CC131 in complicated urinary tract infections (cUTIs) caused by fluoroquinolone-resistant Escherichia coli
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB55220 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Urinary tract infections are one of the most common health problems and entail a high consumption of health system resources. Due to the increase in global antibiotic resistances in recent years, it is increasingly common to find uropathogens with multiple resistance mechanisms, including quinolone-resistant bacteria, broad-spectrum β-lactamase producers and carbapenemase producers. In this scenario, the role of fosfomycin has gained considerable importance, given its spectrum of activity against multidrug resistant microorganisms (Gram-positive and Gram-negative), becoming an attractive alternative therapy. Regarding the use of fosfomycin in complicated urinary tract infections, there is increasing clinical experience with patients with infections caused by multidrug resistant bacteria, those with recurrent urinary tract infection and special populations such as those with kidney transplants. Randomized comparative studies and series are underway, which will provide greater evidence. Nevertheless, more studies are needed to confirm the enormous potential of fosfomycin in complicated urinary tract infection in the era of multiresistance.
| S-EPMC6555162 | biostudies-literature
Project description:Oral fosfomycin is approved in Canada for the treatment of acute uncomplicated cystitis. Several studies have reported "off label" use of oral fosfomycin in the treatment of patients with complicated lower urinary tract infection (cLUTI). This review summarizes the available literature describing the use of oral fosfomycin in the treatment of patients with cLUTI. Collectively, these studies support the use of a regimen of 3 grams of oral fosfomycin administered once every 48 or 72 hours for a total of 3 doses for patients who have previously failed treatment with another agent, are infected with a multidrug-resistant (MDR) pathogen, or cannot tolerate first-line treatment due to intolerance or adverse effects. Additionally, a Phase 2/3 clinical trial, known as the ZEUS study, assessed the efficacy and safety of intravenous (IV) fosfomycin versus piperacillin-tazobactam in the treatment of patients with complicated upper urinary tract infection (cUUTI) or acute pyelonephritis (AP) including in patients with concomitant bacteremia. IV fosfomycin was reported to be noninferior to piperacillin-tazobactam in treating patients with cUUTI and AP; however, when outcomes were independently evaluated according to baseline diagnosis (i.e., cUUTI versus AP), IV fosfomycin was superior to piperacillin-tazobactam in the treatment of patients with cUUTI and demonstrated superior microbiological eradication rates, across all resistant phenotypes including extended-spectrum β-lactamase- (ESBL-) producing Escherichia coli and Klebsiella spp. and carbapenem-resistant (CRE), aminoglycoside-resistant, and MDR Gram-negative bacilli (primarily Enterobacterales). Based on the ZEUS study, IV fosfomycin dosed at 6 grams every 8 hours for 7 days (14 days in patients with concurrent bacteremia) appears to be a safe and effective therapeutic option in treating patients with upper urinary tract infections, particularly those with cUUTI caused by antimicrobial-resistant Enterobacterales.
| S-EPMC7142339 | biostudies-literature
Project description:Background and Objectives. Numerous studies have been conducted to explore the epidemiological characteristics of urinary tract infections (UTI) and sepsis. However, there is still a lack of relevant bacteriological features and prognostic information regarding urosepsis based on bacteriological etiology. The current study aims to evaluate the bacterial etiology of complicated UTI (cUTI) and bacterial resistance to antibiotics and whether they present an intrinsic risk of developing urosepsis. Materials and Methods. A retrospective study was performed that included 102 patients who were diagnosed with cUTI and admitted to the urology department of the "Sfântul Apostol Andrei" County Emergency Clinical Hospital (GCH) from September 2019 to May 2022. Results. A considerable number of patients, n = 41 (40.2%), were diagnosed with multi drug-resistant (MDR) infection. Escherichia coli (E. coli) was identified as the prevailing pathogen, accounting for 51 patients. Klebsiella manifested itself as the subsequent causative agent in 27 instances. The presence of Enterococcus spp. infection was documented in 13 patients, whereas Pseudomonas emerged as the etiological perpetrator in the clinical context of 8 patients. The current study found a substantial prevalence of resistance to first-line antibiotics. The overall resistance rate was 74.5% for penicillin, 58.82% for trimethoprim-sulfamethoxazole and 49% for fluoroquinolones; cephalosporin resistance displayed an inverse correlation with antibiotic generation with fourth-generation cephalosporins exhibiting a resistance rate of 24.5%, and first-generation cephalosporins demonstrating a resistance rate of 35.29%. Conclusions. Age, comorbidities and indwelling urinary catheters are risk factors for developing MDR infections. While the intrinsic characteristics of the causative bacterial agent in cUTI may not be a risk factor for developing urosepsis, they can contribute to increased mortality risk. For empiric antibiotic treatment in patients with cUTI who are at a high risk of developing urosepsis and experiencing a potentially unfavorable clinical course, broad-spectrum antibiotic therapy is recommended. This may include antibiotics, such as amikacin, tigecycline, carbapenems and piperacillin-tazobactam.
| S-EPMC10538164 | biostudies-literature
Project description:NBRP: Genome sequencing of Prototheca cutis JCM 15793
| PRJDB3669 | ENA
Project description:The rise in resistant Gram-negative pathogens continues to challenge clinicians treating infections. These resistant infections have inspired the development of new antimicrobial agents, including ceftolozane-tazobactam, a novel ?-lactam/?-lactamase inhibitor combination approved by the US Food and Drug Administration for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) in combination with metronidazole. Ceftolozane exhibits bactericidal activity by inhibiting penicillin-binding proteins (PBPs), with high affinity for PBP1b, PBP1c, and PBP3. The addition of tazobactam protects ceftolozane from hydrolysis by irreversibly binding to some ?-lactamase enzymes. Ceftolozane-tazobactam is active against a wide range of Gram-negative pathogens, including extended-spectrum ?-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant (MDR) Pseudomonas aeruginosa, several streptococcal species, and Bacteroides fragilis. When anaerobic coverage is needed, it should be used in combination with metronidazole. Ceftolozane demonstrates linear pharmacokinetics, low protein binding, and minimal accumulation with repeated dosing. The major pharmacokinetic/pharmacodynamic index for ceftolozane is the percentage of the dosing interval in which the plasma free drug concentration remains higher than the minimum inhibitory concentration (%T.MIC). Phase III clinical trials for the treatment of cUTIs and cIAIs have been completed, showing that it is an effective and safe alternative for the treatment of these infections. The approved dose for cUTIs and cIAIs is 1.5 g (1 g ceftolozane and 500 mg tazobactam) infused over 1 hour every 8 hours. A higher 3 g dose is currently in Phase III trials for the treatment of ventilated nosocomial pneumonia. Dosage adjustments are necessary for patients with moderate-to-severe renal impairment. Current data suggest that ceftolozane-tazobactam is a promising carbapenem-sparing alternative agent for the treatment of cUTIs and cIAIs, including those caused by ESBL-producing Enterobacteriaceae and MDR P. aeruginosa.
| S-EPMC4878668 | biostudies-literature
Project description:Avibactam is a non-?-lactam ?-lactamase inhibitor that has been approved in combination with ceftazidime for the treatment of complicated intra-abdominal infections, complicated urinary tract infections, and nosocomial pneumonia, including ventilator-associated pneumonia. In Europe, ceftazidime-avibactam is also approved for the treatment of Gram-negative infections with limited treatment options. Selection and validation of the ceftazidime-avibactam dosage regimen was guided by an iterative process of population pharmacokinetic (PK) modelling, whereby population PK models for ceftazidime and avibactam were developed using PK data from clinical trials and updated periodically. These models were used in probability of target attainment (PTA) simulations using joint pharmacodynamic (PD) targets for ceftazidime and avibactam derived from preclinical data. Joint PTA was calculated based on the simultaneous achievement of the individual PK/PD targets (50% free time above the ceftazidime-avibactam MIC for ceftazidime and free time above a critical avibactam threshold concentration of 1?mg/liter for avibactam). The joint PTA analyses supported a ceftazidime-avibactam dosage regimen of 2,000?+?500?mg every 8?h by 2-h intravenous infusion for patients with creatinine clearance (CLCR) >50?ml/min across all approved indications and modified dosage regimens for patients with CLCR ?50?ml/min. Subgroup simulations for individual phase 3 patients showed that the dosage regimen was robust, with high target attainment (>95%) against MICs ?8?mg/liter achieved regardless of older age, obesity, augmented renal clearance, or severity of infection. This review summarizes how the approved ceftazidime-avibactam dosage regimens were developed and validated using PK/PD targets, population PK modeling, and PTA analyses.
| S-EPMC6437548 | biostudies-literature
Project description:The Hospital Infantil de México Federico Gómez (HIMFG) is a tertiary care hospital in Mexico City where Escherichia coli is frequently isolated from the urine samples of pediatric patients with urinary tract infections. A collection of 178 urinary Escherichia coli (UEc) isolates associated with complicated and uncomplicated urinary tract infections were evaluated in this study. The patterns of resistance to 9 antibiotic classes showed that 60.7% of the UEc isolates had a highly multidrug-resistant (MDR) profile. Genetic diversity analyses of the UEc isolates showed a high variability and revealed 16 clusters associated with four phylogenetic groups, namely, groups A, B1, B2, and D. Phylogenetic group B2 was widely associated with the 16 clusters as well as with virulence and fitness genes. The virulence and fitness genes in the UEc isolates, which included fimbriae-, siderophore-, toxin-, and mobility-associated genes, were grouped as occurring at a low, variable, or high frequency. Interestingly, only the papF gene could be amplified from some UEc isolates, and the sequence analysis of the pap operon identified an insertion sequence (IS) element and gene loss. These data suggested pathoadaptability and the development of immune system evasion, which was confirmed by the loss of P fimbriae-associated agglutination in the UEc isolates. E. coli clone O25-ST131 had a prevalence of 20.2% among the UEc isolates; these isolates displayed both a highly MDR profile and the presence of the papGII, fimH, papGIII, iutD, sat, hlyA, and motA genes. In conclusion, the UEc isolates from complicated urinary tract infection (cUTI) were characterized as being MDR, highly genetically diverse, and associated with phylogenetic group B2 and many virulence and fitness genes. Additionally, gene loss and IS elements were identified in some UEc isolates identified as clone O25-ST131.
| S-EPMC6171886 | biostudies-literature
Project description:Background. Urinary tract infections (UTIs) are common and important clinical problem in childhood, and extended-spectrum-beta-lactamase- (ESBL-) producing organisms are the leading cause of healthcare-related UTIs. In this study, we aimed to evaluate the clinical efficacy and safety of ertapenem therapy in children with complicated UTIs caused by ESBL-producing organisms. Methods. Seventy-seven children with complicated UTIs caused by ESBL-producing organisms were included in this retrospective study, and all had been treated with ertapenem between January 2013 and June 2014. Results. Sixty-one (79%) females and sixteen (21%) males with a mean ± standard deviation (SD) age of 76.6 ± 52 months (range 3-204, median 72 months) were enrolled in this study. Escherichia coli (E. coli) (n = 67; 87%) was the most common bacterial cause of the UTIs followed by Klebsiella pneumoniae (K. pneumoniae) (n = 9; 11.7%) and Enterobacter cloacae (E. cloacae) (n = 1; 1.3%). The mean duration of the ertapenem therapy was 8.9 ± 1.6 days (range 4-11). No serious drug-related clinical or laboratory adverse effects were observed, and the ertapenem therapy was found to be safe and well tolerated in the children in our study. Conclusion. Ertapenem is a newer carbapenem with the advantage of once-daily dosing and is highly effective for treating UTIs caused by ESBL-producing microorganisms.
| S-EPMC4461781 | biostudies-other