Paul A. Shurin

Measuring the comparative efficacy of antibacterial agents for acute otitis media: The “Pollyanna phenomenon”

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

Course and outcome of otitis media in earlyinfancy: A prospective study

We determined the course of otitis media in a prospective, longitudinal study of infants who were enrolled at birth and followed to age 1 year. Bilateral chronic otitis media with effusion developed in eight of 24 (33%) with onset of otitis media before age 2 months, compared to two of 30 (7%) with later onset (P = 0.012). Infants with bilateral chronic otitis media with effusion could be identified early: eight of 15 (53%) infants with bilateral middle ear effusion at age 2 months subsequently had bilateral chronic otitis media with effusion, compared to two of 55 (4%) infants without bilateral effusions at age 2 months (P = 0.000007). The onset of otitis media was symptomatic in 29 of 54 (54%), and asymptomatic in 25 of 54 (46%). If regular well-child examinations with otoscopy had not been performed in asymptomatic infants, bilateral chronic otitis media with effusion would not have been detected in six of 10 infants. Infants with otitis media in early infancy may be asymptomatic and are at high risk for chronic otitis media with effusion.

Persistence of Middle-Ear Effusion after Acute Otitis Media in Children

We observed the frequent occurrence of persistent middle-ear effusion in children with acute otitis media and followed them according to standard procedures for otologic diagnosis. We performed a life-table analysis to identify risk factors for such persistent disease. Sixty-two patients were free of middle-ear effusion at one or more clinic visits two to 13 weeks after presentation and were considered cured; 45 had effusion at all clinic visits during this period and were defined as having persistent effusion. The life-table analysis showed that the relative risk for persistence was 3.8 times higher in children less than 24 months of age as compared with children 24 months of age or older (P less than 0.001) and that this risk was 2.8 times greater for white as compared with black children (P less than 0.01). Other factors examined were not identified as significant risk factors. Persistent middle-ear effusion may be associated with impaired hearing and appears to be the most important sequela of otitis media.

Bacterial etiology of otitis media during the first six weeks of life

Tympanocentesis was performed on 70 infants who had otitis media during the first six weeks of life. The bacteria isolated from their middle-ear effusions were Streptococcus pneumoniae (13 patients), Neisseria catarrhalis (11 patients), Hemophilus influenzae (ten patients), Enterobacteriaceae (four patients), Staphylococcus aureus (four patients), streptococci (groups A and B) (three patients), and Pseudomonas aeruginosa (two patients). Thirty patients (42.9%) had middle-ear effusions which did not contain pathogenic bacteria. Twenty-seven infants were followed for at least 12 months and 12 (44.4%) of these infants had six or more episodes of otitis media during the observation period. Further studies will be needed to establish the significance of middle-ear disease at this age and the role of therapy in improving its outcome.

Do children with recurrent Haemophilus influenzae otitis media become infected with a new organism or reacquire the original strain

Using the techniques of outer membrane protein gel analysis and biotyping, we characterized nontypable Haemophilus influenzae isolates from middle ear aspirates of 30 children with recurrent nontypable H, influenzae (NTHI) otitis media. Nine of the 13 children with early recurrence of NTHI otitis (less than 30-day intervals) had respective first and second isolates that were identical. In contrast, 14 of 18 children with late recurrences of NTHI otitis (greater than 30-day intervals) had respective first and second isolates that were different, whereas four children had late recurrences with organisms that appeared to be identical with their respective initial infecting strains. These results suggest that early recurrent NTHI otitis usually is a result of relapse with the initial infecting NTHI strain. In contrast, late recurrent disease is usually the result of infection with a new organism. However, the observation that four children had late recurrences with the original strains suggests that strain-specific protective immunity may not uniformly develop after recovery from NTHI otitis.

Tympanometry in the Diagnosis of Middle-Ear Effusion

Tympanometry measures the flow of sound energy in the external ear canal under conditions of changing ear-canal pressure. To evaluate this technic as a means of detecting middle-ear effusion, we studied acoustic susceptance and conductance in 91 children. We made the measurements using tones of 220 and 660 Hz over a pressure range of -300 to +300 mm of water. The mean value for susceptance at 660 Hz gave best results: 83 of 84 tympanograms of ears with middle-ear effusion had values less than 0.16 millimhos (mmho). Among 128 studies of normal ears, 113 had values greater than or equal to 0.16 mmho (P less than 0.001). We conclude that a mean acoustic susceptance at 660 Hz less than 0.16 mmho in a child four months of age or older indicates the presence of middle-ear effusion.

Trimethoprim-sulfamethoxazole compared with ampicillin in the treatment of acute otitis media.

We treated 132 children with acute otitis media in a randomized trial comparing trimethoprim-sulfamethoxazole and ampicillin. The antibacterial efficacy of the drugs was assessed primarly from the results of cultures of middle ear aspirates obtained during or after the course of therapy; persistent, recurrent, and new infections of the middle ear were documented in both groups of patients but did not differ significantly. Both drug regimens were well accepted by the patients and were not associated with serious side effects or toxicity. TMP-SMZ is an effective alternate to AMP or to other accepted regimens for initial treatment of acute otitis media.

Otitis media caused by non-typable, ampicillin-resistant strains of Haemophilus influenzae

Strains of Haemophilus influenzae, which did not belong to any of the known capsular serotypes and which were resistant in vitro to ampicillin, have been isolated from middle ear exudates of two children with otitis media. These children failed to improve with ampicillin therapy, and the resistant organisms persisted at the site of infection. Patients infected with such ampicillin-resistant organisms require therapy with antimicrobial agents which are not susceptible to degradation by penicillinase.

Identification of children requiring radiologic evaluation for urinary infection.

Sixty-nine children younger than 13 years of age with urinary tract infection were evaluated to identify risk factors for treatable urologic problems; i.e. those requiring surgery or prolonged antibiotic prophylaxis. All children had a renal ultrasound, intravenous pyelogram and voiding cystogram performed 4 to 6 weeks after the infection. Eleven children with treatable problems were identified, 10 with vesicoureteral reflux and 1 with a ureterocele. For identification of treatable problems the predictive value of a positive test was: (1) fever, 10 of 24 (41.7%); (2) abnormal D-deaminoarginine vasopressin renal concentrating ability, 8 of 24 (33.3%); (3) serum C-reactive protein greater than or equal to 1.0, 8 of 25 (32.0%); (4) Elevated urine N-acetylglucosaminidase, 5 of 16 (31.2%); (5) erythrocyte sedimentation rate greater than or equal to 25, 6 of 21 (28.6%); and (6) age less than 5 years, 10 of 43 (23.3%). Absence of fever denotes a low risk (less than 3%) of finding a treatable problem. Afebrile girls older than 5 years of age can have radiologic evaluation deferred until infection recurs. The presence of fever indicates a high risk of treatable urologic problems (41.7%) and warrants complete radiologic evaluation with the first urinary infection.

Ipsilateral and Contralateral Acoustic Reflexes in Neonates

Ipsilateral and contralateral acoustic reflexes were studied in neonates using 220 and 660 Hz probe tones and 500, 1000, 2000, and 4000 Hz activators. Activator sound pressure level was measured in all ears. Ipsilateral and contralateral reflexes were detected three times more frequently with a 660 Hz probe tone than with a 220 Hz probe tone. The maximum detection rate (76%) occurred with 1000 and 2000 Hz ipsilateral activators and the 660 probe tone. There was no significant difference between neonatal and adult ipsilateral thresholds at 500, 1000, and 4000 Hz. Neonatal intrameatal sound pressure levels for ipsilateral activators were found to be significantly higher than would be indicated from the otoadmittance meter manufacturers specifications.