. Because adenoidectomy is also recommended for children whose recurrent episodes of AOM return after extrusion of 1 or more tympanostomy tubes, the frequency of this procedure may also decline; neither adenoidectomy nor adenotonsillectomy is recommended, when OM is the only indication, for children who have not had a prior tube insertion. 59–61 From our past experience at the Children's Hospital of Pittsburgh, the pneumococcus was the most common cause of acute mastoiditis. Pneumococcus and H. influenzae type b were the most common etiologic agents isolated from middle ears and mastoids in children who had intracranial complications of OM (Tables 3 and 5). However, because H. influenzae type b should be an uncommon cause of OM (and its suppurative complications) in the future, the pneumococcus remains a major threat. Thus a pneumococcal vaccine should also reduce the incidence of suppurative complications of OM caused by this organism. QUESTIONS/ANSWERS Question: Were the H. influenzae isolates from meningitis cases typable? Dr. Bluestone: In the meningitis cases all but one of the isolates were H. influenzae type b. Question: Then these were probably not related to OM? Dr. Bluestone:H. influenzae type b was isolated from the middle ear and mastoid. Question: Are these really bacteremic patients be-cause H. influenzae type b meningitis is typically a bacteremic process? Dr. Bluestone: The criteria for entrance into the study was isolation of the organism from the middle ear and mastoid. The children had mastoidectomies as well as tubes placed in their ears. It might be that the meningitis is not cause and effect, but an associated concurrent infection. Question: If you ask parents on follow-up visits what has changed after tubes are placed in the child's ears, the most common thing they mention is the child's behavior. I know of no study that has addressed this outcome. What are your comments on this? Dr. Bluestone: Outcomes studies after tube placement have mentioned irritability. Question: What are the risk factors for intracranial complications and mastoiditis? Dr. Bluestone: I would like to think that type 3 pneumococcus is the reason; however, type 3 is not a major cause of infections in children and I haven't found any support other than type 3 is still important in adults. Question: In suppurative OM there is information from Australia that the same organisms, S. pneumoniae, H. influenzae and M. catarrhalis, are responsible for this condition. Is the information available on the bacteriology of chronic suppurative OM from other parts of the world? Dr. Bluestone: Chronic suppurative otitis media is ubiquitous around the world. Pseudomonas demonstrates an 80 to 90% prevalence. If you examine the results from Aborigines that were followed from birth, the infants were colonized in the nasopharynx by 3 months of age and all had perforated ear drums by the age of 1 year. In humans it seems that the ear drum is perforated as a result of the primary OM; the Pseudomonas becomes a secondary infection.