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The role of antibiotic tolerance in the response to treatment of pyelonephritis due to Staphylococcus aureus in rats.

The effect of tolerance to methicillin on the response to treatment of hematogenous pyelonephritis due to Staphylococcus aureus was evaluated in rats. Tolerance was defined as a ratio of minimal bactericidal concentration to minimal inhibitory concentration of greater than or equal to 32. Rats that were infected with tolerant or nontolerant stains of S. aureus were treated with methicillin with equal success as judged by the number of bacteria in the kidneys and the proportion of rats with infected kidneys. In this animal model, tolerance does not play a role in the outcome of treatment.

Animals↗

Genetic factors and host resistance in experimental pyelonephritis.

There have been no reports suggesting that a genetic component may affect host resistance to renal infection. In rats with experimentally induced unilateral pyelonephritis, consistent level of infection was achieved in the directly challenged (left) kidneys. Retrograde infection in the unmanipulated (right) kidneys was found to be strain dependent in these animals. Infection was readily established in the right kidneys of the AS2 and HO strains but not in the DA strain; however, infection was established in all unmanipulated kidneys of the DA X AS2 F1 hybrid, whereas eight of 10 kidneys from the DA X HO hybrid remained uninfected. These results suggest that host resistance to retrograde renal infection in the rat strains studied was genetically determined, although the relevant host factor(s) has not yet been identified.

Animals↗

Immunomodulatory interactions of suppressor cells, cell-mediated immunity, and cyclophosphamide in experimental pyelonephritis.

The recent observation that the administration of cyclophosphamide, an immunosuppressive agent, leads to the eradication of bacterial infection in experimental pyelonephritis seems paradoxical. However, cyclophosphamide is also an immunostimulator and, on the basis of its known characteristics, could enhance cell-mediated immunity either by modulation of suppressor cell activity or by depletion of infection-induced suppressor cells. This study examined these alternatives and the relation between suppressor cells, cell-mediated immunity, and cyclophosphamide administration. Cyclophosphamide enhanced the resistance of lymphocytes to the activity of suppressor cells but did not enhance cell-mediated immunity.

Animals↗

Effect of insulin treatment on the susceptibility of the diabetic rat to Escherichia coli-induced pyelonephritis.

Escherichia coli-induced pyelonephritis was studied in untreated alloxan-diabetic rats, insulin-treated diabetic rats, glucose water-drinking (diuresing) nondiabetic rats, and tap water-drinking (nondiuresing) nondiabetic rats following injection of E. coli either into the emptied urinary bladder, into the left kidney, or intravenously. For prevention of an ascending infection in the right kidney, the right ureter was ligated and transected immediately prior to bladder or intrarenal inoculation. These experiments established that in normal rats ascending renal infection alone occurred following introduction of small inocula into the bladder--and then only when facilitated by diuresis. In diabetic rats both ascending and hematogenous renal infection occurred following introduction of small inocula into the bladder. Insulin treatment that reduced hyperglycemia also reduced glycosuria and restored urinary antibacterial activity against small inocula of E. coli but only partially reduced polyuria and prevented hematogenous but not ascending infection. Thus, hyperglycemia was probably the major factor promoting hematogenous renal infection, whereas polyuria--and therefore vesicoureteral reflux--was the major factor promoting ascending infection.

Animals↗

Failure of dexamethasone to prevent polymorphonuclear leukocyte infiltration during experimental acute exudative pyelonephritis and to reduce subsequent chronic scarring.

In experimental acute exudative pyelonephritis (AEP), a role for polymorphonuclear leukocyte (PMNL) infiltration in the pathogenesis of kidney scarring has been suggested indirectly. To directly quantitate PMNL infiltration during AEP, we developed an assay for measuring the content in the kidney of myeloperoxidase (MPO), an enzyme present in PMNLs and absent in kidney tissue. This assay was a specific and sensitive marker of the kidney PMNL content. We used this assay to measure in rats with AEP the effect of dexamethasone, administered in an attempt to mitigate the acute inflammatory response. Compared with saline, dexamethasone given during AEP strikingly reduced kidney swelling, measured by the kidney-weight increase, but failed to reduce PMNL infiltration, measured by the kidney MPO content. Despite reduced kidney swelling during AEP, dexamethasone treatment failed to prevent subsequent kidney scarring, an observation indicating that PMNLs play a role in the development of permanent kidney damage during AEP.

Acute Disease↗

Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 606 doses). Antimicrobial resistance necessitated modifying therapy of 14 (32%) of the Amp recipients but of none of the TMP/SMZ recipients (P less than .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% of Amp and in 8% of TMP/SMZ recipients. No patient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance.

Acute Disease↗

Comparative studies of fleroxacin and ofloxacin in experimental pyelonephritis.

Two quinolones, fleroxacin and ofloxacin were used as oral treatment in a model of experimental pyelonephritis in rats. The infecting strains were Escherichia coli, Klebsiella oxytoca and Pseudomonas aeruginosa. Compared to untreated control rats, the rats treated with the quinolones showed a great reduction in bacterial counts in kidney tissue and urine. At lower dosages, fleroxacin had a greater bacterial killing effect than ofloxacin.

Animals↗

Clarithromycin is an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae.

OBJECTIVES: To apply clarithromycin as an immunomodulatory treatment in experimental infection caused by pan-resistant Klebsiella pneumoniae. METHODS: Acute pyelonephritis was induced in 80 rabbits after inoculation of the test isolate in the renal pelvis. Rabbits were divided into eight groups, with 10 animals in each group. In groups A-D, therapy was administered simultaneously with bacterial challenge as follows: A, controls; B, intravenous clarithromycin; C, amikacin; and D, both agents. In groups E-H, therapy was administered 24 h after bacterial challenge as follows: E, controls; F, intravenous clarithromycin; G, amikacin; and H, both agents. Blood was sampled for estimation of tumour necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA); monocytes were isolated for determination of intracellular activity of caspase-3 and ex vivo TNF-alpha secretion. Four days after bacterial challenge, animals were sacrificed for quantitative cultures and biopsies of organs. RESULTS: Serum TNF-alpha at 48 h was lower in groups B, C and D compared with group A. Activity of caspase-3 of monocytes was lower at 48 h in group D compared with group A. Bacterial loads of liver and spleen were decreased in group D compared with those of group A. The numbers of inflammatory cells of spleen of group B were lower compared with those of group A; those of kidney and mesenteric lymph nodes of group D were lower than those of group A. Serum MDA of group H was lower than that of group E and serum TNF-alpha of group F was lower compared with that of group E. TNF-alpha of monocyte supernatants and activity of caspase-3 of monocytes of group F were lower than those of group E. Bacterial tissue loads did not differ among groups E, F, G and H. The numbers of inflammatory cells of liver of groups F and H were lower compared with those of group E; those of kidney of groups F, G and H were lower compared with those of group E. CONCLUSIONS: Clarithromycin administered intravenously in experimental infection caused by pan-resistant K. pneumoniae attenuated systemic inflammatory response and local tissue damage. This effect is probably attributed to immunomodulatory intervention on blood monocytes.

Acute Disease↗

A study of interleukin-8 and defensins in urine and plasma of patients with pyelonephritis and glomerulonephritis.

BACKGROUND: Interleukin-8 (IL-8) plays a crucial role in the recruitment and activation of polymorphonucleated leukocytes (PMN) in the site of inflammation. Defensins are specific cationic proteins from azurophil PMN granules which exert antimicrobial, cytotoxic and proinflammatory activities. METHODS: Urine and plasma levels of IL-8 and defensins were studied using specific enzyme-linked immunosorbent assays. IL-8 was determined in 107 patients, including 45 with chronic glomerulonephritis (GN) and 62 with chronic pyelonephritis (PN). Urine and plasma levels of defensins were studied simultaneously in 29 patients with GN and 29 with PN. None of the patients examined showed any evidence of renal insufficiency. A group of 24 healthy volunteers was used as a control. RESULTS: Urinary IL-8 was significantly increased in all groups of patients comparing with healthy control (< 30 pg/ml). The level of IL-8 in the urine of patients with PN (477 +/- 114 pg/ml, mean +/- SEM) was significantly (P < 0.001) higher than in patients with GN (53 +/- 7 pg/ml). The concentration of defensins in urine of patients with GN was slightly increased in comparison with the normal level (21 +/- 3.5 ng/ml versus 15.7 +/- 2.8 ng/ml). Urinary defensins were significantly elevated in patients with PN (134 +/- 118 ng/ml, P < 0.001), and were significantly higher than in the GN group (P < 0.001). A close correlation was observed between IL-8 and defensin concentrations in urine (r = 0.62), and between the urinary leukocyte count and IL-8 level (r = 0.72). The highest levels of IL-8 were observed in patients with PN, associated with nephrolithiasis (14 patients, 822 +/- 219 pg/ml versus 367 +/- 72 pg/ml in patients with PN alone, P < 0.05). IL-8 and defensin levels increased in older patients with PN, but not in older patients with GN. CONCLUSIONS: The levels of IL-8 and defensins in urine were 6-10-fold higher in patients with PN than in patients with GN. Thus, there is a significant difference in IL-8 production between septic and aseptic chronic inflammatory processes in kidney. It is possible to speculate that the timing and progression of kidney inflammation is mediated by an IL-8 dependent mechanism at least in the case of PN.

Adolescent↗

Prognosis in pyelonephritis: promise or progress?

Prognosis in pyelonephritis, or upper urinary tract infection, is provided. This infection is not responsible for progressive renal disease in young or elderly patients but accounts for frequent febrile episodes in women of all ages and men after the age of 50. Vigorous local immune response develops with the infection, which never succeeds in eradicating bacteria but does limit the infection and provides a diagnostic test: the antibody-coated bacteria test. Emphasis is placed on the need for a localization test for upper tract infection because studies based exclusively on clinical criteria are invalid. Appropriate therapy for mildly ill patients is given with recommendations of combination therapy for severely ill persons. Long-term follow-up is critical because most patients with recurrent infections can be given preventive therapy without subjecting them to needless urologic evaluation.

Adult↗

Case report: acute focal bacterial pyelonephritis (lobar nephronia)--presentation as a palpable abdominal mass.

Acute lobar nephronia, or focal pyelonephritis, is an uncommon form of renal infection with a distinct computerized tomographic appearance. A patient is presented with lobar nephronia characterized by fever, flank pain, urosepsis, and painful abdominal mass. Differentiating this condition from abscess or other renal mass is important, because the treatment of lobar nephronia is nonsurgical. The infection responds to antibiotic therapy.

Abdomen↗

The clinical impact of bacteremia in complicated acute pyelonephritis.

BACKGROUND: Bacteremia has been considered as a surrogate marker of severe infection in several infectious diseases. However, it remains uncertain whether the presence of bacteremia correlates with severe infection in patients with complicated acute pyelonephritis (APN). METHODS: We performed a retrospective study to investigate the relationship between the presence of bacteremia and disease severity in complicated APN. To do this, we reviewed medical records from 128 patients diagnosed with complicated APN admitted to Kaohsiung Veterans General Hospital, Taiwan between January, 2003 and December, 2003. In our analysis, we compared clinical presentation, treatment response, and outcome in patients with and without bacteremia. RESULTS: Fifty-four of 128 patients (42%) were bacteremic. This group of patients presented more frequently with severe sepsis or septic shock (P < 0.001), compared with nonbacteremic patients. Other factors that correlated with the presence of bacteremia were older age, diabetes mellitus, more band forms in neutrophil cell counts, impaired renal function, and a lower level of serum albumin. Using a multivariate logistic regression analysis, we show that lower levels of serum albumin (odds ratio, 0.18; 95% CI, 0.05-0.65; P = 0.008) and presence of severe sepsis (odds ratio, 4.76; 95% CI, 1.43-15.84; P = 0.011) were independent factors associated with bacteremia. Following treatment, the bacteremic group took a longer time to become defervescent than the nonbacteremic group (5.1 +/- 2.3 vs. 4.2 +/- 1.6 days, P = 0.023). Also, the bacteremic group had a greater mean duration of intravenous antibiotics administration and longer hospital stays (P < 0.001). Multiple logistic regression analysis shows that non-Escherichia coli bacteremia, presence of urolithiasis or hydronephrosis, shorter duration of antibiotics administration, and being male were significantly associated with recurrence of urinary tract infection within 6 months. CONCLUSION: Bacteremia in cases of complicated APN indicates a severe disease, which is more likely to recur in patients with non-E coli bacteremia. Our study showed that bacteremia is indeed a useful clinical indicator of severe disease and, if found, should influence patient management. Therefore, we recommend that blood culture samples should be taken in all patients with complicated APN.

Acute Disease↗

Unusual Tc-99m MDP and I-123 MIBG images in focal pyelonephritis.

A 6-year-old boy presented with an inflammatory syndrome. Because Tc-99m MDP bone scintigraphy revealed increased tracer uptake at the upper pole of the right kidney, further studies were oriented towards a diagnosis of renal or adrenal pathology. I-123 metaiodobenzylguanidine (MIBG) accumulated at the site of the abnormal MDP uptake. The diagnosis of neuroblastoma or allied disorder was excluded on the basis of other investigations and further evaluation, suggesting that the MIBG uptake was a false-positive. Findings on clinical imaging, laboratory findings, Tc-99m DMSA imaging, sonography, and CT scanning were highly suggestive of acute focal pyelonephritis.

3-Iodobenzylguanidine↗

Identification of new renal scarring in repeated episodes of acute pyelonephritis using Tc-99m DMSA renal SPECT.

PURPOSE: This prospective study compared the value of Tc-99m DMSA renal planar scintigraphy with SPECT to detect new renal involvement in patients with repeated episodes of acute pyelonephritis (APN). MATERIALS AND METHODS: Children with suspected APN were transferred to our department for DMSA renal scans. Seventy-two children (ages 1 week to 15 years) had DMSA planar and SPECT imaging performed twice because of clinical or laboratory suspicion of repeated APN. In addition, radiographic voiding cystourethrography was also performed in all cases. The presence of vesicoureteral reflux (VUR) was graded on a scale of 0 to 5. RESULTS: New lesions were observed with SPECT in 56 kidneys and with planar scintigraphy in 38 kidneys. No patients had a negative result of Tc-99m DMSA renal SPECT who also had a positive Tc-99m DMSA planar result. The degree of VUR as related to APN was diagnosed better with SPECT than with planar scintigraphy (46 compared with 30 and 10 compared with 8, respectively). There is a significant difference (P < 0.05) between the diagnostic ability of these two methods to identify the increased tendency of repeated APN to occur with high-grade VUR compared with low-grade or no VUR. CONCLUSIONS: High-grade VUR is more commonly associated with renal injury than is low-grade or no VUR. If only Tc-99m DMSA renal planar scintigraphy is performed, renal scarring may be underestimated. Our results suggest that Tc-99m DMSA renal SPECT, rather than planar scintigraphy, should be used routinely in children with a clinical suspicion of APN, especially for those with scarred kidneys and high-grade VUR.

Acute Disease↗

The value of Ga-67 renal SPECT in diagnosing and monitoring complete and incomplete treatment in children with acute pyelonephritis.

PURPOSE: This study evaluated the utility of Ga-67 renal SPECT for diagnosing acute pyelonephritis (APN) in children and monitoring them. METHODS: Seventy-one children (ages 1 week to 12 years) who were thought clinically to have APN were included in the study. The disease was considered present if the patients had all of the following: fever (38.5 degrees C), pyuria (leukocyte counts/per high-power field > or = 10), and a positive result of a urinary culture or blood culture. Tc-99m DMSA, Ga-67 renal SPECT, and voiding cystourethrography were performed, with informed consent from the patients' parents, within 3 days after hospitalization. Three months after treatment, Tc-99m DMSA and Ga-67 renal SPECT were repeated in those patients who had abnormal results of the initial Ga-67 renal SPECT. RESULTS: In the diagnostic study, Ga-67 renal SPECT was superior to DMSA renal SPECT in detecting lesions (97% vs. 79%). Three children had false-negative results with Ga-67 renal SPECT. Seventeen kidneys were negative with Tc-99m DMSA but positive with Ga-67 renal SPECT. No patients had any Ga-67 uptake on post-therapy imaging. However, 32 of 107 kidneys (30%) had permanent renal scars. In these 107 kidneys, 78 (73%) were associated with high-grade vesicoureteral reflux (VUR; VUR grade > or = 3) and 29 (27%) with low-grade or no VUR. CONCLUSIONS: High-grade VUR tends to be associated more with APN than has been reported by others, probably because of an underestimation of APN by ultrasonography or DMSA. Ga-67 renal SPECT is sensitive and useful not only in diagnosis but also for monitoring and follow-up of children with clinical suspicion of APN, especially in those with equivocal results after DMSA renal SPECT studies.

Acute Disease↗

Atlas on acute pyelonephritis in children.

The authors describe various patterns of Tc-99m DMSA images that correspond to a diagnosis of acute pyelonephritis. Only those children with complete scintigraphic healing or considerable improvement after 6 months have been considered.

Acute Disease↗

Follow-up of acute pyelonephritis in children by Tc-99m DMSA scintigraphy: quantitative and qualitative assessment.

PURPOSE: The author's goal was to create a system to identify children at risk for development of progressive renal damage. METHODS: Thirty-four children were examined with Tc-99m DMSA scintigraphy in the acute stage of an initial episode of pyelonephritis, after 6 months, and again after 1 year. The scintigraphic findings were correlated with clinical and laboratory data. RESULTS: All children had parenchymal defects in the acute stage: 93% of the kidneys and 85% bilaterally. After 6 months, the defects had diminished or disappeared in 66% of the kidneys. New defects appeared in 22%. At 1 year, no further improvement was seen in the kidneys, with an improved or unchanged pattern at 6 months. New defects appeared in 34%. Mean kidney activity uptake expressed as the percentage of administered dose (KU/AD), was low in the acute stage, increased at 6 months, with no further significant increase at 1 year. Eighty-three percent of children with urine cultures growing > or = 104 bacteria/ml at follow-up had decreased KU/AD values, whereas all children with urine cultures growing < 104 bacteria/ml had increased KU/AD values. CONCLUSIONS: Quantitative assessment increases the sensitivity of Tc-99m DMSA scintigraphy. Follow-up with this method makes it possible to identify the children with decreasing renal tubular function who may be at risk for progressive renal damage. Moderate bacteruria of 104 bacteria/ml urine is associated with deterioration of renal tubular function.

Acute Disease↗

MR imaging of xanthogranulomatous pyelonephritis.

The magnetic resonance (MR) appearance of a case of xanthogranulomatous pyelonephritis is described and compared with CT and surgical findings. Both CT and MR were comparable in displaying the morphology of this uncommon renal abnormality.

Female↗