Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media

Daniel M. Canafax, Zhi Yuan, Tasnee Chonmaitree, Kamal Deka, Henry Q. Russlie, G. Scott Giebink

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background. Acute otitis media (AOM) is a common childhood infectious disease. The efficacy of antibiotic dosing regimens is usually assessed by antibiotic plasma pharmacokinetics or middle ear fluid (MEF) concentration at one or two time points. Viral coinfection in AOM reduced antibacterial efficacy of antibiotics. Objective. To determine amoxicillin MEF penetration and pharmacokinetics in bacterial and combined bacterial and vital AOM. Methods. Thirty-four children with AOM were enrolled, and MEF was collected by tympanocentesis for bacterial culture and viral studies. Nasal wash and venous blood were also obtained for viral culture and serologic studies, respectively. Subjects were treated with amoxicillin 40 mg/kg/day orally, divided in equal doses every 8 h. During the second visit (48 to 72 h later) the subjects, with the regular morning amoxicillin dose withheld, were given an oral amoxicillin dose of 25 mg/kg. Thereafter two blood samples and one MEF sample by tympanocentesis were collected from each child at selected times between 0.5 and 4.0 h after dosing for bacterial and viral studies and amoxicillin concentration determination by high performance liquid chromatography. Results. Eleven (37%) children had only bacterial infection, 6 (20%) had viral infection only, 6 (20%) had both bacterial and viral infections and in 7 (23%) neither bacterial nor viral pathogens were recovered. MEF bacterial culture was positive in 23 of 40 ears (57.5%) before treatment with amoxicillin (40 mg/kg/day) and was still positive in 4 of 38 ears (10.5%) after 2 to 3 days of treatment. Amoxicillin plasma concentration reached its peak at 1.0 to 1.5 h after a 25-mg/kg oral dose. The estimated MEF concentration peak occurred 3.0 h after the dose with MEF concentrations ranging from undetectable to 20.6 μg/ml and a mean of ~9.5 μg/ml. Geometric mean amoxicillin concentrations were lowest in virus-infected children (2.7 μg/ml), nearly the same in culture-negative samples from children without vital infection (2.9 μg/ml), higher in children with combined bacterial and vital infection (4.1 μg/ ml) and highest in children with bacterial-only infection (5.7 μg/ml). Conclusions. MEF amoxicillin penetration tended to be lower in children with viral infection. The current amoxicillin dosing recommendation of 40 mg/kg/day in three divided dose is inadequate to effectively eradicate resistant Streptococcus pneumoniae, particularly during viral coinfection. A dosing regimen of 75 to 90 mg/kg/day is recommended for AOM.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalPediatric Infectious Disease Journal
Volume17
Issue number2
DOIs
StatePublished - Feb 1998

Fingerprint

Amoxicillin
Otitis Media
Middle Ear
Pharmacokinetics
Bacterial Infections
Virus Diseases
Anti-Bacterial Agents
Coinfection
Ear
Streptococcus pneumoniae
Nose
Communicable Diseases
High Pressure Liquid Chromatography
Viruses

Keywords

  • Acute otitis media
  • Amoxicillin
  • Pharmacokinetics
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)

Cite this

Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media. / Canafax, Daniel M.; Yuan, Zhi; Chonmaitree, Tasnee; Deka, Kamal; Russlie, Henry Q.; Giebink, G. Scott.

In: Pediatric Infectious Disease Journal, Vol. 17, No. 2, 02.1998, p. 149-156.

Research output: Contribution to journalArticle

Canafax, Daniel M. ; Yuan, Zhi ; Chonmaitree, Tasnee ; Deka, Kamal ; Russlie, Henry Q. ; Giebink, G. Scott. / Amoxicillin middle ear fluid penetration and pharmacokinetics in children with acute otitis media. In: Pediatric Infectious Disease Journal. 1998 ; Vol. 17, No. 2. pp. 149-156.
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abstract = "Background. Acute otitis media (AOM) is a common childhood infectious disease. The efficacy of antibiotic dosing regimens is usually assessed by antibiotic plasma pharmacokinetics or middle ear fluid (MEF) concentration at one or two time points. Viral coinfection in AOM reduced antibacterial efficacy of antibiotics. Objective. To determine amoxicillin MEF penetration and pharmacokinetics in bacterial and combined bacterial and vital AOM. Methods. Thirty-four children with AOM were enrolled, and MEF was collected by tympanocentesis for bacterial culture and viral studies. Nasal wash and venous blood were also obtained for viral culture and serologic studies, respectively. Subjects were treated with amoxicillin 40 mg/kg/day orally, divided in equal doses every 8 h. During the second visit (48 to 72 h later) the subjects, with the regular morning amoxicillin dose withheld, were given an oral amoxicillin dose of 25 mg/kg. Thereafter two blood samples and one MEF sample by tympanocentesis were collected from each child at selected times between 0.5 and 4.0 h after dosing for bacterial and viral studies and amoxicillin concentration determination by high performance liquid chromatography. Results. Eleven (37{\%}) children had only bacterial infection, 6 (20{\%}) had viral infection only, 6 (20{\%}) had both bacterial and viral infections and in 7 (23{\%}) neither bacterial nor viral pathogens were recovered. MEF bacterial culture was positive in 23 of 40 ears (57.5{\%}) before treatment with amoxicillin (40 mg/kg/day) and was still positive in 4 of 38 ears (10.5{\%}) after 2 to 3 days of treatment. Amoxicillin plasma concentration reached its peak at 1.0 to 1.5 h after a 25-mg/kg oral dose. The estimated MEF concentration peak occurred 3.0 h after the dose with MEF concentrations ranging from undetectable to 20.6 μg/ml and a mean of ~9.5 μg/ml. Geometric mean amoxicillin concentrations were lowest in virus-infected children (2.7 μg/ml), nearly the same in culture-negative samples from children without vital infection (2.9 μg/ml), higher in children with combined bacterial and vital infection (4.1 μg/ ml) and highest in children with bacterial-only infection (5.7 μg/ml). Conclusions. MEF amoxicillin penetration tended to be lower in children with viral infection. The current amoxicillin dosing recommendation of 40 mg/kg/day in three divided dose is inadequate to effectively eradicate resistant Streptococcus pneumoniae, particularly during viral coinfection. A dosing regimen of 75 to 90 mg/kg/day is recommended for AOM.",
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N2 - Background. Acute otitis media (AOM) is a common childhood infectious disease. The efficacy of antibiotic dosing regimens is usually assessed by antibiotic plasma pharmacokinetics or middle ear fluid (MEF) concentration at one or two time points. Viral coinfection in AOM reduced antibacterial efficacy of antibiotics. Objective. To determine amoxicillin MEF penetration and pharmacokinetics in bacterial and combined bacterial and vital AOM. Methods. Thirty-four children with AOM were enrolled, and MEF was collected by tympanocentesis for bacterial culture and viral studies. Nasal wash and venous blood were also obtained for viral culture and serologic studies, respectively. Subjects were treated with amoxicillin 40 mg/kg/day orally, divided in equal doses every 8 h. During the second visit (48 to 72 h later) the subjects, with the regular morning amoxicillin dose withheld, were given an oral amoxicillin dose of 25 mg/kg. Thereafter two blood samples and one MEF sample by tympanocentesis were collected from each child at selected times between 0.5 and 4.0 h after dosing for bacterial and viral studies and amoxicillin concentration determination by high performance liquid chromatography. Results. Eleven (37%) children had only bacterial infection, 6 (20%) had viral infection only, 6 (20%) had both bacterial and viral infections and in 7 (23%) neither bacterial nor viral pathogens were recovered. MEF bacterial culture was positive in 23 of 40 ears (57.5%) before treatment with amoxicillin (40 mg/kg/day) and was still positive in 4 of 38 ears (10.5%) after 2 to 3 days of treatment. Amoxicillin plasma concentration reached its peak at 1.0 to 1.5 h after a 25-mg/kg oral dose. The estimated MEF concentration peak occurred 3.0 h after the dose with MEF concentrations ranging from undetectable to 20.6 μg/ml and a mean of ~9.5 μg/ml. Geometric mean amoxicillin concentrations were lowest in virus-infected children (2.7 μg/ml), nearly the same in culture-negative samples from children without vital infection (2.9 μg/ml), higher in children with combined bacterial and vital infection (4.1 μg/ ml) and highest in children with bacterial-only infection (5.7 μg/ml). Conclusions. MEF amoxicillin penetration tended to be lower in children with viral infection. The current amoxicillin dosing recommendation of 40 mg/kg/day in three divided dose is inadequate to effectively eradicate resistant Streptococcus pneumoniae, particularly during viral coinfection. A dosing regimen of 75 to 90 mg/kg/day is recommended for AOM.

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