Effect of Streptococcus pneumoniae and influenza A virus on middle ear antimicrobial pharmacokinetics in experimental otitis media

• Published in: Pharmaceutical research Vol. 11; no. 6; pp. 860 - 864
• Main Authors: JOSSART, G. H, CANAFAX, D. M, ERDMANN, G. R, LOVDAHL, M. J, RUSSLIE, H. Q, JUHN, S. K, GIEBINK, G. S
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-06-1994
• Subjects: Amoxicillin - pharmacokinetics; Animals; Anti-Infective Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chinchilla; Half-Life; Influenza A virus; Medical sciences; Mucous Membrane - metabolism; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - virology; Otitis Media - metabolism; Otitis Media - microbiology; Otitis Media - virology; Pharmacology. Drug treatments; Pneumococcal Infections - metabolism; Rabbits; Sulfamethoxazole - pharmacokinetics; Trimethoprim - pharmacokinetics; Sulfanilamide derivatives; Middle ear disease; Rodentia; Orthomyxoviridae; Systemic route; Influenzavirus; Antimicrobial agent; Chinchilla; Streptococcus pneumoniae; Infection; Virus; Penicillin derivatives; Streptococcaceae; Vertebrata; Mammalia; Influenzavirus A; Animal; Viral disease; Bacteria; Micrococcales; ENT disease; Otitis media; Pharmacokinetics
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1018933925707

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.