Antimicrobial treatment of an experimental otitis media caused by a beta-lactamase positive isolate of Haemophilus influenzae.
A gerbil model of otitis media induced by a beta-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (+/-10(6) cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses.
Ponte
C
C
Department of Medical Microbiology, Fundación Jiménez Díaz, Madrid, Spain.
Cenjor
C
C
Parra
A
A
Nieto
E
E
García-Calvo
G
G
Giménez
M J
MJ
Aguilar
L
L
Soriano
F
F
D019980:Amoxicillin-Potassium Clavulanate Combination / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002444:Cefuroxime / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005849:Gerbillinae; D006192:Haemophilus Infections / Q000188:drug therapy* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000201:enzymology / Q000302:isolation & purification; D006801:Humans; D008826:Microbial Sensitivity Tests; D010034:Otitis Media with Effusion / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000378:metabolism
D002511:Cephalosporins; D019980:Amoxicillin-Potassium Clavulanate Combination; D001618:beta-Lactamases; D002444:Cefuroxime