Urinary tract infection guidelines questioned.
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Biomedical subjects
Publications and source records attributed to G A Richard.
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OBJECTIVES: To evaluate, in two randomized, multicenter trials, levofloxacin compared with ciprofloxacin and lomefloxacin for efficacy and safety in treating acute pyelonephritis. METHODS: We enrolled a total of 186 patients with bacteriologically proved infection. Of these, 89 patients in both trials combined received levofloxacin 250 mg once daily; 58 received ciprofloxacin 500 mg twice daily in the first trial (double blind); and 39 received lomefloxacin 400 mg once daily in the second trial (open label). Microbiologic response of patients evaluable for microbiologic efficacy was the primary efficacy variable, and clinical response of microbiologically evaluable patients was the secondary efficacy variable in both studies. RESULTS: Escherichia coli was the most prevalent pathogen. At 5 to 9 days after the end of treatment, 95% of uropathogens were eradicated in patients who received levofloxacin compared with 94% in the ciprofloxacin-treated group and 95% in the lomefloxacin-treated group. The clinical cure rate was 92% for levofloxacin in both studies combined, 88% for ciprofloxacin, and 80% for lomefloxacin. Drug-related adverse events were reported by 2% of levofloxacin-treated patients, 8% of ciprofloxacin-treated patients, and 5% of lomefloxacin-treated patients. CONCLUSIONS: The once-daily oral administration, proven efficacy, and good tolerability make levofloxacin an excellent choice for empiric treatment of acute pyelonephritis.
Analysis of patients with inherited hypokalaemic alkalosis resulting from salt-wasting has proved fertile ground for identification of essential elements of renal salt homeostasis and blood-pressure regulation. We now demonstrate linkage of this phenotype to a segment of chromosome 1 containing the gene encoding a renal chloride channel, CLCNKB. Examination of this gene reveals loss-of-function mutations that impair renal chloride reabsorption in the thick ascending limb of Henle's loop. Mutations in seventeen kindreds have been identified, and they include large deletions and nonsense and missense mutations. Some of the deletions are shown to have arisen by unequal crossing over between CLCNKB and the nearby related gene, CLCNKA. Patients who harbour CLCNKB mutations are characterized by hypokalaemic alkalosis with salt-wasting, low blood pressure, normal magnesium and hyper- or normocalciuria; they define a distinct subset of patients with Bartter's syndrome in whom nephrocalcinosis is absent. These findings demonstrate the critical role of CLCNKB in renal salt reabsorption and blood-pressure homeostasis, and demonstrate the potential role of specific CLCNKB antagonists as diuretic antihypertensive agents.
Two white female infants were seen with congenital nephrotic syndrome at age 6 weeks and 3 months, respectively. Both had hypocomplementemia, elevated antinuclear antibody and anti-double-stranded DNA titers, and diffuse proliferative glomerulonephritis with positive immunofluorescence in their initial renal biopsy samples. Although uncommon, infantile systemic lupus erythematosus should be considered in the evaluation of congenital nephrotic syndrome.
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Renal transplantation is the preferred treatment for end-stage renal disease in children. Most transplant failures are due to allograft rejection. To date, only histopathological findings on renal biopsy can establish this diagnosis. Prior to the availability of cyclosporine, technetium-99m sulfur colloid nuclear scans (TSC) were used in a limited number of institutions to detect rejection episodes. The purpose of this study was to determine whether TSC could predict acute rejection in the cyclosporine era. A prospective study involving 41 pediatric renal transplant patients (M = 25, F = 16) was conducted from 6/1/89 to 10/31/91. Patients who received a TSC and biopsy (41 patients, 62 studies) within one week of clinical and laboratory evidence of acute rejection were included in the study. A qualitative method of determining sulfur colloid uptake was used by comparing allograft uptake with that of the fifth lumbar vertebrae (L5) marrow uptake: 3(+)--allograft with greater than L5 marrow uptake, 2(+)--same as, 1(+)--less than, and 0--no allograft uptake. Transplant accumulation of > or = 2+ was considered consistent with acute rejection (P < 0.001). Acute rejection was noted in 53 of 62 renal biopsies. Of those with biopsy-proved acute rejection, SC was positive (> or = 2+) in 46 of 53. SC of > or = 2+ has proved to be a good predictor of acute rejection. This technique has a sensitivity of 98%, specificity of 53%, positive predictive value of 87%, and negative predictive value of 89%.
Growth was assessed in children following 128 separate kidney transplants using a generalized growth curve multivariate analysis. The height standard deviation score was the dependent variable. Time since transplant, prednisone dosage, and creatinine clearance were the independent variables. For the purposes of comparison patients were grouped according to sex, race, age at transplantation, initial allograft function, acute rejection episodes and the use of cyclosporin A. Patient's height standard deviation scores tended to increase negatively after transplantation. However, children who received transplants before their 7th birthday, with initial allograft function greater than 60 ml/min per 1.73 m2, exhibited "catch-up" growth. Height standard deviation scores positively improved in males but not in females, as prednisone dosage was decreased. Height standard deviation scores became more negative as renal function decreased after transplantation. Changes in renal function produced the greatest effect upon height in black children, children less than 7 years, and males.
The incidence of renal calculi in renal transplant recipients was reviewed. It is an infrequent problem, with an incidence less than 1%. In the pediatric population, only 8 cases had been reported in the literature since 1964. Of the 221 children transplanted at this institution from 1964 to 1989, only these 2 developed renal calculi. One case was related to hyperparathyroidism and the other to idiopathic hypercalcinuria. This represented a frequency of 0.9% which correlates closely with the reported incidence in the transplant population at large.
Eighty-nine college women with acute urinary tract infections were treated orally with either 1,000 mg of cefuroxime axetil in a single dose (n = 59) or 250 mg of cefaclor three times a day for 7 days (n = 30). At 1 week posttherapy, 88% of the patients in the cefuroxime axetil group and 97% in the cefaclor group were clinically and bacteriologically cured (P greater than 0.10). There was no statistically significant difference between the cure rates of the two treatment groups. However, this study has only a 50% power to detect a 10% difference. Therefore, there is a substantial possibility of a type II error, i.e., failing to find a difference that is actually present. At 4 weeks posttherapy, 78% of the patients in the cefuroxime group and 80% in the cefaclor group remained cured. By 36 weeks posttherapy, the cumulative rate of recurrence in both treatment groups was 60%. Of the patients with a positive antibody-coated bacteria test, fewer achieved a short-term cure after single-dose treatment with cefuroxime axetil than those with a negative antibody-coated bacteria test (67 versus 96%; P less than 0.01).
In this 31-site multicenter trial, 565 adult patients with urinary tract infections were randomly assigned to receive either a 10-day course of cefixime 400 mg once daily (n = 279) or amoxicillin 250 mg three times daily (n = 286). Although all patients were included in the safety analysis, only 93 (33 percent) cefixime-treated and 99 (35 percent) amoxicillin-treated patients were fully evaluable for the efficacy analysis. One week after therapy, the evaluable patients treated with cefixime demonstrated a 90 percent clinical cure rate and a 92 percent eradication rate of the baseline pathogen. This compared with an 83 percent clinical cure rate and an 84 percent bacterial eradication rate in the amoxicillin-treated group. The most frequently isolated pathogen was Escherichia coli (80 percent) followed by Proteus mirabilis (10 percent). One hundred thirty-seven (49 percent) of the 279 cefixime-treated and 126 (44 percent) of the 286 amoxicillin-treated patients reported at least one adverse experience during the study. Adverse reactions associated with cefixime were similar to those reported for other beta-lactam antibiotics. The most frequent adverse experiences reported by cefixime-treated patients were diarrhea (15 percent) and stool changes (12 percent). Headaches (11 percent) and diarrhea (9 percent) were the most frequently reported adverse reactions by the amoxicillin-treated patients. Eleven cefixime-treated patients (3.9 percent) and 10 amoxicillin-treated patients (3.5 percent) discontinued therapy because of adverse experiences. Results of this study demonstrate that a once-daily regimen of cefixime is as safe and effective as a three-times-daily regimen of amoxicillin in the treatment of acute urinary tract infections. Although the incidence of bowel changes was somewhat higher in the cefixime treatment group, these events usually resolved when therapy was discontinued.
This study was done to determine whether intravenous methylprednisolone therapy given concomitantly with low-dose daily, oral prednisone would be as effective as high-dose daily prednisone in the treatment of patients with active systemic lupus erythematosus (SLE) nephritis. Thirteen patients with active SLE nephritis were started on 2 mg/kg prednisone per day, considered the high prednisone phase. Therapy was continued until remission was achieved. Prednisone administration was then tapered to less than 0.5 but more than 0.2 mg/kg per day. On later relapse, these patients received three doses of methylprednisolone (20 mg/kg per dose) on alternate days and continued on the same daily dose of prednisone (less than 0.5 greater than 0.2 mg/kg per day) prior to pulse therapy; this was the methylprednisolone phase. The 13 patients were studied in both phases, serving as their own controls. After 1 month of therapy, no significant differences were observed between treatment phases as to improvement in clinical and laboratory findings. A significant increase in the serum concentration of C3 and C4 was seen both in the high-dose prednisone and methylprednisolone phases, while the serum concentration of anti-ds DNA antibody significantly decreased. Methylprednisolone therapy seems as effective as high-dose prednisone in patients with relapse of SLE nephritis. Because side effects are minimal, methylprednisolone administration may be tried as the therapy of choice for these patients.
In a double-blind randomized study, amoxicillin-clavulanic acid (AM-CL) was compared with cefaclor for the treatment of acute urinary tract infections in 107 college women. A total of 53 patients received amoxicillin (250 mg) and clavulanic acid as the potassium salt (125 mg), and 54 received cefaclor (250 mg); each drug was administered every 8 h for 10 days. The cure rates at 1 and 4 weeks after treatment were 96 and 78%, respectively, in the AM-CL group and 92 and 75%, respectively, in the cefaclor group (P greater than 0.10). After AM-CL treatment, the prevalence of amoxicillin-resistant Escherichia coli significantly increased in the rectal flora. Also, the frequency of bacterial resistance to amoxicillin, AM-CL, and cefaclor increased among the urinary pathogens causing subsequent urinary tract infections (P less than 0.05). There were no adverse reactions in the cefaclor group; however, six patients in the AM-CL group (12%) experienced diarrhea, nausea, or vomiting (P less than 0.05). Elevated transaminase enzyme levels were observed in 23% of the patients in the AM-CL group and in 6% of the patients in the cefaclor group (P less than 0.05). Symptomatic Candida vaginitis developed in 16 and 13% of the patients in the AM-CL and cefaclor groups, respectively (P greater than 0.10).
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Fifty-four college women with symptoms of lower urinary tract infections were randomly treated, 25 with 500 mg of ceftriaxone in a single intramuscular dose and 29 with 160 mg of trimethoprim-800 mg of sulfamethoxazole orally twice daily for 7 days. At 1 week after treatment, 23 patients (92%) in the ceftriaxone group and 28 patients (96%) in the trimethoprim-sulfamethoxazole group were cured. Responses of the patients with positive or negative antibody-coated bacteria tests were not significantly different. Four patients (16%) in the ceftriaxone group developed diarrhea and malaise. One patient (4%) in the trimethoprim-sulfamethoxazole group had medication discontinued because of headaches. Leukopenia was found in one patient (4%) in the ceftriaxone group and four patients (14%) in the trimethoprim-sulfamethoxazole group.
The in vitro activity of amifloxacin (WIN 49375), a new fluoroquinolone, was compared with the activities of antimicrobial agents that are commonly used for the treatment of urinary tract infection (cinoxacin, cephalexin, gentamicin, amoxicillin, trimethoprim, and trimethoprim-sulfamethoxazole) against 25 strains of Staphylococcus saprophyticus and 28 strains of Escherichia coli. Bacterial strains were isolated from urine specimens of college women with acute urinary tract infections. Bacterial isolates were more susceptible to trimethoprim-sulfamethoxazole, trimethoprim, and amifloxacin than to the other drugs tested. The in vitro activity of amifloxacin against S. saprophyticus had an inverse relation to increases in the pH of the test medium. Changes in the type of culture medium had no effect on the in vitro activity of amifloxacin. There was a direct relationship between increases in inoculum size and the MICs of amifloxacin.
The growth of children undergoing continuous ambulatory peritoneal dialysis (CAPD) therapy for end-stage renal disease (ESRD) was compared with the growth of children undergoing hemodialysis and that of children after successful kidney transplantation. The bone ages of the children were used to predict expected growth velocities. The actual growth velocities observed were then expressed as percentages of the predicted rates. Children receiving CAPD therapy grew better than those treated by hemodialysis and as well as the children who received a kidney transplant. There was some correlation between growth and allograft function in the transplant recipients. Children receiving CAPD were less acidotic and were more likely to exhibit improvement in renal osteodystrophy than children treated by ongoing hemodialysis. There were no significant differences in reported caloric intake between the two groups.
Eighteen infants, children, and adolescents were trained in the techniques of continuous ambulatory peritoneal dialysis (CAPD) as a therapy for end stage renal disease (ESRD) at the University of Florida. Fourteen patients successfully continued CAPD 4-24 months, for a total of 193 patient-months. Uremic symptoms were well controlled with blood urea nitrogen concentration (BUN) decreased to between 60 and 80 mg/dl. Parathyroid hormone levels increased but roentgenographic evidence of osteodystrophy improved in most patients. The rate of peritonitis was one episode in 7.7 patient-months. Blood transfusion requirements decreased for patients transferred from in-center hemodialysis to CAPD with no significant decrease in average hematocrits. Caloric intake was adequate and anorexia was usually not a major problem. Children who were evaluated for growth were under 15 years of age, with bone ages less than 12 years, and were using CAPD for longer than 6 months. Their mean growth velocity was 74.7 +/- 20.4% (SD) of the predicted velocity.
The effect of prostaglandin (PG) synthesis inhibitors on the primary antibody response to sheep red blood cells (SRBC) in rats with aminonucleoside-of-puromycin (AP) nephrosis was studied. The response to SRBC was determined 5 days after intraperitoneal administration of SRBC by measuring IgM antibody-forming spleen cells (AFC). In nephrotic rats, SRBC were injected when animals were fully nephrotic. A significant decrease in the number of AFC (P less than 0.05) and a significant increase in the plasma concentration of 6-keto-PGF1 alpha (P less than 0.02) were observed in 22 nephrotic rats compared to 24 normal rats. Treatment of nephrotic rats with indomethacin (5 mg/kg per day, 8 rats) and aspirin (200 mg/kg per day, 7 rats) initiated before the development of nephrosis returned the antibody response and the plasma level of 6-keto-PGF1 alpha to normal, while the same treatment in control rats did not alter the antibody response. These data suggest that in AP nephrosis the observed decrease in antibody response to SRBC is likely due to an increase in PG production at the time of immunization.