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PubMed2006

Tetramethylpyrazine induces heme oxygenase-1 expression and attenuates myocardial ischemia/reperfusion injury in rats.

The accumulation of oxygen free radicals and activation of neutrophils are strongly implicated as pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. Heme oxygenase-1 (HO-1) has been reported to play a protective role in oxidative tissue injuries. In this study, the cardioprotective activity of tetramethylpyrazine (TMP), an active ingredient of Chinese medicinal herb Ligusticum wallichii Franchat, was evaluated in an open-chest anesthetized rat model of myocardial ischemia/reperfusion injury. Pretreatment with TMP (5 and 10 mg/kg, i.v.) before left coronary artery occlusion significantly suppressed the occurrence of ventricular fibrillation. After 45 min of ischemia and 1 h of reperfusion, TMP (5 and 10 mg/kg) caused a significant reduction in infarct size and induced HO-1 expression in ischemic myocardium. The HO inhibitor ZnPP (50 microg/rat) markedly reversed the anti-infarct action of TMP. Superoxide anion production in ischemic myocardium after 10 min reperfusion was inhibited by TMP. Furthermore, TMP (200 and 500 microM) significantly suppressed fMLP (800 nM)-activated human neutrophil migration and respiratory burst. In conclusion, TMP suppresses ischemia-induced ventricular arrhythmias and reduces the infarct size resulting from ischemia/reperfusion injury in vivo. This cardioprotective activity of TMP may be associated with its antioxidant activity via induction of HO-1 and with its capacity for neutrophil inhibition.

Animals↗
PubMed1990

A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis.

PURPOSE: To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis. PATIENTS AND METHODS: One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial. RESULTS: Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 0.001). During the transplant hospitalization, a daily dose of 320/1,600 mg was highly effective for prophylaxis whereas 160/800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p less than 0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p less than 0.001). CONCLUSIONS: Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320/1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora.

Absorption↗
PubMed1990

The growth rate of metastatic non-seminomatous germ cell testicular tumours measured by marker production doubling time--I. Theoretical basis and practical application.

Changes in serum tumour marker levels in non-seminomatous germ cell testicular tumours (NSGCTT) are used to monitor tumour growth and response to treatment. A novel method of calculating the actual tumour marker production (TMP) per day is reported; estimation of the rate of change of TMP is a measure of the tumour growth or regression rate. TMP is calculated mathematically from the rate of increase in serum marker level and its natural half life. TMP is assumed to be proportional to the number of marker producing cells in the tumour. TMP was calculated over the time between orchidectomy and the start of chemotherapy. The rate of increase in TMP with time is expressed as the marker production doubling time (MPDT) and is a measure of the growth rate. In a group of 51 patients with metastatic NSGCTT, TMP varied from 0.012 to 5985 iu/l/day (AFP) and 0.08-5404 iu/l/day (HCG). MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients; greater than 80% of cases had a MPDT less than or equal to 32 days. In 45/51 (88%) patients, there was no discrepancy in MPDT between markers. The use of changes in serum marker level to follow tumour progression and regression is simple, but the calculation of actual TMP provides clearer information about the change in number of marker producing cells and can be used as non-invasive method for measuring the tumour growth rate of metastatic disease and response to treatment.

Biomarkers, Tumor↗
PubMed1987

Effects of O,S,S-trimethyl phosphorodithioate on immune function.

The effect of acute administration of 20-80 mg/kg O,S,S-trimethyl phosphorodithioate (OSS-TMP) to C57BL/6 female mice on the murine immune system was determined. The parameters examined to evaluate overt toxicity of the compound included body weight, plasma cholinesterase levels, splenic nucleated cell number and thymic weight and nucleated cell number. Acute administration of 60 or 80 mg/kg OSS-TMP led to a 75 or 63% decrease, respectively, in plasma cholinesterase levels and a decrease in thymic size. At a dose of 80 mg/kg OSS-TMP, the animals also exhibited some lethargy and body weight loss. Below 60 mg/kg OSS-TMP, no overt toxic manifestations were observed. These studies were carried further to determine the effect of OSS-TMP on the generation of in vivo primary and in vitro secondary cellular and humoral immune responses. At nontoxic doses of the compound, i.e. 20 and 40 mg/kg OSS-TMP, the in vivo generation of a primary cytotoxic T lymphocyte (CTL) response to alloantigen was significantly elevated, but this response was unaffected following restimulation of the splenocytes by alloantigen in vitro. The generation of an in vivo primary and in vitro secondary humoral responses to sheep red blood cells (SRBC) was elevated following a single dose of 40 mg/kg OSS-TMP. Administration of toxic doses of OSS-TMP, i.e. 60 and 80 mg/kg, did not alter the ability of splenocytes to generate a primary or secondary CTL response, but suppressed the generation of humoral immune responses. These results differ significantly from those observed in a similar system following acute administration of a structural analog, O,O,S-trimethyl phosphorothioate which was previously shown to have potent immunosuppressive activity at nontoxic doses.

Animals↗
PubMed1996

Prophylactic antibiotics for the prevention of early infection in multiple myeloma.

PURPOSE: Patients with multiple myeloma are at increased risk for bacterial infection. During the first 2 months of initial chemotherapy the rate of infection is twice that experienced during the remainder of the disease course. As many as one-third of these early infections are fatal, and many more prevent adequate administration of chemotherapy. This study was designed to determine whether the morbidity and mortality of early infection can be prevented by prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX). PATIENTS AND METHODS: Eligible patients about to begin chemotherapy for multiple myeloma were randomly assigned to prophylaxis for 2 months or to no prophylaxis (control). Antibiotic prophylaxis consisted of TMP-SMX 160/800 mg orally every 12 hours administered for the first 2 months of initial chemotherapy. All patients were observed for infection for 3 months after the start of chemotherapy. RESULTS: Of 57 patients entered into the study, 54 were evaluable, representing 13.1 patient-years of observation. The 28 TMP-SMX patients and 26 control patients were comparable in terms of chemotherapy regimen, age, gender, stage, and bone marrow function. Bacterial infection during the 3-month study period occurred in 11 control patients but in only 2 patients assigned TMP-SMX (P = 0.004). Eight severe infections occurred in controls compared with 1 in a TMP-SMX patient (P = 0.010) leading to 4 and 1 infection deaths, respectively (P = not significant). Severe infections included 5 pneumonias (3 with sepsis), 2 urinary tract infections with complicating pneumonia or sepsis, 1 diverticulitis with perforation, and 1 staphylococcal scalded skin syndrome. None of the 4 nonbacterial infections was severe. The rate of bacterial infection was 2.43 per patient-year for controls and 0.29 per patient-year for the TMP-SMX group (P = 0.001). Toxicity (skin rash 6 patients, nausea 1 patient) was not life-threatening but required discontinuation of TMP-SMX in 25% of patients. CONCLUSION: Administering TMP-SMX for the first 2 months of initial chemotherapy is effective, inexpensive prophylaxis for early bacterial infection in multiple myeloma.

Aged↗
PubMed1998

Six-hour trimethoprim-sulfamethoxazole-graded challenge in HIV-infected patients.

BACKGROUND: Hypersensitivity reactions to trimethoprim-sulfamethoxazole (TMP-SMX) are very common in HIV-infected patients, leading to drug discontinuation. However, it is the drug of choice as prophylaxis for Pneumocystis carinii pneumonia. OBJECTIVES: We sought to determine the safety and long-term efficacy of a 6-hour TMP-SMX-graded challenge in a group of hypersensitive HIV-infected patients. METHODS: Forty-four consecutive HIV-infected patients with documented TMP-SMX hypersensitivity were seen in our outpatient allergy department. They ingested 12 doses of increasing amounts of TMP-SMX at half-hour intervals. Thereafter, they took 80/400 mg TMP-SMX daily and were advised to "treat through" every nonbullous cutaneous adverse reaction. RESULTS: All 44 patients tolerated the procedure without any adverse reactions during the day of challenge. Eleven of the 44 patients experienced mild hypersensitivity reactions on days 1 to 2 (8 patients) and 8 to 10 (3 patients), consisting mainly on a 1-day pruritic maculopapular eruption. Two patients stopped TMP-SMX at day 1, and 2 stopped it at days 10 and 15, giving an overall success rate at 1 month of 91% (40 of 44). Two were successfully rechallenged late. After a median follow-up of 10 months, 42 patients were taking TMP-SMX without any adverse reaction, giving an overall success rate of 95%. CONCLUSIONS: A 6-hour graded challenge with cautious "treating through" of mild reactions enables more patients to take TMP-SMX and is safe and effective.

Administration, Oral↗
PubMed1986

Zwitterionic 3'-O-acyl derivatives of thymidine 5'-phosphate as potential sources of intracellular thymidine 5'-phosphate in cells in culture.

A convenient route is described for attachment of acyl groups CO(CH2)nN(Et)2(CH2)mNH(Et)2 (n = 3, m = 2; n = 4, m = 2-4), CO(CH2)nN(Et)2(CH2)mNEt3 (n = 4, m = 2-4), or CO(CH2)4N(CH2CH2)3N(CH2)nCH3 (n = 1 or 9) to O-3' of thymidine 5'-phosphate (TMP). The compounds are prototypes of 5'-nucleotide derivatives in which the two anionic charges could become partially masked in intramolecular anionic-cationic interactions and which might be able to diffuse into mammalian cells to furnish intracellular antimetabolite 5'-nucleotides by hydrolytic loss of a dicationic 3'-O-acyl group. At pH 7.6, 37 degrees C, hydrolyses of the 3'-ester linkages were pseudo first order with t1/2 values in the range 28-85 h. Paper chromatography in n-PrOH-H2O at pH 7.6 showed that type 1 or 2 derivatives were equally or slightly less hydrophobic than TMP (Rf 0.24), whereas the n-decyl type 3 compound (Rf 0.66) was markedly more hydrophobic, apparently because chain branching in group 3 is less than in 1 or 2. A sensitive and specific assay was developed for liberation of intracellular TMP in cultured mouse L fibroblasts in which synthesis of TMP and, hence, of DNA was suppressed by a combination of aminopterin and 5'-amino-5'-deoxythymidine (5'-NH2-dT). The TMP derivatives (100 microM) stimulated DNA synthesis, but omission of 5'-NH2-dT increased stimulation 6.5-fold, suggesting that stimulation occurred via degradation of the derivatives to dT. In confirmation, derivatives of type 2 (n = 4, m = 2 or 4) (100 microM) or type 3 (n = 9) (200 microM), in the presence of aminopterin, did not stimulate DNA synthesis in the LM(TK-) strain of L cells, which is genetically deficient in dT kinase. TMP (1 mM) stimulated DNA synthesis 2-3-fold and appeared to enter LM(TK-) cells without dephosphorylation, because dT (1 mM) gave no stimulation. If TMP is assumed to enter solely by passive diffusion, the inactivity of the TMP derivatives can be ascribed in part to their 2-fold higher molecular weight which can be expected to reduce flux through natural membranes ca. 16-fold.

Acylation↗
PubMed2001

Pharmacokinetics of sulfadimethoxine and sulfamethoxazole in combination with trimethoprim after oral single- and multiple-dose administration to healthy pigs.

The pharmacokinetics were studied of sulfadimethoxine (SDM) or sulfamethoxazole (SMX) in combination with trimethoprim (TMP) administered as a single oral dose (25 mg + 5 mg per kg body weight) to two groups of 6 healthy pigs. The elimination half-lives of SMX and TMP were quite similar (2-3 h); SDM had a relatively long half-life of 13 h. Both sulfonamides (S) were exclusively metabolized to N4-acetyl derivatives but to different extents. The main metabolic pathway for TMP was O-demethylation and subsequent conjugation. In addition, the plasma concentrations of these drugs and their main metabolites after medication with different in-feed concentrations were determined. The drug (S:TMP) concentrations in the feed were 250:50, 500:100, and 1000:200 mg per kg. Steady-state concentrations were achieved within 48 h of feed medication, twice daily (SDM+TMP) or three times a day (SMX+TMP). Protein binding of SDM and its metabolite was high (>93%), whereas SMX, TMP and their metabolites showed moderate binding (48-75%). Feed medication with 500 ppm sulfonamide combined with 100 ppm TMP provided minimum steady-state plasma concentrations (C(ss,min)) higher than the concentration required for inhibition of the growth of 90% of Actinobacillus pleuropneumoniae strains (n = 20).

Administration, Oral↗
PubMed2003

Effect of tetramethylpyrazine on potassium channels to lower calcium concentration in cultured aortic smooth muscle cells.

1. Tetramethylpyrazine (TMP) is one of the active principles contained in Ligusticum chuanxiong Hort. (Umbelliferae), a herb that has been used widely in China to treat vascular disorders. 2. In an attempt to elucidate the possible mechanisms of action of TMP, the effect of TMP on intracellular calcium concentrations ([Ca2+]i) was investigated in cultured vascular smooth muscle (A7r5) cells using the Ca(2+)-sensitive dye Fura-2 as an indicator. 3. The increase in [Ca2+]i in A7r5 cells produced by vasopressin (1 micromol/L) or phenylephrine (1 micromol/L) was attenuated by TMP in a concentration-dependent manner. Only inhibitors specific to ATP-sensitive potassium (KATP) channels or small conductance calcium-activated potassium (SKCa) channels attenuated the action of TMP (10 micromol/L) on [Ca2+]i. However, blockers of other K+ channels failed to modify the inhibitory action of TMP (10 micromol/L) on [Ca2+]i. 4. The action of TMP on membrane potential in A7r5 cells was monitored by the fluorescence of bisoxonol. Tetramethylpyrazine caused a concentration-dependent inhibition of changes in membrane potential elicited by KCl (20 mmol/L) or phenylephrine (1 micro mol/L), an effect that was totally reversed by glibenclamide (100 micromol/L) and apamin (100 nmol/L) in combination. 5. The results obtained indicate that the decrease in [Ca2+]i in A7r5 cells produced by TMP is mediated mainly by opening of KATP and/or SKCa channels.

Animals↗
PubMed2002

Hepatoprotective and therapeutic effects of tetramethylpyrazine on acute econazole-induced liver injury.

2,3,5,6-Tetramethylpyrazine (TMP) is well known as a true calcium antagonist. The aim of this study was to investigate the hepatoprotective and therapeutic effects of TMP on acute econazole-induced liver injury. The hepatological effect of various concentrations of TMP was first assessed by the biochemical assays of SGOT and SGPT and then by hepatohistological microscopic examination. The dose-response relationship of liver injury induced by various doses of econazole was observed simultaneously from serum biochemical assay of SGOT and SGPT, and also from hepatohistological microscopic examination, by determination of the hepatoprotective effects of various concentrations of TMP on SGOT and SGPT elevation induced by a hepatotoxic dose of econazole (300 mg/kg). The inhibitory effect of various concentrations of TMP or vitamin E (positive control, 0.5 mM in vitro, 0.69 mM in vivo) on FeCl 2 -induced (in vitro) or econazole-induced (in vivo) lipid peroxidation was also investigated. The superoxide scavenging activity of various concentrations of TMP in econazole-damaged rat liver homogenate was assessed by the cytochrome C reduction method. Results showed that the hepatoprotective effect of TMP might be, at least in part, due to its inhibitory ability on membrane lipid peroxidation and free radical formation, or due to its free radical scavenging ability. Improvement of serum transaminases and MDA levels in rat liver homogenate, hepatohistological microscopic examination, and assessment of free radical scavenging activity by the cytochrome C reduction method were used to detect hepatoprotective and therapeutic effects of TMP on acute econazole-induced liver injury.

Acute Disease↗
PubMed1979

Biochemical determinants of tumor sensitivity to 5-fluorouracil: ultrasensitive methods for the determination of 5-fluoro-2'-deoxyuridylate, 2'-deoxyuridylate, and thymidylate synthetase.

Techniques have been developed to measure FdUMP, the active metabolite of 5-FUra; thymidylate synthetase (TMP synthase; 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45), the target enzyme for this antimetabolite; and dUMP, the substrate that competes with FdUMP for binding to TMP synthetase. As little as 0.02 pmol of FdUMP can be quantitated with a competitive ligand binding assay by using homogeneous Lactobacillus casei/MTX TMP synthetase as a binding protein. A new binding assay for TMP synthetase allows detection of 0.005 pmol of enzyme. The quantitative enzymatic conversion of dUMP to [methyl-(14)C]-TMP using 5,10-methylene[(14)C]tetrahydrofolate by pure L. casei TMP synthetase is used as an assay for dUMP with a sensitivity of 10 pmol. Cultured CCRF-CEM human lymphoblastic leukemia cells formed high levels of FdUMP (2.6 nmol per 10(9) cells) within 11 hr after exposure to 30 muM 5-FUra. Tumor cell TMP synthetase levels dropped, and then free FdUMP appeared. The intracellular dUMP pool was low (2-5 nmol per 10(9) cells) in logarithmically growing cultures of several tumor cell lines but expanded rapidly in CCRF-CEM cells on exposure to 5-FUra after enzyme levels decreased. The levels of dUMP found after exposure to 5-FUra are sufficient to severely retard inhibition of TMP synthetase by FdUMP.The methods described are sufficiently sensitive to allow these biochemical parameters of 5-FUra action to be measured in cell culture or in needle biopsy samples of human tumors.

Cell Line↗
PubMedDate not supplied

Trimethoprim alone for treatment of urinary tract infection.

Studies of the use of trimethoprim (TMP) alone compared with the use of trimethoprim and sulfamethoxazole in combination (TMP-SMZ) have shown that TMP alone is as effective as TMP-SMZ in the treatment of urinary tract infections. With the exception of one study in which use of TMP singly for 28 days for treatment of recurrent urinary tract infections selected resistant nonfermenting bacteria, the use of TMP singly for treatment of urinary tract infections has not resulted in selection of resistant Enterobacteriaceae. However, use of both TMP and TMP-SMZ for prevention of traveler's diarrhea has resulted in plasmid mediated resistance in Escherichia coli.

Chronic Disease↗
PubMedDate not supplied

Resistance to trimethoprim among urinary tract isolates in the United Kingdom.

Sequential surveys of resistance to trimethoprim (TMP) were made from 1978 to 1980 among urinary tract isolates of enterobacteria from the Nottingham area of the United Kingdom. These surveys revealed an increasing trend toward levels of resistance to TMP, both in hospitals and in the general environment. Because of this trend, the chances of initial infection with an organism resistant to TMP are increased. Much of this increased resistance can be accounted for by the accelerated spread of TMP resistance plasmids and transposons. The appearance of chromosomally located resistance to TMP mediated by a transposon in the absence of a plasmid is unfortunate because of the potential stability of this form of resistance. The clinical isolation of organisms resistant to TMP but sensitive to sulfonamides, coupled with the increasing use of TMP by itself in the United Kingdom, emphasizes the need for continued monitoring of the relationship between resistance to TMP and to sulfonamides in urinary tract pathogens.

Bacteria↗
PubMedDate not supplied

Treatment of concomitant Neisseria gonorrhoeae and Chlamydia trachomatis infections in women: comparison of trimethoprim-sulfamethoxazole with ampicillin-probenecid.

Sixty-nine women with known or suspected uncomplicated gonorrhea were treated randomly either with a single dose of 3.5 g of ampicillin plus 1 g of probenecid or with four doses of trimethoprim-sulfamethoxazole (TMP-SMZ) in two double-strength tablets (160 mg of TMP plus 800 mg of SMZ) twice daily for two days. Overall, 56 (81%) of the women had gonococcal infections, 26 (38%) had chlamydial infections, and 23 (33%) had coexisting Chlamydia trachomatis and Neisseria gonorrhoeae infections. Among the women with genital or anal gonorrhea, two (9%) of 23 treated with TMP-SMZ and three (12%) of 25 treated with ampicillin and probenecid remained infected. TMP-SMZ cured four of four pharyngeal gonococcal infections. C. trachomatis was isolated at the first posttreatment visit significantly more often after treatment with ampicillin and probenecid (10 of 11 times) than after treatment with TMP-SMZ (1 of 10 times; P = 0.003). However, at the second follow-up visit, C. trachomatis was isolated from 30% of the women treated with TMP-SMZ. The area of ectopic columnar epithelium (ectopy) on the ectocervix and edema of this area were highly correlated with the presence of C. trachomatis, and persistence of C. trachomatis was associated with persistent edema of ectopy and with friability. TMP-SMZ is as effective as ampicillin-probenecid for the treatment of uncomplicated genital gonorrhea in women and may be more effective for the treatment of pharyngeal gonorrhea. The optimal dose and duration of TMP-SMZ therapy for C. trachomatis infection requires further study.

Adolescent↗
PubMedDate not supplied

Response of typhoid fever caused by chloramphenicol-susceptible and chloramphenicol-resistant strains of Salmonella typhi to treatment with trimethoprim-sulfamethoxazole.

Chloramphenicol remains the drug of choice for the treatment of typhoid fever in most areas despite the risks of relapses and toxicity. In a comparison of the efficacy of trimethoprim-sulfamethoxazole (TMP-SMZ) and chloramphenicol against typhoid fever, 60 patients in Indonesia were randomly assigned to receive either TMP-SMZ (320 mg of TMP and 1,600 mg of SMZ daily) or chloramphenicol (2 g daily) for 14 days. TMP-SMZ was significantly more effective in sterilizing the blood, but the two drugs were equally effective with regard to relapse rate, frequency of prolonged fever, and mortality. Use of TMP-SMZ in Vietnam for the treatment of typhoid fever caused by chloramphenicol-resistant Salmonella typhi showed that TMP-SMZ is as effective as ampicillin. Likewise, a review of other published reports suggests that TMP-SMZ has an overall record in the treatment of typhoid fever that is equal to or better than the records of other available drugs. TMP-SMZ has emerged as a satisfactory alternative to chloramphenicol for the treatment of typhoid fever and should be especially useful in areas where chloramphenicol-resistant S. typhi has been isolated.

Adolescent↗
PubMedDate not supplied

A controlled study of trimethoprim-sulfamethoxazole prophylaxis of urinary tract infection in renal transplant recipients.

Urinary tract infection (UTI) during the four months after renal transplantation occurs in 30%-40% of recipients at the Massachusetts General Hospital and is often associated with gram-negative bacteremia, significant graft dysfunction, and relapse. Of these "early" UTIs, 90% affect the graft itself. In a randomized trial of prophylaxis of UTI with trimethoprim-sulfamethoxazole (TMP-SMZ), 52 consecutive allograft recipients received either no prophylaxis or one TMP-SMZ tablet (160 mg of TMP plus 800 mg of SMZ) daily for four months, beginning on removal of the Foley catheter (usually during the first four days after transplantation). Three of the first five patients given TMP-SMZ developed oral candidiasis; they and all subsequent recipients of TMP-SMZ were given oral mycostatin throughout prophylaxis. Two of 26 patients (8%) taking TMP-SMZ developed UTIs; 10 of 26 patients (38%) not taking the drug developed UTIs with evidence of graft infection (P less than 0.05). The two groups were comparable in age, sex, history of UTI before transplantation, type of donor, type of ureteral anastomosis, and antibiotic use for other types of infection. Only one complication, a skin eruption, was observed among patients taking TMP-SMZ and mycostatin. It is concluded that TMP-SMZ is well tolerated and effective prophylaxis in this setting.

Adult↗
PubMedDate not supplied

Antimicrobial therapy for travelers' diarrhea.

Three clinical trials were carried out to examine the efficacy of various antimicrobial agents in the treatment of travelers' diarrhea among students from the United States in Mexico. Thirty-seven subjects received twice daily for five days 160 mg of trimethoprim (TMP) and 800 mg of sulfamethoxazole (SMZ), 38 received 200 mg of TMP, and 35 received a placebo. Another group of students were given 100 mg of furazolidone (47 students) or ampicillin (47 students) four times a day for five days. In the third study, 500 mg of bicozamycin (72 students) or a placebo (68 students) was given four times a day for three days. Most students who received TMP-SMZ (78%), TMP (84%), or bicozamycin (85%) had recovered by 48 hr after initiation of treatment, as compared with 14% and 47% in the corresponding placebo groups and 55% in the furazolidone group. The agents had a positive effect for all etiologic categories, including diarrhea due to enterotoxigenic Escherichia coli and Shigella strains and illness without any established etiologic agents. Treatment failures were unusual with TMP-SMZ, TMP, and bicozamycin therapy (5% vs. 39% for the placebo-treated students). The drugs were well tolerated. The use of TMP-SMZ or TMP alone in the empiric treatment of moderate to severe travelers' diarrhea is advocated.

Adult↗
PubMed1983

Rifaprim in urinary tract infection: a comparison with co-trimoxazole.

Two regimes of rifaprim (RPM), a 3.75 to 1 combination of rifampicin (RIF) and trimethoprim (TMP), were compared with co-trimoxazole (CO-T) for the treatment of urinary tract infection in 60 patients. Dosages were: A, 450 mg RIF + 120 mg TMP twice daily; B, 600 mg RIF + 160 mg TMP at bedtime and C, 800 mg sulphamethoxazole (SMZ) + 160 mg TMP twice daily. Clinical results were similar but CO-T treatment was accompanied by a greater number of late bacteriological failures. In none of 40 patients receiving RPM did resistance to any of the components develop, while in three of 20 patients receiving CO-T resistance to TMP or SMZ emerged during treatment. There were no side effects in the patients receiving RPM, but three patients developed transient laboratory abnormalities. One patient receiving CO-T had a rash and one further transient laboratory abnormalities. Satisfactory concentrations of RIF and TMP were measured in urine up to 24 h after a dose of 600 mg RIF + 160 mg TMP. RIF may be a better companion to TMP than the sulphonamides for the treatment of urinary tract infection.

Adult↗