In vitro pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii

2020 ◽  
Author(s):  
A R Noel ◽  
M Attwood ◽  
K E Bowker ◽  
A P MacGowan
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Pharmacokinetic Model ◽  
Bacterial Load ◽  
Gram Negative ◽  
E Coli ◽  
Log Reduction ◽  
Static Effect

Abstract Background The pharmacodynamics of omadacycline have been extensively studied against Gram-positive pathogens but less information is available for Gram-negative pathogens. We describe the pre-clinical pharmacodynamics of omadacycline against Escherichia coli and Acinetobacter baumannii. Methods An in vitro dilutional pharmacokinetic model was used. Exposure experiments with fAUC/MIC ratios ranging from 0 to 1200 were performed using five strains of E. coli and five strains of A. baumannii. Reduction in bacterial load and changes in population profiles were measured. Results The fAUC/MIC targets against E. coli for 24 h static and −1 log reduction in load were 25.3 ± 17.2 and 42.7 ± 32.5, respectively. For A. baumannii the fAUC/MIC for 24 h static effect was 108.1 ± 38.6. Changes in population profiles were observed for E. coli at fAUC/MIC ratios of ≤200 and for A. baumannii up to 1200. MICs were increased 2–32 fold. Conclusions fAUC/MIC targets for A. baumannii are greater than for E.coli and changes in population profiles more likely. E. coli fAUC/MIC targets align with in vivo data and will be useful in determining omadacycline dosing for this pathogen.

scholarly journals Paenipeptin Analogues Potentiate Clarithromycin and Rifampin against mcr-1-Mediated Polymyxin-Resistant Escherichia coli In Vivo

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Sun Hee Moon ◽  
Yihong Kaufmann ◽  
En Huang
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Resistance ◽  
Outer Membrane ◽  
Infection Model ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Log Reduction

ABSTRACT Polymyxin resistance mediated by the mcr-1 gene threatens the last-resort antibiotics. Linear lipopeptide paenipeptin analogues 1 and 15 disrupted the outer membrane of Gram-negative pathogens and potentiated clarithromycin and rifampin against mcr-1-positive Escherichia coli from the FDA-CDC Antimicrobial Resistance Isolate Bank. In the presence of paenipeptin, clarithromycin and rifampin resulted in over 3-log reduction of E. coli in vitro. Moreover, paenipeptin-antibiotic combinations significantly reduced E. coli in a murine thigh infection model.

scholarly journals Synergistic effect of a recombinant N-terminal fragment of bactericidal/permeability-increasing protein and cefamandole in treatment of rabbit gram-negative sepsis.

1996 ◽  
Vol 40 (1) ◽  
pp. 65-69 ◽  
Author(s):  
Y Lin ◽  
W J Leach ◽  
W S Ammons
Keyword(s):  
Escherichia Coli ◽  
Septic Shock ◽  
Combined Treatment ◽  
Bacterial Clearance ◽  
Gram Negative ◽  
E Coli ◽  
Terminal Fragment ◽  
Cephalosporin Antibiotic

As a consequence of their bactericidal actions, many antibiotics cause the release of endotoxin, a primary mediator of gram-negative sepsis. Bactericidal/permeability-increasing protein (BPI) has bactericidal activity and neutralizes endotoxin in vitro and in vivo. We sought to examine the effect of a recombinant N-terminal fragment of BPI (rBPI21) in conjunction with cefamandole, a cephalosporin antibiotic, in the treatment of Escherichia coli bacteremia and septic shock in rabbits. Cefamandole (100 mg/kg of body weight) was injected intravenously. This was followed by simultaneous 10-min infusions of E. coli O7:K1 (9 x 10(9) CFU/kg) and rBPI21 (10 mg/kg). rBPI21 was continuously infused for an additional 110 min at 10 mg/kg/h. The administration of rBPI21 in conjunction with the administration of cefamandole prevented the cefamandole-induced increase of free endotoxin in plasma, accelerated bacterial clearance, ameliorated cardiopulmonary dysfunction, and thereby, prevented death, whereas neither agent alone was protective in this animal model. The efficacy of the combined treatment with rBPI21 and cefamandole suggests a synergistic interaction between the two agents. The data indicate that rBPI21 may be useful in conjunction with traditional antibiotic therapy.

scholarly journals Four Carbapenem-Resistant Gram-Negative Species Carrying Distinct Carbapenemases in a Single Patient

2014 ◽  
Vol 53 (3) ◽  
pp. 1031-1033 ◽  
Author(s):  
Baixing Ding ◽  
Fupin Hu ◽  
Yang Yang ◽  
Qinglan Guo ◽  
Jinwei Huang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Acinetobacter Baumannii ◽  
Enterobacter Aerogenes ◽  
Single Patient ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant

Carbapenem-resistantEscherichia coli,Klebsiella pneumoniae,Enterobacter aerogenes, andAcinetobacter baumanniiwere isolated from a single patient, each producing different carbapenemases (NDM-1, KPC-2, IMP, and OXA-23, respectively). The NDM-1-producingE. colistrain was preceded by a clonally related carbapenem-susceptible strain a month earlier, suggestingin vivoacquisition ofblaNDM-1.

Reduction of an Escherichia coli K12 Population by Bdellovibrio bacteriovorus Under Various In Vitro Conditions of Parasite:Host Ratio, Temperature, or pH

1992 ◽  
Vol 55 (11) ◽  
pp. 859-861 ◽  
Author(s):  
LEEANNE JACKSON ◽  
RICHARD C. WHITING
Keyword(s):  
Escherichia Coli ◽  
Bacterial Population ◽  
Bdellovibrio Bacteriovorus ◽  
Gram Negative ◽  
E Coli ◽  
Log Reduction ◽  
Extrinsic Parameters ◽  
High Concentrations ◽  
Intrinsic And Extrinsic Parameters

Intrinsic and extrinsic parameters of food products, as well as bacterial population, were evaluated for their effects on the ability of Bdellovibrio bacteriovorus, a bacterium parasitic upon gram-negative bacteria, to reduce an Escherichia coli population. High concentrations of both parasite and host were the most effective for reducing a specified E. coli population. B. bacteriovorus was able to reduce the E. coli count by 90% (1 log) in < 1 h at ratios of 5:1, 10:1, and 30:1 (parasite:host). Temperatures between 20 and 30°C were more conducive to bdellovibrio attack than temperatures less than 20°C. E. coli populations were reduced by more than 7-log values after 7 h of incubation at 30°C with parasite:host ratios of 2:1, 5:1, and 10:1. Greater than a 5-log reduction in the E. coli population was observed at the ratio of 30:1. B. bacteriovorus reduced the E. coli population by 1 log in approximately 24 min and 20 min at pH 7.2 and 6.8, respectively. At pH values <6.8, the activity of B. bacteriovorus was diminished. These results define some of the conditions where the application of B. bacteriovorus may aid in the reduction/elimination of some gram-negative pathogens and spoilage flora that may be present in foods.

scholarly journals Bacteriostasis of Escherichia coli by milk: I. Colonization of breast-fed infants by milk resistant organisms

1977 ◽  
Vol 78 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Jean M. Dolby ◽  
Pauline Honour ◽  
H. B. Valman
Keyword(s):  
Escherichia Coli ◽  
Human Milk ◽  
Bacteriostatic Effect ◽  
Gram Negative ◽  
E Coli ◽  
Resistant Strains ◽  
Gram Negative Organisms ◽  
Breast Fed

SUMMARYHuman milk has a bacteriostatic effect on Escherichia coli in vitro. The milks of 40 mothers were tested for this effect against E. coli isolated from their stools, from those of their own babies, and from those of babies not breast-fed. The milks had a direct bacteriostatic effect, not dependent on complement, on some but not all the strains of E. coli. Breast-fed babies receiving supplementary bottle feeds were colonized with milk-resistant strains, whereas bottle-fed babies and, surprisingly, babies completely breast-fed were colonized equally with milk-sensitive and milk-resistant strains, as were the mothers. These results suggest that the bacteriostatic effect of human milk, demonstrable in vitro does sometimes operate in vivo.The antibacterial activity of human milk is not influenced by the O, H or K antigens of E. coli and is effective against other Gram-negative organisms, e.g. Salmonella, Klebsiella, Proteus.

scholarly journals In Vitro Characterization and In Vivo Efficacy Assessment in Galleria mellonella Larvae of Newly Isolated Bacteriophages against Escherichia coli K1

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2005
Author(s):  
Céline Antoine ◽  
Fanny Laforêt ◽  
Bob Blasdel ◽  
Abdoulaye Fall ◽  
Jean-Noël Duprez ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Galleria Mellonella ◽  
Bacterial Load ◽  
Bloodstream Infections ◽  
Neonatal Meningitis ◽  
Capsular Type ◽  
In Vivo Efficacy ◽  
E Coli

Extra-intestinal Escherichia coli express several virulence factors that increase their ability to colonize and survive in different localizations. The K1 capsular type is involved in several infections, including meningitis, urinary tract, and bloodstream infections. The aims of this work were to isolate, characterize, and assess the in vivo efficacy of phages targeting avian pathogenic E. coli (APEC) O18:K1, which shares many similarities with the human strains responsible for neonatal meningitis. Eleven phages were isolated against APEC O18:K1, and four of them presenting a narrow spectrum targeting E. coli K1 strains were further studied. The newly isolated phages vB_EcoS_K1-ULINTec2 were similar to the Siphoviridae family, and vB_EcoP_K1-ULINTec4, vB_EcoP_K1-ULINTec6, and vB_EcoP_K1-ULINTec7 to the Autographiviridae family. They are capsular type (K1) dependent and present several advantages characteristic of lytic phages, such as a short adsorption time and latent period. vB_EcoP_K1-ULINTec7 is able to target both K1 and K5 strains. This study shows that these phages replicate efficiently, both in vitro and in vivo in the Galleria mellonella model. Phage treatment increases the larvae survival rates, even though none of the phages were able to eliminate the bacterial load.

scholarly journals Mechanistic insights into synergy between nalidixic acid and tetracycline against clinical isolates of Acinetobacter baumannii and Escherichia coli

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Amit Gaurav ◽  
Varsha Gupta ◽  
Sandeep K. Shrivastava ◽  
Ranjana Pathania
Keyword(s):  
Escherichia Coli ◽  
Acinetobacter Baumannii ◽  
Nalidixic Acid ◽  
Bacterial Infections ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Infection Model ◽  
Drug Resistant ◽  
E Coli

AbstractThe increasing prevalence of antimicrobial resistance has become a global health problem. Acinetobacter baumannii is an important nosocomial pathogen due to its capacity to persist in the hospital environment. It has a high mortality rate and few treatment options. Antibiotic combinations can help to fight multi-drug resistant (MDR) bacterial infections, but they are rarely used in the clinics and mostly unexplored. The interaction between bacteriostatic and bactericidal antibiotics are mostly reported as antagonism based on the results obtained in the susceptible model laboratory strain Escherichia coli. However, in the present study, we report a synergistic interaction between nalidixic acid and tetracycline against clinical multi-drug resistant A. baumannii and E. coli. Here we provide mechanistic insight into this dichotomy. The synergistic combination was studied by checkerboard assay and time-kill curve analysis. We also elucidate the mechanism behind this synergy using several techniques such as fluorescence spectroscopy, flow cytometry, fluorescence microscopy, morphometric analysis, and real-time polymerase chain reaction. Nalidixic acid and tetracycline combination displayed synergy against most of the MDR clinical isolates of A. baumannii and E. coli but not against susceptible isolates. Finally, we demonstrate that this combination is also effective in vivo in an A. baumannii/Caenorhabditis elegans infection model (p < 0.001)

scholarly journals Lysyl-tRNA synthetase from Escherichia coli K12. Chromatographic heterogeneity and the lysU-gene product

1987 ◽  
Vol 248 (1) ◽  
pp. 43-51 ◽  
Author(s):  
J Charlier ◽  
R Sanchez
Keyword(s):  
Escherichia Coli ◽  
Gene Product ◽  
Activity Ratio ◽  
Deae Cellulose ◽  
Trna Synthetase ◽  
Trna Synthetases ◽  
E Coli ◽  
Aminoacyl Trna Synthetases

In contrast with most aminoacyl-tRNA synthetases, the lysyl-tRNA synthetase of Escherichia coli is coded for by two genes, the normal lysS gene and the inducible lysU gene. During its purification from E. coli K12, lysyl-tRNA synthetase was monitored by its aminoacylation and adenosine(5′)tetraphospho(5′)adenosine (Ap4A) synthesis activities. Ap4A synthesis was measured by a new assay using DEAE-cellulose filters. The heterogeneity of lysyl-tRNA synthetase (LysRS) was revealed on hydroxyapatite; we focused on the first peak, LysRS1, because of its higher Ap4A/lysyl-tRNA activity ratio at that stage. Additional differences between LysRS1 and LysRS2 (major peak on hydroxyapatite) were collected. LysRS1 was eluted from phosphocellulose in the presence of the substrates, whereas LysRS2 was not. Phosphocellulose chromatography was used to show the increase of LysRS1 in cells submitted to heat shock. Also, the Mg2+ optimum in the Ap4A-synthesis reaction is much higher for LysRS1. LysRS1 showed a higher thermostability, which was specifically enhanced by Zn2+. These results in vivo and in vitro strongly suggest that LysRS1 is the heat-inducible lysU-gene product.

scholarly journals Biological Cost of Single and Multiple Norfloxacin Resistance Mutations in Escherichia coli Implicated in Urinary Tract Infections

2005 ◽  
Vol 49 (6) ◽  
pp. 2343-2351 ◽  
Author(s):  
Patricia Komp Lindgren ◽  
Linda L. Marcusson ◽  
Dorthe Sandvang ◽  
Niels Frimodt-Møller ◽  
Diarmaid Hughes
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract ◽  
Infection Model ◽  
Resistance Mutations ◽  
Topoisomerase Iv ◽  
E Coli ◽  
Tract Infections ◽  
Subsequent Selection

ABSTRACT Resistance to fluoroquinolones in urinary tract infection (UTIs) caused by Escherichia coli is associated with multiple mutations, typically those that alter DNA gyrase and DNA topoisomerase IV and those that regulate AcrAB-TolC-mediated efflux. We asked whether a fitness cost is associated with the accumulation of these multiple mutations. Mutants of the susceptible E. coli UTI isolate Nu14 were selected through three to five successive steps with norfloxacin. Each selection was performed with the MIC of the selected strain. After each selection the MIC was measured; and the regions of gyrA, gyrB, parC, and parE, previously associated with resistance mutations, and all of marOR and acrR were sequenced. The first selection step yielded mutations in gyrA, gyrB, and marOR. Subsequent selection steps yielded mutations in gyrA, parE, and marOR but not in gyrB, parC, or acrR. Resistance-associated mutations were identified in almost all isolates after selection steps 1 and 2 but in less than 50% of isolates after subsequent selection steps. Selected strains were competed in vitro, in urine, and in a mouse UTI infection model against the starting strain, Nu14. First-step mutations were not associated with significant fitness costs. However, the accumulation of three or more resistance-associated mutations was usually associated with a large reduction in biological fitness, both in vitro and in vivo. Interestingly, in some lineages a partial restoration of fitness was associated with the accumulation of additional mutations in late selection steps. We suggest that the relative biological costs of multiple mutations may influence the evolution of E. coli strains that develop resistance to fluoroquinolones.

scholarly journals The Escherichia coli cysG promoter belongs to the ‘extended −10’ class of bacterial promoters

1993 ◽  
Vol 296 (3) ◽  
pp. 851-857 ◽  
Author(s):  
T Belyaeva ◽  
L Griffiths ◽  
S Minchin ◽  
J Cole ◽  
S Busby
Keyword(s):  
Escherichia Coli ◽  
Point Mutations ◽  
Growth Conditions ◽  
Upstream Region ◽  
E Coli ◽  
Run Off ◽  
A Site ◽  
Specific Sequences

The Escherichia coli cysG promoter has been subcloned and shown to function constitutively in a range of different growth conditions. Point mutations identify the -10 hexamer and an important 5′-TGN-3′ motif immediately upstream. The effects of different deletions suggest that specific sequences in the -35 region are not essential for the activity of this promoter in vivo. This conclusion was confirmed by in vitro run-off transcription assays. The DNAase I footprint of RNA polymerase at the cysG promoter reveals extended protection upstream of the transcript start, and studies with potassium permanganate as a probe suggest that the upstream region is distorted in open complexes. Taken together, the results show that the cysG promoter belongs to the ‘extended -10’ class of promoters, and the base sequence is similar to that of the P1 promoter of the E. coli galactose operon, another promoter in this class. In vivo, messenger initiated at the cysG promoter appears to be processed by cleavage at a site 41 bases downstream from the transcript start point.

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