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Drugs 2006; 66 (9): 1253-126

 2006 Adis Data Information BV. All rights reserved.
Probiotics for Prevention of Recurrent
Urinary Tract Infections in Women
A Review of the Evidence from Microbiological and
Clinical Studies

Matthew E. Falagas,1,2 Gregoria I. Betsi,1 Theodoros Tokas1 and Stavros Athanasiou3 1 Alfa Institute of Biomedical Sciences (AIBS), Athens, Greece2 Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, USA3 First Department of Obstetrics and Gynecology, Athens University School of Medicine, Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12531. Literature Search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12542. Pathophysiology of Recurrent Urinary Tract Infections (UTIs) in Women . . . . . . . . . . . . . . . . . . . . . . . . 12543. Mechanisms of Action of Probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12554. Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12555. Microbiological Studies in Healthy Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12566. Clinical and Microbiological Studies in Women with UTIs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12577. Adverse Effects of Probiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12598. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1259 Abstract
Recurrent urinary tract infections (UTIs) afflict a great number of women around the world. The use of probiotics, especially lactobacilli, has been consid-ered for the prevention of UTIs. Since lactobacilli dominate the urogenital flora ofhealthy premenopausal women, it has been suggested that restoration of theurogenital flora, which is dominated by uropathogens, with lactobacilli mayprotect against UTIs. This review is based on a search of PubMed for relevantarticles. Many in vitro studies, animal experiments, microbiological studies inhealthy women, and clinical trials in women with UTIs have been carried out toassess the effectiveness and safety of probiotics for prophylaxis againsturopathogens. Most of them had encouraging findings for some specific strains oflactobacilli. Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 (previouslycalled L. fermentum RC-14) seemed to be the most effective among the studiedlactobacilli for the prevention of UTIs. L. casei shirota and L. crispatus CTV-05have also shown efficacy in some studies. L. rhamnosus GG did not appear to bequite as effective in the prevention of UTIs. The evidence from the availablestudies suggests that probiotics can be beneficial for preventing recurrent UTIs inwomen; they also have a good safety profile. However, further research is needed to confirm these results before the widespread use of probiotics for this indicationcan be recommended.
Recurrent urinary tract infections (UTIs) are a ‘probiotics’, ‘lactobacillus’, ‘urinary’, ‘urogenic’ common cause of morbidity, especially in postme- and ‘infections’. We focused on articles regarding in nopausal and sexually active premenopausal wo- vitro studies of the effect of probiotics on colonisa- men. Recurrence occurs in 25–30% of adult women tion and infection of the urogenital epithelium; ex- who have a first episode of UTI.[1] The decrease in periments on probiotics in animals; and studies in- quality of life of these women and the high health- vestigating the in vivo effect of intravesical, in- care cost of treating them have made the prevention travaginal and oral probiotics on female vaginal of recurrent UTIs very important. Antibacterials have been used widely for this purpose, but long--term antimicrobial prophylaxis is associated with 2. Pathophysiology of Recurrent Urinary
increased drug resistance and adverse effects. Thus, Tract Infections (UTIs) in Women
efforts have been made to discover and develop The healthy female urogenital flora consists of many species of micro-organisms, among which Probiotics are one of these promising alterna- lactobacilli (especially L. crispatus,[5,6] L. jensenii[5] tives. They are defined as “live micro-organisms and L. iners[6,7]) are dominant in healthy preme- which, when administered in adequate amounts, nopausal women. Bruce et al.[8] were the first to confer a health benefit on the host”.[2] There is show that there is a high prevalence of vaginal strong evidence that they are effective for the treat- lactobacilli in women without any history of UTIs.
ment of rotavirus diarrhoea and the prevention of Lactobacilli and the other microorganisms that dom- antibacterial-associated diarrhoea in children.[3] inate the vaginal flora of some healthy women, such Their usefulness for the prevention of Helicobacter as Atopobium spp., Megasphaera spp. and Lepto- pylori infections, inflammatory bowel diseases, al- trichia spp.,[6] produce lactic acid and other sub- lergy, cancer,[3] respiratory tract infections and other stances which keep the vaginal pH low and prevent diseases[4] is still under investigation. Prevention of the overgrowth of pathogens. Estrogens seem to recurrent UTIs is a further possible clinical use for promote the colonisation of the vagina with probiotics. It should be emphasised that there have lactobacilli and reduce the vaginal pH, thus control- been changes to the nomenclature of the various ling the growth of pathogens.[9] This is thought to be lactobacilli recently. More specifically, Lactobacil- one of the main reasons why postmenopausal wo- lus acidophilus RC-14 and L. fermentum RC-14 men are more susceptible to urogenital infections studied in The Netherlands and Canada have been than premenopausal women. Moreover, vaginal renamed L. reuteri RC-14 and L. casei GR-1, re- microflora often changes considerably during the spectively, and L. casei var rhamnosus has been menstrual cycle, even in women without any epi- renamed L. rhamnosus GR-1. However, in our re- view, we use the terms of lactobacillus species as In patients with UTI, the flora of the urethra and specified in the publications from which we derived the vagina are colonised mainly by uropathogens, especially Escherichia coli and other Enterobacter-iaciae. Uropathogens produce many virulence fac- 1. Literature Search
tors, including adhesins, haemolysin and sider- We searched PubMed (1950–2005) for publica- ophores. The ability of uropathogens to cause infec- tions and relevant references from the initially iden- tion is associated with their adhesion to urogenital tified articles. The key words we used included cells, to each other (autoaggregation) and possibly  2006 Adis Data Information BV. All rights reserved.
to other organisms (coaggregation).[11] Although the vent the adhesion of uropathogens.[14] It has also adhesion of the uropathogens on the urogenital epi- been shown that L. crispatus blocks the adherence thelium has been demonstrated in many studies, it is still not yet well understood how they manage to It is accepted today that there is considerable survive passage through natural flora.
variation among lactobacillus strains regarding theiradherence to uroepithelium, and inhibition of 3. Mechanisms of Action of Probiotics
uropathogen adherence and growth. Under the con-ditions of an agar overlay inhibition assay, a combi- In vitro experimentation is useful for clarifying nation score was allocated to each of 11 tested the ability of probiotics to inhibit the growth of lactobacillus strains based on adherence, exclusion uropathogens. However, the results of such experi- and inhibition of pathogen growth. L. casei GR-1 ments may or may not be clinically relevant. In vitro gained the highest score.[16] The production by L. studies of interactions between micro-organisms casei GR-1 (and probably other lactobacilli, such as may be simplified compared with the complexity of L. acidophilus) of inhibitors against pyelonephrito- interactions within the human flora. Despite these genic mutant E. coli strains was proved in another in limitations, there is sufficient evidence from in vitro vitro study, and this may have clinical implications studies to elucidate the mechanism of action of regarding their role in the urogenital microflora.[17] probiotics in preventing UTIs. Recent in vitro stud-ies have shown that specific lactobacilli strains have 4. Animal Studies
the ability to interfere with the adherence, growthand colonisation of the urogenital human epithelium Since no ideal animal models exist, where vagi- by uropathogenic bacteria. This interaction is be- nal administration of a uropathogen causes UTI, lieved to be important in the maintenance of a nor- pathogens are administered intra-urethrally. In mal urogenital flora and in the prevention of infec- 1985, Reid et al.,[18] using an animal model of fe- male rats, concluded that L. casei prevented the According to one study, using glass and sulfonat- onset of UTIs in 84% of the animals tested. First, ed polystyrene polymers, both of which are hydro- they injected bacteria incorporated into agar beads philic, lactobacilli can be used to coat biomaterial into the animals’ bladders. The uropathogens stimu- surfaces, thus decreasing the adhesion of lated an immune and inflammatory response, there- uropathogens.[12] Precoating the polymers with by establishing a persistent adherence of bacteria on lactobacilli significantly reduced adhesion of staph- the uroepithelium, and causing a chronic UTI. Sub- ylococci and E. coli. Another study from The sequently, L. casei GR-1, isolated from the urethra Netherlands demonstrated that the L. acidophilus of a healthy woman, was incorporated into agar RC-14 biosurfactant ‘surlactin’ inhibited the adhe- beads and instilled into the rat bladders. In 21 of 25 sion of the majority of bacteria from a urine suspen- studied animals, no uropathogens were recovered sion to silicone rubber, 4 hours after urine flow.
from the bladder and kidney tissues up to 60 days Surlactin was especially effective against Entero- after instillation. The lactobacilli excluded the coccus faecalis, E. coli and Staphylococcus epider- uropathogens from colonising the uroepitheliumwithin 48 hours.[18] midis.[13] Some years later, a high anti-adhesive,surface-active protein against E. faecalis 1131 was In 1989, Herthelius and Gorbach[19] established a purified from L. fermentum RC-14. The structure of persistent vaginal colonisation with a pyelonephrito- this protein was identical to that of a collagen- genic strain of E. coli in four adult monkeys. Repeat- binding protein from L. reuteri NCIB 11951 and ed vaginal flushes of lactobacilli or vaginal fluid was closely homologous with the basic surface pro- from a healthy monkey were administered for 5–9 tein from L. fermentum BR11. The experiment days. Vaginal E. coli was eliminated in two of six showed that this protein of lactobacillus could pre- experiments where lactobacilli were instilled and in  2006 Adis Data Information BV. All rights reserved.
all eight experiments where vaginal fluid was ad- studied women were colonised with L. rhamnosus ministered. In the other four experiments where lactobacilli were administered, vaginal E. coli was Cardieux et al.[24] compared the vaginal instilla- only reduced. This result shows that the entire nor- tion (immediately after menses) of L. rhamnosus mal vaginal flora is much more effective in inhib- GR-1 and L. fermentum RC-14 (109 cfu) with that of iting the colonisation of the vagina with E. coli than Lactobacillus GG (109 cfu) in 29 premenopausal healthy women without urogenital infections. No In 1996, Silva de Ruiz et al.[20] investigated adverse effects were reported. L. rhamnosus GR-1/ whether L. fermentum CRL 1058 could control UTIs L. fermentum RC-14 and Lactobacillus GG were caused by uropathogenic E. coli in mice treated with isolated from cultures of vaginal swabs of all wo- ampicillin. Animals where inoculated intra-urethral- men in both groups (15 and 14 women, respectively) ly with agarose beads containing lactobacilli, while 3 days after the instillation of probiotics. However, ampicillin was administered orally. The ampicillin L. rhamnosus GR-1/L. fermentum RC-14 and Lacto- dose used allowed the lactobacilli to persist in the bacillus GG were isolated from 11/15 (73%) and 3/ urinary tract, leading to the elimination of patho- 14 (21%), respectively, at day 14 (p = 0.009).[24] In a similar trial, Burton et al.[7] used two techniques A study by Asahara et al.[21] suggested that L. (polymerase chain reaction denaturing gradient gel casei shirota is a strain possibly useful for the pre- electrophoresis [PCR-DGGE] and randomly ampli- vention of UTIs. E. coli was administered intra- fied polymorphic DNA [RAPD] analysis) to detect urethrally in female mice, causing UTI. L. casei L. rhamnosus GR-1/L. fermentum RC-14 in the va- shirota (108 colony-forming units [cfu]) was also gina at amounts that may not be detectable by cul- administered intra-urethrally 1 day before and daily tures. They detected L. rhamnosus GR-1/L. fermen- after the infection. The growth of E. coli and the tum RC-14 in 80% of ten healthy premenopausal inflammatory responses in the urinary tract were women 1 week after daily vaginal instillation of 109 cfu. L. rhamnosus GR-1 was also detected in 20% of L. crispatus CTV-05 has also been tested in ani- mals as a means of protection from urogenital infec- In another clinical study, Reid et al.[25] compared tions, as it has been detected in the vagina of many the oral administration of Lactobacillus GG with L. healthy women. Patton et al.[22] inserted one capsule rhamnosus GR-1 and L. fermentum RC-14 in 42 of L. crispatus CTV-05 (108 cfu) intravaginally into healthy women aged 17–50 years who were free ten female animals (Macaca) and found that it had from symptomatic urogenital infections. The wo- colonised the vaginas of three animals 2 days later.
men were randomly separated into four groups.
Groups 1 (n = 10), 2 (n = 12) and 3 (n = 11) received 5. Microbiological Studies in
daily oral capsules of L. rhamnosus GR-1/L. fermen- Healthy Women
tum RC-14 at different dosages (8 × 108, 1.6 × 109 The ability of lactobacilli to colonise the vaginal and 6 × 109 cfu per day, respectively), and group 4 epithelium of healthy women after intravaginal or (n = 9) received one capsule of Lactobacillus GG oral administration has been investigated in some 1010 cfu daily. At the start of the study, only 40% studies. In 2003, Colodner et al.[23] suggested that L. (17/42) of women had healthy vaginal flora and rhamnosus GG may not be an effective probiotic 33% (14/42) had asymptomatic bacterial vaginosis.
agent in preventing UTIs. Forty-two post- Within 28 days, the percentage of women whose menopausal healthy women were given one to two vaginal flora converted from abnormal to normal doses of yogurt containing L. rhamnosus GG (109 was greater for groups 1, 2 and 3 compared with cfu) daily for 1 month. The cultures of vaginal fluid group 4 (the difference was statistically significant specimens showed that only 9.5% (4 of 42) of the only for group 2; p = 0.017). This study showed that  2006 Adis Data Information BV. All rights reserved.
oral administration of L. rhamnosus GR-1 and L. lactobacilli and L. fermentum RC-14 was recoveredfrom four.[27] fermentum RC-14 is associated with greater restora-tion and maintenance of normal vaginal flora than The ability of L. crispatus CTV-05 to colonise Lactobacillus GG, and that the required dose of L. the vagina after vaginal administration has been rhamnosus GR-1 and L. fermentum RC-14 for this tested clinically. The subjects in this study had just effect is more than 8 × 108 cfu of viable lactobacil- been treated for bacterial vaginosis, and receivedintravaginal L. crispatus CTV-05 or placebo. Thirty days later, L. crispatus CTV-05 colonised the vagina The same investigators have also studied the of 62% of the patients who received it and only 2% effect of the oral administration of L. rhamnosus of those who received placebo (p < 0.001).[28] GR-1 and L. fermentum RC-14 on the vaginal flora,in a randomised, double-blind, placebo-controlledtrial in 64 healthy women (19–46 years old).[26] 6. Clinical and Microbiological Studies
in Women with UTIs

Thirty-two women received oral freeze-dried cap-sules of L. rhamnosus GR-1/L. fermentum RC-14(>109 cfu per strain) once daily for 60 days and the In the first clinical trial of probiotics in women other 32 received placebo for the same duration.
with UTIs, lactobacilli were given intravesically.
Cultures of vaginal fluid showed a significant in- Newman[29] was the first who used intravesical crease in lactobacilli (p = 0.01), a decrease in yeast lactobacilli in a small number of women for the (p = 0.01) and a reduction of coliforms (p = 0.001) at treatment of bladder infections and claimed that this day 28 in the group receiving the lactobacilli com- approach was effective. Hagberg et al.[30] instilled L. pared with placebo-treated women. Significantly casei GR-1 into the bladder of postmenopausal pa- fewer coliforms remained in the lactobacilli-treated tients with recurrent UTIs and found that lactobacilli group at day 90 (p < 0.01). Moreover, more women did not adhere to the bladder. They also implanted in the lactobacillus group reported improvement in avirulent E. coli strains (6mL of 109 bacilli/mL)from the patients’ own faecal flora intravesically vaginal health (vaginal itchiness or odour) com- and found that they colonised the mucosa.
pared with placebo-treated women, although the Intravaginal administration of lactobacilli met difference was not statistically significant (p = 0.17).
with more success than intravesical administration.
There were no adverse effects in the probiotic-treat- During a small, uncontrolled study conducted by Bruce and Reid[31] in 1988, five women (two of Another smaller, randomised, double-blind, pla- whom were postmenopausal) with recurrent UTIs cebo-controlled clinical trial demonstrating the abil- were given intravaginal L. casei GR-1 twice weekly.
ity of L. rhamnosus GR-1 and L. fermentum RC-14 L. casei GR-1 colonised the vaginal epithelium and to colonise the vagina when received orally was prevented the colonisation of coliform bacteria in conducted by Morelli et al.[27] Ten healthy women most women, without affecting enterococcal received orally either L. rhamnosus GR-1/L. fer- colonisation, which occurred in two women. No mentum RC-14 (n = 8) or lactose placebo (n = 2) adverse effects were mentioned. All studied women once daily for 14 days. The number of lactobacilli had significantly more extended infection-free peri- increased in the vaginas of eight of the ten studied ods (4 weeks to 6 months) than before treatment (<1 women 14 days later, although the increase was very month). One patient received a combination of L. small in three of eight. Genetic typing identified L. fermentum B-54 and L. casei GR-1 after the second rhamnosus GR-1 and L. fermentum RC-14, respec- enterococcal infection that occurred during the tively, in five and two of the studied women. L. study period. This combination treatment resulted in rhamnosus GR-1 was also recovered from faecal an increase in the coloinisation of vaginal epitheli- samples of all eight women who received the  2006 Adis Data Information BV. All rights reserved.
A trial comparing the risk of recurrence of UTI Baerheim et al.[35] concluded that it is uncertain before and after receiving lactobacilli was carried whether vaginal instillation of lactobacilli decreases out by Reid et al.[32] in 1992. They treated 41 adult the incidence of cystitis in women. In a randomised, women with acute lower UTI with norfloxacin or double-blind trial, 47 women (aged 18–50 years), with three or more episodes of distal urinary symp- for 3 days. UTI recurred in 29% of the norfloxacin- toms in the previous year (at least one confirmed as treated group and in 41% of the co-trimoxazole- UTI) received vaginally L. casei var rhamnosus of treated group. Women with recurrent UTI then re- placebo twice weekly. During the next 6 months, the ceived vaginal suppositories of either L. casei var incidence rate ratio of lower UTIs between the treat- rhamnosus GR-1 and L. fermentum B-54 or ster- ed patients and the placebo group was 1.41 (95% CI ilised skimmed milk twice weekly for 2 weeks and 0.88, 1.98), a non-statistically significant result.[35] at the end of each of the next 2 months. The recur- Besides the intravesical and the intravaginal rence of UTIs over 6 months decreased to 21% for route of administration of probiotics, the effective- those receiving lactobacillus compared with 47% ness of the oral administration of these agents in reducing the recurrence of UTIs has also been as- A case report by Reid et al.[33] further supports sessed. Tomoda et al.[36] tested Bifidobacterium the effectiveness of intravaginal lactobacilli as pro- longum for this purpose and showed that lower UTIs tection against UTIs. The vagina of a 33-year-old due to Candida infections were reduced by 70% in woman with a history of recurrent bladder and vagi- women receiving oral B. longum.
nal infections was implanted with one gelatin pessa- Various lactobacilli administered orally have ry of 0.5g freeze-dried L. casei var rhamnosus GR-1 been also studied. Lactobacillus GG was used in (>109 viable cells). Although E. faecalis (and no some studies to test its effect on UTIs, but without lactobacilli) was the dominant organism in her vagi- much success. Kontiokari et al.[37] performed a na at the time of the implantation, 7 weeks after the randomised clinical trial in 150 women (mean age pessary insertion, both viable L. casei and L. 30.3 years) who had a UTI caused by E. coli. After rhamnosus GR-1 were recovered from her vaginal being treated with antibacterials for the UTI epi- swabs. She remained free from vaginal and bladder sode, they were randomly separated into three symptoms for the 7 weeks of the study and for the groups. The first group received cranberry- following 6 months (during which she had two more lingonberry juice 50mL per day for 6 months, the second group took a Lactobacillus GG 100mL (4 x A randomised, double-blind clinical trial, show- 1010 cfu) drink 5 days per week for 1 year, and the ing a significant impact of intravaginal lactobacilli third control group received no further treatment.
on recurrence of UTIs, was conducted in 55 preme- No adverse effects were reported. During 6 months nopausal women by Reid et al.[34] Twenty-five of of observation, 8 women (16%) in the cranberry these women received one vaginal suppository of L. group, 19 (39%) in the lactobacillus group and 18 rhamnosus GR-1 and L. fermentum B-54 109 cfu per (36%) in the control group had at least one episode week and the rest received one vaginal suppository of UTI. Consequently, recurrence in 6 months was of a lactobacillus growth factor weekly for 1 year.
significantly less common (p = 0.014) in the cran- No adverse effects were reported. The UTI rate berry than in the control group, while lactobacillus decreased by 73% (from 6 to 1.6 episodes/year; p < 0.001) in the first group and 79% (from 6 to 1.3 In contrast, Kontiokari et al.[38] found a positive episodes/ year; p < 0.001) in the second.[34] role for fermented milk products containing probiot- It should be emphasised that not all clinical stud- ics, such as L. acidopilus or Lactobacillus GG. They ies showed a beneficial effect of intravaginal probi- conducted a case-controlled study in 324 women otics in preventing the recurrence of UTIs.
(mean age 30.5 years). The patients (n = 139) en-  2006 Adis Data Information BV. All rights reserved.
tered the study 2 weeks after an acute UTI caused by disease.[40] During the past 30 years, 180 cases of E. coli; 109 (78%) had more than one UTI episode.
lactobacillaemia and 69 cases of endocarditis due to The controls (n = 185) had no UTIs during the past 5 lactobacilli have been reported.[41] Gasser[42] report- years. The questionnaire they completed showed ed the isolation of L. rhamnosus, L. acidophilus, L. that frequent consumption of fresh juices, especially casei and other lactobacilli in patients with endocar- berry juices, and fermented milk products contain- ditis. L. rhamnosus was also among other isolates ing probiotics were more common among controls than among patients. Specifically, consumption of Nevertheless, only a few cases have been report- fermented milk products with probiotics, such as ed that connect isolated lactobacilli from sites of Lactobacillus GG or L. acidophilus, more than three infection with those consumed. Rautio et al.[43] re- times per week was associated less commonly with ported the case of a 74-year-old woman who con- UTIs compared with consumption of these products sumed about 500mL of dairy drinks with L. less than once per week (odds ratio [OR] 0.21; 95% rhamnosus GG daily for 4 months and developed a liver abscess, an aspirate from which revealed L. Reid et al.[39] conducted a small, uncontrolled rhamnosus indistinguishable from GG. Mackay et trial to assess the efficacy of L. rhamnosus GR-1 and al.[44] reported the case of a 67-year-old man with a L. fermentum RC-14 in protecting women against mild mitral valve regurgitation who consumed cap- UTIs. Ten women with a recent history of recurrent sules with L. rhamnosus and L. acidophilus and urogenital infections who were asymptomatic at the developed endocarditis after a tooth extraction. L. start of the study were given orally >109 cfu of rhamnosus was isolated from blood cultures of this various strains of L. rhamnosus GR-1 and L. fermen- patient. Generally, these cases are very rare com- tum RC-14 twice daily for 14 days. Vaginal cultures, pared with the increasing consumption of probiotics.
Gram-stain and ribotyping performed 1 week later An EU workshop concluded that lactic acid bacteria revealed colonisation of the vagina with L. are of low risk, with the exception of enterococci.[45] rhamnosus GR-1 and L. fermentum RC-14 of allpatients.[39] The vaginal flora of six patients, which 8. Conclusion
were considered to be intermediate or indicative ofbacterial vaginosis based on the Nugent score at the Conclusively, several in vitro and in vivo studies beginning of the study, was restored to normal 1 support the beneficial effect of some strains of week after receiving lactobacilli. In addition, all lactobacilli on the restoration of the vaginal flora women reported relief from their symptoms of uro- and the prevention of recurrent UTIs. Most of them genital infection and had no adverse effects from the show that L. rhamnosus GR-1 and L. fermentum RC-14, given either intravaginally or orally, areefficacious. However, their use for the prophylaxisof UTIs is still controversial because only a few 7. Adverse Effects of Probiotics
case-controlled, double-blind clinical trials using Probiotics are generally considered to be safe.
strains carefully selected according to their laborato- However, some species of microorganisms that are ry-proven characteristics have been carried out so also used as probiotics have recently been isolated far. More randomised, controlled trials should be from infection sites, causing some concerns regard- conducted to confirm the effectiveness of probiotics ing the safety of these products. Surgical operations, compared with placebo and antibacterials or other cancer, diabetes mellitus and long-term antimicrobi- possible preventive agents. Moreover, although re- al and immunosuppressive therapy are the most ported adverse effects are rare to date, further re-search on the safety of probiotics is needed.[2,3,27,46] common underlying conditions in patients with lac-tobacillus infections. Lactobacillaemia usually oc- Probiotics are not yet approved for UTIs by sev- curs in patients with serious and fatal underlying eral drug licensing organisations, including the US  2006 Adis Data Information BV. All rights reserved.
14. Heineman C, van Hylckama Vlieg JE. Purification and charac- FDA. L. rhamnosus GR-1 and L. fermentum RC-14 terization of a surface-binding protein from Lactobacillus fer- are currently available as Omb’e 1 in Austria (by
mentum RC-14 that inhibit adhesion of Enterococcus faecalis1131. FEMS Microbiol Lett 2000; 190 (1): 177-80 HSO), and are approved in Malaysia and Singapore 15. Osset J, Bartolome RM, Garcia E, et al. Assessment of the as PRO-UTIx by Biolife (Australia). They are also capacity of Lactobacillus to inhibit the growth of uropathogens sold in Malaysia and Hong-Kong and are expected and block their adhesion to vaginal epithelial cells. J Infect Dis2001; 183 (3): 485-91 soon to be available worldwide as Urex-cap-5 by 16. Reid G, Cook RL, Bruce AW. Examination of strains of Urex Biotech Inc. (Canada) and Chr. Hansen (Den- lactobacilli for properties that may influence bacterial interfer-ence in the urinary tract. J Urol 1987; 138 (2): 330-5 mark). It should emphasised that labelling of the 17. McGroaty JA, Reid G. Detection of lactobacillus substance that commercial products should mention the strains and inhibits Escherichia Coli. Can J Microbiol 1998; 34 (8): 974-8 the viability of the probiotics they contain.
18. Reid G, Chan RC, Bruce AW, et al. Prevention of urinary tract infection in rats with an indigenous Lactobacillus casei strain.
Infect Immun 1985; 49 (2): 320-4 Acknowledgements
19. Herthelius M, Gorbach SL. Elimination of vaginal colonisation with Escherichia coli by administration of indigenous flora.
The authors received no funding for the preparation of this manuscript and have no potential conflicts of interest directly 20. Silva de Ruiz C, Lopez de Bocanera ME, Nader de Macias ME, et al. Effect of lactobacilli and antibiotics on E. coli urinaryinfections in mice. Biol Pharm Bull 1996; 19 (1): 88-93 21. Asahara T, Nomoto K, Watanuki M, et al. Antimicrobial activi- References
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