Urinary Source Research Articles

Differentiation of Providencia species bloodstream infections: A population-based analysis

BackgroundAlthough Providencia species are recognised as important causes of bloodstream infections (BSI), their epidemiology is not well defined due to their infrequent occurrence. Our objective was to determine the overall incidence, determinants, and outcomes of Providencia species BSI, and compare the epidemiology of P. stuartii and P. rettgeri in a large population. MethodsAll patients within Queensland, Australia with Providencia species BSI between 2000-2019 were included with clinical and outcome data collected from state-wide datasets. ResultsAmong 268 residents, there was 273 incident episodes of Providencia species BSI; with 118 cases (43.2%) due to P. rettgeri, 150 cases (55.0%) due to P. stuartii, for age and sex adjusted incidence rates of 1.5, and 2.1 per million respectively. Five cases (<2.0%) were due to other Providencia species. The median age was 73.9 years, 80% were male, and most episodes were of community onset. As compared to P. rettgeri, patients with P. stuartii BSI were more likely to have dementia, peptic ulcer disease, and hemiplegia but less likely to have comorbid liver disease. The overall distribution of infection foci were different with P. stuartii more commonly associated with lower respiratory tract source and P. rettgeri with urinary source. All cause 30-day case fatality was significantly higher for P. rettgeri versus P. stuartii (35; 29.7% vs. 24; 16%; p=0.007). ConclusionsProvidencia species are important causes of community onset BSI especially in older males. Although they share similar incidence, P. stuartii and P. rettgeri BSI differ on many clinical aspects.

Amikacin treatment in patients with Enterobacterales bacteraemia: impact of MIC on mortality.

Recently, breakpoints of Enterobacterales to amikacin were changed from MIC ≤ 16 mg/L to MIC ≤ 4 mg/L based mainly on laboratory data with little supporting clinical evidence. Our aim was to investigate the relation between MIC of Enterobacterales to amikacin and mortality among patients with Enterobacterales bacteraemia from a urinary tract source treated with amikacin. This retrospective, single-centre study included patients with Enterobacterales urinary source bacteraemia treated with amikacin, with Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) MICs. A cohort of patients treated with ertapenem was used to assess if amikacin MIC is a marker of severity independent of antimicrobial treatment. The primary outcome was 30-day mortality. Multivariate logistic regression analysis was done to assess risk factors for mortality. We included 85 patients, 46 (54.1%) were male, and mean age was 79.0 years (SD 11.7). Sixty-one patients (71.8%) had Low MIC and 24 (28.2%) had High MIC. Thirty-day mortality was 8.2% and 29.2% in the Low and High MIC groups, respectively (P = 0.031). Risk factors for 30-day mortality were age, infection by Enterobacterales other than Escherichia coli and high amikacin MIC. In a cohort of 88 patients treated with ertapenem, amikacin MIC was not associated with 30-day mortality. We demonstrated a relation between higher amikacin MIC levels (8 and 16 mg/L) and increased 30-day mortality in patients treated with amikacin for bacteraemia secondary to a urinary source. These findings support the new CLSI breakpoint change of Enterobacterales to amikacin.

Carbapenem resistance in Enterobacterales: Predicting clinical outcomes in bloodstream infections

PurposeCarbapenem-resistant Enterobacterales (CRE) are a global concern due to their high mortality rates and limited therapeutics. CRE-caused bloodstream infections (BSIs) are challenging to manage, especially in healthcare settings. This study aimed to investigate the predictors of mortality in BSI patients caused by CRE. MethodsA single center prospective study to examine the characteristics of BSI caused by CRE in a large academic hospital over 15 months. The main outcomes were microbiological characteristics and clinical outcomes of patients at 28 days based on a step-wise regression analysis. ResultsA total of 76 episodes of BSI due to CRE were included. The study found that the most common type of carbapenemase was OXA-48 (69.7 %, n = 53), followed by the co-existence of OXA-48 and MBL (26.3 %, n = 20), with Klebsiella pneumoniae being the most common (90 %, n = 69). Patients with OXA-48-BSI were more likely to have a urinary source of infection, while patients with MBL-BSI were more likely to have a non-urinary source of infection. All cases (100 %) had medical devices. Around 30.3 % of patients received effective empirical treatment, while 61.8 % received adequate therapy at 48 h. The overall mortality rate was 42.1 % (n = 32), and the main predictors of mortality in this study were the presence of sepsis and inadequate initial therapy, while age >65 predicted mortality in the linear regression but not the stepwise regression model. ConclusionCRE-BSIs are a serious health threat. The study highlights the need for preventive strategies focused on high-risk patients and proper device management to reduce BSI.

Early antibiotic de-escalation in patients with severe infections due to bloodstream infection by enterobacterales: A post hoc analysis of a prospective multicentre cohort

Data about antibiotic de-escalation in sepsis associated with the bloodstream and caused by Enterobacterales are scarce. The objectives of this study are to identify factors associated with early de-escalation and to analyse the impact of de-escalation on mortality in patients with Enterobacterales bloodstream infection (BSI) with a Sequential Organ Failure Assessment (SOFA) score ≥ 2. A prospective, multicentre cohort study was performed including episodes of BSI due to Enterobacterales and a SOFA score ≥ 2 who were receiving an active antipseudomonal β-lactam; the isolate should be susceptible to at least 1 narrower-spectrum antibiotic. Variables associated with de-escalation were identified using logistic binary regression. The association of de-escalation with 30-day mortality was investigated. Confounding was controlled by calculating a propensity score used as covariate, as matching variable, and for inverse probability treatment weighting. Of the 582 patients included, de-escalation was performed in 311 (53.4%). Neutropenia (adjusted odds ratio [aOR] = 0.37; 95% confidence interval [95% CI] = 0.18-0.75), central venous catheter (aOR = 0.52; 95% CI = 0.32-0.83), and extended-spectrum β-lactamase (ESBL)-producing isolate (aOR = 0.28; 95% CI = 0.17-0.48) were negatively associated with de-escalation, and urinary tract source was positively associated (aOR = 2.27; 95% CI = 1.56-3.33). The 30-day mortality was 6.8% (21 patients) in de-escalated patients and 14.4% (39) in not de-escalated patients (relative risk, 0.63; 95% CI = 0.44-0.89). In multivariate analysis including the propensity score, de-escalation was not associated with mortality (AOR = 0.98; 95% CI = 0.39-2.47) and was protective in the case of urinary or biliary tract source (AOR = 0.31, 95% CI = 0.09-1.06). Matched and inverse probability treatment weighting analysis showed similar results. These results suggest that early de-escalation from antipseudomonal β-lactams is safe in patients with Enterobacterales bacteremia and SOFA ≥ 2.

Evaluation of a Ureteral Stent Removal Protocol in Adult Kidney Transplant Recipients.

Existing literature on best practices to reduce the risk of infectious complications associated with ureteral stent removal in kidney transplant recipients is limited. Prior to 2021, a formal process surrounding stent removal was not in place at our institution. In June 2021, a stent removal protocol was established. This protocol included the following: obtaining a preprocedure urine culture, prescribing universal culture-directed antimicrobial prophylaxis, earlier stent removal posttransplant, and patient education. We performed a retrospective quasi-experimental study of kidney transplant recipients who had their stents removed between July 2020 and June 2022. The primary outcome was the incidence of infectious complications within 30 days. Infectious complications were defined as urinary tract infection and bacteremia due to urinary source, as well as hospitalization, emergency department visit, or outpatient encounter for possible urinary tract infection. Secondary objectives included infectious and immunologic complications within 30 days to 1 year from transplant. During this study period, 239 adult kidney transplant recipients were included: 88 in the preprotocol group and 151 in the protocol group. The median time to stent removal was shorter in the protocol group (25 vs 36 days, P < .001). More patients in the protocol group received preprocedure antibiotics (99% vs 36%, P < .001). Infectious complications were higher in the preprotocol group (9% vs 3%, P = .035). Overall, the stent removal protocol was associated with fewer infectious complications (odds ratio, 0.18; 95% CI, 0.05-0.73). Further investigation is necessary to determine which individual interventions, if any, drive this benefit.

Clinical characteristics, predisposing factors and outcomes for Enterococcus faecalis versus Enterococcus faecium bloodstream infections: a prospective multicentre cohort study

PurposesEnterococcal BSI is associated with significant morbidity and mortality, with fatality rates of approximately 20–30%. There are microbiological and clinical differences between E. faecalis and E. faecium infections. The aim of this study was to investigate differences in predisposing factors for E. faecalis and E. faecium BSI and to explore prognostic factors.MethodsThis study was a post-hoc analysis of PROBAC, a Spanish prospective, multicenter, cohort in 2016–2017. Patients with E. faecalis or E. faecium BSI were eligible. Independent predictors for BSI development in polymicrobial and monomicrobial BSI and in-hospital mortality in the monomicrobial group were identified by logistic regression.ResultsA total of 431 patients were included. Independent factors associated with E. faecium BSI were previous use of penicillins (aOR 1.99 (95% CI 1.20–3.32)) or carbapenems (2.35 (1.12–4.93)), hospital-acquired BSI (2.58 (1.61–4.12)), and biliary tract source (3.36 (1.84–6.13)), while congestive heart failure (0.51 (0.27–0.97)), cerebrovascular disease (0.45 (0.21–0.98)), and urinary tract source (0.49 (0.26–0.92)) were associated with E. faecalis BSI. Independent prognostic factors for in-hospital mortality in E. faecalis BSI were Charlson Comorbidity Index (1.27 (1.08–1.51)), SOFA score (1.47 (1.24–1.73)), age (1.06 (1.02–1.10)), and urinary/biliary source (0.29 (0.09–0.90)). For E. faecium BSI, only SOFA score (1.34 (1.14–1.58) was associated with in-hospital mortality.ConclusionsThe factors associated with E. faecium and E. faecalis BSI are different. These variables may be helpful in the suspicion of one or other species for empiric therapeutic decisions and provide valuable information on prognosis.

Evaluation of hospital-onset bacteraemia and fungaemia in the USA as a potential healthcare quality measure: a cross-sectional study

BackgroundHospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised...

Child exposure to N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its derived quinone (6PPDQ) in e-waste areas: Urinary concentrations, sources, and health effect assessment

N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ) and its parent 6PPD are ubiquitous in the environment and may induce multi-endpoint toxicity. Electronic waste (e-waste) dismantling is an under-recognized source of 6PPD and 6PPDQ emissions, and there is a lack of epidemiological investigations into their presence and health effects in local populations. This study aimed to determine the urinary concentrations of 6PPD and 6PPDQ in children aged 2–7 years from e-waste dismantling areas and evaluate their potential risk to physical growth. We found that children from the e-waste area had significantly elevated urinary concentrations of 6PPD and 6PPDQ (median: 0.073 and 2.34 ng/mL) compared to those in the reference area (0.020 and 0.24 ng/mL, respectively). The estimated urinary excretions of 6PPDQ in the e-waste exposure group were considerably higher than that in the reference group (p < 0.001). Furthermore, a borderline significant association of co-exposure to high levels of 6PPD and 6PPDQ with lower BMI z-score (OR = 1.99, 95 % Cl: 1.04, 3.82) was observed in the crude model and the model adjusted for age and gender. In conclusion, our study first reported the urinary 6PPD and 6PPDQ concentrations in children from e-waste dismantling areas. The result indicated that e-waste recycling activities contribute to significantly elevated body burdens of 6PPD and 6PPDQ in children, which may be a potential risk factor for physical growth. Further epidemiological and toxicological studies are needed to investigate the exposure and health risks, especially in vulnerable populations.

Presentation, management, and outcomes of older compared to younger adults with hospital-acquired bloodstream infections in the intensive care unit: a multicenter cohort study.

Older adults admitted to the intensive care unit (ICU) usually have fair baseline functional capacity, yet their age and frailty may compromise their management. We compared the characteristics and management of older (≥ 75years) versus younger adults hospitalized in ICU with hospital-acquired bloodstream infection (HA-BSI). Nested cohort study within the EUROBACT-2 database, a multinational prospective cohort study including adults (≥ 18years) hospitalized in the ICU during 2019-2021. We compared older versus younger adults in terms of infection characteristics (clinical signs and symptoms, source, and microbiological data), management (imaging, source control, antimicrobial therapy), and outcomes (28-day mortality and hospital discharge). Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%) were ≥ 75years old. Compared to younger patients, these individuals had higher comorbidity score and lower functional capacity; presented more often with a pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood pressure and temperature at presentation. Pathogens and resistance rates were similar in both groups. Differences in management included mainly lower rates of effective source control achievement among aged individuals. Older adults also had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower rates of discharge from hospital (12% versus 20%, p < 0.001) by this time. Older adults with HA-BSI hospitalized in ICU have different baseline characteristics and source of infection compared to younger patients. Management of older adults differs mainly by lower probability to achieve source control. This should be targeted to improve outcomes among older ICU patients.

Impact of an antimicrobial stewardship program indicator on the appropriateness of the empiric antibiotic treatment of urinary source Escherichia coli bacteraemia

A prospective multicentre study was carried out between 2017 and 2021 to assess (1) the appropriateness of the empirical treatment to the local guidelines of urinary source Escherichia coli bacteraemia, (2) the appropriateness of empirical treatment to antibiotic sensitivity results and (3) the degree of error in the local guidelines regarding the antibiotic sensitivity reported in acute care hospitals enrolled in the vigilància de les infeccions relacionades amb l'atenció sanitària de Catalunya program. During the study period, 79.0% of the empirical treatments analysed complied with the guidelines and 88.1% were appropriate in view of the in vitro activity of the isolated strain. The rate of appropriateness rose from 73.8% in 2017 to 81.0% in 2021 (P < 0.001). The degree of error in the recommendations regarding the in vitro activity of the isolated strains was 5.9% and remained stable during the study period. Antibiotic families correctly prescribed according to the guidelines were third-generation cephalosporins (54.9%), carbapenems (16.8%) and combinations of penicillins and beta-lactamase inhibitors (16.4%). Of the 8009 E. coli strains, 19.0% were extended-spectrum beta-lactamases producers, 36.8% were resistant to quinolones and 0.5% were resistant to carbapenems. The broad implementation of an antimicrobial stewardship program with quality indicators of antibiotic use improved compliance to local guidelines in the empiric treatment of urinary tract E. coli bacteraemia. The degree of error in local guidelines was low but higher in more complex hospitals and in healthcare-associated infections. Guidelines need to be constantly updated with the use of epidemiological data, rapid diagnostic tests and the analysis of patient risk factors specific to each geographical area.

Association of microbiological factors with mortality in Escherichia coli bacteraemia presenting with sepsis/septic shock: a prospective cohort study

ObjectivesThis study aimed to determine the association of Escherichia coli microbiological factors with 30-day mortality in patients with bloodstream infection (BSI) presenting with a dysregulated response to infection (i.e. sepsis or septic shock). MethodsWhole-genome sequencing was performed on 224 E coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance, and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). ResultsMortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02–1.07), Charlson index ≥3 (1.78; 0.95–3.32), urinary BSI source (0.30; 0.16–0.57), and active empirical treatment (0.36; 0.11–1.14) with an AUROC of 0.73 (95% CI, 0.67–0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94–14.04), eilA gene (2.62; 1.14–6.02), and astA gene (2.39; 0.87–6.59) as associated with mortality, with an AUROC of 0.76 (0.69–0.82). DiscussionDespite having a modest overall contribution, some microbiological factors were associated with increased odds of death and deserve to be studied as potential therapeutic or preventive targets.

Comparison of integron mediated antimicrobial resistance in clinical isolates of Escherichia coli from urinary and bacteremic sources

BackgroundAntimicrobial resistance (AMR) is a global threat driven mainly by horizontal gene transfer (HGT) mechanisms through mobile genetic elements (MGEs) including integrons. The variable region (VR) of an integron can acquire or excise gene cassettes (GCs) that confer resistance to antibiotics based on the selection pressure. Escherichia coli plays a significant role in the genetic transfer of resistance determinants to other Gram-negative bacteria. Current study is aimed to detect and compare integron-mediated resistance in clinical isolates of E. coli. Unique isolates of E. coli from urine or blood cultures were studied for their antimicrobial resistance patterns and integrons were detected using polymerase chain reaction assays followed by Sanger sequencing of GCs.ResultsDuring the study period, a total of 470 E. coli isolates were obtained, 361 (76.8%) from urinary and 109 (23.1%) from bacteremic sources. Class 1 integrons were detected in 66 (18.2%) and 26 (23.8%) isolates respectively. Urinary isolates of E. coli harbouring Class 1 integrons demonstrated significantly higher rates of resistance (p < 0.05) for most antibiotics (12/16, 75%) compared to integron negative isolates. Although not statistically significant, similar differences were observed in bacteremic isolates. Among the urinary isolates, 27 (40.9%) had a VR, in which the most common GC array detected was DfrA17-AadA5 (n = 14), followed by DfrA5 (n = 4) and DfrA12 (n = 3). Among bacteremic isolates, only 4 (15.3%) had a VR, all of which were carrying DfrA17. The detected GC array correlated with the respective isolates’ phenotypic resistance patterns.ConclusionWe found a strong correlation between integron positivity and trimethoprim resistance among E. coli from urinary sources. Although higher rates of resistance were observed in bacteremic isolates, they mostly carried empty integrons.

Bacteremia From a Presumed Urinary Source in Hospitalized Adults With Asymptomatic Bacteriuria

Guidelines recommend withholding antibiotics in asymptomatic bacteriuria (ASB), including among patients with altered mental status (AMS) and no systemic signs of infection. However, ASB treatment remains common. To determine prevalence and factors associated with bacteremia from a presumed urinary source in inpatients with ASB with or without AMS and estimate antibiotics avoided if a 2% risk of bacteremia were used as a threshold to prompt empiric antibiotic treatment of ASB. This cohort study assessed patients hospitalized to nonintensive care with ASB (no immune compromise or concomitant infections) in 68 Michigan hospitals from July 1, 2017, to June 30, 2022. Data were analyzed from August 2022 to January 2023. The primary outcome was prevalence of bacteremia from a presumed urinary source (ie, positive blood culture with matching organisms within 3 days of urine culture). To determine factors associated with bacteremia, we used multivariable logistic regression models. We estimated each patient's risk of bacteremia and determined what percentage of patients empirically treated with antibiotics had less than 2% estimated risk of bacteremia. Of 11 590 hospitalized patients with ASB (median [IQR] age, 78.2 [67.7-86.6] years; 8595 female patients [74.2%]; 2235 African American or Black patients [19.3%], 184 Hispanic patients [1.6%], and 8897 White patients [76.8%]), 8364 (72.2%) received antimicrobial treatment for UTI, and 161 (1.4%) had bacteremia from a presumed urinary source. Only 17 of 2126 patients with AMS but no systemic signs of infection (0.7%) developed bacteremia. On multivariable analysis, male sex (adjusted odds ratio [aOR], 1.45; 95% CI, 1.02-2.05), hypotension (aOR, 1.86; 95% CI, 1.18-2.93), 2 or more systemic inflammatory response criteria (aOR, 1.72; 95% CI, 1.21-2.46), urinary retention (aOR, 1.87; 95% CI, 1.18-2.96), fatigue (aOR, 1.53; 95% CI, 1.08-2.17), log of serum leukocytosis (aOR, 3.38; 95% CI, 2.48-4.61), and pyuria (aOR, 3.31; 95% CI, 2.10-5.21) were associated with bacteremia. No single factor was associated with more than 2% risk of bacteremia. If 2% or higher risk of bacteremia were used as a cutoff for empiric antibiotics, antibiotic exposure would have been avoided in 78.4% (6323 of 8064) of empirically treated patients with low risk of bacteremia. In patients with ASB, bacteremia from a presumed urinary source was rare, occurring in less than 1% of patients with AMS. A personalized, risk-based approach to empiric therapy could decrease unnecessary ASB treatment.

Risk factors and outcomes of bloodstream infection from a urinary source in kidney transplant recipients.

Bacteriuria is common among kidney transplant recipients (KTR). Risk factors and outcomes associated with bloodstream infection due to a urinary source (BSIU) in KTR are poorly understood. This single center case-control study from 2010 to 2022 compared KTR with BSIU to those with bacteria without bloodstream infection (BU). Multivariable logistic regression identified BSIU risk factors, and Cox models assessed its impact on graft failure. Among 3435 patients, who underwent kidney transplantation at Emory Hospital, 757 (22%) developed bacteriuria, among whom 142 (18.8%) were BSIU. Male sex, presence of Escherichia coli, Klebsiella pneumoniae, or Pseudomonas species in urine culture, urethral stricture, neuromuscular bladder disorder, and history of diabetes-induced renal failure were independently associated with increased odds of BSIU (Male sex: aOR 2.29, 95% CI 1.52, 3.47, E. coli: aOR 5.14, 95% CI 3.02, 9.13; K. pneumoniae aOR 3.19, 95% CI 1.65, 6.27, Pseudomonas spp aOR 3.06, 95% CI 1.25, 7.18; urethral stricture: 4.10, 95% CI 1.63, 10.3, neuromuscular bladder disorder aOR 1.98, 95% CI 1.09, 3.53, diabetes: aOR 1.64, 95% CI 1.08, 2.49). BSIU was associated with increased hazard of graft failure (HR 1.52, 95% CI 1.05, 2.20). Close monitoring is warranted for male KTR with bacteriuria, those with urine cultures positive for Pseudomonas spp, K. pneumoniae, or E. coli, as well as KTR with a history of diabetes-induced renal failure, urethral stricture, or neuromuscular bladder disorder due to their risk for developing BSIU. Future research should explore strategies to mitigate BSIU risk in these high-risk KTR and reduce the associated risk of long-term graft failure.

Metallo-Beta-Lactamase Producing Isolates of Escherichia coli and Klebsiella pneumoniae and their Resistance Profiles in Enugu, Nigeria: A Threat to Public Health

Background: A potential threat to public health is the rapidly spreading enterobacteriaceae, especially Escherichia coli and Klebsiella pneumoniae which produce metallo-beta-lactamases (MBL). This study evaluated the prevalence of metallo-beta-lactamase (MBL) from clinical and non-clinical sources in Enugu Metropolis.&#x0D; Methodology: The study was conducted in the Microbiology Laboratory of the University of Nigeria Teaching Hospital, Ituku-Ozalla between October 2020 and July 2021. A total of 150 isolates including 85 and 65 isolates of Escherichia coli and Klebsiella pneumoniae respectively was recovered. Standard microbiology procedures were used to identify and characterize the isolates. Antimicrobial susceptibility was done using the Kirby-Bauer disc diffusion technique. Phenotypic detection of Metallo-beta-lactamase production was determined using Combined Disk Tests.&#x0D; Results: Imipenem resistance was detected in 22 (25.9%) isolates of E. coli and 18 (27.7%) isolates of K. pneumoniae. Of the 22 strains of E. coli that were imipenem resistant, 8 (9.4%) and 14 (16.5%) were found to be MBL producers and non-MBL respectively. Of the 18 strains of Klebsiella pneumoniae that were imipenem resistant, 10 (15.4%) were MBL producers and 8 (12.3%) were non-MBL producers. The highest prevalence of MBL was recovered from urine sources in both E. coli and K. pneumonieae. All MBL-producing isolates were multidrug resistant.&#x0D; Conclusion: The overall prevalence of MBL in this study was 12.0%. Public health is at risk due to the occurrence of metallo-beta-lactamase. Antimicrobial stewardship and the implementation of infection control strategies are required to halt the spread of these resistant bacteria in the environment. The use of antibiotics should be with utmost prudence.

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.

Efficacy and safety of a structured de-escalation from antipseudomonal β-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial

De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal β-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal β-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal β-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. De-escalation from an antipseudomonal β-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Effect of automated identification of antimicrobial stewardship opportunities for suspected urinary tract infections

Abstract Objective: We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention. Design: Retrospective before-and-after study. Setting: Tertiary and quaternary care academic medical center. Patients: Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods. Methods: We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020–12/2020) and post-BPA (04/15/2021–04/30/2022) periods. Results: 774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18–65) in the pre-BPA group compared to 16 hours (IQR 2–34) in the post-BPA group (P &lt; 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source. Conclusions: Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review.

Hemodynamic Resuscitation Characteristics of Emergency Department Patients with Sepsis and Hypotension who are and are not Admitted to ICU; a Prospective Cross-sectional Study.

There is an evidence-practice gap in the optimal timing and volume of intravenous fluid as well as vasopressor administration in managing patients with sepsis. This study aimed to explore current hemodynamic resuscitation practice in emergency department (ED) for patients with sepsis and hypotension. This is a sub-analysis of the prospective multicentre ARISE FLUIDS observational study, which was conducted in 70 EDs across Australia and New Zealand. Baseline characteristics, as well as ED management and outcome of sepsis patients were compared between patients who were and were not admitted to intensive care unit (ICU) or high dependency unit (HDU). A total of 587 patients with a median age of 65 years and even sex distribution (49% female) were available for analysis. Almost two-thirds of patients with sepsis (63.2%, n=371) were not admitted to ICU/HDU and were given lower intravenous (IV) fluid volumes over 24-hours, compared to those receiving critical care (4077ml vs. 5421ml, p<0.001). Patients not admitted to an ICU/HDU had a lower Acute Physiology And Chronic Health Evaluation (APACHE) II score (median 14 vs. 18, P<0.001) and serum lactate level (1.8 vs. 2.8 mmol/L, P<0.001) compared to those admitted to ICU/HDU and 5.9% received a vasopressor infusion in the first 24-hours. Females, patients aged <65 years, and those with urosepsis or sepsis of non-respiratory origin received a greater volume of IV fluids. Almost two-thirds of patients were not admitted to ICU/HDU. In patients not admitted to ICU/HDU, 1 in 17 received a vasopressor infusion during their ED or early hospital stay. Patients not admitted to ICU/HDU received less fluid in the first 24 hours than those who were. Greater resuscitation fluid volumes were independently associated with female sex, age <65 years, higher lactate levels, and urinary or non-respiratory source of sepsis.

Molecular Characterization of High and Low Virulent Escherichia coli Clinical Strains Isolated from Patients with Urinary Tract Infections with or without Bacteremia in Southern Taiwan.

The most common extraintestinal pathogen and infection site is uropathogenic Escherichia coli (UPEC), which causes urinary tract infections (UTIs). UPEC is also a common pathogen in bloodstream infections; in severe cases, it can lead to death. Although host and bacterial virulence factors have been demonstrated to be associated with UTI pathogenesis, the role of the related contributing factors in UTI and urinary source bacteremia is not yet fully understood. This study aimed to compare and analyze the factors contributing to urinary bacteremia in patients with UTI. A total of 171 E. coli strains collected from patients with UTI and urinary source bacteremia at Chiayi Christian Hospital were used. Phylogenetic groups and virulence factors were determined using PCR. Drug resistance patterns were determined using the disk diffusion assay. Previous studies have demonstrated that fimbriae and papGII may be associated with first-step infections and severe UTIs, respectively. As expected, highly virulent E. coli strains (belonging to the phylogenetic B2 and D groups) were dominant in the bacteremic UTI (90%) and UTI (86.27%) groups. However, our results showed that the UTI group had a significantly higher prevalence of sfa/focDE (belonging to the S and FIC fimbriae) than the bacteremic UTI group (29.4% vs 12.5%; p=0.008). In the bacteremic group, we found that sfa/focDE was only detected in highly virulent strains. The bacteremic UTI group had a significantly higher prevalence of papGII (belonging to P fimbriae) than the UTI group (55.8% vs 37.3%; p=0.026). In addition, the P fimbriae gene cluster, including papC, papEF, and papGII, was predominant in highly virulent strains. Notably, our results show that multidrug-resistant (MDR) strains were significantly less virulent than non MDR strains. Taken together, our results provide insights into the contributing factors in patients with UTI and urinary bacteremia.