Comparison of sulbactam/cefoperazone with imipenem as empirical monotherapy for febrile granulocytopenic patients.
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Biomedical subjects
Publications and source records attributed to J Borja.
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Enterococci are a frequent cause of nosocomial and community infections, especially the E. faecalis and E. faecium species. They often show intrinsic resistance to cephalosporins and quinolones, and acquired resistance to other antimicrobials, such as glycopeptides, has also been described. In order to test the impact of antibiotic resistance in enterococci isolated from infections, we carried out a multicenter study in 19 hospitals in Spain. We verified whether resistance to a high concentration of aminopenicillins and aminoglycosides was high (30.86% for ampicillin, 32.32% for gentamicin at a 500 micrograms dose, 55.93% for streptomycin at a 1000 micrograms dose) while the resistance to glycopeptides was low (1.8% for vancomycin and 1% for teicoplanin). It was also shown that teicoplanin had greater intrinsic activity than vancomycin, with teicoplanin 0.5 mg/l inhibiting 86.1% of the strains studied, whereas only 12.8% were inhibited with the same concentration of vancomycin.
We conducted a prospective, randomized, open-label trial, comparing oral ofloxacin with intravenous imipenem-cilastatin for the treatment of chronic osteomyelitis in order to evaluate the efficacy and tolerance. Hospitalized patients with diagnosis of chronic osteomyelitis and isolation of susceptible organisms to ofloxacin and imipenem/cilastatin were eligible for enrollment. Ofloxacin was administered orally (400 mg every 12 hours), and imipenem-cilastatin was given intravenously (500 mg every 6 hours). Organisms were considered susceptible to ofloxacin when the minimal inhibitory concentration (MIC) was <2 micrograms/ml, and to imipenem-cilastatin when the MIC was <4 micrograms/ml. Thirty-two patients were enrolled, 16 in each group. In the intent to treat analysis 11 (69%) patients in the ofloxacin group and eight (50%) in the imipenem-cilastatin group were cured (p = 0.473; 95% confidence interval of the difference from -14.7% to 52.2%). In the per protocol analysis 10 (91%) patients in the ofloxacin group and seven (70%) in the imipenem/cilastatin group were cured (p = 0.311; 95% confidence interval of the difference from -12.2% to 54%). Our trial suggests that oral ofloxacin is as effective as parenteral therapy with betalactam antibiotics in the treatment of osteomyelitis, which could allow a reduction of the period of hospitalization and economic costs.
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We describe eight patients suffering from Mercurochrome allergy. Patch and prick tests were carried out with the following organic and inorganic mercury compounds: thimerosal, Mercurochrome, phenylmercuric acetate, phenylmercuric nitrate, metallic mercury, and mercuric chloride, and with sodium fluorescein. Two patients had an anaphylactic reaction a few minutes after application of Mercurochrome. The prick tests with Mercurochrome were positive and they were negative with the other tested products. All patch tests were negative. In the other six patients, the clinical picture was local eczema, and the patch tests were all positive with Mercurochrome and the inorganic mercuric derivatives. Positive patch tests with thimerosal were found only in two patients, and only one had a positive patch test with salts of phenylmercury. In four patients, the prick test with Mercurochrome, negative in immediate reading, gave a late eczematous reaction.
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The methodological quality of 50 clinical trial protocols submitted to our hospital has been assessed by means of a check-list. The most frequent methodological deficiencies found were related to statistical analysis, selection criteria, sample size, incorrect use of placebo, homogeneity of the groups, concomitant medication, randomisation plan, monitoring of adverse events and study design. Lack of insurance for the patients and inadequacies in the investigators' brochure and case report forms were observed in a significant number of cases. The results suggest the importance of a multidisciplinary team in the elaboration of clinical trial protocols to prevent methodological errors.
Aminoglutethimide was the first aromatase inhibitor to be used in breast cancer therapy but, since it interacts with the synthetic glucocorticoids, hydrocortisone must also be given as a replacement. The most important side-effects of aminoglutethimide are at the level of the central nervous system. Other aromatase inhibitors with greater potency and selectivity are being developed. Pyridoglutethimide, a compound resulting from modifications to the structure of aminoglutethimide, seems to be devoid of sedative properties according to preliminary tests on the central nervous system. 4-Hydroxyandrostenedione is significantly more potent and better tolerated than aminoglutethimide. Fadrozole (CGS 16,949 A) is 200-400 times more potent than aminoglutethimide and is now in phase II of its clinical development. CGS 20,267 has no effect on adrenal steroidogenesis and is currently in phase I of its clinical development. Availability of newer aromatase inhibitors could make a worthwhile contribution to endocrine therapy in breast cancer.
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The best therapeutic approach to the therapy of potentially malignant ventricular arrhythmias is still unknown, particularly in view of the increased mortality with flecainide and encainide shown in the CAST study. Various ongoing studies, particularly with amiodarone, will show whether better results can be obtained with other agents. Flecainide and encainide do, however, have a restricted place when other agents cannot be used. Low-dose amiodarone with low-dose flecainide may be worth trying.
One tablet containing 755 mg of lithium tryptophanate (10.8 mEq of lithium) was administered to eight healthy volunteers. The main pharmacokinetic parameters for the group of subjects were estimated. Pharmacokinetic parameters (mean +/- SD) from plasma and saliva were respectively: half life (t1/2) 17 +/- 6 vs. 21.8 +/- 14 h; mean residence time 23.7 +/- 7.4 vs. 24.4 +/- 15.3 h; total clearance 30.6 +/- 9.3 vs. 28.6 +/- 6.2 ml/h/kg; and apparent volume of distribution 0.71 +/- 0.20 vs. 0.84 +/- 0.37 L/kg. Although the mean pharmacokinetic parameters in plasma and saliva were similar, there was no significant correlation between the calculated parameters in the individual subject (p greater than 0.05). The usefulness of monitoring salivary levels of lithium is questionable.
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An open-label, randomized, comparative, parallel-group study of ofloxacin and trimethoprim-sulfamethoxazole was performed in 162 outpatients diagnosed with acute exacerbation of chronic bronchitis. Ofloxacin 400 mg once daily was administered orally; the dose could be increased to 400 mg twice daily if patients had not improved after 72 hours of treatment. The other treatment group received trimethoprim-sulfamethoxazole 960 mg twice daily orally. The duration of treatment was 10 to 14 days for both treatment groups. Successful clinical response (defined as cure or major improvement in symptoms) was achieved in 65 (80.2%) patients in the ofloxacin group and in 42 (51.9%) patients in the trimethoprim-sulfamethoxazole group; the differences between groups were statistically significant. Bacteriologic success (classified as eradication or presumptive eradication of the causative pathogen) was achieved in 27 (50.0%) patients in the ofloxacin group and in 16 (29.1%) patients in the trimethoprim-sulfamethoxazole group; these differences between groups were also statistically significant. Reinfection occurred in 18 (33.3%) and 4 (7.3%) patients treated with ofloxacin and trimethoprim-sulfamethoxazole, respectively. No serious adverse events were reported.