Nosocomial Urinary Tract Infections Research Articles

High efficacy treatment of murine Pseudomonas aeruginosa catheter-associated urinary tract infections using the c-di-GMP modulating anti-biofilm compound Disperazol in combination with ciprofloxacin.

Persistent urinary tract infections (UTIs) in hospitalized patients constitute an important medical problem. It is estimated that 75% of nosocomial UTIs are associated with urinary tract catheters with P. aeruginosa being a species that forms biofilms on these catheters. These infections are highly resistant to standard-of-care antibiotics, and the effects of the host immune defenses, which allows for development of persistent infections. With antibiotics losing their efficacy, new treatment options against resilient infections, such as catheter-associated urinary tract infections (CAUTIs), are critically needed. Central to our anti-biofilm approach is the manipulation of the c-di-GMP signaling pathway in P. aeruginosa to switch bacteria from the protective biofilm to the unprotected planktonic mode of life. We recently identified a compound (H6-335-P1), that stimulates the c-di-GMP degrading activity of the P. aeruginosa BifA protein which plummets the intracellular c-di-GMP content and induces dispersal of P. aeruginosa biofilm bacteria into the planktonic state. In the present study, we formulated H6-335-P1 as a hydrochloride salt (Disperazol), which is water-soluble and facilitates delivery via injection or oral administration. Disperazol can work as a monotherapy, but we observed a 100-fold improvement in efficacy when treating murine P. aeruginosa CAUTIs with a Disperazol/ciprofloxacin combination. Biologically active Disperazol reached the bladder 30 min after oral administration. Our study provides proof of concept that Disperazol can be used in combination with a relevant antibiotic for effective treatment of CAUTIs.

Nosocomial Urinary Tract Infections in a Tertiary Hospital; Preliminary Study of Antibiotics Susceptibility Testing and Pathogen Types

Introduction: Nosocomial urinary tract infections (NUTIs) are the most frequently acquired infection worldwide. This retrospective study aimed to determine the type of pathogens and antibiotic susceptibility testing in hospital-acquired UTIs. Methods: Information from the recorded official database of the Alzahra, Isfahan/Iran tertiary specialist hospital was obtained. Urine was collected based on two methods: 1) central stream and 2) with a urinary catheter in place. The incidence of acquired infections (NUTIs-SUTI; Code 55) was described as a percentage. The statistical calculations were conducted using the statistical software. There were 2210 recorded NUTIs comprised of 1115 males and 1095 females. Among the total recorded data with NUTIs, 251 records were associated with deaths. The distribution of hospital stays in 57% was between 2-30 days. Available data showed that Candida (23%), Escherichia coli (22%), Klebsiella pneumonia (17%), and Enterococcus (faeciumfecalis; 12%) were the most ranked microorganisms in patients with NUTIs. Resulsts: Sensitivity tests for Escherichia coli associated with different antibiotics were ranked as; 1) Meropenem (n= 160; S= 66%), 2) Vancomycin (n= 53; S= 64%), 3) Piperacillin/Tazobactam (n= 144; S= 58%), 4) Amikacin (n= 146; S= 44%), 5) Co-trimoxazole (n= 153; S=42%), 6) Penicillin (n=79; S=41%), 7) Cefepime (n=143; S=31%), 8) Ceftazidime (n=142; S=31%), 9) Ciprofloxacin (n=204; S=25%). Sensitivity tests for Klebsiella pneumonia associated with different antibiotics were ranked as; 1) Piperacillin/Tazobactam (n= 110; S= 55%), 2) Amikacin (n= 125; S= 55%), and 3) Ciprofloxacin (n=177; S=23%). Sensitivity tests for Enterococcus (faecium-fecalis) associated with different antibiotics were ranked as; 1) Piperacillin/Tazobactam (n= 79; S= 62%), 2) Amikacin (n= 83; S= 64%) and 3) Ciprofloxacin (n=120; S=30%). Conclusion: Within the population studied, while Ciprofloxacin showed less than 30% sensitivity, Piperacillin/Tazobactam and Amikacin exhibited a sensitivity of more than 50% regarding Escherichia coli, Klebsiella pneumonia, and Enterococcus (faecium-fecalis) need further evidence-based investigations

A Retrospective Study on UTI by Myroides Species: An Emerging Drug Resistant Nosocomial Pathogen.

Myroides (M.) species are ubiquitous in the environment and cause a variety of infections like urinary tract infections (UTI), sepsis, meningitis, cholecystitis, pneumonia, and soft tissue infections, especially among immunocompromised populations. These are usually resistant to multiple antibiotics. This study aimed to demonstrate the clinical profile, underlying comorbidities, and antimicrobial susceptibility of Myroides isolates obtained from nosocomial UTI cases. A sudden rise in the isolation of Myroides spp. from the repeated urine samples of admitted patients alerted us to conduct this retrospective observational study. Urine cultures that grew M. species were included in this study. Antibiotic susceptibility was performed and the patient's clinical data was analyzed. A total of 14 Myroides spp. isolates were obtained from urine culture. The maximum number of cases (71.4%) were from the Nephrology ward and ICUs. The average (mean) age of patients was 46 years (range 2-80 years). All patients were catheterized. All isolates were multidrug resistant. Minocycline and doxycycline were the only drugs found effective in this study. Myroides species are emerging rare pathogens that can cause UTI in immunocompromised and catheterized patients. Minocycline may be used for treating such infections. Sahu C, Chaudhary R, Bhartiya C, Patel SS, Bhatnagar N. A Retrospective Study on UTI by Myroides Species: An Emerging Drug Resistant Nosocomial Pathogen. Indian J Crit Care Med 2024;28(4):399-403.

Structural dynamics and anti-biofilm screening of novel imidazole derivative to explore their anti-biofilm inhibition mechanism against Pseudomonas Aeruginosa

The biofilm formation is still prevalent mechanism of developing the drug resistance in the Pseudomonas aeruginosa, gram-negative bacteria, known for its major role in nosocomial, ventilator-associated pneumonia (VAP), lung infections and catheter-associated urinary tract infections. As best of our knowledge, current study first time reports the most potent inhibitors of LasR, a transcriptional activator of biofilm and virulence regulating genes in, Pseudomonas aeruginosa LasR, utilizing newly functionalized imidazoles (5a-d), synthesized via 1,3-dipolar cycloaddition using click approach. The synthesized ligands were characterized through Mass Spectrometry and 1H NMR. The binding potency and mode of biding of ligands. Quantum Mechanical(QM) methods were utilized to investigate the electronic basis, HOMO/LUMO and dipole moment of the geometry of the ligands for their binding potency. Dynamics cross correlation matrix (DCCMs) and protein surface analysis were further utilized to explore the structural dynamics of the protein. Free energy of binding of ligands and protein were further estimated using Molecular Mechanical Energies with the Poisson–Boltzmann surface area (MMPBSA) method. Molecular Docking studies revealed significant negative binding energies (5a − 10.33, 5b −10.09, 5c − 10.11, and 5d −8.33 KJ/mol). HOMO/LUMO and potential energy surface map estimation showed the ligands(5a) with lower energy gaps and larger dipole moments had relatively larger binding potency. The significant change in the structural dynamics of LasR protein due to complex formation with newlyfunctionalized imidazoles ligands. Hydrogen bond surface analysis followed by MMPBSA calculations of free energy of binding further complemented the Molecular docking revelations showing the specifically ligand (5a) having the relatively higher energy of binding(-65.22kj/mol). Communicated by Ramaswamy H. Sarma

Cobalt containing antimicrobial bioactive glass coated urinary catheter towards management of catheter associated urinary tract infection (CAUTI): Significant in vitro characterizations

Catheter associated urinary tract infections (CAUTI) contributes to about 75 % of nosocomial urinary tract infections (UTI) and the risk potential is further escalated upon prolonged usage of the urinary catheter. Additionally, there is an increased risk for bloodstream infection from urinary source resulting in neutropenia and plethora of renal diseases. Over the past decades, numerous antibiotics/antimicrobial agents have been surface functionalized on catheter tubes but none proved effective owing to biofilm's tolerance. Further, in case of the indwelling urinary catheters, a thin fibrous capsule develops around the catheter, with no adhesion of the epithelial tissue. Additionally, recent reports of Co based bioactive glass exhibited potent antimicrobial action on both E. coli, P. aeruginosa (gram negative) and Candida albicans (fungus) which are primary causative organisms for CAUTI.In view of the above, we propose to fabricate a Co containing antimicrobial mesoporous bioactive glass (MBGCo) coated indwelling urinary catheter tubing, followed by its in vitro material (XRD, TG-DSC, FTIR, FESEM, BET and water contact angle determination), in-vitro bioactivity study and biological characterization (in-vitro cell cytotoxicity, antibacterial, antifungal studies, initial bacterial adhesion study etc.) of MBGCo coated urinary catheter tubing, along with antimicrobial studies and optimization of the same to obtain a preliminary prototype that is expected to address the issues of the existing urinary catheters.

Candida species in catheter associated urinary tract infection in ICU patients at a tertiary care hospital in North India: An observational study

Introduction: Catheter associated urinary tract infection (CAUTI) is most common nosocomial infection which constitutes ~80% of nosocomial urinary tract infections (UTIs). Candida albicans has been most commonly isolated in past but in recent years non-albicans candida has emerged as the more common agent causing UTI in ICU settings. The study aimed to assess the burden of various candida species in symptomatic CAUTI in ICU patients and to test their susceptibility pattern for various antifungal agents. Materials and methods: Study was performed at a 1050 bed tertiary care hospital of northern India. Over a period of 1 year, total 147 urine samples from symptomatic CAUTI patients admitted in ICU were collected. Gram’s staining and culture on CLED agar was done. All yeast isolates were tested for speciation of Candida & antifungal susceptibility by an automated commercial system - VITEK 2. Results: Among 147 urine samples, 34 (23.12%) were positive for various Candida species. 61.76% positive patients were female and 38.23% were male. Maximum numbers of Candida isolates were found in above 60 years age group. 27 (79.41%) were due to non-albicans Candida spp. and 7 (20.58%) were due to Candida albicans. All Candida species were found to be sensitive to voriconazole, amphotericin B, caspofungin and micafungin. Few isolates of certain species like C.albicans and C.non-albicans showed resistance to fluconazole and/or flucytosine. Conclusion: Changing pattern of Candida species causing UTIs around the world points towards continuous need for surveillance, thus helping us in providing appropriate therapy.

Study of some virulence genes from uropathogenic Klebsiella pneumoniae and Pseudomonas aeruginosa isolated in Wasit Province, Iraq

Abstract Background: Klebsiella pneumoniae and Pseudomonas aeruginosa are the most common causes of nosocomial urinary tract infections (UTIs), and in recent years, these bacteria have become significantly more resistant to antibiotics. Objective: The objective of the study was to determine the frequency of uropathogenic K. pneumoniae and P. aeruginosa in clinical urine samples from patients with UTIs in Wasit Province. Materials and Methods: Initially, 100 clinical urine samples were taken for this investigation from (October 1 to December 1, 2022), and the isolates were initially identified using culture, microscopic analysis, and biochemical assays. Results: The findings of the biochemical results revealed that 16/100 isolates had a 16% positive response for K. pneumonia, and 13/100 isolates had a 13% positive response for P. aeruginosa. When DNA was recovered from the isolates, the nucleic acid purity was diverse from 1.8 to 2.0, and the concentration fluctuated from 50 to 360 mg/µL. By using molecular techniques, including the 16S rRNA gene, for confirmation of the diagnosis. These findings were validated by the polymerase chain reaction method used to detect the virulence genes fimH gene, where 4/16 (25%) and mrkA gene, where result 7/16 (43.75%) were positive in recovered K. pneumoniae isolated. And RNA polymerase subunit B (rpoB) gene where results 10/13 (76.92%) were positive in recovered P. aeruginosa isolated. Conclusion: In conclusion, the outcomes of this study presented a significant increase in biofilm-forming and multidrug-resistant K. pneumoniae isolates, which also harbor a wide range of virulence genes and used rpoB as high molecular identification properties to confirm the P. aeruginosa, the most efficient antibiotics for its treatment were Impinem and Nitrofurantoin for both K. pneumonia and P. aeruginosa.

Low Phase Angle and Skeletal Muscle Index Increase Hospital-Acquired Infections During Stroke Rehabilitation

ObjectivesSarcopenia is common in patients with stroke and may increase the risk of medical complications such as infection. However, assessing sarcopenia in stroke patients with consciousness disturbance, aphasia or severe paralysis is challenging. This study aimed to investigate whether a combined assessment of phase angle (PhA) and skeletal muscle index (SMI), estimated using bioelectrical impedance analysis, was associated with 2 common nosocomial infections, hospital-acquired pneumonia (HAP) and urinary tract infection (UTI), during inpatient stroke rehabilitation. DesignSingle-center retrospective observational study. Settings and ParticipantsA total of 1068 patients with stroke admitted to a rehabilitation hospital between January 2016 and September 2019 were analyzed. MethodsThe study variables included demographic characteristics, comorbidities, stroke severity, blood chemistry and urine analysis, SMI, and PhA obtained using bioelectrical impedance analysis. Patients were classified as normal, low PhA only, low SMI only, and low PhA + SMI. Multivariate Cox proportional analysis was used to determine the variables associated with HAP and UTI. ResultsA combination of low PhA + SMI was observed in 429 (40.2%) patients. Over a median follow-up duration of 46 days, HAP occurred in 187 patients (17.5%) and UTI occurred in 155 patients (14.5%). The low PhA + SMI group showed a significantly higher incidence of HAP and UTI than the normal group (32.6% vs 4.6%, P < .001, for HAP; 20.7% vs 6.2%, P < .001, for UTI). In multivariate Cox analyses, low PhA and SMI were associated with significantly higher rates of HAP [hazard ratio (HR) 3.36, 95% CI 1.796-6.304, P < .001] and UTI (HR 1.71, 95% CI 1.002-2.947, P < .05) after adjusting for confounding variables. Conclusions and ImplicationsCombination of low PhA + SMI was independently associated with a higher risk of HAP and UTI in stroke patients who underwent inpatient rehabilitation. Measuring PhA and SMI using bioelectrical impedance analysis might be helpful in establishing care plans in these population.

Prevalence and Antibiotic Susceptibility Pattern of Enterococcus Spp. Isolated from Urine Samples

Enterococci are the most common cause of healthcare-associated urinary tract infections. Enterococcus spp. were isolated from each of Urine and differences for Enterococcus contamination in urine were determined. Because of its unimportant commensals, Enterococci have developed into diverse, deadly diseases due to the routinely prescribed antibiotics for the treatment of nosocomial UTIs are less effective, the developing antibiotic resistance is concerning. This study aimed to determine the prevalence and antibiotic susceptibility patterns of different enterococcal species isolated from urine samples and to observe the prevalence of microbes in urine samples among the different types of patients. The frequency of enterococci isolation from hospitalized patients' urinary tract has risen. This cross-sectional study was conducted from March 2021 to December 2021 at the Department of Microbiology, AMZ Hospital Dhaka, Bangladesh. A total of 439 urine samples were collected and 96 (21.87%) samples showed growth of different isolates, in growth isolates 29 (30.20%) samples were Enterococcus spp. In this study, the sample was sensitive against Linezolid (95.55%), Vancomycin (89.67%), Penicillin (68.98%), Gentamycin (68.96%), Imepenum (55.17%). From our study revealed that different strains of Enterococcus spp. are resistant to drugs at different rates.

Investigation of Nosocomial Urinary Tract Infections Post Transplantation, Main Pathogens, and Sensitivity Tests

Background: Regarding end-stage organ disease, transplantation is recommended as the best therapeutic management. After organ transplantation, the incidence of nosocomial urinary tract infections (NUTIs) due to multidrug-resistant Gram-negative bacilli increases. background: Regarding end-stage organ disease organ transplantation recommended as the best therapeutic management. After organ transplantation the incidence of urinary tract infections (UTIs) due to multidrug-resistant Gram-negative bacilli is increasing Aim: The study aimed to investigate NUTIs post-transplantation, the main pathogens involved, and sensitivity tests conducted in a tertiary hospital in Isfahan, Iran. Methods: A retrospective survey on patients admitted to a tertiary hospital in Isfahan (Alzahra), Iran, was performed between 27 March, 2017, and 9 February, 2022. The information recorded included the date of infection, date of hospitalization, gender, age, type of pathogens, and resistance or sensitivity to antibiotics. Results: 73 kidney transplant recipients (61% females) with a mean age of 43. 2 ± 15.1 years were included. Within this population involving both genders, the main pathogens involved in NUTIs were as follows: Escherichia coli (30%), Klebsiella pneumonia (19%), Candida albicans and non-albicans (14%), Enterococcus faecalis (12%), Enterobacteriaceae (8%), Pseudomonas aeruginosa (6%), Staphylococcus spp. (6%), Acinetobacter baumannii (4%), and Streptococcus spp. (4%). Antibiotic susceptibility testing showed the most sensitivity of isolates against amikacin (n=29; 66%), meropenem (n= 28; 64%), piperacillin/tazobactam (n=26; 54%), cefepime (n= 25; 40%), ceftazidime (n= 27; 30%), ciprofloxacin (n= 40; 18%), and co-trimoxazole (n= 29; 10%). result: 72 kidney transplant recipients (61 Conclusion: Escherichia coli, Klebsiella pneumonia, and Candida spp. are the major causes of NUTIs within organ-transplanted recipients. Amikacin, meropenem, and piperacillin/tazobactam have shown more than 50% sensitivity against isolates. Further evidence-based management associated with the different spectrum antibiotics and overall antimicrobial success rate is recommended to be advantageous.

The burden of healthcare-associated infection in Moroccan hospitals: systematic review and meta-analysis

Background: Healthcare-associated infections (HAI) continue to be a major public health concern throughout the world because of the associated mortality and socioeconomic costs. The significant financial burden of healthcare-associated infections is especially relevant for developing countries. Meta-analysis can be a major tool that can aid in decision making in the realm of public health, owing to theirevidence level, especially in countries with limited resources, such as Morocco. In Morocco, recently, the Ministry of Health creates the national coordination unit and the technical committee for the surveillance of antimicrobial resistance but still does not have a national HAI surveillance system making it very difficult to systematically assess and report on the burden of hospital-acquired infections HAIs. The main objective of this systematic review and meta-analysis is to estimate the overall prevalence of infections acquired in hospitals in Morocco using data from prevalence studies. We also studied the variability in the evolution of these infections over time.Methods: A multisource search strategy was used to retrieve all published and unpublished data.The search terms were used in databases, conference abstracts, national research banks, the World Health Organization database, Google scholar and were also applied in a manual search. Two reviewers independently extracted and evaluated the data and the concordance between the two examiners was calculated by Kappa (κ) statistical coefficient. The meta-analysis was performed using the R and Stata software with a random effects model.Results: Fourteen studies with 6,532 patients were included. The pooled prevalence of HAI was 10% (CI 95%: 8 - 12, I2= 87%). Of the 14 studies, ten were conducted in tertiary hospitals with pooled prevalence of 10.84% (CI 95%: 8.9 - 13.714 I2=86%), compared with 6.34% (CI 95% 4.43 – 8.99, I2=63%) in non-tertiary hospitals. When subgrouping analysis by infection type, the most common HAI were nosocomialurinary tract infections with a proportion of 24.52% (CI 95 %:14.09 - 39.15, I2=87%). This proportion was followed closely by surgical wound infections at 24.42% (CI 95%: 20.15 – 29.26, I2=51%). Respiratory infections accounted for 16.82% (CI 95%: 12.51 - 22.24, I2=57%) of the HAI. The change in number of HAI over time has increased between 2004 and 2014 (beta =0.05, 95% CI -0.07 to 0.16 and p = 0.9). There were no publication biases, as evaluated by Funnel Plot and Begg and Egger tests (p&gt; 0.05).Conclusion: The pooled prevalence of HAI across 6,632 patients in Morocco was 10%. The most common HAI were nosocomial urinary tract infections (rate of 24.52%), followed by surgical wound infections (rate of 24.42%), and respiratory infections (rate of 16.82%).

Rare Cause of Nosocomial Urinary Tract Infection in Non Catheterised Patient

Background: Leuconostoc Mesenteroides are member of the Streptococcae family and currently has been recognized as potential pathogen.this cause describes a nosocomial infection caused by Leuconostoc Mesenteroides in an patient affected by pulmonary Mucoromycosis. Case Report: A 59 year old diabetic and hypertensive male patient was admitted in infectious diseases department with complaint of intermittent cough with hemoptysis,breathlessness since 6 months,then patient was evaluated and found to have pulmonary Mucoromycosis and hence patient was started on antifungal treatment, during the treatment patient started complaining of burning micturition and increased frequency from 3 days, then patient was suspected to have hospital acquired urinary tract infection and investigated accordingly. Urine routine analysis revealed 12-16 pus cells and ultrasound abdomen showed cystitis, hence patient was started on Piperacillin and tazobactam after sending urine for culture. Automated and conventional culture methods showed culture of Leuconostoc Mesenteroides. Conclusion: We concluded that infections caused by Leuconostoc Mesenteroides is serious and should be considered not only in settings of immunocompromised and on prolonged antibiotic use but also in immunocompetent patient.

Microbiological monitoring in a urological hospital as a method for control of antibiotic resistance of uropathogens

BACKGROUND: A rational choice of antibacterial therapy for hospital infections is a condition for successful treatment of patients.&#x0D; AIM: The aim of this study is a comparative assessment of the species composition of pathogens and the level of their resistance to antibacterial drugs in patients with complicated urinary tract infections in a urological hospital.&#x0D; MATERIALS AND METHODS: An analysis of the results of microbiological examination of urine samples from 1317 patients (795 men and 522 women) with complicated urinary tract infection who were hospitalized in a urology clinic during the period 2020–2021 was carried out.&#x0D; RESULTS: Gram-negative microflora was detected in 703 (53.4%) patients, gram-positive microflora in 531 (40.3%) patients and mixed microflora in 83 (6.3%) patients. Among gram-negative bacteria Escherichia coli (23.1%) and Klebsiella pneumoniae (16.1%) were predominate, Pseudomonas aeruginosa (4.9%) and Proteus mirabilis (2.8%) were less frequently detected. A high frequency of detection of gram-positive microflora of the genera Enterococcus (21.4%) and Staphylococcus (12.7%) was noted. When compared with the results of a similar study from 2018 to 2020 there is a decrease in the detection rate of E. coli from 28.2% to 23.1%. Antibiotic resistance of hospital strains of uropathogens varies significantly for different antimicrobial drugs. Most often resistance to representatives of three or more groups of antibiotics was observed in K. pneumoniae (46.6%), less commonly in E. coli (19.5%) and rarely in Enterococcus spp. (5.9%).&#x0D; CONCLUSIONS: Microbiological monitoring allows us to assess the etiological structure and level of antibiotic resistance of nosocomial urinary tract infections. Local data on the sensitivity of microorganisms to antibacterial drugs make it possible to rationally carry out perioperative antibiotic prophylaxis and prescribe empirical therapy for urinary tract infections before obtaining the results of a microbiological study.

The Causative Agents and Antibiotic Susceptibility Patterns of Healthcare-Associated Urinary Tract Infections (HAUTIs) in Isfahan, Iran: The Impact on Empiric Therapy

Background: Healthcare-associated urinary tract infections (HAUTIs) are the most prevalent healthcare-associated infection worldwide. They can lead to major problems in hospitalized patients, including the increase in the length of the hospital stay, the cost of the hospitalization, and the inappropriate administration of antibiotics. Objectives: We aim to investigate the prevalence and antibacterial sensitivity of various bacteria that cause HAUTIs. Methods: This cross-sectional study was conducted in three referral hospitals in Isfahan, Iran. Urine specimens were taken from urinary catheters of the patients with a suspected diagnosis of HA-UTI. Bacteria were identified by conventional methods, and antimicrobial sensitivity testing was performed by disk diffusion and E-test methods according to standard guidelines. Data was extracted from WHONET software, and further statistical analysis was performed by SPSS v.21. Results: Among 283 HAUTIs, Escherichia coli was the most prevalent pathogen (33.2%), followed by Enterococcus spp. (25.9%), Klebsiella pneumonia (16.6%), Pseudomonas aeruginosa (8.8%), and Acinetobacter baumannii (8.8%). Escherichia coli was more common in females. The most active antibiotics against Gram-negative isolates were nitrofurantoin (69.8%), carbapenems (69.7%), and aminoglycosides (68.3%), and the most effective antibiotics against Gram-positive isolates were linezolid (100%) and nitrofurantoin (74.5%). Conclusions: This study showed that nitrofurantoin, carbapenems, and aminoglycosides are the most effective antibiotics against Gram-negative causes of HAUTIs. Also, linezolid and nitrofurantoin demonstrated significant activity against Gram-positive isolates. As a result, for the empiric treatment of nosocomial UTI in the area under study, judicious use of the mentioned antibiotics is recommended.

Antimicrobial and antibiofilm activities of chromone derivatives against uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is a urinary tract pathogen responsible for most nosocomial urinary tract infections and can cause severe conditions like acute cystitis of the bladder or pyelonephritis. UPEC harbors a host of virulence factors like curli, hemolysin, siderophore, and motility factors and can form biofilm-like communities and quiescent reservoirs that aid its survival. This study was performed to investigate the antibiofilm, antimicrobial, and antivirulence potentials of three chromone derivatives, namely, 6-bromo 3-formylchromone, 6-chloro 3-formylchromone, and 3-formyl 6-isopropylchromone. These chromones had MICs against UPEC of 20, 20, and 50 µg/ml, respectively, inhibited biofilm formation by 72–96% at 20 µg/ml, and inhibited UPEC-associated virulence factors, that is, hemolysis, motility, curli, siderophore production, indole production, quiescent colony formation, and cell surface hydrophobicity. Gene expression analysis indicated these three derivatives downregulated virulence genes associated with toxins, biofilm production, and stress regulation and suggested they might target two-component UvrY response regulator. 3D-QSAR analysis showed that substitutions at the third and sixth positions of the chromone scaffold favor antimicrobial activity against UPEC. Furthermore, ADME profiles and C. elegans cytotoxicity assays indicated that these chromone derivatives are potent, safe drug candidates.

Tackling catheter-associated urinary tract infections with next-generation antimicrobial technologies.

Urinary catheters and other medical devices associated with the urinary tract such as stents are major contributors to nosocomial urinary tract infections (UTIs) as they provide an access path for pathogens to enter the bladder. Considering that catheter-associated urinary tract infections (CAUTIs) account for approximately 75% of UTIs and that UTIs represent the most common type of healthcare-associated infections, novel anti-infective device technologies are urgently required. The rapid rise of antimicrobial resistance in the context of CAUTIs further highlights the importance of such preventative strategies. In this review, the risk factors for pathogen colonization in the urinary tract are dissected, taking into account the nature and mechanistics of this unique environment. Moreover, the most promising next-generation preventative strategies are critically assessed, focusing in particular on anti-infective surface coatings. Finally, emerging approaches in this field and their likely clinical impact are examined.

The incidence of nosocomial bloodstream infection and urinary tract infection in Australian hospitals before and during the COVID-19 pandemic: an interrupted time series study

BackgroundThe COVID-19 pandemic has had a significant impact on healthcare including increased awareness of infection prevention and control (IPC). The aim of this study was to explore if the heightened awareness of IPC measures implemented in response to the pandemic influenced the rates of healthcare associated infections (HAI) using positive bloodstream and urine cultures as a proxy measure.MethodsA 3 year retrospective review of laboratory data from 5 hospitals (4 acute public, 1 private) from two states in Australia was undertaken. Monthly positive bloodstream culture data and urinary culture data were collected from January 2017 to March 2021. Occupied bed days (OBDs) were used to generate monthly HAI incidence per 10,000 OBDs. An interrupted time series analysis was undertaken to compare incidence pre and post February 2020 (the pre COVID-19 cohort and the COVID-19 cohort respectively). A HAI was assumed if positive cultures were obtained 48 h after admission and met other criteria.ResultsA total of 1,988 bloodstream and 7,697 urine positive cultures were identified. The unadjusted incident rate was 25.5 /10,000 OBDs in the pre-COVID-19 cohort, and 25.1/10,000 OBDs in the COVID-19 cohort. The overall rate of HAI aggregated for all sites did not differ significantly between the two periods. The two hospitals in one state which experienced an earlier and larger outbreak demonstrated a significant downward trend in the COVID-19 cohort (p = 0.011).ConclusionThese mixed findings reflect the uncertainty of the effect the pandemic has had on HAI’s. Factors to consider in this analysis include local epidemiology, differences between public and private sector facilities, changes in patient populations and profiles between hospitals, and timing of enhanced IPC interventions. Future studies which factor in these differences may provide further insight on the effect of COVID-19 on HAIs.

Incidence of biofilms among the multidrug resistant E. coli, isolated from urinary tract infections in the Nilgiris district, South India.

Multidrug resistant uropathogenic Escherichia coli (MDRUPEC) significantly correlates with recurrent, complicated, and persistent urinary tract infection (UTI). The leading cause of multidrug resistance is the ability of E. coli to form biofilms. The physiological heterogeneity, genetic incontinency, and putative events in gene expression of biofilms render them resistant to antimicrobials and the host immune system. Understanding the determinants of antimicrobial resistance and its correlation with biofilm formations will, therefore, help the development of a better strategy for treating biofilm-associated UTIs. The present study reports on the in vitro detection of biofilm formation among multidrug resistant E. coli strains isolated from urine, the major cause of communal, nosocomial, and food-borne uropathogenic UTI. This is a cross-sectional study conducted in and around Ooty, Nilgiris, India. From the 869 urine samples analyzed for UTI, 29.34% were found to be caused by E. coli. Among this about 23.92% were found to be multidrug resistant. Among the multidrug resistant E. coli isolates, 36.06% of them were potent biofilm producers. E. coli biofilms (n = 22) were resistant to the antibiotics used to treat UTI, namely, amikacin, amoxicillin, ampicillin, cefepime, cefoperazone, cefotaxime, ceftriaxone, cefuroxime, cephalotin, ciprofloxacin, co-trimoxazole, gentamicin, levofloxacin, and nalidixic acid, but sensitive to imipenem and meropenem. All the biofilm producers exhibited motility and hemaggultination but none were positive for hemolysin production. The isolated E. coli biofilms were confirmed by VITEK R2 Compact (bioMerieux, France) and 16S rRNA gene sequencing.

Enterococcus Species: A Systemic Review

Enterococci are gram-positive facultative anaerobes, these are commensals in the intestinal system of numerous animals, including humans. They affect hospitalized patients and cause nosocomial infections, respiratory infections, endocarditis, wound infections, UTIs, and other enterococcal infections. This discovery can be explained by hemolysin, gelatinase, aggregation substances, hyaluronidase, capsular polysaccharides, and cell wall carbohydrate. Various enterococcal spp. include Enterococcus avium Vancomycin resistance was acquired by enterococci throughout the antibacterial spectrum, primary antibiotic used regimen based on dual β lactams and aminoglycosides.

Analysis of Etiology of Community-Acquired and Nosocomial Urinary Tract Infections and Antibiotic Resistance of Isolated Strains: Results of a 3-Year Surveillance (2020-2022) at the Pediatric Teaching Hospital in Warsaw.

Urinary tract infections (UTIs) remain the most common infections diagnosed in outpatients and hospitalized patients. This study was designed to determine the patterns of antibiotic resistance and the prevalence of uropathogens causing UTIs in pediatric patients hospitalized between 1 January 2020 and 31 December 2022 at Teaching Hospital in Warsaw. The most frequent species isolated from urine samples were E. coli (64.5%), Klebsiella spp. (11.6%), and Enterococcus spp. (6.1%). UTIs caused by Enterobacter spp., Enterococcus spp., and Klebsiella spp. were significantly more common in children younger than three months of age than in children older than three months (p < 0.001). Trimethoprim and trimethoprim-sulfamethoxazole were the least active compounds against Enterobacterales with the resistance of E. coli, Klebsiella spp., P. mirabilis, and Enterobacter spp. in the range of 26.7/25.2%, 48.4/40.4%, 51.1/40.4%, and 15.8/13.2% respectively. Ampicillin was also found to have resistance rates for E. coli of 54.9% and P. mirabilis of 44.7%. Cefalexin and cefuroxime were highly active towards Enterobacterales except for Klebsiella spp., in which the resistance level reached 40%. Regarding third- and fourth- generation cephalosporins, resistance in E. coli and P. mirabilis was observed in approximately 2-10% of the isolates, but in Klebsiella spp. and Enterobacter spp. ranged over 30%. The resistance of Enterobacterales to carbapenems, nitrofurantoin, and fosfomycin was below 1%. The quinolones resistance was very high for Klebsiella spp. (31.1%) and P. mirabilis (29.8%) and three times lower for E. coli (11.9%), P. aeruginosa (9.3%), Enterobacter spp. (2.6%), and E. faecalis (4.6%). Resistance to multiple antibiotic classes was identified in 396 Enterobacterales strains, 394 of which were multi-drug resistant (MDR) and 2 were extensive drug-resistant (XDR). In the case of E. coli, 30% of isolates were MDR, with the proportion of strains having this exact resistance pattern similar in all of the analyzed years; no E. coli XDR strains were isolated. The number of Klebsiella spp. MDR strains was much higher in 2022 (60%) than in 2021 (47.5%). In the analyzed time, only one strain of K. pneumonia XDR, producing New Delhi metallo-β-lactamase, was isolated. Monitoring infection trends is essential to improve control and limit the rise of bacterial resistance.