scholarly journals 500. Prevalence of Extended-Spectrum β-lactamase and Carbapenem-Resistant Gram-Negative Bacteria in Patients with Urinary Tract Infection and Urosepsis Admitted through Emergency Departments in the United States

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S243-S243
Author(s):  
Sukhjit Takhar ◽  
Anusha Krishnadasan ◽  
Gregory J Moran ◽  
William Mower ◽  
Kavitha Pathmarajah ◽  
...  
Keyword(s):  
Risk Factors ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Susceptibility Testing ◽  
The United States ◽  
Gram Negative ◽  
Resistance Risk ◽  
Carbapenem Resistant ◽  
Extended Spectrum

Abstract Background Gram-negative infections due to extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae (CRE) and non-fermenting (CR-NF) strains, are increasingly encountered. Study objectives were to determine prevalence and associated risk factors and outcomes for these strains among emergency department patients hospitalized for urinary tract infection (UTI) at 11 US hospitals. Methods This was a prospective observational study of patients ≥18 years hospitalized for UTI. Clinical data were collected at the index visit. Urine was obtained for culture and susceptibility testing. Electronic medical record and telephone follow-up were conducted after 30 days for site laboratory results, treatment, and clinical outcomes. Positive culture was defined as 1 uropathogen with growth at ≥104 cfu/mL, or 2 with 1 or both at ≥105 cfu/mL, or ≥3 with 1 or 2 at ≥105 cfu/mL. Isolates with ceftriaxone (CRO) or meropenem MIC >1 μg/mL will undergo reference laboratory (IHMA, Inc., Schaumburg, IL) susceptibility testing, including against newer antibiotics and cefiderocol. Results We enrolled 774 participants between 2018 and 2019; 289 (37.3%) excluded due to urine culture not done, no growth, or contamination. Of 485 culture-positive participants (median age 56 years, 62.0% female), 432 (89.1%) grew 1 uropathogen, 48 (9.9%) 2, and 5 (1.0%) ≥3. Prevalences of CRO-resistant Enterobacteriaceae, CRE, and CR-NF were 19.9%, 2.1%, and 10.7%, respectively. At sites, 95.7% of CRO-resistant Enterobacteriaceae isolates were ESBL. Among participants with any or no antibiotic resistance risk factors, i.e., antibiotics, hospitalization, long-term care, or travel within 90 days, prevalence of CRO-resistant Enterobacteriaceae was 68/228 (29.8%) and 10/155 (6.5%), respectively. Among those with CRO-resistant vs. susceptible Enterobacteriaceae infections, ICU admission and death occurred in 9.9% vs. 6.6% and 3.7% vs. 1.0%, with median time home over 30 days, 24 vs. 27 days, respectively. Conclusion Among US hospitalized patients with UTI, infections due to CRE remain uncommon; however, ESBL and CR-NF now account for a substantial proportion of cases and are associated with resistance risk factors and worse outcomes. Disclosures All authors: No reported disclosures.

scholarly journals Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial

2019 ◽  
Vol 69 (12) ◽  
pp. 2045-2056 ◽  
Author(s):  
Keith S Kaye ◽  
Louis B Rice ◽  
Aaron L Dane ◽  
Viktor Stus ◽  
Olexiy Sagan ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Acute Pyelonephritis ◽  
Therapeutic Option ◽  
Elevated Serum ◽  
Complicated Urinary Tract Infection ◽  
The United States ◽  
Success Rates ◽  
Gram Negative

Abstract Background ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States. Methods Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days. Results Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: −0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19–21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient. Conclusions ZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections. Clinical Trial Registration NCT02753946

scholarly journals In Vivo Efficacy of Cefiderocol against Carbapenem-Resistant Gram-Negative Bacilli in Murine Urinary Tract Infection Models

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S472-S472 ◽  
Author(s):  
Shuhei Matsumoto ◽  
Sachi Kanazawa ◽  
Rio Nakamura ◽  
Masakatsu Tsuji ◽  
Takafumi Sato ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
In Vivo Efficacy ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Infection Models

scholarly journals 1367. Clinical Cure in Secondary Efficacy Populations in Patients With Complicated Urinary Tract Infection Treated With ZTI-01 (Fosfomycin for Injection): Findings From the ZEUS Trial

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S418-S419 ◽  
Author(s):  
Keith Kaye ◽  
Louis B Rice ◽  
Viktor Stus ◽  
Olexsiy Sagan ◽  
Elena Fedosiuk ◽  
...  
Keyword(s):  
United States ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Clinical Cure ◽  
Complicated Urinary Tract Infection ◽  
The United States ◽  
Research Support ◽  
Gram Negative ◽  
Cure Rates

Abstract Background ZTI-01 (fosfomycin for injection) is an investigational epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has a broad spectrum of in vitro activity, including multidrug-resistant Gram-negative pathogens, and is being developed for the treatment of patients with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States. Methods ZEUS was a multicenter, double-blind, Phase 2/3 trial in hospitalized adults with cUTI and AP to evaluate safety and efficacy. Randomized patients received 6 g ZTI-01 q8h or 4.5 g IV piperacillin/tazobactam (PIP-TAZ) q8h for 7 days; patients with baseline bacteremia could receive up to 14 days; study continued to late follow-up (LFU, 26 ± 2 days). Oral step-down therapy was prohibited. ZTI-01 met the primary endpoint of noninferiority to PIP-TAZ. Secondary objectives included comparing clinical cure rates (assessed by investigator) in the modified intent-to-treat (MITT), microbiologic MITT (m-MITT), clinical evaluable (CE), and microbiologic evaluable (ME) populations at test-of-cure (TOC, Day 19 ± 2 days). Results There were 464 patients randomized who received study drug. In all populations, clinical cure rates at TOC were high and similar between treatment groups (>90%) (table). Conclusion These results demonstrate consistent efficacy in multiple secondary efficacy populations for patients with cUTI and AP who were treated with either ZTI-01 or PIP-TAZ. If approved by FDA, ZTI-01 may provide a new IV option with a differentiated MOA for patients in the United States with serious Gram-negative infections. 95% confidence intervals (CIs, two-sided) were computed using a continuity-corrected Zstatistic. Disclosures K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. L. B. Rice, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee. V. Stus, Zavante Therapeutics, Inc.: Investigator, Research support. O. Sagan, Zavante Therapeutics, Inc.: Investigator, Research support. E. Fedosiuk, Zavante Therapeutics, Inc.: Investigator, Research support. A. Das, Zavante Therapeutics, Inc.: Consultant, Consulting fee. D. Skarinksy, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. P. B. Eckburg, Zavante Therapeutics, Inc.: Consultant and Shareholder, Consulting fee. K. Manvelian, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary. E. J. Ellis-Grosse, Zavante Therapeutics, Inc.: Employee and Shareholder, Salary.

scholarly journals Quinolone resistance in different uropathogens isolated from urine cultures in patients with urinary tract infection

2020 ◽  
Author(s):  
Jorge Angel Almeida Villegas ◽  
Iris Mellolzy Estrada Carrillo ◽  
Rodolfo Garcia Contreras ◽  
Silvia Patricia Peña
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Urinary Tract Infections ◽  
Gram Positive ◽  
Gram Negative ◽  
Beta Lactamases ◽  
Extended Spectrum ◽  
Extended Spectrum Beta Lactamases ◽  
Tract Infections

AbstractObjectiveTo identify patterns of resistance against quinolones in various uropathogens in urinary tract infections in the population of the Toluca valley, MexicoIntroductionQuinolones are antibiotics with a spectrum of activity for both gram-positives and gram-negatives and are antibiotics used for the empirical treatment of urinary tract infections. Recently, a high index of resistance to quinolones has been reported due to different mechanisms on the part of bacteria, however the one that has taken the greatest importance is the presence of extended spectrum beta-lactamasesMethods155 samples were collected from patients with suspected urinary tract infection without exclusion criteria such as age or gender. Automated equipment was used for the identification of the etiological agent and sensitivity tests to quinolones.ResultsThe results positives were divided to evaluate which of the two antibiotics studied had greater resistance. For ciprofloxacin there are 27 resistant strains 37%, 1 strain with intermediate resistance 1% and 45 susceptible strains 62%. For levofloxacin 26 strains are resistant 36%, 41 strains are sensitive 56% and 6 strains show intermediate sensitivity 8%.ConclusionDifferent microorganisms, both gram-positive and gram-negative, were isolated and it can be observed that gram-negative strains are the ones with the greatest resistance against quinolones, mainly Escherichia coli, which produces extended-spectrum beta-lactamases, in the case of gram-positive resistance patterns are variable with a tendency towards sensitivity.

scholarly journals Sociodemographic inequalities in urinary tract infection in two large California health systems

2021 ◽  
Author(s):  
Joan A Casey ◽  
Kara E Rudolph ◽  
Sarah C Robinson ◽  
Katia Bruxvoort ◽  
Eva Raphael ◽  
...  
Keyword(s):  
Risk Factors ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Low Socioeconomic Status ◽  
The United States ◽  
Sociodemographic Factors ◽  
Antibiotic Prescribing ◽  
Electronic Health Record Data ◽  
Increased Risk

Abstract Background Urinary tract infection (UTI) accounts for a substantial portion of outpatient visits and antibiotic prescriptions in the United States (US). Few studies have considered sociodemographic factors including low socioeconomic status (SES)–which may increase residential crowding, inappropriate antibiotic prescribing, or co-morbidities–as UTI or multi-drug resistant (MDR) UTI risk factors. Methods We used 2015-2017 electronic health record data from two California healthcare systems to assess whether three sociodemographic factors–use of Medicaid, use of an interpreter, and census tract-level deprivation–were associated with overall UTI or MDR UTI. UTI resistant to ≥3 antibiotic classes were considered MDR. Results Analyses included 601,352 UTI cases, 1,303,455 controls, and 424,977 urinary E. coli isolates from Kaiser Permanente Southern California (KPSC) and Sutter Health in Northern California. MDR prevalence was 10.4% at KPSC and 12.8% at Sutter Health. All three sociodemographic factors (i.e., use of Medicaid, using an interpreter, and community deprivation) were associated increased risk of MDR UTI. For example, using an interpreter was associated with a 36% (RR = 1.36, 95% CI: 1.31, 1.40) and a 28% (RR = 1.28, 95% CI: 1.22, 1.34) increased risk of MDR UTI at KPSC and Sutter Health, respectively, adjusted for SES and other potential confounding variables. The three sociodemographic factors were only weakly associated with UTI overall. Conclusions We found low SES and use of an interpreter as novel risk factors for MDR UTI in the US.

Risk Factors for Community-Acquired Urinary Tract Infection by Extended-Spectrum β-Lactamase–Producing Organisms in Children

2015 ◽  
Vol 10 (02) ◽  
pp. 045-046 ◽  
Author(s):  
Shalini Sharma ◽  
Padmanabhan Ramachandran ◽  
Uma Sekar ◽  
Padmasani Venkat Ramanan
Keyword(s):  
Risk Factors ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Extended Spectrum
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