Impact of Widespread Introduction of Pneumococcal Conjugate Vaccines on Pneumococcal and Nonpneumococcal Otitis Media.

BACKGROUND: Pneumococcal conjugated vaccines (PCVs) impact on complex otitis media (OM; including recurrent, nonresponsive, and chronic OM with effusion) was greater than that on simple, acute OM in previous studies. Since complex OM is often a polymicrobial disease, we speculated that reduction of complex OM by PCVs would be associated with reduction of non-pneumococcal OM. METHODS: In a prospective, population-based, active surveillance, all OM episodes submitted for middle ear fluid culture in children <3 years from 2004 through 2015 were included. Three sub-periods were established: pre-PCV, PCV7, and PCV13. Incidence rate ratios (IRRs) comparing the 3 periods were calculated for pneumococcal, nontypable Haemophilus influenzae (NTHi), Moraxella catarrhalis, Streptococcus pyogenes, and culture-negative OM. RESULTS: Overall, 7475 episodes were included. Of all-NTHi cases in the pre-PCV period, 34% were mixed with Streptococcus pneumoniae IRRs (95% confidence interval) comparing the pre-PCV to the PCV13 period were 0.02 (0.01-0.04), 0.12 (0.08-0.20), and 0.18 (0.15-0.21) for PCV7+6A serotypes, 5 additional PCV13 serotypes, and all-pneumococcal OM, respectively; non-PCV13 serotype episodes were not significantly reduced. IRRs for single NTHi, mixed NTHi + S. pneumoniae, and all-NTHi OM were 0.30 (0.25-0.35), 0.18 (0.13-0.24), and 0.25 (0.22-0.29), respectively. Moraxella catarrhalis, S. pyogenes, and culture-negative episodes were also significantly reduced. CONCLUSIONS: Both pneumococcal and non-pneumococcal OM episodes, enriched with complex cases, declined substantially in children <3 years following sequential PCV7/PCV13 introduction. The reduction in non-pneumococcal episodes may be attributed to early OM episodes prevention, resulting in a lower rate of complex, often non-pneumococcal OM.

Near-elimination of otitis media caused by 13-valent pneumococcal conjugate vaccine (PCV) serotypes in southern Israel shortly after sequential introduction of 7-valent/13-valent PCV.

BACKGROUND: Otitis media (OM) is common in early childhood. Streptococcus pneumoniae caused approximately 30%-60% of episodes before the pneumococcal conjugate vaccine (PCV) era. The 7-valent PCV (PCV7) was introduced to the Israeli National Immunization Plan in July 2009, and was gradually replaced by the 13-valent PCV (PCV13) starting in November 2010. We aimed at assessing the impact of PCV7/PCV13 sequential introduction on pneumococcal and overall OM necessitating middle ear fluid culture in children aged <2 years in southern Israel. METHODS: This was a prospective, population-based, active surveillance. Our medical center is the only one in the region, enabling incidence calculation. All pneumococcal episodes submitted for culture between July 2004 and June 2013 were included. Three subperiods were defined: pre-PCV, PCV7, and PCV13. RESULTS: Overall, 6122 OM episodes were recorded, and 1893 were pneumococcal. Compared with the pre-PCV period, OM caused by PCV7 plus serotype 6A and the 5 additional PCV13 serotypes (5VT : 1, 3, 5, 7F, 19A) decreased by 96% and 85%, respectively (incidence rate ratios [IRRs], 0.04 [95% confidence interval {CI}, .02-.08] and 0.15 [95% CI, .07-.30], respectively) in a 2-step pattern: In the PCV7 period, only OM caused by PCV7 + 6A serotypes was decreased; in the PCV13 period, 5VT OM rates decreased, along with an additional PCV7 + 6A OM reduction. A nonsignificant increase in non-PCV13 serotype OM was observed (IRR, 1.07 [95% CI, .72-1.58]). In total, 77% and 60% reductions of all-pneumococcal and all-cause OM incidences, respectively, were observed. CONCLUSIONS: A substantial 2-step reduction of pneumococcal OM rates, with near-elimination of PCV13 disease, was observed shortly after PCV7/PCV13 introduction.

Distribution, dynamics and antibiotic resistance patterns of Streptococcus pneumoniae serotypes causing acute otitis media in children in southern Israel during the 10 year-period before the introduction of the 7-valent pneumococcal conjugate vaccine.

OBJECTIVES: To determine the dynamics of serotype prevalence, potential coverage by pneumococcal conjugate vaccines (PCV) and antibiotic resistance patterns of Streptococcus pneumoniae causing acute otitis media (AOM) in children in southern Israel before PCV7 introduction in the routine immunization program in Israel. METHODS: All S. pneumoniae isolates from middle ear fluid from children with AOM during 1999-2008 were included. Prospectively collected demographic data on S. pneumoniae serotypes and antibiotic resistance patterns were analyzed. RESULTS: A total of 14,911 tympanocenteses yielded 5281 (35%) S. pneumoniae. Proportion of S. pneumoniae-AOM did not vary significantly (overall 35%; 33% in 2007; 38% in 2002 and 2003). The most frequent serotypes were 19F, 14, 23F and 19A; in both Jewish and Bedouin children; serotypes 6A and 19A contributed 6% and 10%, respectively, of all S. pneumoniae isolates. Serotypes included in PCV7, PCV10 and PCV13 represented 60%, 64%, 85% in Jewish children vs. 49%, 55% and 74%, respectively, in Bedouin children (P < 0.001). Nonsusceptibility to TMP/SMX decreased significantly, in parallel with a significant increase in the nonsusceptibility to erythromycin, clindamycin and in multidrug resistant (MDR) isolates. No changes were recorded in the proportion of S. pneumoniae isolates with penicillin MIC ≥ 1.0 µg/ml. The proportion of penicillin- and erythromycin-nonsusceptible and of MDR serotype 6A and 19A isolates increased significantly in Bedouin children. CONCLUSIONS: (1) No significant changes were recorded in the yearly proportions of serotypes 23F, 19F, 19A, 14 and 6A in both ethnic populations; (2) Potential coverage of the 3 PCVs was higher in Jewish children than in Bedouin children; (3) The relatively high coverage of macrolides- and multidrug-resistant S. pneumoniae by PCV13 and lack of increase in penicillin, erythromycin and multidrug nonsusceptibility among non-PCV13 isolates is encouraging.

Rates of tympanic membrane closure in double-tympanocentesis studies.

BACKGROUND: Data on the outcome of tympanic membrane (TM) closure after tympanocentesis in acute otitis media (AOM) patients is limited. OBJECTIVES: To analyze the dynamics of TM perforation closure after 1 or 2 tympanocentesis procedures performed at diagnosis and during AOM treatment. PATIENTS AND METHODS: Study population included 113 children enrolled in 4 double-tympanocentesis studies. Only the files of patients whose first and second examination were performed by the same 2 otorhinolaryngologists were analyzed. Middle ear fluid (MEF) was cultured on day 1 and days 4-6, the latter only in initially culture-positive patients. Patients were also examined on days 11-14 and followed until days 22-28. RESULTS: Ninety-three (82%) patients underwent tympanocentesis on days 4-6; 103 (91%) and 95 (84%) were evaluable on days 11-14 and 22-28, respectively. One hundred seventy-three ears underwent tympanocentesis on day 1 and 139 on days 4-6. Ninety-seven (86%) patients had positive MEF cultures. One hundred fifty-three (88%) tympanocentesis procedures performed at enrollment were closed on days 4-6. No differences were recorded in the closure rates as function of patient age, previous AOM history, MEF culture positivity, pathogens isolated at enrollment, and pathogen eradication on days 4-6. The 20 eardrums still open on days 4-6 were closed on days 11-14. Eleven (9%) of the evaluable ears tapped on days 4-6 were not closed on days 11-14 and 9 of 10 were closed on days 22-28. CONCLUSIONS: TM perforation closed in most cases within a few days regardless of patient and disease characteristics, and 2 consecutive tympanocentesis procedures performed at short-time intervals are associated with good TM closure rates.

Is bilateral acute otitis media clinically different than unilateral acute otitis media?

BACKGROUND: Information regarding the specific characteristics of bilateral acute otitis media (BAOM) versus unilateral acute otitis media (UAOM) is lacking. OBJECTIVES: To compare the epidemiologic, microbiologic, and clinical characteristics of BAOM with UAOM in children. PATIENTS AND METHODS: 1026 children aged 3-36 months (61%, <1 year of age) with AOM were enrolled during 1995-2003. All patients had tympanocentesis and middle ear fluid (MEF) culture at enrollment. Clinical status was determined by a clinical/otologic score evaluating severity (0 = absent to 3 = severe, maximal score 12) of patient's fever and irritability and tympanic membrane redness and bulging. Multivariate logistic regression models were used to estimate the risk of BAOM and UAOM presenting with a high severity score (> or =8). RESULTS: Six-hundred twenty-three (61%) patients had BAOM. Positive MEF cultures were recorded in 786 (77%) patients. More patients with BAOM had positive MEF cultures than patients with UAOM (517 of 623, 83% versus 269 of 403, 67%; P < 0.01). Nontypable Haemophilus influenzae was more common in BAOM than in UAOM (390 of 623, 63% versus 170 of 430, 42%; P < 0.01). Overall, the clinical/otologic score showed higher severity in culture-positive than in culture-negative patients (8.2 +/- 2.0 versus 7.7 +/- 2.2; P < 0.001) and in BAOM than in UAOM (8.3 +/- 2.1 versus 7.8 +/- 2.1; P = 0.001). Clinical/otologic score of > or =8 was more frequent in BAOM than in UAOM patients (371, 61.8% versus 200, 51.3%; P = 0.001). The estimated risk for BAOM patients (compared with UAOM patients) to present with a score > or =8 was 1.5. The association between BAOM and clinical/otologic score > or = 8 was maintained after adjustment for age, previous AOM history, and culture results at enrollment. CONCLUSIONS: (1) BAOM is frequent; (2) Nontypable H. influenzae is more frequently involved in the etiology of BAOM than of UAOM; (3) The clinical picture of BAOM is frequently more severe than that of UAOM, but overlap of clinical symptoms is common.

Bacteriologic and clinical efficacy of oral gatifloxacin for the treatment of recurrent/nonresponsive acute otitis media: an open label, noncomparative, double tympanocentesis study.

BACKGROUND: Gatifloxacin is an 8-methoxyfluoroquinolone with good activity against respiratory pathogens. OBJECTIVES: To document the bacteriologic and clinical efficacy of gatifloxacin in recurrent/nonresponsive acute otitis media (AOM). METHODS: One hundred sixty patients 6 to 48 months of age with recurrent/nonresponsive AOM received gatifloxacin suspension (10 mg/kg once daily for 10 days). Recurrent AOM was defined as > or =3 AOM episodes during the previous 6 months or > or =4 AOM episodes during the previous 12 months. Nonresponsive AOM was defined as AOM occurring < or =14 days after completing antibiotic treatment or not improving after > or =48 h of therapy. Middle ear fluid (MEF) obtained by tympanocentesis pretreatment (Day 1) and 3 to 5 days after initiation of treatment (Days 4 to 6) was cultured. Additional MEF cultures were obtained if clinical failure or recurrence of AOM occurred. Bacteriologic failure was defined by culture-positive MEF during treatment. Patients were followed until Days 22 to 28. Susceptibility was determined by broth microdilution. RESULTS: One hundred twenty-eight (80%) patients completed treatment, and 32 discontinued the study prematurely (adverse events, 17; lost to follow-up, 10; consent withdrawal, 3; and laboratory abnormalities, 2). From 89 patients (median age, 1 year; median number of prior AOM episodes, 4; range, 0 to 12), 121 pathogens were recovered: Haemophilus influenzae, 74 (61%); Streptococcus pneumoniae, 36 (30%); Moraxella catarrhalis, 9 (7%); and Streptococcus pyogenes, 2 (2%). The 36 S. pneumoniae isolates were susceptible to gatifloxacin (MIC50 0.25 microg/ml); 26 of 36 (72%) were penicillin-nonsusceptible (15 fully resistant). All 74 H. influenzae isolates were susceptible to gatifloxacin (MIC < or = 0.03 mg/ml). Fourteen of 74 (19%) and 9 of 9 (100%) H. influenzae and M. catarrhalis isolates, respectively, produced beta-lactamase. Bacteriologic eradication was achieved for 118 of 121 (98%) pathogens: 74 of 74 H. influenzae; 34 of 36 (94%) S. pneumoniae; 9 of 9 M. catarrhalis; and 1 of 2 S. pyogenes. Clinical improvement/cure at end of treatment was seen in 103 of 114 (90%) clinically evaluable patients. Clinical recurrence of AOM after completion of therapy occurred in 31 patients. Of the 27 recurrent AOM cases in which tympanocentesis was performed, there were 16 (59%) new infections, 4 (15%) culture-negative results and only 7 (26%) true bacteriologic relapses. Adverse events were recorded in 21 of 160 (13%) patients: vomiting, 16; diarrhea, 3; maculopapular rash, 2. No articular adverse events were recorded. CONCLUSION: Gatifloxacin is efficacious and safe for the treatment of recurrent/nonresponsive AOM.

Acute mastoiditis in Southern Israel: a twelve year retrospective study (1990 through 2001).

BACKGROUND: Acute mastoiditis is a serious complication of acute otitis media (AOM) and has been increasingly reported in the last decade. OBJECTIVES: To report the experience accumulated with acute mastoiditis at the Soroka University Medical Center, Beer-Sheva, Israel, in a period of increasing antimicrobial resistance with Streptococcus pneumoniae. PATIENTS AND METHODS: We reviewed the records of all children with acute mastoiditis hospitalized from 1990 through 2001. Acute mastoiditis was diagnosed when one or more of the physical signs of mastoiditis (swelling, erythema, tenderness of the retroauricular area and anteroinferior displacement of the auricle) were diagnosed in the presence of concomitant or recent (< or =4 weeks) AOM. RESULTS: One hundred sixteen episodes of acute mastoiditis occurred in 101 children age 2 months to 14 years (median, 25 months; 19% <1 year old). The average yearly incidence was 6.1 cases per 100 000 population <14 years old, with a significant increase in the number of cases during the study period. Acute mastoiditis was the first evidence of AOM in 10 (10%) patients. Fever >38 degrees C and >15,000 WBC/mm3 were present in 67 and 43% of cases, respectively. Irritability, retroauricular swelling, redness and protrusion of the auricle occurred more commonly in patients <3 years old (79, 90, 84 and 76% vs. 28, 42, 45 and 30%, respectively, in patients > or =3 years old; P < 0.002). Computed tomography scans were performed in 54 of 116 (47%) cases and revealed bone destruction in 38 (70%). Periosteal abscess and lateral sinus vein thrombosis were diagnosed in 8 and 2 patients, respectively. Simple mastoidectomy was done in 32 of 116 (28%) cases, after no response to intravenous antibiotics was observed; ventilation tubes were inserted in 12 patients. Cultures were obtained at admission in 83 (72%) episodes (71 by tympanocentesis and 12 from ear discharges). Overall 43 pathogens were isolated: 34 at admission; 14 at surgery; and 5 at both occasions. The most commonly isolated organisms were S. pneumoniae (14 of 43, 33%; 4 penicillin-nonsusceptible), Streptococcus pyogenes (11 of 43, 26%), nontypable Haemophilus influenzae (6 of 43, 14%), Pseudomonas aeruginosa (5 of 43, 12%) and Escherichia coli (4 of 43, 9%). All S. pneumoniae organisms were isolated between 1996 and 2001. CONCLUSIONS: (1) The incidence of acute mastoiditis in children in Southern Israel is greater than that reported in the literature; (2) a significant increase in the number of cases was recorded during the study period; (3) the clinical picture of acute mastoiditis was more severe in infants and young children; (4) the pathogen distribution in acute mastoiditis differs from that of AOM with significantly higher rates of S. pyogenes and lower rates of nontypable H. influenzae recovery; (5) penicillin-nonsusceptible S. pneumoniae played only a minor role in the etiology of acute mastoiditis in Southern Israel.

Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae?

BACKGROUND: Previous limited data suggest that acute otitis media (AOM) caused by Streptococcus pneumoniae can present as a more severe disease than that caused by Haemophilus influenzae or Moraxella catarrhalis, as expressed by both tympanic membrane and systemic findings. OBJECTIVES: To evaluate the severity of disease and impact of various pathogens, age, disease history and previous antibiotic therapy in children with AOM by using a comprehensive clinical/otologic score. PATIENTS AND METHODS: The study group consisted of 372 children ages 3 to 36 months with AOM seen at the pediatric emergency room during 1996 through 2001. All patients had tympanocentesis and middle ear fluid culture performed at enrollment. Clinical status was determined by a clinical/otologic score evaluating severity (0 = absent to 3 = severe) of tympanic membrane findings (redness and bulging) and patient's fever, irritability and ear tugging. Maximal severity score was 15. RESULTS: There were 138 (37%) H. influenzae, 76 (21%) S. pneumoniae, 64 (17%) mixed infections (H. influenzae + S. pneumoniae) and 94 (25%) culture-negative cases. The overall clinical/otologic score was higher in culture-positive than in culture-negative patients (9.27 +/- 2.75 vs.8.38 +/- 3.08, P = 0.01). When analyzed by age groups, this difference was significant only for the youngest age group (3 to 6 months, P = 0.05). The severity scores for AOM caused by H. influenzae and S. pneumoniae were significantly higher than in the culture-negative AOM when tympanic membrane redness and bulging were analyzed separately. No differences were recorded in clinical/otologic scores between different pathogens (9.49 +/- 2.86, 9.03 +/- 2.72 and 9.09 +/- 2.54 for H. influenzae, S. pneumoniae and H. influenzae + S. pneumoniae, respectively). The mean clinical/otologic score was higher in culture-positive than in culture-negative patients without relationship to previous antibiotic treatment or number of previous AOM episodes. CONCLUSIONS: (1) The clinical/otologic score of culture-positive young infants was higher than that of culture-negative infants; (2) the severity of tympanic membrane redness and bulging were the most indicative factors discriminating between a bacterial and nonbacterial etiology of AOM; and (3) the use of a clinical/otologic score could not discriminate among various bacterial etiologies of AOM.

Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children.

BACKGROUND: High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first line therapy of acute otitis media (AOM) in geographic areas where drug-resistant Streptococcus pneumoniae is prevalent. Information on the bacteriologic efficacy of high dose amoxicillin treatment for AOM is limited. OBJECTIVES: To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin as first line therapy in AOM. METHODS: In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment. Twenty-four (48%) patients presented with their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy. Patients were followed until Day 28 +/- 2. Susceptibility to penicillin and amoxicillin was measured by E-test. RESULTS: Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38), Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella catarrhalis (1). Eighteen (75%) S. pneumoniae were nonsusceptible to penicillin (MIC > 0.1 microg/ml). All 24 S. pneumoniae isolates had amoxicillin MIC < or = 2.0 microg/ml. Thirteen (34%) of the 38 H. influenzae were beta-lactamase producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S. pneumoniae, 21 of 25 (84%) beta-lactamase-negative H. influenzae, 8 of 13 (62%) beta-lactamase-positive H. influenzae, 2 of 2 S. pyogenes and 1 of 1 M. catarrhalis. Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae; 1 beta-lactamase-negative H. influenzae; 2 S. pneumoniae; and 1 M. catarrhalis. In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H. influenzae. Three (33%) of the 9 patients with bacteriologic failure (2 beta-lactamase-positive H. influenzae, 1 S. pneumoniae) failed also clinically on Days 4 to 6. CONCLUSIONS: The predominant pathogens isolated from children with AOM failing high dose amoxicillin therapy were beta-lactamase-producing organisms. Because its overall clinical efficacy is good, high dose amoxicillin is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure.

Recurrent acute otitis media occurring within one month from completion of antibiotic therapy: relationship to the original pathogen.

OBJECTIVES: (1) To determine the relationship between acute otitis media (AOM) pathogens isolated in cases of early clinical recurrence of AOM (occurring within 1 month from completion of therapy) to the original pathogens causing the initial AOM episode; and (2) To determine whether shorter time intervals between completion of antibiotic therapy and clinical recurrences of AOM are associated with higher rates of true bacteriologic relapse. PATIENTS AND METHODS: From 1995 through 2000, 1077 infants and young children ages 3 to 36 months with AOM were enrolled in double tympanocentesis (performed on Day 1 in all patients and Days 4 to 6 in those initially culture-positive) studies. Of these, 834 (77%) completed successfully the antibiotic treatment [pathogen eradication on Days 4 to 6 of therapy or no pathogen on middle ear fluid (MEF) culture on Day 1 and clinical improvement at end of therapy]. Patients were followed for 3 to 4 weeks after completion of therapy, and additional MEF cultures were obtained if clinical recurrence occurred. True bacteriologic relapse was defined as the presence of a pathogen identical with that isolated before therapy by serotype and pulsed field gel electrophoresis for and by pulsed field gel electrophoresis for Streptococcus pneumoniae and beta-lactamase production for Haemophilus influenzae. RESULTS: MEF cultures were performed in 108 consecutive patients with early recurrent AOM. One hundred pathogens were isolated at recurrence in 88 of 108 (81%) patients: 54 H. influenzae; 45 S. pneumoniae; and 1 Moraxella catarrhalis. Most recurrent AOM episodes developed during the first 2 weeks of follow-up; 39 (36%), 38 (35%), 21 (19%) and 10 (9%) recurrent AOM episodes occurred on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively. In most patients these episodes were caused by a new pathogen. True bacteriologic relapses were found in 30 (28%) of 108 patients whose MEF cultures were positive for 35 pathogens: 13 of 108 (12%) S. pneumoniae; 12 of 108 (11%) H. influenzae; and 5 of 108 (5%) both. When timing of recurrent AOM after completion of therapy was analyzed, true bacteriologic relapses were found in 16 of 39 (41%), 10 of 38 (26%), 3 of 21 (14%) and 1 of 10 (10%) of all episodes on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively (P = 0.01). The respective rates for were 11 of 17 (65%), 3 of 10 (30%), 3 of 13 (23%) and 1 of 5 (20%) (P = 0.02). For H. influenzae the respective rates were 8 of 19 (42%), 9 of 23 (39%), 0 of 8 (0%) and 0 of 4 (0%) (P = 0.02). CONCLUSIONS: Most recurrent AOM episodes occurring within 1 month from completion of antibiotic therapy are in fact new infections. Most of the true bacteriologic AOM relapses occur within 14 days after completion of therapy, but even during this time interval most of the recurrences are caused by new pathogens. H. influenzae is very unlikely to cause true bacteriologic AOM relapses 14 days or later after completion of therapy.

Acute otitis media in infants younger than two months of age: microbiology, clinical presentation and therapeutic approach.

BACKGROUND: Information on the causative agents of acute otitis media (AOM) in infants <2 months of age is limited. OBJECTIVES OF THE STUDY: To analyze the etiology, pathogen susceptibility patterns, clinical presentation and frequency of serious bacterial infections in infants <2 months of age with AOM and to determine the relationship between the organisms isolated systemically and those isolated from the middle ear fluid in the patients with serious bacterial infections in the presence of AOM. METHODS: The medical records of 137 infants <2 months of age with AOM who underwent tympanocentesis in the emergency room of Soroka University Medical Center between January 1, 1995, and May 30, 1999, were reviewed. The main variables analyzed included demography, frequency of serious bacterial infections, bacteriologic results, susceptibility patterns of the pathogens and clinical presentation. RESULTS: Median age was 38.7 +/- 13 days; 112 of 137 (82%) infants were hospitalized. Six (4%), 27 (20%), 46 (34%) and 58 (42%) episodes were recorded at age 0 to 2, 3 to 4, 5 to 6 and 7 to 8 weeks, respectively. Fever (temperature >38 degrees C) was present in 96 (70%) of the cases. Culture-negative (bacterial) meningitis was diagnosed in 3 cases. Blood and urine cultures were positive in 1 and 6 infants, respectively. None of the afebrile infants developed serious bacterial infection. One hundred twenty-two bacterial pathogens were isolated from the middle ear fluid of 109 of 137 (80%) patients: Streptococcus pneumoniae in 56 (46%), Haemophilus influenzae in 41 (34%), group A Streptococcus in 12 (10%), enteric gram-negative bacilli in 9 (7%), Moraxella catarrhalis in 3 (2%) and Streptococcus faecalis in 1 (1%). Eleven (20%) of the 56 S. pneumoniae isolates were nonsusceptible to penicillin. Serious bacterial infections were diagnosed in 6 of 137 (4%) patients. Whereas blood and urine grew pathogens typical for blood and urinary tract infections, the middle ear fluid isolates represented different pathogens usually isolated in AOM without any correlation between these 2 groups of pathogens. CONCLUSIONS: (1) Most cases of AOM in infants <2 months of age are caused by pathogens similar to those causing AOM in older children; (2) antibiotic resistance may already be present at early age and should be considered in the empiric treatment of AOM in infants <2 months of age; (3) the presence of AOM does not predict a higher risk for serious bacterial infections in afebrile and febrile infants <2 months of age.

Cytology of middle ear fluid during acute otitis media.

BACKGROUND: Limited information is available on the cellular characteristics of the middle ear fluid (MEF) during acute otitis media (AOM). OBJECTIVES: To determine the white blood cell (WBC) composition of the MEF in AOM before and during antibiotic therapy. MATERIALS AND METHODS: Total WBC and differential counts were determined in the MEF of 96 infants and children (ages 2 weeks to 3 years) with AOM who were receiving antibiotics. WBC counts were reported as number of WBC/mg MEF (mean +/- sd). RESULTS: One hundred forty-five MEF samples were obtained by tympanocentesis at enrollment (Day 1), and 36 samples were collected on Days 4 to 5 after initiation of antibiotic therapy. Sixty-one percent of the patients were <1 year of age, and 38% were receiving antibiotic therapy at enrollment. Twenty-eight MEF samples were paired (same ear, Day 1 and Days 4 to 5). One hundred twelve pathogens were isolated from 95 of 145 (66%) culture-positive samples obtained on Day 1: 67 Haemophilus influenzae, 40 Streptococcus pneumoniae and 5 others. MEF WBC counts were lower on Day 1 in patients who had received previous antibiotic therapy than in those who had not (432.4+/- 412.8 vs. 590.5 +/- 436.8, P = 0.03). WBC counts were higher on Day 1 in culture-positive than in culture-negative samples (603.9 +/- 504.9 vs.421.4 +/- 373.4, P = 0.02). WBC counts were higher on Day 1 in MEF samples positive for S. pneumoniae than in those positive for H. influenzae (799.2 +/- 641.5 vs.506.4 +/- 401.9, P = 0.04). There were no differences in the number of neutrophil WBC present in the samples obtained on Day 1 vs. Days 4 to 5 or between samples positive vs.samples negative for bacterial pathogens. CONCLUSIONS: WBC counts were higher in the MEF of patients with culture-positive AOM than in those with culture-negative AOM and in those with AOM caused by S. pneumoniae.