Urinary Tract Infection Susceptibility Research Articles

Ribonuclease 7 polymorphism rs1263872 reduces antimicrobial activity and associates with pediatric urinary tract infections.

Ribonuclease 7 (RNase 7) is an antimicrobial peptide that prevents urinary tract infections (UTI); however, it is yet unknown how RNASE7 genetic variations affect its antimicrobial activity and its mitigation of UTI risk. This study determined whether the RNASE7 SNP rs1263872 is more prevalent in children with UTI and defined how rs1263872 affects RNase 7's antimicrobial activity against uropathogenic E. coli (UPEC). We performed genotyping for rs1263872 in 2 national UTI cohorts, including children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux trial or the Careful Urinary Tract Infection Evaluation study. Genotypes from these cohorts were compared with those of female controls with no UTI. To assess whether rs1263872 affects RNase 7's antimicrobial activity, we generated RNase 7 peptides and genetically modified urothelial cultures encoding wild-type RNase 7 and its variant. Compared with controls, girls in both UTI cohorts had an increased prevalence of the RNASE7 variant. Compared with the missense variant, wild-type RNase 7 peptide showed greater bactericidal activity against UPEC. Wild-type RNase 7 overexpression in human urothelial cultures reduced UPEC invasive infection compared with mutant overexpression. These results show that children with UTI have an increased prevalence of RNASE7 rs1263872, which may increase UTI susceptibility by suppressing RNase 7's antibacterial activity.

Longitudinal Follow-Up of Urinary Tract Infections and Their Treatment in Mice using Bioluminescence Imaging.

Urinary tract infections (UTI) rank among the most common bacterial infections in humans and are routinely treated with empirical antibiotics. However, due to increasing microbial resistance, the efficacy of the most used antibiotics has declined. To find alternative treatment options, there is a great need for a better understanding of the UTI pathogenesis and the mechanisms that determine UTI susceptibility. In order to investigate this in an animal model, a reproducible, non-invasive assay to study the course of UTI is indispensable. For years, the gold standard for the enumeration of bacterial load has been the determination of Colony Forming Units (CFU) for a particular sample volume. This technique requires post-mortem organ homogenates and serial dilutions, limiting data output and reproducibility. As an alternative, bioluminescence imaging (BLI) is gaining popularity to determine the bacterial load. Labeling pathogens with a lux operon allow for the sensitive detection and quantification in a non-invasive manner, thereby enabling longitudinal follow-up. So far, the adoption of BLI in UTI research remains limited. This manuscript describes the practical implementation of BLI in a mouse urinary tract infection model. Here, a step-by-step guide for culturing bacteria, intravesical instillation and imaging is provided. The in vivo correlation with CFU is examined and a proof-of-concept is provided by comparing the bacterial load of untreated infected animals with antibiotic-treated animals. Furthermore, the advantages, limitations, and considerations specific to the implementation of BLI in an in vivo UTI model are discussed. The implementation of BLI in the UTI research field will greatly facilitate research on the pathogenesis of UTI and the discovery of new ways to prevent and treat UTI.

Validation of point-of-care device for rapid detection of urinary tract infection and antibiotic susceptibility

Urinary tract infections (UTI) presents a high prevalence in the community setting. Rapid and accurate microbiological diagnosis is essential to ensure adequate and effective therapy. To evaluate a rapid antibiogram kit (KAR®) in point-of-care format for rapid detection of UTI and antibiotic susceptibility. The KAR® device has been designed and developed in collaboration with technical engineers and clinical microbiologists. Its evaluation has been carried out through a multicenter study in which three Spanish hospitals have participated. Thus, different in vivo tests have been implemented in order to determine device correlation with the reference microbiological techniques. During the study period, a total of 400 urine samples from patients with suspected ITU were tested. The KAR® device provided fast results (mean positivity time of 7,8 ± 1,5 hours) with 97% sensitivity, 89% specificity and 87% agreement for the detection of significant bacteriuria. The percentages of specificity for the antibiotics tested were: ciprofloxacin (97%), fosfomycin (94%),cotrimoxazole (84%), ampicillin (80%) and amoxicillin/clavulanic acid (55%). The KAR® device could be a useful tool for diagnosing UTI in outpatients, especially in areas of low socio-economic level.

Effects of Dapagliflozin-Induced Glucosuria on Urinary Tract Infection Susceptibility

Effects of Dapagliflozin-Induced Glucosuria on Urinary Tract Infection Susceptibility

P0285A COMPARISON OF URINE MICROSCOPY AND CULTURE IN HIV-INFECTED AND NON HIV-INFECTED INDIVIDUALS IN THE ANTI-RETROVIRAL ERA

Abstract Background and Aims Urinary tract infection is among the most common causes of sepsis presenting in hospitals. The aim was to collect data to enable empirical treatment of urinary tract infections in HIV negative and positive nephrology patients while waiting for urine culture results in order to reduce hospital stay. Our aim is also to assess incidence and antimicrobial susceptibility of urinary tract infections in HIV negative and positive patients. Method A retrospective chart review of nephrology patients admitted from January to December 2014 in Nephrology ward and the first consecutive 200 outpatients seen in Nephrology clinic in 2014 at Inkosi Albert Luthuli Central Hospital was conducted. Information was gathered with the use of a data collection sheet and urinary tract infection was based on urine culture results. All data was analysed using Statistical Package for Social Sciences version 23. Percentages of basic characteristics were calculated between groups. Logistic regression analysis was used to identify factors associated with positive urine culture. Results There were 654 patients in the study, 514 (79%) were HIV negative and 139 (21%) were HIV positive. The incidence of UTI in nephrology patients was 9%, 10.1% in inpatients and 6.5% in outpatients. 22% were HIV positive (p value 0.883, 95% CI 0.550-2.003). 19% had Diabetes mellitus, 15% had Systemic Lupus Erythematosus and 5% were post renal transplant patients. Escherichia coli and Klebsiella pneumonia were the common causes of urinary tract infection at 40.7% and 15.3% respectively with 22% cases on extended beta lactam resistance. Conclusion There was no statistically significant difference on the incidence and anti-microbial isolates between HIV infected and HIV negative nephrology patients with urinary tract infection. Hence, empirical treatment for UTI should remain the same in the 2 groups. Escherichia coli and Klebsiella pneumoniae were the most commonly cultured organisms in both groups. There is microbial resistance to commonly used antibiotics. Constant assessment of anti-microbial sensitivity of urinary tract infections is of paramount importance.

Etiology and bacterial susceptibility to antibiotics in patients with recurrent lower urinary tract infections.

Recurrent urinary tract infections (UTIs) are a frequent health problem and a common reason for treatment resistance. The purpose of the study was to evaluate the etiology of community‑ acquired lower recurrent UTI and bacterial antibiotic susceptibility. A total of 796 microbiological urine cultures from 332 patients (280 women and 52 men) treated in a single nephrology outpatient department in central Poland in years 2016 to 2018 were analyzed. The most frequent species responsible for recurrent lower UTI were identified and the susceptibility of all the microbes to specific antibiotics was assessed. The patients' kidney function and inflammation parameters were evaluated. The median (interquartile range [IQR]) age of the patients was 65 (59-77) years (women, 69 [57-78] years; men, 67 [62-77] years), median (IQR) glomerular filtration rate was 56.6 (40.2-81.3) ml/min/1.73 m2 with median (IQR) C‑ reactive protein concentration of 3.2 (1.5-7.0) mg/l. There were 43 bacterial species identified: 24 gram‑positive and 19 gram-negative. The analyzed urine cultures contained 977 microbial samples (563 gram‑negative bacteria, 408 gram-positive, 6 fungi). The most common bacteria was Escherichia coli (39.6%) which showed 100% susceptibility to carbapenems, 98.9% to amikacin, 96.5% to piperacillin / tazobactam, and 94.3% to gentamicin. With regard to oral antibiotics, its highest susceptibility was to fosfomycin 95.5%, nitrofurantoin 85.5%, and cefuroxime 82.3%. In 39.9% of cases, E. coli was resistant to fluoroquinolones and in 46.6% to trimethoprim / sulfamethoxazole. The most frequently occurring bacteria causing recurrent lower UTI are characterized by significant resistance to the antimicrobial therapy recommended as the first‑ line treatment: fluoroquinolones and trimethoprim / sulfamethoxazole. It seems that the first choice in the treatment of lower UTIs should be: fosfomycin, nitrofurantoin, or cefuroxime.

Early Increased Urinary IL-2 and IL-10 Levels Were Associated With Development of Chronic UTI in a Murine Model

To analyze factors during early stage of urinary tract infection (UTI) that are associated with development of chronic UTI. Mice were inoculated with Uropathogenic Escherichia coli (UPEC) 2 times 24 hours apart. At 1, 3, 7, 10, 14, 21 and 28 days post infection (dpi), urine bacterial loads and voiding behavior (voiding spot assay, VSA) were measured. At 1 and 28 dpi, 32 urine inflammatory cytokines/chemokines were measured using enzyme-linked immunosorbent assay (ELISA). Bladder and kidney cytokines/chemokines were measured on 28 dpi. Mice that had no more than 1 episode of urine bacterial load < 104 colony forming unit/ml during the entire 4 weeks were defined as susceptible to chronic UTI, otherwise, mice were considered resistant. At 28 dpi, 64.3% mice developed chronic UTI (susceptible group) and 35.7% mice did not (resistant group). Factors at 1 dpi that were predictive of chronic UTI included increased urine IL-2 (OR 11.9, 95%CI 1.1-130.8, P=.043) and increased urine IL-10 (OR 14.0, 95%CI 1.0-201.2, P=.052). At 28 dpi, there were several significant differences between the susceptible vs resistant groups including urine/tissue bacterial loads and certain urine/tissue cytokines/chemokines. Higher urine IL-2 and IL-10 at 1 dpi predicted chronic UTI infection in this model. There have been recent publications associating both of these cytokines to UTI susceptibility. Further explorations into IL-2 and IL-10 mediated pathways could shed light on the biology of recurrent and chronic UTI which are difficult to treat.

Bacterial Pathogens of Patients with Urinary Tract Infections and Antibiotics Susceptibility in Taiz Governorate-Yemen

One of the most prevalent bacterial infections are urinary tract infections (UTIs), which affect any age of individuals and they appear higher in women than men, the major problem regarding UTIs are the difficult of antibiotics treatment, due to bacterial pathogens resistance. So, the current study aimed to detect the types of bacterial pathogens and their antibiotics susceptibility of UTIs in Taiz Governorate – Yemen. In this cohort study, one hundred and ten (110) mid-stream urine samples were collected from a symptomatic UTIs patient, the type of bacterial pathogens was identified by using standard bacteriological media and biochemical tests and determine the antibiotics sensitivity to these bacteria using disk diffusion tests. Out of one hundred and ten of urine samples:: 65 of patients were females and 45 were males and the bacterial growth in these patients were sixty-four [46(58.2%)] : (33.7%) were females and (24.5%) were males. Our findings showed that the types of bacterial pathogens include: Escherichia coli (32.7%), Klebsiellapneumoniae (9.1%), Staphylococcus aureus (6.4%), Proteus mirabilis (5.5%) and Pseudomonas aeruginosa (4.5%). The majority (57.9%) of the isolates were from female. The prevalence of UTIs is high among patients with age between 16-30 years with the incident rate 20.9 %, age groups 1-15 years have the lower incidence rate 5.5%. UTIs were more prevalent among the rural area population, there were 50% than the population of the city center, there were 8.2% and the rate of infections were more prevalent among illiterate (no read and write) patients with incidence rate 44.5% , compared to literate (read and write) patients 13.6%. Also, our results showed that the sensitivity test against bacterial pathogens as All bacterial isolates was more sensitive to Ciprofloxacin, followed by Amikacin, Gentamycin , Cefotaxime (except Staphylococcus aureus Cefotaxime (42.9%) and Ceftriaxone (except Staphylococcus aureus) (28.6%). Staphylococcus aureus isolated also were sensitive to Erythromycin, Rifampicin, and Cephalothin. Finally, all isolates showed very high rate of resistance against Amoxicillin, ampicillin and penicillin G.

DNA copy number variations in children with vesicoureteral reflux and urinary tract infections.

Vesicoureteral reflux (VUR) is a complex, heritable disorder. Genome-wide linkage analyses of families affected by VUR have revealed multiple genomic loci linked to VUR. These loci normally harbor a number of genes whose biologically functional variant is yet to be identified. DNA copy number variations (CNVs) have not been extensively studied at high resolution in VUR patients. In this study, we performed array comparative genomic hybridization (aCGH) on a cohort of patients with a history of both VUR and urinary tract infection (UTI) with the objective of identifying genetic variations responsible for VUR and/or UTI susceptibility. UTI/VUR-associated CNVs were identified by aCGH results from the 192 Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) patients compared to 683 controls. Rare, large CNVs that are likely pathogenic and lead to VUR development were identified using stringent analysis criteria. Because UTI is a common affliction with multiple risk factors, we utilized standard analysis to identify potential disease-modifying CNVs that can contribute to UTI risk. Gene ontology analysis identified that CNVs in innate immunity and development genes were enriched in RIVUR patients. CNVs affecting innate immune genes may contribute to UTI susceptibility in VUR patients and may provide the first step in assisting clinical medicine in determining adverse outcome risk in children with VUR.

Association between interleukin 8-receptor gene (CXCR1 and CXCR2) polymorphisms and urinary tract infection: Evidence from 4097 subjects.

The aim of this study was to determine whether a correlation exists between interleukin-8 receptor polymorphisms and urinary tract infection (UTI) susceptibility. We systematically searched electronic databases including PubMed, Embase, China National Knowledge Infrastructure, and Web of Science up to 5 November 2017 to select appropriate studies that focused on C-X-C chemokine receptor type 1 and/or 2 (CXCR1, CXCR2) polymorphisms with susceptibility to UTI. Eight case-control studies including 2085 patients with UTI and 2012 controls were enrolled in this study. Seven studies of CXCR1 rs2234671 and two studies of rs3138086 were included in the meta-analyses. Pooled odds ratio (OR) and corresponding 95% confidence interval (CI) were synthesized using fixed-effects or random-effects model according to heterogeneity. No significant correlations were found between CXCR1 rs2234671 and rs3138086 polymorphisms and UTI susceptibility. However, subgroup analysis showed that rs2234671 was associated with an increased risk of UTI under allelic comparisons (C vs. G, OR = 1.95, 95% CI = 1.07-3.55), heterozygous model (GC vs. GG, OR = 1.93, 95% CI = 1.06-3.50), and dominant model (GC + CC vs. GG, OR = 1.98, 95% CI = 1.07-3.69) in children, especially in paediatric patients with acute pyelonephritis (allelic, OR = 2.43, 95% CI = 1.28-4.60; heterozygous, OR = 2.40, 95% CI = 1.24-4.62; dominant, OR = 2.48, 95% CI = 1.26-4.88). Furthermore, these results remained the same after eliminating paediatric patients with vesicoureteral reflux. CXCR1 rs2234671 polymorphism might be associated with an increased risk of UTI in children.

Insulin receptor signaling regulates renal collecting duct and intercalated cell antibacterial defenses.

People with diabetes mellitus have increased infection risk. With diabetes, urinary tract infection (UTI) is more common and has worse outcomes. Here, we investigate how diabetes and insulin resistance impact the kidney's innate defenses and urine sterility. We report that type 2 diabetic mice have increased UTI risk. Moreover, insulin-resistant prediabetic mice have increased UTI susceptibility, independent of hyperglycemia or glucosuria. To identify how insulin resistance affects renal antimicrobial defenses, we genetically deleted the insulin receptor in the kidney's collecting tubules and intercalated cells. Intercalated cells, located within collecting tubules, contribute to epithelial defenses by acidifying the urine and secreting antimicrobial peptides (AMPs) into the urinary stream. Collecting duct and intercalated cell-specific insulin receptor deletion did not impact urine acidification, suppressed downstream insulin-mediated targets and AMP expression, and increased UTI susceptibility. Specifically, insulin receptor-mediated signaling regulates AMPs, including lipocalin 2 and ribonuclease 4, via phosphatidylinositol-3-kinase signaling. These data suggest that insulin signaling plays a critical role in renal antibacterial defenses.

Novel role for androgen signaling in pyelonephritis

Sex differences in urinary tract infection (UTI) susceptibility and severity are known, but have historically focused on anatomic differences between males and females. Until recently, experimental UTI has been limited to female animals due to ease of transurethral bladder catheterization. Olson and colleagues have developed a model of experimental UTI independent of sex that relies on direct bladder inoculation and thus permits investigation of sex differences in UTI susceptibility. They now build upon their prior work in this model by implicating androgens as drivers of tubular invasion by uropathogenic Escherichia coli, which form luminal bacterial communities preceding renal abscess formation.

Bacterial Profile of Urinary Tract Infection and Antimicrobial Susceptibility Pattern Among Patients Attending at Bushra Medical Laboratory, Tripoli, Libya

BACKGROUND: Urinary tract infection (UTI) is a common infection that affects the urinary tract, particularly in women, children and elderly, and it doesn’t always cause classic signs and symptoms. Excessive utilization of antibiotics led to increased incidence of antibiotic resistance among uropathogens worldwide. AIM: To identify the causative bacteria of UTI and antimicrobial susceptibility pattern among patients attended to Bushra Medical laboratory, Tripoli, Libya. METHODS: This prospective study was conducted in Tripoli city, on 1423 urine specimens from untreated patients with clinical symptoms of UTIs. Bacterial identification and antimicrobial susceptibility testing were done on 291 specimens which their colony count ≥ 105 colony forming units (cfu)/mL, using DL-96II (Auto microbial identification and antimicrobial susceptibility testing system). RESULTS: The prevalence of significant bacteriuria was 20.4% (291/1423), among them 81.4% (237/291) were females and 18.6% (54/291) were males. Just 0.7% (2/291) cases of isolated bacteria were gram positive cocci represented in Staphylococcus aureus, that exhibited hugely resistance to Penicillin (100%) and susceptible to many tested antimicrobial agents, while 99.3% (289/291) were gram negative bacilli represented in Klebsiella pneumonia 43.6% (127/291); Escherichia coli 33% (96/291); Klebsiella ozaenae 10.7% (31/291); Proteus mirabilis 9.3% (27/291); Pseudomonas mendocina 1.7% (5/291) and Pseudomonas alcaligenes 1% (3/291). Considering the results of this study, Klebsiella pneumonia isolates were the predominant pathogens in UTI. Except for Pseudomonas isolates, our data demonstrated that gram negative isolates were susceptible to Cefoperazone/Sulbactam followed by Ceftazidime then Levofloxacin (3.9%, 4.9% and 6% resistance, respectively), while Pseudomonas isolates were extremely sensitive to Amikacin, Piperacillin and Norfloxacin. CONCLUSION: Because of highly resistant bacteria to antibiotics, physicians must prescribe appropriate antibiotics depending on antibiotics susceptibility results. Otherwise, routine monitoring of antimicrobial resistance among uropathogens must be accomplished to guide the treatment of UTIs in the country.

Uropathogens and Antibiotic Resistance Among Nursing Home Residents - National Healthcare Safety Network (NHSN)

BackgroundKnowledge of urinary tract infection (UTI) pathogen and susceptibility patterns is necessary to inform antibiotic prescribing and monitor resistance. We describe bacterial pathogens and UTI antibiotic resistance patterns among residents in nursing homes (NHs) reporting to the National Healthcare Safety Network (NHSN) long-term care facility (LTCF) component.MethodsAll UTI events from January 1, 2013 to December 31, 2016 were included; up to three organisms per UTI event may be reported. Pathogen susceptibility results for selected antibiotics are reported as: Susceptible (S), Intermediate (I), Resistant (R), or Not tested (N). For this analysis, resistance was defined as I or R. We described pathogens and summarized antibiotic resistance only when ≥100 isolates of a bacterial species had susceptibility test results for a particular antibiotic reported to NHSN.ResultsIn 166 NHs located in 37 states, a total of 4,054 pathogens were reported for 2,827 residents. Six organisms accounted for 81% of all UTI events (n = 3,599) (Table). A large proportion of Escherichia coli isolates, which accounted for 41% of uropathogens, were resistant to trimethoprim-sulfamethoxazole (35%) and levofloxacin (50%). Among Proteus mirabilis isolates, 53% were resistant to levofloxacin (Figure). Methicillin resistance was 74% among Staphylococcus aureus, and vancomycin resistance among Enterococcus spp. was 18%.ConclusionThis is the first summary of UTI pathogens and susceptibility data from U.S. nursing homes reporting to a national surveillance system. Resistance to antibiotics commonly used to treat UTIs was high. Tracking and preventing resistance for key pathogens is a CDC priority and NHSN reporting by NHs provides a crucial opportunity to track antibiotic resistance, highlighting the importance of enrolling more NHs into NHSN.Table: Top Nursing Home Uropathogens - NHSN, January 2013–December 2016 Pathogen N % Escherichia coli 1,64841 Proteus mirabilis 52413 Enterococcus spp. 44111 Klebsiella pneumoniae 41210 Pseudomonas aeruginosa 2566 Staphylococcus aureus 1223Note: Enterococcus spp. includes E. faecium and E. fecalis.Disclosures All authors: No reported disclosures.

PD12-02 ANTIMICROBIAL GENE EXPRESSION AND UTI SUSCEPTIBILITY IS DEPENDENT ON IL-6/STAT3 SIGNALING

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2017PD12-02 ANTIMICROBIAL GENE EXPRESSION AND UTI SUSCEPTIBILITY IS DEPENDENT ON IL-6/STAT3 SIGNALING Christina Ching, Sudipti Gupta, Birong Li, and Brian Becknell Christina ChingChristina Ching More articles by this author , Sudipti GuptaSudipti Gupta More articles by this author , Birong LiBirong Li More articles by this author , and Brian BecknellBrian Becknell More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.677AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urinary tract infections (UTI) are a significant source of morbidity. Due to rising antibiotic resistance patterns, alternate treatments are needed. Prior work has demonstrated induction of urine and serum IL-6 in pyelonephritis and renal scarring. IL-6 has been linked to antimicrobial peptide (AMP) production in other organs via Stat3 phosphorylation on Tyr705. As a result, we sought to evaluate the potential role of IL-6/Stat3 induced signaling on urothelial AMP expression and UTI susceptibility. METHODS We infected 6 week old female C57BL/6J or C3H/HeOuJ mice transurethrally with UPEC and measured IL-6, phosphorylated (p-)Stat3, and AMP expression by ELISA, qRT-PCR, Western blotting, and immunofluorescence microscopy. The requirement for Lipopolysaccharide (Lps) / Toll-like receptor 4 (Tlr4) signaling was established using Lps-hyporesponsive C3H/HeJ mice, compared to C3H/HeOuJ Lps-sensitive controls. We evaluated the roles of IL-6 in p-Stat3, AMP production, and UPEC clearance using IL-6 neutralizing antibody and IL-6 knock out (KO) mice. We determined the contribution of Stat3 to AMP production via tamoxifen-inducible Stat3 conditional KO mice. We measured bacterial burden by serial plating on LB agar. Results were evaluated by Mann-Whitney U test with p <0.05 being significant. RESULTS Upon UPEC infection, we observed a time dependent induction of urinary IL-6 secretion and bladder p-Stat3. Sustained expression of IL-6 and p-Stat3 required intact Tlr4 signaling. P-Stat3 localized to the nuclei of infected bladder urothelium. Bladder AMP mRNA levels increased following peak IL-6 secretion and p-Stat3. IL-6 KO mice exhibited absent urothelial p-Stat3 and severely blunted AMP mRNA induction following experimental UTI, leading to impaired UPEC clearance. Conversely, intraperitoneal administration of recombinant IL-6 induced bladder p-Stat3 and AMP expression in the absence of infection. Conditional Stat3 deletion reduced bladder AMP mRNA levels at baseline and following experimental UTI. IL-6 neutralizing antibody reduced p-Stat3 levels in C3H/HeOuJ mice, with increased renal UPEC colonization and pyelonephritis severity. CONCLUSIONS IL-6 is both necessary and sufficient for urothelial p-Stat3 and AMP transcription, and genetic or acquired IL-6 deficiency leads to increased UTI susceptibility. This implicates IL-6 and Stat3 as master regulators of urothelial AMP transcription in states of sterility and infection. Therapeutic manipulation of the IL-6/Stat3 axis provides a mechanism to alter AMP expression to treat and even prevent UTI. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e265-e266 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Christina Ching More articles by this author Sudipti Gupta More articles by this author Birong Li More articles by this author Brian Becknell More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Susceptibility to Urinary Tract Infection: Benefits and Hazards of the Antibacterial Host Response.

A paradigm shift is needed to improve and personalize the diagnosis of infectious disease and to select appropriate therapies. For many years, only the most severe and complicated bacterial infections received more detailed diagnostic and therapeutic attention as the efficiency of antibiotic therapy has guaranteed efficient treatment of patients suffering from the most common infections. Indeed, treatability almost became a rationale not to analyze bacterial and host parameters in these larger patient groups. Due to the rapid spread of antibiotic resistance, common infections like respiratory tract- or urinary-tract infections (UTIs) now pose new and significant therapeutic challenges. It is fortunate and timely that infectious disease research can offer such a wealth of new molecular information that is ready to use for the identification of susceptible patients and design of new suitable therapies. Paradoxically, the threat of antibiotic resistance may become a window of opportunity, by encouraging the implementation of new diagnostic and therapeutic approaches. The frequency of antibiotic resistance is rising rapidly in uropathogenic organisms and the molecular and genetic understanding of UTI susceptibility is quite advanced. More bold translation of the new molecular diagnostic and therapeutic tools would not just be possible but of great potential benefit in this patient group. This chapter reviews the molecular basis for susceptibility to UTI, including recent advances in genetics, and discusses the consequences for diagnosis and therapy. By dissecting the increasingly well-defined molecular interactions between bacteria and host and the molecular features of excessive bacterial virulence or host-response malfunction, it is becoming possible to isolate the defensive from the damaging aspects of the host response. Distinguishing "good" from "bad" inflammation has been a long-term quest of biomedical science and in UTI, patients need the "good" aspects of the inflammatory response to resist infection while avoiding the "bad" aspects, causing chronicity and tissue damage.

Genetic Variations in Vesicoureteral Reflux Sequelae.

Urinary tract infections (UTI) are a common condition in children. Vesicoureteral reflux (VUR) represents a common associated condition with childhood UTI. UTI susceptibility appears to have a genetic component based on family and UTI cohort studies. Targeted analysis of innate immune system genetic variations indicate that these variations are important in UTI susceptibility. In this overview, we discuss how current cohorts and genetic strategies can be implemented to discover new susceptibility loci in patients with UTI.

Androgens Enhance Male Urinary Tract Infection Severity in a New Model.

Urinary tract infections (UTIs) occur predominantly in females but also affect substantial male patient populations; indeed, morbidity in complicated UTI is higher in males. Because of technical obstacles, preclinical modeling of UTI in male mice has been limited. We devised a minimally invasive surgical bladder inoculation technique that yields reproducible upper and lower UTI in both male and female mice, enabling studies of sex differences in these infections. Acute uropathogenic Escherichia coli (UPEC) cystitis in C57BL/6 and C3H/HeN males recapitulated the intracellular bacterial community pathway previously shown in females. However, surgically infected females of these strains exhibited more robust bladder cytokine responses and more efficient UPEC control than males. Compared with females, C3H/HeN males displayed a striking predilection for chronic cystitis, manifesting as persistent bacteriuria, high-titer bladder bacterial burdens, and chronic inflammation. Furthermore, males developed more severe pyelonephritis and 100% penetrant renal abscess (a complication that is rare in female mice). These phenotypes were sharply abrogated after castration but restored with exogenous testosterone, suggesting that male susceptibility to UTI is strongly influenced by androgen exposure. These data substantiate the long-standing presumption that anatomic differences in urogenital anatomy confer protection from UTI in males; however, as clinically observed, male sex associated with more severe UTI once these traditional anatomic barriers were bypassed. This study introduces a highly tractable preclinical model for interrogating sex differences in UTI susceptibility and pathogenesis, and illuminates an interplay between host sex and UTI that is more complex than previously appreciated.

Urinary tract infection, its causative microorganism and antibiotic susceptibility in Nagaland

Aim: We studied the causative microorganisms and antibiotic susceptibility of urinary tract infections (UTI) for both male and female in Nagaland, North-Eastern India. Materials and Methods: This is a retrospective study done at Christian Institute of Health Sciences and Research, Dimapur, where urinary samples received for culture and sensitivity in the laboratory from January 2012 to June 2013 were included. Organisms were identified by doing standard culture method, and antibiotic sensitivity was done by Kirby-Bauer Disc diffusion method from mid-stream clean catch urine sample. Results: A total of 1789 samples were analyzed in this study, where 502 (28.1%) showed significant growth, 330 (18.4%) showed insignificant growth, and the rest 957 (53.5%) showed no growth. The most commonly isolated bacterium was Escherichia coli both in an outpatient department (31%) and in-patient department (38%) patients followed by Klebsiella pneumonia, Pseudomonas sp., Enterococcus, Staphylococcus aureus, Candida, and Proteus. Analysis of the samples showed that UTI was more common in females (60%) as compared to males (40%). It was also observed that the samples responded effectively to chloramphenicol (29%), gentamicin (28%), imipenem (26%), and amikacin (21%). High degree of resistance was shown for nalidixic acid, ciprofloxacin, norfloxacin, amoxyclav, and ofloxacin. Conclusion: Antibiotics have been in use for a long period and more often the misuse of antimicrobial drugs has today led to a general rise in the emergence of resistant bacteria. This study may aid health professionals in choosing the appropriate treatment for patients in North-Eastern India.

Impact of host age and parity on susceptibility to severe urinary tract infection in a murine model.

The epidemiology and bacteriology of urinary tract infection (UTI) varies across the human lifespan, but the reasons for these differences are poorly understood. Using established monomicrobial and polymicrobial murine UTI models caused by uropathogenic Escherichia coli (UPEC) and/or Group B Streptococcus (GBS), we demonstrate age and parity as inter-related factors contributing to UTI susceptibility. Young nulliparous animals exhibited 10–100-fold higher bacterial titers compared to older animals. In contrast, multiparity was associated with more severe acute cystitis in older animals compared to age-matched nulliparous controls, particularly in the context of polymicrobial infection where UPEC titers were ∼1000-fold higher in the multiparous compared to the nulliparous host. Multiparity was also associated with significantly increased risk of chronic high titer UPEC cystitis and ascending pyelonephritis. Further evidence is provided that the increased UPEC load in multiparous animals required TLR4-signaling. Together, these data strongly suggest that the experience of childbearing fundamentally and permanently changes the urinary tract and its response to pathogens in a manner that increases susceptibility to severe UTI. Moreover, this murine model provides a system for dissecting these and other lifespan-associated risk factors contributing to severe UTI in at-risk groups.