Urinary tract infections remain a significant cause of morbidity in all age groups. Recent studies have helped to better define the population groups at risk for these infections, as well as the most cost-effective management strategies. Initially, a urinary tract infection should be categorized as complicated or uncomplicated. Further categorization of the infection by clinical syndrome and by host (i.e., acute cystitis in young women, acute pyelonephritis, catheter-related infection, infection in men, asymptomatic bacteriuria in the elderly) helps the physician determine the appropriate diagnostic and management strategies. Uncomplicated urinary tract infections are caused by a predictable group of susceptible organisms. These infections can be empirically treated without the need for urine cultures. The most effective therapy for an uncomplicated infection is a three-day course of trimethoprim-sulfamethoxazole. Complicated infections are diagnosed by quantitative urine cultures and require a more prolonged course of therapy. Asymptomatic bacteriuria rarely requires treatment and is not associated with increased morbidity in elderly patients. (+info)
Local production of inflammatory mediators in an experimental model of acute obstructive pyelonephritis.
To investigate bacterial growth and inflammatory mediator release in the early stage of the immune response, a unilateral acute ascending pyelonephritis was induced in rats by intrabladder inoculation of Escherichia coli. The infected left kidney showed a significant bacterial proliferation, local production of interleukin (IL)-6 and IL-8 as detected by immunocytochemistry, and extensive destruction of renal parenchyma associated with impressive leukocyte recruitment. Inducible and constitutive nitric oxide synthases (NOS) were locally expressed, and a time-dependent increase in urinary secretion of nitric oxide (NO) was seen that could be blocked by NG-monomethyl-L-arginine. However, there was a discrepancy between the NO profile in the kidney and urine. The results demonstrate that in the early stage of acute pyelonephritis kidney tubules participate actively in the local host response by producing important inflammatory mediators and that urinary NO levels are not suitable for predicting renal NOS activity. (+info)
Quantitative 99mTc-DMSA uptake in experimental pyelonephritis.
Quantitative 99mTc-dimercaptosuccinic acid (DMSA) renal uptake was studied in unilateral reflux-related pyelonephritis in pigs. The changes to absolute % dose uptake and differential uptake occurring with induction and after treatment of pyelonephritis were correlated with the DMSA images and renal pathology. METHODS: Quantitative uptake in 53 young pigs was obtained from planar images acquired 6 h after injecting the dose. Baseline studies were made (Q1), and studies were made again after urinary infection was established (Q2), when 8 pigs had normal (no defect) renal images (group A), 23 had photon-deficient (reversible) focal defects (group B) and 22 had photon absent (irreversible) focal defects (group C). Q3 studies were made in 21 animals from groups B and C after 3-wk antimicrobial treatment. RESULTS: At Q2 the affected kidney differential uptake was unchanged for group A and reduced for groups B and C (respective mean changes -1.7%, P < 0.01; and -5.5%, P < 0.01). The absolute % dose uptake was unchanged in pyelonephritic kidneys, but increased in the contralateral nondiseased kidneys in groups B and C (respective mean increases +1.4%, P < 0.05; and +5.4%, P < 0.01), while remaining unchanged for group A. In group C, global renal accumulation was actually increased above the Q1 values. After treatment (Q3) the reduced pyelonephritic kidney differential uptake persisted in groups B and C. In group C, however, the increased absolute % dose uptake by the contralateral kidney was less marked and not significantly different from Q1 values in this small group. CONCLUSION: Induction of unilateral pyelonephritis produced a small reduction in diseased kidney differential uptake that was greatest in the group with irreversible imaging defects. The method did not discriminate individuals with reversible and irreversible imaging defects. The decrease in pyelonephritic kidney differential uptake resulted from increased DMSA accumulation (absolute % dose uptake) by the nondiseased contralateral kidney, while that in pyelonephritic kidneys remained unchanged. After treatment, the reduced pyelonephritic kidney differential uptake persisted, but the elevated global DMSA accumulation seen for group C (with irreversible imaging defects) was not sustained and was variable. (+info)
Effectiveness and toxicity of gentamicin in an experimental model of pyelonephritis: effect of the time of administration.
Temporal variations in the renal toxicity of aminoglycosides have been reported for experimental animals as well as for humans. In fact, maximal renal toxicity of aminoglycosides was observed when the drug was given during the rest period, while a lower toxicity was observed when the drug was injected during the activity period. The aim of the present study was to evaluate temporal variations in the effectiveness and renal toxicity of gentamicin in an experimental model of pyelonephritis in rats. The experiments were carried out with female Sprague-Dawley rats (185 to 250 g). They had free access to food and water throughout the study and were maintained on a 14-h light-10-h dark cycle. Animals were divided into four groups corresponding to the respective time of induction of pyelonephritis and treatment: 0700, 1300, 1900, and 0100 h. Pyelonephritis was induced by a direct inoculation of Escherichia coli (10(7) to 10(8) CFU) in the left kidney. Animals were treated for 3 and 7 days with a single daily dose of gentamicin (20 and 40 mg/kg of body weight, respectively) or saline (NaCl, 0.9%) at either 0700, 1300, 1900, or 0100 h. Animals treated at 0100 h for 3 days with gentamicin (20 mg/kg) showed a significantly lower number of bacteria in their kidneys than did all other groups (P < 0.01). After 7 days of treatment, the efficacy, evaluated by the log CFU per gram of tissue and by the percentage of sterilized kidneys, was also higher when gentamicin was administered at 0100 h. The beta-galactosidase and the N-acetyl-beta-D-glucosaminidase activities were significantly higher in urine of rats given gentamicin at 1300 h than in urine of rats treated at another time of day (P < 0.05). Gentamicin injected at 1300 h induced a significantly greater increase of [3H]thymidine incorporation into DNA of renal cortex (P < 0.01), a significantly greater inhibition of sphingomyelinase activity (P < 0.05), and significantly more histopathological lesions than the same dose injected at another time of the day. Creatinine and blood urea nitrogen levels in serum were significantly higher (P < 0.05) and the creatinine clearance was significantly lower (P < 0.05) when gentamicin was injected at 1300 h than when it was injected at another time of day. Our data suggest temporal variations in both the toxicity and the effectiveness of gentamicin, the drug being more effective and less toxic when injected during the activity period of the animals. (+info)
Inverse relationship between severity of experimental pyelonephritis and nitric oxide production in C3H/HeJ mice.
The contribution of nitric oxide to host resistance to experimental pyelonephritis is not well understood. We examined whether the inhibition of nitric oxide synthesis alters the sensitivity of lipopolysaccharide (LPS) responder (C3H/HeN) and nonresponder (C3H/HeJ) mice to experimental Escherichia coli pyelonephritis. C3H/HeJ and C3H/HeN mice were implanted subcutaneously with minipumps containing an inhibitor of nitric oxide, NG-nitro-L-arginine methyl ester (L-NAME), or a corresponding vehicle. Ascending urinary tract infection by bladder catheterization with two strains of E. coli, an O75 strain bearing Dr fimbriae and an O75 strain bearing P fimbriae, was developed in tested animals. Twenty-four hours following bladder infection, the kidneys of C3H/HeN and C3H/HeJ mice were colonized at a similar rate. However, 5 weeks postinoculation, C3H/HeN mice cleared infection while C3H/HeJ mice showed persistent colonization. Twenty-four hours following infection, C3H/HeN mice treated with L-NAME showed no significant increase of renal tissue infection compared to the saline-treated control group. However, L-NAME-treated C3H/HeJ mice showed an approximately 100-fold increase in E. coli infection rate compared to the saline-treated controls in the Dr+ group but showed no change compared to those in the P+ group. Dissemination of Dr+ E. coli but not P+ E. coli to the liver and uterus was significantly enhanced with L-NAME treatment in C3H/HeJ mice only. Nitric oxide had no direct killing effect on E. coli in vitro. Nitrite production by various organs was found to be significantly lower in C3H/HeJ mice than in C3H/HeN mice. Alteration of nitric oxide and LPS responsiveness was significantly associated with the increased sensitivity of C3H/HeJ mice to experimental Dr+ but not to P+ E. coli pyelonephritis. These findings are consistent with the hypothesis that nitric oxide synthase activity in concert with LPS responsiveness may participate in the antibacterial defense mechanisms of the C3H mouse urinary tract. This phenomenon is strain dependent and possibly related to the invasive properties of E. coli. (+info)
Increased urine interleukin-6 concentrations correlate with pyelonephritic changes on 99mTc-dimercaptosuccinic acid scans in neonates with urinary tract infections.
Interleukin (IL)-6 and -8 are important inflammatory cytokines in bacterial infections. Their serum and urine concentrations were measured in 27 neonates with urinary tract infection (UTI) at onset and the second week of therapy, as well as in 23 control neonates. Escherichia coli was isolated in 89% of cases. 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scans were performed between the 10th and 90th days after UTI and showed pyelonephritic changes in 15 neonates (56%). Increased IL-6 and IL-8 concentrations were found in urine but not in serum within the first 24 h after presumptive diagnosis of UTI (P=.036 and.010, respectively), suggesting that the neonatal urinary tract can respond to uropathogens by producing inflammatory cytokines. Urine concentrations of IL-6 correlated with findings of renal changes in 99mTc-DMSA scans (P=.012) and thus may serve as a marker of renal parenchymal outcome. All neonates exhibited undetectable urine cytokine levels during the second week of therapy. (+info)
Neutrophil recruitment and resistance to urinary tract infection.
This study examined the role of neutrophil leukocytes for the antibacterial defense at mucosal infection sites. Urinary tract infection (UTI) was established by injection into the bladder lumen of Escherichia coli 1177, a fully virulent clinical isolate. Infection of C3H/HeN (lpsn, lpsn) mice recruited neutrophils into the urinary tract, and bacteria were cleared from kidneys and bladders. The neutrophil response was absent in C3H/HeJ (lpsd, lpsd) mice, and bacteria persisted in the tissues. Peripheral neutrophil depletion of C3H/HeN mice was subsequently achieved by pretreatment with the granulocyte-specific antibody RB6-8C5. The E. coli-induced neutrophil recruitment was inhibited, as shown by immunohistochemistry and tissue myeloperoxidase quantitation. As a consequence, bacterial clearance from kidneys and bladders was drastically impaired. Antibody treatment of C3H/HeJ mice had only a marginal effect. The results show that neutrophils are essential for bacterial clearance from the urinary tract and that the neutrophil recruitment deficiency in C3H/HeJ mice explains their susceptibility to gram-negative UTI. (+info)
Virulence characteristics of Escherichia coli in acute bacterial prostatitis.
To assess the urovirulence characteristics of Escherichia coli strains causing acute prostatitis, urinary isolates from men with acute prostatitis (n=107) and from women with acute uncomplicated pyelonephritis (n=76) were examined for the prevalence of sfa, foc, and 3 papG allele genotypes and phenotypes and for the production of alpha-hemolysin and cytotoxic necrotizing factor 1. The papG allele III and foc gene were found more frequently and the papG allele II less frequently among prostatitis than from pyelonephritis isolates. A higher proportion of hly+ cnf1+ genotype in prostatitis strains (64% vs. 36%) was particularly striking. Both prostatitis and pyelonephritis strains expressed virulence factors similarly except for a higher proportion of nonhemolytic prostatitis isolates. Although the pathogenetic mechanisms of urinary tract infections in men and women may differ, virulence factors such as adhesins and cytotoxins may have important roles in the pathogenesis of acute prostatitis. (+info)