No abstract

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 g/mL), amoxicillin/clavulanic acid-and erythromycin-sensitive pneumococcus was evaluated in a gerbil model. Animals were challenged with 5 ϫ 10 6 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 Ͻ25%, but Ͼ75% 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 Ͼ15% 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. Abbreviations AOM, acute otitis media BHIE, brain-heart infusion broth enriched with 5% horse serum C 15 min, concentration at 15 min after antibiotic administration CFU, colony-forming units MBC, minimal bactericidal concentration ME, middle ear MEF, middle ear fluid without washing MEWF, middle ear washing fluid MIC, minimal inhibitory concentration MIC 50 , minimal concentration inhibiting 50% of the strains tested MIC 90 , minimal concentration inhibiting 90% of the strains tested OME, otitis media with effusion Acute otitis media (AOM) is one of the most frequently diagnosed infectious diseases of childhood, and the number of office visits for this pathology is increasing in many countries (1). One of the most common approaches to treating AOM in children is to administer an antibiotic to eradicate the pathogen, as well as an anti-inflammatory or analgesic drug such as acetaminophen (2, 3). Anti-inflammatory activity is mainly exerted through the inhibition of COX-1 and COX-2 isoenzymes that catalyze the rate-limiting step of prostaglandin synthesis (4). Recent data suggest that the little antiinflammatory activity of acetaminophen is due to its activity against COX-3 (that shows Ͻ20% activity of COX-1 and COX-2 and is present at approximately 25% of the level ...

No abstract

A fatal guinea pig model of pneumococcal pneumonia was developed in order to evaluate the efficacy of amoxicillin combined with either pentoxifylline or dexamethasone. Parameters assessed were survival time and lung changes (alterations, bacterial colony counts, inducible nitric oxide synthase [iNOS] and cyclooxygenase-2 [COX-2] protein expression). Animals receiving pentoxifylline (50 mg/kg) showed higher survival rates than controls (p < 0.05). Animals which received amoxicillin (50 mg/kg), alone or combined, showed significantly higher survival rates than controls (p < 0.05). Animals dying in spite of receiving amoxicillin alone or combined had lung colony counts significantly lower than those that did not receive the antibiotic (p < 0.001), but their lungs showed identical changes. The correlation between COX-2 protein expression and mortality was rather high (r = 0.75). The addition of either dexamethasone or pentoxifylline to amoxicillin improved neither survival rates nor lung pathology when compared with the antibiotic alone.