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.
The efficacy of amoxycillin–clavulanic acid (10 and 15 mg/kg amoxycillin) and erythromycin (20 and 50 mg/kg) was assessed in a gerbil model of otitis media with effusion induced by ...β-lactamase-producing
Haemophilus influenzae. Animals were divided into groups receiving acetaminophen concomitantly or not receiving it. Treatment started 2 h post-middle ear inoculation and continued t.i.d. for up to three doses. Middle ear samples were obtained on day 2 post-inoculation. Amoxycillin–clavulanic acid showed significantly higher efficacy than erythromycin, regardless of acetaminophen administration (
P<0.05). Amoxycillin–clavulanic acid middle ear concentrations exceeded the amoxycillin MIC (1/0.5 μg/ml) by 1.88-fold, whereas erythromycin concentrations were below MIC level of 4 μg/ml. Animals receiving acetaminophen showed significantly fewer polymorphonuclear cells and more
Haemophilus organisms in the middle ear exudate.
Se evaluó el reinicio de la actividad ovárica posparto (RAO) y los metabolitos de lípidos en vacas lecheras suplementadas con aceite vegetal durante el posparto temprano. Se emplearon 18 vacas ...Holstein Friesian de tercer parto, de 597,3 ±50,2kg y condición corporal= 3,5 ±0,6. Los animales fueron distribuidos aleatoriamente en dos grupos, uno experimental suplementado con 500g de aceite vegetal durante 8 semanas a partir de la segunda semana posparto (CAV; n=9), y uno control sin suplemento (SAV; n=9). RAO se determinó cuando las concentraciones semanales de P4 fueron ³1ng/ml y se mantuvieron por dos semanas consecutivas. P4 fue medida por radioinmunoensayo y los metabolitos de lípidos (colesterol, lipoproteínas de alta y baja densidad, triglicéridos y lípidos totales) por enzimunocolorimetría, en muestras de sangre colectadas semanalmente durante el período de suplementación grasa. RAO se presentó siete días antes en el grupo CAV respecto a SAV (23,3 ±12,8 vs 29,6 ±12,4 días, P<0,05). La concentración media de P4 no se vio afectada (1,48 ±0,31 vs 1,15 ±0,31ng/ml para CAV y SAV, respectivamente); sin embargo, se observó un efecto significativo entre los días 28 y 56 a favor del grupo CAV. Entre los metabolitos de lípidos, solo colesterol, triglicéridos y lípidos totales mostraron diferencias (P<0,05): 109,3 ±9,9 vs 135,7 ±9,9; 29,3 ±7,9 vs 41,3 ±7,9; y 366,2 ±50,3 vs 434,2 ±50,3mg/dl para SAV y CAV, respectivamente. La suplementación grasa acorta el reinicio de la actividad ovárica posparto e incrementa la concentración plasmática de colesterol, triglicéridos y lípidos totales en vacas lecheras.
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.
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