Penetration of ceftibuten into middle ear fluid.

The penetration of ceftibuten, an extended-spectrum oral cephalosporin, into middle ear fluid (MEF) was evaluated in pediatric patients during a course of daily oral doses of 9 mg/kg of body weight for 10 days. Plasma and MEF collected at 2, 4, 6, or 12 h after at least 3 days of dosing were analyzed for ceftibuten by a high-pressure liquid chromatography method, and the data were used to calculate pharmacokinetic parameters. Plasma and MEF had almost identical maximum concentrations (Cmax) of ceftibuten (14 micrograms/ml). These Cmax values in MEF during acute otitis media were well in excess of the MIC for 90% of the isolates of each of four major pathogens in this disease. The time to Cmax was longer in MEF (4 h) than in plasma (2 h). Excellent penetration (71%) of ceftibuten into MEF was observed on the basis of the area under the curve ratio (MEF/plasma). These data clearly indicate that ceftibuten penetrated well into the MEF to yield clinically effective concentrations.

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Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.45.2.596-600.2001 ◽

2001 ◽

Vol 45 (2) ◽

pp. 596-600 ◽

Cited By ~ 45

Author(s):

Andreas H. Groll ◽

Bryan M. Gullick ◽

Ruta Petraitiene ◽

Vidmantas Petraitis ◽

Myrna Candelario ◽

...

Keyword(s):

High Performance ◽

Pharmacokinetic Model ◽

Area Under The Curve ◽

Apparent Volume ◽

Volume Of Distribution ◽

Pharmacokinetic Parameters ◽

Chromatography Method ◽

Opportunistic Fungi ◽

The Mean ◽

Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

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PENETRATION OF CEFPODOXIME INTO MIDDLE EAR FLUID IN PEDIATRIC PATIENTS WITH ACUTE OTITIS MEDIA

The Pediatric Infectious Disease Journal ◽

10.1097/00006454-199701000-00020 ◽

1997 ◽

Vol 16 (1) ◽

pp. 79-81 ◽

Cited By ~ 5

Author(s):

Jacobus C. van Dyk ◽

Susan A. Terespolsky ◽

Carl S. Meyer ◽

Christo H. van Niekerk ◽

Keith P. Klugman

Keyword(s):

Otitis Media ◽

Middle Ear ◽

Pediatric Patients ◽

Acute Otitis Media ◽

Middle Ear Fluid

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Comprehensive Detection of Respiratory Bacterial and Viral Pathogens in the Middle Ear Fluid and Nasopharynx of Pediatric Patients With Acute Otitis Media

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000002486 ◽

2019 ◽

Vol 38 (12) ◽

pp. 1199-1203 ◽

Cited By ~ 10

Author(s):

Shoichi Sawada ◽

Fumino Okutani ◽

Taisuke Kobayashi

Keyword(s):

Otitis Media ◽

Middle Ear ◽

Pediatric Patients ◽

Acute Otitis Media ◽

Viral Pathogens ◽

Middle Ear Fluid

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Detecting middle ear fluid using smartphones

Science Translational Medicine ◽

10.1126/scitranslmed.aav1102 ◽

2019 ◽

Vol 11 (492) ◽

pp. eaav1102 ◽

Cited By ~ 10

Author(s):

Justin Chan ◽

Sharat Raju ◽

Rajalakshmi Nandakumar ◽

Randall Bly ◽

Shyamnath Gollakota

Keyword(s):

Otitis Media ◽

Middle Ear ◽

Learning Algorithm ◽

Otitis Media With Effusion ◽

Acute Otitis Media ◽

Area Under The Curve ◽

Middle Ear Fluid ◽

Unseen Data ◽

Custom Hardware ◽

Leave One Out

The presence of middle ear fluid is a key diagnostic marker for two of the most common pediatric ear diseases: acute otitis media and otitis media with effusion. We present an accessible solution that uses speakers and microphones within existing smartphones to detect middle ear fluid by assessing eardrum mobility. We conducted a clinical study on 98 patient ears at a pediatric surgical center. Using leave-one-out cross-validation to estimate performance on unseen data, we obtained an area under the curve (AUC) of 0.898 for the smartphone-based machine learning algorithm. In comparison, commercial acoustic reflectometry, which requires custom hardware, achieved an AUC of 0.776. Furthermore, we achieved 85% sensitivity and 82% specificity, comparable to published performance measures for tympanometry and pneumatic otoscopy. Similar results were obtained when testing across multiple smartphone platforms. Parents of pediatric patients (n = 25 ears) demonstrated similar performance to trained clinicians when using the smartphone-based system. These results demonstrate the potential for a smartphone to be a low-barrier and effective screening tool for detecting the presence of middle ear fluid.

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Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Clinical and Vaccine Immunology ◽

10.1128/cvi.05443-11 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1593-1596 ◽

Cited By ~ 15

Author(s):

Ravinder Kaur ◽

Thomas Kim ◽

Janet R. Casey ◽

Michael E. Pichichero

Keyword(s):

Middle Ear ◽

Acute Otitis Media ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Two Dimensional Gel Electrophoresis ◽

Middle Ear Fluid ◽

Iga Antibodies ◽

Iga Antibody ◽

Entire Array

ABSTRACTThe human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. The total IgG and IgA antibodies in the MEF and NW samples of 137 children were compared. The ratio of IgG to IgA in the MEF was significantly different (P< 0.008) compared to NW because IgA levels were higher and IgG levels lower in NW. The IgG/IgA ratio of MEF resembled serum consistent with transudation to the MEF. Small amounts of secretory IgA were detected in MEF but the electrophoresis patterns of the entire array of IgA antibodies in the MEF and NW were virtually identical in each child evaluated; thus, IgA in MEF derived predominantly from serum and the nasopharynx by reflux via the Eustachian tube. The IgG/IgA antibody levels in the MEF and the same composition of IgA antibody in the MEF and NW identifies the predominant source of antibody in the MEF as a transudate of serum combined with nasal secretions refluxed from the nasopharynx in children.

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Acute Mastoiditis in the Pneumococcal Conjugate Vaccine Era

Clinical and Vaccine Immunology ◽

10.1128/cvi.00289-14 ◽

2014 ◽

Vol 21 (8) ◽

pp. 1189-1191 ◽

Cited By ~ 14

Author(s):

Sharon Ovnat Tamir ◽

Yehudah Roth ◽

Ilan Dalal ◽

Abraham Goldfarb ◽

Tal Marom

Keyword(s):

Streptococcus Pneumoniae ◽

Middle Ear ◽

Pneumococcal Conjugate Vaccine ◽

Inverse Relationship ◽

Acute Otitis Media ◽

Acute Mastoiditis ◽

Conjugate Vaccines ◽

Content Type ◽

Bacterial Cultures ◽

Middle Ear Fluid

ABSTRACTFollowing the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive forStreptococcus pneumoniaeamong a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea.

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