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Carmen Ponte

Publications and source records attributed to Carmen Ponte.

12 recordsLinked to original sources
PubMed2006

Impact of ibuprofen therapy in the outcome of experimental pneumococcal acute otitis media treated with amoxicillin or erythromycin.

The impact of ibuprofen combined with amoxicillin or erythromycin for therapy of penicillin-resistant pneumococcal acute otitis media (AOM) was evaluated in a gerbil model. Ibuprofen (at 2.5 or 7.5 mg/kg, orally) and/or amoxicillin or erythromycin (5 mg/kg each, s.c.) were administered at 5 h (early therapy, as single-dose regimen) or at 18 h (delayed therapy, five doses) postinoculation (PI). Each antibiotic alone and combined with ibuprofen was more effective administered as early regimen than as delayed treatment when evaluating the presence of otorrhea, otoscopic aspect, culture-positive and bacterial counts in middle ear (ME) samples, and loss of body weight. There was a trend for a better bacteriological outcome in animals receiving amoxicillin or erythromycin and ibuprofen, especially with the high dose. Such a dose of ibuprofen, associated with each antibiotic regimen, also preserved the animal well-being, avoiding a great weight loss in comparison to those receiving the antibiotic alone but a statistically significant difference was only observed for animals receiving delayed therapy with erythromycin and high-dose ibuprofen. In conclusion, ibuprofen combined with antibiotics seemed to improve the outcome of this experimental pneumococcal AOM.

Amoxicillin↗
PubMed2005

Effect of erythromycin treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae.

OBJECTIVE: To evaluate the effect of delayed administration of erythromycin in the course of acute otitis media caused by an erythromycin-susceptible Streptococcus pneumoniae strain in the gerbil model. METHODS: The bacterium was inoculated by transbullar challenge in the middle ear (ME) and antibiotic treatment at different doses was administered at various times thereafter. RESULTS: When 2.5 mg/kg of erythromycin was administered as a single dose 2, 5, 18 or 21 h post-inoculation (pi) the bacterial eradication rate was 55, 40, 0 and 0%, respectively. A higher dose (5 mg/kg) administered also as a single dose 2, 5, 18 and 21 h pi achieved bacterial eradication rates of 62.5, 43.8, 0 and 0%, respectively. Using a very high dose (50 mg/kg) repeated three times at 3 h intervals (total dose 150 mg/kg) and starting the treatment 21 h pi only achieved bacterial eradication in 25% of cases. The concentration of erythromycin achieved in the ME 90 min after administration of 5 mg/kg 5 or 21 h pi was very similar (0.74 and 0.79 mg/L) but the ME half-life was longer (98.2 min) with the early administration as compared with the delayed form (47.5 min), which could partially explain the different results. Further experiments showed that the failures observed with the delayed administration were not related to the time elapsed from antibiotic administration to ME sampling or selection of antibiotic-resistant mutants. CONCLUSION: Bacteriological and clinical efficacies were significantly diminished if antibiotic administration was delayed.

Animals↗
PubMed2005

Pulmonary damage and bacterial load in assessment of the efficacy of simulated human treatment-like amoxicillin (2,000 milligrams) therapy of experimental pneumococcal pneumonia caused by strains for which amoxicillin MICs differ.

An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, < or =0.015 and 2 microg/ml) and two non-amoxicillin-susceptible (MIC, 4 microg/ml) Streptococcus pneumoniae strains was developed for testing the efficacy of amoxicillin administered to simulate human serum kinetics after treatment with amoxicillin-clavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5 days). The end points for efficacy were reductions in bacterial loads in the lungs and reductions in levels of pulmonary damage. For the amoxicillin-susceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log(10) CFU/pair of lungs was obtained, and the time for which the serum antibiotic concentration (SAC) was higher than the MIC (T(S)(A)(C)(>)(MIC)) was greater than 60% of the dosing interval. For non-amoxicillin-susceptible strains, the decrease in bacterial load was 1.34 to 1.75 log(10) CFU/pair of lungs, with a T(S)(A)(C)(>)(MIC) of 46.7% of the dosing interval. An in vitro study showed that serotype 9V non-amoxicillin-susceptible strains behaved as tolerant-like to concentrations similar to those in the in vivo model. The high and maintained SACs (T(S)(A)(C)(>)(MIC), >46% for all strains) significantly diminished lung injury (affected area of the lung and lung weight), compared to that in controls, by all strains, regardless of the MIC, bactericidal behavior in in vitro killing curves, or the serotype of the infecting strain. These results show the importance of host therapeutic end points in the evaluation of antibiotic efficacy. The antibiotic was more efficacious, for one nonsusceptible strain tested, when the treatment was started early (1 h postinoculation [p.i.]) than when treatment was delayed (24 h p.i.).

Amoxicillin↗
PubMed2004

In vivo activity of amoxicillin/clavulanic acid and erythromycin in experimental otitis media caused by Streptococcus pneumoniae plus Haemophilus influenzae.

A gerbil model of acute otitis media induced by Streptococcus pneumoniae plus Haemophilus influenzae was used to assess the efficacy of amoxicillin/clavulanic acid (A/C) (1.5/0.3, 2.5/0.5 and 10/2 mg/kg) and erythromycin (2.5, 10, 20 and 50 mg/kg) with or without acetaminophen. The amoxicillin/clavulanic acid MIC was 1/0.5 mg/l for both organisms and the erythromycin MICs were 0.12 and 4 mg/l for S. pneumoniae and H. influenzae, respectively. The organisms were inoculated directly into the middle ear (ME) and antibiotic treatment started 2 h post-inoculation and continued at 8h intervals for three doses. Acetaminophen was administered at 50 mg/kg. Samples for bacterial counting were obtained from the ME on day 2. Amoxicillin/clavulanic acid peri-MIC concentrations in ME were effective in eradicating both organisms. Despite the inflammation induced by S. pneumoniae, erythromycin did not eradicate H. influenzae at ME concentrations (2.4 mg/l for erythromycin 50 mg/kg) higher than those obtained in humans but lower than the MIC.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2004

Effect of antibiotic treatment delay on therapeutic outcome of experimental acute otitis media caused by Streptococcus pneumoniae strains with different susceptibilities to amoxicillin.

The effect of delayed administration of amoxicillin on the course of acute otitis media (AOM) caused by two Streptococcus pneumoniae strains with different susceptibilities to amoxicillin (MICs of 0.016 and 1 microg/ml for strains A and B, respectively) was evaluated in the gerbil model. The organisms were inoculated by transbullar challenge into the middle ear, and antibiotic treatment was administered at various times thereafter. The bacteriological and clinical efficacies of treatment diminished significantly with the delay of antibiotic administration. The bacterial eradication rates when antibiotic treatment was started at 2, 5, 8, 18, and 21 h post-bacterial inoculation were different for both strains (95, 95, 90, 55, and 55% for strain A and 95, 95, 65, 10, and 0% for strain B). Results of further experiments using strain B with higher antibiotic doses and numbers of administrations and different follow-up times indicate that the failures observed with the delayed administration were not related to the bacterial burden, selection of antibiotic-resistant mutants, or inadequate pharmacodynamic parameters. Such failures may be related to the metabolic bacterial status. The delayed amoxicillin treatment of AOM caused by S. pneumoniae may lead to therapeutic failures, mainly when organisms with diminished antibiotic susceptibility are involved.

Amoxicillin↗
PubMed2004

Rational basis for optimizing antibiotic dosing regimens.

Adjustment of the antibiotic dosage is usually done taking into account pharmacokinetic parameters. However, as the bacterial response to the antimicrobial effect varies it is important to correlate pharmacokinetics with antimicrobial susceptibility data, the latter measured by determining the Minimum Inhibitory Concentration (MIC). It is now widely accepted that the ratio between the maximum antibiotic concentration achieved in serum and the MIC of the pathogen correlates with efficacy of aminoglycosides and fluoroquinolones. The ratio between the area under the serum concentration-time curve and the MIC correlates with efficacy of aminoglycosides and fluoroquinolones but also of vancomycin, tetracyclines, azithromycin, and quinupristin/dalfopristin. Finally the time for which antibiotic concentration in serum remains above the MIC correlates with efficacy of beta-lactams, most macrolides, and clindamycin. All the above mentioned pharmacodynamic parameters should be considered for optimizing antibiotic dosage.

Animals↗
PubMed2003

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.

Acetaminophen↗
PubMed2003

Is it possible to achieve bacterial eradication in otitis media with effusion by empirical antibiotic high doses and concomitant administration of acetaminophen? A microbiological and pharmacological study in the gerbil model.

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 beta-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 microg/ml) by 1.88-fold, whereas erythromycin concentrations were below MIC level of 4 microg/ml. Animals receiving acetaminophen showed significantly fewer polymorphonuclear cells and more Haemophilus organisms in the middle ear exudate.

Acetaminophen↗
PubMed2002

Optimal dose of amoxicillin in treatment of otitis media caused by a penicillin-resistant pneumococcus strain in the gerbil model.

Amoxicillin at doses of 0.2 to 5 mg/kg of body weight was administered for the treatment of pneumococcal otitis media in a gerbil model. Doses greater than or equal to 2.5 mg/kg, which resulted in concentrations in middle ear fluid of > or = 1.4 microg/ml and concentrations in serum higher than the MIC (1 microg/ml) for > or = 14% of the dosing interval, were both clinically and bacteriologically effective.

Amoxicillin↗