Feeding an acetate-based oral electrolyte reduces the ex vivo Escherichia coli growth potential in the abomasum of calves fed oral electrolytes alone or 30 minutes following a milk feeding when compared to feeding a bicarbonate-based oral electrolyte

Introduction: We previously reported that extracellular vesicles (EVs) released during Escherichia coli bacterial pneumonia were inflammatory, and administration of high molecular weight hyaluronic acid (HMW HA) suppressed several indices of acute lung injury (ALI) from Escherichia coli pneumonia by binding to these inflammatory EVs. The current study was undertaken to study the therapeutic effects of HMW HA in ex vivo perfused human lungs injured with Pseudomonas aeruginosa (PA)103 bacterial pneumonia. Methods: For lungs with baseline alveolar fluid clearance (AFC)<10%/h, HMW HA 1 or 2 mg was injected intravenously after 1 h (N = 4-9), and EVs released during PA pneumonia were collected from the perfusate over 6 h. For lungs with baseline AFC>10%/h, HMW HA 2 mg was injected intravenously after 1 h (N = 6). In vitro experiments were conducted to evaluate the effects of HA on inflammation and bacterial phagocytosis. Results: For lungs with AFC<10%/h, administration of HMW HA intravenously significantly restored AFC and numerically decreased protein permeability and alveolar inflammation from PA103 pneumonia but had no effect on bacterial counts at 6 h. However, HMW HA improved bacterial phagocytosis by human monocytes and neutrophils and suppressed the inflammatory properties of EVs released during pneumonia on monocytes. For lungs with AFC>10%/h, administration of HMW HA intravenously improved AFC from PA103 pneumonia but had no significant effects on protein permeability, inflammation or bacterial counts. Discussion: In the presence of impaired alveolar epithelial transport capacity, administration of HMW HA improved the resolution of pulmonary edema from Pseudomonas PA103 bacterial pneumonia.

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Urinary Pharmacokinetic and Pharmacodynamic Profiles of Fosfomycin against Extended-Spectrum β-Lactamase-Producing Escherichia coli with Canine Ex Vivo Modeling: A Pilot Study

Antibiotics ◽

10.3390/antibiotics9050230 ◽

2020 ◽

Vol 9 (5) ◽

pp. 230

Author(s):

Kazuki Harada ◽

Takae Shimizu ◽

Koji Kawaguchi ◽

Takeshi Furuhashi ◽

Genki Ishihara

Keyword(s):

Escherichia Coli ◽

Drug Administration ◽

Ex Vivo ◽

Area Under The Curve ◽

Urine Concentration ◽

Test Period ◽

Time Curve ◽

Extended Spectrum ◽

Drug Concentrations ◽

Tract Infections

Fosfomycin is a candidate drug for extended-spectrum β-lactamase (ESBL)-producing bacteria, but its efficacy is yet to be investigated in dogs. This study investigated the urinary pharmacokinetic/pharmacodynamic (PK/PD) profile of fosfomycin orally administered at 80 mg/kg to six healthy dogs to assess its efficacy for canine urinary tract infections (UTIs) caused by ESBL-producing bacteria. Four strains of ESBL-producing Escherichia coli (ESBL-EC) characterized by fosfomycin minimum inhibitory concentrations (MICs) of 0.5, 1, 2, and 32 µg/mL were used. Urine samples for the measurement of urinary drug concentrations and urinary bactericidal titers (UBTs) were obtained after drug administration. The urinary concentrations (µg/mL, mean ± SE) were 1348.2 ± 163.5, 1191.6 ± 260.2, and 661.1 ± 190.4 at 0–4, 4–8, and 8–12 h, respectively, after drug administration. The mean urinary area under the curve during the test period (AUC0–12) of fosfomycin was estimated to be 12,803.8 µg·h/mL. The UBTs for all tested strains fluctuated closely with urine concentration during the test period (r = 0.944–1.000), and the area under the UBT-versus-time curve correlated with the urinary AUC/MIC of each strain (r = 0.991). According to the optimal urinary PK/PD target value, fosfomycin at 80 mg/kg twice daily may be suitable for the treatment of canine UTIs caused by ESBL-EC presenting MIC ≤ 128 µg/mL.

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Ex vivo antibacterial properties of rufloxacin compared with those of norfloxacin in a study with healthy volunteers.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.1.17 ◽

1996 ◽

Vol 40 (1) ◽

pp. 17-21 ◽

Cited By ~ 5

Author(s):

L Aguilar ◽

I P Balcabao ◽

P Salvá ◽

M Martín ◽

J Costa ◽

...

Keyword(s):

Escherichia Coli ◽

Clinical Trial ◽

Ex Vivo ◽

Antibacterial Properties ◽

Adult Males ◽

E Coli ◽

Crossover Phase ◽

Uncomplicated Cystitis ◽

And Staphylococcus Aureus ◽

Early Sample

Twelve adult males participated in a randomized crossover phase I clinical trial comparing serum bactericidal titers (SBTs), urine bactericidal titers (UBTs), and urine killing rates (UKRs) against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, after the administration of single 400-mg doses of rufloxacin and norfloxacin at different times up to 72 h postdose. SBTs were significantly higher (P < 0.05) against E. coli from 8 to 48 h and against S. aureus from 4 to 24 h with rufloxacin. UBTs for E. coli were higher (P < 0.05) for norfloxacin at early sample times (0 to 8 h) but higher for rufloxacin (P < 0.05) at sample times from 16 h on for both E. coli and S. aureus. Similar UKRs were obtained for both quinolones for 0 to 2 h and 8 to 12 h, but the UKR was maintained for 72 h with rufloxacin. The high and sustained mean levels of rufloxacin in urine (> 35 micrograms/ml), median UBTs (> 32 for E. coli and 16 for S. aureus) and UKRs for E. coli suggest prolonged urine antibacterial activity (for at least 72 h) and its use as a single 400-mg dose in the treatment of uncomplicated cystitis.

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