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Purpose: Nucleation pH is the pH at which Ca and Mg come out of urine to form crystals. If the safety margin between voiding pH and nucleation pH could be increased, it would increase the possibility of an alternative to controlling the activity of urease producing bacteria as a strategy to control catheter encrustation., Materials and Methods: We performed a 6-week randomized crossover study in 24 patients with catheter blockage who were randomly allocated to a specific sequence of 3 consecutive available treatments, including increased fluid intake, lemon juice and potassium citrate. Each patient received all available regimens. At the end of each week 24-hour urine samples were analyzed for voiding and nucleation pH, citrate, Ca and Mg., Results: Mean +/- SD nucleation pH increased from 7.45 +/- 0.60 at baseline to 7.93 +/- 0.50, 7.68 +/- 0.64 and 7.96 +/- 0.37 in the lemon juice, increased fluid intake and potassium citrate groups, respectively (p <0.0001). Mean urinary citrate increased significantly (p <0.0001), in particular due to lemon juice and potassium citrate effects. The association between treatment and Ca was weak (p = 0.12) while that of Mg was negative due to lemon (p <0.001). Average increase in the safety margin (nucleation pH minus voiding pH) beyond baseline was 0.84 (95% CI 0.63-1.04), 0.57 (95% CI 0.37-0.78) and 0.41 (95% CI 0.20-0.61) for lemon juice, increased fluid intake and potassium citrate, respectively. A strong treatment effect on the safety margin was apparent even when controlling for study design (p <0.001)., Conclusions: Increased fluid intake with lemon juice may be a simple, inexpensive, effective strategy to control catheter encrustation., (Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

We report on a boy with ureteroceles that obstructed the bladder outlet and ureters, who presented with sepsis and hyperammonemia despite normal liver function. The hyperammonemia was most likely caused by excessive absorption of ammonia produced by Proteus mirabilis in the obstructed urinary tract.

Brattleboro strain rats homozygous for hypothalamic diabetes insipidus (DI rat) excrete nearly their body weight per day in dilute urine and yet can form bladders stones composed of struvite and apatite. Studies were undertaken to investigate this apparent paradox. The results show that DI rat urine is indeed undersaturated with respect to struvite and apatite. However, chronic infection of DI rat urine with a urease-containing organism (Proteus mirabilis) results in the rapid formation of large struvite/apatite bladder stones. It is concluded that the Brattleboro strain DI rat, like man and unlike other rats, forms struvite/apatite calculi only in the presence at chronic urinary tract infection.

Nineteen children who underwent extensive nephrotomies and anatrophic nephrotomies for staghorn calculi (bilateral in 4 cases) are presented. Proteus infection was the cause of the calculus in most cases. In the absence of recurrent stones, renal growth and function were excellent post-operatively. Stone recurrence was minimal if all calculi were removed and infection was controlled. Followup ranged from a few months to 13 years.

The purpose of this study was to determine if chronic cystitis interferes with maturation of the ureterovesical junction, thus prolonging vesicoureteral reflux in infant rhesus monkeys (Macaca mulatta). Serial implantations of a Proteus-infested silastic pellet into the bladder wall ensured continued infection as demonstrated by urine culture. Chronic cystitis as evidenced by pathological findings at surgery and sacrifice was created in a group of infant monkeys who had initial spontaneous vesicoureteral reflux. There was no evidence of pyelonephritis. Four animals represent a short term study since they were followed from four months to one year of age. Three animals were long term studies and were evaluated for at least 21/2 years. In no animals did chronic cystitis delay the normal disappearance of vesicoureteral reflux that is commonly seen in these animals as the ureterovesical junction matures, as demonstrated by serial cystograms. In two animals reflux (after initial clearing) reappeared when a bladder calculus formed in these chronically infected animals. Renal damage occurred only in these animals. In conclusion, this animal model failed to demonstrate interference with normal vesicoureteral junction maturation in the face of a chronic bladder infection.

Apart from urine supersaturation with respect to struvite and calcium phosphate, crystal retention is considered to be necessary for the formation of infection stones. This study was performed to investigate the role of the mucous coat in rat bladders in the adhesion of sterile urease-induced crystals and to determine to what extent the adhesion was influenced by infection. Elimination of the mucous coat with 0.1 M HCl increased the adherence of crystals six times compared to that in bladders with an intact mucous coat. Infection with Proteus mirabilis, Escherichia coli, enterococci and Ureaplasma urealyticum increased the adherence six, five, four and two times, respectively. Injury to the mucous coat may thus be one mechanism by which microorganisms can contribute to the formation of infection stones in the urinary tract.

The potential of phosphocitrate to inhibit infection stones in rats when combined with an antibiotic was studied. A significant reduction occurred in both the number and weight of recovered stones from rats receiving combined treatment with amoxycillin (50 mg./kg. body wt./day and phosphocitrate (112 mumol./kg. body wt./day) for four weeks. The inhibitory responses were attributed to the intact phosphocitrate molecule as administration of citrate in equimolar concentrations did not mimic the observed effects of phosphocitrate. In comparison with non-infected controls, antibiotic treatment alone failed to eliminate total stone growth. However, composition of the stone reverted from predominantly struvite to a mixture of struvite and newberyite as urinary parameters normalized. The studies highlight the usefulness of phosphocitrate to restrict magnesium salt deposition in vivo.

The viability and location of bacteria within infection stones were investigated. Many stones were infected with urea-splitting bacteria, such as Proteus mirabilis and Pseudomonas aeruginosa. Large numbers of bacterial impressions and bodies were found in the interstices surrounded by crystals of apatite and struvite from the nuclei to the peripheral layers. The presence of bacterial colonies even in the nuclear portion of the stones suggests that bacteria participate in the initial stone formation as well as in growth of infection stones. Streptococcus faecalis, a nonurea -splitting bacteria, also was found in some infection stones and probably represents a superimposed infection as a result of changes in bacterial flora owing to treatment with antibiotics.

Hyperammonemic coma without liver disease or associated deficiencies in urea cycle enzymes is rare. We report a case and discuss the pathophysiological findings of hyperammonemic coma secondary to Proteus mirabilis urinary tract infection.

Hyperammonemic encephalopathy in the urological patient is a rare but grave condition. In the pediatric urological population it has been associated with massively dilated upper tracts and urinary infection with urea-splitting organisms. We report 2 cases of hyperammonemic encephalopathy in association with the prune belly syndrome. Both patients presented comatose with markedly elevated serum ammonia levels and Proteus mirabilis urinary tract infection. Intravenous antibiotics and catheter drainage resulted in dramatic reversal of the encephalopathy. The pathophysiology of hyperammonemic encephalopathy in association with the prune belly syndrome and a review of the literature are presented.

A newly designed urolithiasis model for rats, inducing a mild urinary tract infection, exhibiting reduced renal damage without pyelonephritis and causing reliable stone formation, was established. This was accomplished by implanting a zinc disc in the bladder and then performing transvesical inoculation of Proteus mirabilis into the bladder. Five days after challenge with 10(7) colony forming units (CFU) of P. mirabilis in each rat, the number of organisms in the bladder urine reached a level of over 10(5) colony forming units per ml. The infection was mostly restricted to the urinary tract organs. Infectious bladder stones were formed 5 days after infection and developed day by day, weighing 88.3 +/- 18.8 mg. on the 21st day. Blood urea nitrogen values stayed in the normal range in all test animals during this experiment. The main composition of the stones formed was shown to be struvite (MgNH4PO4 X 6H2O).

The use of oral penicillin therapy is important in the management of renal stones secondary to Proteus mirabilis urinary tract infections. In 16 of 20 patients (80 per cent) with struvite renal calculi infected with Proteus mirabilis a sterile urine was achieved with appropriate penicillin therapy and diminution in stone size occurred in at least 2 cases. The rationale, supporting data and therapeutic uses are discussed.

Proteus rettgeri is an aerobic gram-negative bacillus that displays marked resistance against most of the antibiotics presently available. This organism causes infections usually confined to the urinary tract of certain types of compromised patients. Occasionally, it is recovered from soft tissue abscesses, and rarely from the blood and respiratory tract. Proteus rettgeri is notorious for causing nosocomial outbreaks of urinary tract infections in urological and physical medicine wards. Our experience with a patient who had bacteremia with a multi-drug resistant strain of Proteus rettgeri prompted a review of the literature concerning infections with this organism. The salient features of these reports are discussed and summarized. Data on the antibiotic sensitivity of 15 other strains of Proteus rettgeri are included.