Clinical efficacy of antimicrobial drugs for acute otitis media: Metaanalysis of 5400 children from thirty-three randomized trialsā˜†,ā˜†ā˜†,ā˜…,ā˜…ā˜…

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Abstract

Objective: To reconcile conflicting published reports concerning the absolute and comparative clinical efficacy of antimicrobial drugs for acute otitis media in children. Study selection: Articles were identified by MEDLINE search, Current Contents, and references from review articles, textbook chapters, and retrieved reports. Randomized, controlled trials of therapeutic antimicrobial drugs used in the initial empiric therapy for simple acute otitis media were selected by independent, blinded observers, and scored on 11 measures of study validity. Thirty English and three foreign-language articles met all inclusion criteria. Data extraction: Data were abstracted for an end point of complete clinical resolution (primary control), exclusive of middle ear effusion, within 7 to 14 days after therapy started. Data synthesis: The spontaneous rate of primary controlā€”without antibiotics or tympanocentesisā€”was 81% (95% confidence interval, 69% to 94%). Compared with placebo or no drug, antimicrobial therapy increased primary control by 13.7% (95% confidence interval, 8.2% to 19.2%). No significant differences were found in the comparative efficacy of various antimicrobial agents. Extending antimicrobial coverage to include Ī²-lactamaseā€“producing organisms did not significantly increase the rates of primary control or resolution of middle ear effusion. Pretreatment tympanocentesis was positively associated with individual group primary control rates, negatively associated with the ability to detect differences in clinical efficacy and unassociated with resolution of MEE. Conclusions: Antimicrobial drugs have a modest but significant impact on the primary control of acute otitis media. Treatment with Ī²-lactamaseā€“stable agents does not increase resolution of acute symptoms or middle ear effusion; initial therapy should be guided by considerations of safety, tolerability, and affordability, and not by the theoretical advantage of an extended antibacterial spectrum. (J Pediatr 1994;124:355-67)

Section snippets

Study identification

To be included in the metaanalysis, a study had to be a randomized, controlled trial of antimicrobial drugs for the initial empiric treatment of simple AOM, as defined below:

  • ā€¢

    Simple AOM new or recurrent episodes of AOM in patients without underlying disorders that might influence susceptibility to infection, such as Down syndrome, cleft palate, craniofacial anomalies, immunodeficiency, otitis media with effusion, or concurrent illness other than a viral upper respiratory tract infection.

  • ā€¢

    AOM

Literature search and trial selection

Our English-language MEDLINE search identified 303 articles. Of these, 160 remained after the initial scanning of the titles. An additional 126 articles were added after searching Current Contents and reviewing bibliographies, for a total of 286 entries in the initial data set. Reasons for excluding 256 studies are summarized in Table I. Of the remaining 30 articles, 28 had been identified from MEDLINE,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52

DISCUSSION

Should antibiotics be part of the initial empiric therapy for AOM in children? Our metaanalysis suggests that the answer is a qualified yes. Qualifications relate to (1) the modestā€”though significantā€”efficacy of antibiotics over placebo or no drug, (2) the limitations of a narrow treatment end point, and (3) the failure of Ī²-lactamase coverage to increase rates of primary control significantly. Six of every seven children with AOM either do not need antibiotics for primary control or will not

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    From the Departments of Otolaryngology and Pediatrics, Children's National Medical Center and George Washington University School of Medicine, Washington, D.C., the Otitis Media Research Center and the Departments of Otolaryngology, Pediatrics, and Surgery, University of Minnesota School of Medicine, and the Department of Pharmacy Practice, University of Minnesota College of Pharmacy, Minneapolis

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    Supported in part by National Institutes of Health grant No. P01-DC00133 from the National Institute of Deafness and Other Communicative Disorders and grant No. GM 08183-02, Public Health Service Short-Term Training Grant: Students in Health Professional Schools.

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    Reprint requests: Richard M. Rosenfeld, MD, MPH, Department of Otolaryngology, Long Island College Hospital, 340 Henry St., Brooklyn, NY 11201.

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    0022-3476/94 $3.00 + 0 9/20/52105

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