Current Pharmaceutical Design, 2003, 9, 975-981 975

Infections and Urinary Stone Disease

Nadeem U. Rahman, Maxwell V. Meng, and Marshall L. Stoller*

Department of Urology, University of California School of Medicine San Francisco, California

Abstract: The relationship between urinary infections and stone formation has been recognized since antiquity and it has
been over a century since bacterial degradation of urea was postulated to cause struvite stones. Specific therapy for
urease-producing bacteria, such as urease-inhibitors and antibiotics, has allowed for treatment for this subset of urinary
stones. Future directions for research include development of novel urease-inhibitors and chemicals to enhance the
protective glycosaminoglycan layer.

An improved understanding of the pathogenesis of calcium-based stones has led to the discovery of potential roles for
nanobacteria and Oxalobacter formingenes. Methods of altering intestinal regulation of oxalate by reintroduction of lactic
acid bacteria may significantly impact the treatment of calcium oxalate stones.

The use of catheters, both urethral and ureteral, is common in the urinary tract and is associated with significant
morbidity, primarily from associated infections. Catheters to prevent bacterial colonization and formation of biofilms have
been created using various coatings, including ciprofloxacin, hydrogel, and silver. Use of these types of catheters may
minimize infections and encrustation inherent with their placement in the urinary tract.

STRUVITE CALCULI 2NH3 + H2O 2NH4+ + 2OH- (increase pH>7.2) and

Urinary tract calculi have plagued humans since the
beginning of civilization and associated infections have long
been thought to play a critical role in their lithogenesis. In
387 B.C., Hippocrates first documented an association
between urinary tract infections, loin abscesses, and urinary
stones. Over two thousand years later, in 1817 Alexander
Marcet noted that there was a relationship between urinary
infections and an alkalotic urine contributing to the
formation of phosphate stones [1]. This was further eluciated
in 1901 by T. R. Brown who suggested that alkalotic urine
and stone formation was a consequence of bacterial splitting
of urea and subsequent ammonia production. In addition, as
three of the six patients in his case series were infected with
Proteus, this was the first time that Proteus species were
implicated in stone formation [2]. In 1925, T.B. Magath and
B.H. Hagar suggested that a bacterial protein, urease, must
be responsible for the breakdown of urea [3]; this was
confirmed one year later upon the isolation of urease by J. B.
Sumner. For isolating the first enzyme in its pure form, he
was awarded the Nobel Prize in Chemistry in 1946 [4].
Bacterial urease, which is normally intracellular, is
released into the urine after bacterial cell lysis [5].
Subsequently, it catalyzes the hydrolysis of urea at a rate 104
times that of spontaneous urea hydrolysis [6]. The following
equations summarize the conversion of urea to ammonia,
ammonia to ammonium, and acidification from carbon
dioxide:
H2NCONH2 + H20 2NH3 + CO2
*Address correspondence to this author at the Department of Urology, U-
575, University of California, San Francisco, San Francisco, CA 94143-
0738, USA; Tel: (415) 476-1611; Fax: (415) 476-8849;
E-mail: mmeng@urol.ucsf.edu
CO2 + H2O H+ + HCO3- 2H+ + CO32-
The hydrolysis of urea increases the local concentration
of ammonia and increases urinary pH. The alkaline urinary
environment favors the formation of trivalent phosphate
(PO43-), normally present in uninfected, non-alkalotic urine
as univalent phosphate (HPO42-). It is the presence of trivalent
phosphate along with the ammonium ion in an alkaline urine
(pH >7.2) which allows the formation of magnesium ammo-
nium phosphate crystals (MgNH4PO4 .6H2O) [7-9]. The
mineral was termed struvite in 1920 by the Swedish
geologist Ulex, who named it after his mentor, the Russian
diplomat H.C. von Struve. Typically these stones are
admixed with carbonate apatite, Ca10(PO4CO3OH)6.(OH)2.
Hence, the term triple phosphate comes from association of
the trivalent phosphate anion with the three cations, calcium
from carbonate apatite and magnesium + ammonium from
the magnesium ammonium phosphate crystal [10].
Under physiological conditions, urinary ammonia levels
are maintained at an approximate concentration of 100
mEq/L. However, as the chemistry of the urine is altered by
infection, the urinary ammonia, hydroxide, and carbonate
levels become significantly elevated. The pathological
supersaturation of these ions leads to particle formation
which aggregate to form crystals and eventually stones. This
stone propogation is enhanced because ammonia also
damages the normally protective urothelial mucopoly-
saccharide (glycosaminoglycan) layer. The struvite crystals
are thus thought to adhere to the damaged glycosamino-
glycan layer, allowing for adhesion to the urothelium and
accelerated growth of the stone. Overall, it is a combination
of the supersaturation of the ions along with increased
crystal adhesion that accounts for the large sizes and rapid
growth rates of struvite stones [11].

1381-6128/03 $41.00+.00 2003 Bentham Science Publishers Ltd.

976 Current Pharmaceutical Design, 2003, Vol. 9, No. 12
Attempts have been made to develop inhibitors of urease
to aid in the treatment of struvite calculi. Acetohydroxamic
acid (AHA) has been used as such an inhibitor. It has both a
high renal clearance and is able to penetrate the bacterial cell
wall. Clinical studies have demonstrated that AHA decreases
the urinary alkalinity and ammonia levels even in the
presence of infection. A double-blind study of AHA versus
placebo revealed that none of the 20 patients taking AHA
doubled the size of their stones, the predetermined endpoint
in the study, compared to 7 of 19 patients receiving placebo
[12]. Furthermore, when one of these patients previously
taking placebo started taking AHA, the stone burden
dramatically decreased after one month of therapy [13].
Unfortunately, the side effects of AHA, including phlebitis,
deep venous thrombosis, and hemolytic anemia, limit its
clinical utility. In addition, many patients with struvite stones
have concomitant impairment in renal function, which not
only increases AHA toxicity but makes the drug less
effective. It is recommended that AHA not be given to
patients with a serum creatinine greater than 2.5 mg/dL. The
clinical utility of urease inhibitors will thus remain limited
until drugs with fewer side effects are developed [14].
ANTI-INFECTIVES
Antibiotics alone are unlikely to sterilize the urine of
patients with struvite stones, as the interstices of the stone
harboring bacteria are not adequately penetrated by drugs.
Thus, treatment for struvite stones requires intervention to
reduce or remove the stones. Chronic suppressive antibiotic
therapy is sub-optimal but may have a role in patients with
residual stone fragments at risk for chronic urinary tract
infections. It must be kept in mind that certain anti-infectives
themselves are considered lithogenic and may be responsible
for as many as 2% of all patients with stones. For instance,
ceftriaxone may induce kidney stones in high dosages,
especially in children. The calculi may be composed of the
drug itself or result from changes in the urinary mileau [15].
Indinavir, a human immunodeficiency viral protease inhibi-
tor, is another common medication known to cause urinary
calculi. It is suspected that indinavir stones are composed of
the un-metabolized drug, indinavir monohydrate. The
incidence of indinavir stones varies in the literature from 3 -
13.1% [16]. Morbidity associated with indinavir therapy is
not affected by treatment duration, as patients who do and do
not develop stones had similar mean treatment times [17].
Other protease inhibitors, such as saquinavir and ritonavir,
have not been reported to result in urinary precipitation and
stones. Recently, medical treatment with another HIV
protease inhibitor, nelfinavir, resulted in urinary stone
formation [18]. Awareness of the association between certain
medications and urinary stones is important for early
identification, cessation of the drug, and initiation of
conservative management, as the majority of these calculi
will pass spontaneously.
GLYCOSAMINOGLYCANS
As mentioned previously, ammonia significantly
damages the urothelium and enhances stone formation by
promoting crystal retention. Semi-synthetic sulfated glyco-
Stoller et al.
saminoglycans are hypothesized to prevent crystal retention
and thus may inhibit stone formation. In a study by Senthil et
al., ammonium oxalate was used to induce stone formation
in rats [19]. The glycosaminoglycan sodium pentosan
polysulphate (Elmiron) was administered and was shown
to significantly reduce urinary stone forming constituents.
However, in a trial using another synthetic glycosamino-
glycan, pentosan polysulphate, the effects as a stone inhibitor
were equivocal. In this study, 121 patients were followed
over a period of three years both before and after treatment.
The study demonstrated that there were no differences in the
stone episode and stone operation rates [20]. Although the
use of glycosaminoglycan for stone inhibition seems feasible
theoretically, restoration of the glycosaminoglycan layer has
not yet been shown to be of use clinically.
Bacteria that produce urease are usually in the
Enterobacteriacae family, with the most common pathogen
being Proteus mirablis (Table 1). Another common pathogen
includes Ureaplasma urealyticum, which requires urea as an
obligate growth factor. All these urease-producing organisms
derive their nitrogen requirements from the breakdown of
urea. It should be noted that Escherichia coli, the most
ubiquitous uropathogen, rarely produces urease.
The gastrointestinal tract harbors the largest urease-
producing bacterial population, including Helicobacter
pylori in the stomach. The discovery of H. pylori has
revolutionized the treatment of peptic ulcer disease [21].
Implicating H. pylori in the etiology of peptic ulcer disease
generated tremendous excitement, because for the first time
it became possible to cure and prevent ulcers with the simple
use of antimicrobial agents to eradicate the bacteria. It is now
believed that H. pylori is the cause of 80% of all gastric
ulcers and 90% of all duodenal ulcers [22]. If we look to the
current situation in kidney stones, release of bacterial urease
and the subsequent formation of struvite stones has been
thought to be the only mechanism for formation of infection-
associated kidney stones. Yet struvite stones represent less
than 15% of all urinary stone disease. Could there be other
pathogens involved in the formation of kidney stones and
what would be the role of anti-microbials in their
prevention? An analogous change in the traditional
paradigms of stone pathogenesis may be required to
significantly impact future work on urolithiasis.
NANOBACTERIA
Kajander et al. suggested that not only struvite stones,
but calcium based stones, may have an infectious origin
nanobacteria [23]. These unconventional, cytotoxic bacteria
were discovered within the past decade in human blood and
blood products, as well as in urine. They are thought to be
the smallest living organism, nearly 100-fold smaller than
most common bacteria. Some forms of nanobacteria may
exist in a calcified state, with a spherical coating of the cell
wall made of carbonate apatite, similar to the common
component thought to be the nidus for most stones.
Nanobacteria have been shown to cause mineralization in
vitro under physiologic concentrations of calcium and
phosphate. Furthermore, the kidney is thought to play a role
in the clearance of nanobacteria. Akerman et al. published a
Infections and Urinary Stone Disease Current Pharmaceutical Design, 2003, Vol. 9, No. 12 977

Table 1. Common Urease Producing Organisms (Data from However, much of the data regarding nanobacteria have
[8-9]) been disputed. Cisar et al. have proposed that biominerali-
zation of calcium apatite, previously attributed to nanobac-
teria, may in fact have been a contaminant. In their study,
Urease Producing Organisms examination of the biomineralization culture failed to reveal
any nucleic acid or protein. Also, it was not inhibited by
Type of sodium azide. They have explained Kajanders results by
Organism
Organism suggesting that the DNA sequences attributed to the
nanabacterium species were in fact a contaminant from a
Gram Positive Staphylococcus aureus Phyllobacterium species present in the environment [28].
Bacteria Staphylococcus epidermidis Thus, the crystallization thought to result from nanobacteria
Corynebacterium species (C .ulcerans, C. renale, C. ovis, may in fact arise from the culture medium itself. More
C. hofmanii, C. murium, C. equi)) importantly, critics have pointed out that there have been no
Mycobacterium rhodochrous group studies which confirm the presence of nanobacteria in human
Micrococcus varians calculi or human urine. Chan et al. as well as Low et al. were
Bacillus species unable to duplicate the results of Kajandar and could not
Clostridium tetani detect nanobacterial antigens in human calculi [29-30].
Peptococcus asaccharolyticus Although the controversy remains and has become publicly
Gram Bacteroides corrodens
heated, it appears unlikely that nanobacteria represent a
Negative Helicobacter pylori
pathogen responsible for the development of human kidney
Bacteria Bordetella pertussis
stones [31].
Bordetella bronchiseptica
Haemophilius influenzae
OXALOBACTER FORMIGENES
Haemophilus parainfluenzae
Proteus species (P. mirabilils, P. morganii, P. rettgeri) Oxalobacter formigenes is known to affect oxalate
Providencia stuartii metabolism and has recently been implicated in calcium
Klebsiella species (K. penumoniae, K. oxytoca) stone formation. The majority of endogenous oxalate
Pasteurella species formation originates from the metabolism of glycine,
Peseudomonas aeruginosa glyoxylate and ascorbic acid. As much as 20% of oxalate is
Aeromonas hydrophilia derived from oral ingestion and colonic absorption.
Yersinia enterocolitica Increased absorption of oxalate can occur in patients with
Brucella species high oxalate intake or in those with intestinal disorders,
Flavobacterium species including small bowel resection, inflammatory bowel
Serratia marcescens disease, steatorrhea, jejeno-ileal bypass surgery, and cystic
Mycoplasma Ureaplasma urealyticum fibrosis [32-34]. The resultant hyperoxaluria has been shown
Mycoplasma T-strain to be a significant risk factor for calcium oxalate stone
disease. In 1985, Allison et al. first isolated Oxalobacter
Yeast Cryptococcus species formigenes from human feces, showing it to be an obligate
Rhodotorula species anaerobic gram negative rod that was able to degrade oxalic
Sporobolmyces species acid. Humans have no known endogenous enzyme capable
Trichosporon cutaneum of degrading oxalate. Thus, O. formigenes plays an
Candida humicola important symbiotic role with its vertebrate host by reducing
enteric absorption of oxalate and regulating oxalate
homeostasis [35]. Allison et al. later examined bacterial
report in which viable, radioactively labeled nanobacteria oxalate degradation rates in normal humans and compared
were injected into rabbits and appeared in urine within them to those who had undergone a jejuno-ileal bypass. The
fifteen minutes [24]. Hjelle et al . reported that nanobacteria latter group had a much slower rate of degradation, and thus
or its antigens were present in polycystic kidneys and in the it was postulated that the decreased rate of oxalate
urine, implicating them as a potential microbial pathogen breakdown resulted in greater oxalate absorption and
responsible for the disease [25]. In another study by associated hyperoxaluria. This hyperoxaluria is thought to be
Kajander et al., fibroblasts were infected with nanobacteria the main risk factor for the development of calcium oxalate
and later analyzed with electron microscopy, which revealed stones in these patients [36].
intra- and extracellular crystal deposits that resembled those
found in stone disease. Additional work demonstrated that Intestinal colonization by O. formigenes begins in
nanobacterial antigens were present in 70 of 72 human infancy and by age eight, nearly all children are colonized
kidney stones analyzed [26]. Also, injecting nanobacteria with the bacteria. However, antibiotic use affects the ability
into rat kidneys suggested that kidneys stones may develop of this bacteria to colonize the gut [37]. Prolonged use of
in a nanobacteria-inoculum dependent manner. Given this antibiotics by patients with cystic fibrosis may either
data, it was thought that nanobacteria acted as a nidus to preclude natural colonization of O. formigenes or destroy the
promote apatite nucleation and crystal growth, representing a existing colonies. Sidhu et al. examined O. formigenes in
novel mechanism by which bacterial infections relate to cystic fibrosis patients, another group of patients at risk for
stone formation [27]. hyperoxaluria and calcium oxalate stone formation. These
978 Current Pharmaceutical Design, 2003, Vol. 9, No. 12
patients were shown to have decreased levels of intestinal O.
formigenes. Stool samples and 24-hour urine collections
from 43 patients with cystic fibrosis and 21 healthy controls
were analyzed for O. formigenes and oxalate, respectively.
Only seven of the 43 cystic fibrosis patients (16%) were
colonized with O. formigenes , compared to 15 of 21 (71%)
of healthy controls. In addition, none of these seven
colonized patients had elevated urinary oxalate levels, while
19 of 36 uncolonized cystic fibrosis patients (53%) had
hyperoxaluria. Thus, the regulation of urinary oxalate
excretion was directly correlated with colonization of O.
formigenes in the intestine [38]. Absence of this bacteria
from the gut flora is associated with an increased suscep-
tibility to hyperoxaluria, which can lead to calcium oxalate
stones in the urinary tract. An epidemiological study
suggested an association between recurrent urinary lithiasis
and the lack of intestinal O. formigenes [39]. Thirty-three of
44 control patients (75%) had detectable O. formigenes in
stool samples. In contrast, in patients with calcium oxalate
stones, there was a direct correlation with the number of
stone episodes and the lack of intestinal O. formigenes
colonization. Twelve of 15 (80%) with only one episode of
urolithiasis were colonized with O. formigenes, while 8 of 21
(38%) with 2-episodes and 3 of 23 (13%) with more than 5
episodes had O. formigenes detected in their stool. These
data have been confirmed by other investigators. Tunaguntla
et al. also correlated urinary oxalate levels with O. formigenes
colonization in gut. Absence of O. formigenes was
associated with hyperoxaluria and an increased risk of
recurrent oxalate stone disease [40]. Sidhu et al. further
documented this in an in vivo rat model. Sprague Dawley
rats not colonized with O. formigenes developed hyper-
oxaluria when fed oxalate-rich diets. After introduction of O.
formigenes into these rats in sufficient concentrations to
cause bowel colonization, there were significant reductions
in urinary oxalate levels. In 2001, Sidhu et al. elaborated on
their previous study where male Sprague Dawley rats were
placed on a diet to induce a state of severe hyperoxaluria.
These rats were then treated with O. formigenes for a two-
week period. The rats with hyperoxaluria showed decreased
levels of urinary oxalate within two days of initiating
bacterial probiotic therapy; the amount of decrease was
proportional to the dose of bacteria. These rats tolerated the
therapy, without adverse affects on health [41]. Feeding rats
other oxalate-degrading factors, including the enzyme
Table 2. In Vitro Growth and Degradation of Oxalate by Different Strains of Lactic Acid Bacteria
Lactic Acid Bacteria for Probiotic Treatment
Bacteria Degradation (%)
in low oxalate
Lactobacillus acidophilus 11.8
Lactobacillus plantarum 1.4
Streptococcus thermophilus 2.3
Bifidobacterium infantis 5.3
Lactobacillus brevis 0.9
Stoller et al.
oxalyl-coenzyme A decarboxylase, reduced urinary oxalate
levels and, more importantly, decreased formation of urinary
tract stones compared to controls [42].
In summary, O. formigenes is likely an important
component in human oxalate degradation and urinary oxalate
levels. Its absence from the gut can increase the intestinal
absorption of oxalate, increasing the risk for hyperoxaluria
and subsequent kidney stone disease. Novel therapeutic
strategies involving oxalobacteria, including recolonization
in the intestine, require further investigation and human
trials.
LACTIC ACID BACTERIA
Campierti et al. evaluated the role of other oxalate-
degrading bacteria in stone formation [43]. They postulated
that oral supplementation with probiotic, freeze dried lactic
acid bacteria may also affect the urinary oxalate excretion, as
many of these bacteria have oxalate consuming metabolic
pathways. Six patients with known mild hyperoxaluria (> 40
mg/24 hr) were administered a mixture of freeze dried lactic
acid bacteria (4 gm slurry, with each gram containing 2 x
1011 bacteria). The specific strains of bacteria are shown in
Table 2.
In addition to the probiotic treatment, each patient was
encouraged to maintain a urine output of at least 1.5 L per
day and restrict consumption of high oxalate foods. In all six
patients, significant reductions in 24-hour urinary oxalate
were noted after 8 weeks of treatment. Fecal excretion of
oxalate was evaluated in two patients and both were found to
have a large reduction of fecal oxalate levels after 30 days of
treatment. Other urinary paramaters, including 24-hour
volume, phosphate, citrate, and calcium excretion, were not
significantly affected. The various bacterial strains differed
in their abilities to degrade oxalate as well as to grow in
media containing different oxalate levels. For example, L.
acidophilus and S. thermophilus degraded oxalate but their
growth was inhibited by the presence of oxalate; conversely,
L. brevis and L. plantarum had only a modest ability to
degrade oxalate yet was able to grow in an oxalate medium.
Only B. infantis showed a significant ability to degrade
oxalate and grow rapidly in an oxalate rich medium (Table
Growth in low oxalate Degradation (%) Growth in high oxalate
(Time zero: end point) in high oxalate (Time zero: end point)
25: 130 3.4 25: 52
32: 270 0.0 32: 230
2.5: 28 3.1 2.5: 9
36: 300 2.2 36: 230
27: 130 0.7 27: 120
Infections and Urinary Stone Disease
2). Thus, manipulation of the endogenous bowel flora may
represent a novel mechanism to alter oxalate absorption and
ultimately impact calcium oxalate stone formation.
FOREIGN BODIES AND INFECTION
Manipulation of the urinary tract with miniaturized
instruments has become increasingly common with the
advent of endourologic techniques. As such, patients with
kidney stones undergoing surgical therapy are theoretically
at an increased risk of infection. Therefore, prevention of
catheter-related infection are potentially important
considerations in the prevention of urinary stones.
ANTIBIOTIC COATED URETHRAL CATHETERS
Nosocomial urinary tract infections are extremely
common, with an estimated incidence of 4.35 cases per 1000
hospitalized patients. Such infections represent a significant
source of morbidity, especially when associated with
indwelling urethral catheters and/or ureteral stents. With
urethral catheterization alone, bacteriuria will develop at a
rate of 5% per day [44-45]. Reports in the literature
demonstrate that symptomatic bacteremia can cause a
mortality rate of up to 30%. In fact, patients with urethral
catheters who subsequently developed urinary tract
infections had as high as a threefold increase in mortality
compared to those patients without urethral catheters [46].
Table 3. Types of Urethral Catheters Under Investigation to
Reduce Infection
Types of Urethral Catheters
Silver-coated
Gentamicin-coated
Ciprofloxacin-coated
Hydrogel-coated
Catheter-related bacteriuria may arise from several
sources - periurethral and/or perineal organisms, colonization
of the collecting bag, or breaks in closed-drainage systems.
The presence of a urethral catheter may also compromise
immune function, with decreased ability of bladder
antibacterial defense activity. Abrasion of the bladder
mucosa from the tip of the catheter disrupts the
glycosaminoglycan layer, enhancing bacterial adherence. As
a result of these multiple insults, bacteria colonizing the
meatus which ascend to the bladder can more easily cause
symptomatic infections [47-48].
Bacterial colonization allows the formation of biofilms
on both the inner and outer catheter surfaces. Biofilms are
the accumulation of organisms and their by-products and
rapidly develop on surfaces. They are thought to be
comprised of three layers -- a film which attaches to tissue
surfaces; a film made of bacteria; and an outer surface film
Current Pharmaceutical Design, 2003, Vol. 9, No. 12 979
where free-floating organisms can arise and spread. Biofilms
make it difficult for antimicrobial agents to be effective by
creating a bacterial reservoir and barrier to drug penetration.
In addition, studies have demonstrated that biofilms on
urethral catheters remain intact despite antibiotics. Bacterial
species can survive within biofilms even in the presence of
antibiotic concentrations 1000 - 1500 times greater than the
minimal inhibitory concentration measured in cultured
bacterial species [49].
Biofilms form not only on urethral catheters but on any
foreign body within the urinary tract, including indwelling
ureteral stents. The rates of ureteral stent colonization vary
from 68-90%, with the incidence of clinical infections
ranging between 2730%, dependent upon the time the stent
remains in vivo. Chronic infection in the presence of a
ureteral stent can lead to encrustation or stone formation,
urinary obstruction, and ultimately urosepsis [49-50].
Preventing the formation of biofilms by altering the
properties of catheter and stent biomaterials has been
undertaken to potentially decrease morbidity. In a
randomized study of 223 patients, Foley catheters coated
with silver alloy on both inner and outer surfaces were
compared to Teflonised latex Foley catheters. There was a
statistically significant reduction in the incidence of
bacteriuria in patients with the silver-coated catheter,
suggesting that this modification may reduce the incidence
of catheter associated urinary tract infections [51]. Another
study compared the ability of urethral catheters coated with
silver or hydrogel, or immersed in antibiotic solutions to
decrease the bacterial adhesion to the catheter surface.
Surprisingly, these new coating materials did not reduce
bacterial adhesion whereas immersion in antibiotic solutions
had a significantly lower adhesion rate [52]. Therefore, other
antibiotic associated catheters have been developed. Cho et
al. developed a gentamicin-releasing urethral catheter. In a
rabbit model study comparing these catheters to untreated
silicone catheters, the surface of the gentamicin-releasing
catheter decreased colonization. Moreover, there was a
decreased rate of bacteriuria after both 3 and 5 days of
catheterization with the gentamicin-releasing catheters.
These studies suggest a potential short-term benefit of these
treated urethral catheters in controlling infection [53].
Several groups have described coating urethral catheters
with a ciprofloxacin liposome hydrogel. In theory, such a
hydrogel would prevent bacterial adhesion to the catheter
[54-55]. Pugach et al. evaluated this hydrogel in rabbit
models and compared these antiobiotic treated catheters to
placebo hydrogel-coated catheters. They report that
bacteriuria developed twice as rapidly in the non-antiobiotic
coated catheters when compared to the ciprofloxacin coated
catheters. This decreased bacteriuria translated to a
significant decrease in urinary tract infections.
In addition to the direct coating of biomaterials, oral
administration of certain antibiotics may also disrupt the
biofilm. A study of oral fluroquinolones demonstrated drug
adsorption on ureteral stents, sufficient to reduce biofilm
formation of certain uropathogens including Escherichia
coli. Forty patients with indwelling ureteral stents received
oral ciprofloxacin and ofloxacin; subsequently, measured
980 Current Pharmaceutical Design, 2003, Vol. 9, No. 12 Stoller et al.

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