In vitro evaluation of the determinants of bactericidal activity of ampicillin dosing regimens against Escherichia coli.

ABSTRACT Pulse dosing is a novel approach to dosing that produces escalating antibiotic levels early in the dosing interval followed by a prolonged dose-free period. Antibiotic is frontloaded by means of four sequential bolus injections, after which antibiotic levels are allowed to diminish until the next dose. This study compares standard thrice-daily dosing and pulse dosing of metronidazole against Bacteroides spp. in an in vitro model. Two American Type Culture Collection Bacteroides fragilis isolates (metronidazole MIC for each organism = 1 mg/liter) were exposed to metronidazole for 48 or 96 h. Human pharmacokinetics were simulated for an oral 500-mg dose given every 8 h (maximum concentration of drug [C max] = 12 mg/liter; half-life = 8 h; area under the curve [AUC] = 294 mg · h/liter) and for pulse dosing. Pulses, each producing an increase in metronidazole concentration of 9 mg/liter, were administered at times 0, 2, 4, and 6 h of each 24-h cycle, with a targeted half-life of 8 h (AUC = 347 mg · h/liter). A metronidazole-resistant B. fragilis strain (metronidazole MIC = 32 mg/liter) was exposed to both dosing regimens and, additionally, to a regimen of 1,500 mg administered once daily (C max = 36 mg/liter; AUC = 364 mg · h/liter). Furthermore, regimens against one B. fragilis isolate and one B. thetaiotaomicron isolate corresponding to one-fourth and one-eighth of the thrice-daily and pulse dosing regimens, mimicking peak metronidazole concentrations achieved in abscesses, were simulated in 48-h experiments (metronidazole MIC = 1 mg/liter). Time-kill curves were generated for each experiment and analyzed for bactericidal activity, defined as a bacterial burden reduction ≥ 3 log10 CFU/ml. The results of paired (Wilcoxon matched-pair signed-rank test) and nonpaired (Mann-Whitney test) statistical analyses conducted on time to 3 log10 kill data and area under the kill curve data from each of the thrice-daily dosing experiments versus each of the pulse dosing experiments were considered not significant for a given isolate-dosing regimen combination. The thrice-daily dosing, pulse dosing, and once-daily dosing regimens all exhibited bactericidal activity. Metronidazole administered in standard or pulse dosing fashion was highly active against both susceptible and resistant strains of Bacteroides spp.

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In Vitro Analysis of the Bactericidal Activity of Escherichia Coli Nissle 1917 Against Pediatric Uropathogens

The Journal of Urology ◽

10.1016/j.juro.2011.04.021 ◽

2011 ◽

Vol 186 (4S) ◽

pp. 1678-1683 ◽

Cited By ~ 15

Author(s):

Douglas W. Storm ◽

Stephen A. Koff ◽

Dennis J. Horvath ◽

Birong Li ◽

Sheryl S. Justice

Keyword(s):

Escherichia Coli ◽

Bactericidal Activity ◽

Escherichia Coli Nissle 1917 ◽

Vitro Analysis ◽

Escherichia Coli Nissle ◽

In Vitro Analysis

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Impact of Daptomycin Dose Exposure Alone or in Combination with β-Lactams or Rifampin against Vancomycin-Resistant Enterococci in an In Vitro Biofilm Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02074-19 ◽

2020 ◽

Vol 64 (5) ◽

Cited By ~ 1

Author(s):

Seyedehameneh Jahanbakhsh ◽

Nivedita B. Singh ◽

Juwon Yim ◽

Razieh Kebriaei ◽

Jordan R. Smith ◽

...

Keyword(s):

Bactericidal Activity ◽

Enterococcus Faecium ◽

Biofilm Reactor ◽

Content Type ◽

Biofilm Model ◽

Vancomycin Resistant Enterococci ◽

Dosing Regimens ◽

Vancomycin Resistant ◽

Reactor Models

ABSTRACT Enterococcus faecium strains are commonly resistant to vancomycin and β-lactams. In addition, E. faecium often causes biofilm-associated infections and these infections are difficult to treat. In this context, we investigated the activity of dosing regimens using daptomycin (DAP) (8, 10, 12, and 14 mg/kg of body weight/day) alone and in combination with ceftaroline (CPT), ampicillin (AMP), ertapenem (ERT), and rifampin (RIF) against 2 clinical strains of biofilm-producing vancomycin-resistant Enterococcus faecium (VREfm), namely, strains S447 and HOU503, in an in vitro biofilm model. HOU503 harbors common LiaS and LiaR substitutions, whereas S447 lacks mutations associated with the LiaFSR pathway. MIC results demonstrated that both strains were susceptible to DAP and resistant to CPT, AMP, ERT, and RIF. The 168-h pharmacokinetic/pharmacodynamic (PK/PD) CDC biofilm reactor models (simulating human antibiotic exposures) were used with titanium and polyurethane coupons to evaluate the efficacy of antibiotic combinations. DAP 12 and 14 achieved bactericidal activity against S447 but lacked such effect against HOU503. Addition of ERT and RIF enhanced DAP activity, allowing DAP 8 and 10 plus ERT or RIF to produce bactericidal activity against both strains at 168 h. While DAP 8 and 10 plus CPT improved killing, they did not reach bactericidal reduction against S447. Combination of AMP, CPT, ERT, or RIF resulted in enhanced and bactericidal activity for DAP against HOU503 at 168 h. Our data provide further support for the use of combinations of DAP with AMP, ERT, CPT, and RIF in infections caused by biofilm producing VREfm. Further research involving DAP combinations against biofilm-producing enterococci is warranted.

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Chemical synthesis of the outer core oligosaccharide of Escherichia coli R3 and immunological evaluation

Organic & Biomolecular Chemistry ◽

10.1039/c5ob00177c ◽

2015 ◽

Vol 13 (14) ◽

pp. 4321-4330 ◽

Cited By ~ 4

Author(s):

Wenjing Shang ◽

Zhongying Xiao ◽

Zaikuan Yu ◽

Na Wei ◽

Guohui Zhao ◽

...

Keyword(s):

Escherichia Coli ◽

Chemical Synthesis ◽

Bactericidal Activity ◽

Outer Core ◽

Core Oligosaccharide ◽

Immunological Evaluation

An all α-linked Escherichia coli R3 outer core pentasaccharide was first synthesized. Its corresponding glycoconjugate can elicit specific anti-pentasaccharide antibodies with in vitro bactericidal activity.

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In vitro bactericidal activity of diterpenoids isolated from Aframomum melegueta K.Schum against strains of Escherichia coli , Listeria monocytogenes and Staphylococcus aureus

Journal of Ethnopharmacology ◽

10.1016/j.jep.2013.12.035 ◽

2014 ◽

Vol 151 (3) ◽

pp. 1147-1154 ◽

Cited By ~ 8

Author(s):

Kenneth G. Ngwoke ◽

Olivier Chevallier ◽

Venasius K. Wirkom ◽

Paul Stevenson ◽

Christopher T. Elliott ◽

...

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Listeria Monocytogenes ◽

Bactericidal Activity ◽

And Staphylococcus Aureus

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Short-Course Gentamicin in Combination with Daptomycin or Vancomycin against Staphylococcus aureus in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.49.7.2735-2745.2005 ◽

2005 ◽

Vol 49 (7) ◽

pp. 2735-2745 ◽

Cited By ~ 80

Author(s):

Brian T. Tsuji ◽

Michael J. Rybak

Keyword(s):

Staphylococcus Aureus ◽

Bactericidal Activity ◽

Pharmacodynamic Model ◽

High Dose ◽

Single High Dose ◽

Short Course ◽

Dosing Regimens ◽

Combination Regimens ◽

The Impact

ABSTRACT The ability to maximize bactericidal activity while minimizing toxicity is a therapeutic goal in the treatment of infective endocarditis. We evaluated the impact of administering short-course regimens of gentamicin in combination with daptomycin or vancomycin against one methicillin-susceptible (MSSA 1199) and one methicillin-resistant (MRSA 494) Staphylococcus aureus isolate using an in vitro pharmacodynamic model with simulated endocardial vegetations over 96 h. Human therapeutic dosing regimens for daptomycin (6 and 8 mg/kg of body weight), vancomycin, and gentamicin were simulated. Short-course combination regimens involving gentamicin were administered either as a single 5-mg/kg dose or three 1-mg/kg doses for only the first 24 h and compared to the regimens administered for the full 96-h duration. For all experiments, physiologic conditions of albumin, calcium, and pH were simulated. Both regimens of daptomycin achieved 99.9% kill by 32 h and maintained bactericidal activity against both isolates, which was significantly different from vancomycin, which displayed bacteriostatic activity (P < 0.05). The effects of all short-course regimens of gentamicin were equal to those of the full-duration regimens in combination with daptomycin. Adding three doses of gentamicin (1 mg/kg) to daptomycin resulted in enhancement and bactericidal activity at 24 h against both MRSA and MSSA. The addition of a single dose of gentamicin (5 mg/kg) enhanced or improved the activity of daptomycin and resulted in early bactericidal activity at 4 h against both isolates. The addition of three doses of gentamicin (1 mg/kg) did not improve the activity of vancomycin. However, the addition of a single 5-mg/kg dose of gentamicin to vancomycin resulted in early enhancement at 4 h and 99.9% kill at 32 h for MRSA. These results suggest that a single high dose of gentamicin in combination with daptomycin or vancomycin may be of utility to maximize synergistic and bactericidal activity and minimize toxicity. Further investigation is warranted.

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