Synthesis, characterization, microbiological evaluation, genotoxicity and synergism tests of new nano silver complexes with sulfamoxole: X-ray diffraction of [Ag2(SMX)2]·DMSO.

The synthesis and microbiological evaluation of two new Ag(I) complexes with sulfamoxole (SMX), [Ag2(SMX)2]·H2O and [Ag4(SCN)3(SMX)]·H2O are described. Both were characterized by elemental analysis, thermogravimetry, powder and single crystal X-ray diffraction, NMR, Raman and experimental and theoretical IR spectroscopies. Their antibacterial and antifungal properties were evaluated by agar and broth dilution assays, respectively. In addition, synergism tests for Pseudomonas aeruginosa were performed, and genotoxicity studies were carried out employing the Allium cepa test. Both complexes displayed good activity against Escherichia coli, Staphylococcus aureus, P. aeruginosa, and 10 fungi strains, with lower minimum inhibitory concentrations (MICs) than that of free SMX in all cases. The nanometrical crystallite particle size determined from XRPD, DLS and TEM might explain the good microbiological activity in spite of the low solubility of both complexes. The fractional inhibitory concentration (FIC) calculated from the P. aeruginosa test data indicated that the activity of the complexes is not due to synergism of the free components in the concentration ratios studied. Moreover, none of the complexes displayed cytotoxic effects on onions in the concentration range tested, and chromosome aberrations were not observed.

Oral bioavailability of sulphamethoxydiazine, sulphathiazole and sulphamoxole in dwarf goats.

To get a better insight into the oral bioavailability of sulphonamides in ruminants, sulphamethoxydiazine (pKa 7.0), sulphathiazole (pKa 7.2), and sulphamoxole (pKa 7.4) were administered to dwarf goats (n = 5). The drugs were given at 2-week intervals by the intravenous or intraruminal route at a dose of 100 mg per kg body weight. After IV injection, the mean half-life (t1/2 beta in h +/- SEM) was 0.80 +/- 0.10 h, 2.35 +/- 0.38 h, and 3.36 +/- 1.25 h, for sulphathiazole, sulphamoxole, and sulphamethoxydiazine, respectively and the mean distribution volume (Vd beta) was 0.23 +/- 0.05 l/kg, 0.23 +/- 0.04 l/kg, and 0.33 +/- 0.02 l/kg. After intraruminal administration, the mean bioavailability varied from 86.0 +/- 11.8% for sulphamethoxydiazine to 46.6 +/- 4.3% for sulphamoxole, and 52.6 +/- 7.2% for sulphathiazole. The elimination half-life was significantly prolonged, probably due to a low rate of drug absorption from the gastrointestinal tract. In contrast to chloramphenicol, the sulphonamides studied were stable when incubated in rumen fluid at 39 degrees C.

[Use of multicomponent ointments on a hydrophilic base in the treatment of suppurative wounds]. / Primenenie mnogokomponentnykh mazei na gidrofil'noi osnove pri lechenii gnoinykh ran.

The results of experimental and clinical studies on the development of multicomponent ointments on a hydrophilic base for local treatment of wounds at phase I of the inflammatory process have been analyzed. A pronounced therapeutic effect of the use of the remedies suggested (levosin, levomecol, dioxycole, sulphamecole, iodmetroxide) resulting from simultaneous dehydrating, antimicrobial, necrolytic and anesthetic effect, 2-fold shortening of the period of wound treatment and improvement of the results of treatment of the patients with different types of purulent surgical infection were noted.

Use of p-benzoquinone for the spectrophotometric determination of certain sulphonamides.

A simple spectrophotometric method for the determination of 15 sulphonamides in bulk and in dosage forms is described. The method is based on the interaction of p-benzoquinone with sulphonamides in 0.1 M hydrochloric acid. The resulting chromophore is measured at 500 nm. The effects of different variables on colour development were established. Beer's law was obeyed in a concentration range of 10-50 micrograms ml-1. Results from the analysis of different sulphonamide tablets and ophthalmic solutions marketed locally were in good agreement with that of a reference method. Correlations between A1cm(1%) and certain physical parameters such as pKa values, characteristic volume Vx, and molecular connectivity indices 1X and 1Xv were determined by linear regression equations. A poor correlation was found between A1cm(1%) and bulkiness parameters but a highly significant negative correlation was obtained with apparent pKa values.

Chancroid in El Salvador. Increasing incidence, clinical features, and therapeutics.

Ninety-five cases of chancroid were studied during a 6-month period in a dermatologic service in San Salvador; 88 (92.6%) were men and 7 (7.4%) were women, with a ratio of 12.5:1. The minimum age was 13 years and the maximum 46, with an average of 21 years. In most of the cases (81.05%), the incubation period varied from 1 to 7 days. Very painful adenopathies, enough to make walking difficult, were a striking feature in 69 cases (72.6%). Treatment was curative in all cases, except two, who received treatment with co-trifamole (sulfatrifamole 400 mg/trimethoprim 80 mg). In two cases in which it was not possible to use co-moxole (allergy, pregnancy), treatment was also curative using erythromycin.

In vitro activity of sulfonamides and sulfones against Leishmania major promastigotes.

We examined the susceptibility of promastigotes of Leishmania major to sulfonamides and sulfones in vitro. In a completely defined medium only sulfamoxole, sulfaquinoxaline, and dapsone were inhibitory; the concentrations required for 50% inhibition of the rate of growth were 150, 600, and 600 microM, respectively. Eleven other sulfa drugs were ineffective at concentrations up to 2 mM. The growth inhibition was similar to that observed in procaryotes: the cells continued logarithmic growth for several cell doublings before inhibition was observed. Surprisingly, the addition of p-aminobenzoate or folate did not reverse the effects of the active sulfa drugs, the effects of sulfamoxole and methotrexate were additive rather than synergistic, and the addition of thymidine reversed methotrexate but not sulfa-drug inhibition. These results suggest that the mode of action of sulfa drugs on L. major is not by the classical route of inhibition of de novo folate synthesis. Promastigotes could be propagated for more than 40 passages in a completely defined medium in which the only added pterin was biopterin. The folate concentration in this medium was less than 10(-10) to 10(-11) M, as determined by a Leishmania bioassay. Although these data suggest that L. major may be capable of de novo synthesis of folate, the nonclassical mode of action of sulfa drugs, as well as other studies, favors the view that L. major is auxotrophic for folate.

Comparative pharmacokinetic study of four different sulfonamides in combination with trimethoprim in human volunteers.

The pharmacokinetics of four different sulfonamides i. e., sulfamethoxazole (SMZ). Sulfamoxole (SMO), Sulfadiazine (SDZ) and Sulfadimidine (SDD) in combination with trimethoprim (TMP) were studied in 12 healthy volunteers. Plasma and urine concentrations of sulfonamides were measured at different time intervals. No significant difference was observed in the area under the plasma curve (AUC) of SMZ, SMO and SDZ, while AUC of SMO was significantly higher than SDD only. Free (unmetabolized) SDZ urinary excretion during a 10-25 h period was significantly higher than SMZ, SMO and SDD. The results suggest that SDZ alone or in combination with TMP would be more effective in urinary tract infections as compared to other sulfonamides studied.

Trimethoprim sulphamoxole in the treatment of chancroid. Comparison of two single dose treatment regimens with a five day regimen.

In a prospective blinded study, 135 men with genital ulcers culture positive for Haemophilus ducreyi, were randomized to one of three regimens. Two single dose regimens, either the combination of sulphamoxole 3200 mg/trimethoprim 640 mg or trimethoprim 700 mg alone were compared to a five day regimen of sulphamoxole 800 mg/trimethoprim 160 mg twice daily. All 31 treated with a five day regimen of trimethoprim sulphamoxole healed without further treatment. Of 27 patients treated with the single dose sulphamoxole/trimethoprim regimen, only 21 were cured and of 34 treated with trimethoprim alone, 25 responded. Antibacterial susceptibilities were performed on 31 H. ducreyi isolates. The laboratory susceptibility of these strains to trimethoprim correlated with the clinical response to the single agent. Trimethoprim alone in a dose of 700 mg or the combination of sulphamoxole (3200 mg) and trimethoprim (640 mg) is not satisfactory for the single dose treatment of genital ulcer disease. However, when prescribed for five days, sulphamoxole/trimethoprim is effective and compares favourably with other treatment regimens.

Estudio comparativo del sulfamoxol trimetoprin y la hidroximetil nitrofurantoina en infeccion urinaria

Se realizo un estudio doble ciego en 60 pacientes utilizando el sulfamoxol trimetoprim y la hidroximetil-nitrofurantoina en el tratamiento de la infeccion urinaria. Habiendose encontrado una buena respuesta terapeutica con ambas drogas aunque algo mayor en el grupo que recibio sulfamoxol trimetoprin; asi mismo en este grupo no se informaron efectos colaterales que se hicieron evidentes con la nitrofurantoina. El germen mas frecuente fue la Ecoli en ambos grupos. Los parametros de eficacia laboratorial se hicieron evidentes al cabo del tercer dia de iniciado el tratamiento.

Experiencia clinica y bacteriologica con co-tripanol (Sulfamoxol trimethoprim) en las infecciones bacterianas de los niños

En esta comunicacion, se informa sobre un trabajo prospectivo realizado en un grupo de cien niños con edades entre los dos a doce anos, portadores de diversos procesos infecciosos y asistidos en el Hospital del Niño de la ciudad de La Paz (Bolivia). La investigacion bacteriologica inicial permitio distinguir a dos grandes grupos: treinta y seis casos cuyo estudio de sensibilidad "in vitro" identifico resistencia a la combinacion: sulfamoxol/trimethoprim; otros sesenta y cuatro ninos se habilitaron para un esquema terapeutico con tal droga, administrada por via oral y en dosis menores a las convencionales. Por los resultados obtenidos, se comenta el beneficio demostrado por el Co-trifamol en una poblacion pediatrica, sugiriendo el desarrollo de investigaciones mas especificas, a fin de precisar la mayor sensibilidad y/o resistencia de ciertos germenes ante esta droga

[Treatment of initial urinary tract infection in children with cotrifamole and cotrimoxazole. A double-blind study]. / Behandlung von ersten Harnwegsinfekten im Kindesalter mit Cotrifamol und Cotrimoxazol.

28 children with initial episodes of urinary tract infection were treated with cotrimoxazole or cotrifamole (dose ratio 3 : 2) for 14 days in a prospective randomized double blind trial. The two groups did not differ as regards clinical signs. The efficacy and cure rates of each regimen were similar. Laboratory studies (hemoglobin, WBC, liver, and renal function) showed no differences between both groups before and after therapy; an alteration of the laboratory values could not be observed during therapy. The number of children with X-ray abnormalities of kidneys and urinary tract was similar in both groups. During an observation time of up to 12 months after the first urinary tract infection no differences in the number of reinfections and relapses were observed. As a result of this study, we recommend cotrifamole in a lower dose (ratio 2 : 3) than cotrimoxazole for the treatment of urinary tract infection.

Combination of trimethoprim with sulfonamides other than sulfamethoxazole.

Early in the development of trimethoprim (TMP), the response to the drug was less than enthusiastic. Preliminary clinical trials were performed with sulfonamides that were unsuitable partners. On the basis of bacteriologic and pharmacokinetic evidence, sulfamethoxazole (SMZ) was chosen for the fixed-ratio (5:1) combination with TMP. Possible criteria on which to base the choice of a sulfonamide partner for TMP have been delineated. The theoretical considerations may be questioned in view of limited clinical experience with some combinations and lack of controlled comparisons in well-designed clinical trials with others. Objective proof of the clinical superiority of newer TMP-sulfonamide combinations over TMP-SMZ is required.