Oral probiotics can resolve urogenital infections

We report the first clinical evidence that probiotic lactobacilli can be delivered to the vagina following oral intake. In 10 women with a history of recurrent yeast vaginitis, bacterial vaginosis (BV) and urinary tract infections, strains Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 suspended in skim milk and given twice daily for 14 days, were recovered from the vagina and identified by morphology and molecular typing within 1 week of commencement of therapy. In six cases of asymptomatic BV or intermediate BV (based upon Nugent scoring) was resolved within 1 week of therapy.     

Lactobacillus inhibitor production against Escherichia coli and coaggregation ability with uropathogens

Previous investigations have shown that certain strains of lactobacilli can competitively exclude uropathogens from attaching to uroepithelial cells and from causing urinary tract infection in animals. The finding of an inhibitory effect produced by Lactobacillus casei ssp. rhamnosus GR-1 against the growth of uropathogens was investigated further using two Escherichia coli indicator strains Hu 734 and ATCC 25922. There were two phases to the inhibitor studies. The first one using an agar sandwich technique showed that the inhibitor activity was heat stable and inhibitory to the E. coli. The second phase showed that MRS broth provided optimum lactobacilli growth and inhibitor production. In addition, the inhibition was present under conditions buffering for acid and pH. The data indicated that the inhibitory effect was not due to bacteriophages or hydrogen peroxide. Strain GR-1 was found to coaggregate with E. coli ATCC 25922 in urine, a phenomenon that has not previously been reported for urogenital bacteria. An in vitro assay system was developed to study the coaggregation of various lactobacilli and uropathogens. The results demonstrated that highest coaggregation scores occurred after 4 h incubation at 37 degrees C with lactobacilli and two type-1 fimbriated E. coli strains. Of the nine lactobacilli strains tested, each was found to coaggregate with 2 or more of the 13 uropathogens. The dominance of inhibitor-producing lactobacilli on the urogenital epithelium and the ability of these organisms to interact closely with uropathogens would constitute an important host defense mechanism against infection.     

Detection of a Lactobacillus substance that inhibits Escherichia coli

Recent studies have shown that certain lactobacilli strains have the ability to interfere with the adherence and growth of uropathogenic bacteria. This interaction is believed to be important in the maintenance of a normal urogenital flora and in the prevention of infection in females. In the present study, Lactobacillus casei ssp. rhamnosus GR-1 and Lactobacillus acidophilus 76 were found to exert an inhibitory effect on pyelonephritogenic mutant Escherichia coli Hu 734 and E. coli ATCC 25922. The bioactivity of the inhibitor produced by strain GR-1 was retained under pH buffered conditions and was bactericidal. The bioactive substance was heat labile, not precipitated by up to 80% ammonium sulphate, and extractable in chloroform. The data indicated that the inhibitor is not lactic acid or hydrogen peroxide and has a molecular weight greater than 12,000-14,000. Human urine supported production of the inhibitor and reduced and delayed outgrowth of the E. coli. The ability of L. casei GR-1 and possibly other lactobacilli strains to produce inhibitors of uropathogenic bacteria may have clinical importance and significance in the microbial ecology of the urogenital tract.     

Use of Lactobacillus to prevent infection by pathogenic bacteria

This review focuses on the use and potential of Lactobacillus to prevent infections of the urogenital and intestinal tracts. The presence and dominance of Lactobacillus in the vagina is associated with a reduced risk of bacterial vaginosis and urinary tract infections. The mechanisms appear to involve anti-adhesion factors, by-products such as hydrogen peroxide and bacteriocins lethal to pathogens, and perhaps immune modulation or signaling effects. The instillation of Lactobacillus GR-1 and B-54 or RC-14 strains into the vagina has been shown to reduce the risk of urinary tract infections, and improve the maintenance of a normal flora. Ingestion of these strains into the gut has also been shown to modify the vaginal flora to a more healthy state. In addition, these strains inhibit the growth of intestinal, as well as urogenital pathogens, colonize the gut and protect against infections as shown in mice. Other probiotic strains, such as Lactobacillus GG, have been shown to prevent and treat gastroenteritis caused by rotavirus and bacteria. Given that lactobacilli are not the dominant commensals in a gut which comprises around 10(10) organisms, much work is still needed to define the mechanisms whereby GR-1, RC-14, GG and other strains contribute to health restoration and maintenance. Such critically important studies will require the medical science community to show a willingness to turn away from pharmaceutical remedies as the only solution to health and disease.     

Urinary Tract Dilatation and Oral Contraceptives

Six nulliparous patients were found to have overdistensiblity of the upper urinary tract on excretion urography. Of these five had had persistent or recurrent urinary infections. All had been or were receiving oral contraceptives. Though overdistensibility associated with contraceptive therapy is unlikely to be life-threatening, it may be associated with increased patient morbidity.     

Therapeutic experience with netilmicin.

Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.     

Adhesion of lactobacilli to polymer surfaces in vivo and in vitro

The ability of bacteria to attach to surfaces has been recognized as an important phenomenon, particularly for pathogenic organisms that utilize this capacity to initiate disease. The present investigation was undertaken to determine whether indigenous urogenital bacteria, lactobacilli, colonized prosthetic devices in vivo and in vitro and attached to specific polymer surfaces in vitro. Polyethylene intrauterine devices (IUDs) in place for 2 years were removed from six women who were asymptomatic and free of signs of cervical or uterine infection. Lactobacilli were found attached to the IUDs, as determined by culture, and fluorescent antibody and acridine orange staining techniques. This demonstrated that bacterial biofilms consisting of indigenous bacteria can occur on prosthetic devices without inducing a symptomatic infection. In vitro studies were then undertaken with well-documented lactobacilli strainsL. acidophilus T-13,L. casei GR-1, GR-2, and RC-17, andL. fermentum A-60. These organisms were found to adhere to IUDs and urinary catheters within 24 hours. A quantitative assay was designed to examine the mechanisms of adhesion ofL. acidophilus T-13 to specific polymer surfaces that are commonly used as prosthetic devices. The lactobacilli adhered optimally to fluorinated ethylene propylene when 10⁸ bacteria were incubated for 9 hours at 37°C in phosphate buffered saline, pH 7.1. Additional experiments verified that the lactobacilli adhered to polyethyleneterephthalate, polystyrene, and sulfonated polystyrene and to silkolatex catheter material. There was a linear relationship found between polymer hydrophobicity and bacterial adherence. These results demonstrate that lactobacilli bind to various surfaces in vivo and in vitro, and that the nature of the substratum can affect the colonization.     

Epidemiology of symptomatic infections of the urinary tract in children.

The epidemiology of symptomatic infections of the urinary tract in children and the factors that may alter the risk of infection are not well known. Numbers of children aged under 15 discharged from hospitals because of symptomatic infections of the urinary tract during 1978-84 were obtained from the database kept by the Finnish National Board of Health. Information on continuous treatment for recurrent urinary tract infections was obtained from records kept by the Social Insurance Institution on patients receiving free medicines. The yearly rate of attacks of symptomatic infections/1000 girls decreased significantly from 2.67 (95% confidence interval 2.52 to 2.82) in 1978 to 1.88 (1.76 to 2.01) in 1984. In boys the rate also decreased significantly, from 0.85 (0.77 to 0.93) in 1978 to 0.59 (0.52 to 0.66) in 1984. The period prevalence of free treatment/1000 girls decreased significantly from 7.80 (7.55 to 8.05) in 1978 to 5.30 (5.10 to 5.51) in 1984 but did not change significantly in boys. Although the findings may partly have been caused by changes in policies of admission to hospital, they suggest a decreasing trend in symptomatic urinary tract infections in childhood, which may be associated with changes in the care of infants.     

Practical management of recurrent urinary tract infections in premenopausal women

Recurrent urinary tract infections (UTIs) are a major healthcare concern for premenopausal, healthy, sexually active women. A practical approach to the management and prevention of recurrent UTIs should be simple, practical, and cost effective. Low-dose or postcoital antimicrobial therapy can be effective for women with constellations of many recurrent UTIs, but for women with 2 to 4 UTIs per year, the most cost-effective and empowering management strategy is patient-initiated antimicrobial treatment.     

Effect of culture media and growth phase on the morphology of lactobacilli and on their ability to adhere to epithelial cells

Previous studies have demonstrated that the ability of lactobacilli to attach to and colonize uroepithelial surfaces is an important characteristic that enhances interference against uropathogenic bacteria. This adherence capacity was found to vary amongst lactobacillus strains and with the type of growth medium used to culture the organisms. The present study was undertaken to examine further the effect of culture media and growth phase on lactobacillus adherence to uroepithelial cells in vitro. In addition, a freeze substitution technique was developed to examine the morphology of strainsLactobacillus casei ssrhamnosus RC-17,L. casei GR-1, andL. acidophilus T-13 in relation to growth conditions and adhesion. A growth curve was plotted for strain GR-1, and adherence was found to be lowest for bacteria in early log phase (39 bacteria per uroepithelial cell) and highest in stationary phase (59 bacteria per uroepithelial cell). Strains RC-17 and GR-1 attached in high numbers to uroepithelial cells, whereas T-13 was poorly adherent. The latter formed a long, relatively dense, fibrous capsule after growth in brain heart infusion yeast extract agar, unlike strains GR-1 and RC-17, which formed a short, tightly bound, electron-dense capsule which surrounded the cells in a radial fashion. Growth of RC-17 in batch cultures of human urine, with and without addition of carbohydrates, resulted in formation of an irregular, fibrous extracellular matrix. These experiments illustrate that growth phase and culture conditions affect the extracellular structure of lactobacilli and also affect the adherence capacity of these bacteria. Structural changes mediated by availability of nutrients may partly explain why lactobacilli vary between species and between hosts in their colonization of the urogenital tract.     

Epidemiology of urinary tract diseases in general practice

During a one-year morbidity survey of urinary tract diseases in general practice 741 cases were diagnosed. Only about half of all the patients with symptoms of urinary tract infection had significant bacteriuria. In young women urinary tract infections and symptoms from the urinary tract without bacteriuria—in particular urethritis—were found to predominate. In middle-aged women, the urinary tract symptoms were ascribed increasingly to genital prolapse, while incidence of urolithiasis was the highest in any group, and urinary tract infections became less frequent. The prevalence of urinary tract infection showed another increase in elderly women, and recurrent/chronic pyelonephritis, which occurs with a steadily increasing prevalence throughout all age groups, became common.In younger male urological patients diseases with symptoms of urinary tract infection without bacteriuria were predominant, whereas prostatitis and urinary tract infections were less frequent. In middle-aged men, urolithiasis was especially frequent, while an increasing proportion of elderly men had prostatic hypertrophy, urinary tract infections, and recurrent/chronic pyelonephritis.     

Urinary tract infections in children. An update.

Urinary tract infection is a common and frequently recurring condition in children. The susceptibility of the host, the presence of urinary tract abnormalities, and the virulence of the urinary pathogens are of primary importance in the development of the infection. Renal parenchymal scarring, hypertension, and renal insufficiency are well-established complications of the infection in children. To reduce the risk of renal damage, diagnosis and treatment must be prompt. The diagnosis demands radiologic evaluation of the urinary tract in all boys, all children younger than 5 years, all patients with voiding dysfunction, and school-aged girls with recurrent infection to identify those patients with vesicoureteral reflux, obstruction, or other urinary tract abnormalities. Both voiding cystourethrography and renal ultrasonography are the initial examinations to use to determine the next appropriate study. Children with vesicoureteral reflux or with recurrent urinary tract infections should receive prophylactic antibiotic therapy and should be observed closely to prevent renal scarring.     

Treatment of Infections with Colistimethate Sodium (Coly-Mycin)

Colistimethate sodium (Coly-Mycin) was used in the treatment of 17 patients: 13 had urinary tract infections (two of these had positive blood cultures), three had respiratory tract infections, and one patient had both urinary and respiratory tract infections. In nine of the 17 a foreign body—either a carcinoma, a catheter, or a stone—complicated the infection.The dosage used was 1.1-2.3 mg./lb./day with a maximum in one case of 2.4 g. given over an eight-day period. The organisms so treated included Pseudomonas, six; Aerobacter, six and E. coli, two. Both Pseudomonas and Aerobacter were encountered in three cases.On bacteriological grounds, six patients were cured, eight relapsed, and in three the infecting agent was replaced by another organism. The best responses were obtained in those patients with Pseudomonas infection. Side effects included nausea, vomiting, vertigo, paresthesias, and pain at the site of injection.Colistimethate sodium has a place in the treatment of Gram-negative infections excluding Proteus organisms.     

Lactobacillus rhamnosus L60, a potential probiotic isolated from the human vagina

The vagina has been increasingly viewed as an "ecosystem" whose normal microflora help protect it from invading pathogens, including those that cause urinary tract infections and sexually transmitted diseases. We tested new strains of lactobacilli as potential probiotics for maintenance of urogenital tract health, as well as prevention and therapy of urogenital infections. A strain of lactobacilli isolated from the vagina of nonpregnant, healthy, premenopausal women was identified as Lactobacillus rhamnosus L60 by 16S rDNA sequence homology. L60 was evaluated for antimicrobial activity, in vitro antibiotic resistance, autoaggregation, surface hydrophobicity, co-aggregation with other bacterial species, hydrogen peroxide (H(2)O(2)) production, and bacterial adherence. It displayed a wide spectrum of antimicrobial activity against urogenital pathogens, and resistance to antibiotics commonly prescribed for infections caused by these pathogens. L60 produced H(2)O(2), adhered to vaginal epithelial cells, co-aggregated with Escherichia coli and Candida albicans, and displayed self-aggregation. In view of these characteristics, L60 is considered a potential probiotic, and will be further evaluated for preventive and therapeutic application locally in the vaginal tract.     

Effect of Beta-Blocker Therapy on the Risk of Infections and Death after Acute Stroke – A Historical Cohort Study

BackgroundInfections are a frequent cause for prolonged hospitalization and increased mortality after stroke. Recent studies revealed a stroke-induced depression of the peripheral immune system associated with an increased susceptibility for infections. In a mice model for stroke, this immunosuppressive effect was reversible after beta-blocker administration. The aim of our study was to investigate the effect of beta-blocker therapy on the risk of infections and death after stroke in humans.Methods625 consecutive patients with ischemic or hemorrhagic stroke, admitted to a university hospital stroke unit, were included in this historical cohort study. The effect of beta-blocker therapy on post-stroke pneumonia, urinary tract infections and death was investigated using multivariable Poisson and Cox regression models.Results553 (88.3%) patients were admitted with ischemic stroke, the remaining 72 (11.7%) had a hemorrhagic stroke. Median baseline NIHSS was 8 (IQR 5–16) points. 301 (48.2%) patients received beta-blocker therapy. There was no difference in the risk of post-stroke pneumonia between patients with and without beta-blocker therapy (Rate Ratio = 1.00, 95%CI 0.77–1.30, p = 0.995). Patients with beta-blocker therapy showed a decreased risk for urinary tract infections (RR = 0.65, 95%CI 0.43–0.98, p = 0.040). 7-days mortality did not differ between groups (Hazard Ratio = 1.36, 95%CI 0.65–2.77, p = 0.425), while patients with beta-blocker therapy showed a higher 30-days mortality (HR = 1.93, 95%CI 1.20–3.10, p = 0.006).ConclusionsBeta-blocker therapy did not reduce the risk for post-stroke pneumonia, but significantly reduced the risk for urinary tract infections. Different immune mechanisms underlying both diseases might explain these findings that need to be confirmed in future studies.     

Survival and retention of the probiotic Lactobacillus casei LAFTI L26 in the gastrointestinal tract of the mouse

AIMS: This study aimed to develop methods for the detection of the probiotic Lactobacillus casei LAFTI L26 (L26) from mouse faeces, and to determine the survival and retention time of L26 in the mouse gastrointestinal tract. METHODS AND RESULTS: A selective medium, de Man Rogosa Sharpe (MRS) + bromocresol green + vancomycin (MGV), was designed for the isolation and enumeration of L26 from faecal samples of mice. PCR primers were designed to confirm the identity of L26-like colonies on MGV. These primers did not produce PCR products from related organisms that grew on MGV. Following the administration of L26 to BALB/c mice, faecal samples were collected and analysed using the designed methods. Survival studies showed viable L26 cells to be present in the faeces of mice for >48 h. CONCLUSIONS: Our results suggest that L26 is able to survive and be retained within the digestive tract of mice for at least 48 h following oral administration. SIGNIFICANCE AND IMPACT OF THE STUDY: MGV allows effective recovery of L26 from the background microbiota, including lactobacilli of mice. PCR was used to confirm that L26-like colonies were correctly identified as L26. Given the long retention time of L26 in the gastrointestinal tract of mice, it would appear that this probiotic strain may survive in the human gastrointestinal tract.     

Trimethoprim in the Treatment of Urinary Infections in Hospital

Success in the cure of urinary infections of hospital patients was compared for five-day courses of sulphamethoxazole alone, sulphamethoxazole plus one-tenth its weight of trimethoprim, and sulphamethoxazole plus one-fifth its weight of trimethoprim (Septrin). The cure rates were 65%, 84%, and 92% respectively. Fifty-four per cent. of 111 patients had urinary tract abnormalities. Forty-three per cent. of the causative organisms were sulphonamide-resistant in vitro. There were no major side-effects, though two patients had pruritus or a rash.The degree of potentiation of sulphamethoxazole activity by one-fifth the weight of trimethoprim was so great that its cure rate of infections due to sulphonamide-resistant organisms exceeded that of sulphamethoxazole alone used in infections due to sulphonamide-sensitive organisms. The degree of synergism between trimethoprim and sulphamethoxazole demonstrated in vitro against urinary organisms was directly related to the cure rate of the combination.     

Human microbial ecology: lactobacilli, probiotics, selective decontamination

Health care-associated infections are closely associated with different medical interventions which interrupt the balance of human microbiota. The occasional predominance of opportunistic pathogens may lead to their translocation into the lymph nodes and bloodstream, causing endogenous (primary or secondary) hospital infections. The question is raised as to if there is a possibility for prevention of the imbalance of GI microbiota during medical interventions in critically ill patients. Prophylactic selective decontamination of the digestive tract (SDD) simultaneously applies three to four different antimicrobials for the suppression of enteric aerobic microbes, which are potentially pathogenic microorganisms. However, there is no convincing evidence that the indigenous beneficial intestinal microbiota are preserved, resulting in reduced mortality of high-risk patients. In this overview, we have evaluated the antimicrobial treatment guidelines of the Infectious Diseases Society of America (IDSA) for intra-abdominal infections in adults and seniors according to their safety for different Lactobacillus spp. The data from our group and in the literature have shown that all tested lactobacilli strains (nearly one hundred) were insusceptible to metronidazole while different species of lactobacilli of the three fermentation groups expressed particular antibiotic susceptibility to vancomycin, cefoxitin, ciprofloxacin and some new tetracyclines. We have relied on microbial ecology data showing that the GI tracts of adults and the elderly are simultaneously colonised at least with several (four to a maximum of 12) Lactobacillus species expressing variable intrinsic insusceptibility to the aforementioned antimicrobials, according to the provided data in table. This finding offers the possibility of preserving the colonisation of the intestine with some beneficial lactobacilli during antimicrobial treatment in critically ill patients with health care-associated infections. Several probiotic Lactobacillus spp. strains are intrinsically resistant to antimicrobials and can be used during antibacterial therapy, however, their application as an additive to antimicrobial treatment in critically ill patients needs to be investigated in well-designed clinical trials.     

Oral Lactobacillus species in type 2 diabetic patients living in southern Thailand

Although lactobacilli are part of normal oral, gastrointestinal and genitourinary flora, they are an uncommon cause of infections in human. Lactobacillus-associated infections have generally occurred in patients with serious underlying conditions e.g. diabetes and cancer that might favour certain microorganisms. The aim of this study was to characterize species and genotypes of lactobacilli isolated from diabetic patients and non-diabetic subjects. One hundred and five type 2 diabetic patients and 103 non-diabetic subjects were recruited in this study. A total of 170 isolates of Lactobacillus were identified using 16S rRNA gene PCR-RFLP and genotyping were performed using AP-PCR by ERIC primers. It was found that type 2 diabetic patients had a significantly higher prevalence (p = 0.008) and level of lactobacilli than non-diabetic controls (p = 0.030). The most frequently isolated Lactobacillus spp. were L. casei/paracasei and L. fermentum in both the diabetic and non-diabetic groups. Strains of L. casei/paracasei and L. fermentum from between and within individuals were genotyped, and the genotyping of Lactobacillus strains showed diversity between individuals. One up to three genotypes of these two species could be found in the same subject. Interestingly, fewer genotypes were found in the diabetic patients than in the non-diabetic subjects.     

Effect of antibiotic treatment on receptivity of uroepithelial cells to uropathogens

The management of female patients with recurrent urinary tract infections still remains a problem, and long-term prophylactic or short intermittent courses of antibiotics are the standard forms of therapy. In this report, 10 patients were examined for the effects of long- and short-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX) antibiotics on the receptivity of uroepithelial cells to bacterial adherence. The urine of all patients was sterile while on antibiotic therapy. Few bacteria were found adherent to the cells from adult patients (group 1, mean age 36 years) on long-term antibiotics, but the cells were highly receptive to uropathogens in vitro, especially for Escherichia coli expressing mannose-resistant adhesins. Controls of age-matched adult females were included and in vitro adherence levels were found to be higher for those women with a history of urinary tract infection compared with those with no past record of infection. In the second group, elderly patients (mean age 87 years) presented with bacteriuria, and their uroepithelial cells were found to be colonized by uropathogens to a significantly greater extent than their controls. The adherent population was reduced during 7-day TMP-SMX antibiotic treatment, but increased posttherapy, particularly in two patients who subsequently became reinfected. The in vitro results showed that uroepithelial cells retain their receptivity to uropathogenic adherence, both during and after treatment. Although antibiotics eradicate uropathogens from the urinary tract, patients remain susceptible to recolonization by uropathogens and are at risk of reinfection after completion of therapy.