title: Effect of Streptococcus pneumoniae and influenza A virus on middle ear antimicrobial pharmacokinetics in experimental otitis media.
abstract: Antimicrobial treatment failures in children with acute otitis media and concomitant viral respiratory tract infection prompted us to study the effects of influenza A virus infection on middle ear antimicrobial drug penetration. Using a chinchilla model of Streptococcus pneumoniae we compared middle ear elimination rates in 4 groups of chinchillas: (1) control, (2) influenza A virus inoculation alone intranasally, (3) both influenza A and S. pneumoniae inoculation directly into the middle ear, and (4) S. pneumoniae inoculation alone into the middle ear. After infection was established, a solution containing amoxicillin, sulfamethoxazole, and trimethoprim was instilled into the middle ear and removed 4 hours later. The rate constant of elimination and half-life were calculated from measured drug concentrations initially and at 4 hours. S. pneumoniae infection alone significantly shortened the middle ear elimination half-life compared with the control group: amoxicillin, 2.65 +/- 0.73 vs. 6.63 +/- 2.55 hr; sulfamethoxazole, 1.75 +/- 0.28 vs. 2.74 +/- 0.6 hr; and trimethoprim, 1.06 +/- 0.14 vs. 1.56 +/- 0.34 hr (n = 16 ears, p values all < 0.01). The combined influenza virus and S. pneumoniae infection significantly lengthened the half-life compared with the S. pneumoniae infection alone: amoxicillin, 5.65 +/- 6.44 vs. 2.65 +/- 0.73 hr; sulfamethoxazole, 2.5 +/- 0.85 vs. 1.75 +/- 0.28 hr; and trimethoprim, 1.26 +/- 0.42 vs. 1.06 +/- 0.14 hr (n = 16 ears, p values all < 0.01). Influenza virus produced the longest half-lives for all 3 antimicrobials: amoxicillin 25.52 +/- 14.96 hr; sulfamethoxazole, 5.46 +/- 0.87 hr; and trimethoprim, 2.57 +/- 0.75 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Otitis Media Research Center, School of Medicine, University of Minnesota, Minneapolis 55455.
authors.forename: G H
authors.initials: GH
authors.lastname: Jossart
authors.forename: D M
authors.initials: DM
authors.lastname: Canafax
authors.forename: G R
authors.initials: GR
authors.lastname: Erdmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Lovdahl
authors.forename: H Q
authors.initials: HQ
authors.lastname: Russlie
authors.forename: S K
authors.initials: SK
authors.lastname: Juhn
authors.forename: G S
authors.initials: GS
authors.lastname: Giebink
mesh_terms: D000658:Amoxicillin / Q000493:pharmacokinetics; D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D002682:Chinchilla; D006207:Half-Life; D009980:Influenza A virus; D009092:Mucous Membrane / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000821:virology; D010033:Otitis Media / Q000378:metabolism* / Q000382:microbiology / Q000821:virology; D011008:Pneumococcal Infections / Q000378:metabolism*; D011817:Rabbits; D013420:Sulfamethoxazole / Q000493:pharmacokinetics; D014295:Trimethoprim / Q000493:pharmacokinetics
chemical_list: D000890:Anti-Infective Agents; D000658:Amoxicillin; D014295:Trimethoprim; D013420:Sulfamethoxazole