Antibiotic-resistant Urinary Tract Infections Research Articles

Current and emerging strategies to curb antibiotic-resistant urinary tract infections.

Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.

Exploring the Antimicrobial Potential of Cyperus rotundus Extract Against Multidrug-Resistant Escherichia coli in Urinary Tract Infections

The widespread use of antibiotics has contributed to the emergence of antibiotic-resistant bacteria, including Escherichia coli (E. coli), a primary cause of urinary tract infections (UTIs). The increasing antimicrobial resistance levels have prompted research into alternative treatments, such as medicinal plants, to counter this global health concern. This study aimed to evaluate the effectiveness of solvent extracts from Cyperus rotundus (C. rotundus) against multidrug-resistant strains of E. coli associated with UTIs, as well as examine the phytochemical characteristics of the plant extract. E. coli isolates from pregnant women with UTIs were collected from several clinical laboratories, and their antibiotic resistance levels were evaluated. The antimicrobial activity of the C. rotundus extract was assessed using the agar-well diffusion method. In addition, GC-MS analysis was employed to screen for qualitative phytochemicals and secondary metabolites. The C. rotundus extract demonstrated significant inhibitory results on the resistant isolates, with a zone of inhibition ranging from 9mm to 17mm. The extract was found to contain various phytochemicals such as alkaloids, flavonoids, phenolics, tannins, and triterpenoids. GC-MS analysis detected bioactive compounds such as 3, 4-Altrosan, Phytol, Isoquinoline, and beta-sitosterol. These findings show that C. rotundus has the potential to be a valuable resource in the fight against antibiotic-resistant UTIs, underscoring the need for further investigation.

Escherichia coli dominance and antimicrobial resistance in urinary tract infections among diabetic patients: Insights from Birnin Kebbi Metropolis, Nigeria

Background: The global rise in antibiotic-resistant urinary tract infections (UTIs) is a growing concern, particularly among diabetic patients. This study examines the antibiotic resistance patterns of bacterial uropathogens in diabetic patients at Sir Yahaya Memorial Hospital in Birnin Kebbi.
 Methods: A purposive sampling approach was used to collect 51 mid-stream urine samples in sterile containers. Cultural and biochemical methods were employed for the isolation and identification of uropathogenic bacteria. Antibiotic sensitivity testing was performed using the disc diffusion method, with results interpreted according to the Clinical Laboratory Standards Institute (CLSI) guidelines.
 Results: UTIs were prevalent in 23.5% (12/51) of the samples. Escherichia coli was the most prevalent uropathogen, accounting for 41.3% (7/17) of cases, followed by Klebsiella pneumoniae at 23.5% (4/17). Staphylococcus aureus and Proteus mirabilis each contributed to 17.6% (3/17) of cases. Notably, E. coli and K. pneumoniae exhibited 100% resistance to chloramphenicol and sparfloxacin, respectively.
 Conclusion: These findings underscore the need for further molecular research to characterize these uropathogens and identify the genes contributing to antibiotic resistance.

Bacteriophage-based approach for treatment of urinary tract infections: a quick outlook.

Urinary tract infections (UTIs) are among the most common bacterial infections affecting millions worldwide. The increasing emergence of antibiotic-resistant bacteria has become a serious concern in managing UTIs. Therefore, there is a growing interest in using bacteriophages as an alternative or adjunct therapy for UTIs. Bacteriophages are viruses that infect and kill bacteria, making them a promising tool for treating UTIs caused by antibiotic-resistant bacteria. This article provides a quick outlook on using bacteriophages to treat UTIs. We summarize the current understanding of the biology of bacteriophages, the challenges associated with developing phage-based therapies, and the promising results of several case reports and clinical trials. We also highlight the potential of phage therapy as a valuable tool in the fight against antibiotic-resistant UTIs. This quick outlook on a bacteriophage-based approach for treating UTIs offers a timely and informative summary of the current research in this field.

Development of a Prediction Model for Antibiotic-Resistant Urinary Tract Infections Using Integrated Electronic Health Records from Multiple Clinics in North-Central Florida.

Urinary tract infections (UTIs) are common infections for which initial antibiotic treatment decisions are empirically based, often without antibiotic susceptibility testing to evaluate resistance, increasing the risk of inappropriate therapy. We hypothesized that models based on electronic health records (EHR) could assist in the identification of patients at higher risk for antibiotic-resistant UTIs and help guide the selection of antimicrobials in hospital and clinic settings. EHR from multiple centers in North-Central Florida, including patient demographics, previous diagnoses, prescriptions, and antibiotic susceptibility tests, were obtained for 9990 patients diagnosed with a UTI during 2011-2019. Decision trees, boosted logistic regression (BLR), and random forest models were developed to predict resistance to common antibiotics used for UTI management [sulfamethoxazole-trimethoprim (SXT), nitrofurantoin (NIT), ciprofloxacin (CIP)] and multidrug resistance (MDR). There were 6307 (63.1%) individuals with a UTI caused by a resistant microorganism. Overall, the population was majority female, white, non-Hispanic, and older aged (mean = 60.7years). The BLR models yielded the highest discriminative ability, as measured by the out-of-bag area under the receiver-operating curve (AUROC), for the resistance outcomes [AUROC = 0.58 (SXT), 0.62 (NIT), 0.64 (CIP), and 0.66 (MDR)]. Variables in the best performing model were sex, history of UTIs, catheterization, renal disease, dementia, hemiplegia/paraplegia, and hypertension. The discriminative ability of the prediction models was moderate. Nonetheless, these models based solely on EHR demonstrate utility for the identification of patients at higher risk for resistant infections. These models, in turn, may help guide clinical decision-making on the ordering of urine cultures and decisions regarding empiric therapy for these patients.

Antibiotic-Resistant Urinary Tract Infections Treated in the Emergency Department: Attention Needed

Community-acquired urinary tract infections (UTIs) caused by multidrug-resistant Gram-negative bacteria are increasingly common, often leading to

Bacteriophages and Lysins as Possible Alternatives to Treat Antibiotic-Resistant Urinary Tract Infections.

Urinary tract infections represent a major public health problem as the rapid emergence of antibiotic-resistant strains among uropathogens is causing the failure of many current treatments. The use of bacteriophages (phages) and their derivatives to combat infectious diseases is an old approach that has been forgotten by the West for a long time, mostly due to the discovery and great success of antibiotics. In the present so-called “post-antibiotic era”, many researchers are turning their attention to the re-discovered phage therapy, as an effective alternative to antibiotics. Phage therapy includes the use of natural or engineered phages, as well as their purified lytic enzymes to destroy pathogenic strains. Many in vitro and in vivo studies have been conducted, and these have proved the great potential for this therapy against uropathogenic bacteria. Nevertheless, to date, the lack of appropriate clinical trials has hindered its widespread clinic application.

Identification and Ranking of Clinical Compounds with Activity Against Log-phase Growing Uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is a major cause of Urinary Tract Infections (UTIs). Due to increasing antibiotic-resistance among UPEC bacteria, new treatment options for UTIs are urgently needed. To identify new agents targeting growing bacteria that may be used for the treatment of antibiotic-resistant UTIs. We screened a clinical compound library consisting of 1,524 compounds using a high throughput 96-well plate assay and ranked the activities of the selected agents according to their MICs against the UPEC strain UTI89. We identified 33 antibiotics which were active against log-phase clinical UPEC strain UTI89. Among the selected antibiotics, there were 12 fluoroquinolone antibiotics (tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin, pazufloxacin, gatifloxacin, enrofloxacin, lomefloxacin, norfloxacin, fleroxacin, flumequine, ciprofloxacin), 15 beta-lactam or cephalosporin antibiotics (cefmenoxime, cefotaxime, ceftizoxime, cefotiam, cefdinir, cefoperazone, cefpiramide, cefamandole, cefixime, ceftibuten, cefmetazole, cephalosporin C, aztreonam, piperacillintazobactam, mezlocillin), 3 tetracycline antibiotics (meclocycline, doxycycline, tetracycline), 2 membrane-acting agents (colistin and clofoctol), and 1 protein synthesis inhibitor (amikacin). Among them, the top 7 hits were colistin, tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin, cefmenoxime and pazufloxacin, where clinafloxacin and pazufloxacin were the newly identified agents active against UPEC strain UTI89. We validated the key results obtained with UTI89 on two other UTI strains CFT073 and KTE181 and found that they all had comparable MICs for fluoroquinolones while CFT073 and KTE181 were more susceptible to cephalosporin antibiotics and tetracycline antibiotics but were less susceptible to colistin than UTI89. Our findings provide possible effective drug candidates for the more effective treatment of antibiotic-resistant UTIs.

Third-generation cephalosporin-resistant urinary tract infections in children presenting to the paediatric emergency department.

The incidence of antibiotic-resistant urinary tract infections (UTIs) in children is increasing. The purpose of this study was to describe the incidence, clinical characteristics, and risk factors for third-generation cephalosporin-resistant UTIs presenting to the paediatric emergency department (ED). This was a retrospective cohort study conducted at British Columbia Children's Hospital. Children aged 0 to 18 years old presenting to the ED between July 1, 2013 and June 30, 2014 and were found to have UTI due to Enterobacteriaceae and Pseudomonas species were included. Patient demographics, clinical features, laboratory findings, and outcomes were compared using standard statistical analyses. Risk factors for resistant UTIs were analyzed using multiple logistic regression analysis. There were 294 eligible patients. The median age was 27.4 months. A third-generation cephalosporin-resistant organism was identified in 36 patients (12%). Patients with resistant UTI had lower rates of appropriate empiric antibiotic therapy (25% versus 95.3%, P<0.05), higher rates of hospitalization (38.9% versus 21.3%, P<0.05), higher rates of undergoing a voiding cystourethrogram (19.4% versus 5.0%, P<0.05), and higher rates of UTI recurrence within 30 days (13.9% versus 4.7%, P<0.05). In multivariate analysis, recent hospitalization (odds ratio [OR] 4.3, confidence interval [CI] 1.2 to 16) and antibiotic therapy (OR 3.5, CI 1.5 to 8.5) within the previous 30 days were risk factors for resistant UTI. Third-generation cephalosporin-resistant organisms account for a significant proportion of community-acquired paediatric UTIs. Recent hospitalization and antibiotic use are associated with increased risk of resistant UTI.

Tube method and Congo red agar versus tissue culture plate method for detection of biofilm production by uropathogens isolated from midstream urine: Which one could be better?

Background: Bacteria tend to live in assemblies called biofilms that aid bacterial virulence. Biofilms contribute to the development of antibiotic resistant urinary tract infection. Therefore, detection of biofilm production by urinary pathogens can assist the physicians to initiate the proper antimicrobial treatment.Methods: We conducted a prospective study that included patients with suspected urinary tract infection. Collected midstream urine samples were processed by standard microbiological techniques. Detection of biofilm production by the isolated uropathogens was conducted by tissue culture plate method (TCPM), tube method (TM) and Congo red agar (CRA).Results: A total of 43 (29.7%) isolated uropathogens showed positive biofilm formation by TCPM which was considered the gold standard for biofilm detection. When compared with the TCPM, TM truly identified 40 biofilm producers and 83 non-biofilm producers showing sensitivity and specificity of 93.0% and 81.4% respectively. The CRA truly identified 38 biofilm producers and 77 non-biofilm producers with sensitivity and specificity of 88.4% and 75.5% respectively.Conclusion: The TM was superior to CRA in biofilm detection and demonstrated better sensitivity and specificity results. Out of the investigated three phenotypic biofilm detection methods, the TCPM was the ideal method for detection of biofilm formation by uropathogens isolated from midstream urine samples. It can be used routinely in the microbiology laboratory with good specificity results and less subjectivity errors.

The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution.

Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.

Antibiotic resistant urinary tract infections in an urology ward

Introduction: UTI (urinary tract infections) represent a central pathology for a urological service. Antibiotic resistance is growing at a steady and alarming rate worldwide and especially in Romania. Method and materials: We have analyzed all the patients that were admitted to our clinic for continuous hospitalization between January 2015 and October 2015. All patients undergone urine culture and all cultures positive had an antibiogram worked up. We have selected all patients that had antibiotic resistance to at least an antibiotic. Results: From 1745 patients admitted for continuous hospitalization, we had 180 positive urine cultures at admission from which 125 had at least an antibiotic resistance. Conclusions: Antibiotic resistance is a serious phenomenon, with potential lethal complications, which we encounter daily in urological practice.

Foodborne Urinary Tract Infections (Futis): a New Paradigm for Food-Associated Disease

Introduction: Extraintestinal pathogenic E. coli harmlessly colonize human and animal gastrointestinal tracts, but can cause serious infections outside of the gut, including bladder, kidney, and bloodstream infections. Antibiotic-resistant extraintestinal E. coli infections are an increasing challenge in clinical medicine, and understanding the epidemiology of these infections is critical. Today there is substantial evidence linking foodborne E. coli to outbreaks of antibiotic-resistant urinary tract infections (UTIs). The goal of the current project is to quantify the proportion of sporadic UTI and urosepsis cases arising from foodborne E. coli exposures. Methods: A prospective, citywide analysis of E. coli from retail meat and human UTIs was conducted in Flagstaff, AZ. All available brands of chicken, turkey and pork were purchased at retail twice per month for an entire calendar year (2012). Simultaneously E. coli isolates were collected from all UTIs and bloodstream infections. All isolates were genome sequenced and tested for their susceptibility to 12 commonly used antibiotics. Results: Among the 2482 retail meat samples tested, 81% were culture positive for E. coli (n = 2,010). Over the course of the year a total of 1,609 E. coli isolates were collected from clinically diagnosed UTIs and bloodstream infections. All 3,619 isolates were genome sequenced and the food and clinical isolates compared using a hierarchical phylogenetic approach to assess relatedness. Whole genome sequence-based phylogenetic analysis revealed that a substantial fraction of the UTI isolates were closely related and some cases indistinguishable from the foodborne E. coli isolates. Conclusions: The current study suggests that a substantial fraction of UTIs in the US may be caused by foodborne E. coli. These findings expand and highlight the public health risks associated with antibiotic use in food-animal production.

Significance of Fluoroquinolone-Resistant &lt;i&gt;Escherichia coli&lt;/i&gt; in Urinary Tract Infections

Antibiotic-resistant urinary tract infections (UTIs) are on the rise. We investigated the recent emergence of representative resistant strains in patients diagnosed with UTIs at Kobe University Hospital between 2000 and 2006, focusing on resistant strains isolated from the urine of UTI patients, especially fluoroquinolone-resistant Escherichia coli (FQRE), multidrug-resistant Pseudomonas aeruginosa (MDRP), and methicillin-resistant Staphylococcus aureus (MRSA). We found 16 MDRP, 108 FQRE, and 251 MRSA UTI cases, reflecting a significant increase in the incidence of FQRE. Our data demonstrated that isolated ratios of FQRE rose as much as 26.3% in 2006 and that there were significantly more isolated cases in 2003 - 2006 than in 2000 - 2002. The data show a significant trend toward FQRE emergence. This trend should be considered when treating UTI.

Detection of extended-spectrum beta-lactamase-producing, multidrug-resistant environmental isolates of Escherichia coli that bind to human bladder cells.

Compared to the number of studies examining extended-spectrum beta-lactamase (ESBL)-producing clinical isolates, environmental ESBL-producers have not been studied extensively. To investigate environmental ESBL-producing Escherichia coli, 22 cephalothin-resistant E. coli were isolated from Han River in Seoul, Korea. These isolates were resistant to ampicillin, cephalothin, and gentamicin, and 14 isolates among these were resistant to norfloxacin. All of these isolates produce AmpC and CMY, OXA, or TEM as determined by isoelectric point focusing (IEF) gel electrophoresis and PCR. One isolate (57-214) producing AmpC and OXA was resistant to all antibiotics (ampicillin, cephalothin, norfloxacin, gentamicin, cefotaxime, ceftazidime) tested in this study. Six isolates, including isolate 57-214, could adhere to T24 human bladder cells, and these isolates were not related to each other as shown with random amplified polymorphic DNA (RAPD). Results showed that environmental ESBL-producing E. coli is able to colonize in bladder cells and directly cause antibiotic-resistant urinary tract infection.