Novel surface biochemical modifications of urinary catheters to prevent catheter-associated urinary tract infections.

More than 70% of hospital-acquired urinary tract infections are related to urinary catheters, which are commonly used for the treatment of about 20% of hospitalized patients. Urinary catheters are used to drain the bladder if there is an obstruction in the tube that carries urine out of the bladder (urethra). During catheter-associated urinary tract infections, microorganisms rise up in the urinary tract and reach the bladder, and cause infections. Various materials are used to fabricate urinary catheters such as silicone, polyurethane, and latex. These materials allow bacteria and fungi to develop colonies on their inner and outer surfaces, leading to bacteriuria or other infections. Urinary catheters could be modified to exert antibacterial and antifungal effects. Although so many research have been conducted over the past years on the fabrication of antibacterial and antifouling catheters, an ideal catheter needs to be developed for long-term catheterization of more than a month. In this review, we are going to introduce the recent advances in fabricating antibacterial materials to prevent catheter-associated urinary tract infections, such as nanoparticles, antibiotics, chemical compounds, antimicrobial peptides, bacteriophages, and plant extracts.

Sulopenem for the Treatment of Complicated Urinary Tract Infections Including Pyelonephritis: A Phase 3, Randomized Trial.

BACKGROUND: Sulopenem is a thiopenem antibiotic being developed for the treatment of multidrug-resistant infections. The availability of both intravenous (IV) and oral formulations will facilitate earlier hospital discharge. METHODS: Hospitalized adults with pyuria, bacteriuria, and signs and symptoms of complicated urinary tract infection (cUTI) were randomized to 5 days of IV sulopenem followed by oral sulopenem etzadroxil/probenecid or 5 days of IV ertapenem followed by oral ciprofloxacin or amoxicillin-clavulanate, depending on uropathogen susceptibility. The primary end point was overall combined clinical and microbiologic response at the test-of-cure visit (day 21). RESULTS: Of 1392 treated patients, 444 and 440 treated with sulopenem and ertapenem, respectively, had a positive baseline urine culture and were eligible for the primary efficacy analyses. Extended-spectrum ß-lactamase-producing organisms were identified in 26.6% of patients and fluoroquinolone-nonsusceptible pathogens in 38.6%. For the primary end point, noninferiority of sulopenem to the comparator regimen was not demonstrated, 67.8% vs 73.9% (difference, -6.1%; 95% confidence interval, -12.0 to -.1%). The difference was driven by a lower rate of asymptomatic bacteriuria in the subgroup of ertapenem-treated patients who stepped down to ciprofloxacin. No substantial difference in overall response was observed at any other time point. Both IV and oral formulations of sulopenem were well-tolerated and compared favorably to the comparator. CONCLUSIONS: Sulopenem followed by oral sulopenem-etzadroxil/probenecid was not noninferior to ertapenem followed by oral step-down therapy for the treatment of cUTIs, driven by a lower rate of asymptomatic bacteriuria in those who received ciprofloxacin. Both formulations of sulopenem were well-tolerated. CLINICAL TRIAL REGISTRATION: NCT03357614.

Therapeutic effects of orally administration of viable and inactivated probiotic strains against murine urinary tract infection.

Urinary tract infections (UTIs) are highly prevalent bacterial infections that pose significant health risks. Specific probiotic strains have been recommended for UTI control and management of antibiotic resistance. Otherwise, para-probiotics, defined as inactivated probiotic cells, offer potential advantages by minimizing risks associated with live microorganisms. However, the effectiveness of heat-killed probiotic strains against UTIs remains uncertain. Additionally, lactoferrin (LF), an iron-binding glycoprotein, exhibits immunomodulatory, antimicrobial, and anti-inflammatory properties. Recently, we had developed recombinant LF-expression probiotics, which can display considerate antibacterial activities against select food-borne pathogens in vitro. Thus, the present study aimed to evaluate the antibacterial activities of heat-killed natural and recombinant LF-expressing probiotics against UTIs in vitro and in vivo. Firstly, using in vitro assays, we assessed the antibacterial activity of heat-killed natural and recombinant LF-expressing probiotics against uropathogenic Escherichia coli and Klebsiella pneumoniae. Among the tested probiotics, 10 heat-killed LF-expressing strains displayed superior antibacterial efficacy compared to 12 natural probiotics. Based on their potent in vitro activity, selected probiotics were formulated into three probiotic mixtures: viable probiotic mixture (LAB), heat-killed probiotic mixture (HK-LAB), and heat-killed LF-expressing probiotic mixture (HK-LAB/LF). To further evaluate the therapeutic potential of these probiotic mixtures in vivo, we established a murine model of UTIs by intraurethral administration of E. coli to 40 female C57BL/6JNarl mice on day 0. Subsequently, mice received oral gavage of placebo, LAB, HK-LAB, or HK-LAB/LF for 21 consecutive days (n = 8 per group). An additional control group (n = 8) received ampicillin treatment for 7 days. To assess protective effects against re-infection or UTI relapse, all mice were challenged with E. coli on day 22 and E. coli plus K. pneumoniae on day 25. Results from the murine UTI model demonstrated that placebo administration did not reduce bacteriuria throughout the experiment. Conversely, supplementation with ampicillin, HK-LAB/LF, HK-LAB, or LAB significantly (p < 0.05) reduced daily bacteriuria by 103 to 104-fold on days 1, 3, 5, and 14, respectively. Furthermore, all four therapeutic treatments improved the bacteriological cure rate (BCR) with varying levels of efficacy. For the 7-day treatment course, the BCR was 25% (placebo), 62.5% (ampicillin), 37.5% (LAB), 37.5% (HK-LAB), and 62.5% (HK-LAB/LF). For the 21-day treatment course, the BCR was 25% (placebo), 75% (ampicillin), 37.5% (LAB), 37.5% (HK-LAB), and 75% (HK-LAB/LF). Notably, HK-LAB and HK-LAB/LF demonstrated superior therapeutic efficacy compared to viable LAB in treating UTIs. Overall, regarding BCR, the three probiotic mixtures can provide benefits against UTI in mice, but ampicillin therapy remains the most efficient among the four treatments. Furthermore, there was no significant difference between pre- and post-challenge courses for the two instances of re-challenging uropathogens in all mice groups, as bacteriuria levels remained below 103 CFU/mL, implying that adaptive responses of mice may help reduce the risk of recurrent UTIs. In conclusion, our results provide new evidence that oral administration of heat-killed probiotic mixtures can confer significant therapeutic efficacy against UTIs in a murine model.

Sulopenem: An Intravenous and Oral Penem for the Treatment of Urinary Tract Infections Due to Multidrug-Resistant Bacteria.

Sulopenem (formerly known as CP-70,429, and CP-65,207 when a component of a racemic mixture with its R isomer) is an intravenous and oral penem that possesses in vitro activity against fluoroquinolone-resistant, extended spectrum ß-lactamases (ESBL)-producing, multidrug-resistant (MDR) Enterobacterales. Sulopenem is being developed to treat patients with uncomplicated and complicated urinary tract infections (UTIs) as well as intra-abdominal infections. This review will focus mainly on its use in UTIs. The chemical structure of sulopenem shares properties of penicillins, cephalosporins, and carbapenems. Sulopenem is available as an oral prodrug formulation, sulopenem etzadroxil, which is hydrolyzed by intestinal esterases, resulting in active sulopenem. In early studies, the S isomer of CP-65,207, later developed as sulopenem, demonstrated greater absorption, higher drug concentrations in the urine, and increased stability against the renal enzyme dehydropeptidase-1 compared with the R isomer, which set the stage for its further development as a UTI antimicrobial. Sulopenem is active against both Gram-negative and Gram-positive microorganisms. Sulopenem's ß-lactam ring alkylates the serine residues of penicillin-binding protein (PBP), which inhibits peptidoglycan cross-linking. Due to its ionization and low molecular weight, sulopenem passes through outer membrane proteins to reach PBPs of Gram-negative bacteria. While sulopenem activity is unaffected by many ß-lactamases, resistance arises from alterations in PBPs (e.g., methicillin-resistant Staphylococcus aureus [MRSA]), expression of carbapenemases (e.g., carbapenemase-producing Enterobacterales and in Stenotrophomonas maltophilia), reduction in the expression of outer membrane proteins (e.g., some Klebsiella spp.), and the presence of efflux pumps (e.g., MexAB-OprM in Pseudomonas aeruginosa), or a combination of these mechanisms. In vitro studies have reported that sulopenem demonstrates greater activity than meropenem and ertapenem against Enterococcus faecalis, Listeria monocytogenes, methicillin-susceptible S. aureus (MSSA), and Staphylococcus epidermidis, as well as similar activity to carbapenems against Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes. With some exceptions, sulopenem activity against Gram-negative aerobes was less than ertapenem and meropenem but greater than imipenem. Sulopenem activity against Escherichia coli carrying ESBL, CTX-M, or Amp-C enzymes, or demonstrating MDR phenotypes, as well as against ESBL-producing Klebsiella pneumoniae, was nearly identical to ertapenem and meropenem and greater than imipenem. Sulopenem exhibited identical or slightly greater activity than imipenem against many Gram-positive and Gram-negative anaerobes, including Bacteroides fragilis. The pharmacokinetics of intravenous sulopenem appear similar to carbapenems such as imipenem-cilastatin, meropenem, and doripenem. In healthy subjects, reported volumes of distribution (Vd) ranged from 15.8 to 27.6 L, total drug clearances (CLT) of 18.9-24.9 L/h, protein binding of approximately 10%, and elimination half-lives (t½) of 0.88-1.03 h. The estimated renal clearance (CLR) of sulopenem is 8.0-10.6 L/h, with 35.5% ± 6.7% of a 1000 mg dose recovered unchanged in the urine. An ester prodrug, sulopenem etzadroxil, has been developed for oral administration. Initial investigations reported a variable oral bioavailability of 20-34% under fasted conditions, however subsequent work showed that bioavailability is significantly improved by administering sulopenem with food to increase its oral absorption or with probenecid to reduce its renal tubular secretion. Food consumption increases the area under the curve (AUC) of oral sulopenem (500 mg twice daily) by 23.6% when administered alone and 62% when administered with 500 mg of probenecid. Like carbapenems, sulopenem demonstrates bactericidal activity that is associated with the percentage of time that free concentrations exceed the MIC (%f T > MIC). In animal models, bacteriostasis was associated with %f T > MICs ranging from 8.6 to 17%, whereas 2-log10 kill was seen at values ranging from 12 to 28%. No pharmacodynamic targets have been documented for suppression of resistance. Sulopenem concentrations in urine are variable, ranging from 21.8 to 420.0 mg/L (median 84.4 mg/L) in fasted subjects and 28.8 to 609.0 mg/L (median 87.3 mg/L) in those who were fed. Sulopenem has been compared with carbapenems and cephalosporins in guinea pig and murine systemic and lung infection animal models. Studied pathogens included Acinetobacter calcoaceticus, B. fragilis, Citrobacter freundii, Enterobacter cloacae, E. coli, K. pneumoniae, Proteus vulgaris, and Serratia marcescens. These studies reported that overall, sulopenem was non-inferior to carbapenems but appeared to be superior to cephalosporins. A phase III clinical trial (SURE-1) reported that sulopenem was not non-inferior to ciprofloxacin in women infected with fluoroquinolone-susceptible pathogens, due to a higher rate of asymptomatic bacteriuria in sulopenem-treated patients at the test-of-cure visit. However, the researchers reported superiority of sulopenem etzadroxil/probenecid over ciprofloxacin for the treatment of uncomplicated UTIs in women infected with fluoroquinolone/non-susceptible pathogens, and non-inferiority in all patients with a positive urine culture. A phase III clinical trial (SURE-2) compared intravenous sulopenem followed by oral sulopenem etzadroxil/probenecid with ertapenem in the treatment of complicated UTIs. No difference in overall success was noted at the end of therapy. However, intravenous sulopenem followed by oral sulopenem etzadroxil was not non-inferior to ertapenem followed by oral stepdown therapy in overall success at test-of-cure due to a higher rate of asymptomatic bacteriuria in the sulopenem arm. After a meeting with the US FDA, Iterum stated that they are currently evaluating the optimal design for an additional phase III uncomplicated UTI study to be conducted prior to the potential resubmission of the New Drug Application (NDA). It is unclear at this time whether Iterum intends to apply for EMA or Japanese regulatory approval. The safety and tolerability of sulopenem has been reported in various phase I pharmacokinetic studies and phase III clinical trials. Sulopenem (intravenous and oral) appears to be well tolerated in healthy subjects, with and without the coadministration of probenecid, with few serious drug-related treatment-emergent adverse events (TEAEs) reported to date. Reported TEAEs affecting ≥1% of patients were (from most to least common) diarrhea, nausea, headache, vomiting and dizziness. Discontinuation rates were low and were not different than comparator agents. Sulopenem administered orally and/or intravenously represents a potentially well tolerated and effective option for treating uncomplicated and complicated UTIs, especially in patients with documented or highly suspected antimicrobial pathogens to commonly used agents (e.g. fluoroquinolone-resistant E. coli), and in patients with documented microbiological or clinical failure or patients who demonstrate intolerance/adverse effects to first-line agents. This agent will likely be used orally in the outpatient setting, and intravenously followed by oral stepdown in the hospital setting. Sulopenem also allows for oral stepdown therapy in the hospital setting from intravenous non-sulopenem therapy. More clinical data are required to fully assess the clinical efficacy and safety of sulopenem, especially in patients with complicated UTIs caused by resistant pathogens such as ESBL-producing, Amp-C, MDR E. coli. Antimicrobial stewardship programs will need to create guidelines for when this oral and intravenous penem should be used.

Causative organisms and antimicrobial susceptibility in jaundiced infants with significant bacteriuria.

BACKGROUND: Jaundice may be one of the first signs of urinary tract infection (UTI) in infants. The most common pathogen is Escherichia coli. Currently recommended antibiotic treatment for neonatal UTI is ampicillin and an aminoglycoside. Recently, increasing ampicillin and gentamicin resistance in strains of E. coli has been isolated. The aim of this study was to determine causative organisms and antimicrobial susceptibility in jaundiced infants with significant bacteriuria (SB). METHODS: We evaluated admitted afebrile, asymptomatic infants younger than 1-month old with hyperbilirubinemia (total bilirubin >15 mg/dl) requiring phototherapy between January 2011 and December 2015. A total of 615 asymptomatic jaundiced infants were enrolled. Urinalysis and urine cultures were performed on all jaundiced infants. A urine culture was defined as SB if a single pathogen with more than 105-colony forming units per milliliter (CFU/ml) by sterile urinary collection bag or 104 CFU/ml by catheterization was isolated. RESULTS: A total of 88 (14.3%) of 615 asymptomatic jaundiced infants had positive urinary culture. E coli was the most common cultured bacteria (40 cases, [45.5%]). Enterococcus faecalis was the second most common bacteria (17 cases, [19.3%]). Seven cases (8.0%) of Streptococcus agalactiae and six cases (6.8%) of Klebsiella pneumoniae were also identified. Ampicillin sensitivity was found in 22.5% of E. coli infections, gentamicin sensitivity was found in 84.2%, and extended-spectrum ß-lactamases were found in 7.5%. CONCLUSION: E. coli was the most common causative organism for infants with SB. We suggest modifying current empiric antibiotics by changing gentamicin to amikacin for neonatal Gram-negative bacterial infections.

[Clinical and pathogenetic aspects of the treatment and prevention of pyelonephritis in children].

INTRODUCTION: Treatment of pyelonephritis in children should be combined, long-term and individual-based. The success of the therapy in children largely depends on the prompt appointment and the correct choice of antimicrobial therapy. AIM: To evaluate the efficiency of the dietary supplement "Cystenium II" in a group of children aged 7 to 14 years with a diagnosis of acute and chronic recurrent pyelonephritis in the acute phase. MATERIALS AND METHODS: A total of 60 children aged 7 to 14 years with a diagnosis of acute or chronic recurrent pyelonephritis in the acute stage were included in the study. The clinical group consisted of 30 patients (mean age 12.1+/-1.8 years), while the control group included 30 patients of mean age 11.2+/-1.7 years. In the control group patients received only standard antibiotic therapy, while in the clinical group it was combined with a dietary supplement "Cystenium II" 1 tablet 2 times a day with meals for 14 days. After the course of antibacterial treatment, the children in the clinical group continued to take the studied dietary supplement for another 14 days in order to prevent the recurrence of pyelonephritis. The results of treatment (patient's condition, presence of pain, dysuria, fever) were assessed on the 3rd, 7th, 14th day, 1 and 6 months after the start of treatment. A urinalysis was performed at the baseline, on the 7th and 14th days, as well as after 1 and 6 months. Urine culture was performed before and after antibiotic therapy at the baseline, on the 14th day, 1 and 6 months after the start of treatment. RESULTS: The main indicators of urinalysis (leukocytes, red blood cells, protein) returned to normal values in 26 (86.7%) patients of the clinical group and in 23 (76.7%) patients of the control group on the 7th day after the start of treatment. At the completion of the basic therapy (after 14 days) normal clinical parameters (absence of leukocyturia, microhematuria, proteinuria) were observed in all patients of the clinical group and in 28 (93.3%) patients of the control group. After a month of follow-up, the disturbances in urinalysis (leukocytes, red blood cells, protein) in the control group were again seen in 3 (10%) patients, as well as after 6 months. However, in the clinical group all patients had normal urinalysis (absence of leukocyturia, microhematuria, proteinuria) after 1 month and only in 1 (3.3%) case leukocyturia, as well as an increase in the number of red blood cells and protein was detected by 6 months. DISCUSSION: According to our results, the use of dietary supplements "Cystenium II" (manufactured by Akvion, Russia), due to the constituents of D-mannose (450 mg), cranberry fruit extract with a standardized activity of 500 mg (36 mg of proanthocyanidins) and vitamin C (60 mg), may cause anti-inflammatory and anti-adhesive effects (resolving of leukocyturia and bacteriuria). This allows to use the dietary supplement Cystenium II in children from 7 years of age in the combination therapy of acute pyelonephritis, as well as exacerbation of chronic pyelonephritis. The obtained results showed a high overall therapeutic efficacy of combination therapy using Cystenium II after 6 months from the start of treatment (relapse in 1 patient), in contrast to the control group (relapse in 6 patients). CONCLUSIONS: the use of dietary supplement "Cystenium II" allowed to reduce the number of repeated courses of antibiotic therapy in children during 6 months of follow-up and, most likely, reduced the frequency of development of chronic pyelonephritis after an acute inflammation. Therefore, the wide clinical use of dietary supplements "Cystenium II" for the combined treatment of acute and exacerbation of chronic pyelonephritis in children older than 7 years seems to be very reasonable.

A Randomized Clinical Trial of Standard versus Expanded Cultures to Diagnose Urinary Tract Infections in Women.

PURPOSE: We compared urinary tract infection (UTI) symptom resolution rates at 7-10 days in symptomatic women randomized to treatment based on standard urine culture (SUC) versus expanded quantitative urine culture (EQUC) results. MATERIALS AND METHODS: Women ≥18 years old who responded "yes" to "do you feel you have a UTI?" agreed to urethral catheterization and followup. Symptoms were assessed using the validated UTI Symptom Assessment (UTISA) questionnaire. Culture method was randomized 2:1 (SUC:EQUC); antibiotics were prescribed to women with positive cultures. The primary outcome, UTI symptom resolution, was determined 7-10 days following enrollment on all participants regardless of treatment. RESULTS: Demographic data were similar between groups. Of the SUC and EQUC groups 63% and 74% had positive cultures (p=0.10), respectively. Of participants with positive cultures 97% received antibiotics. Primary outcome data were provided by 215 of 225 participants (SUC 143 [95%], EQUC 72 [97%]). At the primary outcome assessment, 64% and 69% in the SUC and EQUC groups, respectively, reported UTI symptom resolution (p=0.46); UTISA scores improved from baseline in the EQUC arm compared to the SUC arm (p=0.04). In the subset of women predominated by non-Escherichia coli (76), there was a trend toward more symptom resolution in the EQUC arm (21%, p=0.08). CONCLUSIONS: Symptom resolution was similar for the overall population (E. coli and non-E. coli) of women treated for UTI symptoms based on SUC or EQUC. Although the sample size limits conclusions regarding the utility of EQUC in women with non-E. coli uropathogens, the detected trend indicates that this understudied clinical subset warrants further study.

[Current trends in the treatment of chronic recurrent bacterial cystitis].

INTRODUCTION: Every year, more than 7 million women go to the doctor for chronic cystitis. An important factor is the psychoemotional component of this disease. OBJECTIVE: comparative analysis of various options for complex treatment of women with chronic recurrent bacterial cystitis using phototherapy, chronotherapy and correction of psychoemotional disorders with the anxiolytic drug Adaptol. MATERIALS AND METHODS: 90 women with chronic recurrent bacterial cystitis in the acute stage were examined and divided into 3 groups of 30 people. In group 1, patients received basic therapy with Furamag (furazidin kalium). In group 2, patients received standard therapy in combination with phototherapy in the acrophase of the chronorhythm. In group 3, basic therapy was performed in combination with phototherapy in the acrophase of the chronorhythm and Adaptol. The severity of dysuria and pain, leukocyturia, bacteriuria, chronobiological and psychoemotional status were evaluated. RESULTS: Initially, all patients showed signs of desynchronosis and psychoemotional disorders. All groups showed signs of exacerbation of chronic cystitis. The results obtained on the 5th day of therapy in groups 2 and 3 were statistically significantly different (p<0.05) from those in group 1. In group 3, the number of nocturnal urination (0.9+/-0.7), the number of imperative urges per day (0.7+/-0.5), and the intensity of pain (0.7+/-0.6) were the closest to normal. By day 10, clinical and laboratory parameters in all three groups reached normal values, which indicates the effectiveness of the therapy in each of the groups. CONCLUSION: Thus, the use of Furamag and Adaptol in combination with phototherapy at the maximum peaks of psychoemotional and physiological activity of the body effectively stops the clinical and laboratory manifestations of the disease, corrects the mental status and improves the quality of life of women in a shorter period of treatment.

[Experience in the use of herbal preparations for the complex treatment of uncomplicated lower urinary tract infections in pregnant women].

INTRODUCTION: During pregnancy, therapeutic options which can be used to treat and prevent acute lower urinary tract infections are significantly limited. In this regard, new opportunities to increase time to relapse of urinary tract infections are urgently required. AIM: To evaluate the results of the use of the dietary supplements "Cystenium II" in pregnant women for the complex treatment of acute cystitis and asymptomatic bacteriuria. MATERIALS AND METHODS: The analysis of complex therapy of uncomplicated lower urinary tract infection with the use of dietary supplements "Cystenium II" in 42 pregnant women (mean age 24.5+/-4.3 years), divided into two groups depending on the presence of symptoms of the cystitis. RESULTS: Data on the clinical and microbiological cure and the absence of side effects were obtained. CONCLUSIONS: The use of dietary supplements "Cystenium II" is advisable, both in the complex antimicrobial therapy of acute cystitis, exacerbation of recurrent cystitis or asymptomatic bacteriuria in pregnant women, as well as for the prevention of recurrence of cystitis after the clinical cure.

[Treatment of acute uncomplicated cystitis in women with antibiotic allergy or intolerance].

AIM: A comparative evaluation of the efficacy and safety of Canephron N and Cystone as monotherapy in women with acute uncomplicated cystitis and antibiotic allergy or intolerance was performed. MATERIALS AND METHODS: A prospective, randomized, controlled study of drug Canephron N as monotherapy for acute uncomplicated cystitis in 51 women with a history of antibiotic allergy or intolerance was carried out in 3 urological centers in Perm from 2016 to 2019. In the main group, patients received Canephron N for 30 days, while in comparison group, Cystone was prescribed. The Acute Cystitis Symptom Score (ACSS), microscopic study of urine sediment, urine culture and other methods were used. Results were evaluated 3, 6, 30 days and 1 year after the start of treatment. RESULTS: In the main group, monotherapy with Canephron N for 30 days resulted in a decrease in the total ACSS score from the baseline 12.9 to 0.3 points, while in Cyston group, changes of ACSS score were less pronounced, from baseline 12.8 to 1.4 points (p<0.01). Clinical cure rate in the main and comparison group was 88.5% and 68%, respectively. In another 3.8% and 1% of patients in the main and comparison group, an improvement was seen. The number of patients with leukocyturia in the Canephron N group decreased to 11.5% compared to 28% in Cyston group (p>0.05). Bacteriuria rate in the main group was 7.7%, which was less than in the comparison group (20%, p>0.05). Number of sick days in the main group was 4.9+/-0.4, compared to 7.4+/-0.6 days in Cyston group. In the Canephron N group, 1-year recurrence rate was only 7.7%, while in the Cyston group the recurrence was seen in 16% of patients. CONCLUSION: According to the results, Canephron N is an effective and safe drug as monotherapy for acute uncomplicated cystitis, and can be considered as drug of choice for the treatment of women with antibiotic allergy or intolerance.

Persistent Leptospiruria in Five Dogs Despite Antimicrobial Treatment (2000-2017).

In dogs with leptospirosis, doxycycline therapy is recommended as the preferred therapy for its ability to eliminate the organism from all tissues, including the renal tubules. Elimination of organisms from the renal tubules terminates leptospiruria and prevents transmission of the organism. This report describes the discovery of persistent leptospiruria in the face of therapy with doxycycline in four dogs and enrofloxacin in one dog. Leptospiruria was confirmed by polymerase chain reaction testing for pathogenic leptospires in all five dogs. In two dogs, leptospiruria resolved after a change in therapy to enrofloxacin. In three dogs, doxycycline and/or enrofloxacin were ineffective at eliminating leptospiruria, which then resolved after therapy with clarithromycin. Pet owners could be at risk as persistent leptospiruria poses a potential zoonotic risk. The potential reasons for persistent leptospiruria as demonstrated by polymerase chain reaction testing are discussed.

Bacteriuria and vitamin D deficiency: a cross sectional study of 385 nursing home residents.

BACKGROUND: Up to half of elderly people at nursing homes have asymptomatic bacteriuria, and concentrations of 25-hydroxyvitamin D (25OHD) are generally low. Vitamin D is a modulator of the immune system and involved in protection of the epithelium in the urinary tract as well. The objective was to determine a possible association between bacteriuria and vitamin D deficiency among elderly people at nursing homes. METHODS: Cross-sectional study: Voided urine specimens and blood samples for cultivation and analysis of 25OHD were collected from elderly people at nursing homes in Sweden. Exclusion criteria were: urinary catheter, ongoing antibiotic treatment, incontinence or dementia too severe to provide a voided urine specimen or leave a blood sample, unwillingness to participate or terminal illness. Urine cultures and serum 25OHD concentrations were outcome measures and the association of bacteriuria with vitamin D deficiency was determined by logistic regression. RESULTS: Twenty-two nursing homes participated and 385 of 901elderly people provided voided urine specimens and blood samples. The mean age was 87 (SD 6.7), 69% women, 19% received vitamin D supplement, 13% had diabetes mellitus, and 54% were diagnosed with dementia. There was significant growth of potentially pathogenic bacteria in 32% (123/385) of voided urine specimens. Escherichia coli were present in 83% of positive urine cultures. The mean concentration of 25OHD in serum was 35 nmol/L (SD 21). Thirty-seven per cent (143/385) had 25OHD < 25 nmol/L, and 3.1% (12/385) 25OHD < 12.5 nmol/L. No association between bacteriuria and 25OHD < 25 nmol/L, OR 1.4 (0.86-2.3; p = 0.18) adjusted for age, gender, diabetes mellitus and dementia was found. However, if using 25OHD < 12.5 nmol/L as a cut-off for vitamin D deficiency the adjusted odds-ratio was 4.4 (1.1-17; p = 0.031). CONCLUSIONS: Bacteriuria and vitamin D deficiency was common. No association between bacteriuria and 25OHD < 25 nmol/L was found. If using 25OHD < 12.5 nmol/L as cut-off for vitamin D deficiency there was an association. However, this has to be interpreted with caution as causality cannot be evaluated as well as only few residents had 25OHD < 12.5 nmol/L.

[Comparative effectivenesss of standard antibiotic therapy and Canephron N asymptomatic bacteriuria in pregnant women].

Current international and Russian clinical guidelines recommend treating asymptomatic bacteriuria in pregnancy to prevent acute gestational pyelonephritis. At the same time, the growing resistance of uropathogens and the risks associated with antibiotic therapy in pregnancy dictate the need to limit the use of antibiotics and seek alternative approaches to antibacterial therapy. MATERIALS AND METHODS: A retrospective analysis was performed on 60 pregnant women who received either a standard antibiotic regimen (n=32) or the herbal preparation Canephron N (n=28). The primary outcomes were the incidence of symptomatic infections (cystitis or pyelonephritis), premature birth and low birth weight delivery, and incidence of persistent/recurrent bacteriuria. RESULTS: In the group of antibiotic therapy, one patient developed cystitis and three had pyelonephritis; in the Canephron N group, cystitis occurred in one patient, no pyelonephritis cases were observed. Among the whole study cohort (n=60), the incidence of symptomatic infections and pyelonephritis was 8.3 and 5.0%, respectively. The incidence of symptomatic infections (cystitis, pyelonephritis) did not differ statistically significantly between the study groups (p=0.2157). There were three and one premature births in the group of antibiotic therapy and the Canephron N group, respectively (p=0,373), and two low birth weight deliveries in each group (p=0.891). Recurrent bacteriuria was registered in 17 patients from the group of antibiotic therapy and in three in the Canephron N group (p=0.0006). CONCLUSIONS: The management of asymptomatic bacteriuria in pregnancy using Canephron N is not inferior to standard antibiotic therapy regarding the incidence of symptomatic infection, premature birth, and low birth weight delivery. Persistent/recurrent bacteriuria was more common in women receiving the antibiotic therapy.

L-Methionine associated with Hibiscus sabdariffa and Boswellia serrata extracts are not inferior to antibiotic treatment for symptoms relief in patients affected by recurrent uncomplicated urinary tract infections: Focus on antibiotic-sparing approach.

OBJECTIVE: To evaluate the efficacy of a phytotherapic combination of L-Methionine associated with Hibiscus sabdariffa and Boswellia serrata for treatment of acute episodes of uncomplicated urinary tract infections (UTI) in women affected by recurrent UTIs. MATERIALS AND METHODS: In this randomized phase III clinical trial, adult females with uncomplicated UTI were enrolled into one of the following treatment groups: Group A: phytotherapic combination 1 tablet in the morning and 1 tablet in the evening for 7 days; Group B: Short term antibiotic treatment according to international guidelines recommendations. At baseline, all patients were evaluated by a urologist and quality of life (QoL) questionnaires and mid-stream urine culture. Same clinical and laboratory investigations were repeated at each follow-up visit. RESULTS: Forty-six patients were enrolled in Group A and 47 in Group B. At the first follow-up (30 days), both groups showed a statistically significant improvement in quality of life scores as compared with baseline assessment [Group A: (QoL 94.3 VS 98.5 p < 0.001); Group B: (QoL 94.5 VS 98.7 p < 0.001)]. An improvement from baseline was also seen at the second followup evaluation after 3 months [Group A: (QoL 94.3 VS 99.1 p < 0.001); Group B: (QoL 94.5 VS 98.1 p < 0.001)]. At the second follow-up visit, a statistically significant difference in QoL was reported between the two groups (99.1 VS 98.1; p < 0.003) and a transition from UTI to asymptomatic bacteriuria (ABU) was observed 12 of 46 (26%) patients in Group A, while no patients in Group B demonstrated ABU (p = 0.007). CONCLUSIONS: Here, we demonstrated that this phytotherapic combination is able, in comparison to antibiotic treatment, to improve patients quality of life, reducing symptoms in acute setting and preventing the recurrences. Interestingly, a significantly higher proportion of patients in the phytotherapy group had ABU after three months. Our findings are of great interest in an antibiotic stewardship perspective.

Common microbial causes of significant bacteriuria and their antibiotic resistance pattern in the Isfahan Province of Iran.

Urinary tract infections (UTIs) are considered the most common community-acquired infections worldwide, which have possible complications along with significant economic impact on national healthcare systems. The aim of this study was to identify the most common causes of significant bacteriuria and to assess their antimicrobial resistance pattern in the Isfahan province of Iran. In this cross-sectional study, 11,678 urine samples of the patients referred to Mahdieh Medical Diagnostic Centre Charity were examined over a period of 10 months (from September 2015 to June 2016). Among the cases, 6.85% were positive for bacteriuria (F/M = 11.3). Escherichia coli (62%) was the most frequently isolated bacteria, followed by Staphylococcus epidermidis (13.9%) and Staphylococcus aureus (6.8%). E. coli was more prevalent among patients with diabetes mellitus. E. coli isolates showed the highest resistance to nalidixic acid, Trimethoprim/Sulfamethoxazole and Cefixime. Our results revealed that broad-spectrum antibiotic resistance is frequent among isolated uropathogens in Isfahan, Iran.

Assessment of the comparability of CLSI, EUCAST and Stokes antimicrobial susceptibility profiles for Escherichia coli uropathogenic isolates.

BACKGROUND: As many clinical laboratories convert between Stokes, Clinical and Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) methods, the problem of comparing differently derived sets of antimicrobial susceptibility testing (AST) data with each other arises, owing to a scarcity of knowledge of inter-method comparability. The purpose of the current study was to determine the comparability of CLSI, EUCAST and Stokes AST methods for determining susceptibility of uropathogenic Escherichia coli to ampicillin, amoxicillin-clavulanate, trimethoprim, cephradine/cephalexin, ciprofloxacin and nitrofurantoin. METHODS: A total of 100 E. coli isolates were obtained from boric acid urine samples from patients attending GP surgeries. For EUCAST and CLSI, the Kirby-Bauer disc diffusion method was used and results interpreted using the respective breakpoint guidelines. For the Stokes method, direct susceptibility testing was performed on the urine samples. RESULTS: The lowest levels of agreement were for amoxicillin-clavulanate (60%) and ciprofloxacin (89%) between the three AST methods, when using 2017 interpretive guidelines for CLSI and EUCAST. A comparison of EUCAST and CLSI without Stokes showed 82% agreement for amoxicillin-clavulanate and 94% agreement for ciprofloxacin. Discrepancies were compounded by varying breakpoint susceptibility guidelines issued during the period 2011-2017, and through the inclusion of a definition of intermediate susceptibility in some cases. CONCLUSIONS: Our data indicate that the discrepancies generated through using different AST methods and different interpretive guidelines may result in confusion and inaccuracy when prescribing treatment for urinary tract infection.

Peri-operative antibiotic treatment of bacteriuria reduces early deep surgical site infections in geriatric patients with proximal femur fracture.

PURPOSE: The aim of this study was to conduct a re-evaluation of current strategies for peri-operative prophylaxis of infections in orthopaedic surgery of geriatric patients (≥65 years) with proximal femoral fractures (PFF). METHODS: Between 01/2010 and 08/2014 all post-operative infections after stabilization of PFF of 1,089 geriatric patients were recorded retrospectively. All patients pre-operatively received a single dose of 1.5 g cefuroxime (group 1). These were compared to prospectively determined post-operative rates of surgical site infection (SSI) of 441 geriatric patients, which were operated on between 09/2014 and 03/2017 due to PFF. In this second group we investigated the urinary tract on admission. Bacteriuria was treated with the pre-operative single dose of 1.5 g cefuroxime along with ciprofloxacin for five days, beginning on admission. Level of significance was set to p < 0.05. RESULTS: A total of 141 patients of group 2 had a bacteriuria. Seventy-seven of these patients revealed biochemical signs of manifest urinary tract infection. Multi-resistant pathogens were found in 15 patients and pathogens were cefuroxime-resistant in 37. The differences of SSI after at least three months were 2.1% in group 1 and 0.45% in group 2 for all patients with surgery of PFF (p < 0.02) and for those with arthroplasty (p < 0.037) significant. CONCLUSIONS: The immediate antibiotic therapy of a prevalent bacteriuria for five days decreases the risk of SSI after surgery of PFF. Our single-centre study can only point out the problem of prevalent reservoirs of pathogens and the need for treatment. Evidence-based therapy concepts (indications of antibiotics, classes, duration) have to be developed in multi-centric and prospective studies.