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Effect of Streptococcus pneumoniae and influenza A virus on middle ear antimicrobial pharmacokinetics in experimental
G H Jossart1, D M Canafax, G R Erdmann
1Otitis Media Research Center, School of Medicine, University of Minnesota, Minneapolis 55455.
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)
Insights
Influenza A virus infection significantly impacts middle ear antimicrobial drug penetration, prolonging drug half-lives. This finding is crucial for understanding treatment failures in acute otitis media with viral infections.
Area of Science:
- Otolaryngology
- Virology
- Pharmacology
Background:
- Antimicrobial treatment failures in pediatric acute otitis media (AOM) are often associated with viral respiratory infections.
- Influenza A virus is a common pathogen implicated in these cases, potentially affecting drug efficacy.
Purpose of the Study:
- To investigate the impact of influenza A virus infection on the penetration and elimination of antimicrobial drugs in the middle ear.
Main Methods:
- A chinchilla model was used to study Streptococcus pneumoniae.
- Four groups were established: control, influenza A virus alone, S. pneumoniae alone, and combined influenza A virus and S. pneumoniae.
- Middle ear elimination rates of amoxicillin, sulfamethoxazole, and trimethoprim were measured after direct middle ear instillation.
Main Results:
- S. pneumoniae infection alone significantly shortened antimicrobial elimination half-lives compared to controls.
- Concomitant influenza A virus and S. pneumoniae infection significantly lengthened elimination half-lives compared to S. pneumoniae infection alone.
- Influenza A virus infection alone resulted in the longest antimicrobial half-lives for all tested drugs.
Conclusions:
- Influenza A virus infection impairs middle ear antimicrobial drug penetration and elimination.
- This effect may contribute to antimicrobial treatment failures in AOM cases with concurrent viral infections.
- Further research is warranted to optimize antimicrobial strategies in pediatric AOM with viral co-infections.