A new pharmacodynamic approach to study antibiotic combinations against enterococci in vivo: Application to ampicillin plus ceftriaxone

Jimenez-Toro, Ivone Eliana; Rodríguez, Carlos A.; Zuluaga, Andres F.; Otalvaro, Julian D.; Vesga, Ómar

doi:10.1371/journal.pone.0243365

Cited by 8 publications

(6 citation statements)

References 32 publications

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“…There is only one new parameter to be defined: a certain value of the delayed-healing threshold. In our study, the average wound closure% of the control group was taken as the threshold value, which was used to normalise the data in experimental groups in previous studies ( 19 , 20 ). However, u and l in plan B (the dependent variable was normalised by the control group) failed to meet the application conditions.…”

Section: Resultsmentioning

confidence: 99%

“…In general (e.g., the dependent variable is cell viability), the value of u does not exceed 100% (the formula for cell viability determines the range of this value). Similarly, l was not less than 0% (20,21). In plan A (Table 1), u and l satisfy the conditions in the model (u ≤ 100% and l ≥ 0%).…”

Section: Dose Curves Of Dex For Wound Healing In Mice With and Withou...mentioning

confidence: 93%

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Different effects of a perioperative single dose of dexamethasone on wound healing in mice with or without sepsis

Chen

Zhou

2023

Front. Surg.

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IntroductionSepsis delays wound healing owing to uncontrolled inflammation. A single perioperative dose of dexamethasone is widely used because of its anti-inflammatory effects. However, the effects of dexamethasone on wound healing in sepsis remain unclear.MethodsWe discuss the methods to obtain dose curves and explore the safe dosage range for wound healing in mice with or without sepsis. A saline or LPS intraperitoneal injection was applied to C57BL/6 mice. After 24 hours, the mice received a saline or DEX intraperitoneal injection and full-thickness, dorsal wounding operation. Wound healing was observed by image record, immunofluorescence and histological staining. Inflammatory cytokines and M1/M2 macrophages in wounds were determined by ELISA and immunofluorescence, respectively.ResultsDose-response curves reflected the safe dosage range of DEX in mice with or without sepsis, from 0.121 to 2.03 mg/kg and from 0 to 0.633 mg/kg, respectively. we found that a single dose of dexamethasone (1 mg/kg, i.p.) promoted wound healing in septic mice, but delayed wound healing in normal mice. In normal mice, dexamethasone delays inflammation, resulting in an insufficient number of macrophages during the healing process. In septic mice, dexamethasone alleviated excessive inflammation and maintained the balance of M1/M2 macrophages in the early and late healing process.DiscussionIn summary, the safe dosage range of dexamethasone in septic mice is wider than that in normal mice. A single dose of dexamethasone (1 mg/kg) increased wound healing in septic mice, but delayed it in normal mice. Our findings provide helpful suggestions for the rational use of dexamethasone.

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Section: Resultsmentioning

confidence: 99%

Section: Dose Curves Of Dex For Wound Healing In Mice With and Withou...mentioning

confidence: 93%

Different effects of a perioperative single dose of dexamethasone on wound healing in mice with or without sepsis

Chen

Zhou

2023

Front. Surg.

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“…A recently reported pharmacokinetic/pharmacodynamic study simulating human doses of ampicillin and ceftriaxone has remarked the usefulness of this combination administering ceftriaxone every 12 h [ 197 , 198 ]. This prompted us to abandon this regimen and consider other alternatives such as the co-administration of ampicillin + ceftriaxone in the same infusion.…”

Section: Outpatient Parenteral Antimicrobial Therapy (Opat)mentioning

confidence: 99%

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge

et al. 2023

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Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6–8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

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“…A recently reported pharmacokinetic/pharmacodynamic study simulating human doses of ampicillin and ceftriaxone has remarked the usefulness of this combination administering ceftriaxone every 12 hours 193,194 . This prompted us to abandon this regimen and consider other alternatives.…”

Section: Outpatient Parenteral Antimicrobial Therapy (Opat) With the ...mentioning

confidence: 99%

Treatment of <em>Enterococcus faecalis</em> Infective Endocarditis: A Continuing Challenge

Herrero-Hidalgo¹,

Fernández-Rubio²,

Luque‐Márquez³

et al. 2023

Preprint

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Today, enterococci (mainly Enterococcus faecalis) are one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. enterococci are intrinsically resistant to many commonly used antimicrobial agents. All enterococci exhibit decreased susceptibility to penicillin and ampicillin, as well as high-level resistance to most cephalosporins and all semi-synthetic penicillins, as the result of expression of low-affinity penicillin-binding proteins, that precludes an unacceptable number of therapeutic failures with monotherapy with these drugs. For years, the synergistic combination of penicillins and aminoglycosides was the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, such as dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have forced the search of new alternatives with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has led to the consideration of viable options such as outpatient parenteral therapies or long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

show abstract

A new pharmacodynamic approach to study antibiotic combinations against enterococci in vivo: Application to ampicillin plus ceftriaxone

Cited by 8 publications

References 32 publications

Different effects of a perioperative single dose of dexamethasone on wound healing in mice with or without sepsis

Different effects of a perioperative single dose of dexamethasone on wound healing in mice with or without sepsis

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge

Treatment of <em>Enterococcus faecalis</em> Infective Endocarditis: A Continuing Challenge

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