title: Do orally administered antibiotics reach concentrations in the middle ear sufficient to eradicate planktonic and biofilm bacteria? A review.
abstract: BACKGROUND
  Infectious conditions of the middle ear are a common and significant cause of morbidity and mortality worldwide. Systemic antibiotics are frequently used, but their effectiveness will depend on whether an adequate antibiotic concentration is achieved in the middle ear; this is especially important in biofilm infections such as otitis media with effusion (OME), where high antibiotic concentrations are typically required for effective treatment.
  
  
  OBJECTIVE
  This review examines what antibiotic levels can be reached in the middle ear with oral administration, as a means of guiding rational antibiotic choice in the clinic and future research, and to determine whether levels high enough for biofilm eradication are reached.
  
  
  METHODS
  A literature search of studies measuring levels of antibiotics in the plasma and in the middle ear after oral administration was conducted. These levels were compared to the minimum inhibitory concentrations (MIC) provided by the European Committee for Antimicrobial Susceptibility Testing (EUCAST) to determine if antibiotic doses were reaching sufficient levels to inhibit planktonic bacteria. The middle ear concentrations were then calculated as a multiple of the MIC to determine if the concentrations were reaching biofilm eradication concentrations (typically up to 1000×MIC).
  
  
  RESULTS
  The highest antibiotic levels against Staphylococcus aureus reach 8.3×MIC, against Moraxella catarrhalis 33.2×MIC, against Haemophilus influenzae 31.2×MIC, and against Streptococcus pneumoniae 46.2×MIC. The macrolide antibiotics reach higher levels in the middle ear than in plasma.
  
  
  CONCLUSIONS
  Orally administered antibiotics reach levels above the MIC in the middle ear. However, they do not reach levels that would be likely to eradicate biofilms.
authors.affiliation: Biomaterials-Related Infection Group, School of Medicine, University of Nottingham, Queen's Medical Centre, Derby Rd., Nottingham NG7 2UH, UK. Electronic address: katherine.belfield@nottingham.ac.uk.
authors.forename: Katherine
authors.initials: K
authors.lastname: Belfield
authors.affiliation: Biomaterials-Related Infection Group, School of Medicine, University of Nottingham, Queen's Medical Centre, Derby Rd., Nottingham NG7 2UH, UK. Electronic address: roger.bayston@nottingham.ac.uk.
authors.forename: Roger
authors.initials: R
authors.lastname: Bayston
authors.affiliation: NIHR Nottingham Hearing Biomedical Research Unit, Nottingham University Hospitals, Ropewalk House, 113 The Ropewalk, Nottingham NG1 5DU, UK; Otology and Hearing Group, Division of Clinical Neuroscience, University of Nottingham, Queen's Medical Centre, Derby Rd., Nottingham NG7 2UH, UK; Otorhinolaryngology, Nottingham University Hospitals, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, UK. Electronic address: Wendy.Phillips@nuh.nhs.uk.
authors.forename: J P
authors.initials: JP
authors.lastname: Birchall
authors.affiliation: Biomaterials-Related Infection Group, School of Medicine, University of Nottingham, Queen's Medical Centre, Derby Rd., Nottingham NG7 2UH, UK; NIHR Nottingham Hearing Biomedical Research Unit, Nottingham University Hospitals, Ropewalk House, 113 The Ropewalk, Nottingham NG1 5DU, UK; Otology and Hearing Group, Division of Clinical Neuroscience, University of Nottingham, Queen's Medical Centre, Derby Rd., Nottingham NG7 2UH, UK; Otorhinolaryngology, Nottingham University Hospitals, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, UK. Electronic address: Matija.Daniel@nottingham.ac.uk.
authors.forename: Matija
authors.initials: M
authors.lastname: Daniel
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018441:Biofilms / Q000187:drug effects*; D004432:Ear, Middle / Q000378:metabolism*; D006193:Haemophilus influenzae; D006801:Humans; D008826:Microbial Sensitivity Tests; D001936:Moraxella catarrhalis; D010034:Otitis Media with Effusion / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology*; D010933:Plankton; D013211:Staphylococcus aureus
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antibiotic; Biofilm; Ear; MIC; Otitis media