Virgil M. Howie

Role of leukotriene B4 and interleukin-8 in acute bacterial and viral otitis media.

In order to evaluate the role of polymorphonuclear leukocytes (PMNs) in acute otitis media (AOM), levels of leukotriene B4 (LTB4), a potent inflammatory product of PMNs, and interleukin-8 (IL-8), a PMN chemotactic cytokine, were measured in 271 middle ear fluid (MEF) samples from 106 children with AOM. Forty-two percent of the patients had evidence of respiratory viral infection. At the time of diagnosis, levels of both LTB4 and IL-8 were higher in the MEFs from patients with AOM associated with bacterial or bacterial and viral infection than those MEFs containing no pathogen (p < .05). Antibiotic treatment was not associated with a significant change in levels of LTB4 or IL-8 in the MEFs obtained 2 to 5 days into treatment, compared to those obtained at diagnosis. Bacteriologic failure after 2 to 5 days of treatment was associated with high LTB4 levels in the initial MEFs (p = .05). Recurrence of AOM within 1 month was associated with high IL-8 levels in the initial MEF (p = .04). Our findings suggest that LTB4 and IL-8 are produced during acute infection of the middle ear, and these PMN-related inflammatory substances may play an important role in delaying recovery or in recurrence of AOM. Effective treatment of AOM may require eradication of bacteria by antibiotics, as well as pharmacologic agents that modulate PMN functions.

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.

Increasing incidence of ampicillin resistance in Hemophilus influenzae

The incidence of ampicillin resistance in Hemophilus influenzae and its medical significance have not been extensively determined. During 1975-1977, we tested for ampicillin resistance 489 consecutive middle-ear isolates of HI obtained from children in Huntsville, Alabama, and 719 consecutive laboratory isolates of HI from Childrens Hospital, Boston. The annual incidence of Amp resistance rose progressively in each survey, from initial values of 1.4 to 5.3% in 1975, to 14 to 16% in 1977 (P less than 0.05), a mean annual rate of increase approximately twofold. Resistance was equally prevalent among type b and non-b isolates and among nasally carried and disease-associated isolates (from blood, CSF, middle ears). Patients harboring AmpR isolates were much more likely to have had recent exposure to beta-lactam antibiotics (P less than 0.01).

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.

Bacteriologic failure of amoxicillin-clavulanate in treatment of acute otitis media caused by nontypeable Haemophilus influenzae☆☆☆★★★♢

OBJECTIVEnTo evaluate the rate of bacteriologic failure of amoxicillin-clavulanate in the treatment of acute otitis media (AOM) and to identify the risk factors associated with failure.nnnMETHODSnNinety-nine subjects (mean age, 21.4 months) with AOM were treated with amoxicillin-clavulanate in two prospective study trials that compared efficacy of two experimental antibiotics with amoxicillin-clavulanate. Tympanocentesis for microbiologic studies was performed in all subjects at enrollment; at 3 to 6 days, during amoxicillin-clavulanate therapy; and at other times when clinically indicated. The subjects were followed up for 1 month. Clinical, bacteriologic, and virologic characteristics of the subjects were analyzed.nnnRESULTSnBacteriologic failure of treatment occurred in none of 39 subjects (0%) with Streptococcus pneumoniae, two of 25 (8%) with Moraxella catarrhalis, and 11 of 29 (38%) with nontypeable Haemophilus influenzae (NTHi) infection. The failure rate for NTHi was higher than that for other pathogens (p = 0.0007) and was increased when compared with the preceding study period (p = 0.017). Bacteriologic failure was also associated with clinical failure (p = 0.041). In subjects with AOM caused by NTHi the rates of adequate drug compliance were comparable in both success and failure groups. Antimicrobial susceptibility testing by minimum inhibitory concentration and minimum bactericidal concentration (MIC/MBC) assays showed that amoxicillin-clavulanate resistance was not significantly associated with bacteriologic failure of treatment. However, in two subjects, MIC/MBC of the NTHi isolates during therapy were higher than MIC/MBC of the isolates before therapy; these strains of isolates pretherapy and during therapy were discordant as determined by outer membrane protein analysis. The bacteriologic failure rate was higher in nonwhite boys (p = 0.026) and in subjects with a history of three or more previous episodes of AOM (p = 0.008). Other factors such as age, bilaterality of disease, polymicrobial infection, and biotype pattern of NTHi were not associated with treatment failure. When children with adequate drug compliance were analyzed separately, only those with concomitant viral infection of the nasopharynx or middle ear were found to be at an increased risk of bacteriologic failure of treatment (p = 0.04).nnnCONCLUSIONSnThe bacteriologic failure rate of amoxicillin-clavulanate therapy for AOM caused by NTHi was higher in the current study period than in the preceding period. Factors contributing to treatment failure were race, gender, proneness to otitis, and concomitant viral infection.

EFFECTS OF EARLY OTITIS MEDIA WITH EFFUSION (OME) ON COGNITIVE DEVELOPMENT AT 3 AND 5 YEARS. • 763

EFFECTS OF EARLY OTITIS MEDIA WITH EFFUSION (OME) ON COGNITIVE DEVELOPMENT AT 3 AND 5 YEARS. • 763

EXPLORATORY TYMPANOCENTESIS FOR THE DIAGNOSIS OF ACUTE OTITIS MEDIA WITH EFFUSION IN THE NEONATE: LIMITATIONS IN THE USE OF THE TYMPANOMETER UNDER SEVEN MONTHS OF AGE

Sixty-five patients presenting to a general pediatric practice for either well baby care or acute illness in the first seven months of life over a two year period with signs of acutely discovered otitis media with effusion (AOME) were subjected to tympanometry and subsequent tympanocentesis. The overall sensitivity in detecting AOME of the practitioners on the 129 ears studied varied from 92 to 100 percent using pneumatic otoscopy. The specificity of the practitioners varied from 40 to 67% but there was marked variation in the diagnosis under one month of age. Tympanometry was 44% sensitive and 77% specific in the same patients with some special considerations in the infants head position seeming to account for some of the lack of sensitivity. The presenting author feels that there is a distinct advantage in obtaining a definitive diagnosis by using the technique of exploratory tympanocentesis in suspected AOME under one month of age.

768 PRESENCE OF RESPIRATORY VIRUSES DURING ACUTE OTITIS MEDIA (AOM)

AOM is generally considered to be a bacterial disease. We studied 71 infants and children (1 mo. to 9 yr.) with AOM for evidence of viral infection. During a 2 year period, middle ear fluids (MEF) were cultured for bacteria and viruses and nasal washings (NW) were cultured for viruses. Seventy-nine pathogens were isolated from MEF of 58(82%) cases: 27 strains of H. influenzae; 23 S. pneumoniae; 9 Neisseria; 5 influenza virus (infl); 3 rhino-virus (rhino); 3 enterovirus (entero); 3 S. aureus; 2 S. pyogenes: 2 gram negative bacilli; 1 respiratory syncytial virus(RSV); 1 parainfluenza virus (para). One pathogen was found in MEF of 39 (55%) cases, 2 pathogens in 17 (24%) and 3 pathogens in 2(3%).In 10 of 13 cases the virus in MEF was found in NW. Two had the virus (infl, rhino) in both MEF and NW but no bacteria in MEF. An additional 11 cases had 12 viruses in NW, 2 (adeno and para) had no pathogen in MEF. Total of 24(34%) cases of AOM had viral infection of the upper respiratory tract. Presence of virus in MEF/NW for rhino was 3/3, infl 5/9, para 1/2, entero 1/3, RSV 0/1,adeno 0/1 and CMV 0/3. AOM is often a result of combined viral and bacterial infection although virus alone can cause AOM. Ototropic viruses include rhino, infl, and entero. The relative contribution of viral and bacterial pathogens to the development of AOM requires further study.

772 ACOUSTIC OTOSCOPY (A.O.) COMPARED WITH TYM PANOMETRY AND MYRINGOTOMY IN THE DIAGNOSIS OF MIDDLE EAR EFFUSION IN CHILDREN AND INFANTS

216 outpatients had 346 middle ear aspirates for either acute otitis media (#66) or insertion of pressure equalization tubes (#150). A.O. was available immediately prior to aspiration in 346 ears and both tympanometry and A.O. were available in 162 ears. The sensitivity of the A.O. was 85% with a specificity of 64% in the 346 ears aspirated. The sensitivity of tympanometry was 90% and specificity was 67% in the 162 ears for which both measurements were made. These sensitivities and specificities are not significantly different, but the specificities are better than the prediction of an experienced pediatrician using pneumatic otoscopy on the same patients.

987 COMPARISON OF OUTER MEMBRANE PROTEINS OF TYPE B AND NONTYPE B HAEMOPHILUS INFLUENZAE

We have proposed a subclassification scheme for H. influenzae type b (Hib) based upon distinctive and reproducible strain differences in the SDS-polyacrylamide gel electrophoresis patterns of outer membrane (OM) proteins. Of 49 invasive isolates from patients hospitalized in St. Louis (StL), 92% could be assigned to 1 of 5 subtypes (1L, 1H, 2L, 2H, 3L). In the present study, we used this system to subtype 86 invasive isolates from patients hospitalized in 12 other states. The results were compared to the subtypes in StL, and to the OM protein patterns of nontype b Haemophilus isolates from middle ear (14 isolates), or blood/CSF (4 isolates). The overall distribution of Hib subtypes in other areas of the U.S. was similar to St.L (p>.35). However, there were possible regional differences: Isolates from New Orleans had a higher proportion of 3L strains than the rest of the U.S.,6/15 (40%) compared to 16/120 (13%), p<.01. Also, 3 of 11 apparently unrelated type b isolates from Denver had identical OM protein patterns not identified in 124 other isolates (p<10−8). Nontype b isolates (middle ear or invasive) had OM protein patterns different from the common type b patterns, and exhibited much greater variability. Thus, type b isolates causing invasive infections in the U.S. appear to be derived from a small number of distinctive clones. Nontype b isolates are genetically distinct from type b strains, and are more heterogenous. These findings may have important epidemiologic and immunologic implications.