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Biomedical subjects

Francisco Soriano

Publications and source records attributed to Francisco Soriano.

At least 19 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↗
PubMed2006

Correlation between in vitro and in vivo activity of levofloxacin and moxifloxacin against pneumococcal strains with different susceptibilities to fluoroquinolones.

In vitro and in vivo models were developed to evaluate the efficacy of levofloxacin and moxifloxacin against three serotype 3 pneumococcal strains with different susceptibilities to fluoroquinolones (wild-type, parC mutant, and parC, parE and gyrA mutant). Levofloxacin and moxifloxacin reduced the bacterial burden in the in vitro pharmacodynamic and animal models for the wild-type strain but had very little activity against the fully resistant strain (parC, parE and gyrA mutant). Levofloxacin showed very little activity both in the in vitro pharmacodynamic model and in the animal model for the strain having a mutation in parC (levofloxacin and moxifloxacin minimum inhibitory concentrations, 2mg/L and 0.25mg/L, respectively). However, moxifloxacin still had a significant in vitro and in vivo activity against this strain.

Animals↗
PubMed2006

Local and systemic effects of hypertonic solution (NaCl 7.5%) in experimental acute pancreatitis.

OBJECTIVES: Severe acute pancreatitis (AP) is characterized by hemodynamic alterations and a systemic inflammatory response, leading to a high mortality rate. Treatment of hemorrhagic shock with hypertonic saline solutions significantly reduces mortality through an improvement in the hemodynamic conditions and possibly by an anti-inflammatory effect. Therefore, hypertonic solutions could be effective in AP. METHODS: Wistar rats were divided in 4 groups: group C, control, without AP; group NT, AP, without treatment; group NS, treatment with normal saline solution (NaCl 0.9%) 1 hour after AP; group HTS, treatment with hypertonic saline solution (NaCl 7.5%) 1 hour after AP. AP was induced by injection of 2.5% sodium taurocholate into the pancreatic duct. Mean arterial blood pressure (MAP) and heart rate were recorded at 0 and 2, 4, 24, and 48 hours after AP. After induction of AP, animals were killed at 2, 12, 24, and 48 hours for serum amylase, interleukin (IL)-6, and IL-10 analysis, pancreatic tissue culture and histologic analysis, oxidation and phosphorylation of liver mitochondria, pulmonary myeloperoxidase activity (MPO), and mortality study. RESULTS: In animals of groups NS and NT, a significant decrease of MAP was observed 48 hours after AP (NS: 91 +/- 3 mm Hg; NT: 89 +/- 3 mm Hg) compared with baseline (C: 105 +/- 2 mm Hg) and to HTS group (HTS: 102 +/- 2 mm Hg; P < 0.05). In animals of group NT, NS, and HTS, serum IL-6 and IL-10 levels were significantly higher at 2 hours after AP compared with the control group. However, IL-6 levels at 12 hours after AP and IL-10 levels at 2 and 12 hours after AP were significant lower in group HTS compared with NS and NT groups (P < 0.05). In group HTS, a decrease of pulmonary MPO activity and of pancreatic infection was observed 24 hours after AP compared with NT and NS groups (P < 0.05). A significant reduction on pancreatic acinar necrosis and mitochondrial dysfunction was observed after 48 hours of AP in animals of group HTS compared with groups NT and NS (P < 0.05). A significant reduction on mortality was observed in HTS (0/14) compared with NS (6/17; 35%) and NT (7/20; 35%). CONCLUSIONS: The administration of hypertonic saline solution in experimental AP attenuated hemodynamic alterations, decreased inflammatory cytokines, diminished systemic lesions and pancreatic acinar necrosis, prevented pancreatic infection, and reduced the mortality rate.

Acute Disease↗
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

Urinary concentrations and bactericidal activity against amoxicillin-nonsusceptible strains of Escherichia coli with single-dose, oral, sustained-release amoxicillin/clavulanic acid: a phase I, open-label, noncomparative clinical trial in healthy volunteers.

BACKGROUND: Urinary tract infections (UTIs) account for 5 to 6 million medical consultations in the United States each year. Worldwide, an estimated 20% to 30% of women aged 20 to 40 years have at least 1 episode of the most common type of UTI (uncomplicated cystitis) in their lifetime, with Escherichia coli being the causative pathogen in 80% of cases. Antibacterial activity in urine has been shown to be correlated with outcomes of uncomplicated cystitis. OBJECTIVE: The objectives of this study were to determine urinary concentrations and ex vivo bactericidal activity of sustained-release (SR) amoxicillin/clavulanic acid 2000/125 mg against intermediately resistant and resistant strains of E coli over 72 hours and compare them with those of a susceptible strain. This study also investigated whether urinary concentrations obtained after dosing cover E coli strains categorized as intermediately resistant and resistant based on current Clinical and Laboratory Standards Institute (formerly NCCLS) breakpoints in uncomplicated cystitis. METHODS: This Phase I, open-label, noncomparative study in healthy male volunteers was conducted at the Pharmacology Unit, Autónoma University, Madrid, Spain. Subjects received a single oral dose of amoxicillin/clavulanic acid 2000/125 mg SR. The amoxicillin/clavulanic acid MICs were 8/4 microg/mL (susceptible), 16/8 microg/mL (intermediately resistant), and 32/16 and 64/32 microg/mL (resistant). Urine samples were collected before (baseline; time 0) and at the following intervals: 0-2, 2-4, 4-8, 8-12, 12-16, 16-24, 24-36, 36-48, 48-60, and 60-72 hours after dosing. Killing curves with urine samples were performed with initial inocula of approximately 10(7) colony-forming units (CFU)/mL, and bactericidal activity (defined as >3 log(10) CFU/mL and >99.9% reduction in bacterial counts) was calculated as the difference between log(10) initial inoculum and log(10) CFU/mL after 4 hours of incubation of each sample. RESULTS: Twelve volunteers were included (mean [SD] age, 24.83 [5.64] years; mean [SD] height, 175.75 [7.56] cm; and mean [SD] weight, 73.55 [9.19] kg). No statistically significant differences between the activities in the 12-16-hour interval compared with baseline were found in any of the strains tested. Bactericidal activity against the susceptible and intermediately resistant strains (MICs 8/4 and 16/8 g/mL, respectively) was obtained up to 8 hours after dosing. Bactericidal activity against the resistant strains (MICs 32/16 and 64/32 microg/mL) was obtained in the 2-4-hour interval. CONCLUSIONS: In this Phase I study in healthy volunteers, urinary concentrations after dosing with amoxicillin/clavulanic acid 2000/125 mg SR showed bactericidal activity against the amoxicillin-susceptible and intermediately resistant strains of E coli.

Adult↗
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↗
PubMed2005

[Pneumococcal septic arthritis in a Spanish university hospital (1993- 2003)].

INTRODUCTION: Cases of pneumococcal septic arthritis treated in the Fundación Jiménez Díaz (Madrid, Spain) were reviewed. METHODS: A retrospective record review was conducted for all patients presenting with pneumococcal septic arthritis between January 1993 and August 2003. RESULTS: Four patients out of a total of 267 reviewed had a clinical and microbiological diagnosis of septic arthritis caused by Streptococcus pneumoniae. The most frequent locations were the knee, ankle and tarsus. Three of the four patients had underlying diseases and one patient died. CONCLUSIONS: Pneumococcal septic arthritis, a very rare clinical entity diagnosed by clinical and microbiological findings, should be suspected in patients with underlying disease. Early antibiotic therapy focussed on the most common microorganisms causing septic arthritis is necessary for optimal outcome.

Aged↗
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

The adenosine A3 receptor agonist, N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide, is protective in two murine models of colitis.

This study evaluated the effects of the adenosine A(3) receptor agonist, N(6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA), in two murine models of colitis, the dextran sodium sulphate-induced colitis and the spontaneous colitis found in interleukin-10 gene deficient mice. IB-MECA was given orally twice a day at a dose of either 1 or 3 mg/kg/day. Evaluation of colon damage and inflammation was determined grossly (body weight, rectal bleeding) and biochemically (colon levels of myeloperoxidase, malondialdehyde, chemokines and cytokines). There was significantly increased inflammatory cell infiltration into the colon associated with an increase in colon levels of cytokines and chemokines; with subsequent free radical related damage in both dextran sodium sulphate-induced colitis and 10-week-old interleukin-10(-/-) mice. IB-MECA protected in both models against the colitis induced inflammatory cell infiltration and damage and attenuated the increases in colon inflammatory cytokine and chemokine levels. Thus activation of the adenosine A(3) receptor is effective in protecting against colitis.

Adenosine↗
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

[Pharmacokinetic and pharmacodynamic concepts for an interpretative reading of the antibiogram].

Both microbiological and epidemiological reading of the antibiogram can be performed without additional pharmacokinetic or pharmacodynamic concepts. However, when the aim is a clinical reading of the antibiogram, knowledge of the pharmacokinetics of antimicrobial agents and of all phenomena occurring between antimicrobial agents and microorganisms is imperative. Pharmacokinetics includes the study of absorption, distribution, metabolism and elimination of drugs. These data provide information on the active concentrations of antimicrobial agents in blood and other fluids as well as in the tissues where infection may develop. Knowledge of metabolism and of elimination pathways complete the main pharmacokinetic parameters of antimicrobial agents. The bactericidal effect of antimicrobial agents can be either concentration- or time-dependent. In the former, high concentrations of antimicrobial agents, much higher than their corresponding MICs, are needed, while in the latter, maintaining the concentration of antimicrobial agents at levels slightly higher than their MICs over time is more important. With these concepts, a microbiological-pharmacological reading of the antibiogram, taking into account dosage, administration pathway and location of the infectious process among other factors, can be achieved. Most working groups, either national or from abroad, have considered both pharmacokinetics and pharmacodynamics in interpretative reading of the antibiogram. In all cases, breakpoints for susceptibility and resistance should be corrected on the basis of data from well designed and performed clinical trials. Clinically oriented breakpoints do not necessarily have to be the same as those based on microbiological or epidemiological concepts, but clinical microbiologists should be able to give an appropriate response to the question and to the application based on that response.

Algorithms↗
PubMed2002

The efficacy and safety of oral pharmacokinetically enhanced amoxycillin-clavulanate 2000/125 mg, twice daily, versus oral amoxycillin-clavulanate 1000/125 mg, three times daily, for the treatment of bacterial community-acquired pneumonia in adults.

This double-blind, double-dummy, parallel-group study was designed to show that a pharmacokinetically enhanced formulation of oral amoxycillin-clavulanate (16:1, 2000/125 mg), twice daily, is at least as effective clinically and microbiologically as oral amoxycillin-clavulanate 1000/125 mg, three times daily, in the 10 day treatment of community-acquired pneumonia (CAP) in adults. The pharmacokinetically enhanced formulation is designed to provide higher serum concentrations of amoxycillin for a longer period than standard dosing to achieve coverage of Streptococcus pneumoniae isolates with amoxycillin-clavulanic acid minimum inhibitory concentrations (MICs) up to and including 4 mg/l. A total of 344 patients with CAP from 77 centres received amoxycillin-clavulanate 2000/125 mg twice daily for 10 days (169 patients) or amoxycillin-clavulanate 1000/125 mg three times daily for 10 days (175 patients). The most common pathogen isolated was S. pneumoniae (52.3% of patients, amoxycillin-clavulanate 2000/125 mg group; 46.8% of patients, amoxycillin-clavulanate 1000/125 mg group). In the clinical per-protocol (PP) population at test of cure (days 18-39), the clinical success rate in the amoxycillin-clavulanate 2000/125 mg group was at least as good as in the amoxycillin-clavulanate 1000/125 mg group (91.5 and 93.0%, respectively; 95% CI, -8.3, 5.4). The radiological and bacteriological success rates at test of cure for the PP populations were 92.4 and 90.6% in the amoxycillin-clavulanate 2000/125 mg group and 93.9 and 84.4% in the amoxycillin-clavulanate 1000/125 mg group, respectively. The clinical, bacteriological and radiological success rates at the end of therapy (days 11-17) for the PP populations were all over 85%. Both regimens were well tolerated, with no differences in adverse events between the groups. Amoxycillin-clavulanate 2000/125 mg, twice daily, is well tolerated and at least as effective clinically as amoxycillin-clavulanate 1000/125 mg, three times daily, in patients with CAP and may also be appropriate for the treatment of infections due to S. pneumoniae strains with high-level penicillin resistance.

Adult↗