Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034186 (pyelonephritis)
 6,144 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gentamicin (GM) was intramuscularly injected to 16 children with various infectious disease (1 septicemia, 1 purulent meningitis, 4 bronchopneumonia, 1 pyothorax, 3 pyelonephritis, 2 acute cystitis and 4 RITTER'S dermatitis). The results obtained are as follows: 1. The excellent and good clinical results were noted in all patients except for an indeterminate case with bronchopneumonia because of the concomitant therapy with CEZ. The effective rate was 100.0%. This was possibly because of quite high susceptibility (See Article) of all isolates to gentamicin. 2. Doses of GM were adjusted depending on the style of infectious diseases. The satisfactory clinical results were obtained in some cases by increasing its recommended dosage to about 5-8 mg per kg per day. 3. No kidney dysfunction, liver dysfunction, the 8th cranial nerve damage, etc. were observed by administering 5 to 8 mg per kg per day for at maximum 18 days, in this clinical trial. 4. It has been indicated in this clinical trial that GM is worthy to be used as a first-choice drug in chemotherapy of infectious diseases caused by Staphylococcus, gram-negative bacillus, etc., especially in patients who are hypersensitive to penicillin and cephalosporin derivatives. However, further study would be required for the safety of increase in its dosage and duration of administration.
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PMID:[Further study on gentamicin in pediatrics (author's transl)]. 13 69

1) Gentamicin (GM) was intramuscularly injected to 1 patient with simple acute cystitis and to 21 patients with complicated chronic urinary tract infections in the doses of 40-160 mg per day for 3-12 days (mean: 5-2 days). 2) The clinical effect was excellent in 6, good in 9, poor in 7, which is classified as excellent in 1 with simple acute cystitis, good in 5 and poor in 5 out of 11 with complicated chronic cystitis, and excellent in 4, good in 4 and poor in 2 out of 10 with complicated chronic pyelonephritis. 3) In complicated urinary tract infections, the effective rate was 61.5% (8/13) in GM 80 mg/day dosage group and 75.0% (6/8) in GM 120 mg/day dosage group. 4) No abnormal change was noted in the kidney, liver and auditory function throughout this clinical study. 5) When GM therapy is conducted in the treatment of complicated urinary tract infections, it is considered that more favorable clinical results could be obtained with dosage of GM 120 mg/day or more. However, in this case a caution has to be paid to the kidney and auditory functions.
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PMID:[Clinical experience with gentamicin in urinary tract infections (author's transl)]. 81 18

Ninety nine patients suffering of acute pyelonephritis are prospectively analyzed. Mean age was 39.8 +/- 18.2 (mean +/- DE), 72 of them were females and 19 were males. The most frequent clinical manifestations were fever and side pain in 97% of the cases and lower urinary syndrome in 78%. The duration of symptoms previous to the visit was 3.5 +/- 2.9 days. Bacteremia was confirmed in 99% of cases, it affected the oldest patients (p less than 0.001) and provoked the lasting of fever (p less than 0.05). E. coli was the most frequently isolated microorganism with an incidence of 91% in the isolated samples. Gentamicin was the initial treatment and the definitive treatment was prolonged to a total of 14 days. Fifteen percent of patients were classified after the evaluation as carriers of complicated pyelonephritis and had to undergo afterwards a urologic treatment. Follow up over a minimum of 6 weeks showed a treatment failure in 2% of cases and recurrency in 22%.
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PMID:[Acute pyelonephritis. Prospective analysis of 91 cases]. 178 54

The role of serum levels on the intrarenal accumulation kinetics of gentamicin and netilmicin in normal and infected kidneys was evaluated in a short-term infusion model in conscious rats. Female Sprague-Dawley rats were infused over a period of 6 h with gentamicin and netilmicin achieving individual steady-state serum levels ranging from 0.5 to 120 micrograms/ml. The model of pyelonephritis used resulted in severe left pyelonephritis and mild right pyelonephritis. Only the right infected kidneys were studied. Gentamicin and netilmicin cortical concentrations were analysed as a function of serum levels by linear (least-squares regression analysis) and non-linear regression. For the non-linear regression analysis, the Michaelis-Menten kinetic was the best fitting curve. Steady-state elevation of serum concentrations of gentamicin and netilmicin was associated with a non-linear increase of cortical concentrations in normal kidneys, suggesting a saturable process. By contrast, in the mildly-infected right kidneys, the steady-state elevation of serum concentrations of gentamicin was associated with a linear increase of cortical concentrations while the accumulation kinetic of netilmicin showed a saturable process. At lower serum levels (therapeutic range, from 0.5 to 15 micrograms/ml) both gentamicin and netilmicin showed a first order kinetics of accumulation and netilmicin accumulated less than gentamicin in normal kidneys (p = 0.0004). By contrast, the uptake of netilmicin was higher in the right infected kidneys, as compared to the uptake of netilmicin in the normal kidneys, (p = 0.00005), and as compared to gentamicin in the respective kidneys. We conclude that renal infection modifies the intrarenal accumulation of aminoglycosides.
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PMID:Effect of E. coli pyelonephritis on the intracortical accumulation kinetics of gentamicin and netilmicin in rats. 220 29

Persistent and recurrent infections of the urinary tract are a formidable clinical problem, but several recently developed antibiotics have properties that suggest an increased ability to eradicate such infections. Three of the new-generation antibiotics were compared with established agents by using animal models of urinary tract infection. Of the antibiotics tested, gentamicin and ceftriaxone alone were capable of eradicating infection from acute and chronically infected kidney tissue. Chronic lower urinary tract infection was best managed by using norfloxacin or ceftriaxone. Gentamicin, aztreonam, cotrimoxazole and ampicillin were much less effective. In subacute pyelonephritis, gentamicin, aztreonam, norfloxacin and ceftriaxone successfully eliminated microorganisms from most of the infected kidneys, whereas ampicillin and cotrimoxazole had little effect on bacterial numbers. The data have provided an experimental basis for the selection of antibiotics in the management of persistent urinary tract infection.
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PMID:Antimicrobial agents in the management of urinary tract infection: an experimental evaluation. 268 80

Gentamicin is a commonly used antibiotic in the treatment of gram-negative infections including septicemia and pyelonephritis. Bacterial endotoxin is liberated during antibiotic therapy and may lead to endotoxemic shock. Steroids such as hydrocortisone are generally recommended in the treatment of endotoxemic shock. There are very limited data on the influence of endotoxin or corticosteroids on the pharmacology of antibiotics, especially aminoglycosides, which are nephrotoxic. We studied the influence of both Escherichia coli endotoxin and hydrocortisone succinate on the renal uptake of gentamicin in rats. Animals were injected intravenously with endotoxin (0.25 mg/kg) and/or hydrocortisone (25 mg/kg) plus gentamicin (10 mg/kg). Gentamicin levels in the serum and renal parenchyma as well as renal function and histology were evaluated. Both endotoxin and hydrocortisone given alone increased the concentration of gentamicin in the renal cortex (P less than 0.05). Normal values in serum were observed in all groups at most time intervals. When administered together, endotoxin and hydrocortisone did not potentiate each other. The combination of endotoxin and hydrocortisone gave significantly higher levels of gentamicin than endotoxin or hydrocortisone alone when endotoxin was injected 3 h before hydrocortisone (P less than 0.05). Blood pressure and cardiac frequency were normal when gentamicin was given. Endotoxin alone slightly decreased the glomerular filtration rate, and hydrocortisone alone slightly modified renal plasma flow. The combination of both drugs did not significantly affect renal function. No histological lesion was noted on light microscopy in animals receiving endotoxin. Competitive or synergistic activity of endotoxin, gentamicin, and hydrocortisone at the cellular level, especially on membranes or lysosomes, might explain in part our observation on the renal uptake of gentamicin. By increasing the total amount of drug within the kidney, endotoxin and hydrocortisone might increase the risk of nephrotoxicity associated with aminoglycosides.
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PMID:Influence of hydrocortisone succinate on intrarenal accumulation of gentamicin in endotoxemic rats. 343 28

The experiments with rats treated with gentamicin showed that nitrogen excretion function of the kidneys did not significantly change in the animals 3 months after induction of pyelonephritis, while in the animals not treated with the antibiotic there was a significant increase in excretion of alkaline phosphatase with urine. The nitrogen excretion function of the kidneys was not affected by gentamicin, except an increase in the urea blood level. Gentamicin promoted a significant rise in excretion of enzymes with urine, especially that of alkaline phosphatase. Treatment of healthy animals with gentamicin resulted in the increased excretion of alkaline phosphatase with urine and increased urea blood levels which was evident of the nephrotoxic effect of the aminoglycoside antibiotic. When such animals were treated with furosemide, the renal excretion of the enzyme and the blood creatinine urea levels decreased. Therefore, furosemide lowered nephropathy induced by gentamicin. The increase in the activity of the urine enzymes may be due to inflammatory changes in the kidney parenchymal on the one hand and the pephrotoxic effect of the drugs on the other hand. The urine enzymes may be used as important diagnostic tests in cases with kidney affections and indicators of safe treatment with nephrotoxic antibiotics.
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PMID:[Effect of gentamycin on the kidney functional state in experimental pyelonephritis]. 723 57

Gentamicin, because it is stored in renal tissues, can prevent acute retrograde pyelonephritis. Since different aminoglycosides accumulate and persist to various degrees in the kidney parenchyma, the prophylactic activities of gentamicin, tobramycin, amikacin, and netilmicin were compared. The four antibiotics were given intramuscularly to rats 3 days before initiating ascending unilateral pyelonephritis with Escherichia coli. Despite different degrees of renal accumulation at the time of infection (tobramycin and amikacin accumulated significantly less), all four aminoglycosides displayed similar protection against ascending pyelonephritis. This protection was conferred in the absence of active antibiotic detectable in the urine and was therefore attributed to antibiotic stored in the renal parenchyma. Those animals that developed pyelonephritis despite aminoglycoside prophylaxis had less severe acute kidney infection and inflammation. This resulted 3 months later in an almost complete protection against renal scarring (chronic pyelonephritis). These results in rats suggest that renal accumulation and persistence of aminoglycosides may be used to advantage in the prophylaxis or in the treatment of kidney infections.
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PMID:Prevention of acute and chronic ascending pyelonephritis in rats by aminoglycoside antibiotics accumulated and persistent in kidneys. 724 65

The favourable effect of gentamicin and its combination with furosemid was shown in treatment of rats with experimental pyelonephritis. However, alongside the favourable effect, a danger of the gentamicin nephrotoxic effect, especially in combination with furosemid was noted. The nephrotoxic effect was evident from foci of distrophic and necrobiotic changes in the epithelium of the convoluted tubules, impairment of the cortical hemodynamics and development of the cortical hypoxia of the kidneys resulting in severe renal insufficiency. Gentamicin had no direct inhibitory effect on the tissue respiration, did not block the oxygen uptake and oxidative phosphorilation in isolated mitochondria. To prevent the development of the nephrotoxic effect of gentamicin and its combination with furosemid strict and effective control of the antibiotic plasma levels is necessary. Informative tests for the control of the renal function are the concentration parameters of creatinine and urea, especially at the beginning of the pathological state when the level of hyperazotemia is still of a low informative value. The diurnal urine excretion is not an important informative index of renal function.
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PMID:[Use of gentamycin and furosemide in acute pyelonephritis (an experimental morphological study)]. 736 27

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.
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PMID:Effectiveness and toxicity of gentamicin in an experimental model of pyelonephritis: effect of the time of administration. 1022 9


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