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No changes were found in the trends of the susceptibility patterns over the 4-year study period, with the exception of the semisynthetic penicillins, ticarcillin and mezlocillin. These two agents were found to be relatively ineffective against the strains of P aeruginosa isolated in 1989 (59% and 18% susceptibility, respectively). This finding is in contrast to their effectiveness over the remainder of the study period (96% and 90% susceptibility, respectively), which was excellent. These observations likely reflect a change in the breakpoints for the minimal inhibitory concentrations between these periods. The intravenous agent with the best susceptibility profile was piperacillin (96%). Of the aminoglycosides tested, 94% of the isolates were sensitive to tobramycin, as opposed to only 79% for gentamicin. This finding may have significance when one is empirically selecting ototopical therapy, since both tobramycin and gentamicin are available as topical preparations. Of the oral agents, the combination of sulfamethoxazole-trimethoprim was most effective (46%).
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A 49-year-old male developed bloody diarrhoea whilst on a visit to India. Sigmoidoscopy and rectal biopsy showed acute colitis. Shigella dysentery type I was isolated from stool culture. Cytotoxin production by the organism was demonstrated. The patient developed acute renal failure, thrombocytopaenia and microangiopathic haemolytic anaemia. He required mechanical ventilation, haemodialysis, blood transfusion and antibiotic therapy and achieved a complete recovery. This is an unusual case of haemolytic uraemic syndrome complicating shigellosis in an adult.
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A randomized, double-blind, double-dummy trial was performed comparing 200 mg of cefditoren-pivoxil twice daily for 5 days versus standard cefuroxime-axetil treatment (250 mg twice daily for 10 days) of Anthonisen type I or II acute exacerbations of chronic bronchitis. The modified intention-to-treat population included 541 patients. Patients were assessed during therapy, at the end of therapy (visit 3; primary evaluation time point), and at follow-up. Clinical success was obtained in 79.9% of the 264 patients included in the cefditoren-pivoxil group and in 82.7% of the 277 patients in the cefuroxime-axetil group (treatment difference, 95% confidence interval [CI]: -2.8, -9.7 to 3.6%). Treatment clinical effects were more clearly seen in sputum signs (decreasing volume and purulence from approximately 80% to approximately 10% of the patients). At the end of treatment, exploratory analysis of the per-pathogen bacteriological response showed 72.8% (of 103 isolates) in the cefditoren-pivoxil arm versus 67.0% (of 94 isolates) in the cefuroxime-axetil group (treatment difference; 95% CI: 5.8, -7.0 to 18.6%). Globally, the per-pathogen bacteriological response correlated well with clinical success: 83.5% of 164 baseline isolates from patients with a clinical success were eradicated or presumably eradicated, in contrast to only 3% of 33 isolates from patients with a clinical failure. Clinical success in patients infected with Haemophilus influenzae, the most frequent isolate, was 84% (of 50) and 82.5% (of 40) (treatment difference; 95% CI: 1.5, -14 to 17%) in the cefditoren-pivoxil versus the cefuroxime-axetil group. Although this study does not prove that either drug is better than a placebo, cefditoren-pivoxil and the standard 10-day cefuroxime-axetil course had similar point estimates of success in acute exacerbations of chronic bronchitis.
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Loracarbef is a new oral antimicrobial of the carbacephem class with in vitro activity against the common pathogens associated with skin infections, otitis media, sinusitis, bronchopulmonary infections, and urinary tract infections. A review of the literature shows the following ranges for 90% minimum inhibitory concentration (MIC90) values (microgram/mL) against the organisms that commonly cause these illnesses: Streptococcus pneumoniae, 0.25-2.0; Moraxella (Branhamella) catarrhalis (beta-lactamase positive), 0.5-8.0; M. catarrhalis (beta-lactamase negative), 0.12-0.25; Haemophilus influenzae (beta-lactamase positive), 0.5-16.0; H. influenzae (beta-lactamase negative), 0.25-8.0; Escherichia coli, 2.0-25; Klebsiella pneumoniae, 0.25-8.0; Proteus mirabilis, 1.0-8.0; Streptococcus pyogenes, less than or equal to 0.06-1.0; Staphylococcus aureus (beta-lactamase positive), 8.0; S. aureus (beta-lactamase negative), 1.0-2.0. The in vitro activity of loracarbef against these common outpatient pathogens is similar to that of other oral antimicrobials such as cefaclor, cefuroxime axetil, cefixime, amoxicillin/clavulanate, and trimethoprim/sulfamethoxazole. The results of in vitro susceptibility tests with any antimicrobial, including loracarbef, are somewhat dependent on the specific test method that is employed in the laboratory. This is particularly true with H. influenzae. Furthermore, the results of loracarbef susceptibility tests are of uncertain value in predicting therapeutic outcome.
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The stability of the amorphous form of cefuroxime axetil was studied by means of the stress stability test. The degradation was evaluated using the HPLC method with UV detection (278 nm), as described in the monograph of Cefuroxime Axetil in European Pharmacopoeia. Liquid chromatography was performed with a H5 SAS Hypersil column (5 microm particle size, 250 mmx4 mm), the mobile phase consisted of a mixture of 38 volumes of methanol and 62 volumes of a 23 g l-1 solution of ammonium dihydrogen phosphate, a flow rate of 1.2 ml min-1, and the internal standard was a solution of acetanilide in a mixture (1:1) of acetonitrile and water at a concentration of 0.2 mg ml-1. At an increased temperature at RH=0%, the degradation of cefuroxime axetil (CFA) diastereoisomers is the reversible first-order reaction, while that occurring in humid air (RH>25%) is the reversible first-order autocatalytic reaction with Delta3-isomers and E-isomers of cefuroxime axetil and cefuroxime as the main products.
Cefuroxime axetil (CA) was encapsulated in pH-sensitive acrylic microspheres in order to formulate a suspension dosage form. Using this microencapsulated form it was expected to prevent leaching of the drug from the microspheres into the suspension medium and to assure the release of the drug in the first part of the intestine, thus avoiding changes to its bioavailability. For this purpose, CA was microencapsulated within several types of acrylic polymers by the solvent evaporation and the solvent extraction techniques. The acrylic polymers selected were: Eudragit E (positively charged and soluble at pH 5), Eudragit L-55 (negatively charged and soluble at pH > 5.5) and Eudragit RL (neutral, insoluble, but readily permeable). The influence of the polymer electrical charge on the stability and in vitro release of CA was investigated. Though Eudragit E microspheres presented good morphological characteristics and dissolution behaviour, the analysis of the stability of CA in the presence of Eudragit E by HPLC, indicated a negative interaction between both compounds. However, formulations made of Eudragit L-55 and RL in the ratios 100:0 and 90:10 were adequate in terms of the stability of the encapsulated CA. The dissolution studies showed a critical pH between 5.2 and 6.0, which allowed the complete release of CA in a short period. Furthermore, these polymer microspheres were shown to be efficient in masking the taste of CA.