Untitled

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)

Viral–Bacterial Interactions in Acute Otitis Media

“…Influenza A virus (IAV), coronavirus NL63 and respiratory syncytial virus (RSV) augment bacterial adherence to epithelial cells [17–19]; IAV has also been shown to promote nasopharyngeal colonization of S. pneumoniae [20]. Viruses also modify host immune functions [21, 22], and interfere with antibiotic activity [23–25]. Viruses alter mucous property and diminish the normal mucociliary clearance of the coating epithelial cells by reducing the production of bactericidal substances in the nasopharynx, ET, and the middle ear cavity, and hence increase bacterial pathogenicity [26, 27].…”

“…If the virus infects the middle ear along with bacteria or viral URI is still ongoing at the time of AOM diagnosis, many earlier studies have shown that viral–bacterial interaction can lead to adverse AOM outcome. Prolonged AOM symptoms and bacteriologic failure result from concurrent viral infections [6, 74, 75], through mechanisms such as virus-induced inflammation [76, 77] and interference of antibiotic penetration into the middle ear [23, 24]. These earlier studies detected viruses by the conventional diagnostics (viral culture and antigen detection), which are less sensitive than molecular diagnostics such as PCR and, therefore, detected viruses only in cases with larger inoculums.…”

Presence of Viral Nucleic Acids in the Middle Ear

“…In MEF from children with AOM, concentrations of interleukin-8, histamine and leukotriene B4, have been found to be higher in MEF containing both bacteria and virus, than in MEF containing bacteria or virus alone (8, 9). Another explanation related to the ability of the viruses to induce local inflammation and immunologic reactions that interfere with penetration of antibiotic or dilute antibiotic concentration in the MEF; evidence to support these observations come from both data obtained in chinchilla experiments and in children with AOM (10, 11). …”

Gene Expression Regulation in Airway Pathogens: Importance for Otitis Media

“…The course of othopathogen-dependent OM involves bacterial colonization on the ME epithelium (Hendrixson and St Geme, 1998;Thornton et al, 2011). Bacterial infection in the ME usually occurs as a secondary infection to viral infection in the nasopharynx that subsequently progresses to ME via the Eustachian tube (Jossart et al, 1994;Jiang et al, 1999) (Figure 1). According to general guidelines in various countries, antimicrobial agents, depending on the age group of children are the treatment of choice of OM.…”