Clinical Urinary Tract Infections Research Articles

Detection and diagnosis of bacterial pathogens in urine using laser-induced breakdown spectroscopy

The presence of bacterial cells from three species has been detected in clinical specimens of human urine using laser-induced breakdown spectroscopy (LIBS) by using a partial least squares discriminant analysis (PLS-DA) of 360 spectra obtained from 12 specimens of infected urine and 239 spectra obtained from eight specimens of sterile urine. Nominally sterile urine specimens obtained from four patients at a local hospital after being screened negative for the presence of bacterial pathogens were spiked with known aliquots of Escherichia coli, Staphylococcus aureus, and Enterobacter cloacae to simulate clinical urinary tract infections. Fifteen emission line intensities measured from the LIBS spectra and 92 ratios of those line intensities were used as 107 independent variables in the PLS-DA for discrimination between bacteria-containing specimens and sterile specimens. The PLS-DA models possessed a 98.3% sensitivity and a 97.9% specificity for the detection of pathogenic cells in urine when single-shot LIBS spectra were tested. To increase the signal to noise ratio, thirty spectra acquired from a single specimen were also averaged together and the averaged spectra were used to construct a model. When each averaged spectrum was withheld from the model individually for testing, the diagnostic test possessed a 100% sensitivity and a 100% specificity for the detection of bacterial cells in urine, although the number of test spectra was necessarily reduced.The entire LIBS spectrum from 200 nm – 590 nm was input into an artificial neural network analysis with principal component analysis pre-processing (PCA-ANN) to diagnose the bacterial species once detected. This PCA-ANN test possessed an overall sensitivity of 97.2%, an overall specificity of 98.6%, and an overall classification accuracy of 97.9% when using 80% of the data to build a model and withholding 20% for cross-validation testing. The PCA-ANN was also performed on each of the 12 bacteria-containing filters individually, using the other 11 filters to build the model. The average sensitivity of this test, calculated by averaging the sensitivities measured for each of the three bacterial species, was 70.9% and the average specificity was 85.5%. Based on these results, the average classification accuracy for the test when used to discriminate between the three microorganisms was 80.6%. These results indicate the potential usefulness of LIBS for rapidly detecting and possibly diagnosing urinary tract infections in a clinical setting.

Multi-step strategies for synergistic treatment of urinary tract infections based on D-xylose-decorated antimicrobial peptide carbon dots

Urinary tract infections (UTIs) caused by Uropathogenic Escherichia coli (UPEC), often reoccur due to the formation of intracellular bacterial colonies (IBCs) and antibiotic resistance. Given the significance of YadC for UPEC infection in our previous study, we developed D-xylose-decorated ɛ-poly-L-lysine (εPL)-based carbon dots (D-xyl@εPLCDs) that can be traced, and employed multi-step approaches to elucidate the functional roles of D-xyl@εPLCDs in UPEC infection. Compared to undecorated particles, D-xyl@εPLCDs demonstrate YadC-dependent bacterial targeting and exhibit enhanced bactericidal activities both intracellularly and extracellularly. Moreover, pre-treatment of D-xyl@εPLCDs before infection blocked the subsequent adhesion and invasion of UPEC to bladder epithelial cells 5637. Increase of ROS production and innate immune responses were observed in bladder epithelial cells 5637 treated with D-xyl@εPLCDs. In addition, treatment of D-xyl@εPLCDs post-infection facilitated clearance of UPEC in the bladders of the UTI mouse model, and reduced ultimate number of neutrophils, macrophages and inflammatory responses raised by invaded bacteria. Collectively, we presented a comprehensive evaluating system to show that D-xyl@εPLCDs exhibits superior bactericidal effects against UPEC, making them a promising candidate for drug development in clinical UTI therapeutics.

Uropathogenic Escherichia coli wield enterobactin-derived catabolites as siderophores

Uropathogenic Escherichia coli (UPEC) secrete multiple siderophore types to scavenge extracellular iron(III) ions during clinical urinary tract infections, despite the metabolic costs of biosynthesis. Here, we find the siderophore enterobactin (Ent) and its related products to be prominent components of the iron-responsive extracellular metabolome of a model UPEC strain. Using defined Ent biosynthesis and import mutants, we identify lower molecular weight dimeric exometabolites as products of incomplete siderophore catabolism, rather than prematurely released biosynthetic intermediates. In E.coli, iron acquisition from iron(III)-Ent complexes requires intracellular esterases that hydrolyze the siderophore. Although UPEC are equipped to consume the products of completely hydrolyzed Ent, we find that Ent and its derivatives may be incompletely hydrolyzed to yield products with retained siderophore activity. These results are consistent with catabolic inefficiency as means to obtain more than one iron ion per siderophore molecule. This is compatible with an evolved UPEC strategy to maximize the nutritional returns from metabolic investments in siderophore biosynthesis.

Urine-mediated suppression of Klebsiella pneumoniae mucoidy is counteracted by spontaneous Wzc variants altering capsule chain length.

Klebsiella pneumoniae is a hospital-associated pathogen primarily causing urinary tract infections (UTIs), pneumonia, and septicemia. Two challenging lineages include the hypervirulent strains, causing invasive community-acquired infections, and the carbapenem-resistant classical strains, most frequently isolated from UTIs. While hypervirulent strains are often characterized by a hypermucoid phenotype, classical strains usually present with low mucoidy. Since clinical UTI isolates tend to exhibit limited mucoidy, we hypothesized that environmental conditions may drive K. pneumoniae adaptation to the urinary tract and select against mucoid isolates. We found that both hypervirulent K. pneumoniae and classical Klebsiella UTI isolates significantly suppressed mucoidy when cultured in urine without reducing capsule abundance. A genetic screen identified secondary mutations in the wzc tyrosine kinase that overcome urine-suppressed mucoidy. Over-expressing Wzc variants in trans was sufficient to boost mucoidy in both hypervirulent and classical Klebsiella UTI isolates. Wzc is a bacterial tyrosine kinase that regulates capsule polymerization and extrusion. Although some Wzc variants reduced Wzc phospho-status, urine did not alter Wzc phospho-status. Urine does, however, increase K. pneumoniae capsule chain length diversity and enhance cell-surface attachment. The identified Wzc variants counteract urine-mediated effects on capsule chain length and cell attachment. Combined, these data indicate that capsule chain length correlates with K. pneumoniae mucoidy and that this extracellular feature can be fine-tuned by spontaneous Wzc mutations, which alter host interactions. Spontaneous Wzc mutation represents a global mechanism that could fine-tune K. pneumoniae niche-specific fitness in both classical and hypervirulent isolates. IMPORTANCE Klebsiella pneumoniae is high-priority pathogen causing both hospital-associated infections, such as urinary tract infections, and community-acquired infections. Clinical isolates from community-acquired infection are often characterized by a tacky, hypermucoid phenotype, while urinary tract isolates are usually not mucoid. Historically, mucoidy was attributed to capsule overproduction; however, recent reports have demonstrated that K. pneumoniae capsule abundance and mucoidy are not always correlated. Here, we report that human urine suppresses K. pneumoniae mucoidy, diversifies capsule polysaccharide chain length, and increases cell surface association. Moreover, specific mutations in the capsule biosynthesis gene, wzc, are sufficient to overcome urine-mediated suppression of mucoidy. These Wzc variants cause constitutive production of more uniform capsular polysaccharide chains and increased release of capsule from the cell surface, even in urine. These data demonstrate that K. pneumoniae regulates capsule chain length and cell surface attachment in response host cues, which can alter bacteria-host interactions.

P30 A longitudinal perspective of antimicrobial resistance evolution within urinary tract infection-based clinical trials

Abstract Background The mainstay treatments for urinary tract infections (UTIs) are nitrofurantoin and trimethoprim. The common route to acquire trimethoprim resistance (TriR) is via horizontal transfer of the trimethoprim-insensitive dihydrofolate reductase: dfrA. In contrast, nitrofurantoin resistance (NitR) requires the inactivation of two chromosomally encoded nitroreductases: nfsA and nfsB. The difference in antimicrobial resistance (AMR) evolution is reflected in community surveillance data: NitR incidence = ∼10% and for TriR > 30%. Longitudinal clinical UTI trials provide a unique opportunity to monitor in situ evolution of AMR and correlate its appearance to trial outcomes and the impact on uropathogens. Objectives To explore the in situ AMR evolution and its impact in Escherichia coli isolates from patients participating in the clinical trials: AnTIC and ALTAR. AnTIC was an open label randomized trial assessing the efficacy of antibiotic prophylaxis use in clean intermittent self-catheterizing patients. ALTAR compared the efficacy of the non-antibiotic alternative methenamine hippurate to antibiotic prophylaxis to treat recurrent UTIs. Methods The investigation of the evolution of nitrofurantoin and trimethoprim resistance in E. coli used general microbiology techniques, bioinformatic genome analysis and genetics to model known AMR mutations in susceptible E. coli strains. Results Trimethoprim resistance amongst E. coli trial isolates was driven by 14 out of ∼45 known dfrA allelic variants; the most common being dfrA1 and dfrA17. Growth analysis identified an allelic bias when strains were exposed to sub-MIC concentrations of trimethoprim. Growth rate analysis identified a 2%–10% slower doubling time for nitrofurantoin-resistant strains: NitS: 20.8 ± 0.7 min compared to NitR: 23 ± 0.8 min. Statistically, these data suggested no fitness advantage of evolved strains compared to the sensitive predecessor (P value = 0.13). Genetic manipulation of E. coli to mimic NitR evolution, however, supported a selective advantage. Conclusions Longitudinal sampling during antibiotic based clinical trials has provided a new perspective to the response of E. coli to UTI-related antibiotics. Correlation of nitrofurantoin response to pharmacokinetic data suggests that the low incidence of E. coli NitR is driven by selection not fitness. However, fitness correlates to dfrA allele carriage and could potentially be exploited to benefit the use of trimethoprim if other antibiotics are impeded by AMR.

P26 Evaluating the antibacterial activity of recombinant phage-encoded lysin against drug-resistant uropathogenic Escherichia coli

Abstract Background Atrocious use of antibiotics has led to the emergence of MDR in uropathogenic Escherichia coli (UPEC) that poses a serious challenge in the management of urinary tract infections (UTIs). The WHO has described antibiotic resistance in uropathogens as a key pressure point in the burgeoning global antimicrobial resistance crisis. Given this grim situation, we are exploring phage-encoded lysins as plausible alternatives. Objectives Our study involved an in silico strategy for the discovery and characterization of lysin sequences (seq) targeting E. coli cell wall and evaluating the bactericidal activity of these recombinant lysins using in-vitro assays. Methods Novel lysin sequences were searched by BLAST homology and by screening E. coli prophages in the database (using PHASTER). Lysozyme-like domain was observed in 9 out of 16 lysins. Their characterization depicted modular or globular structure. Based on the physicochemical properties, 7 out of 16 lysins were selected for cloning, expression, and purification as recombinant proteins for evaluating the bactericidal activity. Results Among the several lysins screened, lysin seq 5 demonstrated the highest activity using in vitro assays. Using static biofilm assay, lysin seq 5 (180 μg) showed efficient reduction (>50%) in the biofilm formed by ATCC UPEC 700928 strain. As per turbidity reduction method, lysin seq 5 (50 μg) showed 37% drop in OD600nm on UPEC 700928 strain after 3 h of incubation at 37°C. Using spot on lawn assay, lysin seq 5 (20 μg) exhibited lytic activity (zone of inhibition) on five drug-resistant clinical UTI isolates, which were pretreated with an outer membrane permeabilizer (OMP), viz., EDTA (0.3 mM). Conclusions Lysin seq 5 exhibited antibiofilm activity against UPEC 700928 strain as well as lytic activity against drug-resistant clinical UTI isolates. Screening of additional drug-resistant clinical isolates from UTI patients is underway.

In vitro Studies of Non-Diphtheriae Corynebacterium Isolates on Antimicrobial Susceptibilities, Drug Resistance Mechanisms, and Biofilm Formation Capabilities.

ObjectiveThis study aimed to investigate the antimicrobial susceptibilities, drug resistance mechanisms, and biofilm formation capacities of non-diphtheriae Corynebacterium strains isolated from sterile midstream urine of hospitalized patients with clinical urinary tract infections (UTIs).MethodsA total of 45 non-diphtheriae Corynebacterium isolates were recovered from sterile midstream urine. The available data of 45 patients were collected. Minimum inhibitory concentrations (MICs) of 10 commonly used antibiotics were determined. Meanwhile, the molecular resistance mechanisms of each agent were performed through PCR with specific primers. Moreover, the biofilm formation capability of each isolate on abiotic surfaces was detected with the MTT method.ResultsIn this study, the most prevalent three species were C. striatum (15/45, 33.3%), C. glucuronolyticum (9/45, 20.0%) and C. urealyticum (8/45, 17.8%). These three species also accounted for most renal and ureteral calculi cases. Male patients older than 50 years, especially those with underlying diseases, were more susceptible to non-diphtheriae Corynebacterium infection. All the 45 isolates were 100% susceptible to vancomycin and linezolid, but highly resistant to macrolide–lincosamide–streptogramin B (MLSB), fluoroquinolones, tetracyclines and β-lactams with corresponding mechanisms. The detection rate of multidrug–resistant (MDR) non-diphtheriae Corynebacterium is 91.1%. All isolates are able to form biofilm on abiotic surfaces, except those of C. urealyticum, C. tuberculostearicum and C. jeikeium. Isolates of C. glucuronolyticum and C. Striatum possessed the strongest biofilm formation capacity. C. amycolatum could form biofilm, but varied greatly among different isolates.ConclusionC. striatum, C. glucuronolyticum and C. urealyticum were the most prevalent species relevant to UTIs. The high occurrence of MDR isolates and high diversities in resistance profiles, and the distinctive abilities of biofilm formation highlighted the urgency for identification to species level. We should pay more attention to the drug resistance profiles of non-diphtheriae Corynebacterium, which would help improve empirical antibiotic therapy and reduce drug resistance transmission.

Assessment of extended – spectrum beta lactamases (ESBL) gene among gram-negative bacilli bacteria causing community acquired urinary tract infection among females in southwestern Nigeria

Background: Urinary tract infections (UTI) is commoner in females and mainly caused by Gram Negative bacilli. The emergence of Extended – spectrum beta lactamases (ESBL) has made its treatment difficult especially in the community because of limited therapeutic options. This study was undertaken to determine the prevalence of ESBL-producing Gram negative bacilli causing UTI among females in Babcock University Community; evaluate the associated risk factors and to determine the prevalence of the associated genes among the ESBL isolates.
 Methods: A descriptive cross-sectional study of which 200 female participants with clinical UTI were recruited in Babcock University Community. Pretested interviewer–based structured questionnaire was used to obtain the socio-demographic and risk factors. Mid-stream urine was also collected for evaluation of ESBL- producing Gram-negative bacilli. DNA extraction was done for ESBL positive isolates and SHV, TEM, CTX-M and OXA ESBL genes were detected by PCR. SPSS Version 23.0 was used for data analysis.
 Results: The 200-urine samples tested from the participants yielded 33-Gram negative bacilli isolates. Out of these 33 isolates, 17/33(51.5%) were ESBL-producers giving prevalence rate of 8.5% among the participants. The distribution of the ESBL genes among the ESBL isolates was as follows: SHV 12/17(70.6%), TEM 4/17(23.5%), CTX-M 3/17(17.6%) and OXA 5/17(29.4%). No associated risk factors were found.
 Conclusion: All the four types of ESBL genes evaluated were present among the participants. Routine screening for ESBL for Community acquired UTI is necessary to curb treatment failure.

Assessment of extended – spectrum beta lactamases (ESBL) gene among gram-negative bacilli bacteria causing community acquired urinary tract infection among females in southwestern Nigeria

Background: Urinary tract infections (UTI) is commoner in females and mainly caused by Gram Negative bacilli. The emergence of Extended – spectrum beta lactamases (ESBL) has made its treatment difficult especially in the community because of limited therapeutic options. This study was undertaken to determine the prevalence of ESBL-producing Gram negative bacilli causing UTI among females in Babcock University Community; evaluate the associated risk factors and to determine the prevalence of the associated genes among the ESBL isolates.
 Methods: A descriptive cross-sectional study of which 200 female participants with clinical UTI were recruited in Babcock University Community. Pretested interviewer–based structured questionnaire was used to obtain the socio-demographic and risk factors. Mid-stream urine was also collected for evaluation of ESBL- producing Gram-negative bacilli. DNA extraction was done for ESBL positive isolates and SHV, TEM, CTX-M and OXA ESBL genes were detected by PCR. SPSS Version 23.0 was used for data analysis.
 Results: The 200-urine samples tested from the participants yielded 33-Gram negative bacilli isolates. Out of these 33 isolates, 17/33(51.5%) were ESBL-producers giving prevalence rate of 8.5% among the participants. The distribution of the ESBL genes among the ESBL isolates was as follows: SHV 12/17(70.6%), TEM 4/17(23.5%), CTX-M 3/17(17.6%) and OXA 5/17(29.4%). No associated risk factors were found.
 Conclusion: All the four types of ESBL genes evaluated were present among the participants. Routine screening for ESBL for Community acquired UTI is necessary to curb treatment failure.

The Relationship between Antibiotic Susceptibility and pH in the Case of Uropathogenic Bacteria.

Urinary tract infections (UTIs) are common bacterial infections caused mainly by enteric bacteria. Numerous virulence factors assist bacteria in the colonization of the bladder. Bacterial efflux pumps also contribute to bacterial communication and to biofilm formation. In this study, the phenotypic and genetic antibiotic resistance of clinical UTI pathogens such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were determined by disk diffusion method and polymerase chain reaction (PCR). Following this, different classes of antibiotics were evaluated for their antibacterial activity at pH 5, 6, 7 and 8 by a microdilution method. Gentamicin (GEN) was the most potent antibacterial agent against E. coli strains. The effect of GEN on the relative expression of marR and sdiA genes was evaluated by quantitative PCR. The slightly acidic pH (pH 6) and GEN treatment induced the upregulation of marR antibiotic resistance and sdiA QS activator genes in both E. coli strains. Consequently, bacteria had become more susceptible to GEN. It can be concluded that antibiotic activity is pH dependent and so the artificial manipulation of urinary pH can contribute to a more effective therapy of multidrug resistant bacterial infections.

Are Foley Catheters Needed during Hysterectomies? an Appraisal of 426 MIGS Hysterectomies without Bladder Catheterization or Cystoscopy

<h3>Study Objective</h3> The standard technique for hysterectomies has long included the insertion of a Foley catheter to theoretically reduce operative complications of urinary injury. Urinary Tract Infections (UTIs) following Gynecologic procedures have been cited in the literature from 5-28%. One study suggested that 69% of CAUTI (catheter-associated UTI) can be avoided, and for each day of catheterization, infection risk increases significantly. Additionally, avoiding bladder catheterization, thus allowing bladder distention, may assist in correctly identifying the bladder during dissection, reducing intraoperative injury. <h3>Design</h3> This is a retrospective case series of 426 MIGS hysterectomies performed without initial bladder catheterization from 12/2015 - 2/2021 by a single surgeon. <h3>Setting</h3> MIGS hysterectomies including Total Laparoscopic Hysterectomies and Robot Assisted Laparoscopic Hysterectomies. <h3>Patients or Participants</h3> Inclusion criteria included MIGS hysterectomywithout concurrent cystoscopy, prolapse, or urinary incontinence procedures. <h3>Interventions</h3> 20% of participants underwent perioperative catheterization. <h3>Measurements and Main Results</h3> Of the 426 MIGS hysterectomies, 80% were completed without bladder catheterization or cystoscopy and20% (84) underwent perioperative catheterization. Intraoperatively 18.5% (79) underwent straight catheterizations secondary to bladder overdistention, and 1 underwent indwelling catheterization for hemodynamic monitoring. Postoperatively, 1.8% (8) developed postoperative urinary retention with 6 requiring straight catheterization and 2 indwelling catheterization. At postoperative follow up, 15% complained of bladder discomfort, of which 1.6 % (5) were treated for clinical UTI with 3 undergoing a negative culture. A total of 29 patients had a urine culture performed, with only 2 (0.5%) positive. In spite of a mean of uterine size of 274g, 6.3% endometriosis and 26.9% cancer diagnoses, no bladder or ureteral injuries were encountered. <h3>Conclusion</h3> This study reveals that MIGS hysterectomies without routine bladder catheterization or cystoscopy are feasible and can be safely performed without bladder or ureteral injury with a subsequent decrease in the incidence of UTIs. Further prospective research is warranted to evaluate the benefits of hysterectomy without routine foley placement.

Tailoring Antibiotic Prophylaxis for Ureteroscopic Procedures Based on Local Resistance Profiles May Lead to Reduced Rates of Infections and Urosepsis

Introduction and Objectives: Urinary tract infections (UTI) following ureteroscopy (URS) occur in about 4% of patients. Due to the resistant bacterial strains we encounter in our institution, we retrospectively examined whether a double-drug antibiotic prophylactic treatment (APT) can reduce urosepsis after URS. Materials and Methods: Between February 2015 and March 2016, we performed 344 URS for stone treatment. Starting from September 2015, we changed the APT. Exclusion criteria included procedures involving percutaneous nephrolithotomy, pediatric or pregnant patients, and patients with preoperative clinical UTI. Results: Fifty-seven patients were excluded. Group 1 (n = 106) were the last to receive the conventional APT (oral ciprofloxacin), while the second group (n = 181) were the first to receive the new ­regimen (intravenous gentamycin and ampicillin). A distinct percentage of both groups had a preoperative positive urine culture (29% in group 1 and 19% in group 2). Seven of 9 septic events developed in patients with preoperative positive urine culture (p < 0.001). Patients undergoing retrograde intrarenal surgery were at increased risk for sepsis when treated with conventional APT (p < 0.01). Post-URS sepsis was 7.5% using the conventional APT and 0.5% with the new APT (p < 0.0001). Conclusions: A distinct number of patients undergoing URS stone treatment have positive preoperative urine cultures. “One size fits all” APT is not sufficient according to our data. A regimen tailored to the local antibiotic resistance of the uropathogens can lower the rate of sepsis.

1082. Hold the Phone: Antibiotic Prescribing Practices Associated with Nonvisit Encounters for Urinary Tract Infections (UTIs) in Urology Clinics

BackgroundSurveillance data uncovers a high proportion of multidrug-resistant Gram-negative organisms found in the outpatient setting, often in patients with recurrent urinary tract infections (UTIs), underlying urologic abnormalities, and prior treatment for UTIs. We assessed prescribing practices at urology clinics to identify potential stewardship strategies for UTI management.MethodsAntibiotic prescription encounters for adult patients from nine urology clinics were obtained from July to September 2018 using the EHR. We collected encounter types (visit or nonvisit), ordering medical provider types, antibiotic classes and patient demographics. A subset of 50 randomized, unique patient telephone encounters (TEs) was reviewed for documentation of a UTI diagnosis, symptoms, urinalysis and culture results, antibiotic prescriptions and duration.ResultsA total of 1,704 antibiotic orders were identified for 1,210 patients (48% female, median age 69 years, IQR 20). The majority (75%) of antibiotic encounters were from nonvisits: TEs (39%), orders only (25%), refills (9%), and patient email (2%). Major prescribers were advanced practice providers (APPs, 61%) followed by attending physicians (38%). Antibiotics prescribed were fluoroquinolones (FQs, 27%), nitrofurantoin (24%), first-generation cephalosporins (16%), and trimethoprim–sulfamethoxazole (15%). From the subset of 50 TEs, APPs wrote 76% of prescriptions and 32% of all orders were FQs. Thirty-nine patients had a clinical UTI diagnosis, yet 33% (13/39) did not have documentation of at least one urinary sign or symptom. For symptomatic patients, 15% (4/26) did not have a urine culture result within one week before or after the TE date. The distribution of antibiotics prescribed was similar to overall use and the median duration was 7 days.ConclusionUrology practices care for patients with the most complicated urinary tract pathology and appropriate antibiotic use in this population is a challenge. We found that urology providers often prescribe antibiotics to elderly patients without in-person visits, documentation of symptoms or microbiologic evidence of a UTI. Stewardship efforts should involve APPs, developing diagnostic and treatment guidelines for UTIs and improving documentation for antibiotic orders.Disclosures All authors: No reported disclosures.

Combinatorial effect of probiotics and some medicinal oils on pathogenic bacteria

Probiotics (PB) and medicinal oils (MO) have beneficial effects against microbial gut infections. The present study aimed to evaluate the in vitro combined antibacterial activities of PB and MO against pathogenic strains. Antibacterial activities of three probiotic strains (Lactobacillus plantarum, Lactobacillus casei, and Lactobacillus acidophilus) and five MO (Bitter almond, Clove, Eucalyptus, Peppermint and Thyme oils) were investigated using agar well diffusion method. Cell-free supernatant (CFS) from PB combined with MO showed antagonistic effects against most of the tested pathogenic strains. Thyme and clove oils showed the highest activity. The combinations of CFS from PB and MO were tested by agar well diffusion method. These combinations showed synergistic activity against the S. aureus especially combinations containing clove, peppermint and thyme oils. Combinations were investigated also by Checkerboard dilution method. Most of CSF significantly lowered the minimum inhibitory concentrations (MICs) of MO against the tested bacteria and fractional inhibitory concentration indices (FICIs) for these combinations ranged from 0.12 to 0.75. Most of the tested CFS-MO combinations showed marked synergistic activity against S. aureus, E.coli and K. pneumoniae. In a conclusion, in vitro antibacterial study for CFS-MO combinations in our ongoing work suggests the possibility of using these combinations in clinical urinary and gastrointestinal tract infections.

Urinary tract infections in a geriatric sub-acute ward-health correlates and atypical presentations

PurposeBacterial urinary tract infections (UTIs) are the most frequently occurring infectious diseases in the geriatric population. The aim of the study was to determine the prevalence and clinical features of UTIs in geriatric in-patients and their association with health and functional ability characteristics.MethodsA prospective cross-sectional cohort study was conducted among patients hospitalized on the geriatric ward. Patients were interviewed, examined, and had their hospital records analyzed. An uncontaminated midstream urine sample was collected and cultured in all of the cases suspected for UTI. Relative risks for UTI were counted and multivariable logistic regression model was built.Results246 patients were included, 179 (72.8%) women, 210 (85.4%) 75 + -year-olds. Bacterial UTIs occurred in 18.3% of the patients. The main etiological agent was Escherichia coli (73.3%). The most significant predictors of UTI were recurrent UTI and urinary catheter. The typical clinical UTI symptoms occurred in less than half of the cases (only in 11.1% of cases fever was observed). More often, than in patients without UTIs, they reported symptoms such as delirium (28.9% vs. 18%), tachycardia (11.1% vs. 1.5%) or hypotension (20% vs. 12.1%).ConclusionsBacterial UTIs affect about 1/5 of hospitalized geriatric patients. The clinical picture of these infections very often is atypical and it indicates a need for diagnostic vigilance.

Emergency Department Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae: Many Patients Have No Identifiable Risk Factor and Discordant Empiric Therapy Is Common

Community-onset urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, which are resistant to ceftriaxone and usually coresistant to fluoroquinolones, are increasing worldwide. We investigate and describe in detail UTIs caused by ESBL-producing Enterobacteriaceae in our emergency department (ED), and determine the proportion that occurred in patients without health care-associated risk factors and who received discordant initial antibiotic therapy. At an urban public hospital in Northern California, microbiology staff prospectively reviewed ED urine culture results weekly for 1 year and presumptively identified ESBL-producing isolates by ceftriaxone plus ceftazidime resistance. For isolates associated with a clinical UTI, patient demographic and case clinical features were abstracted retrospectively. Health care-associated infections were defined by standard risk factors plus aged 65 years or older, bladder catheter, urologic procedure, functional dependence, or antibiotics in the previous 90 days. Community-associated infections were defined by absence of these. A subset of community-associated ESBL-producing Escherichia coli isolates underwent genotyping. Electronic health record query was used to determine the denominator of ED UTI patients who underwent urine culture during the study period. Between August 2016 and July 2017, there were 1,045 unique ED patients diagnosed with a UTI, whose specimens underwent culture. There were 62 ESBL-producing isolates (5.9%; 95% confidence interval [CI] 4.6% to 7.5%). Selected characteristics of the entire ESBL UTI cohort were median age 50 years, 37 (60%) patients were women, 28 (44%) Hispanic, 11 (18%) had been hospitalized in the previous 3 months, 19 (31%) had pyelonephritis, 49 (79%) of isolates were E coli, 44 (71%) were levofloxacin-resistant, and 24 (23%) nitrofurantoin-resistant. Initial antibiotic choice was discordant with isolate susceptibility in 26 of 56 cases (46%; 95% CI 33% to 60%), and the initial oral antibiotic prescred was discordant in 19 of 41 cases (46%; 95%CI 31% to 63%). Twenty-seven infections (44%; 95% CI 31% to 57%) were categorized as community-associated. Eight patientswith community-associated infection were women younger than 50 years, with no comorbidities and no more than 1 UTIin the previous year. Of 12 community-associated E coli isolates tested, all were confirmed to harbor ESBL genes; the CTX-M1 β-lactamase gene was found in 8 (67%); 4 belong to genotype ST131. At this single Northern California ED, greater than 5% of culture-proven UTI were caused by ESBL-producing Enterobacteriaceae, and in nearly half of cases there was no identifiable health care-associated risk factor. Levofloxacin co-resistance and discordant antibiotic therapy were common.

Convergence of plasmid architectures drives emergence of multi-drug resistance in a clonally diverse Escherichia coli population from a veterinary clinical care setting

The purpose of this study was to determine the plasmid architecture and context of resistance genes in multi-drug resistant (MDR) Escherichia coli strains isolated from urinary tract infections in dogs. Illumina and single-molecule real-time (SMRT) sequencing were applied to assemble the complete genomes of E. coli strains associated with clinical urinary tract infections, which were either phenotypically MDR or drug susceptible. This revealed that multiple distinct families of plasmids were associated with building an MDR phenotype. Plasmid-mediated AmpC (CMY-2) beta-lactamase resistance was associated with a clonal group of IncI1 plasmids that has remained stable in isolates collected up to a decade apart. Other plasmids, in particular those with an IncF replicon type, contained other resistance gene markers, so that the emergence of these MDR strains was driven by the accumulation of multiple plasmids, up to 5 replicons in specific cases. This study indicates that vulnerable patients, often with complex clinical histories provide a setting leading to the emergence of MDR E. coli strains in clonally distinct commensal backgrounds. While it is known that horizontally-transferred resistance supplements uropathogenic strains of E. coli such as ST131, our study demonstrates that the selection of an MDR phenotype in commensal E. coli strains can result in opportunistic infections in vulnerable patient populations. These strains provide a reservoir for the onward transfer of resistance alleles into more typically pathogenic strains and provide opportunities for the coalition of resistance and virulence determinants on plasmids as evidenced by the IncF replicons characterised in this study.

Asymptomatic Bacteriuria and Urinary Tract Infection in Pregnant Women with and without Diabetes Mellitus and Gestational Diabetes Mellitus—A Case-Control Study

Background: Asymptomatic bacteriuria (ASB) and urinary tract infections (UTI) during pregnancy may contribute to adverse pregnancy outcomes. Diabetes mellitus (DM) and gestational diabetes mellitus (GDM) are considered to be important additional risk factor for ASB and UTI during pregnancy. Aims: To investigate differences in prevalence of ASB and incidence of UTI in pregnant women with and without DM and GDM to inform ASB screening and treatment policies. Methods: Data from 214 pregnant women who gave birth during 2010 at the Women’s and Children’s Hospital, Adelaide, Australia where cases were women with a clinical diagnosis of (G)DM and controls were matched on date of birth. ASB was defined as the growth of at least 10e5 colony forming units/ml of one organism or any presence of group B streptococcus (GBS) at the first urine culture collected during pregnancy without complaints of a UTI. A clinical UTI was diagnosed by the treating physician, in combination with a positive urine culture it was defined as culture-confirmed UTI. Results: No significant differences in prevalence of ASB (5.6% and 3.7%; relative risk (RR) 1.50; 95% confidence intervals (CI) 0.44 - 5.17), incidence of clinical UTI (4.7% and 11.2%; RR 0.42; 95% CI 0.15 - 1.14) or culture-confirmed UTI (2.8% and 3.7%; RR 0.75; 95% CI 0.17 - 3.27) between pregnant women with and without (G)DM were present. No association was found between ASB and UTI. GBS was the most common causative organism of ASB in women with and without DM (66.7% and 50.0%). Conclusion: In contrast with earlier research, no significant differences in prevalence of ASB or incidence of UTI was found between pregnant women with and without (G)DM.

The economic burden of urinary tract infections in women visiting general practices in France: a cross-sectional survey.

BackgroundUrinary tract infections (UTIs) are among the most common bacterial infections. Despite this burden, there are few studies of the costs of UTIs. The objective of this study was to determine the costs of UTIs in women over 18 years of age who visit general practitioners in France.MethodsThe direct and indirect costs of clinical UTIs were estimated from societal, French National Health Insurance and patient perspectives. The study population was derived from a national cross-sectional survey entitled the Drug-Resistant Urinary Tract Infection (Druti). The Druti included every woman over 18 years of age who presented with symptoms of UTI and was conducted in France in 2012 and 2013 to estimate the annual incidence of UTIs due to antibiotic-resistant Enterobacteriaceae in women visiting general practitioners (GPs) for suspected UTIs.ResultsOf the 538 women included in Druti, 460 were followed over 8 weeks and included in the cost analysis. The mean age of the women was 46 years old. The median cost of care for one episode of a suspected UTI was €38, and the mean cost was €70. The annual societal cost was €58 million, and €29 million of this was reimbursed by the French National Health Insurance system. In 25 % of the cases, the suspected UTIs were associated with negative urine cultures. The societal cost of these suspected UTIs with negative urine cultures was €13.5 million. No significant difference was found between the costs of the UTIs due to antibiotic-resistant E. coli and those due to wild E. coli (p = 0.63).ConclusionIn the current context in which the care costs are continually increasing, the results of this study suggests that it is possible to decrease the cost of UTIs by reducing the costs of suspected UTIs and unnecessary treatments, as well as limiting the use of non-recommended tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-016-1620-2) contains supplementary material, which is available to authorized users.

Consumption of a cranberry juice beverage lowered the number of clinical urinary tract infection episodes in women with a recent history of urinary tract infection

Urinary tract infections (UTIs) are among the most common bacterial infections and are often treated with antibiotics. Concerns about multidrug-resistant uropathogens have pointed to the need for safe and effective UTI-prevention strategies such as cranberry consumption. We assessed the effects of the consumption of a cranberry beverage on episodes of clinical UTIs. In this randomized, double-blind, placebo-controlled, multicenter clinical trial, women with a history of a recent UTI were assigned to consume one 240-mL serving of cranberry beverage/d (n = 185) or a placebo (n = 188) beverage for 24 wk. The primary outcome was the clinical UTI incidence density, which was defined as the total number of clinical UTI events (including multiple events per subject when applicable) per unit of observation time. The dates of the random assignment of the first subject and the last subject's final visit were February 2013 and March 2015, respectively. The mean age was 40.9 y, and characteristics were similar in both groups. Compliance with study product consumption was 98%, and 86% of subjects completed the treatment period in both groups. There were 39 investigator-diagnosed episodes of clinical UTI in the cranberry group compared with 67 episodes in the placebo group (antibiotic use-adjusted incidence rate ratio: 0.61; 95% CI: 0.41, 0.91; P = 0.016). Clinical UTI with pyuria was also significantly reduced (incidence rate ratio: 0.63; 95% CI: 0.40, 0.97; P = 0.037). One clinical UTI event was prevented for every 3.2 woman-years (95% CI: 2.0, 13.1 woman-years) of the cranberry intervention. The time to UTI with culture positivity did not differ significantly between groups (HR: 0.97; 95% CI: 0.56, 1.67; P = 0.914). The consumption of a cranberry juice beverage lowered the number of clinical UTI episodes in women with a recent history of UTI. This study was registered at clinicaltrials.gov as NCT01776021.