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PubMed2003

A cost-effectiveness analysis of treatment strategies for acute uncomplicated pyelonephritis in women.

UNLABELLED: At least 250,000 episodes of acute uncomplicated pyelonephritis are treated annually in the emergency department (ED). Trimethoprim-sulfamethoxazole (TMP-SMX) and norfloxacin have both been used as treatments for acute uncomplicated pyelonephritis. OBJECTIVES: To investigate the cost-effectiveness of two outpatient treatment strategies, TMP-SMX and norfloxacin, for acute uncomplicated pyelonephritis in adult women between the ages of 18 and 65 years. METHODS: Common principles of cost-effectiveness analysis were used for this evaluation. The authors developed a decision tree to estimate the costs and effectiveness of two different treatment strategies: TMP-SMX 160/800 mg twice per day for 10 days and norfloxacin 400 mg twice per day for 10 days. The time frame of the decision tree was 11 days. Outcomes were expressed in U.S. dollars, quality-adjusted life-days (QALDs), and dollars per QALD. Sensitivity analyses were performed on most variables. RESULTS: Norfloxacin is more effective and less costly than the alternative, TMP-SMX. Norfloxacin treatment will save $195.85 per patient, resulting in an aggregate saving of more than $40 million annually. Patients are expected to enjoy a better quality of life with an incremental 0.0601 QALD per patient, if they are treated with norfloxacin. These results are robust across a wide range of probabilities and costs. CONCLUSIONS: In this analysis, norfloxacin 400 mg twice a day was a more cost-effective treatment than TMP/SMX 160/800 mg twice a day for women with pyelonephritis.

Acute Disease↗

PubMed1986

Alterations of urinary carbon dioxide tension, electrolyte handling and low molecular weight protein excretion in acute pyelonephritis.

Renal tubular function tests were performed in 45 children suffering from upper and lower urinary tract infections. Determinations were made of the urinary carbon dioxide tension in maximally alkaline urine as an index of distal tubular H+-ion secretion, of urinary protein excretion, and of urinary sodium and phosphate handling. Urinary PCO2 was low (2.7 +/- 13.9 mmHg) in acute pyelonephritis compared to values in healthy children (52 +/- 32 mmHg) or those with cystitis (48 +/- 34 mmHg). At the onset of pyelonephritis an elevated fractional excretion of sodium (1.38 +/- 0.38 vs. 0.50 +/- 0.20%) and decreased phosphate reabsorption (69.2 +/- 7.1 vs. 90.4 +/- 4.9%) were also observed. Significantly elevated urinary low molecular weight protein excretion was also found in pyelonephritis. These data indicate the existence of proximal and distal tubular dysfunction at the onset of acute bacterial pyelonephritis.

Acute Disease↗

PubMed1996

Interleukin-1 alpha and interleukin-1 receptor antagonist in the urine of children with acute pyelonephritis and relation to renal scarring.

Urinary concentrations of interleukin-1 alpha (IL-1 alpha) and interleukin-1 receptor antagonist (IL-lra) standardized to urinary creatinine concentrations were studied. The median standardized IL-1 alpha creatinine quotient in children with first-time acute pyelonephritis was 3.6 pg/mumol, but was nondetectable in children with recurrent pyelonephritis, children with non-renal febrile conditions and children convalescent after acute pyelonephritis (p < 0.05-0.01). IL-lra levels were also significantly higher in children with acute first-time pyelonephritis (median of 239 pg/mumol) compared to these three groups of children (p < 0.01-0.001). The highest urinary IL-lra levels, however, were found in the healthy controls (median value 1.019; p < 0.001). Both cytokines were higher among children younger than one year compared to older children. The acute IL-1 alpha creatinine quotients were lowest in children with uptake defects on 99mTC-dimercaptosuccinic acid (DMSA) scintigraphy both during the acute infection (reflecting the acute inflammation) (p < 0.001) and 1 year after the acute infection (reflecting permanent kidney scarring) (p < 0.001). In conclusion, persisting high urinary levels of IL-1 alpha were associated with less renal inflammation and scarring.

Acute Disease↗

PubMed1994

L-651,392, a potent leukotriene inhibitor, controls inflammatory process in Escherichia coli pyelonephritis.

In this study, the relationship between leukotrienes, peritubular cell infiltration with polymorphonuclear cells (PMNs) and renal tubular damage was investigated in a rat model of acute ascending pyelonephritis. Infection was induced by the injection of 10(5) CFU of Escherichia coli into the bladder and occlusion of the left ureter for 24 h. Treatment of infected animals was started 24 h after the induction of pyelonephritis with either hydrocortisone (25 mg/kg of body weight per day), the leukotriene inhibitor L-651,392 (10 mg/kg/day), or the vehicle of L-651,392 and was maintained for 5 days. At the end of treatment, the animals were killed, serum was collected, and both kidneys were removed for colony counts and histopathology. Renal function was evaluated by the measurement of blood urea nitrogen levels and creatinine clearance. The numbers of PMNs and mononuclear cells (MNs) in the cortex and medulla were recorded for all groups on plastic sections done from the left kidney. Infection alone (vehicle of L-651,392) resulted in intensive interstitial infiltration and a severe tubular destruction in the cortex. Treatment with hydrocortisone did not prevent PMN migration and tissue damage. By contrast, treatment with L-651,392 resulted in a significant reduction in PMNs (P < 0.001 in comparisons with all other groups) and greater preservation of the tubular structure despite identical bacterial counts than in the group receiving hydrocortisone. We conclude that L-651,392 prevents inflammatory cells from reaching the site of infection and protects the kidney from tubular damage associated with inflammation during pyelonephritis. Inhibitors of leukotrienes should be further investigated for their potential benefit as adjuvants to antibiotherapy in the treatment of pyelonephritis.

Animals↗

PubMed2001

Cytokine profiles of pediatric patients treated with antibiotics for pyelonephritis: potential therapeutic impact.

Urinary tract infections are common in infants and children. Pyelonephritis may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the timing of release of inflammatory cytokines in relation to pyelonephritis and its treatment is essential for designing interventions that would minimize tissue damage. To this end, we measured urinary cytokine concentrations of interleukin-1 beta (IL-1 beta), IL-6, and IL-8 in infants and children with pyelonephritis and in healthy children. Children that presented to our institution with presumed urinary tract infection were given the diagnosis of pyelonephritis if they had a positive urine culture, pyuria, and one or more of the following indicators of systemic involvement: fever, elevated peripheral white blood cell count, or elevated C-reactive protein. Urine samples were obtained at the time of presentation prior to the administration of antibiotics, immediately after completion of the first dose of antibiotics, and at follow up 12 to 24 h after presentation. IL-1 beta, IL-6, and IL-8 concentrations were measured by enzyme-linked immunosorbent assay. Creatinine concentrations were also determined, and cytokine/creatinine ratios were calculated to standardize samples. Differences between pre-antibiotic and follow-up cytokine/creatinine ratios were significant for IL-1 beta, IL-6, and IL-8 (P < 0.01). Differences between pre-antibiotic and control cytokine/creatinine ratios were also significant for IL-1 beta, IL-6, and IL-8 (P < 0.01). Our study revealed that the urinary tract cytokine response to infection is intense but dissipates shortly after the initiation of antibiotic treatment. This suggests that renal damage due to inflammation begins early in infection, underscoring the need for rapid diagnosis and intervention.

Anti-Bacterial Agents↗

PubMed1977

Experimental model of corynebacterium renale pyelonephritis produced in mice.

Corynebacterium renale type I (strain 115), 1.7 X 10(7) to 4.5 X 10(7) organisms, introduced intravenously into mice disappeared from the blood less than 24 h after inoculation and did not produce pyelonephritis. The same strain, 1 X 10(7) to 5 X 10(7) organisms, inoculated into the urinary bladder of mice was not recovered from the blood in any of the mice, but caused pyelonephritis accompanied by ureteritis and cystitis in 16 of 21 (76%) mice. Pyelonephritis and cystitis in mice were histopathologically similar to those found in cows. The antibody response was observed only in the mice with pyelonephritis or pyelitis, but not in those with only cystitis or in those without lesions, as found in cows. Similar diseases were produced in mice by C. renale types II and III but less frequently than by type I. It is suggested, therefore, that mice may be useful in the study of bovine C. renale infection.

Animals↗

PubMed1978

Interaction of human serum and neutrophils with Escherichia coli strains: differences between strains isolated from urine of patients with pyelonephritis or asymptomatic bacteriuria.

Strains of Escherichia coli isolated from the urine of children with pyelonephritis (n = 18) or asymptomatic bacteriuria (ABU) (n = 20) were serotyped and compared with respect to opsonic requirements, sensitivity to serum, amount of chemiluminescence produced by normal neutrophils during phagocytosis of the various strains, and amount of capsular antigen. Strains isolated from cases of ABU more often had the capacity to activate the alternative complement pathway than had strains causing pyelonephritis. The ABU strains were also better opsonized in fresh human serum and were more often serum sensitive than the pyelonephritic strains. There were individual variations in neutrophil chemiluminescence during phagocytosis of the various strains, but the two groups of strains did not differ significantly. The strains from pyelonephritis cases produced a greater amount of capsular antigens than the ABU strains. There was no correlation between presence of a particular O or K antigen and capacity to activate the alternative complement pathway. The observed differences between strains isolated from patients with ABU and those isolated from patients with pyelonephritis may be relevant for further studies on differences in bacterial virulence or host defense factors.

Antigens, Bacterial↗

PubMed1991

Alpha-hemolysin contributes to the pathogenicity of piliated digalactoside-binding Escherichia coli in the kidney: efficacy of an alpha-hemolysin vaccine in preventing renal injury in the BALB/c mouse model of pyelonephritis.

Digalactoside-binding (Gal-Gal) pili and alpha-hemolysin of Escherichia coli have been implicated as important virulence determinants in the pathogenesis of human ascending, nonobstructive pyelonephritis. The pathogenic significance of these determinants was evaluated in vitro and in the BALB/c mouse pyelonephritis model by employing wild-type, avirulent laboratory, and genetically defined cosmids, transformants, and recombinant strains. In vitro data suggest that the cytolytic activity of hemolysin is significantly (P less than 0.05) enhanced among digalactoside-binding strains which agglutinate erythrocytes. The basis of increased hemolysis is related presumably to more efficient delivery of the toxin to target lipid substrate in the host plasma membrane. Intravesicular administration of bacteria that express both digalactoside binding and hemolysin generally resulted in greater mortality and renal parenchymal injury in mice than strains that expressed none or only one of these determinants. Analyses convincingly demonstrate that digalactoside-binding pili are correlated with upper urinary tract colonization and that hemolysin is correlated with septicemia and renal parenchymal damage. These determinants collectively constitute the minimal virulence factors to produce disease in this model. Their efficacy as vaccines for the prevention of pyelonephritis was also assessed. A purified Gal-Gal pilus vaccine prevented (P less than 0.05) subsequent colonization by a challenge wild-type strain that exhibited homologous pili. The hemolysin vaccine did not abrogate subsequent bacterial renal colonization on challenge, but it did protect (P less than 0.05) mice which survived challenge from subsequent renal injury compared with those in the saline control group. The combination of these determinants was also protective. The combination of Gal-Gal pili and hemolysin in a vaccine preparation represents a potentially worthwhile strategy for human immunoprophylaxis against pyelonephritis by interdicting several steps in the pathogenesis of a bacterial mucosal infection.

Animals↗

PubMed1993

Contribution of Proteus mirabilis urease to persistence, urolithiasis, and acute pyelonephritis in a mouse model of ascending urinary tract infection.

Proteus mirabilis, a significant cause of bacteriuria and acute pyelonephritis in humans, produces urease. This high-molecular-weight, multimeric, cytoplasmic enzyme hydrolyzes urea to ammonia and carbon dioxide. To assess the role of urease in colonization, urolithiasis, and acute pyelonephritis in an animal model of ascending urinary tract infection, we compared a uropathogenic strain of P. mirabilis with its isogenic urease-negative mutant, containing an insertion mutation within ureC, the gene encoding the large subunit of the enzyme. Mice challenged transurethrally with the parent strain developed significant bacteriuria and urinary stones. The urease-negative mutant had a 50% infective dose of 2.7 x 10(9) CFU, a value more than 1,000-fold greater than that of the parent strain (2.2 x 10(6) CFU). The urease-positive parent strain reached significantly higher concentrations and persisted significantly longer in the bladder and kidney than did the mutant. Indeed, in the kidney, the parent strain increased in concentration while the mutant concentration fell so that, by 1 week, the parent strain concentration was 10(6) times that of the mutant. Similarly, the urease-positive parent produced significantly more severe renal pathology than the mutant. The initial abnormalities were in and around the pelvis and consisted of acute inflammation and epithelial necrosis. By 1 week, pyelitis was more severe, crystals were seen in the pelvis, and acute pyelonephritis, with acute interstitial inflammation, tubular epithelial cell necrosis, and in some cases abscesses, had developed. By 2 weeks, more animals had renal abscesses and radial bands of fibrosis. We conclude that the urease of P. mirabilis is a critical virulence determinant for colonization, urolithiasis, and severe acute pyelonephritis.

Acute Disease↗

PubMed1988

Renal parenchymal volume during and after acute pyelonephritis measured by ultrasonography.

A total of 47 children with acute pyelonephritis were investigated using water delay ultrasonographic equipment (Octoson) for determination of renal parenchymal volume by the stepped section technique. Thirty two patients were repeatedly investigated every to every other week up to seven weeks. Median renal parenchymal volume during acute pyelonephritis of the right kidney was 2.70 cm3/kg body weight and of the left kidney 3.10 cm3/kg; this was significantly larger than the volume of control kidneys, which was 1.82 and 2.07 cm3/kg, respectively. The most enlarged kidneys were found among the youngest children. A significant successive decrease in renal size was found during the first four to five weeks after the acute pyelonephritis. Because of enlargement of the kidneys during acute pyelonephritis we suggest that the first renal size determination to be used for following renal growth should be performed after at least four to six weeks.

Acute Disease↗

PubMed1999

Xanthogranulomatous pyelonephritis in childhood.

BACKGROUND: Xanthogranulomatous pyelonephritis is a severe, atypical form of chronic renal parenchymal infection accounting for 6/1000 surgically proved cases of chronic pyelonephritis. Its manifestations mimic those of neoplastic and other inflammatory renal parenchymal diseases and, consequently, it is often misdiagnosed preoperatively. AIM: To examine the relation between clinical history and the results of renal investigations performed in children with xanthogranulomatous pyelonephritis. METHOD: A retrospective review of 31 cases presenting with the histopathological diagnosis of xanthogranulomatous pyelonephritis between 1963 and 1999. RESULTS: The mean follow up was 8.2 years. The male:female ratio was 1:1.1. The left kidney was affected in 26 of the 31 patients. The positive findings on examination and investigation at presentation were: fever, 16 children; pyuria, 26 children; positive urine culture, 16 children. A haemoglobin of < 100 g/l was measured in 27 of 31 patients and 15 of 18 patients tested had a raised erythrocyte sedimentation rate of > 20 mm in the first hour. Twenty six children had renal calculi, with a large reduction in the function of the affected kidney on isotope scintigraphy in 27 of the 29 patients tested. Hypertrophy of the contralateral kidney, shown on imaging, was present in 17 of 31 patients. CONCLUSIONS: Increasing awareness of this condition should lead to the diagnosis being suspected preoperatively.

Adolescent↗

PubMed2002

Plasma and urinary soluble adhesion molecule expression is increased during first documented acute pyelonephritis.

BACKGROUND: The degree of inflammatory reaction and leucocyte trafficking during acute pyelonephritis has been related to the risk of developing renal parenchymal scarring. Adhesion molecules play a central role in leucocyte recruitment during inflammation. AIMS: (1) To determine whether circulating and urinary concentrations of E-selectin and intercellular adhesion molecule 1 (ICAM-1) were abnormal during first documented acute pyelonephritis; (2) to investigate whether circulating or urinary concentrations were predictive for the development of abnormalities on DMSA imaging. METHODS: Plasma and urine samples were collected from 40 children with a first episode of acute pyelonephritis within one week of infection (acute sample) and at six weeks (late sample). Control samples were collected from 21 healthy age matched controls and 18 age matched controls with febrile illness not secondary to urinary tract infection. RESULTS: Plasma and urinary sE-selectin were higher in acute samples (median 176.3 ng/ml and 0.12 ng/mmol respectively) compared with late (97.8 ng/ml and 0.029 ng/mmol) and both control (65.6 ng/ml and 0 ng/mmol) and febrile control (urine 0 ng/mmol) samples. Plasma sICAM-1 was higher in acute samples (428 ng/ml) than controls (365.2 ng/ml), and acute sICAM-1 urine concentrations were higher than febrile control concentrations (3.2 v 0.7 ng/mmol). No correlations were detected between sE-selectin or sICAM-1 and acute or late DMSA scan changes. CONCLUSION: Plasma and urinary sE-selectin and sICAM-1 are significantly increased during acute pyelonephritis, though no correlation exists between the presence of high plasma or urine concentrations and DMSA scan changes, both during acute infection and six weeks post-infection.

Acute Disease↗

PubMed2002

Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women. A randomised controlled trial.

OBJECTIVE: To compare the short-term effectiveness of ceftriaxone single dose followed by cefixime with a standard treatment of acute uncomplicated pyelonephritis in women. METHODS: An open, prospective, and randomised trial of women with acute uncomplicated pyelonephritis was performed. Group A were given a daily intravenous dose of 1 g ceftriaxone; group B: ceftriaxone 1 g intravenous single dose followed by oral cefixime. When urine culture was received, both groups completed a 10 day treatment based in sensitivity studies. Only women with positive initial urine culture were included. After three days of treatment, clinical and bacteriological efficacy was assessed. Clinical response was classified as "cured" if acute symptoms (fever, urinary syndrome and flank pain) were settled. Bacteriological response was classified as: eradication, or no eradication. RESULTS: Of 144 eligible patients, urine culture was positive in 54 of 72 (75%) women in group A and 51 of 72 (71%) in group B. There were no significant differences between groups in resolution of acute symptoms. Clinical cure was observed in 49 of 54 (91%) patients in the group A and in 47 of 51 (92%) patients in the group B (p = 0.68). After three days of treatment urine culture was negative for all patients. No adverse effects were observed in either of the groups. CONCLUSION: These data suggest that a intravenous single dose of ceftriaxone followed by oral cefixime is both effective and safe for the initial treatment of acute uncomplicated pyelonephritis in women. This regimen could be useful in managing selected patients with pyelonephritis as outpatients.

Acute Disease↗

PubMed1981

Evaluation of penicillin in conjunction with acetohydroxamic acid in treatment of experimental Corynebacterium renale pyelonephritis.

The therapeutic efficacies of procaine penicillin G and acetohydroxamic acid, when administered alone or in combination, were evaluated in rats with experimentally induced pyelonephritis at 24 h and 4 days after intrabladder inoculation with Corynebacterium renale. Penicillin alone prevented the development of pyelonephritis when administered in a once daily dose of 50,000 units for 5 days beginning within 24 h of infection challenge. However, if therapy was not initiated until the 4th day after induction of infection, pyelonephritis ensued which could not be differentiated from untreated rat pyelonephritis. Acetohydroxamic acid, when administered by itself in a once daily dose of 100 mg for 5 days, was completely ineffective whether therapy was started at 24 h or 4 days after initiation of infection. On the other hand, the combination of penicillin and acetohydroxamic acid prevented progression of pyelonephritic infection and facilitated healing when rat kidneys were examined at 14 and 30 days after initiation of infection. The kidneys of those rats sacrificed at 30 days after cessation of treatment revealed the presence of increased interstitial fibrous connective tissue in the renal medulla suggesting prior damage followed by recovery and repair. In vitro studies on the action of penicillin and acetohydroxamic acid against C. renale revealed no signs of synergism or antagonism.

Animals↗

PubMed2001

Renal fibrosis: prediction from acute pyelonephritis focus volume measured at 99mTc dimercaptosuccinic acid SPECT.

PURPOSE: To evaluate whether acute pyelonephritis lesion volume derived from acute technetium 99m ((99m)Tc) dimercaptosuccinic acid (DMSA) renal single photon emission computed tomographic (SPECT) images is predictive of the development of subsequent renal fibrosis. MATERIALS AND METHODS: Children with acute pyelonephritis underwent (99m)Tc DMSA renal SPECT during acute infection and 6-10 months later. At quantitative analysis, the volume of photopenic lesions and the ratio of radioactivity in the photopenic lesion to that in normal renal tissue were calculated. Sensitivity, specificity, and positive and negative predictive values were determined. RESULTS: Sixty-nine acute pyelonephritis foci in 44 children were analyzed. Thirty-seven (54%) of these lesions were normal on follow-up renal scans, while 32 (46%) developed scars. Significant differences in the photopenic lesion volume were found between the two groups (P < .001). When photopenic lesion volume indicated a positive diagnosis (>or=4.6-cm(3) lesion volume), sensitivity, specificity, positive predictive, and negative predictive values were 96.7%, 92.3%, 90.6%, and 97.3%, respectively. CONCLUSION: Quantitative analysis of acute DMSA renal SPECT findings is valuable in predicting renal fibrosis. The volume of an acute pyelonephritis lesion is useful in predicting the development of fibrosis.

Adolescent↗

PubMed1976

Hypertension and plasma renin activity in experimentally induced chronic pyelonephritis.

The present authors conducted a series of experiments with mongrel dogs, in which unilateral chronic pyelonephritis was induced and postoperative changes in blood pressure and plasma renin activity were observed over a period of 3 months. The pyelonephritis infection was brought about by a method involving vesicoureteral reflux and ureteral dysfunction, as described in a previous paper. Pre- and postoperative levels of systolic pressure were compared, but no definite trends were found for the first 3 weeks after operation. At 30, 60 and 90 days the pressures were found to have risen by 21.2 +/- 14.6 and 17.1 +/- 16.7 mm Hg, respectively. No appreciable change in the plasma renin activity was found, however, at any stage. From these results it was concluded that experimentally induced chronic pyelonephritis in dogs caused a rise in blood pressure. No connection between the pyelonephritis and the renin angiotensin system was found.

Animals↗

PubMed1985

Fever and proximal tubular function in acute pyelonephritis.

The urinary excretion of alpha 1-microglobulin (alpha 1M), beta 2-microglobulin (beta 2M), retinol-binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) as markers of proximal tubular dysfunction was measured in various forms of urinary tract infections (UTI) and in fever due to non-renal infections. The urinary concentration of these proteins was significantly increased in acute pyelonephritis compared with acute cystitis and asymptomatic bacteriuria. Tubular proteinuria and enzymuria could also be demonstrated in subjects with fever of non-renal origin and corresponded to the findings of pyelonephritis. It is suggested that fever per se is the most likely cause of the tubular proteinuria seen in acute pyelonephritis. In localizing an acute UTI characterization of the urinary protein profile seems to have no advantage over a carefully measured body temperature. The urinary excretion of alpha 1M,beta 2M and RBP were highly correlated, while urinary NAG activity was less correlated to these low-molecular weight proteins. Fibrin degradation product D (FDP-D) was detected in the urines in 60% of the patients with acute pyelonephritis and in one third of those with acute cystitis. The estimation of FDP in urine therefore seems to be of little value in the level diagnosis of UTI.

Acetylglucosaminidase↗

PubMed1988

Antibody-dependent cell-mediated cytotoxicity against Tamm-Horsfall protein in acute pyelonephritis.

The cytotoxic activity of leukocytes from humans and rats with pyelonephritis were examined in an antibody-dependent cell-mediated cytotoxicity assay (ADCC) with CrCl3-treated erythrocytes coated with Tamm-Horsfall (TH) as target cells. The specificity of the ADCC was confirmed by absorption with TH urinary glycoprotein and inhibition of the ADCC activity seen with polyclonal rabbit anti-TH antisera by monoclonal mouse antibodies. The ADCC activity detected in children with acute pyelonephritis was low in the initial phase of the disease, but increased significantly 9 days after the start of antibacterial treatment. In rats with experimental pyelonephritis, ADCC activity decreased significantly with increased duration of infection. Depletion of cells adhering to carbonyl iron led to higher ADCC activity. During the course of the infection the difference in ADCC activity between effector cell preparations depleted using carbonyl iron and those not depleted decreased. The decreased ADCC activity demonstrated during acute pyelonephritis may point to mechanisms operating to diminish the risk of tissue damage.

Acute Disease↗