Evidence against the diffusion of sulfisoxazole and sulfamethizole into the prostatic fluid of dogs.
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The efficiency of treatment of acute urinary tract infections with sulfamethizole for 3 days, sulfamethizole for 10 days, and pivmecillinam for 3 days was compared in a randomized multicentre study comprising 264 girls aged 1-15 years. For ethical reasons children with complicated diseases were not included. In these treatment groups no significant growth after treatment was found in 81%, 77%, and 74%, respectively (NS). New bacteria after treatment were found less frequently after sulfamethizole for 3 days (4%) when compared to sulfamethizole for 10 days (14%) and pivmecillinam for 3 days (13%) (p = 0.048). After pivmecillinam treatment 75% of new bacteria were Streptococcus faecalis versus 25% after sulfamethizole for 3 days and 18% after sulfamethizole for 10 days (p = 0.016). In the subgroup with nephro-urological abnormalities no significant growth after treatment was found in 68% of the sulfamethizole 3-day treated group, 54% of the sulfamethizole 10-day treated group, and 67% of the pivmecillinam 3-day treated group (NS). All treatments resulted in a change in the bacterial sensitivity pattern when bacteria isolated 1-10 days after treatment was compared to those found before treatment. This was more pronounced after the 10-day treatment when compared to the 3-day treatment. The sensitivity patterns of the bacteria isolated from recurrences were similar to those seen before treatment. After treatment there was no difference in the actuarial percentage recurrence-free curves of the 3 treatment groups. Side effects were rare in the sulfamethizole treated groups, and seen more often in the pivmecillinam treated group. 3-day treatment with sulfamethizole or alternatively pivmecillinam is recommended as first choice for treatment of uncomplicated acute urinary tract infections in girls.
OBJECTIVES: The efficacy of sulfamethizole and pivmecillinam in the treatment of urinary tract infections (UTI) has been questioned because of an increase in the prevalence of resistant strains. The aim of this study was to describe the risk of treatment failures over the last 10 years. DESIGN: Retrospective cohort study. MATERIAL: Data were retrieved from Odense Pharmaco Epidemiological Database and consisted of women receiving sulfamethizole (n = 44,716) or pivmecillinam (n = 3093) during the period 1990-99. MAIN OUTCOME MEASURES: Prescription of a new antibiotic drug appropriate for UTI within 4 weeks after the initial treatment was considered as an indicator for a treatment failure. The risk of treatment failure was estimated by calculating the cumulative incidence proportion of new antibiotic prescriptions within 4 weeks after the initial treatment. RESULTS: A new antibiotic followed 8% of sulfamethizole and 9.5% of pivmecillinam treatments. The cumulative incidence proportion of treatment failures did not change during the study period. A logistic regression model showed pivmecillinam to be associated with a higher risk of treatment failure (OR 1.42, CI 1.14-1.77) than sulfamethizole. CONCLUSION: This study does not support a change in current Danish practice of sulfamethizole being first-line treatment for uncomplicated UVI.
INTRODUCTION: The aim of the study was to determine the antibiotic susceptibility of E. coli isolates in stools from healthy Danes. METHODS: Sixty-nine persons from Copenhagen participated in the study. Three faecal samples from each participant were examined by culture for each of three periods. E. coli was isolated selectively and tested for sensitivity against sulfamethizole, trimethoprim, the combination of sulfamethizole and trimethoprim, ampicillin, mecillinam, cefuroxime, nitrofurantoin, and ciprofloxacin. RESULTS: Altogether, 184 strains of E. coli were isolated from 66 of the 69 persons. Fifty-eight (31.5%) of the strains isolated from 30 persons (43.5%) were resistant to sulfamethizole, 32 (17.4%) strains isolated from 18 persons (26.1%) were resistant to trimethoprim, 31 (16.8%) strains isolated from 17 persons (24.6%) were resistant to trimethoprim + sulfamethizole, 57 (31%) strains from 31 persons (44.9%) were resistant to ampicillin, 29 (15.8%) of the strains from 24 persons (34.8%) were resistant to nitrofurantoin, two (1.1%) strains from two persons (2.9%) were resistant to cefuroxime, whereas none of the strains was resistant to mecillinam and ciprofloxacin. DISCUSSION: The high prevalence of resistance to sulfamethizole, ampicillin, trimethoprim, and nitrofurantoin is surprising, as none of the persons had been treated with antibiotics, but it may reflect the widespread use of antibiotics in animals for food production. The consequences of the results for empiric antibiotic treatment of, for instance, urinary tract infection are discussed.
BACKGROUND/AIMS: Close observation and evaluation of the function of the transposed stomach after esophagectomy is essential. The present study uses the sulfamethizole capsule meal test to evaluate differences in gastric emptying between the anterior and posterior mediastinal approaches in patients undergoing esophagectomy. METHODOLOGY: Thirty-eight patients who underwent the esophagectomy and esophagogastrostomy for esophageal cancer were randomly divided into 2 groups: Group 1: anterior mediastinal approach, and Group 2: posterior mediastinal approach. Gastric emptying was studied using the sulfamethizole capsule meal test. Patients received sulfamethizole food capsules, 65 g of bread, and 150 ml of water. Plasma sulfamethizole levels were determined by high performance liquid chromatography (HPLC). RESULTS: Gastric emptying in both groups was significantly accelerated compared to healthy volunteers. Gastric emptying did not differ significantly between groups 1 and 2. CONCLUSIONS: The present data show that the sulfamethizole capsule meal test is an effective means of evaluating the emptying of the transposed stomach. Furthermore, when the stomach is used as an esophageal substitute following esophagectomy, gastric emptying does not differ according to the access route.
Neonatal and adult albumin was isolated by gel chromatography on Sephacryl S-300, from adult and umbilical cord serum, respectively. Binding of monoacetyl-diamino-diphenyl sulfone, warfarin, sulfamethizole, and diazepam was studied by means of equilibrium dialysis and the binding data were analyzed by the method of several acceptable fitted curves. It was found that the binding affinity to neonatal albumin is less than to adult albumin for monoacetyl-diamino-diphenyl sulfone and warfarin. Sulfamethizole binding to the neonatal protein is similarly reduced when more than one molecule of the drug is bound per albumin molecule, and binding of the first sulfamethizole molecule is possibly reduced as well. Diazepam binds with equal affinity to the fetal and adult proteins. Among the two main albumin drug-binding functions, for warfarin and diazepam, the former is thus compromised in the newborn infant while the diazepam binding function is at the adult level.
Decreased susceptibility in vitro to erythromycin has been demonstrated for few C. trachomatis isolates outside Scandinavia, making local susceptibility-screening indicated. Eleven recent isolates of C. trachomatis found in a Danish hospital have been examined for susceptibility, expressed as minimal inhibitory concentration (MIC) to antibacterial agents commonly used in genito-urinary infections. Full susceptibility to doxycycline and erythromycin was demonstrated. Clindamycin and ampicillin showed moderate activity, and sulfamethizole had a MIC value in the border area of what is needed for therapeutic effect in non-urinary infections. C. trachomatis, being a major pathogen in pelvic inflammatory disease, makes combination chemotherapy desirable in order to protect against resistance development, to obtain synergistic effect and to ensure effect in infections of mixed etiology - provided antagonism could not be anticipated. In three checkerboard trials, with the combinations doxycycline plus ampicillin, erythromycin plus sulfamethizole and ampicillin plus sulfamethizole, using MIC as end-point, neither synergism nor antagonism could be demonstrated in the concentration range from 1/8 to 4 times the MIC values of each drug.
The photochemical fate of five sulfa drugs with varying five-membered heterocyclic substituents (sulfamethoxazole, sulfisoxazole, sulfamethizole, sulfathiazole, and sulfamoxole) was investigated in aqueous solution. The rate of direct photolysis of these compounds is dependent upon the identity of the heterocyclic R group as well as the pH of the solution. Matrix deconvolution methods were employed to determine the absorption spectrum and photolysis rate of each protonation state (cationic, neutral, and anionic). From these data, quantum yields for direct photodegradation were calculated for each protonation state of the sulfa drugs. The quantum yields calculated range from <0.005 for the neutral state of sulfamethizole to 0.7 +/- 0.3 for the protonated state of sulfisoxazole. The protonation state that is most photoreactive varies among the sulfa drugs and cannot be attributed to the rate of photon absorption. Products arising from the direct photolysis of the sulfa drugs were also investigated. For all the compounds, sulfanilic acid was observed as a common product. The singlet oxygen quenching rates of the sulfa drugs were determined by laser flash photolysis and range from (2 +/- 1) x 10(4) M(-1) s(-1) for sulfamethoxazole to (3.0 +/- 0.7) x 10(8) M(-1) s(-1) for sulfamoxole. Reaction of the sulfa drugs with hydroxyl radical is not modulated by the R group, and the rate constants are all near the bimolecular diffusion-controlled limit of 10(10) M(-1) s(-1). The photodegradation of the sulfa drugs in natural water samples of Lake Josephine (St. Paul, MN) and Lake Superior was attributed solely to direct photolysis. This study indicates thatthese similarly structured antibiotics will be subject to a wide range of photodegradation rates with sulfathiazole degrading relatively quickly, sulfisoxazole and sulfamethizole degrading moderately, and sulfamethoxazole degrading much more slowly.
Multiple resistance and antibiotic resistance were examined in coliforms isolated at slaughter from the large intestines of two groups of growing pigs that had received antibiotic-free diets since weaning. One group of pigs was from an antibiotic-fed (AB) herd that routinely received chlortetracycline (CTC) in feed, while the other group was from a nonantibiotic-fed (NAB) herd that had not received antibiotics for 8 yr. After a 20-d adjustment period in a common production facility, the mean number of antibiotics in the resistant pattern of isolates from NAB pigs was found to be lower (P less than .05) than that in isolates from AB pigs. The proportions of isolates resistant to ampicillin, kanamycin, neomycin, penicillin, streptomycin and sulfamethizole were lower (P less than .05) in NAB pigs than in AB pigs. Similar herd differences were not observed after pigs from both herds were maintained in a common production facility on an antibiotic-free diet for 105 d. Oral administration of CTC at therapeutic (220 micrograms/g of diet) and at subtherapeutic (27.5 micrograms/g) levels for 14 d increased (P less than .05) the mean numbers of antibiotics in the resistance patterns of isolates from NAB pigs, but did not alter multiple resistance in isolates from AB pigs. After 14 d, subtherapeutic CTC increased the percentage of isolates resistant to ampicillin, kanamycin, penicillin, streptomycin, tetracycline and sulfamethizole, while therapeutic CTC only increased the percentage of isolates from NAB pigs resistant to penicillin, tetracycline and sulfamethizole. Similar antibiotic effects were not seen in isolates from AB pigs after 14 d and were not seen in isolates from either group of pigs at the end of an 85-d feeding trial.
Drug-drug interactions between tolbutamide and sulfonamides have extensively been reported. We attempted to predict the in vivo interaction between tolbutamide and sulfonamides from the in vitro metabolic inhibition studies. The inhibition constant (K(i)) was derived from the inhibitory effects of eight sulfonamides (sulfaphenazole, sulfadiazine, sulfamethizole, sulfisoxazole, sulfamethoxazole, sulfapyridine, sulfadimethoxine, and sulfamonomethoxine) on tolbutamide metabolism. We found that the inhibitory effect of sulfaphenazole was greatest among the eight sulfonamides examined. Furthermore, the contribution of each P450 enzyme to tolbutamide metabolism was investigated by using recombinant P450 enzymes. Although cytochrome P450 (CYP) 2C8, 2C9, and 2C19 metabolized tolbutamide, the main enzyme involved was CYP2C9. The K(i) values of several sulfonamides were comparable between human liver microsomes and recombinant CYP2C9. The maximum unbound plasma concentration of sulfonamides in the portal vein was calculated from literature data on the pharmacokinetics of sulfonamides. Using the K(i) values obtained from in vitro inhibition studies, the degree of increase in tolbutamide area under the plasma concentration-time curve (AUC) was predicted. About 4.8- and 1.6-fold increases in tolbutamide AUC were predicted by coadministration of sulfaphenazole and sulfamethizole, respectively, which agreed well with the reported increases in humans. Furthermore, the increase in tolbutamide AUC by coadministration of sulfadiazine, sulfisoxazole, and sulfamethizole was predicted to be 1.5- to 2. 6-fold, although the corresponding in vivo effects have not been reported. It is concluded that some of these sulfonamides have to be carefully coadministered with CYP2C9 substrates such as tolbutamide although coadministration of sulfaphenazole needs the greatest care.
The solubilities of silver sulfapyridine, silver sulfamethazine, and silver sulfamethizole as a function of pH were determined in nitric acid-potassium nitrate, acetate, and sulfonic acid buffers. All silver sulfonamides showed an increase in solubility with increasing hydrogen-ion concentration, a behavior which closely paralleled the protonation of the p-amino function of the sulfonamide. A silver-ion selective electrode was used to measure silver-ion concentration in solution and the methods of known subtraction and known addition were used to measure total silver. Both silver sulfamethizole and silver sulfamethazine were ionized completely in solution. Silver sulfapyridine was ionized completely only in the more acidic pH 2-3 range. A comparison of the physical properties of the silver salts for which mortality studies were available revealed a unique set of properties for silver sulfadiazine.
A renal clearance method based on a computer analysis after administration of a single dose of drug was developed for measuring the renal handling of several drugs in rabbits, dogs, and humans. Secretion and reabsorption of sulfamethizole, sulfanilamide, cephalexin, and ampicillin in the nephron were analyzed quantitatively using the plasma concentration and the urinary excretion rate of the drugs. The validity of the proposed model was demonstrated. It appears that tubular secretion of sulfamethizole, cephalexin, and ampicillin depend on the active transport system which is described by Michaelis-Menten kinetics; the tubular reabsorption of these drugs is expressed by first-order kinetics. The maximum velocity of renal secretion per unit weight of these drugs was much higher in rabbits than in dogs or humans. Reabsorption showed similar values in dogs and humans. These findings suggest that an analysis of the renal handling of drugs in dogs might provide useful information when considering the appropriate therapeutic dose in humans.
Fecal specimens were collected on 22 different Nebraska ranches and at the Department of Veterinary Science from young calves and pigs with neonatal diarrhea. Enterobacteriaceae isolated from these fecal specimens were screened for resistance to tetracycline, streptomycin, sulfamethizole, kanamycin, chloramphenicol, colistin, nitrofurantoin, and nalidixic acid. Of the 92 strains studied, 57 were resistant to one or more of these antimicrobial agents. Resistant strains were obtained from all herds involved in the study. The two most common resistance patterns were tetracycline streptomycin sulfamethizole (22 of 57) and tetracycline (13 of 57). None of the strains were resistant to chloramphenicol, colistin, nitrofurantoin, or nalidixic acid. The 57 resistant strains were studied to determine whether the resistance was transferable. Forty-three of the 57 resistant strains could transfer part or all of their resistance pattern to a drug-sensitive recipient. The 43 R(+) strains were obtained from 17 of the 23 herds studied. Considerable variation was observed between different R(+) strains in the frequency of transfer of resistance to a particular drug. In addition, variation in the frequency of transfer of different resistance determinants in individual R(+) strains was noted.
Pseudomonas mallei was isolated from pus samples obtained from 34 mallein-positive horses. The isolates were subjected to in vitro sensitivity test using 16 different antimicrobial discs. All isolates (34) were sensitive to sulfamethizole, gentamycin, tetracycline, sulfathiazole, kanamycin, tobramycin, streptomycin and a combination of trimethoprim and sulfamethoxazole while none of them were sensitive to cephalothin, colistin, ampicillin, penicillin and nitrofurantoin. Rifapicin, chloramphenicol and carbenicillin were effective against 32, 26 and 18 isolates respectively. The minimum inhibitory concentrations (MICs) of gentamycin, tetracycline, tobramycin, sulfamethizole, streptomycin, rifampicin and a combination of trimethoprim and sulfamethoxazole were 0.28, 0.38, 0.67, 1.40, 3.40, 5.86 and 5.30 micrograms/ml, respectively.
Removal of tetracycline and sulfonamide antibiotics from water by micelles pre-adsorbed on montmorillonite was studied. Micelles of benzyldimethylhexadecylammonium (BDMHDA) were used. Batch experiments demonstrated that the micelle-clay complexes (1% w/w) removed 96-99.9% of antibiotics from their water solutions containing from 5 to 50 mg/L of pharmaceuticals. Column filters (25 cm) made of a mixture of quartz sand and BDMHDA micelle-clay complex at 100:1 w/w ratio removed 94-99.9% of above pharmaceuticals from initial solutions containing 10mg/L and 89% of sulfamethizole from an initial solution containing 10 microg/L of this antibiotic. These filters were also very efficient in the removal of antibiotics in the presence of dissolved soil organic matter removing 89-99% of tetracycline and sulfamethizol from initial solutions containing 10 mg/L of antibiotic in the presence of 8 mg/L of humic acid, or 9 mg/L of fulvic acid. These data indicate that micelle-clay complexes are very efficient for water purification from tetracycline and sulfonamide antibiotics.
Antibiotic resistance of urinary tract pathogens has increased worldwide. Our aim was to provide information regarding resistance patterns of Escherichia coli in urinary tract infections (UTIs) and E. coli bacteraemia in Denmark. The overall resistance ranged from: ampicillin 20-47%, mecillinam 0-7%, trimethoprim 10-28%, sulfamethizole 22-47% and nitrofurantoin 0-3%. In strains with sulfamethizole MICs > 2048 mg/L, 97% carried sulI, sulII or both genes, with sulII being the most common. Among the sulI gene-positive strains, 96% were intI 1 gene positive.