Susceptibilities of Gram-Negative Bacteria to Combinations of Antimicrobial Agents In Vitro

Leng, B; Meyers, Burt R.; Hirschman, Shalom Z.; Keusch, Gerald T.

doi:10.1128/aac.8.2.164

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…Consistently, in depth interaction studies by Leng, Meyers & Hirschman (1975) have reported similar findings against Gramnegative organisms and further demonstrated synergism against many Ε coli, Enterobacter sp, Klebsiella sp and Pseudomonas sp. Although antibacterial effectiveness is a prerequisite for clinical effectiveness, the ability of the cement to deliver active anti biotic will ultimately effect potential usability.…”

Section: Discussionsupporting

confidence: 65%

Polyacrylic Bone Cement Containing Erythromycin and Colistin I. In vitro Bacteriological Activity and Diffusion Properties of Erythromycin, Colistin and Erythromycin/Colistin Combination

Rosenthal¹,

Rovell²,

Girard

1976

J Int Med Res

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Erythromycin and colistin demonstrate a non-antagonistic ability to inhibit the growth of a wide variety of aerobic and anaerobic bacterial isolates. When incorporated in Surgical Simplex P Radiopaque Bone Cement, fabricated cement pellets were effective in inhibiting 98% of all anaerobic and aerobic test isolates. Separate experiments indicate that each antibiotic can diffuse from polymerized cement, and that the concentration of each antibiotic is consistently above the minimum inhibitory concentration of 96% of the isolates. We conclude that erythromycin/colistin Surgical Simplex P radiopaque Bone Cement is a worthy candidate for clinical investigation.

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Section: Discussionsupporting

confidence: 65%

Polyacrylic Bone Cement Containing Erythromycin and Colistin I. In vitro Bacteriological Activity and Diffusion Properties of Erythromycin, Colistin and Erythromycin/Colistin Combination

Rosenthal¹,

Rovell²,

Girard

1976

J Int Med Res

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“…We could not verify preliminary reports made by various investigators regarding an impairment of the bactericidal activity of gentamicin by clindamycin against gram-negative bacilli. Our results are in accordance with those of Leng and co-workers (7) and thosepresented by Fass and co-workers (4), who showed that clindamycin did not interfere with the activity of gentamicin; however, we did not observe any instance of synergism between clindamycin and gentamicin.…”

supporting

confidence: 83%

“…Several in vitro studies reported additive or synergistic activity of clindamycin plus gentamicin against gram-positive and gram-negative microorganisms (2,3,7).…”

mentioning

confidence: 99%

Bactericidal Activity of the Combinations of Gentamicin with Clindamycin or Chloramphenicol Against Species of Escherichia coli and Bacteroides fragilis

Klastersky

Husson

1977

Antimicrob Agents Chemother

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The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of Escherichia coli and 10 strains of Bacteroides fragilis isolated from clinical material. Gentamicin did not interfere with the activity of clindamycin or chloramphenicol against B. fragilis . The activity of gentamicin against E. coli was not influenced by clindamycin, but chloramphenicol suppressed the rapid bactericidal activity of gentamicin in seven out of eight strains of E. coli examined.

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“…It is known that the macrolide ERY shows only marginal activity against Gram-negative bacteria. Among clinical E. coli isolates, MICs ranging from 16 µg/ml to 1024 µg/ml have been reported [41][42] , whereas MICs range from 4 µg/ml to 150 µg/ml for lab strains 38,[43][44] . For the E. coli wildtype strain, we recorded a MIC of 32.9 µg/ml.…”

Section: Uptake Of Trimethoprim Tetracycline and Erythromycinmentioning

confidence: 99%

Subcellular Quantification of Uptake in Gram-Negative Bacteria

et al. 2018

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Infections by Gram-negative pathogens represent a major health care issue of growing concern due to a striking lack of novel antibacterial agents over the course of the last decades. The main scientific problem behind the rational optimization of novel antibiotics is our limited understanding of small molecule translocation into, and their export from the target compartments of Gram-negative species. To address this issue, a versatile, label-free assay to determine the intracellular localization and concentration of a given compound has been developed for Escherichia coli and its effluximpaired TolC mutant. The assay applies a fractionation procedure to antibiotic-treated bacterial cells to obtain periplasm, cytoplasm and membrane fractions of high purity, as demonstrated by Western Blots of compartment-specific marker proteins. This is followed by an LC-MS/MS-based quantification of antibiotic content in each compartment. Antibiotic amounts could be converted to antibiotic concentrations by assuming that an E. coli cell is a cylinder flanked by two half spheres and calculating the volumes of bacterial compartments. The quantification of antibiotics from different classes, namely ciprofloxacin, tetracycline, trimethoprim and erythromycin demonstrated pronounced differences in uptake quantities and distribution patterns across the compartments. For example, in the case of ciprofloxacin a higher amount of compound was located in the cytoplasm than in the periplasm (592 pg ±50 pg vs 277 ±13 pg per 3.9x10 9 cells), but owing to the smaller volume of the periplasmic compartment, its concentration in the cytoplasm was much lower (37 ±3 pg/µl vs. 221 ±10 pg/µl for the periplasm). For erythromycin and tetracycline, differences in MICs between WT and TolC mutant strains were not reflected by equal differences in uptake, illustrating that additional experimental data are needed to predict antibiotic efficacy. We believe that our assay, providing the antibiotic concentration at the compartment in which the drug target is expressed, constitutes an essential piece of information for a more rational optimization of novel antibiotics against Gram-negative infections.

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Susceptibilities of Gram-Negative Bacteria to Combinations of Antimicrobial Agents In Vitro

Cited by 12 publications

References 23 publications

Polyacrylic Bone Cement Containing Erythromycin and Colistin I. In vitro Bacteriological Activity and Diffusion Properties of Erythromycin, Colistin and Erythromycin/Colistin Combination

Polyacrylic Bone Cement Containing Erythromycin and Colistin I. In vitro Bacteriological Activity and Diffusion Properties of Erythromycin, Colistin and Erythromycin/Colistin Combination

Bactericidal Activity of the Combinations of Gentamicin with Clindamycin or Chloramphenicol Against Species of Escherichia coli and Bacteroides fragilis

Subcellular Quantification of Uptake in Gram-Negative Bacteria

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