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 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.

Cefiderocol- A New Antimicrobial for Complicated Urinary Tract Infection (CUTI) Caused by Carbapenem Resistant Enterobacteriaceae (CRE)

2021 ◽  
Vol 13 ◽  
Author(s):  
Suparna Chatterjee ◽  
Dwaipayan Sarathi Chakraborty ◽  
Shouvik Choudhury ◽  
Sandeep Lahiry
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Bacterial Infections ◽  
Rapid Development ◽  
Complicated Urinary Tract Infection ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Tract Infections ◽  
Carbapenem Resistant Enterobacteriaceae

: The incidence of Carbapenem resistant gram negative (CRGNB) bacterial infections has increased globally. The wide diversity of strains, multiplicity of infections and rapid development and spread of resistance are a matter of great concern both in community and hospital settings. Cefiderocol is a novel injectable siderophore containing cephalosporin with potent microbicidal activity against most Carbapenem Resistant Enterobacteriaceae (CRE). It has recently been approved by USFDA for the treatment of complicated urinary tract infections (cUTI) caused by susceptible gram-negative microorganisms. This review focuses on the salientpharmacological profile of the drug and the clinical studies that were undertaken.

Does the urinary tract infection caused by carbapenem-resistant Gram-negative bacilli impact the outcome of kidney transplant recipients?

2018 ◽  
Vol 20 (4) ◽  
pp. e12923
Author(s):  
Maristela Pinheiro Freire ◽  
Clara V. Mendes ◽  
Affonso C. Piovesan ◽  
Flavio Jota de Paula ◽  
Fernanda Spadão ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Gram Negative ◽  
Carbapenem Resistant

scholarly journals degS Is Necessary for Virulence and Is among Extraintestinal Escherichia coli Genes Induced in Murine Peritonitis

2003 ◽  
Vol 71 (6) ◽  
pp. 3088-3096 ◽  
Author(s):  
Peter Redford ◽  
Paula L. Roesch ◽  
Rodney A. Welch
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Luria Bertani ◽  
Broth Culture ◽  
Wild Type ◽  
E Coli ◽  
Virulence Attenuation

ABSTRACT Extraintestinal Escherichia coli strains cause meningitis, sepsis, urinary tract infection, and other infections outside the bowel. We examined here extraintestinal E. coli strain CFT073 by differential fluorescence induction. Pools of CFT073 clones carrying a CFT073 genomic fragment library in a promoterless gfp vector were inoculated intraperitoneally into mice; bacteria were recovered by lavage 6 h later and then subjected to fluorescence-activated cell sorting. Eleven promoters were found to be active in the mouse but not in Luria-Bertani (LB) broth culture. Three are linked to genes for enterobactin, aerobactin, and yersiniabactin. Three others are linked to the metabolic genes metA, gltB, and sucA, and another was linked to iha, a possible adhesin. Three lie before open reading frames of unknown function. One promoter is associated with degS, an inner membrane protease. Mutants of the in vivo-induced loci were tested in competition with the wild type in mouse peritonitis. Of the mutants tested, only CFT073 degS was found to be attenuated in peritoneal and in urinary tract infection, with virulence restored by complementation. CFT073 degS shows growth similar to that of the wild type at 37°C but is impaired at 43°C or in 3% ethanol LB broth at 37°C. Compared to the wild type, the mutant shows similar serum survival, motility, hemolysis, erythrocyte agglutination, and tolerance to oxidative stress. It also has the same lipopolysaccharide appearance on a silver-stained gel. The basis for the virulence attenuation is unclear, but because DegS is needed for σE activity, our findings implicate σE and its regulon in E. coli extraintestinal pathogenesis.

TREATMENT OF CARBAPENEM RESISTANT ENTEROBACTERIACEAE URINARY TRACT INFECTION WITH COMBINATION OF AMIKACIN AND MEROPENEM

2021 ◽  
pp. 54-55
Author(s):  
Jayesh Kalbhande ◽  
Vicky Kuldeep
Keyword(s):  
Drug Resistance ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
New Drugs ◽  
Resistant Organism ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Multiple Drugs ◽  
Near Future

Drug resistance of bacteria is biggest challenge humanity is going to face in near future. Bacteria are rapidly developing resistant to multiple drugs and there are not many new drugs in pipeline. Infection because of drug resistant organism is a common cause of morbidity and mortality in intensive care unit. If acquisition of drug resistance by microorganism progresses at this rate, that time is not very far when we will be pushed in to preantibiotic era. We need to develop new strategies to combat drug resistant by microorganism. We report a case of highly drug resistant urinary tract infection caused by Klebsiella. This strain was resistant to both Inj. Meropenem and Inj. Amikacin. This case was successfully treated by combination of Inj. Meropenem and Inj. Amikacin and complete resolution of infection was observed.

scholarly journals Heterogeneity of Recent Phase 3 Complicated Urinary Tract Infection Clinical Trials

2021 ◽  
Vol 8 (3) ◽  
Author(s):  
Simon Portsmouth ◽  
Almasa Bass ◽  
Roger Echols ◽  
Glenn Tillotson
Keyword(s):  
Clinical Trials ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Study Design ◽  
Patient Population ◽  
Complicated Urinary Tract Infection ◽  
Gram Negative ◽  
Regulatory Guidelines ◽  
New Antibiotics

Abstract Background For new antibiotics developed to treat antibiotic-resistant Gram-negative infections, the US Food and Drug Administration (FDA) regulatory pathway includes complicated urinary tract infection (cUTI) clinical trials in which the clinical isolates are susceptible to the active control. This allows for inferential testing in a noninferiority study design. Although complying with regulatory guidelines, individual clinical trials may differ substantially in design and patient population. To determine variables that impacted patient selection and outcome parameters, 6 recent cUTI trials that were pivotal to an new drug application (NDA) submission were reviewed. Methods This selective descriptive analysis utilized cUTI trial data, obtained from publicly disclosed information including FDA documents and peer-reviewed publications, from 6 new antibiotics developed to treat multidrug-resistant Gram-negative infections: ceftolozane-tazobactam, ceftazidime-avibactam, meropenem-vaborbactam, cefiderocol, plazomicin, and fosfomycin. Eravacycline was not approved for cUTI and is not included. Results Microbiologic modified intent-to-treat sample size, age, proportions of female patients, acute pyelonephritis (AP), Escherichia coli and other pathogens at baseline, protocol-specified switch to oral antibiotic, and the noninferiority margin were compared. Outcome data included clinical response, microbiologic eradication, and composite outcomes, including a subset of patients with AP. Conclusions A study design can follow regulatory guidelines but still have variable populations. The proportion of AP within a study varied greatly and influenced population demographics (age, gender) and baseline microbiology. A smaller proportion of AP resulted in an older patient population, fewer females, less E coli, and lower proportions of patients achieving success. Fluoroquinolones and piperacillin/tazobactam should be reconsidered as active comparators given the high rates of resistance to these antibiotics.

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