title: Clinical outcome in children with culture-negative acute otitis media.
abstract: BACKGROUND
  Culture-negative AOM is often milder and associated with lower local/systemic inflammatory responses than culture-positive AOM.
  
  
  OBJECTIVE
  To compare the clinical outcome of culture-negative AOM with that of culture-positive AOM children.
  
  
  METHODS
  Children aged 3 to 35 months with AOM were enrolled in 11 double-tympanocentesis antibiotic efficacy studies documenting both bacteriologic (days 4-6 of treatment) and clinical outcome (days 11-14, end of treatment). Univariate analysis (age, gender, ethnicity, previous AOM history, and antibiotic treatment) between culture-negative and culture-positive AOM patients was performed by Student t test, ANOVA, or chi2 test. Those found to be significant were further submitted to multivariable regression analysis.
  
  
  RESULTS
  A total of 1088 patients (mean age, 11.95 +/- 5.96 months, 209 culture-negative and 879 culture-positive AOM) were enrolled. No differences were recorded between culture-negative AOM and culture-positive AOM patients in age, gender, ethnicity and number of previous episodes. Seventy-four percent (650/879) culture-positive AOM patients achieved bacteriologic eradication within 3 to 5 days. Successful outcome (cured + improved) was recorded in 90% (189/209) culture-negative AOM patients versus 86% (758/879) in culture-positive AOM (P = 0.086). Successful clinical outcome was more frequent in culture-negative than in culture-positive AOM without bacteriologic eradication (90% vs. 67% [154/229], P < 0.001). No difference in successful clinical outcome was found between culture-negative versus culture-positive AOM patients with bacterial eradication (90% vs. 93% [604/650], P = 0.24). Overall, the inclusion of culture-negative AOM patients in the evaluation of clinical failures rates in study patients decreased the total clinical failure rate by 9%. We present a hypothetical antibiotic efficacy study enrolling 300 patients in whom 2 drugs with different bacteriologic efficacy rates (A-90% and B-60%) were used. When the culture-negative cases (5% clinical failure) enrolled increased from 50/300 (16.7%) to 150/300 (50%), the overall clinical failure rate decreased by 36% (from 17.4% to 11.2%, P = 0.08) for the less efficacious drug, while remaining unmodified for the more efficacious drug (9.6% and 8.8%, respectively).
  
  
  CONCLUSIONS
  (1) Clinical outcome in culture-negative AOM was similar to that of culture-positive AOM with bacteriologic eradication and both were superior to that of culture-positive AOM without eradication; (2) Inclusion of culture-negative AOM patients in series aiming at antibiotic efficacy may falsely improve the clinical outcome for antibiotics with reduced ability to eradicate AOM pathogens.
authors.affiliation: Pediatric Infectious Diseases Unit, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. eugenel@bgu.ac.il
authors.forename: Eugene
authors.initials: E
authors.lastname: Leibovitz
authors.forename: Eyal
authors.initials: E
authors.lastname: Nakash
authors.forename: Noga
authors.initials: N
authors.lastname: Givon-Lavi
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.forename: Robert
authors.initials: R
authors.lastname: Satran
authors.forename: Semion
authors.initials: S
authors.lastname: Raiz
authors.forename: Lolita
authors.initials: L
authors.lastname: Piglansky
authors.forename: Alberto
authors.initials: A
authors.lastname: Leiberman
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
mesh_terms: D000208:Acute Disease; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010033:Otitis Media / Q000188:drug therapy* / Q000382:microbiology*; D010034:Otitis Media with Effusion / Q000382:microbiology; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents