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Respiratory Viruses Interfere with Bacteriologic Response to Antibiotic in Children with Acute Otitis Media Thsnee Chonmaitree, Mary J. Owen, and Virgil M. Howie

From the Departments of Pediatrics and Pathology, University of Texas Medical Branch, Galveston

Acute otitis media (AOM) is a common childhood disease. Because bacteria are isolated from the middle ear fluid (MEF) of rv70 % of these cases [1, 2], antibiotics are generally given for treatment. However, some cases of AOM do not respond to antibiotic therapy, and available data suggest that most cases of unresponsive AOM are not caused by bacteria resistant to the prescribed therapy [3]. Several observations suggest a relation between viral respiratory illness and AOM. These include epidemiologic data that link AOM with viral illness [4], the lack of proven bacterial cause in 30 % of cases, and data suggesting that viral infection predisposes animals to bacterial ear infection [5]. Recent studies have confirmed the significance of viruses in the pathogenesis of AOM by demonstrating viruses or viral antigens in MEF of 18 %-24 % of children with AOM [6-8]. We previously reported a relatively high prevalence of AOM of combined viral and bacterial infection [8]. Here we evaluate the relationship between the presence of virus in combination with bacteria and the clinical and bacteriologic responses of the middle ear infection to antibiotic therapy.

Received 20 November 1989; revised 15 February 1990. Presented in part: Interscience Conference on Antimicrobial Agents and Chemotherapy, Houston, September 1989. Informed consent was obtained from parents or guardians of all subjects; all procedures conformed to the guidelines of the US Department of Health and Human Services and the University of Texas Medical Branch Institutional Review Board. Financial support: American Cyanamid. Reprints and correspondence: Dr. Thsnee Chonmaitree, Department of Pediatrics, C-71, University of Texas Medical Branch, Galveston, TX 77550. The Journal of Infectious Diseases 1990;162:~549 © 1990 by The University of Chicago. All rights reserved. 0022-1899/90/6202-0041$01.00

Methods This study took place in conjunction with a nonblinded study of the efficacy of cefixime compared with amoxicillin for treatment of AOM [9]. At the enrollment visit (visit 1), the diagnosis of AOM was established by the presence of symptoms of acute infection (fever, irritability, or otalgia by history), signs of inflammation (red or yellow color or bulging) of the tympanic membrane, and middle ear effusion. The presence of fluid in the middle ear was confirmed by tympanocentesis; patients were excluded if tympanocentesis yielded no fluid. Bacterial and viral cultures were done on the MEF obtained at this enrollment visit (MEF 1). Patients with a history of AOM were enrolled only if new symptoms had developed within the past week and otoscopy revealed signs of inflammation. After the tympanocentesis at visit 1, the patients were randomly assigned to be treated with 10 days of cefixime (8 mg/kg/day) or amoxicillin (40 mg/kg/day). The prescribed antibiotic suspension and a calibrated measuring syringe were given to the parents, and the first dose was given to the patient in front of the parent to demonstrate proper dosing technique. The parents were asked to record dates and times the medicine was given and return the medicine bottles at the end of therapy with any remaining unused medication. Compliance was measured by calculating the weight of medicine absent from the bottle divided by the expected weight of medicine that would have been consumed if taken as prescribed. The on-therapy visit (visit 2) was scheduled 2-4 days into the course, after a minimum of 48 h of antibiotic therapy. The clinical response to therapy was assessed. Repeat tympanocentesis was performed, and the MEF obtained (MEF 2) was cultured for bacteria and viruses. The patient was considered improved or cured when signs and symptoms were improved or absent, there was no drainage of MEF, and bacterial culture was negative. Clinical failure was defined by ongoing inflammation of the tympanic membrane or purulent drainage with negative bacterial culture. Bacteriologic failure was defined by a pathogenic bacterium present in MEF 2, with or without clinical symptoms. The patients were scheduled to return for two additional visits, one at the end of therapy (visit 3) and another 1 month after enrollment (visit 4). Tympanocentesis was

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Fifty-eight infal'.ts and children with acute otitis media were prospectively studied for bacterial and viral pathogenesis and response to antibiotic therapy. Tympanocentesis for bacterial and viral cultures of middle ear fluids (MEF) was done before and 2-4 days after beginning treatment. Patients were followed until the end of antibiotic course. Bacteria were cultured from the preantibiotic MEF in 43 cases (74%). Viruses were cultured from the preantibiotic MEF in 11 cases (19%); all of these MEFs also contained bacterial pathogens. A significantly higher proportion of patients with both virus and bacteria (50%) failed to respond with clearing of bacteria 2-4 days into therapy compared with the group with bacteria alone (13%). The patients with persistently positive viral cultures of the MEF seemed to have purulent otitis of longer duration. Presence ofvirus in the MEF may interfere with bacteriologic and clinical responses to antibiotic. The mechanism of interference deserves further investigation.

JID 1990;162 (August)

547

Concise Communications

Results During a single winter respiratory season (NovemberMarch), 64 infants and children were enrolled in the study. Six were excluded from data analysis because of inadequate follow-up or viral culture data. Ofthe 58 subjects, all returned for visit 2, 54 (93%) returned for visit 3, and 38 (66%) returned for visit 4. The reported population contained 29 boys and 29 girls, 26 whites, 16 Hispanics, and 16 blacks. The age range was 5 months to 8 years; 60% of the patients were 23 mm and MIC

Respiratory viruses interfere with bacteriologic response to antibiotic in children with acute otitis media.

Fifty-eight infants and children with acute otitis media were prospectively studied for bacterial and viral pathogenesis and response to antibiotic th...
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