Does acetaminophen interfere in the antibiotic treatment of acute otitis media caused by a penicillin-resistant pneumococcus strain? A gerbil model.
The possible interference of acetaminophen, combined with antibiotics, in the treatment of acute otitis media (AOM) caused by a penicillin-resistant (minimal inhibitory concentration [MIC], 2 microg/mL), amoxicillin/clavulanic acid- and erythromycin-sensitive pneumococcus was evaluated in a gerbil model. Animals were challenged with approximately 5 x 106 bacteria in each ear through transbullar instillation. Acetaminophen was administered s.c. at 50 mg/kg 30 min before each antibiotic dose. Amoxicillin/clavulanic acid and erythromycin (2.5 and 10 mg/kg) were administered s.c. at 2, 10, and 18 h after inoculation. Samples were obtained from the middle ear (ME) on day 2 after inoculation for bacterial count. The overall results showed no difference between animals that received acetaminophen, with or without antibiotics, and those that did not receive acetaminophen. The antibiotic concentrations in the ME were practically identical in both groups of animals, so acetaminophen did not interfere with the pharmacokinetics of antibiotics in the ME. However, both antibiotics significantly reduced the number of culture-positive and the bacterial concentration in ME samples when compared with antibiotic-untreated animals. Both antibiotics, whether combined with acetaminophen or not, lowered the number of AOM to <25%, but >75% of animals presented otitis media with effusion, and no differences were shown between groups. A high rate of bacterial eradication from the ME correlated with antibiotic serum concentrations being over the MIC of the infecting organism for only >15% of the dose interval and with an ME concentration exceeding the MIC by a factor of 1.7. In this experimental model, acetaminophen had neither a synergistic nor an antagonistic effect on the antibiotics tested.
Ponte
Carmen
C
Department of Medical Microbiology, Fundación Jiménez Díaz, 28040 Madrid, Spain.
Parra
Araceli
A
Cenjor
Carlos
C
Garcia-Olmos
Marta
M
Gimenez
Maria Jose
MJ
Aguilar
Lorenzo
L
Carcas
Antonio
A
Soriano
Francisco
F
D000082:Acetaminophen / Q000493:pharmacokinetics*; D000208:Acute Disease; D000658:Amoxicillin / Q000493:pharmacokinetics*; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019818:Clavulanic Acid / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004347:Drug Interactions; D004917:Erythromycin / Q000493:pharmacokinetics; D005260:Female; D005849:Gerbillinae; D010033:Otitis Media / Q000188:drug therapy* / Q000382:microbiology; D010403:Penicillin Resistance; D011008:Pneumococcal Infections / Q000188:drug therapy*; D013296:Streptococcus pneumoniae / Q000187:drug effects
D018712:Analgesics, Non-Narcotic; D000900:Anti-Bacterial Agents; D019818:Clavulanic Acid; D000082:Acetaminophen; D004917:Erythromycin; D000658:Amoxicillin