scholarly journals In VitroActivities of 21 Antimicrobial Agents Alone and in Combination with Aminoglycosides or Fluoroquinolones against Extended-Spectrum-β-Lactamase-Producing Escherichia coli Isolates Causing Bacteremia

2015 ◽  
Vol 59 (9) ◽  
pp. 5834-5837 ◽  
Author(s):  
Min Kyeong Cha ◽  
Cheol-In Kang ◽  
So Hyun Kim ◽  
Sun Young Cho ◽  
Young Eun Ha ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Therapy ◽  
Antimicrobial Agents ◽  
Empirical Therapy ◽  
Gram Negative ◽  
Content Type ◽  
South Korean ◽  
Extended Spectrum ◽  
High Prevalence

ABSTRACTWe evaluated thein vitroactivity of various antimicrobials alone and in combination against 291 extended-spectrum-β-lactamase-producingEscherichia coli(ESBL-EC) isolates causing bacteremia in South Korean hospitals. Ceftazidime, cefepime, and piperacillin-tazobactam in combination with amikacin showed greater activity than found in combination with ciprofloxacin. In settings with a high prevalence of ESBL-producing pathogens, combination aminoglycoside antimicrobial therapy, especially with amikacin, may be considered for empirical therapy against suspected Gram-negative sepsis as a carbapenem-saving strategy.

scholarly journals In Vitro Activity of Imipenem-Relebactam and Ceftolozane-Tazobactam against Resistant Gram-Negative Bacilli

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Suzannah M. Schmidt-Malan ◽  
Avisya J. Mishra ◽  
Ammara Mushtaq ◽  
Cassandra L. Brinkman ◽  
Robin Patel
Keyword(s):  
Antimicrobial Agents ◽  
Empirical Therapy ◽  
Drug Resistant ◽  
Rapid Diagnostics ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Content Type ◽  
Inhibitor Combination ◽  
Selection Of

ABSTRACT Understanding which antimicrobial agents are likely to be active against Gram-negative bacilli can guide selection of antimicrobials for empirical therapy as mechanistic rapid diagnostics are adopted. In this study, we determined the MICs of a novel β-lactam–β-lactamase inhibitor combination, imipenem-relebactam, along with ceftolozane-tazobactam, imipenem, ertapenem, meropenem, ceftriaxone, and cefepime, against 282 drug-resistant isolates of Gram-negative bacilli. For isolates harboring blaKPC (n = 110), the addition of relebactam to imipenem lowered the MIC50/MIC90 from 16/>128 μg/ml for imipenem alone to 0.25/1 μg/ml. For isolates harboring blaCTX-M (n = 48), the MIC50/MIC90 of ceftolozane-tazobactam were 0.5/16 μg/ml (83% susceptible). For isolates harboring blaCMY-2 (n = 17), the MIC50/MIC90 of ceftolozane-tazobactam were 4/8 μg/ml (47% susceptible). Imipenem-relebactam was active against most KPC-producing (but not NDM- or IMP-producing) Enterobacteriaceae and is an encouraging addition to the present antibiotic repertoire.

scholarly journals A Novel Method of Serum Resistance by Escherichia coli That Causes Urosepsis

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Carrie F. Coggon ◽  
Andrew Jiang ◽  
Kelvin G. K. Goh ◽  
Ian R. Henderson ◽  
Mark A. Schembri ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Serum Resistance ◽  
Gram Negative ◽  
Content Type ◽  
Bacterial Surface ◽  
O Antigen ◽  
High Prevalence ◽  
Novel Method ◽  
Inhibitory Antibodies

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection, which in some patients can develop into life-threatening urosepsis. Serum resistance is a key virulence trait of strains that cause urosepsis. Recently, we identified a novel method of serum resistance in patients with Pseudomonas aeruginosa lung infections, where patients possessed antibodies that inhibited complement-mediated killing (instead of protecting against infection). These inhibitory antibodies were of the IgG2 subtype, specific to the O-antigen component of lipopolysaccharide (LPS) and coated the bacterial surface, preventing bacterial lysis by complement. As this mechanism could apply to any Gram-negative bacterial infection, we hypothesized that inhibitory antibodies may represent an uncharacterized mechanism of serum resistance in UPEC. To test this, 45 urosepsis patients with paired blood culture UPEC isolates were screened for serum titers of IgG2 specific for their cognate strain’s LPS. Eleven patients had sufficiently high titers of the antibody to inhibit serum-mediated killing of UPEC isolates by pooled healthy control sera. Depletion of IgG or removal of O-antigen restored sensitivity of the isolates to the cognate patient serum. Importantly, the isolates from these 11 patients were more sensitive to killing by serum than isolates from patients with no inhibitory antibodies. This suggests the presence of inhibitory antibodies may have allowed these strains to infect the bloodstream. The high prevalence of patients with inhibitory antibodies (24%) suggests that this phenomenon is an important mechanism of UPEC serum resistance. LPS-specific inhibitory antibodies have now been identified against three Gram-negative pathogens that cause disparate diseases. IMPORTANCE Despite improvements in the early detection and management of sepsis, morbidity and mortality are still high. Infections of the urinary tract are one of the most frequent sources of sepsis with Escherichia coli the main causative agent. Serum resistance is vital for bacteria to infect the bloodstream. Here we report a novel method of serum resistance found in patients with UPEC-mediated sepsis. Antibodies in sera usually protect against infection, but here we found that 24% of patients expressed “inhibitory antibodies” capable of preventing serum-mediated killing of their infecting isolate. Our data suggest that these antibodies would allow otherwise serum-sensitive UPEC strains to cause sepsis. The high prevalence of patients with inhibitory antibodies in this cohort suggests that this is a widespread mechanism of resistance to complement-mediated killing in urosepsis patients, invoking the potential for the application of new methods to prevent and treat sepsis.

scholarly journals Transposition of Tn1213Encoding the PER-1 Extended-Spectrum β-Lactamase

2018 ◽  
Vol 62 (3) ◽  
pp. e02453-17 ◽  
Author(s):  
Stefano Mancini ◽  
Laurent Poirel ◽  
Nicolas Kieffer ◽  
Patrice Nordmann
Keyword(s):  
Escherichia Coli ◽  
Low Frequency ◽  
Insertion Sequences ◽  
Content Type ◽  
Very Low Frequency ◽  
Extended Spectrum

ABSTRACTPER-1 is an extended-spectrum β-lactamase that is encoded by a gene located in composite transposon Tn1213made by two distinct insertion sequences, namely, ISPa12and ISPa13. In vitromobilization performed inEscherichia colishows that Tn1213is functional and is able to mobilize theblaPER-1gene, although at a very low frequency (ca. 1 × 10−9).

scholarly journals In Vitro Activity of Newer and Conventional Antimicrobial Agents, Including Fosfomycin and Colistin, against Selected Gram-Negative Bacilli in Kuwait

Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 75 ◽  
Author(s):  
Wadha Alfouzan ◽  
Rita Dhar ◽  
David Nicolau
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Agents ◽  
The Other ◽  
In Vitro Activity ◽  
Limited Data ◽  
Gram Negative ◽  
E Coli ◽  
Microbroth Dilution

Limited data are available on susceptibilities of these organisms to some of the recently made accessible antimicrobial agents. The in vitro activities of newer antibiotics, such as, ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) along with some “older” antibiotics, for example fosfomycin (FOS) and colistin (CL) were determined against selected strains (resistant to ≥ 3 antimicrobial agents) of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MIC) were determined by Clinical and Laboratory Standards Institute microbroth dilution. 133 isolates: 46 E. coli, 39 K. pneumoniae, and 48 P. aeruginosa were tested. Results showed that E. coli isolates with MIC50/90, 0.5/1 μ g / mL for CL; 4/32 μ g / mL for FOS; 0.25/32 μ g / mL for C/T; 0.25/8 μ g / mL for CZA, exhibited susceptibility rates of 95.7%, 97.8%, 76.1%, and 89.1%, respectively. On the other hand, K. pneumoniae strains with MIC50/90, 0.5/1 μ g / mL for CL; 256/512 μ g / mL for FOS; 2/128 μ g / mL for C/T; 0.5/128 μ g / mL for CZA showed susceptibility rates of 92.3%, 7.7%, 51.3%, and 64.1%, respectively. P. aeruginosa isolates with MIC50/90, 1/1 μ g / mL for CL; 128/128 μ g / mL for C/T; 32/64 μ g / mL for CZA presented susceptibility rates of 97.9%, 33.3%, and 39.6%, respectively. Higher MICs were demonstrated against most of the antibiotics. However, CL retained efficacy at low MICs against most of the isolates tested.

scholarly journals In vitro activity of premafloxacin, a new extended-spectrum fluoroquinolone, against pathogens of veterinary importance.

1997 ◽  
Vol 41 (5) ◽  
pp. 1190-1192 ◽  
Author(s):  
J L Watts ◽  
S A Salmon ◽  
M S Sanchez ◽  
R J Yancey
Keyword(s):  
Antimicrobial Agents ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Negative ◽  
Extended Spectrum ◽  
Veterinary Importance

The in vitro activity of premafloxacin against 673 veterinary pathogens was evaluated. Premafloxacin was equivalent to ciprofloxacin, enrofloxacin, and danofloxacin in activity against the gram-negative bacilli but was much more active (MIC for 90% of the strains tested [MIC90], 0.015 to 0.25 microg/ml) than the comparison antimicrobial agents (MIC90, 0.13 to 16.0 microg/ml) against the staphylococci, streptococci, and anaerobes tested.

scholarly journals In VitroSusceptibility of Characterized β-Lactamase-Producing Strains Tested with Avibactam Combinations

2014 ◽  
Vol 59 (3) ◽  
pp. 1789-1793 ◽  
Author(s):  
Henry Li ◽  
Mark Estabrook ◽  
George A. Jacoby ◽  
Wright W. Nichols ◽  
Raymond T. Testa ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Enterobacter Cloacae ◽  
Gram Negative ◽  
Content Type ◽  
Extended Spectrum ◽  
Lactamase Inhibitor

ABSTRACTAvibactam, a broad-spectrum β-lactamase inhibitor, was tested with ceftazidime, ceftaroline, or aztreonam against 57 well-characterized Gram-negative strains producing β-lactamases from all molecular classes. Most strains were nonsusceptible to the β-lactams alone. Against AmpC-, extended-spectrum β-lactamase (ESBL)-, and KPC-producingEnterobacteriaceaeorPseudomonas aeruginosa, avibactam lowered ceftazidime, ceftaroline, or aztreonam MICs up to 2,048-fold, to ≤4 μg/ml. Aztreonam-avibactam MICs against a VIM-1 metallo-β-lactamase-producingEnterobacter cloacaeand a VIM-1/KPC-3-producingEscherichia coliisolate were 0.12 and 8 μg/ml, respectively.

scholarly journals Membrane Protein Complex ExbB4-ExbD1-TonB1from Escherichia coli Demonstrates Conformational Plasticity

2015 ◽  
Vol 197 (11) ◽  
pp. 1873-1885 ◽  
Author(s):  
Aleksandr Sverzhinsky ◽  
Jacqueline W. Chung ◽  
Justin C. Deme ◽  
Lucien Fabre ◽  
Kristian T. Levey ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Iron Acquisition ◽  
Proton Translocation ◽  
Three Dimensional ◽  
Structural Data ◽  
Structural Features ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type

ABSTRACTIron acquisition at the outer membrane (OM) of Gram-negative bacteria is powered by the proton motive force (PMF) of the cytoplasmic membrane (CM), harnessed by the CM-embedded complex of ExbB, ExbD, and TonB. Its stoichiometry, ensemble structural features, and mechanism of action are unknown. By panning combinatorial phage libraries, periplasmic regions of dimerization between ExbD and TonB were predicted. Using overexpression of full-length His6-taggedexbB-exbDand S-taggedtonB, we purified detergent-solubilized complexes of ExbB-ExbD-TonB fromEscherichia coli. Protein-detergent complexes of ∼230 kDa with a hydrodynamic radius of ∼6.0 nm were similar to previously purified ExbB4-ExbD2complexes. Significantly, they differed in electronegativity by native agarose gel electrophoresis. The stoichiometry was determined to be ExbB4-ExbD1-TonB1. Single-particle electron microscopy agrees with this stoichiometry. Two-dimensional averaging supported the phage display predictions, showing two forms of ExbD-TonB periplasmic heterodimerization: extensive and distal. Three-dimensional (3D) particle classification showed three representative conformations of ExbB4-ExbD1-TonB1. Based on our structural data, we propose a model in which ExbD shuttles a proton across the CM via an ExbB interprotein rearrangement. Proton translocation would be coupled to ExbD-mediated collapse of extended TonB in complex with ligand-loaded receptors in the OM, followed by repositioning of TonB through extensive dimerization with ExbD. Here we present the first report for purification of the ExbB-ExbD-TonB complex, molar ratios within the complex (4:1:1), and structural biology that provides insights into 3D organization.IMPORTANCEReceptors in the OM of Gram-negative bacteria allow entry of iron-bound siderophores that are necessary for pathogenicity. Numerous iron-acquisition strategies rely upon a ubiquitous and unique protein for energization: TonB. Complexed with ExbB and ExbD, the Ton system links the PMF to OM transport. Blocking iron uptake by targeting a vital nanomachine holds promise in therapeutics. Despite much research, the stoichiometry, structural arrangement, and molecular mechanism of the CM-embedded ExbB-ExbD-TonB complex remain unreported. Here we demonstratein vitroevidence of ExbB4-ExbD1-TonB1complexes. Using 3D EM, we reconstructed the complex in three conformational states that show variable ExbD-TonB heterodimerization. Our structural observations form the basis of a model for TonB-mediated iron acquisition.

scholarly journals Fur Represses Adhesion to, Invasion of, and Intracellular Bacterial Community Formation within Bladder Epithelial Cells and Motility in Uropathogenic Escherichia coli

2016 ◽  
Vol 84 (11) ◽  
pp. 3220-3231 ◽  
Author(s):  
Kumiko Kurabayashi ◽  
Tomohiro Agata ◽  
Hirofumi Asano ◽  
Haruyoshi Tomita ◽  
Hidetada Hirakawa
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Antimicrobial Agents ◽  
Host Cells ◽  
Type I ◽  
Wild Type ◽  
Content Type ◽  
Type I Fimbriae ◽  
Tract Infections

Uropathogenic Escherichia coli (UPEC) is a major pathogen that causes urinary tract infections (UTIs). This bacterium adheres to and invades the host cells in the bladder, where it forms biofilm-like polymicrobial structures termed intracellular bacterial communities (IBCs) that protect UPEC from antimicrobial agents and the host immune systems. Using genetic screening, we found that deletion of the fur gene, which encodes an iron-binding transcriptional repressor for iron uptake systems, elevated the expression of type I fimbriae and motility when UPEC was grown under iron-rich conditions, and it led to an increased number of UPEC cells adhering to and internalized in bladder epithelial cells. Consequently, the IBC colonies that the fur mutant formed in host cells were denser and larger than those formed by the wild-type parent strain. Fur is inactivated under iron-restricted conditions. When iron was depleted from the bacterial cultures, wild-type UPEC adhesion, invasion, and motility increased, similar to the case with the fur mutant. The purified Fur protein bound to regions upstream of fimA and flhD , which encode type I fimbriae and an activator of flagellar expression that contributes to motility, respectively. These results suggest that Fur is a repressor of fimA and flhD and that its repression is abolished under iron-depleted conditions. Based on our in vitro experiments, we conclude that UPEC adhesion, invasion, IBC formation, and motility are suppressed by Fur under iron-rich conditions but derepressed under iron-restricted conditions, such as in patients with UTIs.

scholarly journals Global Assessment of Antimicrobial Susceptibility among Gram-Negative Organisms Collected from Pediatric Patients between 2004 and 2012: Results from the Tigecycline Evaluation and Surveillance Trial

2015 ◽  
Vol 53 (4) ◽  
pp. 1286-1293 ◽  
Author(s):  
Sue C. Kehl ◽  
Michael J. Dowzicky
Keyword(s):  
North America ◽  
Antimicrobial Susceptibility ◽  
Antimicrobial Agents ◽  
Pediatric Patients ◽  
Age Groups ◽  
Active Agent ◽  
Asia Pacific ◽  
Gram Negative ◽  
Content Type

The Tigecycline Evaluation and Surveillance Trial (TEST) was designed to monitor susceptibility to commonly used antimicrobial agents among important pathogens. We report here on susceptibility among Gram-negative pathogens collected globally from pediatric patients between 2004 and 2012. Antimicrobial susceptibility was determined using guidelines published by the Clinical and Laboratory Standards Institute (CLSI). MostEnterobacteriaceaeshowed high rates of susceptibility (>95%) to amikacin, tigecycline, and the carbapenems (imipenem and meropenem); 90.8% ofAcinetobacter baumanniiisolates were susceptible to minocycline, and susceptibility rates were highest in North America, Europe, and Asia/Pacific Rim. Amikacin was the most active agent againstPseudomonas aeruginosa(90.4% susceptibility), with susceptibility rates being highest in North America. Extended-spectrum β-lactamases (ESBLs) were reported for 11.0% ofEscherichia coliisolates and 24.2% ofKlebsiella pneumoniaeisolates globally, with rates reaching as high as 25.7% in the Middle East and >43% in Africa and Latin America, respectively. Statistically significant (P< 0.01) differences in susceptibility rates were noted between pediatric age groups (1 to 5 years, 6 to 12 years, or 13 to 17 years of age), globally and in some regions, for all pathogens exceptHaemophilus influenzae. Significant (P< 0.01) differences were reported for all pathogens globally and in most regions, considerably more frequently, when pediatric and adult susceptibility results were compared. Amikacin, tigecycline, and the carbapenems were activein vitroagainst most Gram-negative pathogens collected from pediatric patients;A. baumanniiandP. aeruginosawere susceptible to fewer antimicrobial agents. Susceptibility rates among isolates from pediatric patients were frequently different from those among isolates collected from adults.

scholarly journals Gentamicin-Loaded Borate Bioactive Glass Eradicates Osteomyelitis Due to Escherichia coli in a Rabbit Model

2013 ◽  
Vol 57 (7) ◽  
pp. 3293-3298 ◽  
Author(s):  
Zongping Xie ◽  
Xu Cui ◽  
Cunju Zhao ◽  
Wenhai Huang ◽  
Jianqiang Wang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bioactive Glass ◽  
Rabbit Model ◽  
Radiographic Evaluation ◽  
Sustained Drug Release ◽  
Gram Negative ◽  
Content Type ◽  
Rabbit Tibia ◽  
Borate Bioactive Glass

ABSTRACTThe treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillusEscherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluatedin vitroandin vivofor the treatment of osteomyelitis induced byEscherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.

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