struvite and acetohydroxamic-acid

In a prospective, double-blind, placebo-controlled study, the efficacy and safety of acetohydroxamic acid (AHA) in preventing urinary calculogenesis was evaluated in 94 patients with chronic urinary infection. Stone growth occurred in 17% of the AHA group and in 46% of the placebo group (p less than 0.005). Completely reversible side effects consisting predominantly of psychoneurologic and musculo-integumentary symptoms were more prevalent in the AHA group (p less than 0.01). Side effects which were judged 'intolerable' were experienced by 10 (22.2%) of patients in the AHA group and 2 (4.1%) in the placebo group. It is concluded that AHA treatment is effective, relatively safe, and clinically useful in preventing infection-induced urinary calculogenesis.

Topics: Adult; Aged; Bacteriuria; Chronic Disease; Double-Blind Method; Female; Humans; Hydroxamic Acids; Magnesium; Magnesium Compounds; Male; Middle Aged; Palliative Care; Phosphates; Placebos; Prospective Studies; Struvite; Urinary Calculi

Long-term administration of acetohydroxamic acid to dogs with experimentally induced urease-positive staphylococcal urinary tract infections and struvite urolithiasis resulted in dose-dependent inhibition of urolith growth or urolith dissolution. Inhibition of urolith growth was associated with drug dose-dependent reduction of urine urease activity, urine pH, crystalluria, pyuria, hematuria, and proteinuria. Lesions of the urinary tract of dogs treated with acetohydroxamic acid were less severe than those of control dogs. Dose-dependent adverse drug reactions included reversible hemolytic anemia, abnormal red cell morphology, and abnormalities of bilirubin metabolism.

Topics: Animals; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme Inhibitors; Female; Hydroxamic Acids; Magnesium Compounds; Phosphates; Struvite; Urinary Bladder Calculi; Urinary Tract Infections

We studied the effects of the bacterial urease inhibitor acetohydroxamic acid on the growth of struvite stones in the urinary tract. Eighteen patients who received acetohydroxamic acid (15 mg per kilogram of body weight per day, in divided oral doses) for a mean of 15.8 months were compared in a randomized double-blind study with 19 patients who received placebo for a mean of 19.6 months. Seven patients given placebo reached a pre-determined end point: a 100 per cent increase in the two-dimensional surface area of their stones. No patient who received acetohydroxamic acid had a doubling of stone size (P less than 0.01). Nine patients receiving the drug and one patient receiving placebo required a decrease in dosage or cessation of treatment because of adverse effects (P less than 0.01). Episodes of tremulousness (n = 5, P less than 0.05), which reversed with a decrease in drug dose, and phlebothrombosis (n = 3, P not significant) were limited to the group given acetohydroxamic acid. We conclude that acetohydroxamic acid effectively inhibits the growth of struvite stones in the short term in patients infected with urea-splitting bacteria, but the prevalence of adverse reactions appears to be high and the toxicity and effectiveness of long-term therapy for struvite nephrolithiasis remain to be defined.

Topics: Adult; Double-Blind Method; Drug Evaluation; Female; Humans; Hydroxamic Acids; Kidney Calculi; Magnesium; Magnesium Compounds; Male; Middle Aged; Phosphates; Radiography; Random Allocation; Struvite; Urine

Struvite stones have been associated with significant morbidity and mortality, yet there has not been a report on the medical management of struvite stones in almost 20 years. We report on the contemporary outcomes of the surgical and medical management of struvite stones in a contemporary series.. A retrospective review of patients who were treated with percutaneous nephrolithotomy (PCNL) for struvite stones at Duke University Medical Center between January 2005 and September 2012 identified a total of 75 patients. Of these, 43 patients had adequate follow-up and were included in this analysis. Stone activity, defined as either stone recurrence or stone-related events, and predictors of activity were evaluated after combined surgical and medical treatment.. The study included 43 patients with either pure (35%) or mixed (65%) struvite stones with a median age of 55±15 years (range 21-89 years). The stone-free rate after PCNL was 42%. Stone recurrence occurred in 23% of patients. Postoperatively, 30% of patients had a stone-related event, while 60% of residual stones remained stable with no growth after a median follow-up of 22 months (range 6-67 mos). Kidney function remained stable during follow-up. Independent predictors of stone activity included the presence of residual stones >0.4 cm(2), preoperative large stone burden (>10 cm(2)), and the presence of medical comorbidities (P<0.05).. Struvite stones can be managed safely with PCNL followed by medical therapy. The majority of patients with residual fragments demonstrated no evidence of stone growth on medical therapy. With careful follow-up and medical management, kidney function can be maintained and stone morbidity can be minimized. Initial large stone burden, residual stones after surgery, and associated medical comorbidities may have deleterious effect on stone recurrence or residual stone-related events.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Calcium Citrate; Chlorthalidone; Comorbidity; Diuretics; Enzyme Inhibitors; Female; Humans; Hydroxamic Acids; Kidney Calculi; Male; Middle Aged; Nephrostomy, Percutaneous; Postoperative Complications; Potassium Citrate; Recurrence; Retrospective Studies; Sodium Bicarbonate; Struvite; Treatment Outcome; Young Adult

Struvite (MgNH4PO46H2O) crystals were produced by Proteus mirabilis growth in artificial urine, in the presence and absence of the urease inhibitor, acetohydroxamic acid (AHA). In the absence of AHA, struvite crystals assumed an "X-shaped" or dendritic crystal habit due to rapid growth along their 100 axis. When AHA was present, crystal growth, as monitored by phase contrast light microscopy, was greatly slowed, and the crystals assumed an octahedral crystal habit. Scanning electron microscopy revealed that crystals grown in the presence of AHA were pitted on their surface. This pitting was absent in control samples. While most of this inhibition by AHA was due to lowered urease activity, some crystal growth inhibition occurred in struvite produced in the absence of urease activity through NH4OH titration of artificial urine. We conclude that while AHA is primarily a urease inhibitor, it may also disrupt struvite growth and formation directly through interference with the molecular growth processes on crystal surfaces.

Topics: Animals; Crystallization; Hydroxamic Acids; Magnesium; Magnesium Compounds; Phosphates; Proteus mirabilis; Struvite; Urine

After 24 h incubation of human urine experimentally inoculated with Corynebacterium group D2, struvite crystals appeared with an increase in pH and ammonium concentration as well as a decrease in the urea concentration. These changes were prevented by the addition of variable concentrations of acetohydroxamic acid. From these results it seems that the prevention of such crystal formation by Corynebacterium group D2 could be due to the inhibition of its urease activity besides acetohydroxamic acid having a significant antimicrobial activity, principally when tested in human urine. These effects were dose-related.

Topics: Corynebacterium; Crystallization; Humans; Hydroxamic Acids; In Vitro Techniques; Magnesium; Magnesium Compounds; Phosphates; Struvite; Time Factors; Urea; Urine

Topics: Enterobacteriaceae Infections; Humans; Hydroxamic Acids; Hydroxyurea; Magnesium; Magnesium Compounds; Phosphates; Pseudomonas Infections; Struvite; Urease; Urinary Calculi; Urinary Tract Infections

The effect of 3 hydroxamic acid derivatives on urease-induced crystalluria was studied in vitro. Acetohydroxamic acid is more effective than salicylhydroxamic and gentisohydroxamic acids in inhibiting the kinetic of urease enzymatic reaction and in retarding the formation of struvite and apatite. Crystal deposits studied by scanning electron microscope (S.E.M.) and X-ray microanalysis indicated that acetohydroxamic acid favours the formation of large crystals of struvite, and less aggregation is observed. Salicyl and gentiso derivatives favour the formation of brushite together with struvite and apatite.

Topics: Apatites; Calcium; Crystallization; Humans; Hydroxamic Acids; Kinetics; Magnesium; Magnesium Compounds; Microscopy, Electron, Scanning; Phosphates; Phosphorus; Salicylamides; Struvite; Urease; Urinary Calculi

Crystallization of struvite and calcium phosphates was studied in vitro as encrustations on glass rods immersed in synthetic urine, to evaluate the crystallization capacity of Ureaplasma urealyticum and compare it with that of known urease and non-urease-producing bacteria. Inoculation of the synthetic urine with Ureaplasma urealyticum resulted in alkalinization of the synthetic urine and crystallization of struvite and brushite. Inoculation with Proteus mirabilis caused a faster and more pronounced alkalinization as well as crystallization of struvite and apatite. The alkalinization and crystallization caused by Ureaplasma urealyticum and Proteus mirabilis was completely prevented by acetohydroxamic acid, a potent urease inhibitor, linking the crystallization to the urease activity of the microorganisms. When the synthetic urine was inoculated with urease-negative Escherichia coli no alkalinization and no crystallization were seen.

Topics: Calcium Phosphates; Crystallization; Escherichia coli; Hydrogen-Ion Concentration; Hydroxamic Acids; Magnesium; Magnesium Compounds; Phosphates; Proteus mirabilis; Struvite; Ureaplasma; Urease; Urine

Topics: Humans; Hydroxamic Acids; Kidney Calculi; Magnesium; Magnesium Compounds; Phosphates; Struvite; Urinary Tract Infections

Struvite urinary stones are commonly associated with infections by urease possessing bacteria (Proteus). Ureaplasma urealyticum, a genital mycoplasma, is predominantly located in the human genito-urinary tract and produces urease. Its possible role in the formation of infection stones was studied in the rat model described by Friedlander and Braude. Struvite bladder stones were produced in 60% of Sprague-Dawley male rats after infection of ureaplasmas (serotype 1, 2, 3, 7) into the renal medulla. Mycoplasma hominis, another genital mycoplasma, produced bladder stones in only 10% of animals. A kinetic study showed that pure struvite stones appeared into the bladder 4 to 5 days after inoculation and that U. urealyticum did not usually remain viable more than 6 days. Acetohydroxamic acid and doxycycline prevented the formation of the stones.

Topics: Animals; Doxycycline; Hydroxamic Acids; Kidney; Magnesium; Magnesium Compounds; Male; Mycoplasma; Mycoplasma Infections; Mycoplasmatales Infections; Phosphates; Rats; Rats, Inbred Strains; Struvite; Ureaplasma; Ureter; Urinary Bladder; Urinary Bladder Calculi; Urine

Most staghorn calculi occur in patients who have chronic urinary tract infections with urea-splitting organisms. Acetohydroxamic acid, an inhibitor of the bacterial urease enzyme, is currently undergoing clinical trials to determine whether or not it can prevent stone growth in patients at risk. We report on a patient whose stones grew while she was taking placebo and then decreased in size when she took the active drug.

Topics: Administration, Oral; Adult; Colic; Female; Humans; Hydroxamic Acids; Kidney; Kidney Calculi; Kidney Diseases; Magnesium; Magnesium Compounds; Phosphates; Proteus Infections; Proteus mirabilis; Radiography; Recurrence; Solubility; Struvite

This report describes the results obtained with a combination of acetohydroxamic acid (AHA) and antibacterial agents in 13 patients with recurrent struvite stones complicated by refractory infections with urease-producing bacteria. Intravenous antibiotic pulses plus oral AHA achieved urine sterilisation in all. Then oral chemotherapy plus AHA was given for a mean period of 10.8 +/- 5.4 months. In four patients, the urine remained sterile, but in all the patients urinary pH remained below 6.4 and urinary NH4+ below 40 mg/dl. Despite the persistence of urea-splitting bacteria, the radiographic data showed an arrest of stone growth during the first year of treatment.

Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Humans; Hydroxamic Acids; Magnesium; Magnesium Compounds; Phosphates; Struvite; Urease; Urinary Calculi; Urinary Tract Infections

Chronic urinary infection is thought to be a major factor in the causation of urinary calculi in paraplegic patients. Acetohydroxamic acid is reported to be effective in some patients for the management of this type of stone disease, but there have been no studies of urinary saturation levels during therapy with this drug. In this study 10 patients received oral acetohydroxamic acid for seven days. Marked lowering of urinary pH and ammonium levels were observed, but decreases in urinary saturation were small. The administration of acetohydroxamic acid resulted in increased urinary excretion of magnesium and phosphate, effects that have not previously been reported.

Topics: Adult; Calcium Phosphates; Humans; Hydrogen-Ion Concentration; Hydroxamic Acids; Magnesium; Magnesium Compounds; Male; Middle Aged; Paraplegia; Phosphates; Struvite; Urinary Calculi; Urinary Tract Infections