Pharmacokinetics and Pharmacodynamics of Amoxicillin-Sulbactam, a Novel Aminopenicillin–β-Lactamase Inhibitor Combination, against Escherichia coli

ABSTRACT We evaluated the pharmacokinetics of amoxicillin-sulbactam (AMX-SUL), a novel drug combination, and its pharmacodynamics againstEscherichia coli in 12 volunteers receiving a single oral dose (1,000 mg). Peak serum bactericidal and urine inhibitory activities in most volunteers were observed against E. colistrains for which AMX-SUL MICs were low (2- to 4-mg/liter) (2 strains) and high (≥16-mg/liter) (47 strains), respectively.

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

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02498-16 ◽

2017 ◽

Vol 61 (8) ◽

Cited By ~ 12

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.

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Genetic Features Leading to Reduced Susceptibility to Aztreonam-Avibactam among Metallo-β-Lactamase-Producing Escherichia coli Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01659-20 ◽

2020 ◽

Vol 64 (12) ◽

Author(s):

Mustafa Sadek ◽

Mario Juhas ◽

Laurent Poirel ◽

Patrice Nordmann

Keyword(s):

Escherichia Coli ◽

Amino Acid ◽

Drug Combination ◽

Protein Sequence ◽

Specific Amino Acid ◽

Content Type ◽

E Coli ◽

Genetic Features ◽

Inhibitor Drug ◽

Lactamase Inhibitor

ABSTRACT Metallo-β-lactamase (MBL)-producing Escherichia coli isolates resistant to the newly developed β-lactam/β-lactamase inhibitor drug combination aztreonam-avibactam (ATM-AVI) have been reported. Here, we analyzed a series of 118 clinical MBL-producing E. coli isolates of various geographical origins for susceptibility to ATM-AVI. The nature of the PBP3 protein sequence and the occurrence of blaCMY genes for susceptibility to ATM-AVI were investigated. We showed here that elevated MICs of ATM-AVI among MBL-producing E. coli isolates resulted from a combination of different features, including modification of PBP3 protein sequence through specific amino acid insertions and production of CMY-type enzymes, particularly, CMY-42. We showed here that those insertions identified in the PBP3 sequence are not considered the unique basis of resistance to ATM-AVI, but they significantly contribute to it.

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Changes in the Frequencies of β-Lactamase Genes among Enterobacteriaceae Isolates in U.S. Hospitals, 2012 to 2014: Activity of Ceftazidime-Avibactam Tested against β-Lactamase-Producing Isolates

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00540-16 ◽

2016 ◽

Vol 60 (8) ◽

pp. 4770-4777 ◽

Cited By ~ 38

Author(s):

Mariana Castanheira ◽

Rodrigo E. Mendes ◽

Ronald N. Jones ◽

Helio S. Sader

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

South Atlantic ◽

Content Type ◽

E Coli ◽

Carbapenem Resistant ◽

Inhibitor Combination ◽

Lactamase Inhibitor ◽

M 14 ◽

Over Time

ABSTRACTAmong 15,588Enterobacteriaceaeisolates collected in 63 U.S. hospitals from 2012 to 2014, 2,129 (13.7%) displayed an extended-spectrum β-lactamase (ESBL) phenotype. These rates were similar over time (13.2 to 13.9%); however, differences amongEscherichia coli(12.7 and 15.1% in 2012 and 2014;P= 0.007) andKlebsiella pneumoniae(18.9 and 15.5% in 2012 and 2014;P= 0.006) were noted when comparing 2014 and 2012. Carbapenem-resistantEnterobacteriaceae(CRE) (2.3 and 1.8%) and carbapenem-resistantK. pneumoniae(6.8 and 5.1%;P= 0.003) rates were lower in 2014 than in 2012. Isolates carryingblaCTX-M-15-like genes were stable (42.1 to 42.4%), but a decrease amongE. coliisolates (59.1 and 49.7%;P= 0.008) and an increase amongK. pneumoniaeisolates (32.7 and 41.2%;P= 0.022) in 2014 were observed. Isolates carryingblaKPC(304) decreased over the years (16.5 and 10.9%;P= 0.008), mainly due to the decrease inK. pneumoniaeisolates harboringblaKPC(n= 285; 35.6 and 28.4%;P= 0.041) in hospitals in the Mid-Atlantic and South Atlantic regions, where these isolates were highly prevalent during 2012 and 2013. Isolates carryingblaCMY-2-like andblaCTX-M-14-like genes increased (8.2 and 11.9% and 9.1 and 12.9%, respectively;P= 0.04 for both), and those producingblaSHVESBL decreased (24.9 and 12.7%;P< 0.001) over the studied years, due to a decreased occurrence of the enzymes amongK. pneumoniaeisolates. Other enzymes were detected in smaller numbers of isolates, including fourK. pneumoniaeisolates carryingblaNDM-1metallo-β-lactamase (two in 2012 and two in 2014). Ceftazidime-avibactam, a recently approved β-lactamase inhibitor combination, was very active against the ESBL phenotype isolates (MIC50/90, 0.12 and 1 μg/ml; 99.7% susceptible) and CRE strains (MIC50/90, 0.5 and 2 μg/ml; 98.5% susceptible) that displayed elevated MIC values for many comparator agents. In conclusion, significant changes were noted in the frequencies of isolates harboring various β-lactamases among U.S. hospitals between 2012 and 2014 that will require continued monitoring.

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Abstract #1027: Acute Suppurative and Necrotizing Thyroiditis Due to Extended Spectrum Beta Lactamase Inhibitor(ESBL) Escherichia Coli (E COLI)

Endocrine Practice ◽

10.1016/s1530-891x(20)44151-5 ◽

2017 ◽

Vol 23 ◽

pp. 224-225

Author(s):

Sindhura Gogineni ◽

Uppalapati Aditya

Keyword(s):

Escherichia Coli ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

E Coli ◽

Extended Spectrum ◽

Lactamase Inhibitor

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Urinary Excretion and Bactericidal Activities of a Single Oral Dose of 400 Milligrams of Fleroxacin versus a Single Oral Dose of 800 Milligrams of Pefloxacin in Healthy Volunteers

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.7.1659 ◽

1998 ◽

Vol 42 (7) ◽

pp. 1659-1665 ◽

Cited By ~ 15

Author(s):

Kurt G. Naber ◽

Ursula Theuretzbacher ◽

Martina Kinzig ◽

Orlin Savov ◽

Fritz Sörgel

Keyword(s):

Oral Dose ◽

Healthy Volunteers ◽

Single Oral Dose ◽

E Coli ◽

Wide Range ◽

The Mean ◽

Bactericidal Activities ◽

Tract Infections ◽

Time Kill ◽

Randomized Crossover Study

ABSTRACT Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of fleroxacin and pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of fleroxacin or 800 mg of pefloxacin. The mean cumulative renal excretion of unchanged fleroxacin,N-demethyl-fleroxacin, and N-oxide-fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of pefloxacin and the active metabolite norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects’ urine not supplemented with broth was used. With most tested organisms and both quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 μg/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 μg/ml) of both antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of pefloxacin are significantly higher than those of fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true forEnterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both quinolones. Overall, a single oral dose of 400 mg of fleroxacin exhibits UBTs comparable to those of 800 mg of pefloxacin. Therefore, it may be expected that half of the dose of fleroxacin gives comparable results in the treatment of urinary tract infections; this should be substantiated in comparative clinical trials.

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In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Panel Strains

Antibiotics ◽

10.3390/antibiotics9050267 ◽

2020 ◽

Vol 9 (5) ◽

pp. 267 ◽

Cited By ~ 3

Author(s):

Le Phuong Nguyen ◽

Naina Adren Pinto ◽

Thao Nguyen Vu ◽

Hyunsook Lee ◽

Young Lag Cho ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Vitro Activity ◽

Intrinsic Activity ◽

In Vitro Activity ◽

E Coli ◽

Acinetobacter Spp ◽

Resistant Strains ◽

Lactamase Inhibitor

This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-β-lactam β-lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (≤2 μg/mL MICs) against many MDR isolates, including extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2–8 μg/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1–resistant strains. Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1–resistant strains.

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Escherichia coli ATCC 35218 as a Quality Control Isolate for Susceptibility Testing of Haemophilus influenzae with Haemophilus Test Medium

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.43.2.283 ◽

1999 ◽

Vol 43 (2) ◽

pp. 283-286 ◽

Cited By ~ 5

Author(s):

D. L. Butler ◽

C. J. Jakielaszek ◽

L. A. Miller ◽

J. A. Poupard

Keyword(s):

Escherichia Coli ◽

Quality Control ◽

Clavulanic Acid ◽

Susceptibility Testing ◽

Test Medium ◽

E Coli ◽

Mueller Hinton ◽

Quality Control Testing ◽

Amoxicillin Clavulanic Acid ◽

Lactamase Inhibitor

ABSTRACT Current National Committee for Clinical Laboratory Standards (NCCLS) susceptibility guidelines for quality control testing withHaemophilus influenzae do not include a β-lactamase-producing strain that could detect the deterioration of the β-lactamase inhibitor components of amoxicillin-clavulanic acid, ampicillin-sulbactam, and piperacillin-tazobactam. The objective of the study was to determine if comparable quality control results forEscherichia coli ATCC 35218, a β-lactamase-producing strain, would be produced for the three β-lactam–β-lactamase inhibitor agents with Haemophilus test medium and Mueller-Hinton medium. The criteria used in this study to determine if Haemophilus test medium was acceptable for quality control testing of E. coli ATCC 35218 was that 100% of the results obtained with an antimicrobial agent-methodology combination needed to be within the acceptable NCCLS ranges established with Mueller-Hinton medium. The MIC testing results obtained by the broth microdilution and E-test methods with amoxicillin-clavulanic acid and piperacillin-tazobactam were all within the NCCLS ranges; however, the results obtained with ampicillin-sulbactam by both methods were not within the NCCLS ranges. Acceptable results were obtained by the disk diffusion methodology with ampicillin-sulbactam and piperacillin-tazobactam but not with amoxicillin-clavulanic acid. When performing susceptibility testing with H. influenzae with the β-lactam–β-lactamase inhibitors, in addition to quality control testing with H. influenzae ATCC 49247, testing of E. coli ATCC 35218 on Haemophilus test medium is an effective way to monitor the β-lactamase inhibitors in some antimicrobial agent-methodology combinations.

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Interactions between Penicillin-Binding Proteins (PBPs) and Two Novel Classes of PBP Inhibitors, Arylalkylidene Rhodanines and Arylalkylidene Iminothiazolidin-4-ones

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.3.961-969.2004 ◽

2004 ◽

Vol 48 (3) ◽

pp. 961-969 ◽

Cited By ~ 48

Author(s):

Astrid Zervosen ◽

Wei-Ping Lu ◽

Zhouliang Chen ◽

Ronald E. White ◽

Thomas P. Demuth ◽

...

Keyword(s):

Escherichia Coli ◽

Cell Wall ◽

Cell Wall Synthesis ◽

Bacterial Strains ◽

Gram Negative ◽

Penicillin Binding Proteins ◽

E Coli ◽

Peptidoglycan Biosynthesis ◽

Vancomycin Resistant ◽

Inhibitory Activities

ABSTRACT Several non-β-lactam compounds were active against various gram-positive and gram-negative bacterial strains. The MICs of arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-ones were lower than those of ampicillin and cefotaxime for methicillin-resistant Staphylococcus aureus MI339 and vancomycin-resistant Enterococcus faecium EF12. Several compounds were found to inhibit the cell wall synthesis of S. aureus and the last two steps of peptidoglycan biosynthesis catalyzed by ether-treated cells of Escherichia coli or cell wall membrane preparations of Bacillus megaterium. The effects of the arylalkylidene rhodanines and arylalkylidene iminothiazolidin-4-one derivatives on E. coli PBP 3 and PBP 5, Streptococcus pneumoniae PBP 2xS (PBP 2x from a penicillin-sensitive strain) and PBP 2xR (PBP 2x from a penicillin-resistant strain), low-affinity PBP 2a of S. aureus, and the Actinomadura sp. strain R39 and Streptomyces sp. strain R61 dd-peptidases were studied. Some of the compounds exhibited inhibitory activities in the 10 to 100 μM concentration range. The inhibition of PBP 2xS by several of them appeared to be noncompetitive. The dissociation constant for the best inhibitor (Ki = 10 μM) was not influenced by the presence of the substrate.

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