scholarly journals Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Gram-Negative Organisms Isolated from Patients with Urinary Tract Infections in U.S. Medical Centers, 2012 to 2014

2016 ◽  
Vol 60 (7) ◽  
pp. 4355-4360 ◽  
Author(s):  
Helio S. Sader ◽  
Mariana Castanheira ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Activities ◽  
Broth Microdilution ◽  
Gram Negative ◽  
Content Type ◽  
Medical Centers ◽  
Gram Negative Organisms ◽  
Tract Infections

ABSTRACTA total of 7,272 unique patient clinical isolates were collected from 71 U.S. medical centers from patients with urinary tract infections in 2012 to 2014 and tested for susceptibility to ceftazidime-avibactam and comparators by broth microdilution methods. Ceftazidime-avibactam inhibited >99.9% of allEnterobacteriaceaeat the susceptible breakpoint of ≤8 μg/ml (there were only three nonsusceptible strains). Ceftazidime-avibactam was also active againstPseudomonas aeruginosaisolates (MIC50, 2 μg/ml; MIC90, 4 μg/ml; 97.7% susceptible), including many isolates not susceptible to meropenem, ceftazidime, and/or piperacillin-tazobactam.

scholarly journals 1436. Comparison of Ceftazidime–Avibactam, Ceftolozane–Tazobactam, Piperacillin–Tazobactam, and Meropenem Activities When Tested Against Gram-Negative Organisms Isolated From Complicated Urinary Tract Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S524-S524
Author(s):  
Helio S Sader ◽  
Robert K Flamm ◽  
Mariana Castanheira ◽  
Rodrigo E Mendes
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Activities ◽  
Healthcare Associated Infection ◽  
Gram Negative ◽  
Highly Active ◽  
The Us ◽  
Gram Negative Organisms ◽  
Tract Infections ◽  
Esbl Producers

Abstract Background Complicated urinary tract infections (cUTIs) represent a major cause of healthcare-associated infection and a major source of gram-negative (GN) bacteremia. We evaluated the antimicrobial activities of recently approved β-lactamase inhibitor combinations and comparators against GN bacteria isolated from patients with cUTIs in the US hospitals in 2018. Methods Unique patient isolates were consecutively collected from patients with cUTIs in 65 hospitals in 2018, and the GN organisms (n = 4,371) were susceptibility (S) tested by reference broth microdilution methods. Enterobacterales (ENT) with elevated cephalosporin MICs were screened for β-lactamase-encoding genes by whole-genome sequencing. Results The most common GN organisms were E. coli (44.5%), K. pneumoniae (19.6%), P. mirabilis (6.7%), and P. aeruginosa (PSA; 5.3%). The most active agents against ENT were ceftazidime–avibactam (CAZ-AVI; 99.9%S), amikacin (AMK; 99.7%S), and meropenem (MEM; 99.4%S; table). Extended-spectrum β-lactamase (ESBL) genes were identified in 315 ENT (7.6%; excluding carbapenemase co-producers), including CTX-M-15 (63% of ESBL producers), other CTX-M types (25%), OXA-1/OXA-30 (39%), and SHV type (30%); approximately 50% of ESBL producers had ≥2 ESBL genes, mainly a CTX-M-type and an OXA-type (37% of isolates). The most active agents against ESBL producers were CAZ-AVI (100.0%S), AMK (99.7%S), and MEM (99.4%S); whereas ceftolozane–tazobactam (C-T) and piperacillin–tazobactam (PIP-TAZ) were active against 90.6% and 84.8% of ESBL producers, respectively. Only CAZ-AVI (87.0%S), colistin (COL; 87.0%S), and tigecycline (95.7%S) exhibited good activity against carbapenem-resistant ENT (CRE). Only 3 ENT isolates (0.07%) were CAZ-AVI resistant and all had a metallo-β-lactamase gene (2 VIM-1 and 1 NDM-1). CAZ-AVI (97.0%S) and C-T (99.1%S) were the most active β-lactams tested against PSA; other compounds with > 90%S for PSA were COL (99.6%), AMK (97.8%), tobramycin (93.5%), and CAZ (90.4%). Conclusion CAZ-AVI was highly active against a large collection of contemporary GN bacteria isolated from patients with cUTIs in US hospitals and provided greater coverage than the agents currently available in the US to treat cUTIs. Disclosures All authors: No reported disclosures.

scholarly journals Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
The United States ◽  
Phase Iii ◽  
In Vitro Susceptibility ◽  
Gram Negative ◽  
Tract Infections ◽  
Abdominal Infections

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Nayara Helisandra Fedrigo ◽  
Josmar Mazucheli ◽  
James Albiero ◽  
Danielle Rosani Shinohara ◽  
Fernanda Gomes Lodi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Urinary Tract Infections ◽  
Bacterial Isolates ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Tract Infections

ABSTRACT Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158 Escherichia coli isolates and 87 Klebsiella isolates which were collected from patients with urinary tract infections, were determined at pH 6.0 and 7.0 using the agar dilution method. Monte Carlo simulation of the urinary fosfomycin area under the concentration-time curve (AUC) after a single oral dose of 3,000 mg fosfomycin and the MIC distribution were used to determine the probability of target attainment (PTA). Fosfomycin was effective against E. coli (MIC90 ≤ 16 μg/ml) but not against Klebsiella spp. (MIC90 > 512 μg/ml). Acidification of the environment increased the susceptibility of 71% of the bacterial isolates and resulted in a statistically significant decrease in bacterial survival. The use of a regimen consisting of a single oral dose of fosfomycin against an E. coli isolate with an MIC of ≤64 mg/liter was able to achieve a PTA of ≥90% for a target pharmacodynamic index (AUC/MIC) of 23 in urine; PTA was not achieved when the MIC was higher than 64 mg/liter. The cumulative fractions of the bacterial responses (CFR) were 99% and 55% against E. coli and Klebsiella spp., respectively, based on simulated drug exposure in urine with an acidic pH of 6.0. A decrease of the pH from 7.0 to 6.0 improved the PTA and CFR of the target pharmacodynamic index in both E. coli and Klebsiella isolates.

scholarly journals Complete Genome Sequence of Proteus mirabilis Siphophage Saba

2019 ◽  
Vol 8 (41) ◽  
Author(s):  
James Nguyen ◽  
Laith Harb ◽  
Russell Moreland ◽  
Mei Liu ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Proteus Mirabilis ◽  
Genome Annotation ◽  
Complete Genome ◽  
Enteric Bacterium ◽  
Gram Negative ◽  
Content Type ◽  
Protein Levels ◽  
Tract Infections

Proteus mirabilis is a Gram-negative enteric bacterium associated with complicated human urinary tract infections. Here, we present the complete genome annotation for P. mirabilis siphophage Saba. With a 60,056-bp genome and 75 predicted genes, Saba is most similar at the nucleotide and protein levels to phage Chi and Chi-like viruses.

scholarly journals URINARY TRACT INFECTIONS

2016 ◽  
Vol 23 (01) ◽  
pp. 010-014
Author(s):  
Muhammad Usman Anjum ◽  
Muhammad Safdar Khan ◽  
Abdul Razzaq Shahid ◽  
Syed Humayun Shah
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Antimicrobial Susceptibility ◽  
Geographical Area ◽  
Gram Negative ◽  
E Coli ◽  
Amoxicillin Clavulanic Acid ◽  
Gram Negative Organisms ◽  
Tract Infections ◽  
Micro Organisms

Background: Urinary tract infections (UTIs) constitute important bacterialdisease which contributes to significant morbidity world-wide. Empirical treatment in patientssuffering from UTI depends upon the local knowledge of common microorganisms responsiblefor UTI in that geographical area as well as their antimicrobial susceptibility patterns.Objectives: To determine the frequency and antimicrobial susceptibility of uropathogenswhich are responsible for urinary tract infections. Study Design: Experimental study. Setting:Department of Pathology, Frontier Medical & Dental College and Mohi Ud Din Islamic MedicalCollege. Period: January 2015 to June 2015. Material & methods: Total of 113 patients wereincluded in the study. Urine samples were cultured on MacConkey’s agar and Cysteine LactoseElectrolyte Deficient (CLED) agar. Micro-organisms were identified using standard tests andantimicrobial susceptibility was checked using modified Kirby Bauer method following Clinicaland Laboratory Standards Institute (CLSI) guidelines. Results: The average age of patientswas 32.19±16.47 years. Gram negative organisms accounted for majority of cases, about 89(78.76%) cases. Escherichia coli was the most common micro-organism which was found in50 (44.24%) cases followed by Staphylococcus aureus in 24 (21.24%), Enterobacter spp. in19 (16.81%), Klebsiella spp. in 11 (9.73%) and Proteus spp. in 9 (7.96%) cases. E. coli wassensitive to imipenem and ciprofloxacin and was resistant to amoxicillin/clavulanic acid andgentamicin. Conclusion: Gram negative organisms are largely responsible for UTIs and E. colibeing the most common etiological agent. E. coli is sensitive to commonly prescribed drugs forUTI like ciprofloxacin.

scholarly journals Rapid diagnosis of Pseudomonas aeruginosa urinary tract infections by radioimmunoassay

1979 ◽  
Vol 9 (2) ◽  
pp. 253-258
Author(s):  
R B Kohler ◽  
L J Wheat ◽  
A White
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Solid Phase ◽  
Bacterial Species ◽  
Phase Growth ◽  
Gram Negative ◽  
Solid Phase Radioimmunoassay ◽  
Tract Infections ◽  
Urine Specimens

A solid-phase radioimmunoassay designed to detect serotype 6 Pseudomonas aeruginosa antigens was evaluated for its ability to rapidly diagnose urinary tract infections. Twelve P. aeruginosa serotypes were easily differentiated in the assay from eight other gram-negative bacterial species. During log-phase growth, the assay detected antigens in culture when approximately 10(6) or more serotype 6 P. aeruginosa organisms were present. Both cell-associated and solubilized antigens were detected. The assay detected antigens in 13 of 17 urine specimens which grew greater than 10(5) P. aeruginosa, 3 of 38 which grew other gram-negative rods, and none of 83 with no growth. Two of the three positive specimens from the other gram-negative rod group probably also contained P. aeruginosa. No preincubation of the urine specimens was required, and results were available within 2.5 h. The assay represents an improvement over other procedures for rapidly diagnosing urinary tract infections in that it allows diagnosis by species and should be adaptable to semiautomation.

scholarly journals Results of a Multicenter Population Pharmacokinetic Study of Ciprofloxacin in Children with Complicated Urinary Tract Infection

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Kevin Meesters ◽  
Robin Michelet ◽  
Reiner Mauel ◽  
Ann Raes ◽  
Jan Van Bocxlaer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Body Weight ◽  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Complicated Urinary Tract Infection ◽  
Fat Free Mass ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Tract Infections ◽  
Significant Covariates

ABSTRACTResistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10 to 15 mg/kg body weight every 12 h) orper os(15 to 20 mg/kg every 12 h), were enrolled. One hundred eight serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ciprofloxacin in 22 patients (age range, 0.31 to 15.51 years). A one-compartment model best described our data. Fat-free mass and glomerular filtration rate (estimated by a formula using cystatin C and creatinine), standardized for body surface area, were significant covariates for ciprofloxacin clearance. In our population, ciprofloxacin clearance is 0.16 to 0.43 liter/h/kg of body weight, volume of distribution 0.06 to 2.88 liters/kg, and bioavailability 59.6%. All of our patients had a clinical cure of their infection. Based on target attainment simulations across doses, all children reached the pharmacodynamic target forEnterobacteriaceae, but on average only 53% did forPseudomonas aeruginosaand 3% forStaphylococcus aureus, at the 15-mg/kg oral dose. For treating urinary tract infections caused byPseudomonas aeruginosa, oral doses should be at least 20 mg/kg. Furthermore, in our population, fat-free mass and kidney function should be considered, as they prove to be significant covariates for ciprofloxacin clearance and, hence, exposure. (This study has been registered at ClinicalTrials.gov under identifier NCT02598362.)

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