Gram-negative Urinary Tract Infections Research Articles

Comparing amoxicillin and trimethoprim: Overall performance in combating Escherichia coli-causing urinary tract infection

Urinary Tract Infection (UTI) is one of the most prevalent bacterial infections in the world, and 80% of reported UTI cases are derived by gram negative bacteria Escherichia coli. Uropathogenic Escherichia coli is strongly adaptive and resilient against immune response, forming Intracellular Bacterial Communities (IBC) inside uroepithelium cells that constitute the urethra and the bladder. Their rapid absorption of cellular nutrients enables them to advance upward toward the kidney and cause inflammation. Hence, based on the perceived severity of UTI, multiple antibiotics are used to treat UPEC-causing UTI. This article provides a detailed review on the contemporary performance of amoxicillin and trimethoprim, both widely used to treat UPEC-causing UTI for decades. Amoxicillin is a penicillin-derivative that produces bactericidal by inhibiting transpeptidase to disrupt peptidoglycan synthesis, causing rapid-growing bacteria to lyse. It is a well-tolerated drug that can be used on pregnant patients. Resistant UPEC develop beta-lactamase to counter amoxicillin. Trimethoprim, on the other hand, is a dihydropyrimidine antibiotic that impedes the production of tetrahydrofolic acids, producing either bacteriostatic or bactericidal effects. Resistant UPEC transforms the shape of tetrahydrofolic acids-producing enzyme, dihydrofolic reductase, to resist trimethoprim. Although amoxicillin and trimethoprim are competitive inhibitors are effective against a variety of gram-positive and gram-negative species, trimethoprim, in statistical study, is proven to be more effective than amoxicillin in treating gram-negative UTI. Today, the wide-spread resistant strains of UPEC exists for both drugs. Thus, amoxicillin and trimethoprim are implemented mainly through combination therapies, amoxicillin/clavulanate and trimethoprim sulfamethoxazole, respectively. These combinations are more effective than the drugs to be used alone and are able to counter some resistant strains, but UPEC that are resistant to combinations also exists. Regardless, both amoxicillin and trimethoprim are still used as first-line antibiotics, while more powerful antibiotics are reserved for special multi-resistant superbugs.

Molecular study of antibiotic resistance gene among nitrofurantoin-resistant gram-negative bacteria isolates from pregnant women

In pregnancy, urinary tract infection (UTIs) is a significant risk factor for morbidity, and nitrofurantoin is a common UTI therapy. The goal was to identify gram-negative UTI isolates and detect antibiotic resistance genes. The research involved 350 pregnant women hospitalised to Al-Zahraa teaching hospital for children’s health and maternity between September and December 2024. Out of 250 pregnant patients, 200 (57.14%) urine samples were bacterial-free, whereas 150 (42.86%) were positive for gram-negative bacteria. The findings showed that 105 isolates (70%) were Escherichia coli, 33 (22%) were Klebsiella pneumoniae, 8 (5.3%) were Pseudomonas aeruginosa, 3 (2%) were Proteus mirabilis, and 1 (0.7%) were Acinetobacter baumannii. The disc diffusion Kirby-Bauer method determined 150 (100%) gramme negative bacteria’s nitrofurantoin sensitivity. 33 (22%) isolates were antibiotic-resistant, 16 (10.66%) intermediate, and 101 (67.33%) susceptible. PCR analysis showed that all 33 out of 33 (100%) gram negative isolates had Ribe, and AcrAB genes. Additionally, a significant prevalence of nfsA-2 genes was discovered in 32 out of 33 isolates (96.96%) the nfsA-1 gene in 78.78% (26/33) of the isolates. The NfsB gene was detected in 30 out of 33 (90.90%) distinct isolates of nitrofurantoin-resistant gram-negative bacteria. The Nucleic acid and amino acid sequence study of NfsA and Ribe genes in some local isolates of K. pneumoniae reveals variations in sequence when compared to other global strains with the same genes.

Identification of beta-lactamase genes in Nitrofurantoin-resistant gram-negative bacteria isolated from pregnant women using molecular techniques

The predominant infection among pregnant women is urinary tract infection (UTIs), which may lead to various complications. So, this investigation was to detect gram-negative UTIs isolates and beta-lactam resistance genes. The study included 100 (28.57%) inpatient pregnant women and 250 (71.42%) outpatient pregnant women treated at Al-Zahraa teaching hospital for children’s health and maternity, Al-Najaf City, Iraq. Finding showed that The majority of the age group was 31-40 years old which involved 80 (22.85%) growth and 45 (12.85%) no growth. Results also showed the high rate of bacteria among pregnant women in third-trimester was 127 (36.28%). According Kirby-Bauer methods, only 33/150 (22%) of gram-negative isolates were nitrofurantoin-resistant. Results of PCR amplification showed that all 33 out of 33 (100%) gram negative isolates had the ctx-m gene. Additionally, a significant prevalence of AmpC gene was discovered in 32 out of 33 isolates (96.96%). The veb gene, on the other hand, was only detected in P. aeruginosa isolates, with a prevalence of 1 out of 33 (3.03%). The PCR findings revealed the presence of oxa-like 5 genes in 12.12% (4/33) of the isolates. Although oxa-69 was not identified in this study.

Rapid Antibiotic Susceptibility Testing of Gram-Negative Bacteria Directly from Urine Samples of UTI Patients Using MALDI-TOF MS.

Urinary tract infections (UTIs) are one of the most common human infections and are most often caused by Gram-negative bacteria such as Escherichia coli. In view of the increasing number of antibiotic-resistant isolates, rapidly initiating effective antibiotic therapy is essential. Therefore, a faster antibiotic susceptibility test (AST) is desirable. The MALDI-TOF MS-based phenotypic antibiotic susceptibility test (MALDI AST) has been used in blood culture diagnostics to rapidly detect antibiotic susceptibility. This study demonstrates for the first time that MALDI AST can be used to rapidly determine antibiotic susceptibility in UTIs directly from patients' urine samples. MALDI-TOF MS enables the rapid identification and AST of Gram-negative UTIs within 4.5 h of receiving urine samples. Six urinary tract infection antibiotics, including ciprofloxacin, cotrimoxazole, fosfomycin, meropenem, cefuroxime, and nitrofurantoin, were analyzed and compared with conventional culture-based AST methods. A total of 105 urine samples from UTI patients contained bacterial isolates for MALDI AST. The combination of ID and AST by MALDI-TOF allowed us to interpret the result according to EUCAST guidelines. An overall agreement of 94.7% was found between MALDI AST and conventional AST for the urinary tract pathogens tested.

Fundamental Role for the Urothelial Plaque in Gram-Negative Urinary Tract Infections

Fundamental Role for the Urothelial Plaque in Gram-Negative Urinary Tract Infections

Impact of Early Oral Antibiotic Therapy in Infants With Bacteremic Urinary Tract Infections.

To determine the effect of early conversion to oral antibiotics in infants ≤90 days with gram-negative bacteremia and concomitant urinary tract infection on hospital length of stay (LOS) and 30-day revisits for urinary tract infection. This retrospective cohort study included infants ≤ 90 days who had concomitant positive blood and urine cultures with gram-negative bacteremia at 22 hospitals from January 1, 2002 through January 31, 2020. Early oral conversion was defined as a maximum intravenous (IV) duration of 4 days. We conducted a noninferiority test to compare early oral conversion to long IV therapy. A propensity score framework was used to assess comparisons in survey-weighted regression models using matched weights. Among 174 infants, 73 infants received early oral conversion. The LOS was shorter in infants receiving early oral conversion compared to long IV therapy (median 2 days [interquartile range 2, 3] vs 4 days [3, 5]), descriptively (P < .001) and in noninferiority analysis (ratio = 0.43; 90% CI 0.35, 0.53, P < .001). Thirty-day revisits occurred in 5 of 174 (2.8%) of total patients. Early oral conversion did not meet our noninferiority criteria for the 30-day revisits (odds ratio: 4.22, 90%; confidence interval: 0.83, 21.34, P = .91). Early oral conversion was associated with shorter LOS. The rate of 30-day revisit rates overall was low.

1417. Fosfomycin Use in the Treatment of Complicated Urinary Tract Infections at a Veterans Affairs Medical Center

BackgroundThe prevalence of multidrug resistant gram-negative urinary tract infections (UTIs) is increasing, often requiring intravenous antimicrobial therapy. Oral fosfomycin is a recommended alternative agent for the treatment of cystitis caused by extended spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli). The primary objective of this study is to evaluate the efficacy of fosfomycin in the treatment of UTIs at the Veterans Affairs Long Beach Healthcare System. The secondary objective is to assess the incidence of adverse drug reactions associated with fosfomycin. MethodsThis is a retrospective, single-center, cohort study. Patients who received fosfomycin between June 1st, 2015 – June 30th, 2020 were included. Data collection was completed by chart review through the Computerized Patient Record System (CPRS). Descriptive analysis was used to evaluate data. Treatment outcomes were analyzed using a composite of clinical and microbiological cure. Clinical cure was defined as resolution of UTI symptoms. Microbiological cure was defined as urine sterilization within 1 month after completing treatment course with fosfomycin.ResultsA total of 62 unique patients were evaluated in this study. The mean age was 71.9 years. 56 patients (90.3%) were male, 31 patients (50.0%) had an indwelling catheter present at the time of treatment, and 48 patients (77.4%) had the presence of genitourinary tract pathology that may increase the risk of developing UTIs. Majority of patients (50%) had a urine culture result positive for E. coli prior to treatment, of which 43.5% were ESBL-producing. 60 patients (96.8%) received more than 1 dose of Fosfomycin. Out of 29 patients who were eligible to be evaluated for clinical outcomes, 20 patients (68.9%) met a positive composite outcome of either microbiological cure, clinical cure, or both. 4 patients (6.5%) experienced an adverse drug reaction of diarrhea that was self-limited. ConclusionFosfomycin is an effective and well-tolerated antimicrobial agent that may be considered for treatment of complicated UTIs without evidence of pyelonephritis or bacteremia caused by multi-drug resistant organisms in the veteran population.Disclosures All Authors: No reported disclosures

Antibacterial data synthesis challenges: a systematic review of treatments for complicated Gram-negative urinary tract infections.

Aim: To determine the suitability of network meta-analysis (NMA) using antibacterial treatment evidence in complicated urinary tract infection. Materials& methods: We conducted a systematic literature review to identify published clinical trial data for complicated urinary tract infection treatments. We performed a feasibility assessment to determine whether the available evidence would support the creation of a robust NMA, considering key assumptions of homogeneity, similarity and consistency. Results: Twenty-five trials met eligibility criteria. Risk of bias was low, and individual studies met their primary end point(s). Assumptions central to the conduct of a robust NMA were not met. Heterogeneity was ubiquitous, including baseline pathogen, treatment and patient characteristics. Conclusion: Limited and heterogeneous data identified make the use of NMA to compare novel antibacterial agents impractical and likely unreliable.

Interplay between Phenotypic Resistance to Relevant Antibiotics in Gram-Negative Urinary Pathogens: A Data-Driven Analysis of 10 Years’ Worth of Antibiogram Data

The global emergence of antimicrobial resistance (AMR) has become a critical issue for clinicians, as it puts the decades of developments in the medical field in jeopardy, by severely limiting the useful therapeutic arsenal of drugs, both in nosocomial and community-acquired infections. In the present study, a secondary analysis of taxonomic and resistance data was performed, corresponding to urinary tract infections (UTIs) caused by Gram-negative bacteria, detected between 1 January 2008 to 31 December 2017 at the Albert Szent-Györgyi Health Center, University of Szeged. The following were identifiable from the data collected: year of isolation; outpatient (OP)/inpatient (IP) origin of the isolate; taxonomy; and susceptibility/resistance to selected indicator antibiotics. Principal component analysis (PCA) and a correlation matrix were used to determine the association between the presences of resistance against indicator antibiotics in each taxonomic group. Overall, data from n = 16,240 outpatient and n = 13,964 inpatient Gram-negative UTI isolates were included in the data analyses. In E. coli, strong positive correlations were seen between resistance to ciprofloxacin (CIP) and gentamicin (GEN) resistance (OP: r = 0.6342, p = 0.049; IP: r = 0.9602, p < 0.001), whereas strong negative correlations were shown for fosfomycin (FOS) and nitrofurantoin (NIT) resistance (OP: r = −0.7183, p = 0.019; IP: r = −0.7437; p = 0.014). For Klebsiella spp. isolates, CIP resistance showed strong positive correlation with resistance to third-generation cephalosporins (3GC) and GEN (r = 0.7976, p = 0.006 and r = 0.7428, p = 0.014, respectively) in OP isolates, and with resistance to trimethoprim-sulfamethoxazole (SXT) and FOS (r = 0.8144, p = 0.004 and r = 0.7758, p < 0.001, respectively) in IP isolates. For members of the Citrobacter-Enterobacter-Serratia group, the resistance among indicator antibiotics showed a strong positive correlation, with the exception of FOS resistance. In the Proteus-Providencia-Morganella group, the strongest association was noted between CIP and SXT resistance (OP: r = 0.9251, p < 0.001; IP: r = 0.8007; p = 0.005). In the case of OP Acinetobacter spp., CIP showed strong and significant positive correlations with most indicator antibiotics, whereas for IP isolates, strong negative correlations arose among imipenem (IMI) resistance and resistance to other drugs. For Pseudomonas spp., strong and positive correlations were noted among resistance to β-lactam antibiotics and aminoglycosides, with the exception of ceftazidime (CEFT), showing strong, but negative correlations. Though molecular tests and sequencing-based platforms are now considered as the gold-standard for AMR surveillance, standardized collection of phenotypic resistance data and the introduction of Big Data analytic methods may be a viable alternative for molecular surveillance, especially in low-resource settings.

Burden of illness in US hospitals due to carbapenem-resistant Gram-negative urinary tract infections in patients with or without bacteraemia

BackgroundUrinary tract infections (UTIs) are the most common infections caused by Gram-negative bacteria and represent a major healthcare burden. Carbapenem-resistant (CR) strains of Enterobacterales and non-lactose fermenting pathogens further complicate treatment approaches.MethodsWe conducted a retrospective analysis of the US Premier Healthcare Database (2014–2019) in hospitalised adults with a UTI to estimate the healthcare burden of Gram-negative CR UTIs among patients with or without concurrent bacteraemia.ResultsAmong the 47,496 patients with UTI analysed, CR infections were present in 2076 (4.4%). Bacteraemia was present in 24.5% of all UTI patients, and 1.7% of these were caused by a CR pathogen. The most frequent CR pathogens were Pseudomonas aeruginosa (49.4%) and Klebsiella pneumoniae (14.2%). Patients with CR infections had a significantly longer hospital length of stay (LOS) (median [range] 8 [5–12] days vs 6 [4–10] days, P < 0.001), were less likely to be discharged home (38.4% vs 51.0%, P < 0.001), had a higher readmission rate (22.6% vs 13.5%, P < 0.001), and had greater LOS-associated charges (mean US$ 91,752 vs US$ 66,011, P < 0.001) than patients with carbapenem-susceptible (CS) infections, respectively. The impact of CR pathogens was greater in patients with bacteraemia (or urosepsis) and these CR urosepsis patients had a significantly higher rate of mortality than those with CS urosepsis (10.5% vs 6.0%, P < 0.001).ConclusionsAmong hospitalised patients with UTIs, the presence of a CR organism and bacteraemia increased the burden of disease, with worse outcomes and higher hospitalisation charges than disease associated with CS pathogens and those without bacteraemia.

High Rates of Antibiotic Nonsusceptibility in Gram-negative Urinary Tract Infection in Children With Risk Factors Occurring in the Preceding Month: Considerations for Choosing Empiric Treatment.

Choosing an empiric treatment for urinary tract infections (UTIs) requires epidemiologic data on antibiotic nonsusceptibility (ANS) rates, and risk factors for UTI and ANS in the individual patient. We assessed ANS in community-acquired UTI, and its association with risk factors exposure (previous antibiotic treatment, UTI and hospital visit) <1 month or 1-11 months before the current UTI episode. This was a retrospective, cohort study. Children <2 years with hospital visits and a positive urine culture obtained <48 hours from hospital admission whose culture yielded Gram-negative bacteria during the years 2015-2016, were included. Of the overall 744 episodes, 80% were Escherichia coli. Overall ANS rates were 66% for ampicillin; 27%-29% for amoxicillin/clavulanic acid, cephalosporins (indicating extended-spectrum beta-lactamase) and trimethoprim-sulfamethoxazole; 14% for nitrofurantoin; 5%-6% for gentamicin, ciprofloxacin and piperacillin/tazobactam; and <1% for meropenem and amikacin. Higher ANS rates were associated with Bedouin (vs. Jewish) ethnicity, exposure to risk factors <1 month, and to a lesser extent during the 1-11 months before the studied UTI episode. In episodes with risk factors <1 month, ANS rates were 81% for ampicillin; 47%-58% for amoxicillin/clavulanic acid, cephalosporins and trimethoprim-sulfamethoxazole; 19% for nitrofurantoin; 12%-23% for gentamicin, ciprofloxacin and piperacillin/tazobactam; and 2% for meropenem and amikacin. Previous antibiotic treatment, hospital admission and UTI, especially <1 month before the current episode, and Bedouin ethnicity, were all associated with high rates of ANS. These findings are important and may assist the treating physician in choosing an adequate empiric treatment for UTI.

1677. Evaluation of Optimal Treatment for Urinary Tract Infections in Outpatient Clinics at an Academic Medical Center

BackgroundInappropriate prescribing of antibiotics is an important modifiable risk factor for antibiotic resistance. The Joint Commission has identified the need for outpatient antimicrobial stewardship efforts. The purpose of this study was to assess the incidence of optimal empiric antibiotic therapy for urinary tract infections (UTIs) in outpatient clinics at VCU Health.MethodsThis was a retrospective study of patients seen in internal medicine (IM) and urology clinics between July 1, 2018 and June 30, 2019. Patients were included if they were ≥ 18 years old, had a diagnosis of UTI per ICD-10 code, and received a prescription to treat a UTI at the visit. Patients were excluded if they had a concurrent infection, currently prescribed antibiotics, or pregnant. The primary outcome was to evaluate the incidence of optimal empiric treatment for UTIs. Appropriateness of antibiotic therapy was assessed based on prior culture data along with our institutional UTI treatment guideline.ResultsTwo hundred and twenty-six patients were included: 136 in IM clinics and 90 in urology clinics. Patients in the IM clinics were significantly older (mean age 64.8 vs. 60.5, p= 0.033) and more were female (88% vs. 38%, p< 0.001). More patients in the urology clinics had a history of a UTI within 24 months (72% vs. 57%, p= 0.016), history of fluoroquinolone-resistant Gram-Negative UTIs (35% vs. 13%, p= 0.007), and history of genitourinary cancer (28% vs. 1%, p< 0.001). Overall, 61% of patients were treated with optimal empiric antibiotics. Incidence of optimal prescribing in the IM clinics was significantly higher compared to urology clinics (69% vs 49%, p= 0.002). See table 1 for additional results.Table 1. Optimal UTI Treatment in Internal Medicine Clinics vs Urology Clinics ConclusionIM clinics more frequently prescribed optimal empiric antibiotics for UTIs compared to urology clinics. Resident prescribers were more likely to prescribe optimal empiric therapy. Presence of a beta-lactam allergy was not predictive of optimal prescribing. These data highlight opportunities for antibiotic therapy optimization for UTIs at our health system.Disclosures All Authors: No reported disclosures

Treatment outcome and predictors of poor clinical response in extensively drug-resistant gram-negative urinary tract infection among children: A single-institution experience.

Extensively drug-resistant (XDR) is defined as isolates sensitive only to two or fewer antimicrobial categories. This paper aims to present the treatment outcome and identify factors associated with poor clinical response among children with XDR gram-negative urinary tract infection (UTI). This is a retrospective cohort conducted at a tertiary pediatric hospital from January 2014 to June 2017. All patients diagnosed with culture-proven XDR gram-negative UTI were identified and analyzed. Descriptive statistics were used to summarize demographic and clinical characteristics. Patients were categorized according to treatment outcomes: success vs. failure. Univariate analysis and multivariate logistic regression were used to assess statistical differences between the groups and determined patient variables that are predictive of poor response. Odds ratio (OR) and corresponding 95% confidence interval (CI) were generated. A total of 29 (19.2%) XDR gram-negative pediatric UTIs were identified within the 42-month study period. No significant differences were noted in demographic characteristics between the groups. Treatment outcome of XDR gram-negative UTI patients showed that combination therapy with colistin had the highest success rate (40.9%), followed by non-colistin (36.4%) and combination therapy without colistin (22.7%). However, univariate analysis showed no significant difference among the different treatment groups (p=0.65). On multivariate logistic regression, receiving immunosuppressant and the presence of indwelling urinary catheters were independent predictors of poor clinical response among pediatric patients with XDR gram-negative UTI (OR 19.44, 95% CI 1.50-251.4, p=0.023 and OR 20.78, 95% CI 1.16-371.28, p=0.039; respectively). The treatment success rate of XDR gram-negative pediatric UTI ranged from 22.7-36.4%. This finding emphasizes the need to advocate antibiotic stewardship to prevent further increase in XDR UTIs. Indwelling urinary catheters and receipt of immunosuppressants are associated with poor clinical outcome.

Contributing Factors to the Clinical and Economic Burden of Patients with Laboratory-Confirmed Carbapenem-Nonsusceptible Gram-Negative Urinary Tract Infections.

PurposeWe explored patient- and hospital-level predictor variables for worse clinical and economic outcomes in carbapenem-nonsusceptible urinary tract infections (UTIs).Patients and MethodsWe used electronic data (January 2013–September 2015; 78 US hospitals) from a large multicenter clinical database. Nonduplicate gram-negative isolates were considered carbapenem-nonsusceptible if they had resistant/intermediate susceptibility. Potential predictors of outcomes (mortality, 30-day readmissions, length of stay [LOS], hospital total cost, and net gain/loss per case) were examined using generalized linear mixed models. Significant predictors were identified based on statistical significance and model goodness-of-fit criteria.ResultsA total of 1439 carbapenem-nonsusceptible urine cases were identified. The mortality rate was 5.5%; the hospital readmission rate was 25.0%. Mean (standard deviation [SD]) LOS, total cost, and loss per case were 12 (14) days, $21,502 ($37,172), and $5828 ($26,540), respectively. Hospital-onset (vs community-onset) infection significantly impacted all outcomes: mortality (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19–4.11; P=.01), 30-day readmissions (OR, 2.35; 95% CI, 1.49–3.71; P<.001), LOS (25.7 vs 10.2 days; P<.001), hospital total cost ($67,810 vs $22,141; P<.001), and loss per case (–$28,054 vs –$10,809; P<.001). Mechanical ventilation/intensive care unit status, neoplasms, and other underlying diseases were also common predictors for worse outcomes overall; polymicrobial infection was significantly associated with worse economic outcomes. Other key predictors were >1 prior hospitalization for 30-day readmissions, high Acute Laboratory Risk of Mortality Score for mortality, LOS, cost, and hospital teaching status for cost.ConclusionHospital-onset infections, polymicrobial infections, higher clinical severity, and underlying diseases are key predictors for worsened overall burden of carbapenem-nonsusceptible gram-negative UTIs.

Predictive factors for Enterococcus faecalis in complicated community-acquired urinary tract infections in older patients.

Risk factors for complicated community acquired Enterococcus faecalis urinary tract infection (UTI) in older patients are not well known. We identified the predictive factors for E. faecalis on a cohort of 659 older patients admitted to hospital with complicated UTI. We also examined the adequacy of empirical antimicrobial therapy and outcomes in E. faecalis UTI. Multivariable logistic regression was used to identify predictors of E. faecalis UTI. A total of 87 (13.2%) patients had E. faecalis UTI; of these 63.2% were men, their mean age was 82.3 years and they had a great number of comorbidities. Severe sepsis or septic shock was present in 50.5%, and bacteremia was present in 26%. Indwelling urinary catheter and previous urinary instrumentation were risk factors for E. faecalis UTI by multivariate analysis (OR 2.05; 95% CI 1.15-3.65 and OR 2.16; 95% CI 1.08-4.34, respectively). Inadequate empirical antimicrobial therapy was higher in E. faecalis UTI than in UTI caused by Gram-negative microorganisms (66.6% vs 19%, P < 0.001). No significant differences in length of hospital stay or mortality were noted between E. faecalis and Gram-negative UTI. In older patients admitted to hospital with complicated community-acquired UTI, E. faecalis should be considered for empirical treatment if the patient has a urinary catheter or previous urinary tract instrumentation in order to avoid inadequate empirical antibiotic therapy. Geriatr Gerontol Int 2019; ••: ••-••.

1433. Predictive Models for Antibiotic Coverage of Gram-Negative Urinary Tract Infections

BackgroundProviders use institutional recommendations, national guidelines, and antibiograms to decide on empiric antibiotics. As local antibiograms are most effective after organisms are known, we sought to use local microbiology and clinical data to develop predictive models for antibiotic coverage prior to identifying the organism. We focused on Gram-negative organisms as they are common urinary pathogens and are often the cause of sepsis originating in the urinary tract. As such, they are important to cover in hospitalized patients with urinary tract infections (UTI).MethodsHospitalized patients, with a diagnosis of UTI and a positive urine culture in the first 48 hours were included. Gram-positive organisms, yeast, and cultures without susceptibilities were excluded. Unknown susceptibilities were filled in using expert-derived rules. Clinical information from electronic health record (EHR) data were extracted on each patient. Penalized logistic regression with 10-fold cross validation was used to develop final models for coverage for five antibiotics (cefazolin, ceftriaxone, ciprofloxacin, cefepime, piperacillin–tazobactam). Final models were chosen based on their discrimination, calibration, and number of predictors, and then tested on a held-out validation dataset.ResultsIncluded were 5,096 patients (80% training; 20% validation). Coverage ranged from 65% for cefazolin to 90% for cefepime. Positive blood cultures were present in 544 (11%) with 388 (71%), including a urinary pathogen. In the first 24 hours, 2329 (46%) were hypotensive, 2179 (43%) had a respiratory rate > 22, 2049 (40%) had a WBC > 12, 1079 (21%) were febrile, and 584 (11%) required ICU care. Final model covariates included demographics, antibiotic exposure, prior resistant pathogens, and antibiotic allergies. The five predictive models had a point-estimate for the area under the ROC on the validation set that ranged from 0.70 for ciprofloxacin to 0.73 for ceftriaxone.ConclusionIn this cohort of moderate to high acuity hospitalized patients with Gram-negative urinary pathogens, we used EHR data to develop 5 models that predict antibiotic coverage which could be used to support empiric prescribing. These models performed well in a held-out validation set.Disclosures All authors: No reported disclosures.

Epidemiology, susceptibility, and risk factors for acquisition of MDR/XDR Gram-negative bacteria among kidney transplant recipients with urinary tract infections.

BackgroundMultiple drug resistant/extensively drug resistant (MDR/XDR) Gram-negative urinary tract infections (UTIs) represent a growing threat to kidney transplant recipients. This retrospective study aimed to assess the incidence and microbiological profile of MDR/XDR Gram-negative UTIs, to identify drug susceptibility of MDR/XDR bacteria, and to determine the potential risk factors for MDR/XDR UTIs in kidney recipients.Materials and methodsDuring the study period, 1569 patients underwent consecutive kidney transplantation in two transplantation centers. We studied the demographics, clinical characteristics, and urine culture data from kidney recipients with MDR/XDR Gram-negative UTIs, and verified the risk factors associated with MDR/XDR infections.ResultsEighty-one kidney recipients yielded 88 episodes of MDR/XDR Gram-negative UTIs with five patients (6.2%) succumbing to all-cause in-hospital mortality. The most frequently isolated bacterium was Escherichia coli (62.5%). Almost all MDR/XDR Gram-negative bacteria were resistant to first- and second-generation cephalosporin, and monocyclic beta-lactam. They were relatively sensitive to meropenem, amikacin, and tigecycline. As for the 12 XDR bacteria, all of them were resistant to meropenem and 25% of them were resistant to tigecycline. All XDR Acinetobacter baumannii and E. coli were susceptible to tigecycline. Nosocomial infection (odds ratio [OR] = 11.429, 95% CI = 1.311–99.625, P = 0.027) was the only independent predictor of MDR/XDR Gram-negative UTIs. Non-fermenting bacterial infection (OR = 20.161, 95% CI = 3.409–119.240, P = 0.001), polycystic kidney disease (OR = 39.871, 95% CI = 1.979–803.384, P = 0.016), and serum creatinine level > 1.5 mg/dL (OR = 8.688, 95% CI = 1.354–55.747, P = 0.023) were significantly different between XDR and MDR Gram-negative UTIs.ConclusionMeropenem, amikacin, and/or tigecycline can be prescribed for MDR/XDR Gram-negative infections. Tigecycline can also be prescribed for XDR A. baumannii and E. coli. Nosocomial infection was a risk factor for MDR/XDR Gram-negative UTIs, while XDR UTIs were associated with non-fermenting bacterial infection, polycystic kidney disease, and impaired renal function.

Antimicrobial susceptibility survey on bacterial agents of canine and feline urinary tract infections: Weight of the empirical treatment.

This work characterised the antimicrobial susceptibility of uropathogens isolated from empirically treated dogs and cats. Within-household transmission of uropathogens can involve humans and companion animals. Knowledge on the prevalence and susceptibility pattern of isolates from canine and feline urine samples and the impact of prior antimicrobial treatment is important to prevent the dissemination of antimicrobial resistance. A retrospective study was conducted selecting antibiotic-treated companion animals. Urine samples were collected by cystocentesis and were submitted to an Italian diagnostic laboratory over a 2-year period (2013-2015). The antimicrobial susceptibility of the isolates was analysed both using Clinical and Laboratory Standards Institute (CLSI) guidelines and a formula to help select rational antimicrobial therapy. Gram-negative bacteria were clearly prevalent. Gentamicin had the highest impact factors. Amoxicillin/clavulanic acid and doxycycline appeared to be the most effective compounds against Gram-positive infections, whilst marbofloxacin may be a useful option against Gram-negative urinary tract infections (UTIs) as well as doxycycline and trimethoprim/sulfamethoxazole in cats and dogs, respectively. Consulting published studies, a comparable overall trend regarding bacterial species incriminated in canine and feline UTIs and their susceptibilities seems likely, despite different circumstances where the studies were conducted. Companion animals are potential reservoirs of drug-resistant uropathogens. Judicious use of antibiotics is necessary to maintain the efficacy of antimicrobials in human and veterinary medicine. Antimicrobial susceptibility monitoring programmes are therefore essential to facilitate the choice of antimicrobial agent that is most likely to be effective, particularly in cases of prior antimicrobial treatment.

Spectrum and antibiotic resistance of uropathogens between 2004 and 2015 in a tertiary care hospital in Hungary.

Surveillance of the bacterial spectrum and antibiotic-resistance patterns of locally occurring uropathogens is essential to serve as a basis for empirical treatment of urinary tract infections (UTIs), as antibiotic-resistance rates may vary geographically with significant differences between countries and regions, and with time. We retrospectively analysed all urine samples taken in the department of urology in a tertiary care hospital in Hungary from January 2004 to December 2015.Results/Key findings. The five most commonly occurring bacteria were Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. Resistance of Escherichia coli to ciprofloxacin increased significantly from 19 to 25 %. Although the resistance of Escherichia coli against cephalosporins showed an increasing trend, it still remained generally low. However, resistance rates of K. pneumoniae to cephalosporins were very high, reaching 60 %, due to the high rate of extended-spectrum-β-lactamase-positive Klebsiella strains. We observed a significant increase in the rate of carbapenem-resistant Pseudomonas aeruginosa. Fluoroquinolones cannot be recommended for empirical treatment in our region. Cephalosporins can be a good empirical choice for treating Gram-negative UTIs, but should be avoided when multi-drug resistant (MDR) bacteria are suspected. Increases in the rate of carbapenem-resistant Pseudomonas aeruginosa, and in the general rate of MDR bacteria, are both a very alarming trend. We recommend practising prudent antibiotic policy, preferably using antibiotics with the narrowest possible spectrum.

Decreasing Vancomycin Utilization in the NICU by Optimizing Treatment Decisions in Suspected Late Onset Sepsis

BackgroundLate Onset Sepsis (LOS) is frequently suspected in NICU patients in the setting of nonspecific clinical symptoms. Based on institutional antibiogram data, empiric treatment of LOS in our NICU is vancomycin and amikacin with a plan to deescalate or discontinue based on culture results and symptomatology. Baseline data in our NICU revealed vancomycin overuse where vancomycin was continued past 48 hours of culture negativity, after Gram-negative urinary tract infection (UTI) was diagnosed, or for urine cultures reported with multiple organisms or < 10,000 CFU/mL. Our objective was to eliminate inappropriately prolonged empiric use of vancomycin for suspected LOS or UTI.MethodsTo institute timely discontinuation of vancomycin when cultures are negative at 48 hours, group education sessions were conducted for physicians, nurse practitioners, and nurses that included evidence-based criteria for diagnosing “true UTI”. Vancomycin indication for use and duration were added to the rounding script for the night shift.ResultsAt baseline over a 6 month period, extra vancomycin doses were administered in 39% of LOS courses, typically because late-night doses (past 48 hours culture negativity) preceded the decision to discontinue empiric therapy on morning rounds. After intervention, during a 6 month period, extra vancomycin doses were reduced to 3%. A baseline anonymous survey revealed that some prescribers advocated continuing vancomycin in the setting of urine cultures with < 10,000 CFU/mL (18%) or for Gram-negative UTI until sensitivities are reported (24%). After intervention, these were both reduced to 7%. At baseline over a 9 month review of UTI data, the use of vancomycin past 48 hours occurred in 86% of patients with negative or contaminated urine cultures (< 10,000 CFU/mL or > 1 organism) and in 48% of patients with Gram-negative UTI. In the post intervention phase, this occurred in 0% and 50% (N = 2) of cases respectively.ConclusionA high incidence of overtreatment with vancomycin was found to be related to inconsistent system processes and knowledge deficiencies. Through improved documentation, staff education and creation of evidence based guidelines for the diagnosis and management of UTI, we successfully minimized vancomycin overutilization for suspected LOS and UTI in the NICU.Disclosures All authors: No reported disclosures.